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1. Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysis

Author

Anstee, Quentin M, Daly, Ann K, Govaere, Olivier, Cockell, Simon, Tiniakos, Dina, Bedossa, Pierre, Burt, Alastair, Oakley, Fiona, Cordell, Heather J, Day, Christopher P, Wonders, Kristy, Missier, Paolo, McTeer, Matthew, Vale, Luke, Oluboyede, Yemi, Breckons, Matt, Bossuyt, Patrick M, Zafarmand, Hadi, Vali, Yasaman, Lee, Jenny, Nieuwdorp, Max, Holleboom, Adriaan G, Verheij, Joanne, Ratziu, Vlad, Clément, Karine, Patino-Navarrete, Rafael, Pais, Raluca, Paradis, Valerie, Schuppan, Detlef, Schattenberg, Jörn M, Surabattula, Rambabu, Myneni, Sudha, Straub, Beate K, Vidal-Puig, Toni, Vacca, Michele, Rodrigues-Cuenca, Sergio, Allison, Mike, Kamzolas, Ioannis, Petsalaki, Evangelia, Campbell, Mark, Lelliott, Chris J, Davies, Susan, Orešič, Matej, Hyötyläinen, Tuulia, McGlinchey, Aiden, Mato, Jose M, Millet, Óscar, Dufour, Jean-François, Berzigotti, Annalisa, Masoodi, Mojgan, Pavlides, Michael, Harrison, Stephen, Neubauer, Stefan, Cobbold, Jeremy, Mozes, Ferenc, Akhtar, Salma, Olodo-Atitebi, Seliat, Banerjee, Rajarshi, Kelly, Matt, Shumbayawonda, Elizabeth, Dennis, Andrea, Andersson, Anneli, Wigley, Ioan, Romero-Gómez, Manuel, Gómez-González, Emilio, Ampuero, Javier, Castell, Javier, Gallego-Durán, Rocío, Fernández, Isabel, Montero-Vallejo, Rocío, Karsdal, Morten, Rasmussen, Daniel Guldager Kring, Leeming, Diana Julie, Sinisi, Antonia, Musa, Kishwar, Sandt, Estelle, Tonini, Manuela, Bugianesi, Elisabetta, Rosso, Chiara, Armandi, Angelo, Marra, Fabio, Gastaldelli, Amalia, Svegliati, Gianluca, Boursier, Jérôme, Francque, Sven, Vonghia, Luisa, Driessen, Ann, Ekstedt, Mattias, Kechagias, Stergios, Yki-Järvinen, Hannele, Porthan, Kimmo, Arola, Johanna, van Mil, Saskia, Papatheodoridis, George, Cortez-Pinto, Helena, Rodrigues, Cecilia M P, Valenti, Luca, Pelusi, Serena, Petta, Salvatore, Pennisi, Grazia, Miele, Luca, Geier, Andreas, Trautwein, Christian, Reißing, Johanna, Aithal, Guruprasad P, Francis, Susan, Palaniyappan, Naaventhan, Bradley, Christopher, Hockings, Paul, Schneider, Moritz, Newsome, Philip, Hübscher, Stefan, Wenn, David, Rosenquist, Christian, Trylesinski, Aldo, Mayo, Rebeca, Alonso, Cristina, Duffin, Kevin, Perfield, James W, Chen, Yu, Yunis, Carla, Tuthill, Theresa, Harrington, Magdalena Alicia, Miller, Melissa, Chen, Yan, McLeod, Euan James, Ross, Trenton, Bernardo, Barbara, Schölch, Corinna, Ertle, Judith, Younes, Ramy, Oldenburger, Anouk, Coxson, Harvey, Ostroff, Rachel, Alexander, Leigh, Biegel, Hannah, Kjær, Mette Skalshøi, Harder, Lea Mørch, Davidsen, Peter, Ellegaard, Jens, Balp, Maria-Magdalena, Brass, Clifford, Jennings, Lori, Martic, Miljen, Löffler, Jürgen, Applegate, Douglas, Shankar, Sudha, Torstenson, Richard, Lindén, Daniel, Fournier-Poizat, Céline, Llorca, Anne, Kalutkiewicz, Michael, Pepin, Kay, Ehman, Richard, Horan, Gerald, Ho, Gideon, Tai, Dean, Chng, Elaine, Patterson, Scott D, Billin, Andrew, Doward, Lynda, Twiss, James, Thakker, Paresh, Derdak, Zoltan, Landgren, Henrik, Lackner, Carolin, Gouw, Annette, Hytiroglou, Prodromos, Mózes, Ferenc E, Lee, Jenny A, Alzoubi, Osama, Staufer, Katharina, Trauner, Michael, Paternostro, Rafael, Stauber, Rudolf E, van Dijk, Anne-Marieke, Mak, Anne Linde, de Saint Loup, Marc, Shima, Toshihide, Gaia, Silvia, Shalimar, Lupșor-Platon, Monica, Wong, Vincent Wai-Sun, Li, Guanlin, Wong, Grace Lai-Hung, Karlas, Thomas, Wiegand, Johannes, Sebastiani, Giada, Tsochatzis, Emmanuel, Liguori, Antonio, Yoneda, Masato, Nakajima, Atsushi, Hagström, Hannes, Akbari, Camilla, Hirooka, Masashi, Chan, Wah-Kheong, Mahadeva, Sanjiv, Rajaram, Ruveena, Zheng, Ming-Hua, George, Jacob, Eslam, Mohammed, Viganò, Mauro, Ridolfo, Sofia, Aithal, Guruprasad Padur, Lee, Dae Ho, Nasr, Patrik, Cassinotto, Christophe, de Lédinghen, Victor, Mendoza, Yuly P, Noureddin, Mazen, Truong, Emily, and Harrison, Stephen A

Published
2023
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4. Quantitative magnetic resonance imaging in evaluating haemodynamic changes in portal hypertension

Author

Palaniyappan, Naaventhan

Subjects
616.1, WI Digestive system
Abstract

The majority of complications in patients with cirrhosis result from the development and progression of portal hypertension characterised by increased intrahepatic resistance and progressive splanchnic vasodilation. Hepatic venous pressure gradient (HVPG) measurement is the only validated technique to accurately evaluate changes in portal pressure. However, HVPG measurements are invasive and available only in specialised hepatology units, precluding its use in routine clinical practice. In the first study, we evaluated the use of non-contrast quantitative magnetic resonance imaging (MRI) as a surrogate measure of portal pressure. 30 patients undergoing HVPG measurement were prospectively recruited. MR parameters of longitudinal relaxation time (T1), perfusion of the liver and spleen (by arterial spin labelling), and blood flow in the portal, splanchnic and collateral circulation (by phase-contrast MRI) were assessed. We estimated the liver stiffness measurement (LSM) and Enhanced Liver Fibrosis (ELF) score. The correlation of all non-invasive parameters with HVPG was evaluated. The mean (range) HVPG of the patients was 9.8 (1-22) mmHg, and 14 patients (48%) had clinically significant portal hypertension (CSPH, HVPG ≥10 mmHg). Liver T1 relaxation time, splenic artery and superior mesenteric artery velocity correlated significantly with HVPG. Using multiple linear regression, liver T1 and splenic artery velocity remained as the two parameters in the multivariate model significantly associated with HVPG (R=0.90, p < 0.001). This correlation was maintained in patients with CSPH (R=0.85, p < 0.001). A validation cohort (n=10) showed this linear model provided a good prediction of HVPG. LSM and ELF score correlated significantly with HVPG in the whole population but the correlation was absent in CSPH. In conclusion, MR parameters related to both hepatic architecture and splanchnic haemodynamics correlate significantly with HVPG. This proposed model, confirmed in a validation cohort, could replace the invasive HVPG measurement. In the second part, we studied the use non-invasive MRI to dynamically assess changes in hepatic and collateral blood flow, liver perfusion and oxygenation in response to ingestion of a test meal (meal challenge), and hyperoxia and hypercapnia (gas challenge). These changes were compared between healthy subjects and patients with compensated cirrhosis (CC). In the meal challenge study, we evaluated the blood flow in the portal vein, hepatic artery and azygos vein, liver perfusion and blood oxygenation (using transverse relaxation time (T2*) mapping). Measures were collected at baseline and at 6-7 minute intervals from 20 to 65 minutes following a test meal (440 ml; 660 kcal) in 10 healthy participants and 10 CC patients. In healthy participants, we observed a postprandial increase in portal vein flow from baseline coupled with a reduction in hepatic artery flow from baseline, reflecting the hepatic artery buffer response (HABR). In CC patients, changes in portal vein and hepatic artery flow were smaller, with no clear HABR. In healthy participants, postprandial liver perfusion increased, but not in CC patients. There was no change in liver T2* for either group. In the gas challenge study, we evaluated the blood flow in portal vein and hepatic artery, liver perfusion and liver T2* during hyperoxia and hypercapnia in 10 healthy subjects and 4 patients with compensated cirrhosis. A sequential gas delivery breathing circuit and a prospective, feed-forward gas delivery system (RespiractTM, Thornhill Research Inc., Toronto, Canada) was used to control and monitor end-tidal O2 (PETO2) and CO2 (PETCO2) partial pressures. Hyperoxia was targeted at PETO2 ~500mmHg and hypercapnia was aimed at PETCO2 ~6mmHg above resting value. The study design consisted of 5 blocks. Blocks 1, 3 and 5 were 5 min periods at resting PETCO2 and PETO2. Blocks 2 and 4 were, in a random order, 5 mins of hyperoxia (with a 2 min transition up and down) or 5 mins of hypercapnia. We observed an increase in portal vein velocity during hypercapnia among the healthy subjects and patients with cirrhosis. There was no significant changes in liver T2* but the full-width-half-maximum (FWHM) of the distribution of the liver T2* increased in response to hyperoxia and hypercapnia in both groups. Subjects with low T2* at baseline exhibited a smaller change in FWHM following the gas challenge. The within session and inter-session coefficient of variation (CoV) the blood flow measurement using phase-contrast MRI in healthy subjects was less than 15%. If our findings are confirmed in external validation studies, non-invasive MRI can be used as a surrogate measure of HVPG. Assessment of postprandial dynamic changes in hepatic, splanchnic and collateral circulation using MRI could potentially be used to stratify patients with portal hypertension and study the effects of potential novel treatments for portal hypertension.

