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1. Ursodeoxycholic acid in intrahepatic cholestasis of pregnancy: a systematic review and individual participant data meta-analysis

Author: Agata Majewska, Jessica A Marathe, Jenny Chambers, Romana Brun-Furrer, Ugo Indraccolo, Yue Cui, Stefan C. Kane, George Attilakos, Maria C. Estiú, L.F. Audris Wong, Andrew Shennan, Rachel M. Tribe, Michael J. Peek, Richard H. Lee, Keren Zloto, Jim G Thornton, Hanns-Ulrich Marschall, Tharni Vasavan, Yoav Yinon, Yannick Bacq, Caroline Ovadia, Berrin Günaydin, Xiaohua Liu, Yayi Hu, Catherine Williamson, Jūratė Kondrackienė, Ayse Gul Kebapcilar, Martijn A. Oudijk, Qianwen Zhang, Kasia Maksym, Victoria Geenes, William M. Hague, Alexander Juusela, Min Ding, Levent Kebapcilar, Valeria Tripodi, Deniz Oztekin, Kajol Patel, Rocio I.R. Macias, Nicholas A. Williamson, Christian Haslinger, Monika Grymowicz, Linoy Batsry, Fergus W. Gardiner, Naciye Turk Ozterlemez, Riza Madazli, Lucy C Chappell, Peter H. Dixon, Paul T. Seed, Anna Locatelli, Kelsey Broom, Maria P.H. Koster, Laura N. Bull, Jenna Sajous, Adam Morton, Francesco Azzaroli, Katherine Kohari, Ovadia C., Sajous J., Seed P.T., Patel K., Williamson N.J., Attilakos G., Azzaroli F., Bacq Y., Batsry L., Broom K., Brun-Furrer R., Bull L., Chambers J., Cui Y., Ding M., Dixon P.H., Estiu M.C., Gardiner F.W., Geenes V., Grymowicz M., Gunaydin B., Hague W.M., Haslinger C., Hu Y., Indraccolo U., Juusela A., Kane S.C., Kebapcilar A., Kebapcilar L., Kohari K., Kondrackiene J., Koster M.P.H., Lee R.H., Liu X., Locatelli A., Macias R.I.R., Madazli R., Majewska A., Maksym K., Marathe J.A., Morton A., Oudijk M.A., Oztekin D., Peek M.J., Shennan A.H., Tribe R.M., Tripodi V., Turk Ozterlemez N., Vasavan T., Wong L.F.A., Yinon Y., Zhang Q., Zloto K., Marschall H.-U., Thornton J., Chappell L.C., Williamson C., Obstetrics and Gynaecology, ARD - Amsterdam Reproduction and Development, Ovadia, C, Sajous, J, Seed, P, Patel, K, Williamson, N, Attilakos, G, Azzaroli, F, Bacq, Y, Batsry, L, Broom, K, Brun-Furrer, R, Bull, L, Chambers, J, Cui, Y, Ding, M, Dixon, P, Estiu, M, Gardiner, F, Geenes, V, Grymowicz, M, Gunaydin, B, Hague, W, Haslinger, C, Hu, Y, Indraccolo, U, Juusela, A, Kane, S, Kebapcilar, A, Kebapcilar, L, Kohari, K, Kondrackiene, J, Koster, M, Lee, R, Liu, X, Locatelli, A, Macias, R, Madazli, R, Majewska, A, Maksym, K, Marathe, J, Morton, A, Oudijk, M, Oztekin, D, Peek, M, Shennan, A, Tribe, R, Tripodi, V, Turk Ozterlemez, N, Vasavan, T, Wong, L, Yinon, Y, Zhang, Q, Zloto, K, Marschall, H, Thornton, J, Chappell, L, Williamson, C, Obstetrics & Gynecology, and Amsterdam Reproduction & Development (AR&D)
Subjects: Cholagogues and Choleretics, medicine.medical_specialty, medicine.drug_class, Cholestasis, Intrahepatic, 03 medical and health sciences, 0302 clinical medicine, Cholestasis, Pregnancy, Internal medicine, Cholestasis of pregnancy, Humans, Medicine, Hepatology, Bile acid, business.industry, Obstetrics, Individual participant data, Gastroenterology, Obstetrics and Gynecology, General Medicine, Odds ratio, medicine.disease, Ursodeoxycholic acid, Pregnancy Complications, 030220 oncology & carcinogenesis, Meta-analysis, Female, 030211 gastroenterology & hepatology, stillbirth, Ursodeoxycholic acid, pregnancy, intrahepatic cholestasis of pregnancy, business, medicine.drug, Cohort study
Abstract: Background: Ursodeoxycholic acid is commonly used to treat intrahepatic cholestasis of pregnancy, yet its largest trial detected minimal benefit for a composite outcome (stillbirth, preterm birth, and neonatal unit admission). We aimed to examine whether ursodeoxycholic acid affects specific adverse perinatal outcomes. Methods: In this systematic review and individual participant data meta-analysis, we searched PubMed, Web of Science, Embase, MEDLINE, CINAHL, Global Health, MIDIRS, and Cochrane without language restrictions for relevant articles published between database inception, and Jan 1, 2020, using search terms referencing intrahepatic cholestasis of pregnancy, ursodeoxycholic acid, and perinatal outcomes. Eligible studies had 30 or more study participants and reported on at least one individual with intrahepatic cholestasis of pregnancy and bile acid concentrations of 40 μmol/L or more. We also included two unpublished cohort studies. Individual participant data were collected from the authors of selected studies. The primary outcome was the prevalence of stillbirth, for which we anticipated there would be insufficient data to achieve statistical power. Therefore, we included a composite of stillbirth and preterm birth as a main secondary outcome. A mixed-effects meta-analysis was done using multi-level modelling and adjusting for bile acid concentration, parity, and multifetal pregnancy. Individual participant data analyses were done for all studies and in different subgroups, which were produced by limiting analyses to randomised controlled trials only, singleton pregnancies only, or two-arm studies only. This study is registered with PROSPERO, CRD42019131495. Findings: The authors of the 85 studies fulfilling our inclusion criteria were contacted. Individual participant data from 6974 women in 34 studies were included in the meta-analysis, of whom 4726 (67·8%) took ursodeoxycholic acid. Stillbirth occurred in 35 (0·7%) of 5097 fetuses among women with intrahepatic cholestasis of pregnancy treated with ursodeoxycholic acid and in 12 (0·6%) of 2038 fetuses among women with intrahepatic cholestasis of pregnancy not treated with ursodeoxycholic acid (adjusted odds ratio [aOR] 1·04, 95% CI 0·35–3·07; p=0·95). Ursodeoxycholic acid treatment also had no effect on the prevalence of stillbirth when considering only randomised controlled trials (aOR 0·29, 95% CI 0·04–2·42; p=0·25). Ursodeoxycholic acid treatment had no effect on the prevalence of the composite outcome in all studies (aOR 1·28, 95% CI 0·86–1·91; p=0·22), but was associated with a reduced composite outcome when considering only randomised controlled trials (0·60, 0·39–0·91; p=0·016). Interpretation: Ursodeoxycholic acid treatment had no significant effect on the prevalence of stillbirth in women with intrahepatic cholestasis of pregnancy, but our analysis was probably limited by the low overall event rate. However, when considering only randomised controlled trials, ursodeoxycholic acid was associated with a reduction in stillbirth in combination with preterm birth, providing evidence for the clinical benefit of antenatal ursodeoxycholic acid treatment. Funding: Tommy's, the Wellcome Trust, ICP Support, and the National Institute for Health Research.
Published: 2021

2. Approaches to the Diagnosis of Portal Hypertension: Non-Invasive or Invasive Tests?

Author: Elton Dajti, Giovanni Marasco, Francesco Azzaroli, Marco Montagnani, Luigina Vanessa Alemanni, Dajti, Elton, Alemanni, Luigina Vanessa, Marasco, Giovanni, Montagnani, Marco, and Azzaroli, Francesco
Subjects: medicine.medical_specialty, Hepatology, liver cirrhosi, business.industry, liver cirrhosis, Portal venous pressure, Non invasive, liver stiffne, portal hypertension, Review, medicine.disease, Chronic liver disease, Clinical trial, liver stiffness, hepatic venous pressure gradient, Esophageal varices, Internal medicine, medicine, Cardiology, Portal hypertension, Decompensation, Varices, business, spleen stiffness
Abstract: Portal hypertension is the main driver of complications in patients with advanced chronic liver disease (ACLD) and is defined by values of hepatic venous pressure gradient measurement (HVPG) >5 mmHg. Values of HVPG >= 10 mmHg determine the presence of clinically significant portal hypertension (CSPH), the main predictor of the risk of variceal bleeding, hepatic decompensation, and mortality. However, its measurement is invasive and requires high expertise, so its routine use outside third level centers or clinical trials is limited. In the last decades, several non-invasive tests (NITS) have been developed and validated for the diagnosis of portal hypertension. Among these, liver (LSM) and spleen stiffness measurement (SSM) are the most promising tools available, as they have been proven accurate to predict CSPH, high-risk esophageal varices, decompensation, and mortality in patients with ACLD. In the last Baveno VI Consensus proceedings, LSM evaluation was recommended for the first time for diagnosis of CSPH (LSM >20-25 kPa) and the screening of patients with a low probability of having high-risk varices (LSM 150.000/mm(3)). In this review, we aimed to summarize the growing evidence supporting the use of non-invasive tests for the evaluation of portal hypertension in patients with chronic liver disease.
Published: 2021

3. Spleen Stiffness Measurements Predict the Risk of Hepatic Decompensation After Direct-Acting Antivirals in HCV Cirrhotic Patients

Author: Francesco Azzaroli, Maria Letizia Bacchi Reggiani, Davide Festi, Pietro Andreone, Giovanni Marasco, Elton Dajti, Luigina Vanessa Alemanni, Stefano Brillanti, Federico Ravaioli, Agostino Colli, Antonio Colecchia, Mariarosa Tamè, Giuseppe Mazzella, DIPARTIMENTO DI MEDICINA SPECIALISTICA, DIAGNOSTICA E SPERIMENTALE, DIPARTIMENTO DI SCIENZE MEDICHE E CHIRURGICHE, and Facolta' di MEDICINA e CHIRURGIA
Subjects: Liver Cirrhosis, medicine.medical_specialty, Hepacivirus, Chronic liver disease, Antiviral Agents, Gastroenterology, spleen stiffness measurement, 030218 nuclear medicine & medical imaging, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, Decompensation, liver stiffness measurement, 030219 obstetrics & reproductive medicine, business.industry, Incidence (epidemiology), sustained virologic response, Hepatitis C, Chronic, medicine.disease, transient elastography, medicine.anatomical_structure, Cohort, Propensity score matching, abdomen, Abdomen, Transient elastography, business, Spleen, Cohort study
Abstract: Little evidence is available regarding the risk of hepatic decompensation (HD) after direct-acting antivirals (DAAs) in patients with advanced chronic liver disease. Our aim was to assess the risk of decompensation and the prognostic role of noninvasive tests, such as liver (LSM) and spleen (SSM) stiffness measurements, in the prediction of decompensation after sustained virologic response (SVR) by DAAs.A cohort study involving 146 cirrhotic patients treated with DAAs in our tertiary center with LSM and SSM available both before and six months after treatment (SVR24). A historical cohort of 92 consecutive cirrhotic patients with active HCV was used as a control group. A propensity score inverse probability weighting method was used to account for differences between the groups. Time-dependent models for the prediction of decompensation were applied to account for changes in noninvasive tests after therapy.The decompensation incidence in the DAA cohort was 7.07 (4.56-10.96) per 100 person-years (PYs), which was significantly lower than in the active HCV cohort. The DAA therapy was an independent protective factor for HD development (SHR: 0.071, 95 %-CI: 0.015-0.332). SSM ≥ 54 kPa was independently associated with decompensation despite SVR achievement (SHR: 4.169, 95 %-CI: 1.050-16.559), alongside with a history of decompensation (SHR: 7.956, 95 %-CI: 2.556-24.762). SSM reduction 10 % also predicted the risk of decompensation after SVR24.The risk of decompensation was markedly reduced after DAA therapy, but it was not eliminated. Paired SSM values stratified the risk of decompensation after SVR better than other noninvasive tests.ZIEL: Über das Risiko einer hepatischen Dekompensation (HD) nach direkt antiviral wirksamen Substanzen (DAA) bei Patienten mit fortgeschrittener chronischer Lebererkrankung gibt es nur wenig Evidenz. Unser Ziel war es, das Risiko einer Dekompensation und den prognostischen Wert nichtinvasiver Tests wie Messungen der Lebersteifigkeit (LSM) und Milzsteifigkeit (SSM) zur Vorhersage einer Dekompensation nach anhaltendem virologischem Ansprechen (SVR) unter DAA zu bewerten.Kohortenstudie mit 146 Zirrhose-Patienten, die in unserem Tertiärzentrum mit DAAs behandelt wurden, wobei LSM und SSM sowohl vor als auch 6 Monate nach der Behandlung verfügbar waren (SVR24). Eine historische Kohorte von 92 konsekutiven zirrhotischen Patienten mit aktiver HCV wurde als Kontrollgruppe verwendet. Um die Unterschiede zwischen den Gruppen zu berücksichtigen, wurde die Propensity-Score-Methode („inverse probability weighting“) verwendet. Zeitabhängige Modelle zur Prädiktion der Dekompensation wurden angewandt, um Veränderungen in den nichtinvasiven Tests nach Therapie zu berücksichtigen.Die Dekompensations-Inzidenz in der DAA-Kohorte betrug 7,07 (4,56–10,96) pro 100 Personenjahre (PYs), was signifikant niedriger war als in der aktiven HCV-Kohorte. Die DAA-Therapie war ein unabhängiger protektiver Faktor für die Entwicklung einer HD (SHR: 0,071; 95 %-KI 0,015–0,332). SSM ≥ 54kPa war trotz erfolgreichem SVR unabhängig mit Dekompensation assoziiert (SHR: 4,169; 95 %-KI 1,050–16,559), zusammen mit früher aufgetretener Dekompensation (SHR: 7,956; 95 %-KI 2,556–24,762). Eine SSM-Reduktion 10 % sagte auch das Risiko einer Dekompensation nach SVR24 voraus.Das Risiko einer Dekompensation war nach DAA-Therapie deutlich reduziert, aber nicht eliminiert. Gepaarte SSM-Werte stratifizierten das Risiko einer Dekompensation nach SVR besser als andere nichtinvasive Tests.
Published: 2020

4. Surveillance for hepatocellular carcinoma with a 3-months interval in 'extremely high-risk' patients does not further improve survival

Author: Filippo Pelizzaro, Giulia Peserico, Marco D'Elia, Nora Cazzagon, Francesco Paolo Russo, Alessandro Vitale, Edoardo G. Giannini, Manuela Piccinnu, Gian Ludovico Rapaccini, Maria Di Marco, Eugenio Caturelli, Marco Zoli, Rodolfo Sacco, Giuseppe Cabibbo, Fabio Marra, Andrea Mega, Filomena Morisco, Antonio Gasbarrini, Gianluca Svegliati-Baroni, Francesco Giuseppe Foschi, Andrea Olivani, Alberto Masotto, Gerardo Nardone, Giovanni Raimondo, Francesco Azzaroli, Gianpaolo Vidili, Filippo Oliveri, Franco Trevisani, Fabio Farinati, Maurizio Biselli, Paolo Caraceni, Francesca Garuti, Annagiulia Gramenzi, Andrea Neri, Valentina Santi, Fabio Piscaglia, Francesco Tovoli, Alessandro Granito, Luca Muratori, Francesca Benevento, Elton Dajti, Giovanni Marasco, Federico Ravaioli, Alberta Cappelli, Rita Golfieri, Cristina Mosconi, Matteo Renzulli, Angela Imondi, Anna Sartori, Barbara Penzo, Elisa Pinto, Ester Marina Cela, Antonio Facciorusso, Valentina Cacciato, Edoardo Casagrande, Alessandro Moscatelli, Gaia Pellegatta, Nicoletta De Matthaeis, Gloria Allegrini, Valentina Lauria, Giorgia Ghittoni, Giorgio Pelecca, Fabrizio Chegai, Fabio Coratella, Mariano Ortenzi, Gabriele Missale, Alessandro Inno, Fabiana Marchetti, Anita Busacca, Calogero Cammà, Vincenzo Di Martino, Giacomo Emanuele Maria Rizzo, Maria Stella Franzè, Carlo Saitta, Assunta Sauchella, Vittoria Bevilacqua, Alberto Borghi, Andrea Casadei Gardini, Fabio Conti, Anna Chiara Dall'aglio, Giorgio Ercolani, Federica Mirici, Claudia Campani, Chiara Di Bonaventura, Stefano Gitto, Pietro Coccoli, Antonio Malerba, Maria Guarino, Maurizia Brunetto, Veronica Romagnoli, Pelizzaro, F., Peserico, G., D'Elia, M., Cazzagon, N., Russo, F. P., Vitale, A., Giannini, E. G., Piccinnu, M., Rapaccini, G. L., Di Marco, M., Caturelli, E., Zoli, M., Sacco, R., Cabibbo, G., Marra, F., Mega, A., Morisco, F., Gasbarrini, A., Svegliati-Baroni, G., Foschi, F. G., Olivani, A., Masotto, A., Nardone, G., Raimondo, G., Azzaroli, F., Vidili, G., Oliveri, F., Trevisani, F., Farinati, F., Biselli, M., Caraceni, P., Garuti, F., Gramenzi, A., Neri, A., Santi, V., Piscaglia, F., Tovoli, F., Granito, A., Muratori, L., Benevento, F., Dajti, E., Marasco, G., Ravaioli, F., Cappelli, A., Golfieri, R., Mosconi, C., Renzulli, M., Imondi, A., Sartori, A., Penzo, B., Pinto, E., Cela, E. M., Facciorusso, A., Cacciato, V., Casagrande, E., Moscatelli, A., Pellegatta, G., De Matthaeis, N., Allegrini, G., Lauria, V., Ghittoni, G., Pelecca, G., Chegai, F., Coratella, F., Ortenzi, M., Missale, G., Inno, A., Marchetti, F., Busacca, A., Camma, C., Di Martino, V., Rizzo, G. E. M., Franze, M. S., Saitta, C., Sauchella, A., Bevilacqua, V., Borghi, A., Casadei Gardini, A., Conti, F., Dall'Aglio, A. C., Ercolani, G., Mirici, F., Campani, C., Di Bonaventura, C., Gitto, S., Coccoli, P., Malerba, A., Guarino, M., Brunetto, M., Romagnoli, V., Pelizzaro, Filippo, Peserico, Giulia, D'Elia, Marco, Cazzagon, Nora, Russo, Francesco Paolo, Vitale, Alessandro, Giannini, Edoardo G., Piccinnu, Manuela, Rapaccini, Gian Ludovico, Di Marco, Maria, Caturelli, Eugenio, Zoli, Marco, Sacco, Rodolfo, Cabibbo, Giuseppe, Marra, Fabio, Mega, Andrea, Morisco, Filomena, Gasbarrini, Antonio, Svegliati-Baroni, Gianluca, Foschi, Francesco Giuseppe, Olivani, Andrea, Masotto, Alberto, Nardone, Gerardo, Raimondo, Giovanni, Azzaroli, Francesco, Vidili, Gianpaolo, Oliveri, Filippo, Trevisani, Franco, Farinati, Fabio, Biselli, Maurizio, Caraceni, Paolo, Garuti, Francesca, Gramenzi, Annagiulia, Neri, Andrea, Santi, Valentina, Piscaglia, Fabio, Tovoli, Francesco, Granito, Alessandro, Muratori, Luca, Benevento, Francesca, Dajti, Elton, Marasco, Giovanni, Ravaioli, Federico, Cappelli, Alberta, Golfieri, Rita, Mosconi, Cristina, Renzulli, Matteo, Imondi, Angela, Sartori, Anna, Penzo, Barbara, Pinto, Elisa, Cela, Ester Marina, Facciorusso, Antonio, Cacciato, Valentina, Casagrande, Edoardo, Moscatelli, Alessandro, Pellegatta, Gaia, De Matthaeis, Nicoletta, Allegrini, Gloria, Lauria, Valentina, Ghittoni, Giorgia, Pelecca, Giorgio, Chegai, Fabrizio, Coratella, Fabio, Ortenzi, Mariano, Missale, Gabriele, Inno, Alessandro, Marchetti, Fabiana, Busacca, Anita, Cammà, Calogero, Di Martino, Vincenzo, Rizzo, Giacomo Emanuele Maria, Franzè, Maria Stella, Saitta, Carlo, Sauchella, Assunta, Bevilacqua, Vittoria, Borghi, Alberto, Casadei Gardini, Andrea, Conti, Fabio, Dall'aglio, Anna Chiara, Ercolani, Giorgio, Mirici, Federica, Campani, Claudia, Di Bonaventura, Chiara, Gitto, Stefano, Coccoli, Pietro, Malerba, Antonio, Guarino, Maria, Brunetto, Maurizia, and Romagnoli, Veronica
Subjects: medicine.medical_specialty, Carcinoma, Hepatocellular, Survival, Hepatocellular carcinoma, Cancer stage, Surveillance interval, Internal medicine, medicine, Humans, Propensity Score, Survival analysis, High risk patients, Hepatology, business.industry, Liver Neoplasms, Settore MED/09 - MEDICINA INTERNA, Gastroenterology, Patient survival, medicine.disease, Survival Analysis, Propensity score matching, Survival Analysi, Liver cancer, business, Median survival, Human
Abstract: Background An enhanced surveillance schedule has been proposed for cirrhotics with viral etiology, who are considered at extremely high-risk of hepatocellular carcinoma (HCC). Aims We compared the 3- and 6-months surveillance interval, evaluating cancer stage at diagnosis and patient survival. Methods Data of 777 HBV and HCV cirrhotic patients with HCC diagnosed under a 3-months (n = 109, 3MS group) or a 6-months (n = 668, 6MS group) surveillance were retrieved from the Italian Liver Cancer database. Survival in the 3MS group was considered as observed and adjusted for lead-time bias, and survival analysis was repeated after a propensity score matching. Results The 3-months surveillance interval neither reduced the share of patients diagnosed outside the Milano criteria, nor increased their probability to receive curative treatments. The median survival of 6MS patients (55.0 months [45.9–64.0]) was not significantly different from the observed (47.0 months [35.0–58.9]; p = 0.43) and adjusted (44.9 months [33.4–56.4]; p = 0.30) survival of 3MS patients. A propensity score analysis confirmed the absence of a survival advantage for 3MS patients. Conclusions A tightening of surveillance schedule does not increase the diagnosis of early-stage tumors, the feasibility of curative treatments and the survival. Therefore, we should maintain the 6-months interval in the surveillance of viral cirrhotics.
Published: 2022

