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1. Effects of immunosuppressive drugs on COVID-19 severity in patients with autoimmune hepatitis

Author

George N. Dalekos, Cristina Rigamonti, Godolfino Miranda Zazueta, Ali Rıza Calışkan, Annarosa Floreani, Berat Ebik, Kadri Atay, Aylin Demirezer Bolat, Nazım Ekin, Eric M. Yoshida, Graciela Castro Narro, Fatih Güzelbulut, Murat Biyik, Manuel Mendizabal, Renumathy Dhanasekaran, Stefano Fagiuoli, Thomas D. Schiano, Ellina Lytvyak, Shalom Frager, Nataly Chris Escajadillo Vargas, Yucel Ustundag, Ramazan Idilman, Andreea M. Catana, Alvaro Urzúa, Ahmet Yavuz, Staffan Wahlin, Mesut Aydin, Cumali Efe, Laura Cristoferi, Hatef Massoumi, Maria Vincent, Sandro Ruiz Garcia, Evrim Kahramanoğlu-Aksoy, Natalia Ratusnu, Craig Lammert, Sümeyra Yıldırım, Mário Reis Álvares-da-Silva, Murat Harputoğlu, Marina Silveira, Murat Kiyici, Fátima Higuera-de la Tijera, Nurhan Demir, Cynthia Levy, Einar Bjornsson, Javier Brahm, Rotonya M. Carr, Nidah S. Khakoo, Andres Jose Gomez Aldana, Murat Akyildiz, Leyla Nazal, Alessio Gerussi, Tuğçe Eşkazan, Zeynep Ellik, Pietro Invernizzi, Fulya Gunsar, Ezequiel Ridruejo, Eleonora De Martin, Tugrul Purnak, Fatih Eren, Hüseyin Kaçmaz, Margarita Anders, Nikolaos K. Gatselis, Romee Snijders, Sezgin Barutçu, Costica Aloman, Alexandra Heurgue-Berlot, Bianca Magro, Jonathan Aguirre, Kader Irak, Koray Tascilar, Aldo J. Montano-Loza, Marcelo Silva, David N. Assis, Joost P.H. Drenth, Eira Cerda Reyes, Ibrahim Hatemi, Mirta Peralta, Sanjaya K. Satapathy, James L. Boyer, Yasemin H. Balaban, Efe, C, Lammert, C, Tascilar, K, Dhanasekaran, R, Ebik, B, Higuera-de la Tijera, F, Caliskan, A, Peralta, M, Gerussi, A, Massoumi, H, Catana, A, Purnak, T, Rigamonti, C, Aldana, A, Khakoo, N, Nazal, L, Frager, S, Demir, N, Irak, K, Melekoglu-Ellik, Z, Kacmaz, H, Balaban, Y, Atay, K, Eren, F, Alvares-da-Silva, M, Cristoferi, L, Urzua, A, Eskazan, T, Magro, B, Snijders, R, Barutcu, S, Lytvyak, E, Zazueta, G, Demirezer-Bolat, A, Aydin, M, Heurgue-Berlot, A, De Martin, E, Ekin, N, Yildirim, S, Yavuz, A, Biyik, M, Narro, G, Kiyici, M, Akyildiz, M, Kahramanoglu-Aksoy, E, Vincent, M, Carr, R, Gunsar, F, Reyes, E, Harputluoglu, M, Aloman, C, Gatselis, N, Ustundag, Y, Brahm, J, Vargas, N, Guzelbulut, F, Garcia, S, Aguirre, J, Anders, M, Ratusnu, N, Hatemi, I, Mendizabal, M, Floreani, A, Fagiuoli, S, Silva, M, Idilman, R, Satapathy, S, Silveira, M, Drenth, J, Dalekos, G, Assis, D, Bjornsson, E, Boyer, J, Yoshida, E, Invernizzi, P, Levy, C, Montano-Loza, A, Schiano, T, Ridruejo, E, Wahlin, S, Akyıldız, Murat (ORCID 0000-0002-2080-7528 & YÖK ID 123080), Efe, Cumalı, Lammert, Craig, Taşçılar, Koray, Dhanasekaran, Renumathy, Ebik, Berat, Higuera-de la Tijera, Fatima, Çalışkan, Ali R., Peralta, Mirta, Gerussi, Alessio, Massoumi, Hatef, Catana, Andreea M., Purnak, Tuğrul, Rigamonti, Cristina, Aldana, Andres J. G., Khakoo, Nidah, Nazal, Leyla, Frager, Shalom, Demir, Nurhan, Irak, Kader, Melekoğlu-Ellik, Zeynep, Kaçmaz, Hüseyin, Balaban, Yasemin, Atay, Kadri, Eren, Fatih, Alvares-da-Silva, Mario R., Cristoferi, Laura, Urzua, Alvaro, Eskazan, Tugce, Magro, Bianca, Snijders, Romee, Barutçu, Sezgin, Lytvyak, Ellina, Zazueta, Godolfino M., Demirezer-Bolat, Aylin, Aydın, Mesut, Heurgue-Berlot, Alexandra, De Martin, Eleonora, Ekin, Nazım, Yıldırım, Sumeyra, Yavuz, Ahmet, Bıyık, Murat, Narro, Graciela C., Kıyıcı, Murat, Kahramanoğlu-Aksoy, Evrim, Vincent, Maria, Carr, Rotonya M., Günsar, Fulya, Reyes, Eira C., Harputluoğlu, Murat, Aloman, Costica, Gatselis, Nikolaos K., Üstündağ, Yücel, Brahm, Javier, Vargas, Nataly C. E., Güzelbulut, Fatih, Garcia, Sandro R., Aguirre, Jonathan, Anders, Margarita, Ratusnu, Natalia, Hatemi, İbrahim, Mendizabal, Manuel, Floreani, Annarosa, Fagiuoli, Stefano, Silva, Marcelo, İdilman, Ramazan, Satapathy, Sanjaya K., Silveira, Marina, Drenth, Joost P. H., Dalekos, George N., Assis, David N., Bjornsson, Einar, Boyer, James L., Yoshida, Eric M., Invernizzi, Pietro, Levy, Cynthia, Montano-Loza, Aldo J., Schiano, Thomas D., Ridruejo, Ezequiel, Wahlin, Staffan, and School of Medicine