Published
2017

6. Long-term outcomes (beyond 5 years) of liver transplant recipients - a transatlantic multicentre study

Author

Palaniyappan, Naaventhan, primary, Peach, Emily, additional, Pearce, Fiona, additional, Dhaliwal, Amritpal, additional, Campos-Varela, Isabel, additional, Cant, Matthew R., additional, Dopazo, Cristina, additional, Trotter, James, additional, Divani-Patel, Sapna, additional, Hatta, Ayiesha AZ, additional, Hopkins, Laurence, additional, Testa, Giuliano, additional, Bilbao, Angela, additional, Kasmani, Zain, additional, Faloon, Sarah, additional, Mirza, Darius F, additional, Klintmalm, Goran B, additional, Bilbao, Itxarone, additional, Asrani, Sumeet K, additional, Rajoriya, Neil, additional, and Aravinthan, Aloysious D, additional

Published
2023
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7. Long-term outcomes (beyond 5 years) of liver transplant recipients—A transatlantic multicenter study.

Author

Palaniyappan, Naaventhan, Peach, Emily, Pearce, Fiona, Dhaliwal, Amritpal, Campos-Varela, Isabel, Cant, Matthew R., Dopazo, Cristina, Trotter, James, Divani-Patel, Sapna, Hatta, Ayiesha A. Z., Hopkins, Laurence, Testa, Giuliano, Bilbao, Angela, Kasmani, Zain, Faloon, Sarah, Mirza, Darius F., Klintmalm, Goran B., Bilbao, Itxarone, Asrani, Sumeet K., and Rajoriya, Neil

Published
2024
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8. Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysis

Author

Mozes, Ferenc E., Lee, Jenny A., Vali, Yasaman, Alzoubi, Osama, Staufer, Katharina, Trauner, Michael, Paternostro, Rafael, Stauber, Rudolf E., Holleboom, Adriaan G., van Dijk, Anne-Marieke, Mak, Anne Linde, Boursier, Jerome, Loup, Marc de Saint, Shima, Toshihide, Bugianesi, Elisabetta, Gaia, Silvia, Armandi, Angelo, Shalimar, Lupsor-Platon, Monica, Wong, Vincent Wai-Sun, Li, Guanlin, Wong, Grace Lai-Hung, Cobbold, Jeremy, Karlas, Thomas, Wiegand, Johannes, Sebastiani, Giada, Tsochatzis, Emmanuel, Liguori, Antonio, Yoneda, Masato, Nakajima, Atsushi, Hagstrom, Hannes, Akbari, Camilla, Hirooka, Masashi, Chan, Wah-Kheong, Mahadeva, Sanjiv, Rajaram, Ruveena, Zheng, Ming-Hua, George, Jacob, Eslam, Mohammed, Petta, Salvatore, Pennisi, Grazia, Vigano, Mauro, Ridolfo, Sofia, Aithal, Guruprasad Padur, Palaniyappan, Naaventhan, Lee, Dae Ho, Ekstedt, Mattias, Nasr, Patrik, Cassinotto, Christophe, de Ledinghen, Victor, Berzigotti, Annalisa, Mendoza, Yuly P., Noureddin, Mazen, Truong, Emily, Fournier-Poizat, Celine, Geier, Andreas, Martic, Miljen, Tuthill, Theresa, Anstee, Quentin M., Harrison, Stephen A., Bossuyt, Patrick M., Pavlides, Michael, Mozes, Ferenc E., Lee, Jenny A., Vali, Yasaman, Alzoubi, Osama, Staufer, Katharina, Trauner, Michael, Paternostro, Rafael, Stauber, Rudolf E., Holleboom, Adriaan G., van Dijk, Anne-Marieke, Mak, Anne Linde, Boursier, Jerome, Loup, Marc de Saint, Shima, Toshihide, Bugianesi, Elisabetta, Gaia, Silvia, Armandi, Angelo, Shalimar, Lupsor-Platon, Monica, Wong, Vincent Wai-Sun, Li, Guanlin, Wong, Grace Lai-Hung, Cobbold, Jeremy, Karlas, Thomas, Wiegand, Johannes, Sebastiani, Giada, Tsochatzis, Emmanuel, Liguori, Antonio, Yoneda, Masato, Nakajima, Atsushi, Hagstrom, Hannes, Akbari, Camilla, Hirooka, Masashi, Chan, Wah-Kheong, Mahadeva, Sanjiv, Rajaram, Ruveena, Zheng, Ming-Hua, George, Jacob, Eslam, Mohammed, Petta, Salvatore, Pennisi, Grazia, Vigano, Mauro, Ridolfo, Sofia, Aithal, Guruprasad Padur, Palaniyappan, Naaventhan, Lee, Dae Ho, Ekstedt, Mattias, Nasr, Patrik, Cassinotto, Christophe, de Ledinghen, Victor, Berzigotti, Annalisa, Mendoza, Yuly P., Noureddin, Mazen, Truong, Emily, Fournier-Poizat, Celine, Geier, Andreas, Martic, Miljen, Tuthill, Theresa, Anstee, Quentin M., Harrison, Stephen A., Bossuyt, Patrick M., and Pavlides, Michael

Abstract

Background Histologically assessed liver fibrosis stage has prognostic significance in patients with non-alcoholic fatty liver disease (NAFLD) and is accepted as a surrogate endpoint in clinical trials for non-cirrhotic NAFLD. Our aim was to compare the prognostic performance of non-invasive tests with liver histology in patients with NAFLD. Methods This was an individual participant data meta-analysis of the prognostic performance of histologically assessed fibrosis stage (F0-4), liver stiffness measured by vibration-controlled transient elastography (LSM-VCTE), fibrosis-4 index (FIB-4), and NAFLD fibrosis score (NFS) in patients with NAFLD. The literature was searched for a previously published systematic review on the diagnostic accuracy of imaging and simple non-invasive tests and updated to Jan 12, 2022 for this study. Studies were identified through PubMed/MEDLINE, EMBASE, and CENTRAL, and authors were contacted for individual participant data, including outcome data, with a minimum of 12 months of follow-up. The primary outcome was a composite endpoint of all-cause mortality, hepatocellular carcinoma, liver transplantation, or cirrhosis complications (ie, ascites, variceal bleeding, hepatic encephalopathy, or progression to a MELD score >= 15). We calculated aggregated survival curves for trichotomised groups and compared them using stratified log-rank tests (histology: F0-2 vs F3 vs F4; LSM: <10 vs 10 to <20 vs >= 20 kPa; FIB-4: <13 vs 13 to <= 267 vs >267; NFS: <-1455 vs -1455 to <= 0676 vs >0676), calculated areas under the time-dependent receiver operating characteristic curves (tAUC), and performed Cox proportional-hazards regression to adjust for confounding. This study was regist, Funding Agencies|Innovative Medicines Initiative 2 (IMI2) Joint Undertaking [777377]; EU; EFPIA; Fonds de Recherche du Quebec-Sante [296306]; Wellcome Trust [221805/Z/20/Z]; Royal Society [221805/Z/20/Z]; KHIDI - Ministry of Health Welfare, Korea [HI14C1135]; Newcastle NIHR Biomedical Research Centre