5. Size and location of spontaneous portosystemic shunts predict the risk of decompensation in cirrhotic patients

Author: Benedetta Rossini, Giovanni Marasco, Matteo Renzulli, Massimo Pinzani, Federico Ravaioli, Francesco Azzaroli, Matteo Milandri, Rita Golfieri, Anna Maria Ierardi, Elton Dajti, Antonio Colecchia, Giuseppe Mazzella, Gianpaolo Carrafiello, Luigina Vanessa Alemanni, Davide Festi, Maria Letizia Bacchi-Reggiani, Dajti E., Renzulli M., Colecchia A., Bacchi-Reggiani M.L., Milandri M., Rossini B., Ravaioli F., Marasco G., Alemanni L.V., Ierardi A.M., Carrafiello G., Pinzani M., Azzaroli F., Mazzella G., Golfieri R., and Festi D.
Subjects: Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, Vascular Malformations, Chronic liver disease, Risk Assessment, Liver imaging, 03 medical and health sciences, 0302 clinical medicine, Predictive Value of Tests, Risk Factors, Clinical Decision Rules, Internal medicine, medicine, Humans, Decompensation, Portal hypertension, Hepatic encephalopathy, Retrospective Studies, Hepatology, Portal Vein, business.industry, Gastroenterology, Retrospective cohort study, Collaterals, Prognosis, medicine.disease, 030220 oncology & carcinogenesis, Chronic Disease, Etiology, Cardiology, Elasticity Imaging Techniques, Collateral, Female, 030211 gastroenterology & hepatology, business, Transient elastography, Follow-Up Studies
Abstract: Background The prognostic role of spontaneous portosystemic shunts (SPSS) has been poorly investigated. Aims To evaluate the impact of the presence of SPSS, as well as their characteristics, on the risk of decompensation. Methods This is a retrospective cohort study of 235 advanced chronic liver disease (ACLD) patients with available imaging examination, transient elastography, and upper endoscopy. ACLD was defined as liver stiffness measurement (LSM) >10 kPa. Competitive risk analyses were performed to identify the factors associated with the main outcome. Results SPSS were reported in 141 (60%) of the patients. Non-viral etiology was independently associated with SPSS presence [Odds-Ratio (OR): 2.743;95%-Interval-of-Confidence (IC):1.129–6.664]. During a follow-up of 37 (20–63) months, SPSS were found predictors of any decompensation type [Subhazard Ratio (SHR):2.264; 95%-IC:1.259–4.071], independently from a history of decompensation or high-risk-varices presence. The risk of complications was higher in patients with large (SHR: 3.775; 95%-IC: 2.016–7.070) and multiple (SHR:3.832; 95%-IC: 2.004–7.330) shunts, and in those with gastrorenal shunts (SHR:2.636; 95%-IC:1.521–4.569). Conclusions The presence, size, and number of SPSS predict not only the risk of hepatic encephalopathy but that of any type of decompensation across all stages of cirrhosis. Future studies should explore the possibility of treating shunts to prevent decompensation.
Published: 2022

6. Validation of a standardized CT protocol for the evaluation of varices and porto-systemic shunts in cirrhotic patients

Author: Davide Festi, Rita Golfieri, Anna Maria Ierardi, Elton Dajti, Matteo Renzulli, Gianpaolo Carrafiello, Giovanni Marasco, Matteo Milandri, Annalisa Berzigotti, Benedetta Rossini, Alfredo Clemente, Francesco Azzaroli, Nicolò Brandi, Antonio Colecchia, Federico Ravaioli, Renzulli M., Dajti E., Ierardi A.M., Brandi N., Berzigotti A., Milandri M., Rossini B., Clemente A., Ravaioli F., Marasco G., Azzaroli F., Carrafiello G., Festi D., Colecchia A., and Golfieri R.
Subjects: Liver Cirrhosis, medicine.medical_specialty, Esophageal and gastric varices, Hepatic failure, Portal hypertension, Radiologic technology, Radiology, Gastrointestinal Hemorrhage, Humans, Retrospective Studies, Tomography, X-Ray Computed, Carcinoma, Hepatocellular, Esophageal and Gastric Varices, Liver Neoplasms, Portasystemic Shunt, Transjugular Intrahepatic, Varicose Veins, medicine.medical_treatment, Liver transplantation, Ascites, medicine, Transjugular Intrahepatic, Radiology, Nuclear Medicine and imaging, Decompensation, Portasystemic Shunt, 610 Medicine & health, Tomography, business.industry, Carcinoma, Retrospective cohort study, Hepatocellular, General Medicine, Esophageal and gastric varice, medicine.disease, Portal vein thrombosis, X-Ray Computed, medicine.symptom, Varices, business, Transjugular intrahepatic portosystemic shunt
Abstract: PURPOSE The aim of the present study was to propose and validate a standardized CT protocol for evaluating all the types of portosystemic collaterals (P-SC), including gastroesophageal varices and spontaneous portosystemic shunts (SPSS), and to evaluate the prognostic role of portal hypertension CT features for the prediction of the hepatic decompensation risk in cirrhotic patients. METHODS A retrospective cohort study of 184 advanced chronic liver disease who underwent CT scan between January 2014 and December 2017. Patients with an interval��>��6��months between the imaging, elastometric, endoscopic and biochemical evaluation were excluded, as well as patients with previous transjugular intrahepatic portosystemic shunt (TIPS), liver transplantation (LT) or terminal medical conditions. Data on liver disease history, co-morbidities, endoscopic and radiologic findings were collected. The incidence of hepatic decompensation and other events, such as portal vein thrombosis, HCC, TIPS placement, LT, death, and its cause, were also recorded. The procedure was performed at baseline and after the administration of contrast agent using a multiphasic technique and bolus tracking. Two senior radiologists working in different centres and a non-expert radiologist reviewed all CT examinations, to evaluate both intra-observer and inter-observer variability of the CT protocol and to obtain an external validation. The radiological variables were evaluated using both univariate and adjusted multivariate competing risk regression models. RESULTS Both intra-observer and inter-observer agreement were excellent in detection and measurement of almost all types of P-SC. The presence of SPSS, a spleen diameter��>��16��cm, a portal vein diameter��>��17��mm and the presence of ascites resulted independent predictors of decompensation-free survival for cirrhotic patients and were incorporated in an easy-to-use score (AUROC��=��0.799, p-value��=��0.732) which can the risk of decompensation at 5��years, ranking it as low (11.3%), moderate (35.6%) or high (70.8%). CONCLUSIONS The CT protocol commonly performed during the HCC surveillance program for cirrhotic patients is valid for detecting all types of P-SC. The radiological score identified to predict the decompensation-free survival for cirrhotic patients could be an easy-to-use clinical tool.
Published: 2022

7. Interleukin 28 Polymorphisms and Hepatocellular Carcinoma Development after Direct Acting Antiviral Therapy for Chronic Hepatitis C

Author: Francesco Azzaroli, Maria Letizia Bacchi-Reggiani, Giuseppe Mazzella, Franco Bazzoli, Federico Ravaioli, Angelo Simili, A. Porro, Davide Festi, Simili A., Mazzella G., Ravaioli F., Festi D., Bacchi-Reggiani M.L., Porro A., Bazzoli F., and Azzaroli F.
Subjects: TIMP1, Male, TIMP2, medicine.medical_specialty, Carcinoma, Hepatocellular, Sustained Virologic Response, Hepatocellular carcinoma, Hepatitis C virus, IL28, Single-nucleotide polymorphism, medicine.disease_cause, Antiviral Agents, Polymorphism, Single Nucleotide, Gastroenterology, MBOAT7, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, 0502 economics and business, medicine, Carcinoma, Humans, SNP, Viral hepatitis C, Genetic Predisposition to Disease, Interleukin 28, Vitamin A, Prospective cohort study, PNPLA3, Aged, Retinol, business.industry, Liver Neoplasms, 05 social sciences, Hepatitis C, Hepatitis C, Chronic, Middle Aged, medicine.disease, digestive system diseases, Female, 050211 marketing, 030211 gastroenterology & hepatology, Interferons, Neoplasm Recurrence, Local, business
Abstract: Background and Aims: Cirrhotic patients with hepatitis C virus (HCV) infection remain at risk of developing hepatocellular carcinoma (HCC) even after the sustained virologic response (SVR). We aimed to evaluate whether the IL28 (rs12979860) single nucleotide polymorphism (SNP) may constitute a predisposing genetic factor and to identify the SVR patients at risk of HCC. Methods: Two hundred patients undergoing DAAs treatment for chronic hepatitis C with advanced fibrosis (F3- F4) were consecutively enrolled. Besides normal routine laboratory testing for HCV, patients’ sera were evaluated also for retinol, retinol-binding protein 4 and the following SNPs: PNPLA3 (rs738409), TM6SF2 (rs58542926), MBOAT7 (rs641738), IL28B (rs12979860), TIMP-1 (rs4898), TIMP-2 (rs8179090), NF-kB promoter (rs28362491). Statistical analyses were conducted using Stata/SE 14.2 statistical software (Stata Corp, College Station, TX). Results: Almost all patients (197/200) obtained SVR24. Seventeen patients had a previous history of treated HCC before DAAs. Six patients developed HCC recurrence and five patients developed de novo HCC after a mean period of 18 months since EOT. All these patients had SVR. A significant association between IL28B – TT genotype and HCC development after DAAs therapy was observed (OR 4.728, CI 95% 1.222 – 18.297, p=0.024). Conclusion: IL28B rs12979860 polymorphism was significantly associated with HCC development after DAAs. Assessment of this SNP may better identify patients at risk of developing HCC after treatment. Further prospective studies are required to confirm these hypotheses.
Published: 2019

8. Complete Remission of Advanced Hepatocellular Carcinoma Treated with Sorafenib and Concomitant Appearance of IgG4- related Diseases. A Case Report

Author: Francesco Azzaroli, Rita Golfieri, Giovanni Marasco, Giovanna Impellizzeri, Giuseppe Mazzella, Matteo Renzulli, Giovanna, Impellizzeri, Matteo, Renzulli, Francesco, Azzaroli, Rita, Golfieri, Giuseppe, Mazzella, and Giovanni, Marasco
Subjects: Male, 0301 basic medicine, Sorafenib, medicine.medical_specialty, Carcinoma, Hepatocellular, Paraproteinemias, Antineoplastic Agents, Retroperitoneal fibrosis, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Maintenance therapy, Internal medicine, medicine, Humans, neoplasms, business.industry, Liver Neoplasms, Remission Induction, Complete remission, Sorafenib − IgG4-related disease − hepatocellular carcinoma − HCC, Middle Aged, medicine.disease, digestive system diseases, Regimen, 030104 developmental biology, Immunoglobulin G, 030220 oncology & carcinogenesis, Concomitant, Hepatocellular carcinoma, IgG4-related disease, medicine.symptom, business, medicine.drug
Abstract: Sorafenib is currently the gold standard therapy for palliative treatment of advanced hepatocellular carcinoma (HCC) in patients with compensated liver disease. There are few cases reported in literature describing patients with HCC achieving a complete remission (CR) due to Sorafenib therapy. We report the case of a 62-year old patient who obtained CR despite single, long drug discontinuation and kept it without any maintenance therapy. Furthermore, this is the first case describing the onset of a likely IgG4-related retroperitoneal fibrosis and cholangitis during Sorafenib administration. Further studies are required to define the predictors of a good response to Sorafenib and to codify a therapeutic maintenance regimen for patients who achieve CR.
Published: 2020

9. Anorectal emergencies: WSES-AAST guidelines

Author: Raul Coimbra, Belinda De Simone, Justin Davies, Mario Testini, Federica Gaiani, Fausto Catena, Nicola de’Angelis, Vishal G Shelat, Ari Leppäniemi, Gianluigi de’Angelis, Ernest E. Moore, Walter L. Biffl, Marco Ceresoli, Andreas Hecker, Vanni Agnoletti, Manos Pikoulis, Boris Sakakushev, Giorgio Rossi, Vittoria Pattonieri, Paolo Carcoforo, Mario Giuffrida, Federico Coccolini, Salomone Di Saverio, Fikri M. Abu-Zidan, Alain Chichom-Mefire, Imtiaz Wani, Andrey Litvin, Luca Ansaloni, Gian Luca Baiocchi, Gennaro Perrone, Michael D. Kelly, Edward C.T.H. Tan, Gaetano Gallo, Andrew B. Peitzman, Yoram Kluger, Hariscine K. Abongwa, George C. Velmahos, Andrew W. Kirkpatrick, Massimo Sartelli, Kenji Inaba, Dieter G. Weber, Carlos A. Ordoñez, Francesco Azzaroli, Antonio Tarasconi, Tarasconi, A, Perrone, G, Davies, J, Coimbra, R, Moore, E, Azzaroli, F, Abongwa, H, De Simone, B, Gallo, G, Rossi, G, Abu-Zidan, F, Agnoletti, V, De'Angelis, G, De'Angelis, N, Ansaloni, L, Baiocchi, G, Carcoforo, P, Ceresoli, M, Chichom-Mefire, A, Di Saverio, S, Gaiani, F, Giuffrida, M, Hecker, A, Inaba, K, Kelly, M, Kirkpatrick, A, Kluger, Y, Leppaniemi, A, Litvin, A, Ordonez, C, Pattonieri, V, Peitzman, A, Pikoulis, M, Sakakushev, B, Sartelli, M, Shelat, V, Tan, E, Testini, M, Velmahos, G, Wani, I, Weber, D, Biffl, W, Coccolini, F, Catena, F, Tarasconi, Antonio [0000-0001-6588-2268], Apollo - University of Cambridge Repository, Tarasconi A., Perrone G., Davies J., Coimbra R., Moore E., Azzaroli F., Abongwa H., De Simone B., Gallo G., Rossi G., Abu-Zidan F., Agnoletti V., de'Angelis G., de'Angelis N., Ansaloni L., Baiocchi G.L., Carcoforo P., Ceresoli M., Chichom-Mefire A., Di Saverio S., Gaiani F., Giuffrida M., Hecker A., Inaba K., Kelly M., Kirkpatrick A., Kluger Y., Leppaniemi A., Litvin A., Ordonez C., Pattonieri V., Peitzman A., Pikoulis M., Sakakushev B., Sartelli M., Shelat V., Tan E., Testini M., Velmahos G., Wani I., Weber D., Biffl W., Coccolini F., Catena F., HUS Abdominal Center, and II kirurgian klinikka
Subjects: Non-operative management, Review, Guideline, 0302 clinical medicine, Antibiotics, Diagnosis, PNEUMATIC BALLOON DILATATION, Angiography, Anorectal bleeding, Anorectal foreign bodies, Anorectal sepsis, Anorectal Varices, Embolization, Fournier’s gangrene, Guidelines, Hemorrhoids, Surgery, Technique, Timing, Emergencie, Consensus conference, FISTULA-IN-ANO, Medical emergencies. Critical care. Intensive care. First aid, BLEEDING RECTAL VARICES, 3. Good health, LABORATORY RISK INDICATOR, FOURNIERS-GANGRENE, Fournier's gangrene, THROMBOSED EXTERNAL HEMORRHOIDS, 030220 oncology & carcinogenesis, Emergency Medicine, CHRONIC ANAL-FISSURE, 030211 gastroenterology & hepatology, Medical emergency, Human, Diagnosi, United State, Anorectal disease, RD1-811, NO, 03 medical and health sciences, Emergency surgery, Anorectal foreign bodie, Anorectal pain, medicine, Humans, Anorectal varices, LATERAL INTERNAL SPHINCTEROTOMY, LS7_4, business.industry, RC86-88.9, Anorectal Varice, Antibiotic, Anorectal sepsi, GANGRENE SEVERITY INDEX, 3126 Surgery, anesthesiology, intensive care, radiology, medicine.disease, United States, Review article, Inpatient management, Rectal Diseases, COLORECTAL FOREIGN-BODIES, Diagnosis, Non-operative management, Surgery, Antibiotics, Hemorrhoids, Fournier’s gangrene, Anorectal bleeding, Anorectal sepsis, Anorectal foreign bodies , Anorectal Varices, Technique, Timing, Angiography, Embolization, Guidelines, diagnosis, non-operative management, surgery, antibiotics, hemorrhoids, anorectal bleeding, anorectal sepsis, anorectal foreign bodies, anorectal Varices, technique, timing, angiography, embolization, guidelines, Emergencies, business, Hemorrhoid
Abstract: Anorectal emergencies comprise a wide variety of diseases that share common symptoms, i.e., anorectal pain or bleeding and might require immediate management. While most of the underlying conditions do not need inpatient management, some of them could be life-threatening and need prompt recognition and treatment. It is well known that an incorrect diagnosis is frequent for anorectal diseases and that a delayed diagnosis is related to an impaired outcome. This paper aims to improve the knowledge and the awareness on this specific topic and to provide a useful tool for every physician dealing with anorectal emergencies.The present guidelines have been developed according to the GRADE methodology. To create these guidelines, a panel of experts was designed and charged by the boards of the World Society of Emergency Surgery (WSES) and American Association for the Surgery of Trauma (AAST) to perform a systematic review of the available literature and to provide evidence-based statements with immediate practical application. All the statements were presented and discussed during the WSES-AAST-WJES Consensus Conference on Anorectal Emergencies, and for each statement, a consensus among the WSES-AAST panel of experts was reached. We structured our work into seven main topics to cover the entire management of patients with anorectal emergencies and to provide an up-to-date, easy-to-use tool that can help physicians and surgeons during the decision-making process.
Published: 2021

10. Hepatocellular Carcinoma Recurrence after Hepatitis C Virus Therapy with Direct-Acting Antivirals. A Systematic Review and Meta-Analysis

Author: Giuseppe Mazzella, Franco Bazzoli, Lorenzo Fuccio, Usama Sikandar, Leonardo Frazzoni, Sinan Sadalla, Francesco Azzaroli, Flavio Metelli, Frazzoni, Leonardo, Sikandar, Usama, Metelli, Flavio, Sadalla, Sinan, Mazzella, Giuseppe, Bazzoli, Franco, Fuccio, Lorenzo, and Azzaroli, Francesco
Subjects: medicine.medical_specialty, Cirrhosis, Hepatitis C virus, lcsh:Medicine, Review, DIRECT ACTING ANTIVIRALS, medicine.disease_cause, Gastroenterology, 03 medical and health sciences, hepatocellular carcinoma (HCC), 0302 clinical medicine, Internal medicine, Medicine, Complete response, business.industry, lcsh:R, General Medicine, medicine.disease, digestive system diseases, Regimen, 030220 oncology & carcinogenesis, Relative risk, Hepatocellular carcinoma, Meta-analysis, direct-acting antivirals (DAAs), 030211 gastroenterology & hepatology, business, hepatitis C virus (HCV)
Abstract: Background: Hepatocellular carcinoma (HCC) is a major cause of morbidity and mortality among patients with cirrhosis. The risk of HCC recurrence after a complete response among patients treated with direct-acting antivirals (DAAs) has not been fully elucidated yet. Aim: To assess the risk of HCC recurrence after DAA therapy for hepatitis C virus (HCV). Methods: A systematic review across PubMed, Scopus and Scholar up to November 2020, including full-text studies that assessed the pattern of HCC recurrence after DAA therapy for HCV. Random-effect meta-analysis and univariable metaregression were applied to obtain pooled estimates for proportions and relative risk (RR) and variables influential for the outcome, respectively. Results: Thirty-one studies with 2957 patients were included. Overall, 30% (CI, 26–34%) of the patients with a history of HCC experienced HCC recurrence after DAA therapy, at mean time intervals ranging from 4 to 21 months. This result increased when going from European studies (23%, CI, 17–28%) to US studies (34%, CI, 30–38%), to Egyptian studies (37%, CI, 27–47%), and to Asian studies (33%, CI, 27–40%). Sixty-eight percent (CI, 45–91%) of recurrent HCCs developed within 6 months of follow-up since DAA treatment, among the eight studies providing stratified data. Among the studies providing head-to-head comparisons, the HCC recurrence risk was significantly lower after DAA therapy than IFN (RR, 0.64; CI, 0.51–0.81), and after DAA therapy than no intervention (RR, 0.68; CI, 0.49–0.94). Conclusions: The recurrence of HCC after DAA is not negligible, being higher soon after the end of treatment and among non-European countries. DAA therapy seems to reduce the risk of HCC recurrence compared to an IFN regimen and no intervention.
Published: 2021