Subjects
Adult, Male, medicine.medical_specialty, budesonide, Cirrhosis, Adolescent, Gastroenterology and hepatology, medicine.medical_treatment, Azathioprine, Autoimmune hepatitis, mercaptopurine, Liver transplantation, Gastroenterology, Young Adult, Sars-Cov-2 Infection, Internal medicine, medicine, Humans, Autoimmunity, Budesonide, Mercaptopurine, SARS-CoV-2, Aged, Retrospective Studies, Mechanical ventilation, Aged, 80 and over, azathioprine, liver transplantation, Hepatology, business.industry, autoimmunity, COVID-19, Immunosuppression, Odds ratio, Middle Aged, medicine.disease, Tacrolimus, Liver-Transplant Recipients, Hospitalization, Hepatitis, Autoimmune, Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11], Pharmaceutical Preparations, Female, business, medicine.drug
Abstract

Background We investigated associations between baseline use of immunosuppressive drugs and severity of Coronavirus Disease 2019 (COVID-19) in autoimmune hepatitis (AIH). Patients and methods Data of AIH patients with laboratory confirmed COVID-19 were retrospectively collected from 15 countries. The outcomes of AIH patients who were on immunosuppression at the time of COVID-19 were compared to patients who were not on AIH medication. The clinical courses of COVID-19 were classified as (i)-no hospitalization, (ii)-hospitalization without oxygen supplementation, (iii)-hospitalization with oxygen supplementation by nasal cannula or mask, (iv)-intensive care unit (ICU) admission with non-invasive mechanical ventilation, (v)-ICU admission with invasive mechanical ventilation or (vi)-death and analysed using ordinal logistic regression. Results We included 254 AIH patients (79.5%, female) with a median age of 50 (range, 17-85) years. At the onset of COVID-19, 234 patients (92.1%) were on treatment with glucocorticoids (n = 156), thiopurines (n = 151), mycophenolate mofetil (n = 22) or tacrolimus (n = 16), alone or in combinations. Overall, 94 (37%) patients were hospitalized and 18 (7.1%) patients died. Use of systemic glucocorticoids (adjusted odds ratio [aOR] 4.73, 95% CI 1.12-25.89) and thiopurines (aOR 4.78, 95% CI 1.33-23.50) for AIH was associated with worse COVID-19 severity, after adjusting for age-sex, comorbidities and presence of cirrhosis. Baseline treatment with mycophenolate mofetil (aOR 3.56, 95% CI 0.76-20.56) and tacrolimus (aOR 4.09, 95% CI 0.69-27.00) were also associated with more severe COVID-19 courses in a smaller subset of treated patients. Conclusion Baseline treatment with systemic glucocorticoids or thiopurines prior to the onset of COVID-19 was significantly associated with COVID-19 severity in patients with AIH., Italian Ministry of University and Research (MIUR)-Department of Excellence project PREMIA (PREcision MedIcine Approach: bringing biomarker research to clinic), A. Gerussi, L. Cristoferi, and P. Invernizzi acknowledge that this research was partially supported by the Italian Ministry of University and Research (MIUR)-Department of Excellence project PREMIA (PREcision MedIcine Approach: bringing biomarker research to clinic).

Published
2021

2. Low recurrence rate of hepatocellular carcinoma following ledipasvir and sofosbuvir treatment in a real‐world chronic hepatitis C patients cohort