Published
2023
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9. Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysis

Author

Mózes, Ferenc E, Lee, Jenny A, Vali, Yasaman, Alzoubi, Osama, Staufer, Katharina, Trauner, Michael, Paternostro, Rafael, Stauber, Rudolf E, Holleboom, Adriaan G, van Dijk, Anne-Marieke, Mak, Anne Linde, Boursier, Jérôme, de Saint Loup, Marc, Shima, Toshihide, Bugianesi, Elisabetta, Gaia, Silvia, Armandi, Angelo, Shalimar, Null, Lupșor-Platon, Monica, Wong, Vincent Wai-Sun, Li, Guanlin, Wong, Grace Lai-Hung, Cobbold, Jeremy, Karlas, Thoma, Wiegand, Johanne, Sebastiani, Giada, Tsochatzis, Emmanuel, Liguori, Antonio, Yoneda, Masato, Nakajima, Atsushi, Hagström, Hanne, Akbari, Camilla, Hirooka, Masashi, Chan, Wah-Kheong, Mahadeva, Sanjiv, Rajaram, Ruveena, Zheng, Ming-Hua, George, Jacob, Eslam, Mohammed, Petta, Salvatore, Pennisi, Grazia, Viganò, Mauro, Ridolfo, Sofia, Aithal, Guruprasad Padur, Palaniyappan, Naaventhan, Lee, Dae Ho, Ekstedt, Mattia, Nasr, Patrik, Cassinotto, Christophe, de Lédinghen, Victor, Berzigotti, Annalisa, Mendoza, Yuly P, Noureddin, Mazen, Truong, Emily, Fournier-Poizat, Céline, Geier, Andrea, Martic, Miljen, Tuthill, Theresa, Anstee, Quentin M, Harrison, Stephen A, Bossuyt, Patrick M, Pavlides, Michael, Miele, Luca, Litmus, Investigators, Miele, Luca (ORCID:0000-0003-3464-0068), Mózes, Ferenc E, Lee, Jenny A, Vali, Yasaman, Alzoubi, Osama, Staufer, Katharina, Trauner, Michael, Paternostro, Rafael, Stauber, Rudolf E, Holleboom, Adriaan G, van Dijk, Anne-Marieke, Mak, Anne Linde, Boursier, Jérôme, de Saint Loup, Marc, Shima, Toshihide, Bugianesi, Elisabetta, Gaia, Silvia, Armandi, Angelo, Shalimar, Null, Lupșor-Platon, Monica, Wong, Vincent Wai-Sun, Li, Guanlin, Wong, Grace Lai-Hung, Cobbold, Jeremy, Karlas, Thoma, Wiegand, Johanne, Sebastiani, Giada, Tsochatzis, Emmanuel, Liguori, Antonio, Yoneda, Masato, Nakajima, Atsushi, Hagström, Hanne, Akbari, Camilla, Hirooka, Masashi, Chan, Wah-Kheong, Mahadeva, Sanjiv, Rajaram, Ruveena, Zheng, Ming-Hua, George, Jacob, Eslam, Mohammed, Petta, Salvatore, Pennisi, Grazia, Viganò, Mauro, Ridolfo, Sofia, Aithal, Guruprasad Padur, Palaniyappan, Naaventhan, Lee, Dae Ho, Ekstedt, Mattia, Nasr, Patrik, Cassinotto, Christophe, de Lédinghen, Victor, Berzigotti, Annalisa, Mendoza, Yuly P, Noureddin, Mazen, Truong, Emily, Fournier-Poizat, Céline, Geier, Andrea, Martic, Miljen, Tuthill, Theresa, Anstee, Quentin M, Harrison, Stephen A, Bossuyt, Patrick M, Pavlides, Michael, Miele, Luca, Litmus, Investigators, and Miele, Luca (ORCID:0000-0003-3464-0068)

Abstract

Background: Histologically assessed liver fibrosis stage has prognostic significance in patients with non-alcoholic fatty liver disease (NAFLD) and is accepted as a surrogate endpoint in clinical trials for non-cirrhotic NAFLD. Our aim was to compare the prognostic performance of non-invasive tests with liver histology in patients with NAFLD. Methods: This was an individual participant data meta-analysis of the prognostic performance of histologically assessed fibrosis stage (F0-4), liver stiffness measured by vibration-controlled transient elastography (LSM-VCTE), fibrosis-4 index (FIB-4), and NAFLD fibrosis score (NFS) in patients with NAFLD. The literature was searched for a previously published systematic review on the diagnostic accuracy of imaging and simple non-invasive tests and updated to Jan 12, 2022 for this study. Studies were identified through PubMed/MEDLINE, EMBASE, and CENTRAL, and authors were contacted for individual participant data, including outcome data, with a minimum of 12 months of follow-up. The primary outcome was a composite endpoint of all-cause mortality, hepatocellular carcinoma, liver transplantation, or cirrhosis complications (ie, ascites, variceal bleeding, hepatic encephalopathy, or progression to a MELD score ≥15). We calculated aggregated survival curves for trichotomised groups and compared them using stratified log-rank tests (histology: F0-2 vs F3 vs F4; LSM: <10 vs 10 to <20 vs ≥20 kPa; FIB-4: <1·3 vs 1·3 to ≤2·67 vs >2·67; NFS: <-1·455 vs -1·455 to ≤0·676 vs >0·676), calculated areas under the time-dependent receiver operating characteristic curves (tAUC), and performed Cox proportional-hazards regression to adjust for confounding. This study was registered with PROSPERO, CRD42022312226. Findings: Of 65 eligible studies, we included data on 2518 patients with biopsy-proven NAFLD from 25 studies (1126 [44·7%] were female, median age was 54 years [IQR 44-63), and 1161 [46·1%] had type 2 diabetes). After a me

Published
2023

10. Noninvasive assessment of liver disease severity in patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes

Author

Pennisi, Grazia, primary, Enea, Marco, additional, Falco, Vincenzo, additional, Aithal, Guruprasad P., additional, Palaniyappan, Naaventhan, additional, Yilmaz, Yusuf, additional, Boursier, Jerome, additional, Cassinotto, Christophe, additional, de Lédinghen, Victor, additional, Chan, Wah Kheong, additional, Mahadeva, Sanjiv, additional, Eddowes, Peter, additional, Newsome, Philip, additional, Karlas, Thomas, additional, Wiegand, Johannes, additional, Wong, Vincent Wai-Sun, additional, Schattenberg, Jörn M., additional, Labenz, Christian, additional, Kim, Won, additional, Lee, Myoung Seok, additional, Lupsor-Platon, Monica, additional, Cobbold, Jeremy F. L., additional, Fan, Jian-Gao, additional, Shen, Feng, additional, Staufer, Katharina, additional, Trauner, Michael, additional, Stauber, Rudolf, additional, Nakajima, Atsushi, additional, Yoneda, Masato, additional, Bugianesi, Elisabetta, additional, Younes, Ramy, additional, Gaia, Silvia, additional, Zheng, Ming-Hua, additional, Cammà, Calogero, additional, Anstee, Quentin M., additional, Mózes, Ferenc Emil, additional, Pavlides, Michael, additional, and Petta, Salvatore, additional

Published
2023
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14. Long-term outcomes (beyond 5 years) of liver transplant recipients-a transatlantic multicentre study

Author

Palaniyappan, Naaventhan, primary, Peach, Emily, additional, Pearce, Fiona, additional, Dhaliwal, Amritpal, additional, Campos-Varela, Isabel, additional, Cant, Matthew, additional, Dopazo, Cristina, additional, Divani-Patel, Sapna, additional, Trotter, James F., additional, Hatta, Ayiesha, additional, Hopkins, Laurence, additional, Testa, Giuliano, additional, Bilbao, Angela, additional, Kasmani, Zain, additional, Faloon, Sarah, additional, Mirza, Darius F., additional, Klintmalm, Goran, additional, Bilbao, Itxarone, additional, Asrani, Sumeet, additional, Rajoriya, Neil, additional, and Aravinthan, Aloysious, additional

Published
2022
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15. Diagnostic accuracy of non-invasive tests for fibrotic NASH-An individual participant data meta-analysis