11. Changes in hepatocellular carcinoma aggressiveness characteristics with an increase in tumor diameter

Author: Giovanni Raimondo, Alberto Masotto, Edoardo G. Giannini, Filippo Oliveri, Fabio Piscaglia, Francesco Giuseppe Foschi, Giuseppe Cabibbo, Gianpaolo Vidili, Francesco Azzaroli, Gian Ludovico Rapaccini, Antonio Gasbarrini, Rodolfo Sacco, Franco Trevisani, Gerardo Nardone, Maria Di Marco, Fabio Marra, Brian I. Carr, Eugenio Caturelli, Andrea Mega, Marco Zoli, Filomena Morisco, Vito Guerra, Gianluca Svegliati-Baroni, Fabio Farinati, Gabriele Missale, Rossella Donghia, Carr B.I., Guerra V., Donghia R., Farinati F., Giannini E.G., Piscaglia F., Rapaccini G.L., Di Marco M., Caturelli E., Zoli M., Sacco R., Cabibbo G., Marra F., Mega A., Morisco F., Gasbarrini A., Svegliati-Baroni G., Foschi F.G., Missale G., Masotto A., Nardone G., Raimondo G., Azzaroli F., Vidili G., Oliveri F., Trevisani F., Carr, B. I., Guerra, V., Donghia, R., Farinati, F., Giannini, E. G., Piscaglia, F., Rapaccini, G. L., Di Marco, M., Caturelli, E., Zoli, M., Sacco, R., Cabibbo, G., Marra, F., Mega, A., Morisco, F., Gasbarrini, A., Svegliati-Baroni, G., Foschi, F. G., Missale, G., Masotto, A., Nardone, G., Raimondo, G., Azzaroli, F., Vidili, G., Oliveri, F., and Trevisani, F.
Subjects: Male, Cancer Research, Pathology, medicine.medical_specialty, Carcinoma, Hepatocellular, Prognosi, Settore MED/12 - GASTROENTEROLOGIA, Clinical Biochemistry, size, Pathology and Forensic Medicine, evolution, medicine, Humans, Prospective Studies, HCC, Tumor size, business.industry, Liver Neoplasms, Carcinoma, Settore MED/09 - MEDICINA INTERNA, Hepatocellular, Middle Aged, Prognosis, medicine.disease, Portal vein thrombosis, trend, Oncology, Liver Neoplasm, Hepatocellular carcinoma, Female, business, Human
Abstract: Background: Hepatocellular carcinoma prognosis depends on both liver and tumor determinants, especially on maximum tumor diameter, multifocality, and presence of portal vein thrombosis, despite apparently complete tumor removal by resection or liver transplantation. Aims: To examine parameters of hepatocellular carcinoma aggressiveness as tumor size increases. Methods: A large hepatocellular carcinoma database was examined for trends in serum alpha-fetoprotein and the percentage of patients with macroscopic portal vein thrombosis or tumor multifocality. Results: A total of 13,016 hepatocellular carcinoma patients were identified having full tumor and survival data. Of these, 76.56% were male and 23.44% were female, with a median age of 64.4 years. We found that as the maximum tumor diameter increased, there was a significant trend for increased alpha-fetoprotein levels ( PConclusions: The greater fold-increases in alpha-fetoprotein and portal vein thrombosis compared with increases in maximum tumor diameter imply that hepatocellular carcinoma characteristics may change with increasing size to a more aggressive phenotype, suggesting that follow-up tumor sampling might be useful, in addition to baseline tumor sampling, for optimal therapeutic choices to be made.
Published: 2021

12. Prenatal noninvasive trio-WES in a case of pregnancy-related liver disorder

Author: Sabrina Giglio, Anna Seidenari, Carla Serra, Aldesia Provenzano, Antonio Farina, Anna Nunzia Della Gatta, Orsetta Zuffardi, Francesco Azzaroli, Provenzano A., Farina A., Seidenari A., Azzaroli F., Serra C., Gatta A.D., Zuffardi O., and Giglio S.R.
Subjects: Exome sequencing, Medicine (General), medicine.medical_specialty, Pregnancy, In vitro fertilisation, Obstetrics, business.industry, medicine.medical_treatment, Clinical Biochemistry, Benign Recurrent Intrahepatic Cholestasis, Case Report, Disease, Jaundice, medicine.disease, Liver disorder, Liver disease, Fetal cell free DNA, R5-920, medicine, Non-invasive WES, medicine.symptom, business, Twin Pregnancy
Abstract: Liver disease in pregnancy may present as an acute condition related to the gestational period, characterized by pruritus, jaundice, and abnormal liver function. The disease may be misdiagnosed with other liver diseases, some of which may have consequences for fetal health. It is therefore advisable to implement rapid diagnostic strategies to provide information for the management of pregnancy in these conditions. We report the case of a healthy woman with a twin pregnancy from homologous in vitro fertilization (IVF), who in the third trimester presented jaundice and malaise. Biochemical investigations and liver hyperechogenicity raised the suspicion of acute fatty liver disease of pregnancy (AFLP). Non-invasive prenatal whole-exome sequencing (WES) in the trio identified the Phe305Ile heterozygous variant in the ATP8B1 gene. Considering the twin pregnancy, the percentage of the variant versus the wild allele was of 31%, suggesting heterozygosity present in the mother alone. This analysis showed that the mother was affected by benign recurrent intrahepatic cholestasis of pregnancy (ICP1: # 147480) and indicated the opportunity to anticipate childbirth to avoid worsening of the mother’s health. WES after the birth of the twins confirmed the molecular data.
Published: 2021

13. Identification of clinical phenotypes and related survival in patients with large hccs

Author: Rossella Donghia, Antonio Gasbarrini, Giovanni Raimondo, Elisabetta Biasini, Francesco Giuseppe Foschi, Gianpaolo Vidili, Maria Guarino, Andrea Mega, Marco Zoli, Rodolfo Sacco, Fabio Farinati, Brian I. Carr, Gianluca Svegliati-Baroni, Ciro Celsa, Eugenio Caturelli, Edoardo G. Giannini, Vito Guerra, Gian Ludovico Rapaccini, Maria Di Marco, Gerardo Nardone, Franco Trevisani, Claudia Campani, Luca Muratori, Francesco Azzaroli, Maurizia Rossana Brunetto, Alberto Masotto, Carr B.I., Guerra V., Donghia R., Farinati F., Giannini E.G., Muratori L., Rapaccini G.L., Di Marco M., Caturelli E., Zoli M., Sacco R., Celsa C., Campani C., Mega A., Guarino M., Gasbarrini A., Svegliati-Baroni G., Foschi F.G., Biasini E., Masotto A., Nardone G., Raimondo G., Azzaroli F., Vidili G., Brunetto M.R., Trevisani F., Carr, B. I., Guerra, V., Donghia, R., Farinati, F., Giannini, E. G., Muratori, L., Rapaccini, G. L., Di Marco, M., Caturelli, E., Zoli, M., Sacco, R., Celsa, C., Campani, C., Mega, A., Guarino, M., Gasbarrini, A., Svegliati-Baroni, G., Foschi, F. G., Biasini, E., Masotto, A., Nardone, G., Raimondo, G., Azzaroli, F., Vidili, G., Brunetto, M. R., and Trevisani, F.
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, PVT, Settore MED/12 - GASTROENTEROLOGIA, Serum albumin, lcsh:RC254-282, Gastroenterology, Article, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Medicine, Platelet, HCC, neoplasms, Survival rate, biology, business.industry, Proportional hazards model, Albumin, Hazard ratio, Settore MED/09 - MEDICINA INTERNA, Multifocality, large, phenotypes, multifocality, albumin, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, digestive system diseases, Portal vein thrombosis, Large, Phenotypes, Phenotype, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, biology.protein, business
Abstract: Background. Hepatocellular carcinoma (HCC) factors, especially maximum tumor diameter (MTD), tumor multifocality, portal vein thrombosis (PVT), and serum alpha-fetoprotein (AFP), influence survival. Aim. To examine patterns of tumor factors in large HCC patients. Methods. A database of large HCC patients was examined. Results. A multiple Cox proportional hazard model on death identified low serum albumin levels and the presence of PVT and multifocality, with each having a hazard ratio ≥2.0. All combinations of these three parameters were examined in relation to survival. Using univariate Cox analysis, the combination of albumin &gt, 3.5 g/dL and the absence of both PVT and multifocality had the best survival rate, while all combinations that included the presence of PVT had poor survival and hazard ratios. We identified four clinical phenotypes, each with a distinct median survival: patients with or without PVT or multifocality plus serum albumin ≥3.5 (g/dL), with each subgroup displaying high (≥100 IU/mL) or low (&lt, 100 IU/mL) blood AFP levels. Across a range of MTDs, we identified only two significant trends, blood AFP and platelets. Conclusions. Patients with large HCCs have distinct phenotypes and survival, as identified by the combination of PVT, multifocality, and blood albumin levels.
Published: 2021

14. Time-Varying mHAP-III Is the Most Accurate Predictor of Survival in Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization

Author: Francesco Giuseppe Foschi, Gianpaolo Vidili, Andrea Mega, Antonio Gasbarrini, Marco Zoli, Edoardo G. Giannini, Rodolfo Sacco, Alessandro Vitale, Francesco Tovoli, Giacomo Laffi, Maria Di Marco, Giovanni Raimondo, Gianluca Svegliati-Baroni, Claudia Campani, Francesco Azzaroli, Fabio Farinati, Umberto Arena, Fabio Marra, Gabriele Dragoni, Alberto Masotto, Franco Trevisani, Maurizia Rossana Brunetto, Giuseppe Cabibbo, Elisabetta Biasini, Gian Ludovico Rapaccini, Eugenio Caturelli, Gerardo Nardone, Maria Guarino, Umberto Cillo, Campani, C., Vitale, A., Dragoni, G., Arena, U., Laffi, G., Cillo, U., Giannini, E. G., Tovoli, F., Rapaccini, G. L., Di Marco, M., Caturelli, E., Zoli, M., Sacco, R., Cabibbo, G., Mega, A., Guarino, M., Gasbarrini, A., Svegliati-Baroni, G., Foschi, F. G., Biasini, E., Masotto, A., Nardone, G., Raimondo, G., Azzaroli, F., Vidili, G., Brunetto, M. R., Farinati, F., Trevisani, F., Marra, F., Campani C., Vitale A., Dragoni G., Arena U., Laffi G., Cillo U., Giannini E.G., Tovoli F., Rapaccini G.L., Di Marco M., Caturelli E., Zoli M., Sacco R., Cabibbo G., Mega A., Guarino M., Gasbarrini A., Svegliati-Baroni G., Foschi F.G., Biasini E., Masotto A., Nardone G., Raimondo G., Azzaroli F., Vidili G., Brunetto M.R., Farinati F., Trevisani F., and Marra F.
Subjects: ALBI grade, Barcelona Clinic Liver Cancer, Cancer of the Liver Italian Program, ITALICA staging system, MESIAH, medicine.medical_specialty, lcsh:RC254-282, Gastroenterology, Internal medicine, Medicine, In patient, Radiologic Response, Settore MED/12 - Gastroenterologia, Original Paper, Hepatology, business.industry, Proportional hazards model, Confounding, Hazard ratio, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Oncology, Hepatocellular carcinoma, Akaike information criterion, business, Liver cancer
Abstract: Introduction: The prognosis of patients undergoing transarterial chemoembolization (TACE) is extremely variable, and a confounding factor is that TACE is often repeated several times. We retrospectively evaluated the accuracy of different prognostic scores and staging systems in estimating overall survival (OS) in patients with hepatocellular carcinoma (HCC). Methods: An analysis considering prognostic models as time-varying variables was performed, calculating OS from the time of TACE to the time of the subsequent treatment. Total follow-up time for each patient was therefore split into several observation times accounting for each TACE procedure. Values of the likelihood ratio test (LRT) and Akaike information criterion (AIC) were used to compare different systems. Univariable and multivariable analyses were conducted to identify additional factors predictive of OS. We analyzed 1,610 TACE performed in 1,058 patients recorded in the Italian Liver Cancer database from 2008 through 2016. Results: The median OS of the enrolled patients was 41 months. According to LRT χ2 and AIC values based on the time-varying analysis, mHAP-III achieved the best values (41.72 and 4,625.49, respectively, p < 0.0001), indicating the highest predictive performance compared with all other scores (HAP, mHAP-II, ALBI, and pALBI) and staging systems (MELD, ITALICA, CLIP, MESH, MESIAH, JIS, HKLC, and BCLC). In the multivariable Cox proportional hazards model, mHAP-III maintained an independent effect on OS (hazard ratio 1.31, 95% CI: 1.10–1.55, p < 0.0001). Time-varying age, alcoholic etiology, radiologic response to TACE, and performing ablation or surgery after TACE were additional significant variables resulting from the multivariable model. Conclusion: An innovative time-varying analysis revealed that mHAP-III was the most accurate model in predicting OS in patients with HCC undergoing TACE. Other clinical pre- and post-TACE variables were also found to be relevant for this prediction.
Published: 2021