Author

Alkim, Huseyin, Kaymakoglu, Sabahattin, TABAK, Ömer Fehmi, GÜNŞAR, FULYA, AKHAN, SILA, İDİLMAN, RAMAZAN, DEMİR, MEHMET, ALADAĞ, MURAT, Erol, Cihan, Cavus, Bilger, Iliaz, Raim, Koklu, Hayrettin, Cakaloglu, Yilmaz, Sahin, Memduh, ERSÖZ, GALİP, Koksal, Iftihar, KARASU, ABDULLAH ZEKİ, Ozgenel, Meric, TURAN, İLKER, GÜNDÜZ, FEYZA, ATASEVEN , HÜSEYİN, Akdogan, Meral, KIYICI, MURAT, Ozkan, Hasan, Ozer, Birol, AKARSU, MESUT, Kuruuzum, Ziya, Yurdaydin, Cihan, Yozgat, Ahmet, Yilmaz, Hasan, Yilmaz, Bulent, Yildirim, Beytullah, Yildirim, Abdullah E., KÖKSAL, AYDIN ŞEREF, Yaras, Serkan, Unal, Hakan, Toka, Bilal, Simsek, Halis, Senates, Ebubekir, Poturoglu, Sule, Ozenirler, Seren, Ozbakir, Omer, Ormeci, Necati, ÖNDER, Fatih Oğuz, Kav, Taylan, Kamilli, Cemil, Inkaya, Ahmet Cagan, Gursoy, Sebnem, Gurel, Selim, Gokcan, Hale, Ensaroglu, Fatih, Cosgun, Suleyman, Celik, Ilhami, Bolat, Aylin, Baysal, Birol, Barut, Huseyin S., Balik, Ismail, Aygen, Bilgehan, Ates, Fehmi, Araz, Filiz, Akarca, Ulus S., Idilman, R, Demir, M, Aladag, M, Erol, C, Cavus, B, Iliaz, R, Koklu, H, Cakaloglu, Y, Sahin, M, Ersoz, G, Koksal, I, Karasu, Z, Ozgenel, M, Turan, I, Gunduz, F, Ataseven, H, Akdogan, M, Kiyici, M, Koksal, AS, Akhan, S, Gunsar, F, Tabak, F, Kaymakoglu, S, Akarca, US, Akarsu, M, Alkim, H, Araz, F, Ates, F, Aygen, B, Balik, I, Barut, HS, Baysal, B, Bolat, A, Celik, I, Cosgun, S, Ensaroglu, F, Gokcan, H, Gurel, S, Gursoy, S, Inkaya, AC, Kamilli, C, Kav, T, Kuruuzum, Z, Onder, FO, Ormeci, N, Ozbakir, O, Ozenirler, S, Ozer, B, Ozkan, H, Poturoglu, S, Senates, E, Simsek, H, Toka, B, Unal, H, Yaras, S, Yildirim, AE, Yildirim, B, Yilmaz, B, Yilmaz, H, Yozgat, A, Yurdaydin, C, Sakarya Üniversitesi/Tıp Fakültesi/Dahili Tıp Bilimleri Bölümü, Köksal, Aydın Şeref, and Toka, Bilal

Subjects
Male, Cirrhosis, Sustained Virologic Response, Sofosbuvir, viruses, medicine.medical_treatment, Hepacivirus, Liver transplantation, Gastroenterology, Cohort Studies, chemistry.chemical_compound, Liver disease, 0302 clinical medicine, 030212 general & internal medicine, Aged, 80 and over, Liver Neoplasms, Middle Aged, Infectious Diseases, Hepatocellular carcinoma, RNA, Viral, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology, Uridine Monophosphate, medicine.drug, Adult, Ledipasvir, medicine.medical_specialty, Carcinoma, Hepatocellular, Genotype, Antiviral Agents, 03 medical and health sciences, Virology, Internal medicine, Ribavirin, medicine, Humans, Aged, Fluorenes, Hepatology, business.industry, Hepatitis C, Chronic, medicine.disease, digestive system diseases, Liver Transplantation, chemistry, Benzimidazoles, Liver function, Neoplasm Recurrence, Local, business
Abstract

The aims of the present study were to evaluate the efficacy and tolerability of ledipasvir/sofosbuvir (LDV/SOF) with or without ribavirin in the treatment of chronic hepatitis C (CHC) in patients with advanced liver disease and to analyse whether the use of LDV/SOF treatment is associated with a new occurrence of hepatocellular carcinoma (HCC) during and after LDV/SOF treatment. The Turkish Early Access Program provided LDV/SOF treatment to a total of 200 eligible CHC patients with advanced liver disease. The median follow-up period was 22 months. All patients were Caucasian, 84% were infected with genotype 1b, and 24% had a liver transplantation before treatment. The sustained virological response (SVR12) was 86.0% with ITT analysis. SVR12 was similar among patients with Child-Pugh classes A, B and C disease and transplant recipients. From baseline to SVR12, serum ALT level and MELD score were significantly improved (P < 0.001). LDV/SOF treatment was generally well tolerated. Only one patient developed a new diagnosed HCC. Seventeen of the 35 patients, who had a history of previous HCC, developed HCC recurrence during the LDV/SOF treatment or by a median follow-up of 6 months after treatment. HCC recurrence was less commonly observed in patients who received curative treatment for HCC compared with those patients who received noncurative treatment (P = 0.007). In conclusion, LDV/SOF with or without ribavirin is an effective and tolerable treatment in CHC patients with advanced liver disease. Eradication is associated with improvements in liver function and a reduced risk of developing a new occurrence of HCC.