Author

Mozes, Ferenc, primary, Lee, Jenny, additional, Vali, Yasaman, additional, Selvaraj, Emmanuel, additional, Jayaswal, Arjun, additional, Boursier, Jerome, additional, Bugianesi, Elisabetta, additional, Younes, Ramy, additional, Lupsor-Platon, Monica, additional, Petta, Salvatore, additional, Shima, Toshihide, additional, Okanoue, Takeshi, additional, Mahadeva, Sanjiv, additional, Chan, Wah-Kheong, additional, Hirschfield, Gideon, additional, Eddowes, Peter, additional, Newsome, Philip N., additional, Wong, Vincent Wai-Sun, additional, de Lédinghen, Victor, additional, Cobbold, Jeremy, additional, Sumida, Yoshio, additional, Okajima, Akira, additional, Schattenberg, Jörn, additional, Labenz, Christian, additional, Kim, Won, additional, Lee, Myoung Seok, additional, Aithal, Guruprasad, additional, Palaniyappan, Naaventhan, additional, Cassinotto, Cristophe, additional, Aggarwal, Sandeep, additional, Garg, Harshit, additional, Ooi, Geraldine, additional, Nakajima, Atsushi, additional, Yoneda, Masato, additional, Zheng, Ming-Hua, additional, Fournier, Céline, additional, Trauner, Michael, additional, Geier, Andreas, additional, Tuthill, Theresa, additional, Yunis, Carla, additional, Anstee, Quentin, additional, Harrison, Stephen, additional, Bossuyt, Patrick, additional, and Pavlides, Michael, additional

Published
2022
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16. Diagnostic accuracy of non-invasive tests for cirrhotic NASH-an individual participant data meta-analysis

Author

Mozes, Ferenc, primary, Lee, Jenny, additional, Vali, Yasaman, additional, Selvaraj, Emmanuel, additional, Jayaswal, Arjun, additional, Boursier, Jerome, additional, Bugianesi, Elisabetta, additional, Younes, Ramy, additional, Lupsor-Platon, Monica, additional, Petta, Salvatore, additional, Shima, Toshihide, additional, Okanoue, Takeshi, additional, Mahadeva, Sanjiv, additional, Chan, Wah-Kheong, additional, Hirschfield, Gideon, additional, Eddowes, Peter, additional, Newsome, Philip N., additional, Wong, Vincent Wai-Sun, additional, de Lédinghen, Victor, additional, Cobbold, Jeremy, additional, Sumida, Yoshio, additional, Okajima, Akira, additional, Schattenberg, Jörn, additional, Labenz, Christian, additional, Kim, Won, additional, Lee, Myoung Seok, additional, Aithal, Guruprasad, additional, Palaniyappan, Naaventhan, additional, Cassinotto, Cristophe, additional, Aggarwal, Sandeep, additional, Garg, Harshit, additional, Ooi, Geraldine, additional, Nakajima, Atsushi, additional, Yoneda, Masato, additional, Zheng, Ming-Hua, additional, Fournier, Céline, additional, Geier, Andreas, additional, Tuthill, Theresa, additional, Yunis, Carla, additional, Anstee, Quentin, additional, Harrison, Stephen, additional, Bossuyt, Patrick, additional, and Pavlides, Michael, additional

Published
2022
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18. sj-pdf-1-imr-10.1177_03000605221140310 - Supplemental material for Diagnostic accuracy of serum ascites albumin gradient (SAAG) in a contemporary unselected medical cohort

Author

Subhani, Mohsan, Sheth, Abhishek, Palaniyappan, Naaventhan, Sugathan, Peuish, Wilkes, Emilie A, and Aithal, Guruprasad P

Subjects
111199 Nutrition and Dietetics not elsewhere classified, Cardiology, 170199 Psychology not elsewhere classified, 111799 Public Health and Health Services not elsewhere classified, 110604 Sports Medicine, FOS: Health sciences, 110306 Endocrinology, 110308 Geriatrics and Gerontology, 111099 Nursing not elsewhere classified, 111708 Health and Community Services, 160807 Sociological Methodology and Research Methods, 111702 Aged Health Care, 111403 Paediatrics, 110904 Neurology and Neuromuscular Diseases, 110203 Respiratory Diseases, 110315 Otorhinolaryngology, FOS: Clinical medicine, 110319 Psychiatry (incl. Psychotherapy), FOS: Sociology, FOS: Psychology, 110599 Dentistry not elsewhere classified, 110323 Surgery, 110305 Emergency Medicine, 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified, 111299 Oncology and Carcinogenesis not elsewhere classified, 110314 Orthopaedics
Abstract

Supplemental material, sj-pdf-1-imr-10.1177_03000605221140310 for Diagnostic accuracy of serum ascites albumin gradient (SAAG) in a contemporary unselected medical cohort by Mohsan Subhani, Abhishek Sheth, Naaventhan Palaniyappan, Peuish Sugathan, Emilie A Wilkes and Guruprasad P Aithal in Journal of International Medical Research

Published
2022
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20. Diagnostic accuracy of elastography and magnetic resonance imaging in patients with NAFLD: a systematic review and meta-analysis

Author

Selvaraj, Emmanuel Anandraj, Jayaswal, Arjun Narayan Ajmer, Zafarmand, Mohammad Hadi, Vali, Yasaman, Lee, Jenny A., Levick, Christina Kim, Young, Liam Arnold Joseph, Palaniyappan, Naaventhan, Liu, Chang-Hai, Aithal, Guruprasad Padur, Brosnan, M. Julia, Tuthill, Theresa A., Anstee, Quentin M., Neubauer, Stefan, Harrison, Stephen A., Bossuyt, Patrick M., and Pavlides, Michael

Subjects
Non-alcoholic fatty liver disease, Non-alcoholic steatohepatitis, Biomarkers, Liver fibrosis, Transient elastography, Shear wave elastography, Magnetic resonance elastography, Magnetic resonance imaging, Iron-corrected T1, Diffusion weighted imaging, deMI
Abstract

Background and Aims: Vibration-controlled transient elastography (VCTE), point shear wave elastography (pSWE), two-dimensional shear wave elastography (2DSWE), magnetic resonance elastography (MRE), and magnetic resonance imaging (MRI) are proposed as non-invasive tests for patients with non-alcoholic fatty liver disease (NAFLD). This study evaluated their diagnostic accuracy for liver fibrosis and non-alcoholic steatohepatitis (NASH).Methods: PubMED/MEDLINE, EMBASE and the Cochrane Library were searched for studies examining the diagnostic accuracy of these index tests against histology as the reference standard, in adult patients with NAFLD. Two authors independently screened and assessed methodological quality of studies and extracted data. Summary estimates of sensitivity, specificity and area under the curve (sAUC) were calculated for fibrosis stages and NASH, using a random effects bivariate logit-normal model.Results: We included 82 studies (14,609 patients). Meta-analysis for diagnosing fibrosis stages was possible in 53 VCTE, 11 MRE, 12 pSWE and four 2DSWE studies, and for diagnosing NASH in four MRE studies. sAUC for diagnosis of significant fibrosis were: 0.83 for VCTE, 0.91 for MRE, 0.86 for pSWE and 0.75 for 2DSWE. sAUC for diagnosis of advanced fibrosis were: 0.85 for VCTE, 0.92 for MRE, 0.89 for pSWE and 0.72 for 2DSWE. sAUC for diagnosis of cirrhosis were: 0.89 for VCTE, 0.90 for MRE, 0.90 for pSWE and 0.88 for 2DSWE. MRE had sAUC of 0.83 for diagnosis of NASH. Three (4%) studies reported intention-to-diagnose analyses and 15 (18%) studies reported diagnostic accuracy against pre-specified cut-offs.Conclusions: When elastography index tests are acquired successfully, they have acceptable diagnostic accuracy for advanced fibrosis and cirrhosis. The potential clinical impact of these index tests cannot be assessed fully as intention-to-diagnose analyses and validation of pre-specified thresholds are lacking.Lay summary:Non-invasive tests that measure liver stiffness or use magnetic resonance imaging (MRI) have been suggested as alternatives to liver biopsy in assessing the severity of liver scarring (fibrosis) and fatty inflammation (steatohepatitis) in patients with non-alcoholic fatty liver disease (NAFLD). In this study, we summarise the results of previously published studies on how accurately these non-invasive tests can diagnose liver fibrosis and inflammation, using liver biopsy as the reference. We found that some techniques that measure liver stiffness had a good performance for the diagnosis of severe liver scarring.