15. An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs

Author: Heather J. Cordell, James J. Fryett, Kazuko Ueno, Rebecca Darlay, Yoshihiro Aiba, Yuki Hitomi, Minae Kawashima, Nao Nishida, Seik-Soon Khor, Olivier Gervais, Yosuke Kawai, Masao Nagasaki, Katsushi Tokunaga, Ruqi Tang, Yongyong Shi, Zhiqiang Li, Brian D. Juran, Elizabeth J. Atkinson, Alessio Gerussi, Marco Carbone, Rosanna Asselta, Angela Cheung, Mariza de Andrade, Aris Baras, Julie Horowitz, Manuel A.R. Ferreira, Dylan Sun, David E. Jones, Steven Flack, Ann Spicer, Victoria L. Mulcahy, Jinyoung Byan, Younghun Han, Richard N. Sandford, Konstantinos N. Lazaridis, Christopher I. Amos, Gideon M. Hirschfield, Michael F. Seldin, Pietro Invernizzi, Katherine A. Siminovitch, Xiong Ma, Minoru Nakamura, George F. Mells, Andrew Mason, Catherine Vincent, Gang Xie, Jinyi Zhang, Andrea Affronti, Piero L. Almasio, Domenico Alvaro, Pietro Andreone, Angelo Andriulli, Francesco Azzaroli, Pier Maria Battezzati, Antonio Benedetti, MariaConsiglia Bragazzi, Maurizia Brunetto, Savino Bruno, Vincenza Calvaruso, Vincenzo Cardinale, Giovanni Casella, Nora Cazzagon, Antonio Ciaccio, Barbara Coco, Agostino Colli, Guido Colloredo, Massimo Colombo, Silvia Colombo, Laura Cristoferi, Carmela Cursaro, Lory Saveria Crocè, Andrea Crosignani, Daphne D’Amato, Francesca Donato, Gianfranco Elia, Luca Fabris, Stefano Fagiuoli, Carlo Ferrari, Annarosa Floreani, Andrea Galli, Edoardo Giannini, Ignazio Grattagliano, Pietro Lampertico, Ana Lleo, Federica Malinverno, Clara Mancuso, Fabio Marra, Marco Marzioni, Sara Massironi, Alberto Mattalia, Luca Miele, Chiara Milani, Lorenzo Morini, Filomena Morisco, Luigi Muratori, Paolo Muratori, Grazia A. Niro, Sarah O’Donnell, Antonio Picciotto, Piero Portincasa, Cristina Rigamonti, Vincenzo Ronca, Floriano Rosina, Giancarlo Spinzi, Mario Strazzabosco, Mirko Tarocchi, Claudio Tiribelli, Pierluigi Toniutto, Luca Valenti, Maria Vinci, Massimo Zuin, Hitomi Nakamura, Seigo Abiru, Shinya Nagaoka, Atsumasa Komori, Hiroshi Yatsuhashi, Hiromi Ishibashi, Masahiro Ito, Kiyoshi Migita, Hiromasa Ohira, Shinji Katsushima, Atsushi Naganuma, Kazuhiro Sugi, Tatsuji Komatsu, Tomohiko Mannami, Kouki Matsushita, Kaname Yoshizawa, Fujio Makita, Toshiki Nikami, Hideo Nishimura, Hiroshi Kouno, Hirotaka Kouno, Hajime Ota, Takuya Komura, Yoko Nakamura, Masaaki Shimada, Noboru Hirashima, Toshiki Komeda, Keisuke Ario, Makoto Nakamuta, Tsutomu Yamashita, Kiyoshi Furuta, Masahiro Kikuchi, Noriaki Naeshiro, Hironao Takahashi, Yutaka Mano, Seiji Tsunematsu, Iwao Yabuuchi, Yusuke Shimada, Kazuhiko Yamauchi, Rie Sugimoto, Hironori Sakai, Eiji Mita, Masaharu Koda, Satoru Tsuruta, Hiroshi Kamitsukasa, Takeaki Sato, Naohiko Masaki, Tatsuro Kobata, Nobuyoshi Fukushima, Yukio Ohara, Toyokichi Muro, Eiichi Takesaki, Hitoshi Takaki, Tetsuo Yamamoto, Michio Kato, Yuko Nagaoki, Shigeki Hayashi, Jinya Ishida, Yukio Watanabe, Masakazu Kobayashi, Michiaki Koga, Takeo Saoshiro, Michiyasu Yagura, Keisuke Hirata, Atsushu Tanaka, Hajime Takikawa, Mikio Zeniya, Masanori Abe, Morikazu Onji, Shuichi Kaneko, Masao Honda, Kuniaki Arai, Teruko Arinaga-Hino, Etsuko Hashimoto, Makiko Taniai, Takeji Umemura, Satoru Joshita, Kazuhiko Nakao, Tatsuki Ichikawa, Hidetaka Shibata, Satoshi Yamagiwa, Masataka Seike, Koichi Honda, Shotaro Sakisaka, Yasuaki Takeyama, Masaru Harada, Michio Senju, Osamu Yokosuka, Tatsuo Kanda, Yoshiyuki Ueno, Kentaro Kikuchi, Hirotoshi Ebinuma, Takashi Himoto, Michio Yasunami, Kazumoto Murata, Masashi Mizokami, Kazuhito Kawata, Shinji Shimoda, Yasuhiro Miyake, Akinobu Takaki, Kazuhide Yamamoto, Katsuji Hirano, Takafumi Ichida, Akio Ido, Hirohito Tsubouchi, Kazuaki Chayama, Kenichi Harada, Yasuni Nakanuma, Yoshihiko Maehara, Akinobu Taketomi, Ken Shirabe, Yuji Soejima, Akira Mori, Shintaro Yagi, Shinji Uemoto, Egawa H, Tomohiro Tanaka, Noriyo Yamashiki, Sumito Tamura, Yasuhiro Sugawara, Norihiro Kokudo, Naga Chalasani, Vel Luketic, Joseph Odin, Kapil Chopra, Goncalo Abecasis, Michael Cantor, Giovanni Coppola, Aris Economides, Luca A. Lotta, John D. Overton, Jeffrey G. Reid, Alan Shuldiner, Christina Beechert, Caitlin Forsythe, Erin D. Fuller, Zhenhua Gu, Michael Lattari, Alexander Lopez, Thomas D. Schleicher, Maria Sotiropoulos Padilla, Karina Toledo, Louis Widom, Sarah E. Wolf, Manasi Pradhan, Kia Manoochehri, Ricardo H. Ulloa, Xiaodong Bai, Suganthi Balasubramanian, Leland Barnard, Andrew Blumenfeld, Gisu Eom, Lukas Habegger, Alicia Hawes, Shareef Khalid, Evan K. Maxwell, William Salerno, Jeffrey C. Staples, Marcus B. Jones, Lyndon J. Mitnaul, Richard Sturgess, Christopher Healey, Andrew Yeoman, Anton VJ. Gunasekera, Paul Kooner, Kapil Kapur, V. Sathyanarayana, Yiannis Kallis, Javaid Subhani, Rory Harvey, Roger McCorry, Paul Rooney, David Ramanaden, Richard Evans, Thiriloganathan Mathialahan, Jaber Gasem, Christopher Shorrock, Mahesh Bhalme, Paul Southern, Jeremy A. Tibble, David A. Gorard, Susan Jones, George Mells, Victoria Mulcahy, Brijesh Srivastava, Matthew R. Foxton, Carole E. Collins, David Elphick, Mazn Karmo, Francisco Porras-Perez, Michael Mendall, Tom Yapp, Minesh Patel, Roland Ede, Joanne Sayer, James Jupp, Neil Fisher, Martyn J. Carter, Konrad Koss, Jayshri Shah, Andrzej Piotrowicz, Glyn Scott, Charles Grimley, Ian R. Gooding, Simon Williams, Judith Tidbury, Guan Lim, Kuldeep Cheent, Sass Levi, Dina Mansour, Matilda Beckley, Coral Hollywood, Terry Wong, Richard Marley, John Ramage, Harriet M. Gordon, Jo Ridpath, Theodore Ngatchu, Vijay Paul Bob Grover, Ray G. Shidrawi, George Abouda, L. Corless, Mark Narain, Ian Rees, Ashley Brown, Simon Taylor-Robinson, Joy Wilkins, Leonie Grellier, Paul Banim, Debasish Das, Michael A. Heneghan, Howard Curtis, Helen C. Matthews, Faiyaz Mohammed, Mark Aldersley, Raj Srirajaskanthan, Giles Walker, Alistair McNair, Amar Sharif, Sambit Sen, George Bird, Martin I. Prince, Geeta Prasad, Paul Kitchen, Adrian Barnardo, Chirag Oza, Nurani N. Sivaramakrishnan, Prakash Gupta, Amir Shah, Chris DJ. Evans, Subrata Saha, Katharine Pollock, Peter Bramley, Ashis Mukhopadhya, Stephen T. Barclay, Natasha McDonald, Andrew J. Bathgate, Kelvin Palmer, John F. Dillon, Simon M. Rushbrook, Robert Przemioslo, Chris McDonald, Andrew Millar, Cheh Tai, Stephen Mitchell, Jane Metcalf, Syed Shaukat, Mary Ninkovic, Udi Shmueli, Andrew Davis, Asifabbas Naqvi, Tom JW. Lee, Stephen Ryder, Jane Collier, Howard Klass, Matthew E. Cramp, Nichols Sharer, Richard Aspinall, Deb Ghosh, Andrew C. Douds, Jonathan Booth, Earl Williams, Hyder Hussaini, John Christie, Steven Mann, Douglas Thorburn, Aileen Marshall, Imran Patanwala, Aftab Ala, Julia Maltby, Ray Matthew, Chris Corbett, Sam Vyas, Saket Singhal, Dermot Gleeson, Sharat Misra, Jeff Butterworth, Keith George, Tim Harding, Andrew Douglass, Harriet Mitchison, Simon Panter, Jeremy Shearman, Gary Bray, Michael Roberts, Graham Butcher, Daniel Forton, Zahid Mahmood, Matthew Cowan, Debashis Das, Chin Lye Ch’ng, Mesbah Rahman, Gregory C.A. Whatley, Emma Wesley, Aditya Mandal, Sanjiv Jain, Stephen P. Pereira, Mark Wright, Palak Trivedi, Fiona H. Gordon, Esther Unitt, Altaf Palejwala, Andrew Austin, Vishwaraj Vemala, Allister Grant, Andrew D. Higham, Alison Brind, Ray Mathew, Mark Cox, Subramaniam Ramakrishnan, Alistair King, Simon Whalley, Jocelyn Fraser, S.J. Thomson, Andrew Bell, Voi Shim Wong, Richard Kia, Ian Gee, Richard Keld, Rupert Ransford, James Gotto, Charles Millson, Cordell, H. J., Fryett, J. J., Ueno, K., Darlay, R., Aiba, Y., Hitomi, Y., Kawashima, M., Nishida, N., Khor, S. -S., Gervais, O., Kawai, Y., Nagasaki, M., Tokunaga, K., Tang, R., Shi, Y., Li, Z., Juran, B. D., Atkinson, E. J., Gerussi, A., Carbone, M., Asselta, R., Cheung, A., de Andrade, M., Baras, A., Horowitz, J., Ferreira, M. A. R., Sun, D., Jones, D. E., Flack, S., Spicer, A., Mulcahy, V. L., Byan, J., Han, Y., Sandford, R. N., Lazaridis, K. N., Amos, C. I., Hirschfield, G. M., Seldin, M. F., Invernizzi, P., Siminovitch, K. A., Ma, X., Nakamura, M., Mells, G. F., Mason, A., Vincent, C., Xie, G., Zhang, J., Affronti, A., Almasio, P. L., Alvaro, D., Andreone, P., Andriulli, A., Azzaroli, F., Battezzati, P. M., Benedetti, A., Bragazzi, M., Brunetto, M., Bruno, S., Calvaruso, V., Cardinale, V., Casella, G., Cazzagon, N., Ciaccio, A., Coco, B., Colli, A., Colloredo, G., Colombo, M., Colombo, S., Cristoferi, L., Cursaro, C., Croce, L. S., Crosignani, A., D'Amato, D., Donato, F., Elia, G., Fabris, L., Fagiuoli, S., Ferrari, C., Floreani, A., Galli, A., Giannini, E., Grattagliano, I., Lampertico, P., Lleo, A., Malinverno, F., Mancuso, C., Marra, F., Marzioni, M., Massironi, S., Mattalia, A., Miele, L., Milani, C., Morini, L., Morisco, F., Muratori, L., Muratori, P., Niro, G. 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A., Overton, J. D., Reid, J. G., Shuldiner, A., Beechert, C., Forsythe, C., Fuller, E. D., Gu, Z., Lattari, M., Lopez, A., Schleicher, T. D., Padilla, M. S., Toledo, K., Widom, L., Wolf, S. E., Pradhan, M., Manoochehri, K., Ulloa, R. H., Bai, X., Balasubramanian, S., Barnard, L., Blumenfeld, A., Eom, G., Habegger, L., Hawes, A., Khalid, S., Maxwell, E. K., Salerno, W., Staples, J. C., Jones, M. B., Mitnaul, L. J., Sturgess, R., Healey, C., Yeoman, A., Gunasekera, A. V., Kooner, P., Kapur, K., Sathyanarayana, V., Kallis, Y., Subhani, J., Harvey, R., Mccorry, R., Rooney, P., Ramanaden, D., Evans, R., Mathialahan, T., Gasem, J., Shorrock, C., Bhalme, M., Southern, P., Tibble, J. A., Gorard, D. A., Jones, S., Mells, G., Mulcahy, V., Srivastava, B., Foxton, M. R., Collins, C. E., Elphick, D., Karmo, M., Porras-Perez, F., Mendall, M., Yapp, T., Patel, M., Ede, R., Sayer, J., Jupp, J., Fisher, N., Carter, M. J., Koss, K., Shah, J., Piotrowicz, A., Scott, G., Grimley, C., Gooding, I. 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Panter S., Shearman J., Bray G., Roberts M., Butcher G., Forton D., Mahmood Z., Cowan M., Ch'ng C.L., Rahman M., Whatley G.C.A., Wesley E., Mandal A., Jain S., Pereira S.P., Wright M., Trivedi P., Gordon F.H., Unitt E., Palejwala A., Austin A., Vemala V., Grant A., Higham A.D., Brind A., Mathew R., Cox M., Ramakrishnan S., King A., Whalley S., Fraser J., Thomson S.J., Bell A., Wong V.S., Kia R., Gee I., Keld R., Ransford R., Gotto J., Millson C., Medical Research Council (MRC), LiveR North, Cordell, H, Fryett, J, Ueno, K, Darlay, R, Aiba, Y, Hitomi, Y, Kawashima, M, Nishida, N, Khor, S, Gervais, O, Kawai, Y, Nagasaki, M, Tokunaga, K, Tang, R, Shi, Y, Li, Z, Juran, B, Atkinson, E, Gerussi, A, Carbone, M, Asselta, R, Cheung, A, de Andrade, M, Baras, A, Horowitz, J, Ferreira, M, Sun, D, Jones, D, Flack, S, Spicer, A, Mulcahy, V, Byan, J, Han, Y, Sandford, R, Lazaridis, K, Amos, C, Hirschfield, G, Seldin, M, Invernizzi, P, Siminovitch, K, Ma, X, Nakamura, M, Mells, G, Mason, A, Vincent, C, Xie, G, Zhang, J, Affronti, A, Almasio, P, Alvaro, D, Andreone, P, Andriulli, A, Azzaroli, F, Battezzati, P, Benedetti, A, Bragazzi, M, Brunetto, M, Bruno, S, Calvaruso, V, Cardinale, V, Casella, G, Cazzagon, N, Ciaccio, A, Coco, B, Colli, A, Colloredo, G, Colombo, M, Colombo, S, Cristoferi, L, Cursaro, C, Croce, L, Crosignani, A, D'Amato, D, Donato, F, Elia, G, Fabris, L, Fagiuoli, S, Ferrari, C, Floreani, A, Galli, A, Giannini, E, Grattagliano, I, Lampertico, P, Lleo, A, Malinverno, F, Mancuso, C, Marra, F, Marzioni, M, Massironi, S, Mattalia, A, Miele, L, Milani, C, Morini, L, Morisco, F, Muratori, L, Muratori, P, Niro, G, O'Donnell, S, Picciotto, A, Portincasa, P, Rigamonti, C, Ronca, V, Rosina, F, Spinzi, G, Strazzabosco, M, Tarocchi, M, Tiribelli, C, Toniutto, P, Valenti, L, Vinci, M, Zuin, M, Nakamura, H, Abiru, S, Nagaoka, S, Komori, A, Yatsuhashi, H, Ishibashi, H, Ito, M, Migita, K, Ohira, H, Katsushima, S, Naganuma, A, Sugi, K, Komatsu, T, Mannami, T, Matsushita, K, Yoshizawa, K, Makita, F, Nikami, T, Nishimura, H, Kouno, H, Ota, H, Komura, T, Nakamura, Y, Shimada, M, Hirashima, N, Komeda, T, Ario, K, Nakamuta, M, Yamashita, T, Furuta, K, Kikuchi, M, Naeshiro, N, Takahashi, H, Mano, Y, Tsunematsu, S, Yabuuchi, I, Shimada, Y, Yamauchi, K, Sugimoto, R, Sakai, H, Mita, E, Koda, M, Tsuruta, S, Kamitsukasa, H, Sato, T, Masaki, N, Kobata, T, Fukushima, N, Ohara, Y, Muro, T, Takesaki, E, Takaki, H, Yamamoto, T, Kato, M, Nagaoki, Y, Hayashi, S, Ishida, J, Watanabe, Y, Kobayashi, M, Koga, M, Saoshiro, T, Yagura, M, Hirata, K, Tanaka, A, Takikawa, H, Zeniya, M, Abe, M, Onji, M, Kaneko, S, Honda, M, Arai, K, Arinaga-Hino, T, Hashimoto, E, Taniai, M, Umemura, T, Joshita, S, Nakao, K, Ichikawa, T, Shibata, H, Yamagiwa, S, Seike, M, Honda, K, Sakisaka, S, Takeyama, Y, Harada, M, Senju, M, Yokosuka, O, Kanda, T, Ueno, Y, Kikuchi, K, Ebinuma, H, Himoto, T, Yasunami, M, Murata, K, Mizokami, M, Kawata, K, Shimoda, S, Miyake, Y, Takaki, A, Yamamoto, K, Hirano, K, Ichida, T, Ido, A, Tsubouchi, H, Chayama, K, Harada, K, Nakanuma, Y, Maehara, Y, Taketomi, A, Shirabe, K, Soejima, Y, Mori, A, Yagi, S, Uemoto, S, H, E, Tanaka, T, Yamashiki, N, Tamura, S, Sugawara, Y, Kokudo, N, Chalasani, N, Luketic, V, Odin, J, Chopra, K, Abecasis, G, Cantor, M, Coppola, G, Economides, A, Lotta, L, Overton, J, Reid, J, Shuldiner, A, Beechert, C, Forsythe, C, Fuller, E, Gu, Z, Lattari, M, Lopez, A, Schleicher, T, Padilla, M, Toledo, K, Widom, L, Wolf, S, Pradhan, M, Manoochehri, K, Ulloa, R, Bai, X, Balasubramanian, S, Barnard, L, Blumenfeld, A, Eom, G, Habegger, L, Hawes, A, Khalid, S, Maxwell, E, Salerno, W, Staples, J, Jones, M, Mitnaul, L, Sturgess, R, Healey, C, Yeoman, A, Gunasekera, A, Kooner, P, Kapur, K, Sathyanarayana, V, Kallis, Y, Subhani, J, Harvey, R, Mccorry, R, Rooney, P, Ramanaden, D, Evans, R, Mathialahan, T, Gasem, J, Shorrock, C, Bhalme, M, Southern, P, Tibble, J, Gorard, D, Jones, S, Srivastava, B, Foxton, M, Collins, C, Elphick, D, Karmo, M, Porras-Perez, F, Mendall, M, Yapp, T, Patel, M, Ede, R, Sayer, J, Jupp, J, Fisher, N, Carter, M, Koss, K, Shah, J, Piotrowicz, A, Scott, G, Grimley, C, Gooding, I, Williams, S, Tidbury, J, Lim, G, Cheent, K, Levi, S, Mansour, D, Beckley, M, Hollywood, C, Wong, T, Marley, R, Ramage, J, Gordon, H, Ridpath, J, Ngatchu, T, Bob Grover, V, Shidrawi, R, Abouda, G, Corless, L, Narain, M, Rees, I, Brown, A, Taylor-Robinson, S, Wilkins, J, Grellier, L, Banim, P, Das, D, Heneghan, M, Curtis, H, Matthews, H, Mohammed, F, Aldersley, M, Srirajaskanthan, R, Walker, G, Mcnair, A, Sharif, A, Sen, S, Bird, G, Prince, M, Prasad, G, Kitchen, P, Barnardo, A, Oza, C, Sivaramakrishnan, N, Gupta, P, Shah, A, Evans, C, Saha, S, Pollock, K, Bramley, P, Mukhopadhya, A, Barclay, S, Mcdonald, N, Bathgate, A, Palmer, K, Dillon, J, Rushbrook, S, Przemioslo, R, Mcdonald, C, Millar, A, Tai, C, Mitchell, S, Metcalf, J, Shaukat, S, Ninkovic, M, Shmueli, U, Davis, A, Naqvi, A, Lee, T, Ryder, S, Collier, J, Klass, H, Cramp, M, Sharer, N, Aspinall, R, Ghosh, D, Douds, A, Booth, J, Williams, E, Hussaini, H, Christie, J, Mann, S, Thorburn, D, Marshall, A, Patanwala, I, Ala, A, Maltby, J, Matthew, R, Corbett, C, Vyas, S, Singhal, S, Gleeson, D, Misra, S, Butterworth, J, George, K, Harding, T, Douglass, A, Mitchison, H, Panter, S, Shearman, J, Bray, G, Roberts, M, Butcher, G, Forton, D, Mahmood, Z, Cowan, M, Ch'Ng, C, Rahman, M, Whatley, G, Wesley, E, Mandal, A, Jain, S, Pereira, S, Wright, M, Trivedi, P, Gordon, F, Unitt, E, Palejwala, A, Austin, A, Vemala, V, Grant, A, Higham, A, Brind, A, Mathew, R, Cox, M, Ramakrishnan, S, King, A, Whalley, S, Fraser, J, Thomson, S, Bell, A, Wong, V, Kia, R, Gee, I, Keld, R, Ransford, R, Gotto, J, Millson, C, Cordell HJ, Fryett JJ, Ueno K, Darlay R, Aiba Y, Hitomi Y, Kawashima M, Nishida N, Khor SS, Gervais O, Kawai Y, Nagasaki M, Tokunaga K, Tang R, Shi Y, Li Z, Juran BD, Atkinson EJ, Gerussi A, Carbone M, Asselta R, Cheung A, de Andrade M, Baras A, Horowitz J, Ferreira MAR, Sun D, Jones DE, Flack S, Spicer A, Mulcahy VL, Byan J, Han Y, Sandford RN, Lazaridis KN, Amos CI, Hirschfield GM, Seldin MF, Invernizzi P, Siminovitch KA, Ma X, Nakamura M, Mells GF, PBC Consortia, Canadian PBC Consortium, Chinese PBC Consortium, Italian PBC Study Group, Japan-PBC-GWAS Consortium, US PBC Consortium, UK-PBC Consortium, and Calvaruso V. .
Subjects: Liver Cirrhosis, ALSPAC, ERN RARE-LIVER, Genomic co-localization, Network-based in silico drug efficacy screening, UK-PBC, 0301 basic medicine, Candidate gene, Genome-Wide Association Study, Humans, Liver Cirrhosis, Biliary, Italian PBC Study Group, LD SCORE REGRESSION, Japan-PBC-GWAS Consortium, Genome-wide association study, Locus (genetics), Disease, SUSCEPTIBILITY, PBC, Chronic liver disease, Bioinformatics, GENETIC ASSOCIATION, 1117 Public Health and Health Services, 03 medical and health sciences, 0302 clinical medicine, UK-PBC Consortium, Genotype, Medicine, Genetic association, Science & Technology, Gastroenterology & Hepatology, Hepatology, business.industry, Biliary, Chinese PBC Consortium, 1103 Clinical Sciences, medicine.disease, PBC Consortia, 030104 developmental biology, Meta-analysis, ERN RARE LIVER, 030211 gastroenterology & hepatology, US PBC Consortium, Canadian PBC Consortium, business, Life Sciences & Biomedicine, Human
Abstract: [BACKGROUND & AIMS] Primary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intra-hepatic bile ducts eventually leads to cirrhosis. Many patients have inadequate response to licensed medications, motivating the search for novel therapies. Previous genome-wide association studies (GWAS) and meta-analyses (GWMA) of PBC have identified numerous risk loci for this condition, providing insight into its aetiology. We undertook the largest GWMA of PBC to date, aiming to identify additional risk loci and prioritise candidate genes for in silico drug efficacy screening. [METHODS] We combined new and existing genotype data for 10, 516 cases and 20, 772 controls from five European and two East Asian cohorts. [RESULTS] We identified 56 genome-wide significant loci (20 novel) including 46 in European, 13 in Asian, and 41 in combined cohorts; and a 57th genome-wide significant locus (also novel) in conditional analysis of the European cohorts. Candidate genes at newly identified loci include FCRL3, INAVA, PRDM1, IRF7, CCR6, CD226, and IL12RB1, each having key roles in immunity. Pathway analysis reiterated the likely importance of pattern recognition receptor and TNF signalling, Jak-STAT signalling, and differentiation of TH1 and TH17 cells in the pathogenesis of this disease. Drug efficacy screening identified several medications predicted to be therapeutic in PBC, some well-established in the treatment of other autoimmune disorders. [CONCLUSIONS] This study has identified additional risk loci for PBC, provided a hierarchy of agents that could be trialled in this condition, and emphasised the value of genetic and genomic approaches to drug discovery in complex disorders. [Lay summary] Primary biliary cholangitis (PBC) is a chronic liver disease that eventually leads to cirrhosis. In this study, we analysed genetic information from 10, 516 people with PBC and 20, 772 healthy individuals recruited in Canada, China, Italy, Japan, UK, or USA. We identified several genetic regions associated with PBC. Each of these regions contains several genes. For each region, we used diverse sources of evidence to help us choose the gene most likely to be involved in causing PBC. We used these ‘candidate genes’ to help us identify medications that are currently used for treatment of other conditions, which might also be useful for treatment of PBC., 原発性胆汁性胆管炎のゲノムワイド関連解析 --国際メタ解析による新規疾患感受性遺伝子と治療薬候補の同定--. 京都大学プレスリリース. 2021-06-28.
Published: 2021

16. Spleen stiffness measurement predicts the development of primary hepatocellular carcinoma better than hepatic venous pressure gradient

Author: Antonio Colecchia, Davide Festi, Federico Ravaioli, Giovanni Marasco, G. Silva, Matteo Renzulli, Rita Golfieri, Elton Dajti, Francesco Azzaroli, Benedetta Rossini, Giuseppe Mazzella, Marasco, G, Colecchia, A, Ravaioli, F, Dajti, E, Renzulli, M, Silva, G, Rossini, B, Azzaroli, F, Mazzella, G, Golfieri, R, and Festi, D
Subjects: Pathology, medicine.medical_specialty, medicine.anatomical_structure, Hepatology, business.industry, Hepatocellular carcinoma, Portal venous pressure, spleen stiffness, hepatocellular carcinoma, Gastroenterology, Medicine, Spleen, business, medicine.disease
Published: 2020