Published
2019

3. Outcome of COVID-19 in Patients With Autoimmune Hepatitis: An International Multicenter Study

Author

Fátima Higuera-de la Tijera, Renumathy Dhanasekaran, Mirta Peralta, C. Levy, Laura Cristoferi, Hüseyin Kaçmaz, Romee Snijders, David N. Assis, Cristina Rigamonti, Ali Rıza Calışkan, Nidah S. Khakoo, Alessio Gerussi, Alvaro Urzúa, Ezequiel Ridruejo, Yasemin H. Balaban, Craig Lammert, Ersin Batıbay, Kader Irak, Thomas D. Schiano, Marina Silveira, Fatih Eren, Berat Ebik, Kadri Atay, Andreea M. Catana, Cumali Efe, Staffan Wahlin, Murat Harputluoglu, Ibrahim Hatemi, Einar Bjornsson, Nurhan Demir, Murat Akyildiz, Manuel Mendizabal, Murat Kiyici, Costica Aloman, Rotonya M. Carr, Nazım Ekin, Ramazan Idilman, Marcelo Silva, Andres Jose Gomez Aldana, James L. Boyer, Murat Torgutalp, Tugrul Purnak, Zeynep Ellik, Leyla Nazal, Shalom Frager, Joost P.H. Drenth, Hatef Massoumi, Pietro Invernizzi, Efe, C, Dhanasekaran, R, Lammert, C, Ebik, B, Higuera-de la Tijera, F, Aloman, C, Riza Caliskan, A, Peralta, M, Gerussi, A, Massoumi, H, Catana, A, Torgutalp, M, Purnak, T, Rigamonti, C, Gomez Aldana, A, Khakoo, N, Kacmaz, H, Nazal, L, Frager, S, Demir, N, Irak, K, Ellik, Z, Balaban, Y, Atay, K, Eren, F, Cristoferi, L, Batibay, E, Urzua, A, Snijders, R, Kiyici, M, Akyildiz, M, Ekin, N, Carr, R, Harputluoglu, M, Hatemi, I, Mendizabal, M, Silva, M, Idilman, R, Silveira, M, Drenth, J, Assis, D, Bjornsson, E, Boyer, J, Invernizzi, P, Levy, C, Schiano, T, Ridruejo, E, Wahlin, S, Akyıldız, Murat, Efe, C., Dhanasekaran, R., Lammert, C., Ebi, B., Higuera-de la Tijera, F., Aloman, C., Çalışkan, A. R., Peralta, M., Gerussi, A., Massoumi, H., Catana, A. M., Torgutalp, M., Pürnak T., Rigamonti, C., Aldana, A. J. G., Khakoo, N., Kaçmaz, H., Nazal, L., Frager, S., Demir, N., Irak, K., Ellik, Z. M., Balaban, Y., Atay, K., Eren, F., Cristoferi, L., Batıbay, E., Urzua, Á., Snijders, R., Kıyıcı, M., Ekin, N., Carr, R. M., Harputoğlu, M., Hatemi, İ., Mendizabal, M., Silva, M., İdilman, R., Silveira, M., Drenth, J. P. H., Assis, D. N., Björnsson, E., Boyer, J. L., Invernizzi, P., Levy, C., Schiano, T. D., Ridruejo, E., Wahlin, S., and School of Medicine

Subjects
Adult, Male, medicine.medical_specialty, Cirrhosis, Adolescent, medicine.medical_treatment, America, Autoimmune hepatitis, Liver transplantation, liver, Gastroenterology, Young Adult, AIH, Retrospective Studie, Internal medicine, purl.org/becyt/ford/3.2 [https], medicine, Humans, Propensity Score, Determinants, Retrospective Studies, Aged, Hepatitis, Liver injury, Aged, 80 and over, Hepatology, business.industry, COVID-19, Immunosuppression, Retrospective cohort study, Middle Aged, medicine.disease, Autoimmunity, Liver failure, Mycophenolate mofetil, Steroids, Tacrolimus, Europe, Hepatitis, Autoimmune, Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11], Cohort, Female, purl.org/becyt/ford/3 [https], Americas, Erratum, business, Rapid Communication, Human
Abstract

Background: data regarding outcome of Coronavirus disease 2019 (COVID-19) in patients with autoimmune hepatitis (AIH) are lacking. Patients and methods: we performed a retrospective study on AIH patients with COVID-19 from 34 centres in Europe and the Americas. We analyzed factors associated with severe COVID-19 outcomes defined as the need for mechanical ventilation, intensive care admission, and/or death. The outcomes of patients with AIH were compared to a propensity-score matched cohort of non-AIH patients with chronic liver diseases (CLD) and COVID-19. The frequency and clinical significance of new-onset liver injury (alanine aminotransferase>2xupper limit of normal) during COVID-19 was also evaluated. Results: we included 110 AIH patients (80%,female) with a median age of 49 (range:18-85) years at COVID-19 diagnosis. New-onset liver injury was observed in 37.1% (33/89) of the patients. Use of antivirals was associated with liver injury (p=0.041; odds ratio (OR) 3.36[1.05-10.78]) while continued immunosuppression during COVID-19 was associated with a lower rate of liver injury (p=0.009; OR 0.26[0.09-0.71]). The rates of severe COVID-19 (15.5% vs 20.2% p=0.231) and all-cause mortality (10% vs 11.5%; p=0.852) were not different between AIH and non-AIH CLD. Cirrhosis was an independent predictor of severe COVID-19 in patients with AIH (p, Italian Ministry of University; Research (MIUR)-Department of Excellence Project PREMIA; AMAF Monza ONLUS; AIRCS

Published
2021

4. Extrahepatic autoimmune diseases in primary biliary cholangitis: Prevalence and significance for clinical presentation and disease outcome