Published
2021

22. Diagnostic accuracy of non-invasive tests for advanced fibrosis in patients with NAFLD: an individual patient data meta-analysis

Author

Lee, Jenny A., Selvaraj, Emmanuel A., Jayaswal, Arjun N.A., Trauner, Michael, Staufer, Katharina, Stauber, Rudolf E., Bugianesi, Elisabet-ta, Younes, Ramy, Gaia, Silvia, Lup?or-Platon, Monica, Petta, Salvatore, Shima, Toshihide, Okanoue, Takeshi, Mahadeva, Sanjiv, Chan, Wah-Kheong, Eddowes, Peter J., Newsome, Philip N., Wai-Sun Wong, Vincent, Fan, Jian-Gao, Shen, Feng, Cobbold, Jeremy F., Sumida, Yoshio, Okajima, Akira, Labenz, Christian, Kim, Won, Lee, Myoung Seok, Wiegand, Johannes, Karlas, Thomas, Yilmaz, Yusuf, Aithal, Guruprasad Padur, Palaniyappan, Naaventhan, Cassinotto, Christophe, Aggarwal, Sandeep, Garg, Harshit, Ooi, Geraldine, Nakajima, Atsushi, Yoneda, Masato, Ziol, Marianne, Barget, Nathalie, Geier, Andreas, Tuthill, Theresa, Brosnan, Julia M., Anstee, Quentin M., Neubauer, Stefan, Harrison, Stephen A., Bossuyt, Patrick M., and Pavlides, Michael

Subjects
Gastroenterology
Abstract

Objective: Liver biopsy is still needed for fibrosis staging in many patients with non-alcoholic fatty liver disease. The aims of this study were to evaluate the individual diagnostic performance of liver stiffness measurement by vibration controlled transient elastography (LSM- VCTE), Fibrosis-4 index (FIB-4) and NAFLD Fibrosis Score (NFS) and to derive diagnostic strategies that could reduce the need for liver biopsies.Design: Individual patient data meta-analysis of studies evaluating LSM-VCTE against liver histology was conducted. FIB-4 and NFS were computed where possible. Sensitivity, specificity and area under the receiver operating curve (AUROC) were calculated. Biomarkers were assessed individu-ally and in sequential combinations.Results: Data were included from 37 primary studies (n=5735; 45% female; median age: 54 years; median BMI: 30 kg/m2; 33% had type 2 diabetes; 30% had advanced fibrosis). AUROCs of individual LSM-VCTE, FIB-4 and NFS for advanced fibrosis were 0.85, 0.76 and 0.73. Sequential combination of FIB-4 cut-offs (

Published
2021

25. enDiagnostic accuracy of non-invasive tests for advanced fibrosis in patients with NAFLD: an individual patient data meta-analysis

Author

Mózes, Ferenc Emil, Lee, Jenny A, Selvaraj, Emmanuel Anandraj, Jayaswal, Arjun Narayan Ajmer, Trauner, Michael, Boursier, Jerome, Fournier, Céline, Staufer, Katharina, Stauber, Rudolf E, Bugianesi, Elisabetta, Younes, Ramy, Gaia, Silvia, Lupșor-Platon, Monica, Petta, Salvatore, Shima, Toshihide, Okanoue, Takeshi, Mahadeva, Sanjiv, Chan, Wah-Kheong, Eddowes, Peter J, Hirschfield, Gideon M, Newsome, Philip Noel, Wong, Vincent Wai-Sun, de Ledinghen, Victor, Fan, Jiangao, Shen, Feng, Cobbold, Jeremy F, Sumida, Yoshio, Okajima, Akira, Schattenberg, Jörn M, Labenz, Christian, Kim, Won, Lee, Myoung Seok, Wiegand, Johannes, Karlas, Thomas, Yılmaz, Yusuf, Aithal, Guruprasad Padur, Palaniyappan, Naaventhan, Cassinotto, Christophe, Aggarwal, Sandeep, Garg, Harshit, Ooi, Geraldine J, Nakajima, Atsushi, Yoneda, Masato, Ziol, Marianne, Barget, Nathalie, Geier, Andreas, Tuthill, Theresa, Brosnan, M Julia, Anstee, Quentin Mark, Neubauer, Stefan, Harrison, Stephen A, Bossuyt, Patrick M, and Pavlides, Michael

Subjects
610 Medicine & health
Abstract

OBJECTIVE Liver biopsy is still needed for fibrosis staging in many patients with non-alcoholic fatty liver disease. The aims of this study were to evaluate the individual diagnostic performance of liver stiffness measurement by vibration controlled transient elastography (LSM-VCTE), Fibrosis-4 Index (FIB-4) and NAFLD (non-alcoholic fatty liver disease) Fibrosis Score (NFS) and to derive diagnostic strategies that could reduce the need for liver biopsies. DESIGN Individual patient data meta-analysis of studies evaluating LSM-VCTE against liver histology was conducted. FIB-4 and NFS were computed where possible. Sensitivity, specificity and area under the receiver operating curve (AUROC) were calculated. Biomarkers were assessed individually and in sequential combinations. RESULTS Data were included from 37 primary studies (n=5735; 45% women; median age: 54 years; median body mass index: 30 kg/m2; 33% had type 2 diabetes; 30% had advanced fibrosis). AUROCs of individual LSM-VCTE, FIB-4 and NFS for advanced fibrosis were 0.85, 0.76 and 0.73. Sequential combination of FIB-4 cut-offs (

Published
2021
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26. Diagnostic accuracy of elastography and magnetic resonance imaging in patients with NAFLD: A systematic review and meta-analysis

Author

Innovative Medicines Initiative, European Commission, European Federation of Pharmaceutical Industries and Associations, Selvaraj, Emmanuel Anandraj, Mózes, Ferenc Emil, Jayaswal, Arjun Narayan Ajmer, Zafarmand, Mohammad Hadi, Vali, Yasaman, Lee, Jenny A., Levick, Christina Kim, Young, Liam Arnold Joseph, Palaniyappan, Naaventhan, Liu, Chang-Hai, Aithal, Guruprasad P., Romero-Gómez, Manuel, Brosnan, M. Julia, Tuthill, Theresa A., Anstee, Quentin M., Neubauer, Stefan, Harrison, Stephen A., Bossuyt, Patrick M., Pavlides, Michael, Innovative Medicines Initiative, European Commission, European Federation of Pharmaceutical Industries and Associations, Selvaraj, Emmanuel Anandraj, Mózes, Ferenc Emil, Jayaswal, Arjun Narayan Ajmer, Zafarmand, Mohammad Hadi, Vali, Yasaman, Lee, Jenny A., Levick, Christina Kim, Young, Liam Arnold Joseph, Palaniyappan, Naaventhan, Liu, Chang-Hai, Aithal, Guruprasad P., Romero-Gómez, Manuel, Brosnan, M. Julia, Tuthill, Theresa A., Anstee, Quentin M., Neubauer, Stefan, Harrison, Stephen A., Bossuyt, Patrick M., and Pavlides, Michael

Abstract

[Background and Aims] Vibration-controlled transient elastography (VCTE), point shear wave elastography (pSWE), 2-dimensional shear wave elastography (2DSWE), magnetic resonance elastography (MRE), and magnetic resonance imaging (MRI) have been proposed as non-invasive tests for patients with non-alcoholic fatty liver disease (NAFLD). This study evaluated their diagnostic accuracy for liver fibrosis and non-alcoholic steatohepatitis (NASH)., [Methods] PubMED/MEDLINE, EMBASE and the Cochrane Library were searched for studies examining the diagnostic accuracy of these index tests, against histology as the reference standard, in adult patients with NAFLD. Two authors independently screened and assessed methodological quality of studies and extracted data. Summary estimates of sensitivity, specificity and area under the curve (sAUC) were calculated for fibrosis stages and NASH, using a random effects bivariate logit-normal model., [Results] We included 82 studies (14,609 patients). Meta-analysis for diagnosing fibrosis stages was possible in 53 VCTE, 11 MRE, 12 pSWE and 4 2DSWE studies, and for diagnosing NASH in 4 MRE studies. sAUC for diagnosis of significant fibrosis were: 0.83 for VCTE, 0.91 for MRE, 0.86 for pSWE and 0.75 for 2DSWE. sAUC for diagnosis of advanced fibrosis were: 0.85 for VCTE, 0.92 for MRE, 0.89 for pSWE and 0.72 for 2DSWE. sAUC for diagnosis of cirrhosis were: 0.89 for VCTE, 0.90 for MRE, 0.90 for pSWE and 0.88 for 2DSWE. MRE had sAUC of 0.83 for diagnosis of NASH. Three (4%) studies reported intention-to-diagnose analyses and 15 (18%) studies reported diagnostic accuracy against pre-specified cut-offs., [Conclusions] When elastography index tests are acquired successfully, they have acceptable diagnostic accuracy for advanced fibrosis and cirrhosis. The potential clinical impact of these index tests cannot be assessed fully as intention-to-diagnose analyses and validation of pre-specified thresholds are lacking., [Lay summary] Non-invasive tests that measure liver stiffness or use magnetic resonance imaging (MRI) have been suggested as alternatives to liver biopsy for assessing the severity of liver scarring (fibrosis) and fatty inflammation (steatohepatitis) in patients with non-alcoholic fatty liver disease (NAFLD). In this study, we summarise the results of previously published studies on how accurately these non-invasive tests can diagnose liver fibrosis and inflammation, using liver biopsy as the reference. We found that some techniques that measure liver stiffness had a good performance for the diagnosis of severe liver scarring.