17. Fatty liver in pregnancy: a narrative review of two distinct conditions

Author: Lucia Brodosi, Giuseppe Mazzella, Francesco Azzaroli, Giulio Marchesini, Maria Letizia Petroni, Azzaroli, Francesco, Mazzella, Giuseppe, Marchesini, Giulio, Brodosi, Lucia, and Petroni, Maria Letizia
Subjects: nonalcoholic fatty liver disease, Pediatrics, medicine.medical_specialty, HELLP syndrome, Population, metabolic syndrome, Acute fatty liver of pregnancy, Diagnosis, Differential, 03 medical and health sciences, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, Risk Factors, Nonalcoholic fatty liver disease, medicine, Humans, Obesity, education, Pregnancy, education.field_of_study, Hepatology, business.industry, Fatty liver, Age Factors, Pregnancy Outcome, Gastroenterology, ultrasonography, Acute fatty liver, medicine.disease, gestational diabete, Fatty Liver, Pregnancy Complications, Transplantation, Liver, 030220 oncology & carcinogenesis, hellp syndrome, Female, 030211 gastroenterology & hepatology, liver enzyme, pregnancy, Metabolic syndrome, business, fibrosi
Abstract: Introduction: Fatty liver is rather common in pregnancy, occurring in two totally different conditions, i.e. nonalcoholic fatty liver disease (NAFLD) in pregnancy and acute fatty liver of pregnancy (AFLP). The former is a common condition, resulting by chance association because of the epidemics of obesity and the older age of many pregnant women in Western countries; the latter is a rare disease whose pathophysiology is still incompletely understood. Areas covered: We reviewed the evidence-based knowledge on fatty liver in/of pregnancy. For NAFLD, a few large retrospective and prospective studies identify immediate and late risks for both the mother and the fetus. For AFLP, only small retrospective studies are available, indicating that prompt delivery and eventual referral to Liver Units for liver support or transplantation are mandatory to avoid maternal and fetal death. Expert opinion: The number of pregnant women with fatty liver is expected to increase in the next years. Pharmacologic treatment of NAFLD might be postponed, even when new drugs are approved by health authorities for the general population. In the case of AFLP, we need to improve our ability to correctly identify and treat the most severe cases not resolving with delivery.
Published: 2020

18. Spleen stiffness mirrors changes in portal hypertension after successful interferon-free therapy in chronic-hepatitis C virus patients

Author: Luigina Vanessa Alemanni, Davide Festi, Antonio Colecchia, Francesco Azzaroli, Mariarosa Tamè, Giovanni Marasco, Giuseppe Mazzella, Stefano Brillanti, Federico Ravaioli, Elton Dajti, Ravaioli, Federico, Colecchia, Antonio, Dajti, Elton, Marasco, Giovanni, Alemanni, Luigina Vanessa, Tamè, Mariarosa, Azzaroli, Francesco, Brillanti, Stefano, Mazzella, Giuseppe, and Festi, Davide
Subjects: musculoskeletal diseases, medicine.medical_specialty, animal structures, Spleen, Direct-acting antiviral, Direct-acting antivirals, Gastroenterology, Virus, Spleen stiffness measurement, 03 medical and health sciences, 0302 clinical medicine, Chronic hepatitis, Internal medicine, medicine, Retrospective Cohort Study, Advanced chronic liver disease, Clinically significant portal hypertension, Hepatitis C, Non-invasive test, Portal hypertension, Hepatology, skin and connective tissue diseases, business.industry, Interferon free, equipment and supplies, medicine.disease, medicine.anatomical_structure, Non invasive test, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, sense organs, business
Abstract: AIM To investigate changes in spleen stiffness measurements (SSMs) and other non-invasive tests (NITs) after treatment with direct-acting antivirals (DAAs) and identify predictors of SSM change after sustained virological response (SVR). METHODS We retrospectively analysed 146 advanced-chronic liver disease (ACLD) patients treated with DAA with available paired SSM at baseline and SVR24. Liver stiffness (LSM), spleen diameter (SD), platelet count (PLT) and liver stiffness-spleen diameter to platelet ratio score(LSPS) were also investigated. LSM ≥ 21 kPa was used as a cut-off to rule-in clinically significant portal hypertension (CSPH). SSM reduction > 20% from baseline was defined as significant. RESULTS SSM significantly decreased at SVR24, in both patients with and without CSPH; in 44.8% of cases, SSM reduction was > 20%. LSPS significantly improved in the entire cohort at SVR24; SD and PLT changed significantly only in patients without CSPH. LSM significantly decreased in 65.7% of patients and also in 2/3 patients in whom SSM did not decrease. The independent predictor of decreased SSM was median relative change of LSM. CSPH persisted in 54.4% patients after SVR. Delta LSM and baseline SSM were independent factors associated with CSPH persistence. CONCLUSION SSM and other NITs significantly decrease after SVR, although differently according to the patient’s clinical condition. SSM faithfully reflects changes in portal hypertension and could represent a useful NIT for the follow-up of these patients.
Published: 2018

19. A multimedia multilanguage web-based platform can assess and increase the awareness on HCV infection of Pakistani people living in Italy

Author: Stefano Brillanti, Leonardo Frazzoni, Usama Sikandar, Franco Bazzoli, Giuseppe Mazzella, Francesco Azzaroli, Lorenzo Fuccio, Frazzoni L., Sikandar U., Mazzella G., Fuccio L., Bazzoli F., Brillanti S., and Azzaroli F.
Subjects: Male, assessment, Ethnic group, Hepacivirus, educational, computer.software_genre, Rate ratio, Antiviral Agents, 03 medical and health sciences, Health services, 0302 clinical medicine, McNemar's test, Virology, Ethnicity, Prevalence, chronic hepatitis C, hepatitis C viru, Humans, Medicine, Web application, survey, Pakistan, 030212 general & internal medicine, Language preference, Male gender, Internet, Hepatology, Multimedia, Hepatitis C virus, business.industry, Gastroenterology, virus diseases, Hepatitis C, digestive system diseases, Northern italy, Infectious Diseases, Italy, Assessment, Chronic hepatitis C, Survey, 030211 gastroenterology & hepatology, Educational interventions, business, computer
Abstract: Global eradication of Hepatitis C Virus (HCV) is hindered by infection persistence among high-prevalence ethnic groups with insufficient access to care. Educational interventions to raise awareness on HCV have led to identification of submerged HCV cases. Our aim was to evaluate the effectiveness of a web-based platform to assess and raise the awareness of HCV among Pakistani people living in northern Italy. We created a website in Italian and Urdu language (https://survey-hcv6.webnode.it), and shared it to Pakistani people in Emilia-Romagna through Facebook groups. Participants had to fill a 15-item questionnaire on HCV infection, then watch a video on HCV, and respond to the questionnaire again. McNemar's chi-square and negative binomial multivariable regression analysis yielding incidence rate ratio (IRR) were applied. 339 subjects from 600 (57%) participated and filled the baseline questionnaire. The knowledge on HCV infection was scanty. For instance, 32% were not aware of HCV, 42% only knew that HCV infection may be long term, and only 14% knew the access to DAA treatment is provided by the Health Service. Independent predictors of worse knowledge on HCV were male gender (IRR 1.19), low instruction level (IRR 1.26), Urdu language preference (IRR 1.22), past use of intravenous drugs (1.2) and no previous HCV testing (IRR 1.36). The educational video significantly improved the knowledge on HCV among 67 subjects who refilled the questionnaire, as 97% were later aware of HCV, 99% of the long-term duration of HCV infection and 93% of the access to DAAs provided by Italian Health Service. We found a modest level of knowledge on HCV infection among Pakistani people in northern Italy, identifying predictors of worse awareness. We provided a multimedia platform which significantly improved the knowledge on HCV infection. Consequently, this approach might translate into an improved linkage to care.
Published: 2021

20. Chronic non-allergic rhinitis with neutrophils is associated with higher acid exposure time: A pH-impedance monitoring study

Author: F. Torresan, Elisa Liverani, Franco Bazzoli, Maria Chiara Cimatti, Antonio Pirodda, Chiara Pierantoni, A. Ioannou, P. Schiavon, Michela Mancini, Daniele Mandolesi, Francesco Azzaroli, and Roberto De Giorgio
Subjects: Adult, Male, medicine.medical_specialty, Esophageal pH Monitoring, Time Factors, Adolescent, Manometry, Neutrophils, Non-allergic rhinitis, Non-Allergic rhinitis, Disease, Gastroenterology, NO, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Cytology, Throat, Internal medicine, otorhinolaryngologic diseases, Electric Impedance, Medicine, Humans, Reflux disease, Nose, Aged, Rhinitis, AET, Hepatology, business.industry, Reflux, AET, GERD, Non-Allergic rhinitis, Reflux disease, GERD, Middle Aged, medicine.disease, Nasal Mucosa, medicine.anatomical_structure, Logistic Models, Nasal cytology, 030220 oncology & carcinogenesis, Chronic Disease, Multivariate Analysis, Gastroesophageal Reflux, 030211 gastroenterology & hepatology, Female, business
Abstract: Background & Aim Chronic rhinitis, a diffuse disease with a prevalence of 40%, can be classified in allergic (AR) and non-allergic rhinitis (NAR). Nasal cytology allows for the identification of different NAR sub-types according to the inflammatory cell infiltrate. NAR etiopathogenesis is not well clarified and, for NARNE (non-allergic rhinitis with neutrophils) subtype, gastroesophageal reflux disease (GERD) has been suggested as one of the etiopathogenetic factors. Aim of this study is to evaluate the role of GERD in patients with NARNE. Methods Fifty-one consecutive patients referred to our Ear, Nose and Throat (ENT) unit with nasal symptoms and cytology suggestive for NAR, were enrolled in the study. All the patients performed a gastroenterological evaluation, high resolution esophageal manometry and a 24-h pH-Impedance monitoring. Results Twenty-five (49%) patients tested positive at nasal cytology for NARNE. A pathologic pH-impedance was identified in seven patients (28%) with NARNE, as opposed to only one (4%) with different NAR subtypes. Statistical analysis showed that higher acid exposure time (AET) and weaker post nasal drainage were more common in NARNE vs. other NAR patients. Conclusions NARNE strongly correlates with higher AET and refluxes number; thus, NARNE patients should be tested with pH-impedance monitoring in addition to nasal cytology.
Published: 2019

21. Prognostic Value of the Albumin-Bilirubin Grade for the Prediction of Post-Hepatectomy Liver Failure: A Systematic Review and Meta-Analysis

Author: Marco Montagnani, Franco Bazzoli, Antonio Colecchia, Francesco Azzaroli, Davide Festi, Giuseppe Mazzella, Luigina Vanessa Alemanni, Giovanni Marasco, Marasco G., Alemanni L.V., Colecchia A., Festi D., Bazzoli F., Mazzella G., Montagnani M., and Azzaroli F.
Subjects: medicine.medical_specialty, medicine.medical_treatment, MEDLINE, Review, ALBI, PHLF, Gastroenterology, 03 medical and health sciences, hepatectomy, 0302 clinical medicine, Internal medicine, medicine, liver surgery, albumin-bilirubin, business.industry, liver failure, hepatocellular carcinoma, General Medicine, Odds ratio, Publication bias, medicine.disease, Confidence interval, 030220 oncology & carcinogenesis, Meta-analysis, Hepatocellular carcinoma, Medicine, 030211 gastroenterology & hepatology, Liver function, Hepatectomy, business
Abstract: (1) Introduction: Liver resection (LR) for hepatocellular carcinoma (HCC) is often burdened by life-threatening complications, such as post-hepatectomy liver failure (PHLF). The albumin-bilirubin (ALBI) score can accurately evaluate liver function and the long-term prognosis of HCC patients, including PHLF. We aimed to evaluate the diagnostic value of the ALBI grade in predicting PHLF in HCC patients undergoing LR. (2) Methods: MEDLINE, Embase, and Scopus were searched through January 17th, 2021. Studies reporting the ALBI grade and PHLF occurrence in HCC patients undergoing LR were included. The Odds Ratio (OR) prevalence with 95% confidence intervals (CI) was pooled, and the heterogeneity was expressed as I2. The quality of the studies was assessed using QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies). (3) Results: Seven studies met the inclusion criteria and were included in the analysis. A total of 5377 patients who underwent LR for HCC were considered, of whom 718 (13.4%) developed PHLF. Patients with ALBI grades 2 and 3 before LR showed increased rates of PHLF compared to ALBI grade 1 patients. The pooled OR was 2.572 (95% CI, 1.825 to 3.626, p < 0.001), with substantial heterogeneity between the studies (I2 = 69.6%) and no publication bias (Begg’s p = 0.764 and Egger’s p = 0.851 tests). All studies were at a ‘low risk’ or ‘unclear risk’ of bias. Univariate meta-regression analysis showed that heterogeneity was not dependent on the country of study, the age and sex of the participants, the definition of PHLF used, the rate of patients in Child–Pugh class A or undergoing major hepatectomy. (4) Conclusions: In this meta-analysis of published studies, individuals with ALBI grades of 2 and 3 showed increased rates of PHLF compared to ALBI grade 1 patients.
Published: 2021

22. The future of dual therapy for hepatitis C virus

Author: Francesco Azzaroli, Domenico Fiorillo, Giuseppe Mazzella, A. Porro, Marco Montagnani, Francesco Azzaroli, Marco Montagnani, Alberto Porro, Domenico Fiorillo, and Giuseppe Mazzella
Subjects: INTERFERON, Response rate (survey), therapy, business.industry, Ribavirin, Hepatitis C virus, Hepatitis C, Pharmacology, medicine.disease_cause, medicine.disease, DIRECT ACTING ANTIVIRALS, Virology, chemistry.chemical_compound, FUTURE, chemistry, Interferon, ANTIVIRAL, HCV, HEPATITIS C, PEGylation, medicine, Dual therapy, business, medicine.drug
Abstract: ABSTRACT Treatment of hepatitis C is rapidly changing. It began with IFN monotherapy; then the addition of ribavirin doubled the rate of response and pegylation of IFN further improved it. The development of direct-acting antivirals has brought up combinations of even three or more drugs with the aim of reaching the 100% response rate. However, the development of potent direct-acting antivirals with high barrier to resistance gives the possibility of reaching this aim with just two drugs. This review will focus on dual therapy moving on from the past to the near future.
Published: 2014

23. Pretreatment prediction of response to ursodeoxycholic acid in primary biliary cholangitis: development and validation of the UDCA Response Score