Author

Fredrik Rorsman, Ellina Lytvyak, Mårten Werner, Aldo J. Montano-Loza, Fatema Alalkim, Benedetta Terziroli Beretta-Piccoli, Paolo Muratori, Thomas Berg, Thomas D. Schiano, Emma Nilsson, Tugrul Purnak, Ida Henriksson, David Semela, Staffan Wahlin, Eric M. Yoshida, Luigi Muratori, Alan Bonder, Murat Kiyici, Kristina Önnerhag, Janett Fischer, Ersan Ozaslan, Maneerat Chayanupatkul, Hanns-Ulrich Marschall, Murat Torgutalp, Claudia Coppo, Alexandra Heurgué-Berlot, Hirsh D. Trivedi, Nurhan Demir, Cumali Efe, Fatih Eren, Efe C., Torgutalp M., Henriksson I., Alalkim F., Lytvyak E., Trivedi H., Eren F., Fischer J., Chayanupatkul M., Coppo C., Purnak T., Muratori L., Werner M., Muratori P., Rorsman F., Onnerhag K., Nilsson E., Heurgue-Berlot A., Demir N., Semela D., Kiyici M., Schiano T.D., Montano-Loza A.J., Berg T., Ozaslan E., Yoshida E.M., Bonder A., Marschall H.-U., Beretta-Piccoli B.T., Wahlin S., Bursa Uludağ Üniversitesi/Tıp Fakültesi/İç Hastalıkları Anabilim Dalı., CPU-6796-2022, and Eren, Fatih

Subjects
Male, Anti-nuclear antibody, PBC, Gastroenterology, Inflammatory bowel disease, 0302 clinical medicine, Lichen sclerosus et atrophicus, Antiphospholipid syndrome, Ascites, Undifferentiated connective tissue disease, Temporal arteritis, Myasthenia gravis, Hepatic encephalopathy, Hashimoto disease, Addison disease, Crohn disease, Pemphigus vulgaris, IgA nephropathy, Prognosis, Liver cell carcinoma, Management, Risk-factors, Retrospective study, Blood, Cirrhosis, Smooth muscle antibody, Biochemical response, Ursodeoxycholic acid, Primary biliary cirrhosis, 030220 oncology & carcinogenesis, Rheumatoid arthritis, Graves disease, Systemic sclerosis, 030211 gastroenterology & hepatology, Cohort analysis, Lichen planus, Anti-phospholipid syndrome, Human, Sex factor, medicine.medical_specialty, Cholangitis, Biliary Liver Cirrhosis, Obeticholic Acid, Sarcoidosis, Immunology, Major clinical study, Aspartate aminotransferase, Article, Dermatomyositis, Multiple sclerosis, 03 medical and health sciences, Humans, Clinical significance, Aspartate Aminotransferases, Autoimmune hemolytic anemia, Autoantibodies, Polymyositi, Ankylosing spondylitis, Bullous pemphigoid, Wegener granulomatosis, Medical record, Biliary cirrhosis, Follow up, medicine.disease, Event free survival, Ankylosing spondyliti, Ulcerative colitis, Pernicious anemia, Idiopathic thrombocytopenic purpura, Gastroenterology & hepatology, Complication, Biomarkers, Sarcoidosi, Autoantibody, Immunoglobulin A nephropathy, Autoimmune disease, Prevalence, Celiac disease, Middle aged, Variceal bleeding, Liver Cirrhosis, Biliary, Chronic urticaria, Mitochondria, Gastritis, Antibodies, Antinuclear, Female, medicine.symptom, Adult, Vitiligo, Autoimmune Diseases, Antinuclear antibody, Systemic lupus erythematosus, Sex Factors, Decompensated liver cirrhosis, Mitochondrion antibody, Internal medicine, Psoriasis, medicine, Multiple sclerosi, Collagenous colitis, Mitochondrion, Membranous glomerulonephritis, Hepatology, business.industry, Bleeding, Bilirubin, Polyarteritis nodosa, Alkaline Phosphatase, Polymyositis, Biological marker, business, Controlled study, Sjoegren syndrome
Abstract

Background and Aim: The prevalence and clinical significance of extrahepatic autoimmune diseases (EHAIDs) have not been evaluated in a large cohort of primary biliary cholangitis (PBC). Methods: The medical records of 1554 patients with PBC from 20 international centers were retrospectively reviewed. Development of decompensated cirrhosis (ascites, variceal bleeding, and/or hepatic encephalopathy) and hepatocellular carcinoma were considered clinical endpoints. Results: A total of 35 different EHAIDs were diagnosed in 440 (28.3%) patients with PBC. Patients with EHAIDs were more often female (92.5% vs 86.1%, P&nbsp