Published
2021

27. Diagnostic accuracy of non-invasive tests for advanced fibrosis in patients with NAFLD: an individual patient data meta-analysis

Author

Mózes, Ferenc Emil, primary, Lee, Jenny A, additional, Selvaraj, Emmanuel Anandraj, additional, Jayaswal, Arjun Narayan Ajmer, additional, Trauner, Michael, additional, Boursier, Jerome, additional, Fournier, Céline, additional, Staufer, Katharina, additional, Stauber, Rudolf E, additional, Bugianesi, Elisabetta, additional, Younes, Ramy, additional, Gaia, Silvia, additional, Lupșor-Platon, Monica, additional, Petta, Salvatore, additional, Shima, Toshihide, additional, Okanoue, Takeshi, additional, Mahadeva, Sanjiv, additional, Chan, Wah-Kheong, additional, Eddowes, Peter J, additional, Hirschfield, Gideon M, additional, Newsome, Philip Noel, additional, Wong, Vincent Wai-Sun, additional, de Ledinghen, Victor, additional, Fan, Jiangao, additional, Shen, Feng, additional, Cobbold, Jeremy F, additional, Sumida, Yoshio, additional, Okajima, Akira, additional, Schattenberg, Jörn M, additional, Labenz, Christian, additional, Kim, Won, additional, Lee, Myoung Seok, additional, Wiegand, Johannes, additional, Karlas, Thomas, additional, Yılmaz, Yusuf, additional, Aithal, Guruprasad Padur, additional, Palaniyappan, Naaventhan, additional, Cassinotto, Christophe, additional, Aggarwal, Sandeep, additional, Garg, Harshit, additional, Ooi, Geraldine J, additional, Nakajima, Atsushi, additional, Yoneda, Masato, additional, Ziol, Marianne, additional, Barget, Nathalie, additional, Geier, Andreas, additional, Tuthill, Theresa, additional, Brosnan, M. Julia, additional, Anstee, Quentin Mark, additional, Neubauer, Stefan, additional, Harrison, Stephen A., additional, Bossuyt, Patrick M, additional, and Pavlides, Michael, additional

Published
2021
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28. Guidelines on the management of ascites in cirrhosis

Author

Aithal, Guruprasad P, Palaniyappan, Naaventhan, China, Louise, Macken, Lucia, Ryan, Jennifer M, Wilkes, Emilie A, Moore, Kevin, Leithead, Joanna A, Hayes, Peter C, O'Brien, Alastair J, and Verma, Sumita

Subjects
Gastroenterology
Abstract

The British Society of Gastroenterology in collaboration with British Association for the Study of the Liver has prepared this document. The aim of this guideline is to review and summarise the evidence that guides clinical diagnosis and management of ascites in patients with cirrhosis. Substantial advances have been made in this area since the publication of the last guideline in 2007. These guidelines are based on a comprehensive literature search and comprise systematic reviews in the key areas, including the diagnostic tests, diuretic use, therapeutic paracentesis, use of albumin, transjugular intrahepatic portosystemic stent shunt, spontaneous bacterial peritonitis and beta-blockers in patients with ascites. Where recent systematic reviews and meta-analysis are available, these have been updated with additional studies. In addition, the results of prospective and retrospective studies, evidence obtained from expert committee reports and, in some instances, reports from case series have been included. Where possible, judgement has been made on the quality of information used to generate the guidelines and the specific recommendations have been made according to the ‘Grading of Recommendations Assessment, Development and Evaluation (GRADE)’ system. These guidelines are intended to inform practising clinicians, and it is expected that these guidelines will be revised in 3 years’ time.

Published
2020

30. Long-term outcomes of liver transplant recipients followed up in non-transplant centres: Care closer to home

Author

Tsien, Cynthia, primary, Tan, Huey, additional, Sharma, Sowmya, additional, Palaniyappan, Naaventhan, additional, Wijayasiri, Pramudi, additional, Leung, Kristel, additional, Hayre, Jatinder, additional, Mowlem, Elizabeth, additional, Kang, Rachel, additional, Eddowes, Peter J, additional, Wilkes, Emilie, additional, Venkatachalapathy, Suresh V, additional, Guha, Indra N, additional, Antonova, Lilia, additional, Cheung, Angela C, additional, Griffiths, William JH, additional, Butler, Andrew J, additional, Ryder, Stephen D, additional, James, Martin W, additional, Aithal, Guruprasad P, additional, and Aravinthan, Aloysious D, additional

Published
2021
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32. Diagnostic accuracy of magnetic resonance elastography for the staging of fibrosis and diagnosis of steatohepatitis in patients with non-alcoholic fatty liver disease: a systematic review and meta-analysis

Author

Mozes, Ferenc, primary, Zafarmand, Hadi, additional, Jayaswal, Arjun, additional, Selvaraj, Emmanuel, additional, Levick, Christina, additional, Palaniyappan, Naaventhan, additional, Liu, Chang-Hai, additional, Neubauer, Stefan, additional, Gomez, Manuel Romero, additional, Aithal, Guruprasad, additional, Anstee, Quentin, additional, Harrison, Stephen, additional, Bossuyt, Patrick, additional, and Pavlides, Michael, additional

Published
2020
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34. Diagnostic accuracy of acoustic radiation force impulse elastography for the staging of hepatic fibrosis in non-alcoholic fatty liver disease: a systematic review and meta-analysis

Author

Selvaraj, Emmanuel, primary, Zamarfand, Hadi, additional, Mozes, Ferenc, additional, Jayaswal, Arjun, additional, Levick, Christina, additional, Palaniyappan, Naaventhan, additional, Liu, Chang-Hai, additional, Aithal, Guruprasad, additional, Gomez, Manuel Romero, additional, Neubauer, Stefan, additional, Harrison, Stephen, additional, Anstee, Quentin, additional, Boussy, Patrick, additional, and Pavlides, Michael, additional

Published
2020
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36. Time to endoscopy for acute upper gastrointestinal bleeding: Results from a prospective multicentre trainee‐led audit

Author

Siau, Keith, primary, Hodson, James, additional, Ingram, Richard, additional, Baxter, Andrew, additional, Widlak, Monika M, additional, Sharratt, Caroline, additional, Baker, Graham M, additional, Troth, Tom, additional, Hicken, Ben, additional, Tahir, Faraz, additional, Magrabi, Malik, additional, Yousaf, Nouman, additional, Grant, Claire, additional, Poon, Dennis, additional, Khalil, Hesham, additional, Lee, Hui Lin, additional, White, Jonathan R, additional, Tan, Huey, additional, Samani, Syazeddy, additional, Hooper, Patricia, additional, Ahmed, Saeed, additional, Amin, Muhammad, additional, Mahgoub, Sara, additional, Asghar, Khayal, additional, Leet, Farique, additional, Harborne, Matthew J, additional, Polewiczowska, Beata, additional, Khan, Sheeba, additional, Anjum, Muhammad R, additional, McFarlane, Michael, additional, Mozdiak, Ella, additional, O'Flynn, Lauren D, additional, Blee, Ilona C, additional, Molyneux, Rachel M, additional, Kurian, Ashok, additional, Abbas, Syed N, additional, Abbasi, Abdullah, additional, Karim, Aadil, additional, Yasin, Asif, additional, Khattak, Fawad, additional, White, Josephine, additional, Ahmed, Ruhina, additional, Morgan, James A, additional, Alleyne, Lance, additional, Alam, Mohamed A, additional, Palaniyappan, Naaventhan, additional, Rodger, Victoria J, additional, Sawhney, Paramvir, additional, Aslam, Nasar, additional, Okeke, Theodore, additional, Lawson, Adam, additional, Cheung, Danny, additional, Reid, Jeremy P, additional, Awasthi, Ashish, additional, Anderson, Mark R, additional, Timothy, Joe R, additional, Pattni, Sanjeev, additional, Ahmad, Saqib, additional, Townson, Gillian, additional, Shearman, Jeremy, additional, Giljaca, Vanja, additional, Brookes, Matthew J, additional, Disney, Ben R, additional, Guha, Neil, additional, Thomas, Titus, additional, Norman, Anthony, additional, Wurm, Peter, additional, Shah, Ashit, additional, Fisher, Neil C, additional, Ishaq, Sauid, additional, and Major, Giles, additional