Author: Marco Carbone, Alessandra Nardi, Steve Flack, Guido Carpino, Nikoletta Varvaropoulou, Caius Gavrila, Ann Spicer, Jonathan Badrock, Francesca Bernuzzi, Vincenzo Cardinale, Holly F Ainsworth, Michael A Heneghan, Douglas Thorburn, Andrew Bathgate, Rebecca Jones, James M Neuberger, Pier Maria Battezzati, Massimo Zuin, Simon Taylor-Robinson, Maria F Donato, John Kirby, Robert Mitchell-Thain, Annarosa Floreani, Fotios Sampaziotis, Luigi Muratori, Domenico Alvaro, Marco Marzioni, Luca Miele, Fabio Marra, Edoardo Giannini, Eugenio Gaudio, Vincenzo Ronca, Giulia Bonato, Laura Cristoferi, Federica Malinverno, Alessio Gerussi, Deborah D Stocken, Heather J Cordell, Gideon M Hirschfield, Graeme J Alexander, Richard N Sandford, David E Jones, Pietro Invernizzi, George F Mells, Caradog Thomas, Meshbah Rahman, Tom Yapp, Chin Lye Ch'ng, Melanie Harrison, Richard Sturgess, Roman Galaska, Chris Healey, Jessica Whiteman, Marek Czaijkowski, Catherine Gray, Anton Gunasekera, Pranab Gyawli, Purushothaman Premchand, Steven Mann, Keith Elliott, Kapil Kapur, Alan Watson, Graham Foster, Paul Trembling, Javaid Subhani, Rory Harvey, Roger McCorry, Carolyn Adgey, Lucie Hobson, Caroline Mulvaney-Jones, Richard Evans, Thiriloganathan Mathialahan, David Ramanaden, Jaber Gasem, Greta Van Duyvenvoorde, Christopher Shorrock, Katie Seward, Paul Southern, Jeremy Tibble, Ruth Penn, David Gorard, Jane Maiden, Rose Damant, Altaf Palegwala, Susan Jones, Graeme Alexander, George Mells, Richard Sandford, Sunil Dolwani, Martin Prince, Valeria Silvestre, Matthew Foxton, Eleanor Dungca, Harriet Mitchison, Natalie Wheatley, Ian Gooding, Helen Doyle, Mazn Karmo, Melanie Kent, Sushma Saksena, Delyth Braim, Minesh Patel, Susan Lord, Roland Ede, Alison Paton, Andrew Austin, Nicola Lancaster, Joanna Sayer, Andrew Gibbins, Karen Hogben, Chris Hovell, Neil Fisher, Martyn Carter, Konrad Koss, Janine Musselwhite, Florin Muscariu, Andrzej Piotreowicz, Alexandra McKay, Charles Grimley, David Neal, Lai Ting Tan, Guan Lim, Jacqueline Brighton, Carole Foale, Aftab Ala, Athar Saeed, Kerry Flahive, Gordon Wood, Paula Townshend, Chris Ford, Jonathan Brown, Jean Kordula, Jane Bowles, Mark Wilkinson, Caroline Palmer, John Ramage, Harriet Gordon, James Featherstone, Jo Ridpath, Theodore Ngatchu, Sass Levi, Syed Shaukat, Joy Sadeghian, Ray Shidrawi, Bronwen Williams, George Abouda, Sarah Jones, Claire Duggan, Abigail Hynes, Mark Narain, Ian Rees, Imroz Salam, Mary Crossey, Ashley Brown, Carolyn MacNicol, Simon Williams, Elva Wilhelmsen, Paul Banim, Parizade Raymode, Andrew Chilton, Debasish Das, Hye-Jeong Lee, Howard Curtis, Michael Heneghan, Markus Gess, Emma Durant, IM Drake, Rebecca Bishop, Mervyn Davies, Mark Aldersley, Noma Ncube, Alistair McNair, Raj Srirajaskanthan, Sambit Sen, Rebecca Casey, George Bird, Mike Mendall, Caroline Cowley, Adrian Barnardo, Paul Kitchen, Kevin Yoong, Kelly Amore, Dawn Sirdefield, Jacky Orpe, Ray Mathew, George MacFaul, Aruna Wrigth, Amir Shah, Chris Evans, Janie Keggans, Bridget Bird, Gwen Baxter, Subrata Saha, Katharine Pollock, Maggie Hughes, Peter Bramley, Emma Grieve, Karin Young, Andrew Fraser, Ashis Mukhopadhya, Kate Ocker, Peter Mills, Francis Hines, Chris Shallcross, Joy Wilkins, Leonie Grellier, Stewart Campbell, Kirsty Martin, Caron Innes, Alan Shepherd, Simon Rushbrook, Talal Valliani, Robert Przemioslo, Helen Fairlamb, Chris Macdonald, Anne Eastick, Jane Metcalf, Elizabeth Tanqueray, Udi Shmueli, Becky Holbrook, Andrew Davis, Julie Browning, Asifabbas Naqvi, Kirsten Walker, Tom Lee, Juliette Verheyden, Susan Slininger, Stephen D Ryder, Roger Chapman, Jane Collier, Denise O'Donnell, Lizzie Stafford, Kate Williamson, Linda Kent, Howard Klass, Mary Ninkovic, Linda March, Matthew Cramp, Diane Simpson, Christine Dickson, Nicholas Sharer, Maria Hayes, Patrick Goggin, Mary Quinne, Sallyanne Pearson, Barbara Hoeroldt, Linda Jones, Alice Wright, Jonathan Booth, Alison Loftus, George Lipscomb, Hannah Dewhurst, Emma Gunter, Earl Williams, Anna Fouracres, Liz Farrington, Lyn Graves, Hyder Hussaini, Bill Stableforth, Suzie Marriott, Reuben Ayres, Marina Leoni, Andrew Burroughs, Eileen Marshall, David Tyrer, Kate Martin, Martin Lombard, Imran Patanwala, Lola Dali-Kemmery, Victoria Lambourne, Julia Maltby, Samir Vyas, Julie Colley, Bal Shinder, Saket Singhal, Jayne Jones, Marisa Mills, Dermot Gleeson, Mandy Carnahan, Jeff Butterworth, Kerenza Boulton, Natalie Taylor, Keith George, Tim Harding, Julie Tregonning, Andrew Douglass, Carly Brown, Gayle Clifford, Simon Panter, Denise Gocher, Jeremy Shearman, Gary Bray, Maria Hamilton, Graham Butcher, Daniel Forton, John Mclindon, Janette Curtis, Debashis Das, Tracey Shewan, Matthew Cowan, Gregory Whatley, Mariam Nasseri, Bob Grover, Nurani Sivaramakrishnan, Samantha Ducker, Kathryn Houghton, David Jones, Laura Griffiths, Sherill Tripoli, Maxton Pitcher, Ervin Shpuza, Nikki White, Deb Ghosh, Andrew Douds, Marie Green, Matthew Brookes, Lourdes Cumlat, Voi Shim Wong, Karen Warner, Kimberley Netherton, Adtya Mandal, Snjiv Jain, Hemant Gupta, Pradeep Sanghi, Steve Pereira, James Neuberger, Bridget Gunson, Gideon Hirschfield, Reina Teegan Lim, Susan Gallagher, Darren Clement, Alison Brind, Gill Watts, Mcdonald Mupudzi, Mark Wright, Jane Gitahi, Fiona Gordon, Denis Gocher, Esther Unitt, Hilary Pateman, Sally Batham, Toby Delahooke, Allister Grant, Jill Conder, Andrew Higham, Mark Cox, Lynn O'Donohoe, Lynn Currie, Alistair King, Metod Oblak, Carole Collins, Simon Whalley, Marie Quinn, Yolanda Baird, Isobel Amey, Jocelyn Fraser, Andy Li, Donna Cotterill, Andrew Bell, Amit Singhal, Ian Gee, Sandra Greer, Yeng Ang, Rupert Ransford, Joanna Allison, James Gotto, Simon Dyer, Helen Sweeting, Charles Millson, Giancarlo Labbadia, Maria Consiglia Bragazzi, Pietro Andreone, Francesco Azzaroli, Andrea Galli, Mirko Tarocchi, Antonio Gasbarrini, Antonio Grieco, Giuseppe Marrone, Maria Francesca Donato, Luca Valenti, Luca Maroni, Cristina Rigamonti, Antonino Picciotto, Carbone, M, Nardi, A, Flack, S, Carpino, G, Varvaropoulou, N, Gavrila, C, Spicer, A, Badrock, J, Bernuzzi, F, Cardinale, V, Ainsworth, H, Heneghan, M, Thorburn, D, Bathgate, A, Jones, R, Neuberger, J, Battezzati, P, Zuin, M, Taylor-Robinson, S, Donato, M, Kirby, J, Mitchell-Thain, R, Floreani, A, Sampaziotis, F, Muratori, L, Alvaro, D, Marzioni, M, Miele, L, Marra, F, Giannini, E, Gaudio, E, Ronca, V, Bonato, G, Cristoferi, L, Malinverno, F, Gerussi, A, Stocken, D, Cordell, H, Hirschfield, G, Alexander, G, Sandford, R, Jones, D, Invernizzi, P, Mells, G, Thomas, C, Rahman, M, Yapp, T, Lye Ch'ng, C, Harrison, M, Sturgess, R, Galaska, R, Healey, C, Whiteman, J, Czaijkowski, M, Gray, C, Gunasekera, A, Gyawli, P, Premchand, P, Mann, S, Elliott, K, Kapur, K, Watson, A, Foster, G, Trembling, P, Subhani, J, Harvey, R, Mccorry, R, Adgey, C, Hobson, L, Mulvaney-Jones, C, Evans, R, Mathialahan, T, Ramanaden, D, Gasem, J, Van Duyvenvoorde, G, Shorrock, C, Seward, K, Southern, P, Tibble, J, Penn, R, Gorard, D, Maiden, J, Damant, R, Palegwala, A, Jones, S, Dolwani, S, Prince, M, Silvestre, V, Foxton, M, Dungca, E, Mitchison, H, Wheatley, N, Gooding, I, Doyle, H, Karmo, M, Kent, M, Saksena, S, Braim, D, Patel, M, Lord, S, Ede, R, Paton, A, Austin, A, Lancaster, N, Sayer, J, Gibbins, A, Hogben, K, Hovell, C, Fisher, N, Carter, M, Koss, K, Musselwhite, J, Muscariu, F, Piotreowicz, A, Mckay, A, Grimley, C, Neal, D, Ting Tan, L, Lim, G, Brighton, J, Foale, C, Ala, A, Saeed, A, Flahive, K, Wood, G, Townshend, P, Ford, C, Brown, J, Kordula, J, Bowles, J, Wilkinson, M, Palmer, C, Ramage, J, Gordon, H, Featherstone, J, Ridpath, J, Ngatchu, T, Levi, S, Shaukat, S, Sadeghian, J, Shidrawi, R, Williams, B, Abouda, G, Duggan, C, Hynes, A, Narain, M, Rees, I, Salam, I, Crossey, M, Brown, A, Macnicol, C, Williams, S, Wilhelmsen, E, Banim, P, Raymode, P, Chilton, A, Das, D, Lee, H, Curtis, H, Gess, M, Durant, E, Drake, I, Bishop, R, Davies, M, Aldersley, M, Ncube, N, Mcnair, A, Srirajaskanthan, R, Sen, S, Casey, R, Bird, G, Mendall, M, Cowley, C, Barnardo, A, Kitchen, P, Yoong, K, Amore, K, Sirdefield, D, Orpe, J, Mathew, R, Macfaul, G, Wrigth, A, Shah, A, Evans, C, Keggans, J, Bird, B, Baxter, G, Saha, S, Pollock, K, Hughes, M, Bramley, P, Grieve, E, Young, K, Fraser, A, Mukhopadhya, A, Ocker, K, Mills, P, Hines, F, Shallcross, C, Wilkins, J, Grellier, L, Campbell, S, Martin, K, Innes, C, Shepherd, A, Rushbrook, S, Valliani, T, Przemioslo, R, Fairlamb, H, Macdonald, C, Eastick, A, Metcalf, J, Tanqueray, E, Shmueli, U, Holbrook, B, Davis, A, Browning, J, Naqvi, A, Walker, K, Lee, T, Verheyden, J, Slininger, S, Ryder, S, Chapman, R, Collier, J, O'Donnell, D, Stafford, L, Williamson, K, Kent, L, Klass, H, Ninkovic, M, March, L, Cramp, M, Simpson, D, Dickson, C, Sharer, N, Hayes, M, Goggin, P, Quinne, M, Pearson, S, Hoeroldt, B, Jones, L, Wright, A, Booth, J, Loftus, A, Lipscomb, G, Dewhurst, H, Gunter, E, Williams, E, Fouracres, A, Farrington, L, Graves, L, Hussaini, H, Stableforth, B, Marriott, S, Ayres, R, Leoni, M, Burroughs, A, Marshall, E, Tyrer, D, Lombard, M, Patanwala, I, Dali-Kemmery, L, Lambourne, V, Maltby, J, Vyas, S, Colley, J, Shinder, B, Singhal, S, Jones, J, Mills, M, Gleeson, D, Carnahan, M, Butterworth, J, Boulton, K, Taylor, N, George, K, Harding, T, Tregonning, J, Douglass, A, Brown, C, Clifford, G, Panter, S, Gocher, D, Shearman, J, Bray, G, Hamilton, M, Butcher, G, Forton, D, Mclindon, J, Curtis, J, Shewan, T, Cowan, M, Whatley, G, Nasseri, M, Grover, B, Sivaramakrishnan, N, Ducker, S, Houghton, K, Griffiths, L, Tripoli, S, Pitcher, M, Shpuza, E, White, N, Ghosh, D, Douds, A, Green, M, Brookes, M, Cumlat, L, Wong, V, Warner, K, Netherton, K, Mandal, A, Jain, S, Gupta, H, Sanghi, P, Pereira, S, Gunson, B, Lim, R, Gallagher, S, Clement, D, Brind, A, Watts, G, Mupudzi, M, Wright, M, Gitahi, J, Gordon, F, Unitt, E, Pateman, H, Batham, S, Delahooke, T, Grant, A, Conder, J, Higham, A, Cox, M, O'Donohoe, L, Currie, L, King, A, Oblak, M, Collins, C, Whalley, S, Quinn, M, Baird, Y, Amey, I, Fraser, J, Li, A, Cotterill, D, Bell, A, Singhal, A, Gee, I, Greer, S, Ang, Y, Ransford, R, Allison, J, Gotto, J, Dyer, S, Sweeting, H, Millson, C, Labbadia, G, Bragazzi, M, Andreone, P, Azzaroli, F, Galli, A, Tarocchi, M, Gasbarrini, A, Grieco, A, Marrone, G, Valenti, L, Maroni, L, Rigamonti, C, Picciotto, A, Sampaziotis, Fotios [0000-0003-0812-7586], Sandford, Richard [0000-0002-7437-0560], Apollo - University of Cambridge Repository, Carbone, Marco, Nardi, Alessandra, Flack, Steve, Carpino, Guido, Varvaropoulou, Nikoletta, Gavrila, Caiu, Spicer, Ann, Badrock, Jonathan, Bernuzzi, Francesca, Cardinale, Vincenzo, Ainsworth, Holly F, Heneghan, Michael A, Thorburn, Dougla, Bathgate, Andrew, Jones, Rebecca, Neuberger, James M, Battezzati, Pier Maria, Zuin, Massimo, Taylor-Robinson, Simon, Donato, Maria F, Kirby, John, Mitchell-Thain, Robert, Floreani, Annarosa, Sampaziotis, Fotio, Muratori, Luigi, Alvaro, Domenico, Marzioni, Marco, Miele, Luca, Marra, Fabio, Giannini, Edoardo, Gaudio, Eugenio, Ronca, Vincenzo, Bonato, Giulia, Cristoferi, Laura, Malinverno, Federica, Gerussi, Alessio, Stocken, Deborah D, Cordell, Heather J, Hirschfield, Gideon M, Alexander, Graeme J, Sandford, Richard N, Jones, David E, Invernizzi, Pietro, Mells, George F, Thomas, Caradog, Rahman, Meshbah, Yapp, Tom, Lye Ch'ng, Chin, Harrison, Melanie, Sturgess, Richard, Galaska, Roman, Healey, Chri, Whiteman, Jessica, Czaijkowski, Marek, Gray, Catherine, Gunasekera, Anton, Gyawli, Pranab, Premchand, Purushothaman, Mann, Steven, Elliott, Keith, Kapur, Kapil, Watson, Alan, Foster, Graham, Trembling, Paul, Subhani, Javaid, Harvey, Rory, McCorry, Roger, Adgey, Carolyn, Hobson, Lucie, Mulvaney-Jones, Caroline, Evans, Richard, Mathialahan, Thiriloganathan, Ramanaden, David, Gasem, Jaber, Van Duyvenvoorde, Greta, Shorrock, Christopher, Seward, Katie, Southern, Paul, Tibble, Jeremy, Penn, Ruth, Gorard, David, Maiden, Jane, Damant, Rose, Palegwala, Altaf, Jones, Susan, Alexander, Graeme, Mells, George, Sandford, Richard, Dolwani, Sunil, Prince, Martin, Silvestre, Valeria, Foxton, Matthew, Dungca, Eleanor, Mitchison, Harriet, Wheatley, Natalie, Gooding, Ian, Doyle, Helen, Karmo, Mazn, Kent, Melanie, Saksena, Sushma, Braim, Delyth, Patel, Minesh, Lord, Susan, Ede, Roland, Paton, Alison, Austin, Andrew, Lancaster, Nicola, Sayer, Joanna, Gibbins, Andrew, Hogben, Karen, Hovell, Chri, Fisher, Neil, Carter, Martyn, Koss, Konrad, Musselwhite, Janine, Muscariu, Florin, Piotreowicz, Andrzej, McKay, Alexandra, Grimley, Charle, Neal, David, Ting Tan, Lai, Lim, Guan, Brighton, Jacqueline, Foale, Carole, Ala, Aftab, Saeed, Athar, Flahive, Kerry, Wood, Gordon, Townshend, Paula, Ford, Chri, Brown, Jonathan, Kordula, Jean, Bowles, Jane, Wilkinson, Mark, Palmer, Caroline, Ramage, John, Gordon, Harriet, Featherstone, Jame, Ridpath, Jo, Ngatchu, Theodore, Levi, Sa, Shaukat, Syed, Sadeghian, Joy, Shidrawi, Ray, Williams, Bronwen, Abouda, George, Jones, Sarah, Duggan, Claire, Hynes, Abigail, Narain, Mark, Rees, Ian, Salam, Imroz, Crossey, Mary, Brown, Ashley, MacNicol, Carolyn, Williams, Simon, Wilhelmsen, Elva, Banim, Paul, Raymode, Parizade, Chilton, Andrew, Das, Debasish, Lee, Hye-Jeong, Curtis, Howard, Heneghan, Michael, Gess, Marku, Durant, Emma, Drake, I.M., Bishop, Rebecca, Davies, Mervyn, Aldersley, Mark, Ncube, Noma, McNair, Alistair, Srirajaskanthan, Raj, Sen, Sambit, Casey, Rebecca, Bird, George, Mendall, Mike, Cowley, Caroline, Barnardo, Adrian, Kitchen, Paul, Yoong, Kevin, Amore, Kelly, Sirdefield, Dawn, Orpe, Jacky, Mathew, Ray, MacFaul, George, Wrigth, Aruna, Shah, Amir, Evans, Chri, Keggans, Janie, Bird, Bridget, Baxter, Gwen, Saha, Subrata, Pollock, Katharine, Hughes, Maggie, Bramley, Peter, Grieve, Emma, Young, Karin, Fraser, Andrew, Mukhopadhya, Ashi, Ocker, Kate, Mills, Peter, Hines, Franci, Shallcross, Chri, Wilkins, Joy, Grellier, Leonie, Campbell, Stewart, Martin, Kirsty, Innes, Caron, Shepherd, Alan, Rushbrook, Simon, Valliani, Talal, Przemioslo, Robert, Fairlamb, Helen, Macdonald, Chri, Eastick, Anne, Metcalf, Jane, Tanqueray, Elizabeth, Shmueli, Udi, Holbrook, Becky, Davis, Andrew, Browning, Julie, Naqvi, Asifabba, Walker, Kirsten, Lee, Tom, Verheyden, Juliette, Slininger, Susan, Ryder, Stephen D, Chapman, Roger, Collier, Jane, O'Donnell, Denise, Stafford, Lizzie, Williamson, Kate, Kent, Linda, Klass, Howard, Ninkovic, Mary, March, Linda, Cramp, Matthew, Simpson, Diane, Dickson, Christine, Sharer, Nichola, Hayes, Maria, Goggin, Patrick, Quinne, Mary, Pearson, Sallyanne, Hoeroldt, Barbara, Jones, Linda, Wright, Alice, Booth, Jonathan, Loftus, Alison, Lipscomb, George, Dewhurst, Hannah, Gunter, Emma, Williams, Earl, Fouracres, Anna, Farrington, Liz, Graves, Lyn, Hussaini, Hyder, Stableforth, Bill, Marriott, Suzie, Ayres, Reuben, Leoni, Marina, Burroughs, Andrew, Marshall, Eileen, Tyrer, David, Martin, Kate, Lombard, Martin, Patanwala, Imran, Dali-Kemmery, Lola, Lambourne, Victoria, Maltby, Julia, Vyas, Samir, Colley, Julie, Shinder, Bal, Singhal, Saket, Jones, Jayne, Mills, Marisa, Gleeson, Dermot, Carnahan, Mandy, Butterworth, Jeff, Boulton, Kerenza, Taylor, Natalie, George, Keith, Harding, Tim, Tregonning, Julie, Douglass, Andrew, Brown, Carly, Clifford, Gayle, Panter, Simon, Gocher, Denise, Shearman, Jeremy, Bray, Gary, Hamilton, Maria, Butcher, Graham, Forton, Daniel, Mclindon, John, Curtis, Janette, Das, Debashi, Shewan, Tracey, Cowan, Matthew, Whatley, Gregory, Nasseri, Mariam, Grover, Bob, Sivaramakrishnan, Nurani, Ducker, Samantha, Houghton, Kathryn, Jones, David, Griffiths, Laura, Tripoli, Sherill, Pitcher, Maxton, Shpuza, Ervin, White, Nikki, Ghosh, Deb, Douds, Andrew, Green, Marie, Brookes, Matthew, Cumlat, Lourde, Wong, Voi Shim, Warner, Karen, Netherton, Kimberley, Mandal, Adtya, Jain, Snjiv, Gupta, Hemant, Sanghi, Pradeep, Pereira, Steve, Neuberger, Jame, Gunson, Bridget, Hirschfield, Gideon, Lim, Reina Teegan, Gallagher, Susan, Clement, Darren, Brind, Alison, Watts, Gill, Mupudzi, Mcdonald, Wright, Mark, Gitahi, Jane, Gordon, Fiona, Gocher, Deni, Unitt, Esther, Pateman, Hilary, Batham, Sally, Delahooke, Toby, Grant, Allister, Conder, Jill, Higham, Andrew, Cox, Mark, O'Donohoe, Lynn, Currie, Lynn, King, Alistair, Oblak, Metod, Collins, Carole, Whalley, Simon, Quinn, Marie, Baird, Yolanda, Amey, Isobel, Fraser, Jocelyn, Li, Andy, Cotterill, Donna, Bell, Andrew, Singhal, Amit, Gee, Ian, Greer, Sandra, Ang, Yeng, Ransford, Rupert, Allison, Joanna, Gotto, Jame, Dyer, Simon, Sweeting, Helen, Millson, Charle, Labbadia, Giancarlo, Bragazzi, Maria Consiglia, Andreone, Pietro, Azzaroli, Francesco, Galli, Andrea, Tarocchi, Mirko, Gasbarrini, Antonio, Grieco, Antonio, Marrone, Giuseppe, Donato, Maria Francesca, Valenti, Luca, Maroni, Luca, Rigamonti, Cristina, Picciotto, Antonino, and Medical Research Council (MRC)
Subjects: Male, Cholagogues and Choleretics, Cirrhosis, medicine.medical_treatment, PROGRESSION, Liver transplantation, PHENOTYPE, Gastroenterology, UDCA, 0302 clinical medicine, Primary biliary cirrhosis, Risk Factors, Medicine, Age of Onset, CIRRHOSIS, TREE, OUTCOMES, Settore MED/12 - Gastroenterologia, medicine.diagnostic_test, Liver Cirrhosis, Biliary, Ursodeoxycholic Acid, Area under the curve, URSODIOL, Middle Aged, Ursodeoxycholic acid, Treatment Outcome, Primary biliary cholangitis, ursodeoxycholic acid, 030220 oncology & carcinogenesis, Liver biopsy, Area Under Curve, 030211 gastroenterology & hepatology, Female, Life Sciences & Biomedicine, medicine.drug, medicine.medical_specialty, CONTROLLED-TRIAL, Hepatology, Decision Support Techniques, Time-to-Treatment, Biliary injury, 03 medical and health sciences, Internal medicine, Humans, Transaminases, Science & Technology, Gastroenterology & Hepatology, Italian PBC Study Group and the UK–PBC Consortium, business.industry, Bilirubin, medicine.disease, Alkaline Phosphatase, ROC Curve, CELLS, Linear Models, business
Abstract: Background: Treatment guidelines recommend a stepwise approach to primary biliary cholangitis: all patients begin treatment with ursodeoxycholic acid (UDCA) monotherapy and those with an inadequate biochemical response after 12 months are subsequently considered for second-line therapies. However, as a result, patients at the highest risk can wait the longest for effective treatment. We determined whether UDCA response can be accurately predicted using pretreatment clinical parameters. Methods: We did logistic regression analysis of pretreatment variables in a discovery cohort of patients in the UK with primary biliary cholangitis to derive the best-fitting model of UDCA response, defined as alkaline phosphatase less than 1Â·67 times the upper limit of normal (ULN), measured after 12 months of treatment with UDCA. We validated the model in an external cohort of patients with primary biliary cholangitis and treated with UDCA in Italy. Additionally, we assessed correlations between model predictions and key histological features, such as biliary injury and fibrosis, on liver biopsy samples. Findings: 2703 participants diagnosed with primary biliary cholangitis between Jan 1, 1998, and May 31, 2015, were included in the UK-PBC cohort for derivation of the model. The following pretreatment parameters were associated with lower probability of UDCA response: higher alkaline phosphatase concentration (p
Published: 2018

24. Noninvasive Assessment of Portal Hypertension in Advanced Chronic Liver Disease: An Update

Author: Davide Festi, Francesco Azzaroli, Federico Ravaioli, Giuseppe Mazzella, Andrea Lisotti, Marco Montagnani, Ravaioli, Federico, Montagnani, Marco, Lisotti, Andrea, Festi, Davide, Mazzella, Giuseppe, and Azzaroli, Francesco
Subjects: medicine.medical_specialty, indocyanine green, Portal venous pressure, MEDLINE, Review Article, Newly diagnosed, Chronic liver disease, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine, lcsh:RC799-869, elastometric techniques, ultrasonography, endoscopy, serum fibrosis markers, Baveno criteria, Hepatology, medicine.diagnostic_test, business.industry, Gastroenterology, Advanced chronic liver disease, Portal hypertension, Gold standard (test), medicine.disease, Endoscopy, chemistry, Portal hypertension, lcsh:Diseases of the digestive system. Gastroenterology, 030211 gastroenterology & hepatology, Radiology, HVPG, business, Indocyanine green
Abstract: The assessment of portal hypertension is a relevant step in the evaluation of newly diagnosed advanced chronic liver disease (ACLD). The current gold standard includes the invasive evaluation of hepatic venous pressure gradient (HVPG) and endoscopy. However, noninvasive or minimally invasive techniques to assess portal hypertension have been proposed and well established. In the present manuscript, we review clinical studies on the use of noninvasive or minimally invasive techniques to assess portal hypertension in ACLD patients.
Published: 2018