Published
2021

5. Validation of risk scoring systems in ursodeoxycholic acid-treated patients with primary biliary Cholangitis

Author

Fatema Alalkim, Benedetta Terziroli Beretta-Piccoli, Thomas Berg, Cumali Efe, Fulya Gunsar, Ellina Lytvyak, Janett Fischer, Fredrik Rorsman, Ali Riza Caliskan, Hanns-Ulrich Marschall, Kristina Önnerhag, Tugrul Purnak, Ida Henriksson, Maneerat Chayanupatkul, Claudia Coppo, Can Gonen, David Semela, Staffan Wahlin, Murat Kiyici, Ersan Ozaslan, Alexandra Heurgué-Berlot, Emma Nilsson, Alan Bonder, Koray Tascilar, Luigi Muratori, Fatih Güzelbulut, Murat Aladağ, Aldo J. Montano-Loza, Fatih Eren, Mårten Werner, Nurhan Demir, Henriette Ytting, Paolo Muratori, Thomas D. Schiano, Hirsh D. Trivedi, Eric M. Yoshida, Johanna Eliasson, Bursa Uludağ Üniversitesi/Tıp Fakültesi/Dahili Tıp Bilimleri., Eren, Fatih, AAS-6286-2020, Ege Üniversitesi, Efe C., Tascilar K., Henriksson I., Lytvyak E., Alalkim F., Trivedi H., Eren F., Eliasson J., Beretta-Piccoli B.T., Fischer J., Caliskan A.R., Chayanupatkul M., Coppo C., Ytting H., Purnak T., Muratori L., Werner M., Muratori P., Rorsman F., Onnerhag K., Gunsar F., Nilsson E., Heurgue-Berlot A., Guzelbulut F., Demir N., Gonen C., Semela D., Aladag M., Kiyici M., Schiano T.D., Montano-Loza A.J., Berg T., Ozaslan E., Yoshida E.M., Bonder A., Marschall H.-U., and Wahlin S.

Subjects
Male, Scoring system, Survival rate, Kaplan Meier method, Cholagogues and choleretics, Gastroenterology, 0302 clinical medicine, Cholagogue, Pathology, Histological progression, Treatment outcome, Child, Hepatic encephalopathy, Prognosis, Ursodeoxycholic acid, Multicenter study, Clinical trial, Retrospective study, Cirrhosis, Biochemical response, Primary biliary cirrhosis, liver, autoimmune, human, 030220 oncology & carcinogenesis, Predictive value of tests, Risk stratification, Disease Progression, Dose-response relationship, drug, Cohort studies, 030211 gastroenterology & hepatology, Cohort analysis, Human, medicine.medical_specialty, Sex factor, Cholangitis, Biliary Liver Cirrhosis, Obeticholic Acid, Major clinical study, Article, Adverse outcome, 03 medical and health sciences, Age, Severity of illness, Dose response, Humans, Disease exacerbation, Survival analysis, Confidence interval, Biliary cirrhosis, Follow up, Globe, digestive system diseases, Event free survival, United States, Retrospective studies, International cooperation, Gastroenterology & hepatology, Internationality, Survival, Middle aged, Priority journal, Risk assessment, Liver Cirrhosis, Biliary, Ascites, Validation study, Europe, Female, France, Sex factors, Age factors, medicine.drug, Adult, Canada, Proportional hazards models, Adolescent, Kaplan-Meier estimate, Hazard ratio, Placebo-controlled trial, Predictive value, macromolecular substances, Outcomes, Proportional hazards model, Internal medicine, medicine, Mortality, Hepatology, business.industry, Drug administration, Bleeding, Drug administration schedule, Retrospective cohort study, Severity of illness index, Spain, Bezafibrate, business, Prediction, Controlled study
Abstract

EgeUn###, INTRODUCTION: Risk stratification based on biochemical variables is a useful tool for monitoring ursodeoxycholic acid (UDCA)-treated patients with primary biliary cholangitis (PBC). Several UDCA response criteria and scoring systems have been proposed for risk prediction in PBC, but these have not been validated in large external cohorts. METHODS: We performed a study on data of 1746 UDCA-treated patients with PBC from 25 centers in Europe, United States, and Canada. The prognostic performance of the risk scoring systems (GLOBE and UK-PBC) and the UDCA response criteria (Barcelona, Paris I, Paris II, Rotterdam, and Toronto) were evaluated. We regarded cirrhosis-related complications (ascites, variceal bleeding, and/or hepatic encephalopathy) as clinical end points. RESULTS: A total of 171 patients reached a clinical end point during a median 7 years (range 1-16 years) of follow-up. The 5-, 10- and 15-year adverse outcome-free survivals were 95%, 85%, and 77%. The GLOBE and UK-PBC scores predicted cirrhosis-related complications better than the UDCA response criteria. The hazard ratio (HR) for a 1 standard deviation increase was HR 5.05 (95% confidence interval (CI): 4.43-5.74, P < 0.001) for the GLOBE score and HR 3.39 (95% CI: 3.10-3.72, P < 0.001) for the UK-PBC score. Overall, the GLOBE and UK-PBC risk scores showed similar and excellent prognostic performance (C-statistic, 0.93; 95% CI: 0.91%-95% vs 0.94; 95% CI: 0.91%-0.96%). DISCUSSION: In our international, multicenter PBC cohort, the GLOBE and UK-PBC risk scoring systems were good predictors of future cirrhosis-related complications.