Published
2019
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37. Diagnostic accuracy of non-invasive tests for advanced fibrosis in patients with NAFLD: an individual patient data meta-analysis

Author

Mózes, Ferenc Emil, Lee, Jenny A, Selvaraj, Emmanuel Anandraj, Jayaswal, Arjun Narayan Ajmer, Trauner, Michael, Boursier, Jerome, Fournier, Céline, Staufer, Katharina, Stauber, Rudolf E, Bugianesi, Elisabetta, Younes, Ramy, Gaia, Silvia, Lupsor-Platon, Monica, Petta, Salvatore, Shima, Toshihide, Okanoue, Takeshi, Mahadeva, Sanjiv, Chan, Wah-Kheong, Eddowes, Peter J, Hirschfield, Gideon M, Newsome, Philip Noel, Wong, Vincent Wai-Sun, de Ledinghen, Victor, Fan, Jiangao, Shen, Feng, Cobbold, Jeremy F, Sumida, Yoshio, Okajima, Akira, Schattenberg, Jo¨rn M, Labenz, Christian, Kim, Won, Lee, Myoung Seok, Wiegand, Johannes, Karlas, Thomas, Yılmaz, Yusuf, Aithal, Guruprasad Padur, Palaniyappan, Naaventhan, Cassinotto, Christophe, Aggarwal, Sandeep, Garg, Harshit, Ooi, Geraldine J, Nakajima, Atsushi, Yoneda, Masato, Ziol, Marianne, Barget, Nathalie, Geier, Andreas, Tuthill, Theresa, Brosnan, M. Julia, Anstee, Quentin Mark, Neubauer, Stefan, Harrison, Stephen A., Bossuyt, Patrick M, and Pavlides, Michael

Abstract

ObjectiveLiver biopsy is still needed for fibrosis staging in many patients with non-alcoholic fatty liver disease. The aims of this study were to evaluate the individual diagnostic performance of liver stiffness measurement by vibration controlled transient elastography (LSM-VCTE), Fibrosis-4 Index (FIB-4) and NAFLD (non-alcoholic fatty liver disease) Fibrosis Score (NFS) and to derive diagnostic strategies that could reduce the need for liver biopsies.DesignIndividual patient data meta-analysis of studies evaluating LSM-VCTE against liver histology was conducted. FIB-4 and NFS were computed where possible. Sensitivity, specificity and area under the receiver operating curve (AUROC) were calculated. Biomarkers were assessed individually and in sequential combinations.ResultsData were included from 37 primary studies (n=5735; 45% women; median age: 54 years; median body mass index: 30 kg/m2; 33% had type 2 diabetes; 30% had advanced fibrosis). AUROCs of individual LSM-VCTE, FIB-4 and NFS for advanced fibrosis were 0.85, 0.76 and 0.73. Sequential combination of FIB-4 cut-offs (<1.3; ≥2.67) followed by LSM-VCTE cut-offs (<8.0; ≥10.0 kPa) to rule-in or rule-out advanced fibrosis had sensitivity and specificity (95% CI) of 66% (63–68) and 86% (84–87) with 33% needing a biopsy to establish a final diagnosis. FIB-4 cut-offs (<1.3; ≥3.48) followed by LSM cut-offs (<8.0; ≥20.0 kPa) to rule out advanced fibrosis or rule in cirrhosis had a sensitivity of 38% (37–39) and specificity of 90% (89–91) with 19% needing biopsy.ConclusionSequential combinations of markers with a lower cut-off to rule-out advanced fibrosis and a higher cut-off to rule-in cirrhosis can reduce the need for liver biopsies.

Published
2022
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38. Guidelines on the management of ascites in cirrhosis.

Author

Aithal, Guruprasad P., Palaniyappan, Naaventhan, China, Louise, Härmälä, Suvi, Macken, Lucia, Ryan, Jennifer M., Wilkes, Emilie A., Moore, Kevin, Leithead, Joanna A., Hayes, Peter C., O'Brien, Alastair J., and Verma, Sumita

Subjects
HYPONATREMIA, HEPATORENAL syndrome, FATTY liver, ASCITES, RENIN-angiotensin system, CIRRHOSIS of the liver
Published
2021
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40. Non-invasive assessment of portal hypertension using quantitative magnetic resonance imaging

Author

Palaniyappan, Naaventhan, Cox, Eleanor, Bradley, Christopher, Scott, Robert, Austin, Andrew, Ramjas, Greg, Travis, Simon, White, Hilary, Singh, Rajeev, Thurley, Peter, Guha, Indra Neil, Francis, Susan, and Aithal, Guruprasad Padur

Subjects
Magnetic resonance imaging, Hepatic venous pressure gradient, Portal hypertension, Longitudinal T1 relaxation time
Abstract

Background & AimsHepatic venous pressure gradient (HVPG) measurement is currently the only validated technique to accurately evaluate changes in portal pressure. In this study, we evaluate the use of non-contrast quantitative magnetic resonance imaging (MRI) as a surrogate measure of portal pressure.MethodsThirty patients undergoing HVPG measurement were prospectively recruited. MR parameters of longitudinal relaxation time (T1), perfusion of the liver and spleen (by arterial spin labelling), and blood flow in the portal, splanchnic and collateral circulation (by phase contrast MRI) were assessed. We estimated the liver stiffness measurement (LSM) and enhanced liver fibrosis (ELF) score. The correlation of all non-invasive parameters with HVPG was evaluated.ResultsThe mean (range) HVPG of the patients was 9.8 (1–22) mmHg, and 14 patients (48%) had clinically significant portal hypertension (CSPH, HVPG ⩾10 mmHg). Liver T1 relaxation time, splenic artery and superior mesenteric artery velocity correlated significantly with HVPG. Using multiple linear regression, liver T1 and splenic artery velocity remained as the two parameters in the multivariate model significantly associated with HVPG (R = 0.90, p

Published
2016

41. Using MRI to study the alterations in liver blood flow, perfusion, and oxygenation in response to physiological stress challenges: Meal, hyperoxia, and hypercapnia.

Author

Cox, Eleanor F., Palaniyappan, Naaventhan, Aithal, Guruprasad P., Guha, I. Neil, and Francis, Susan T.

Abstract

Background: Noninvasive assessment of dynamic changes in liver blood flow, perfusion, and oxygenation using MRI may allow detection of subtle hemodynamic alterations in cirrhosis.Purpose: To assess the feasibility of measuring dynamic liver blood flow, perfusion, and T2 * alterations in response to meal, hypercapnia, and hyperoxia challenges.Study Type: Prospective.Subjects: Ten healthy volunteers (HV) and 10 patients with compensated cirrhosis (CC).Field Strength/sequence: 3T; phase contrast, arterial spin labeling, and T2* mapping.Assessment: Dynamic changes in portal vein and hepatic artery blood flow (using phase contrast MRI), liver perfusion (using arterial spin labeling), and blood oxygenation ( T2* mapping) following a meal challenge (660 kcal), hyperoxia (target PET O2 of 500 mmHg), and hypercapnia (target increase PET CO2 of ∼6 mmHg).Statistical Tests: Tests between baseline and each challenge were performed using a paired two-tailed t-test (parametric) or Wilcoxon-signed-ranks test (nonparametric). Repeatability and reproducibility were determined by the coefficient of variation (CoV).Results: Portal vein velocity increased following the meal (70 ± 9%, P < 0.001) and hypercapnic (7 (5-11)%, P = 0.029) challenge, while hepatic artery flow decreased (-30 ± 18%, P = 0.005) following the meal challenge in HV. In CC patients, portal vein velocity increased (37 ± 13%, P = 0.012) without the decrease in hepatic artery flow following the meal. In both groups, the meal increased liver perfusion (HV: 82 ± 50%, P < 0.0001; CC: 27 (16-42)%, P = 0.011) with faster arrival time of blood (HV: -54 (-56-30)%, P = 0.074; CC: -42 ± 32%, P = 0.005). In HVs, T2* increased after the meal and in response to hyperoxia, with a decrease in hypercapnia (6 ± 8% P = 0.052; 3 ± 5%, P = 0.075; -5 ± 6%, P = 0.073, respectively), but no change in CC patients. Baseline between-session CoV <15% for blood flow and <10% for T2* measures.Data Conclusion: Dynamic changes in liver perfusion, blood flow, and oxygenation following a meal, hyperoxic, and hypercapnic challenges can be measured using noninvasive MRI and potentially be used to stratify patients with cirrhosis.Level Of Evidence: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:1577-1586. [ABSTRACT FROM AUTHOR]

Published
2019
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42. A study of T 1 relaxation time as a measure of liver fibrosis and the influence of confounding histological factors

Author

Hoad, Caroline L., primary, Palaniyappan, Naaventhan, additional, Kaye, Philip, additional, Chernova, Yulia, additional, James, Martin W., additional, Costigan, Carolyn, additional, Austin, Andrew, additional, Marciani, Luca, additional, Gowland, Penny A., additional, Guha, Indra N., additional, Francis, Susan T., additional, and Aithal, Guruprasad P., additional

Published
2015
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46. A study of T1 relaxation time as a measure of liver fibrosis and the influence of confounding histological factors.