25. P.09.6 IL28 POLYMORPHISM AND HCC DEVELOPMENT AFTER DAAS FOR CHRONIC HEPATITIS C

Author: Giuseppe Mazzella, F. Bazzoli, Federico Ravaioli, M.L. Bacchi Reggiani, A. Porro, Davide Festi, A. Simili, Francesco Azzaroli, Simili, A., Mazzella, G., Ravaioli, F., Festi, D., Reggiani, M.L. Bacchi, Porro, A., Bazzoli, F., and Azzaroli, F.
Subjects: medicine.medical_specialty, Hepatology, business.industry, IL28, Gastroenterology, DAAS, Hepatitis C, medicine.disease, Chronic hepatitis, Polymorphism (computer science), Internal medicine, HEPATITIS C, Medicine, business
Published: 2018

26. SAT-427-The role of liver and spleen stiffness measurement in predicting hepatic decompensation after HCV eradication with direct antiviral agents therapy

Author: Mariarosa Tamè, Federico Ravaioli, Maria Letizia Bacchi Reggiani, Antonio Colecchia, Stefano Brillanti, Davide Festi, Francesco Azzaroli, Elton Dajti, Giuseppe Mazzella, Giovanni Marasco, and Luigina Vanessa Alemanni
Subjects: medicine.medical_specialty, medicine.anatomical_structure, Hepatology, business.industry, Internal medicine, medicine, Spleen, business, Gastroenterology, Hepatic decompensation
Published: 2019

27. SAT-225-The risk of hepatic decompensation is reduced, but not abolished after direct-acting antivirals: The role of portal hypertension

Author: Maria Letizia Bacchi Reggiani, Mariarosa Tamè, Francesco Azzaroli, Giovanni Marasco, Elton Dajti, Davide Festi, Antonio Colecchia, Stefano Brillanti, Giuseppe Mazzella, Luigina Vanessa Alemanni, and Federico Ravaioli
Subjects: medicine.medical_specialty, Hepatology, business.industry, Internal medicine, medicine, Cardiology, Portal hypertension, medicine.disease, DIRECT ACTING ANTIVIRALS, business, Hepatic decompensation
Published: 2019

28. Increased portal pressure is associated with elevated liver enzymes during pregnancy: the role of doppler-ultrasound and liver stiffness measurement

Author: A. Perolo, Giuseppe Mazzella, Elton Dajti, Carla Serra, A. Farina, E. Tiratterra, Francesco Azzaroli, Marco Montagnani, Federico Ravaioli, V. Gabusi, and Cristina Felicani
Subjects: Pregnancy, medicine.medical_specialty, Hepatology, business.industry, Portal venous pressure, Gastroenterology, Elevated liver enzymes, medicine.disease, Liver stiffness, Internal medicine, medicine, Cardiology, Doppler ultrasound, business
Published: 2019

29. The impact of assisted reproductive technology and chorionicity in twin pregnancies complicated by obstetric cholestasis

Author: Antonio Farina, T. Arcangeli, Ginevra Salsi, Nicola Rizzo, Maria Letizia Bacchi-Reggiani, Aly Youssef, Federica Bellussi, G. Pacella, Tullio Ghi, Eleonora Porcu, Francesco Azzaroli, Giuseppe Mazzella, Giuseppina Pacella, Ginevra Salsi, Tiziana Arcangeli, Aly Youssef, Antonio Farina, Maria Letizia Bacchi-Reggiani, Federica Bellussi, Giuseppe Mazzella, Francesco Azzaroli, Eleonora Porcu, Nicola Rizzo, and Tullio Ghi
Subjects: Adult, medicine.medical_specialty, Reproductive Techniques, Assisted, medicine.medical_treatment, Twins, Cholestasis, Intrahepatic, 03 medical and health sciences, 0302 clinical medicine, Obstetrics and gynaecology, Pregnancy, medicine, Humans, Twin Pregnancy, Retrospective Studies, Gynecology, 030219 obstetrics & reproductive medicine, Assisted reproductive technology, business.industry, Obstetrics, Obstetrics and Gynecology, Retrospective cohort study, Obstetric Cholestasis, medicine.disease, Pregnancy Complications, Italy, Pediatrics, Perinatology and Child Health, Cohort, Pregnancy, Twin, Population study, 030211 gastroenterology & hepatology, Female, business, twin pregnancies, obstetric cholestasis,chorionicity, assisted reproductive technology
Abstract: Objective: To assess in a cohort of twin pregnancies the prevalence of obstetric cholestasis (OC) and its correlation with the type of conception and chorionicity.Methods: A retrospective cohort study including all the twin pregnancies delivered between 2005 and 2013 at our University Hospital was carried out. In the study population, the prevalence of OC was investigated in relationship to the impact of assisted reproductive technology (ART) and of chorionicity.Results: Overall, 569 twin pregnancies were included in the study population. Among those complicated by OC, the rate of ART was 3-fold higher (OR 3.4, 95% CI 1.2–9.5, p = 0.02), whereas the rate of dichorionicity did not differ significantly (OR 1.6, 95% CI 0.3–7.9, p = 0.53).Conclusion: The risk of developing OC seems to be significantly higher among twin pregnancies obtained after ART in comparison with those conceived spontaneously.
Published: 2016

30. Severe hypernatremia as a predictor of mortality after percutaneous endoscopic gastrostomy (PEG) placement

Author: Nicole Brighi, Leonardo Henry Eusebi, Franco Bazzoli, Francesco Azzaroli, G. Gibiino, Guglielmo Altimari, Andrea Lisotti, Alessandra Caponi, Rosangela Muratori, Pietro Fusaroli, Muratori, Rosangela, Lisotti, Andrea, Fusaroli, Pietro, Caponi, Alessandra, Gibiino, Giulia, Eusebi, Leonardo Henry, Azzaroli, Francesco, Brighi, Nicole, Altimari, Guglielmo, and Bazzoli, Franco
Subjects: Male, Palliative care, Survival, medicine.medical_treatment, Comorbidity, Kaplan-Meier Estimate, 0302 clinical medicine, Risk Factors, Percutaneous endoscopic gastrostomy, Neoplasms, 030212 general & internal medicine, Cancer, Aged, 80 and over, Gastrostomy, education.field_of_study, Hypernatremia, Mortality rate, Hazard ratio, Gastroenterology, Neurodegenerative Diseases, Dysphagia, Stroke, C-Reactive Protein, Italy, 030211 gastroenterology & hepatology, Female, medicine.medical_specialty, Population, 03 medical and health sciences, Enteral Nutrition, Internal medicine, medicine, Humans, education, Aged, Proportional Hazards Models, Retrospective Studies, Hepatology, business.industry, Odds ratio, medicine.disease, Surgery, Logistic Models, ROC Curve, Multivariate Analysis, Quality of Life, Dementia, business, Swallowing disorder
Abstract: Background: Percutaneous endoscopic gastrostomy is the preferred option for providing enteral nutrition, allowing for an improvement in survival and quality of life. Aim: To evaluate risk factors for early and delayed mortality after gastrostomy placement. Methods: A single-center retrospective analysis of a prospectively-collected database including all patients undergoing gastrostomy placement for enteral nutrition was performed. Two operators performed all the procedures according to the most recent guidelines. Results: Analysis included data on 438 patients [178 male; 80.5 (72-86) year-old]. Indications for PEG were stroke (34.0%), dementia (31.3%), neurodegenerative disorders (18.5%), coma (9.1%) and cancer (7.1%). No periprocedural adverse events was observed. Mean survival was 14.6. ±. 3.4. months; 1-month and 3-month mortality rates were 4.0% and 8.1%, respectively. Severe hypernatremia (≥150. mmol/L) was independently related to 1-month mortality (odds ratio 25.4; P < 0.0001), while C-reactive protein level. >. 4.3. mg/dL was independently related to 3-month mortality (odds ratio 5.3; P = 0.003). Kaplan-Meier and Cox-regression analysis identified male gender (hazard ratio 2.32; P = 0.0002), severe hypernatremia (hazard ratio 4.3; P < 0.0001), C-reactive protein. >. 4.3. mg/dL (hazard ratio 3.5; P = 0.0014), leukocytosis (hazard ratio 1.97; P = 0.0036) and presence of underlying malignancy (hazard ratio 2.4; P = 0.0013) as independent risk factors for long-term mortality. Discussion: Presence of severe hypernatremia and increased C-reactive protein levels were strongly correlated with early and delayed mortality in our population. Studies are necessary to understand whether correcting underlying dehydration and inflammation further improves patients' outcomes.
Published: 2017

31. IL28 polymorphism and HCC after DAAs for chronic hepatitis C

Author: F. Davide, A. Porro, Franco Bazzoli, Francesco Azzaroli, Maria Letizia Bacchi-Reggiani, Giuseppe Mazzella, A. Simili, Federico Ravaioli, Simili, A., Mazzella, G., Ravaioli, F., Davide, F., Bacchi-Reggiani, M.L., Porro, A., Bazzoli, F., and Azzaroli, F.
Subjects: medicine.medical_specialty, Hepatology, Chronic hepatitis, Polymorphism (materials science), business.industry, Internal medicine, IL28, Gastroenterology, medicine, HCC, business, DAA
Published: 2018

32. FRI-290-The role of bile acids profile and insulin reistance for the prediction of gallstone disease in a prospective cohort of blood donors

Author: Patrizia Simoni, Franco Bazzoli, Francesco Azzaroli, Federico Ravaioli, Elton Dajti, A. Porro, Davide Festi, Silvia Spinozzi, Franco Placido, Giuseppe Mazzella, R. Arena, Cecilia Camborata, Aldo Roda, Marco Montagnani, Annarita Belardinelli, and Rocco Maurizio Zagari
Subjects: medicine.medical_specialty, Hepatology, business.industry, Internal medicine, Insulin, medicine.medical_treatment, medicine, Disease, Prospective cohort study, business, Gastroenterology
Published: 2019

33. P.01.27 PROTON PUMP INHIBITOR THERAPY IMPROVES BOTH NASAL SYMPTOMS AND CYTOLOGY IN PATIENTS WITH NON-ALLERGIC RHINITIS WITH NEUTROPHILS

Author: Francesco Azzaroli, Elisa Liverani, A. Ioannou, P. Schiavon, F. Bazzoli, Daniele Mandolesi, F. Torresan, and Antonio Pirodda
Subjects: medicine.medical_specialty, Hepatology, business.industry, Non-allergic rhinitis, Gastroenterology, medicine.disease, Internal medicine, Cytology, medicine, In patient, Proton pump inhibitor therapy, business, Nasal symptoms
Published: 2019

34. Indocyanine green retention test predict the risk of portal hypertension-related events after direct-acting antiviral therapy in compensated advanced chronic liver disease patients

Author: Elton Dajti, Giuseppe Mazzella, Federico Ravaioli, Antonio Colecchia, Mariarosa Tamè, Stefano Brillanti, Giovanni Marasco, Luigina Vanessa Alemanni, Francesco Azzaroli, Patrizia Simoni, A. Porro, Marco Montagnani, Davide Festi, Ravaioli, F., Dajti, E., Simoni, P., Porro, A., Marasco, G., Alemanni, L.V., Tamè, M., Brillanti, S., Colecchia, A., Montagnani, M., Festi, D., Mazzella, G., and Azzaroli, F.
Subjects: medicine.medical_specialty, indocyanine green retention test, portal hypertension, Hepatology, business.industry, Gastroenterology, Antiviral therapy, medicine.disease, Chronic liver disease, chemistry.chemical_compound, chemistry, Internal medicine, medicine, Portal hypertension, business, Indocyanine green, Direct acting
Published: 2019

35. The role of bile acids profile and insulin resistance for the prediction of gallbladder disease in a prospective cohort of blood donors

Author: Davide Festi, Rocco Maurizio Zagari, Patrizia Simoni, Marco Montagnani, A. Porro, A. Belardinelli, Elton Dajti, Federico Ravaioli, F. Placido, Silvia Spinozzi, R. Arena, Aldo Roda, F. Bazzoli, Giuseppe Mazzella, Francesco Azzaroli, and Cecilia Camborata
Subjects: medicine.medical_specialty, Insulin resistance, Hepatology, business.industry, Internal medicine, Gallbladder disease, Gastroenterology, medicine, medicine.disease, Prospective cohort study, business
Published: 2019

36. The role of liver and spleen stiffness measurement in predicting hepatic decompensation after HCV eradication with direct-acting antiviral agents therapy

Author: Giuseppe Mazzella, Mariarosa Tamè, Maria Letizia Bacchi-Reggiani, Agostino Colli, Antonio Colecchia, Davide Festi, Federico Ravaioli, Giovanni Marasco, Stefano Brillanti, Elton Dajti, Francesco Azzaroli, and Luigina Vanessa Alemanni
Subjects: medicine.medical_specialty, medicine.anatomical_structure, Hepatology, business.industry, Internal medicine, Gastroenterology, Medicine, Spleen, business, Direct acting, Hepatic decompensation
Published: 2019

37. Relationship between indocyanine green retention test, decompensation and survival in patients with Child-Pugh A cirrhosis and portal hypertension

Author: Marco Montagnani, Giuseppe Mazzella, Rita Golfieri, R. Arena, Davide Festi, Alessandro Cucchetti, Antonio Colecchia, Claudio Calvanese, Federica Buonfiglioli, Patrizia Simoni, Francesco Azzaroli, Paolo Cecinato, Andrea Lisotti, Lisotti, Andrea, Azzaroli, Francesco, Cucchetti, Alessandro, Buonfiglioli, Federica, Cecinato, Paolo, Calvanese, Claudio, Simoni, Patrizia, Arena, Rosario, Montagnani, Marco, Golfieri, Rita, Colecchia, Antonio, Festi, Davide, and Mazzella, Giuseppe
Subjects: Indocyanine Green, Liver Cirrhosis, Male, medicine.medical_specialty, upper endoscopy, Cirrhosis, Carcinoma, Hepatocellular, Portal venous pressure, Kaplan-Meier Estimate, Esophageal and Gastric Varices, Gastroenterology, Risk Assessment, Endoscopy, Gastrointestinal, 03 medical and health sciences, 0302 clinical medicine, Liver Function Tests, Internal medicine, Ascites, Hypertension, Portal, medicine, Humans, Decompensation, Cumulative incidence, Prospective Studies, Aged, Hepatology, business.industry, Incidence, Liver Neoplasms, non-invasive assessment, Middle Aged, medicine.disease, bleeding, Prognosis, Portal Pressure, Portal vein thrombosis, hepatic venous pressure gradient, ascite, 030220 oncology & carcinogenesis, Portal hypertension, Regression Analysis, 030211 gastroenterology & hepatology, Female, ascites, Biomarkers, medicine.symptom, business, Varices
Abstract: Background & Aims Indocyanine green retention test (ICG-r15) is a non-invasive marker of functional hepatic reserve. Among patients with compensated cirrhosis, ICG-r15 correlates to the degree of portal hypertension (PH); however, its prognostic relationship with the occurrence of decompensation events still requires clarification. Methods ICG-r15 was prospectively measured in 154 patients with compensated cirrhosis. Patients with hepatocellular carcinoma (HCC), Child–Pugh B-C, MELD>15, bilirubin > 2 mg/dl, INR > 1.5 or portal vein thrombosis were excluded. All patients underwent laboratory tests, upper endoscopy and hepatic venous pressure gradient (HVPG). Decompensation, development of HCC, liver transplant and death were recorded and analysed through competing-risk analysis. Results The study group was composed of 134 patients who were followed for a median of 39 months. During follow-up, 46 patients (34.3%) developed liver decompensation. Hepatocellular carcinoma occurred in 18 patients and two patients died from non-liver-related causes. The 1-, 2- and 3-year cumulative incidences of decompensation were 9.7%, 28.4% and 33.4% respectively. Patients with ICG-r15 < 10% did not experience any decompensation events during follow-up, while the 3-year cumulative incidence of decompensation of patients with ICG-r15 between 10% and 22.9% was 29.2% and that of patients with ICG-r15 ≥ 23% was 70.0% (P < 0.001). ICG-r15 gave the lowest pseudo-log-likelihood value, in comparison to oesophageal varices present, MELD, low platelet count and HVPG. Conclusions ICG-r15 appears to be strictly related to liver decompensation, longitudinally confirming the preliminary findings of its correlation with PH among patients with compensated cirrhosis, and can be used for patient prognostication.
Published: 2016

38. The Pharmacological Management of Intrahepatic Cholestasis of Pregnancy

Author: Francesco Azzaroli, Giuseppe Mazzella, Laura Turco, Andrea Lisotti, Claudio Calvanese, Azzaroli F, Turco L, Lisotti A, Calvanese C, and Mazzella G.
Subjects: medicine.medical_specialty, CHOLESTASIS, Cholestasis, Intrahepatic, Disease, Bile Acids and Salts, Liver disease, Liver Function Tests, Cholestasis, medicine, Animals, Humans, Pharmacology (medical), General Pharmacology, Toxicology and Pharmaceutics, Pregnancy, Fetus, Respiratory distress, medicine.diagnostic_test, Obstetrics, business.industry, Pruritus, MRP2, Pregnancy Outcome, General Medicine, Prognosis, medicine.disease, URSODEOXYCHOLIC ACID, Pregnancy Complications, PREGNANCY, BSEP, Female, Liver function tests, business, Cholestasis of pregnancy
Abstract: Intrahepatic cholestasis of pregnancy is the most common liver disease occurring in the second half of pregnancy, characterized by pruritus and elevated serum bile acids often coupled to abnormal liver tests. Maternal prognosis is favourable with a complete symptom resolution after delivery, while preterm deliveries, fetal respiratory distress and stillbirths may occur. The goal of the pharmacological treatment of the disease is to improve maternal symptoms and biochemical alterations and, most importantly, to reduce fetal adverse events.The present manuscript will review the current knowledge on the pharmacological treatment of intrahepatic cholestasis of pregnancy.
Published: 2011

39. P.01.24 IMPACT OF PNEUMATIC DILATATION ON THE MANOMETRIC SUBTYPES OF THE ESOPHAGEAL ACHALASIA

Author: F. Bazzoli, Francesco Azzaroli, Daniele Mandolesi, Elisa Liverani, F. Torresan, and A. Ioannou
Subjects: medicine.medical_specialty, Hepatology, business.industry, Internal medicine, Gastroenterology, medicine, Achalasia, business, medicine.disease
Published: 2018

40. Clinical trial: modulation of human placental multidrug resistance proteins in cholestasis of pregnancy by ursodeoxycholic acid

Author: James L. Boyer, V. Feletti, Francesca Lodato, E. Baglivo, Albert Mennone, Enrico Roda, Patrizia Simoni, Marco Montagnani, Giuseppe Pelusi, Nicola Rizzo, Antonio Colecchia, Domenico De Aloysio, Davide Festi, Francesco Azzaroli, and Giuseppe Mazzella
Subjects: medicine.medical_specialty, Pregnancy, Hepatology, Bile acid, business.industry, Bilirubin, medicine.drug_class, Multidrug resistance-associated protein 2, Gastroenterology, medicine.disease, Ursodeoxycholic acid, chemistry.chemical_compound, Endocrinology, medicine.anatomical_structure, chemistry, Internal medicine, Cord blood, Placenta, Medicine, Pharmacology (medical), business, Cholestasis of pregnancy, medicine.drug
Abstract: Summary Background The effects of ursodeoxycholic acid on human placental bile acids and bilirubin transporters in intrahepatic cholestasis of pregnancy are still undefined. Aim To evaluate whether ursodeoxycholic acid affects MRP2, MRP3 and MRP4 expression in the placenta. Materials and methods Forty-three pregnant women were enrolled; fourteen subjects had physiological pregnancies. Intrahepatic cholestasis of pregnancy patients were divided into two groups: (i) 13 received ursodeoxycholic acid (20 mg/kg/day) and (ii) 16 untreated. Total bile acid and bilirubin in serum and cord blood were determined in each subject. Multidrug resistance proteins expression (immunoblot, quantitative real-time PCR) was evaluated in placentas collected at delivery. anova test was used for statistical analysis of data. Results Ursodeoxycholic acid administration significantly improved maternal serum bile acid and cord blood bilirubin and bile acid levels. MRP2 protein and RNA expression was significantly increased in placentas from treated patients compared to controls (P
Published: 2007