Published
2019

6. The relation between liver histopathology and GGT levels in viral hepatitis: More important in hepatitis B

Author

Enver Dolar, Macit Gülten, Kader Irak, Murat Kiyici, Selim Giray Nak, Ahmet Tarık Eminler, Selim Gürel, Murat Keskin, Talat Ayyildiz, Uludağ Üniversitesi/Tıp Fakültesi/İç Hastalıkları Anabilim Dalı., Eminler, Ahmet Tarık, Irak, Kader, Ayyıldız, Talat, Keskin, Murat, Kıyıcı, Murat, Gürel, Selim, Gülten, Macit, Dolar, Enver, Nak, Selim Giray, AAG-9177-2021, R-8751-2019, AAI-4213-2021, Eminler, AT, Irak, K, Ayyildiz, T, Keskin, M, Kiyici, M, Gurel, S, Gulten, M, Dolar, E, Nak, SG, Sakarya Üniversitesi/Tıp Fakültesi/Dahili Tıp Bilimleri Bölümü, and Gürel, Selda

Subjects
Male, Liver Cirrhosis, Pathology, Biopsy, Gamma glutamyl transferase blood level, Chronic hepatitis C, Severity of Illness Index, Gastroenterology, Questionnaires and rating scales, Liver pathology, Fibrosis, Outpatient clinic, Viral hepatitis, medicine.diagnostic_test, Biochemical markers, food and beverages, Alanine Transaminase, gamma-Glutamyltransferase, Hepatitis C, Liver biopsy, Patient referral, Middle Aged, Hepatitis B, Histological activity index, Blood, Liver, RNA, Viral, Female, Human, Adult, medicine.medical_specialty, Adolescent, Gamma glutamyltransferase, Virus RNA, Liver fibrosis, C virus-infection, Histopathology, Major clinical study, Aspartate aminotransferase, Article, Young Adult, Hepatitis B, Chronic, Internal medicine, Virus DNA, Thrombocyte count, medicine, Humans, Aspartate Aminotransferases, International Normalized Ratio, Human tissue, Aged, Platelet Count, business.industry, Gamma-Glutamyltransferase, Alanine Aminotransferase, Biomarkers, Hepatitis C, Chronic, Alkaline Phosphatase, medicine.disease, Ishak Score, GGT, Ishak score, DNA, Viral, Alanine aminotransferase, Enzymology, Comparative study, business, Gastroenterology & hepatology, Named inventories
Abstract

Background/Aims: To investigate the relationship between gamma-glutamyl transpeptidase (GGT) levels and histopathological status determined by biopsy in patients with chronic hepatitis B and C. Materials and Methods: Patients with chronic hepatitis B and C who were referred to the Uludag University Faculty of Medicine Gastroenterology outpatient clinic between January 2005-January 2011 and underwent liver biopsy were included in the study. Overall, 246 patients with hepatitis B and 151 patients with hepatitis C were enrolled. According to the evaluation based on the Ishak score, patients with a histological activity index (HAI) between 0-12 were defined as low activity, and those with an HAI between 13-18 were defined as high activity. In addition, patients with a fibrosis score of 0-2 were defined as low fibrosis, and those with a score between 3-6 were defined as high fibrosis; comparisons were made accordingly. Results: In patients with hepatitis B, the mean GGT level was 38.86 +/- 42.4 (IU/L) in the low activity group and 60.44 +/- 44.4 (IU/L) in the high activity group (p

Published
2014

7. AST/ALT ratio is not useful in predicting the degree of fibrosis in chronic viral hepatitis patients

Author

Kader Irak, Enver Dolar, Macit Gülten, Murat Kiyici, Selim Giray Nak, Ahmet Tarık Eminler, Selim Gürel, Talat Ayyildiz, Uludağ Üniversitesi/Tıp Fakültesi/Gastroenteroloji Anabilim Dalı., Irak, Kader, Kıyıcı, Murat, Gürel, Selim, Dolar, Enver, Gülten, Macit, Nak, Selim G., AAG-9177-2021, AAI-4213-2021, Eminler, AT, Ayyildiz, T, Irak, K, Kiyici, M, Gurel, S, Dolar, E, Gulten, M, Nak, SG, Sakarya Üniversitesi/Tıp Fakültesi/Dahili Tıp Bilimleri Bölümü, Eminler, Ahmet Tarık, and Ondokuz Mayıs Üniversitesi

Subjects
Liver Cirrhosis, Male, Aspartate aminotransferase blood level, Scoring system, Cirrhosis, Blood-tests, Receiver operating characteristic, Chronic hepatitis C, Procedures, Chronic liver disease, Chronic hepatitis B, Gastroenterology, Severity of Illness Index, Evaluation study, Aspartate aminotransferase to platelet ratio index, Chronic liver-disease, Digestive system disease assessment, Investigative procedures, Accuracy, Priority journal, biology, AST/ALT ratio, Alanine Transaminase, Hepatitis C, Liver biopsy, Hepatitis B, Middle Aged, Aspartate aminotransferase alanine aminotransferase ratio, Retrospective study, Blood, King s score, Non invasive procedure, Aspartate-aminotransferase, Alanine aminotransferase blood level, Female, Viral hepatitis, Human, Adult, medicine.medical_specialty, Liver fibrosis, C virus-infection, Predictive value, Major clinical study, Aspartate aminotransferase, Transaminase, Sensitivity and Specificity, Age platelet index, Article, Hepatitis B, Chronic, Predictive Value of Tests, Virology, Internal medicine, Thrombocyte count, medicine, Humans, Aspartate Aminotransferases, Human tissue, Elasticity Imaging Techniques, Esophagus Varices, Fibrosis, Retrospective Studies, Hepatology, business.industry, Platelet Count, Bonacini cirrhosis discriminant score, fibrosis, Noninvasive assessment, Clinical Enzyme Tests, Hepatitis C, Chronic, Enzyme assay, medicine.disease, Index, Biological marker, Ishak score, Alanine transaminase, Immunology, Alanine aminotransferase, biology.protein, hepatitis B, hepatitis C, Hepatic fibrosis, business, Gastroenterology & hepatology, Complication, Biomarkers
Abstract

WOS: 000364330100001 PubMed: 26352130 Background and aim Noninvasive tests are primarily used for staging hepatic fibrosis in patients with chronic liver disease. In clinical practice, serum aminotransferase levels, coagulation parameters, and platelet count have been used to predict whether or not a patient has cirrhosis. In addition, several studies have evaluated the accuracy of combinations (or ratios) of these measures. The present study aimed to investigate the relationship between five noninvasive models [AST/ALT ratio (AAR), aspartate aminotransferase to platelet ratio index (APRI), Bonacini cirrhosis discriminant score (CDS), age-platelet index (APind), and King's score] and the degree of hepatic fibrosis as determined by biopsy in patients with chronic hepatitis B and C. Patients and methods A total of 380 patients with viral hepatitis (237 with chronic hepatitis B and 143 with chronic hepatitis C) who were seen at our clinic between January 2005 and January 2011 were retrospectively analyzed. The degree of fibrosis was determined using the Ishak score. Patients with a fibrosis score of 0-2 were considered to have low fibrosis and those with a score between 3 and 6 were considered to have high fibrosis. Five noninvasive models were compared between the groups with low and high fibrosis. Results There were statistically significant differences between the hepatitis B and C patients with high and low fibrosis with respect to APind (4.492.35 vs. 2.41 +/- 1.84; P

Published
2015

8. Mean platelet volume is an important predictor of hepatitis C but not hepatitis B liver damage

Author

Selim Gürel, Kader Irak, Ahmet Tarık Eminler, Mustafa Ihsan Uslan, Enver Dolar, Macit Gülten, Talat Ayyildiz, Selim Giray Nak, Murat Kiyici, OMÜ, Eminler, AT, Uslan, MI, Ayyildiz, T, Irak, K, Kiyici, M, Gurel, S, Dolar, E, Gulten, M, Nak, SG, Sakarya Üniversitesi/Tıp Fakültesi/Dahili Tıp Bilimleri Bölümü, Eminler, Ahmet Tarık, and Uslan, Mustafa İhsan

Subjects
medicine.medical_specialty, lcsh:Medicine, Gastroenterology, Fibrosis, Internal medicine, General & Internal Medicine, medicine, Mean platelet volume, Hepatitis, mean platelet volume, medicine.diagnostic_test, business.industry, lcsh:R, General Medicine, Hepatitis C, Hepatitis B, medicine.disease, Surgery, Liver biopsy, Histopathology, Original Article, hepatitis B, hepatitis C, Viral hepatitis, business
Abstract

USLAN, MUSTAFA IHSAN/0000-0002-8890-8026 WOS: 000367668900008 PubMed: 26759574 Background: The mean platelet volume (MPV) is the most commonly used measure of platelet size and is a potential marker of platelet reactivity. In this study, we aimed to explore the relationship between hepatic histopathology in viral hepatitis and MPV levels, which are associated with platelet count and activity. Materials and Methods: We performed a retrospective case-control study of baseline histological and clinical parameters in chronic hepatitis B and C patients in our tertiary reference center between January 2005 and January 2011. Two hundred and five chronic hepatitis B patients and 133 chronic hepatitis C patients who underwent liver biopsy were included in the study. The patients were divided into two groups: Chronic hepatitis B and chronic hepatitis C and were additionally divided into groups of two according to histological activity index (HAI) and fibrosis scores obtained by liver biopsy results (according to the Ishak scoring system). The clinical characteristics of chronic viral hepatitis patients, including demographics, laboratory (especially MPV), and liver biopsy findings, were reviewed. Results: One hundred and forty-three patients were male (69.1%), and the mean age was 41.9 +/- 12.75 with an age range of 18-71 years in hepatitis B patients. In the classification made according to HAI, 181 patients were in the low activity group (88.3%) and 24 in the high activity group (11.7%). In the evaluation made according to fibrosis score, 169 patients were found to have early fibrosis (82.4%) and 36 were found to have advanced fibrosis (17.6%). In patients with hepatitis B, there was no statistically significant difference in terms of their MPV values between the two groups, separated according to their degree of activity and fibrosis. Sixty-three patients were male (47.3%), and the mean age was 50.03 +/- 12.75 with an age range of 19-75 years. In the classification made according to HAI, 109 patients were in low activity group (81.9%) and 24 in high activity group (18.1%). In the evaluation made according to fibrosis score, 101 patients were found to have early fibrosis (75.9%) and 32 have advanced fibrosis (24.1%). There was a statistically significant difference between the activity and fibrosis groups of the hepatitis C patients (P = 0.04 and P = 0.02, respectively). Conclusion: MPV values are more reliable in hepatitis C patients than hepatitis B for predicting the advanced damage in liver histology. This finding might be useful for the detection of early fibrosis and also starting early treatment, which is important in hepatitis C.

Published
2015

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