41. Reply

Author: Andrea Lisotti, Francesco Azzaroli, Giuseppe Mazzella, Lisotti, Andrea, Azzaroli, Francesco, and Mazzella, Giuseppe
Subjects: Indocyanine Green, Male, Hepatology, business.industry, Liver Cirrhosi, Medicine (all), Esophageal and Gastric Varice, Hypertension, Portal, Medicine, Female, business, Human
Published: 2015

42. Fasting serum bile acids profile and insulin resistance in healthy blood donors

Author: Giuseppe Mazzella, Marco Montagnani, R. Arena, Aldo Roda, A. Porro, Rocco Maurizio Zagari, Franco Bazzoli, A. Belardinelli, Francesco Azzaroli, Silvia Spinozzi, Cecilia Camborata, and Patrizia Simoni
Subjects: medicine.medical_specialty, Insulin resistance, Endocrinology, Hepatology, business.industry, Internal medicine, medicine, medicine.disease, business
Published: 2017

43. Correlation between Indocyanine green retention test and esophageal varices among patients with hepatocellular carcinoma

Author: A. Porro, Andrea Lisotti, Francesco Azzaroli, Giuseppe Mazzella, Marco Montagnani, Lisotti, Andrea, Azzaroli, Francesco, Montagnani, Marco, Porro, Alberto, and Mazzella, Giuseppe
Subjects: medicine.medical_specialty, education.field_of_study, Cirrhosis, Carcinoma, Hepatocellular, business.industry, Population, Liver Neoplasms, Gastroenterology, Endoscopy, Hepatology, medicine.disease, chemistry.chemical_compound, Esophageal varices, chemistry, Internal medicine, Hepatocellular carcinoma, Esophageal and Gastric Varice, Medicine, Liver function, business, education, Varices, Indocyanine green, Human
Abstract: We recently read with great interest the manuscript entitled ‘‘Prophylactic impact of endoscopic treatment for esophageal varices in liver resection: a prospective study’’ [1] in which Dr. Yamazaki et al. demonstrated the usefulness of endoscopic prophylactic treatment of esophageal varices (EV) and evaluated different risk factors for post-operative progression and bleeding. The authors observed that in patients with hepatocellular carcinoma (HCC), various laboratory variables were significantly different according to the presence or absence of EV; for example, indocyanine green (ICG) retention rate at 15 min (ICG-r15) was 10.9 % (2.1–37.7) in patients without EV and 15.4 % (3.7–46.0) in patients with EV (P \ 0.001). Finally, they observed that ICG-r15 [ 30 % is independently correlated with the risk of worsening varices. We recently reported our experience [2] aimed to evaluate ICG 15-min retention test as a non-invasive marker of PH and EV in patients with compensated liver cirrhosis in which we demonstrated that among patients with well-preserved liver function, ICG retention tests indirectly correlate with the presence and degree of portal hypertension and its complications (EV). According to the observations of Dr. Yamazaki et al., ICG-r15 correlated with the presence of esophageal varices; we found two different ICG-r15 cut-off points able to accurately rule out and rule in the presence of EV (\10 % and C22.9 %, respectively). Liver-mediated uptake of organic anions (drugs or xenobiotics) is mainly mediated by organic anion transporting polypeptides (OATPs) and organic anion transporters (OATs); ICG presents a potent inhibitor effect on OATP isoforms and Na-taurocholate transporting polypeptide (NTCP). OATP1B3 and NTCP are the transporters involved in the hepatic uptake of ICG [3]. The organic anion transporter peptides (OATP) 1B1 and 1B3 are variably and progressively lost during liver carcinogenesis; a previous study performed on patients who underwent OLT because of HCC demonstrated a correlation between the loss of OATP 1B1/ 1B3 and tumor morphological features [4]. These molecular findings could, in our opinion, justify the higher ICG-r15 values observed by Dr. Yamazaki et al. in their population. Indeed, the ICG retention test, among patients with liver cirrhosis, represents both liver parenchymal reserve and hepatic blood flow; in patients with HCC, this interplay is altered by the introduction of a third variable (cancer biology) and could not be argued. This comment refers to the article available at doi:10.1007/s00535013-0841-y.
Published: 2014

44. An unusual cause of weight loss in a young Caucasian man

Author: Alessandra Caponi, Paolo Cecinato, Lorenzo Fuccio, Liboria Laterza, Elena Sabattini, Francesco Azzaroli, Giuseppe Mazzella, P. Cecinato, L. Fuccio, E. Sabattini, L. Laterza, A. Caponi, F. Azzaroli, and G. Mazzella
Subjects: Enteroscopy, medicine.medical_specialty, Pathology, medicine.diagnostic_test, business.industry, Esophagogastroduodenoscopy, digestive, oral, and skin physiology, Gastroenterology, Ileum, medicine.disease, digestive system, Enteral administration, Lymphoma, Endoscopy, Jejunum, medicine.anatomical_structure, Internal medicine, medicine, Duodenum, weight lo, endoscopy, business, celiac disease
Abstract: A 37-year-old Caucasian male presented to our institution for progressive weight loss and recurrent abdominal pain. An enteral CT performed in another centre showed a diffuse thickening of the duodenal walls suggestive of lymphoma or Crohn’s disease. Esophagogastroduodenoscopy showed a normal appearance of gastroesophageal mucosa while the duodenal and proximal jejunal mucosa appeared completely covered with pseudo-polypoid lesions with maximum size of 5 mm (figure 1A,B). At the ileocolonoscopy, the colorectal mucosa was diffusely micronodular (figure 1D), while the terminal ileum presented same lesions detected in the duodenum (figure 1C). Figure 1 Endoscopic view: (A) duodenum, (B) jejunum, (C) ileum, (D) colon. Enteroscopy confirmed the presence of pseudopolypoid lesions also in the jejunum and ileum, …
Published: 2014

45. Severe immune thrombocytopenia after peg-interferon-alpha2a, ribavirin and telaprevir treatment completion: A case report and systematic review of literature

Author: Giuseppe Grande, R. Arena, Federica Buonfiglioli, Paolo Cecinato, Francesco Azzaroli, Andrea Lisotti, Giuseppe Mazzella, Claudio Calvanese, Marco Montagnani, Rosario Arena, Paolo Cecinato, Andrea Lisotti, Federica Buonfiglioli, Claudio Calvanese, Giuseppe Grande, Marco Montagnani, Francesco Azzaroli, and Giuseppe Mazzella
Subjects: medicine.medical_specialty, Hepatitis C virus, Case Report, Chronic hepatitis C, medicine.disease_cause, Viral hepatiti, Autoimmune thrombocytopenia, Telaprevir, chemistry.chemical_compound, Pegylated interferon, Internal medicine, medicine, Hepatology, business.industry, Ribavirin, medicine.disease, Discontinuation, chemistry, Immunology, Rituximab, Antiplatelet antibody, Viral hepatitis, business, medicine.drug
Abstract: Mild to moderate autoimmune thrombocytopenia (AITP) is a common finding in patients receiving interferon-based antiviral treatment, due to bone marrow suppression. Here we report the case of a patient with chronic genotype 1b hepatitis C virus (HCV) infection treated with pegylated-interferon alpha-2a, ribavirin and telaprevir for 24 wk; the patient developed severe AITP three weeks after treatment withdrawal. We performed a systematic literature search in order to review all published cases of AITP related to HCV antiviral treatment. To our knowledge, this is the second case of AITP observed after antiviral treatment withdrawal. In most published cases AITP occurred during treatment; in fact, among 24 cases of AITP related to interferon-based antiviral treatment, only one occurred after discontinuation. Early diagnosis of AITP is a key factor in order to achieve an early interferon discontinuation; in the era of new direct antiviral agents those patients have to be considered for interferon-free treatment regimens. Prompt prescription of immuno-suppressant treatment (i.e., corticosteroids, immunoglobulin infusion and even rituximab for unresponsive cases) leads to favourable prognosis in most of cases. Physicians using interferon-based treatments should be aware that AITP can occur both during and after treatment, specially in the new era of interferon-free antiviral treatment. Finally, in the case of suspected AITP, presence of anti-platelet antibodies should be checked not only during treatment but also after discontinuation.
Published: 2015

46. [Untitled]

Author: Alessandro Pezzoli, Patrizia Simoni, Davide Festi, Laura Zambonin, Giuseppe Mazzella, Costanza Mazzeo, Francesco Azzaroli, Pietro Fusaroli, and Enrico Roda
Subjects: medicine.medical_specialty, Cirrhosis, Physiology, business.industry, Cholesterol, Biliary cirrhosis, Deoxycholic acid, Gastroenterology, Cholic acid, Hepatology, medicine.disease, chemistry.chemical_compound, Endocrinology, Primary biliary cirrhosis, chemistry, Methylprednisolone, Internal medicine, Medicine, business, medicine.drug
Abstract: As immunosuppressive agents, corticosteroids maybe considered an appropriate treatment for primarybiliary cirrhosis, even if bone loss and other sideeffects may occur. We studied biliary lipid metabolism in 10 nonicteric patients, with histologicallyproven primary biliary cirrhosis (stage I-IV). Weadministered methylprednisolone (24 mg daily) for 30days to ascertain its effects on biliary lipidmetabolism, which are largely still unknown. All patientsunderwent a 30-day drug-washout period before enteringthe trial. The following parameters were studied beforeand after methylprednisolone treatment: serum biochemistry; cholic acid pool size, kineticsand synthesis; biliary lipid secretion; biliary bileacid pattern; biliary lipid molar percentage; andcholesterol saturation index. Methylprednisolone induced a statistically significant (Wilcoxon ranktest) increase in cholic acid turnover (from 0.26± 0.04 to 0.50 ± 0.05 K/day, P = 0.005)and synthesis (from 0.42 ± 0.12 to 0.78 ±0.11 mmol/day, P = 0.04), and in bile deoxycholic acid molarpercentage (from 19.4 ± 2.7 to 30.6 ± 4.4%molar, P = 0.01). On the other hand, a significantdecrease in biliary cholesterol molar percentage (from7.9 ± 0.7 to 6.4 ± 0.5 % molar, P =0.005), cholesterol saturation index (from 1.11 ±0.11 to 0.95 ± 0.07, P = 0.05), and biliarycholesterol secretion (from 64.7 ± 5.4 to 53.0± 4.5 μmol/hr, P = 0.005) was observed. These findings show thatshort-term administration of methylprednisolone inpatients with primary biliary cirrhosis does not induceexpansion of the cholic acid pool but increases cholicacid synthesis and turnover, as well as intestinalproduction of deoxycholic acid. If long-term treatmentis considered, the beneficial immunosuppressive effectsof corticosteroids have to be weighed against the hepatotoxic properties of deoxycholicacid.
Published: 1999

47. Extracorporeal shock wave lithotripsy for difficult common bile duct stones: a comparison between 2 different lithotripters in a large cohort of patients

Author: Cesare Hassan, Paolo Cecinato, Giulio Cariani, Franco Bazzoli, Andrea Lisotti, Giuseppe Mazzella, Loredana Correale, Federica Buonfiglioli, Francesco Azzaroli, Rosangela Muratori, Lorenzo Fuccio, Cecinato P, Fuccio L, Azzaroli F, Lisotti A, Correale L, Hassan C, Buonfiglioli F, Cariani G, Mazzella G, Bazzoli F, and Muratori R
Subjects: Male, medicine.medical_specialty, medicine.medical_treatment, Gallstones, Lithotripsy, Risk Factors, medicine, Humans, Radiology, Nuclear Medicine and imaging, Adverse effect, BILIARY TRACT, Aged, Retrospective Studies, Aged, 80 and over, Common bile duct, business.industry, Bile duct, Incidence (epidemiology), Patient Selection, Gastroenterology, Retrospective cohort study, Equipment Design, medicine.disease, Extracorporeal shock wave lithotripsy, Surgery, medicine.anatomical_structure, Treatment Outcome, CHOLELITHIASIS, Female, business, ESWL
Abstract: Background Extracorporeal shock wave lithotripsy (ESWL) for difficult common bile duct (CBD) stones is a safe and effective treatment strategy allowing for bile duct clearance in approximately 90% of patients with a low incidence of mild adverse events. Objective To compare the CBD clearance rates achieved after ESWL performed with 2 different lithotripters (Siemens Lithostar Plus and Storz Modulith SLX-F2) in a large cohort of patients with difficult CBD stones. Design A retrospective analysis of a prospectively collected database. Setting Tertiary care center. Patients All of the consecutive patients who underwent ESWL because of difficult CBD stones between 1990 and 2012 were considered suitable for inclusion. Interventions ESWL with Lithostar Plus or with Modulith SLX-F2. Main Outcome Measurements CBD clearance. Results Three hundred ninety-two patients with difficult CBD stones were treated; 199 patients were treated with the Lithostar Plus and 193 patients with the Modulith SLX-F2. CBD clearance was achieved in 349 patients (89.0%) with no significant difference between the patients treated with Lithostar Plus and those treated with Modulith SLX-F2 (90.5% vs 87.6%; P = .45). Patients treated with Modulith SLX-F2 underwent a significantly lower number of ESWL sessions (3 [range, 2 to 4] vs 3 [range, 2 to 4]; P = .0015), had a lower incidence of ESWL-related adverse events (5.2% vs 13.6%; P = .009), and never required opioid analgesia ( P Limitations Retrospective design. Conclusions The Modulith SLX-F2 allows the same clearance rate as the Lithostar Plus but has a significantly lower incidence of adverse events and requires fewer ESWL sessions.
Published: 2013

48. High dose lamivudine in HBV-related cirrhotic patients with unsatisfactory response after adefovir add-on

Author: Marina Giandinoto, Marco Montagnani, Rita Aldini, Giuseppe Mazzella, Silvia Galli, Laura Turco, Andrea Lisotti, Federica Buonfiglioli, Francesco Azzaroli, Montagnani M., Giandinoto M., Lisotti A., Galli S., Azzaroli F., Buonfiglioli F., Turco L., Aldini R., and Mazzella G.
Subjects: Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, Physiology, Organophosphonates, Virus Replication, LAMIVUDINE, Gastroenterology, Antiviral Agents, chemistry.chemical_compound, Hepatitis B, Chronic, Internal medicine, medicine, Adefovir, Humans, Decompensation, Treatment Failure, Adverse effect, CIRRHOSIS, Creatinine, business.industry, Adenine, Lamivudine, virus diseases, Hepatology, Middle Aged, Viral Load, medicine.disease, Virology, RESCUE THERAPY, chemistry, DNA, Viral, TENOFOVIR, Reverse Transcriptase Inhibitors, Drug Therapy, Combination, Female, business, Viral load, RESISTANCE, medicine.drug
Abstract: Background: Before tenofovir approval for chronic hepatitis B therapy, the clinical management of patients with suboptimal response or virological breakthrough during combination treatment with lamivudine and adefovir dipivoxil was a difficult clinical challenge. Aims In order to improve virologic response and reduce the risk of decompensation, we evaluate the efficacy of a high dose of lamivudine on chronic HBV patients who have previously presented an unsatisfactory response during treatment with lamivudine 100mg/day and adefovir 10mg/day. Methods: Six patients with HBV-related liver cirrhosis were prospectively enrolled. All were HBeAg-negative and presented a suboptimal response or virological breakthrough after ‘‘adefovir add-on’’ because of development of clinical breakthrough during Lamivudine treatment. Lamivudine dose was increased to 200 or 300mg, depending on viral load. After 12 months of follow-up, virological and biochemical response were evaluated. Results: After 12 months of high-dose lamivudine, all patients (6/6, 100%) achieved a significant decrease of serum HBV DNA (mean reduction 2,62 ± 1,15 Log10 UI/ml, P = 0.03) and normalized ALT. In three patients (3/6, 50%), HBV DNA became undetectable within 6 months. No patient developed liver decompensation and no significant changes occurred in serum creatinine, serum and urinary electrolytes. No adverse events were registered. Conclusions: In our experience, rescue strategy with highdose lamivudine inhibited viral replication leading to undetectability of serum HBVDNA. This rescue treatment presented a good safety profile, without adverse events during the study period. Customized increase of nucleos(t)ide analogues dose in difficult-to-treat patients may be a proficient approach in challenging clinical setting.
Published: 2012

49. Transjugular intrahepatic portosystemic shunt placement for refractory ascites: a single-centre experience

Author: Rita Golfieri, Giuseppe Mazzella, Federica Buonfiglioli, Annalisa Berzigotti, Emanuela Giampalma, Francesco Azzaroli, Cristina Mosconi, Marco Zoli, Alberta Cappelli, Andrea Lisotti, Francesca Lodato, Matteo Renzulli, Claudio Calvanese, Lodato F, Berzigotti A, Lisotti A, Azzaroli F, Mosconi C, Giampalma E, Renzulli M, Cappelli A, Buonfiglioli F, Calvanese C, Zoli M, Golfieri R, and Mazzella G
Subjects: Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, medicine.medical_treatment, Kaplan-Meier Estimate, Severity of Illness Index, Gastroenterology, Liver cirrhosi, End Stage Liver Disease, Internal medicine, Hypertension, Portal, Ascites, medicine, Humans, Aspartate Aminotransferases, Survival rate, Aged, Proportional Hazards Models, Retrospective Studies, Receiver operating characteristic, business.industry, Bilirubin, Middle Aged, medicine.disease, Surgery, Survival Rate, ROC Curve, Area Under Curve, Multivariate Analysis, Ascite, Portal hypertension, TIPS, Female, Liver function, HVPG, Portasystemic Shunt, Transjugular Intrahepatic, Refractory ascites, medicine.symptom, business, Transjugular intrahepatic portosystemic shunt
Abstract: BACKGROUND: The presence of refractory ascites is a common indication for transjugular intrahepatic portosystemic shunt (TIPS). Different models have been proposed for the prediction of survival after TIPS. The aim of this study was to evaluate the predictive factors associated with patients' survival after TIPS placement for refractory ascites. METHODS: Data from all consecutive patients undergoing TIPS placement in our center for refractory ascites between February 2003 and January 2008 were prospectively recorded. RESULTS: Seventy-three patients (52M/21F; 57 ± 10 years) met the inclusion criteria; mean follow-up was 17 ± 2 months. Mean MELD value, before TIPS placement, was 15.7 ± 5.3. TIPS placement led to an effective resolution of refractory ascites in 54% of patients (n = 40) with no significant increase in severe portosystemic encephalopathy. The 1-year survival rate observed was 65.7%, while the overall mortality was 23.3% (n = 17) with a mean survival of 17 ± 14 months. MELD score (B = 0.161, p = 0.042), basal AST (B = 0.020, p = 0.090), and pre-TIPS HVPG (B = 0.016, p = 0.093) were independent predictors of overall mortality, while MELD (B = 0.419, p = 0.018) and HVPG (B = 0.223, p = 0.060) independently predicted 1-year survival. ROC curves identified MELD ≥ 19 and HVPG ≥ 25 mmHg as the best cut-off points for the prediction of 1-year mortality. CONCLUSIONS: TIPS is an effective treatment for refractory ascites in cirrhotic patients, leading to an effective ascites control in more than half patients. Improvement in patients' selection criteria could lead to better outcome and survival after this procedure. Liver function (MELD), presence of active necroinflammation (AST), and portal hypertension (HVPG) are independent predictors of patients' outcome after TIPS.
Published: 2012

50. Alisporivir for the treatment of chronic HCV

Author: Claudio Calvanese, Laura Turco, Andrea Lisotti, Giuseppe Mazzella, Monica Cevenini, Marco Montagnani, Federica Buonfiglioli, Francesco Azzaroli, Paolo Cecinato, Azzaroli F, Turco L, Lisotti A, Cecinato P, Calvanese C, Buonfiglioli F, Cevenini M, Montagnani M, and Mazzella G.
Subjects: Drug, Alisporivir, Combination therapy, medicine.drug_class, business.industry, media_common.quotation_subject, CYCLOPHILLIN INHIBITORS, Phases of clinical research, Hepatitis C, ALISPORIVIR, Pharmacology, medicine.disease, PEG-IFN, Virology, Viral replication, Cyclosporin a, HCV, medicine, Antiviral drug, business, RIBAVIRIN, media_common
Abstract: Alisporivir (DEB025), a cyclosporin A derivative, is a new antiviral drug which targets host cell factors (cyclophilins) inhibiting viral replication without immunosuppressive effects. This drug potently inhibits cyclophilin-dependent HCV replication with an additive antiviral effect to standard-of-care (SoC) therapy for HCV. The administration of alisporivir in addition to SoC enhances activity against all HCV genotypes, with a good safety profile. Currently, two trials are ongoing: a Phase III and a Phase II trial assessing the efficacy of alisporivir plus SoC in genotype-1 treatment-naive patients and nonresponders or relapsers. Another Phase II study is examining the potential use of alisporivir for IFN-free treatment in HCV genotype 2 and 3 patients naive to treatment. In this review, we describe the unique characteristics of this cyclophilin inhibitor and benefit afforded by this drug in combination therapy with current and future HCV treatments.
Published: 2012

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