Author

Hoad, Caroline L., Palaniyappan, Naaventhan, Kaye, Philip, Chernova, Yulia, James, Martin W., Costigan, Carolyn, Austin, Andrew, Marciani, Luca, Gowland, Penny A., Guha, Indra N., Francis, Susan T., and Aithal, Guruprasad P.

Abstract

Liver biopsy is the standard test for the assessment of fibrosis in liver tissue of patients with chronic liver disease. Recent studies have used a non-invasive measure of T1 relaxation time to estimate the degree of fibrosis in a single slice of the liver. Here, we extend this work to measure T1 of the whole liver and investigate the effects of additional histological factors such as steatosis, inflammation and iron accumulation on the relationship between liver T1 and fibrosis. We prospectively enrolled patients who had previously undergone liver biopsy to have MR scans. A non-breath-holding, fast scanning protocol was used to acquire MR relaxation time data ( T1 and T2*), and blood serum was used to determine the enhanced liver fibrosis (ELF) score. Areas under the receiver operator curves (AUROCs) for T1 to detect advanced fibrosis and cirrhosis were derived in a training cohort and then validated in a second cohort. Combining the cohorts, the influence of various histology factors on liver T1 relaxation time was investigated. The AUROCs (95% confidence interval (CI)) for detecting advanced fibrosis ( F ≥ 3) and cirrhosis ( F = 4) for the training cohort were 0.81 (0.65-0.96) and 0.92 (0.81-1.0) respectively ( p < 0.01). Inflammation and iron accumulation were shown to significantly alter T1 in opposing directions in the absence of advanced fibrosis; inflammation increasing T1 and iron decreasing T1. A decision tree model was developed to allow the assessment of early liver disease based on relaxation times and ELF, and to screen for the need for biopsy. T1 relaxation time increases with advanced fibrosis in liver patients, but is also influenced by iron accumulation and inflammation. Together with ELF, relaxation time measures provide a marker to stratify patients with suspected liver disease for biopsy. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Published
2015
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47. Diagnostic accuracy of non-invasive tests for advanced fibrosis in patients with NAFLD: an individual patient data meta-analysis

Author

Mózes, Ferenc Emil, Lee, Jenny A, Selvaraj, Emmanuel Anandraj, Jayaswal, Arjun Narayan Ajmer, Trauner, Michael, Boursier, Jerome, Fournier, Céline, Staufer, Katharina, Stauber, Rudolf E, Bugianesi, Elisabetta, Younes, Ramy, Gaia, Silvia, Lupșor-Platon, Monica, Petta, Salvatore, Shima, Toshihide, Okanoue, Takeshi, Mahadeva, Sanjiv, Chan, Wah-Kheong, Eddowes, Peter J, Hirschfield, Gideon M, Newsome, Philip Noel, Wong, Vincent Wai-Sun, de Ledinghen, Victor, Fan, Jiangao, Shen, Feng, Cobbold, Jeremy F, Sumida, Yoshio, Okajima, Akira, Schattenberg, Jörn M, Labenz, Christian, Kim, Won, Lee, Myoung Seok, Wiegand, Johannes, Karlas, Thomas, Yılmaz, Yusuf, Aithal, Guruprasad Padur, Palaniyappan, Naaventhan, Cassinotto, Christophe, Aggarwal, Sandeep, Garg, Harshit, Ooi, Geraldine J, Nakajima, Atsushi, Yoneda, Masato, Ziol, Marianne, Barget, Nathalie, Geier, Andreas, Tuthill, Theresa, Brosnan, M Julia, Anstee, Quentin Mark, Neubauer, Stefan, Harrison, Stephen A, Bossuyt, Patrick M, and Pavlides, Michael

Subjects
2. Zero hunger, 610 Medicine & health, 3. Good health
Abstract

OBJECTIVE Liver biopsy is still needed for fibrosis staging in many patients with non-alcoholic fatty liver disease. The aims of this study were to evaluate the individual diagnostic performance of liver stiffness measurement by vibration controlled transient elastography (LSM-VCTE), Fibrosis-4 Index (FIB-4) and NAFLD (non-alcoholic fatty liver disease) Fibrosis Score (NFS) and to derive diagnostic strategies that could reduce the need for liver biopsies. DESIGN Individual patient data meta-analysis of studies evaluating LSM-VCTE against liver histology was conducted. FIB-4 and NFS were computed where possible. Sensitivity, specificity and area under the receiver operating curve (AUROC) were calculated. Biomarkers were assessed individually and in sequential combinations. RESULTS Data were included from 37 primary studies (n=5735; 45% women; median age: 54 years; median body mass index: 30 kg/m2; 33% had type 2 diabetes; 30% had advanced fibrosis). AUROCs of individual LSM-VCTE, FIB-4 and NFS for advanced fibrosis were 0.85, 0.76 and 0.73. Sequential combination of FIB-4 cut-offs (

48. Individual patient data meta-analysis of the diagnostic performance of single and sequentially combined non-invasive tests in detecting advanced fibrosis

Author

Mozes, Ferenc, Lee, Jenny, Selvaraj, Emmanuel, Jayaswal, Arjun, Trauner, Michael, Boursier, Jerome, Fournier, Celine, Staufer, Katharina, Stauber, Rudolf, Bugianesi, Elisabetta, Younes, Ramy, Gaia, Silvia, Lupsor-Platon, Monica, Petta, Salvatore, Shima, Toshihide, Okanoue, Takeshi, Mahadeva, Sanjiv, Chan, Wah-Kheong, Eddowes, Peter, Newsome, Philip N., Wong, Vincent Wai-Sun, Ledinghen, Victor, Fan, Jian-Gao, Shen, Feng, Cobbold, Jeremy, Sumida, Yoshio, Okajima, Akira, Schattenberg, Jorn, Labenz, Christian, Kim, Won, Lee, Myoung Seok, Wiegand, Johannes, Karlas, Thomas, Yusuf Yilmaz, Aithal, Guruprasad, Palaniyappan, Naaventhan, Cassinotto, Cristophe, Aggarwal, Sandeep, Harshit, Garg, Ooi, Geraldine, Nakajima, Atsushi, Yoneda, Masato, Ziol, Marianne, Barget, Nathalie, Geier, Andreas, Tunill, Theresa, Brosnan, M. Julia, Anstee, Quentin, Neubauer, Stefan, Harrison, Stephen, Bossuyt, Patrick, and Pavlides, Michael

49. Quantitative magnetic resonance imaging in evaluating haemodynamic changes in portal hypertension

Author

Palaniyappan, Naaventhan and Palaniyappan, Naaventhan

Abstract

The majority of complications in patients with cirrhosis result from the development and progression of portal hypertension characterised by increased intrahepatic resistance and progressive splanchnic vasodilation. Hepatic venous pressure gradient (HVPG) measurement is the only validated technique to accurately evaluate changes in portal pressure. However, HVPG measurements are invasive and available only in specialised hepatology units, precluding its use in routine clinical practice. In the first study, we evaluated the use of non-contrast quantitative magnetic resonance imaging (MRI) as a surrogate measure of portal pressure. 30 patients undergoing HVPG measurement were prospectively recruited. MR parameters of longitudinal relaxation time (T1), perfusion of the liver and spleen (by arterial spin labelling), and blood flow in the portal, splanchnic and collateral circulation (by phase-contrast MRI) were assessed. We estimated the liver stiffness measurement (LSM) and Enhanced Liver Fibrosis (ELF) score. The correlation of all non-invasive parameters with HVPG was evaluated. The mean (range) HVPG of the patients was 9.8 (1-22) mmHg, and 14 patients (48%) had clinically significant portal hypertension (CSPH, HVPG ≥10 mmHg). Liver T1 relaxation time, splenic artery and superior mesenteric artery velocity correlated significantly with HVPG. Using multiple linear regression, liver T1 and splenic artery velocity remained as the two parameters in the multivariate model significantly associated with HVPG (R=0.90, p<0.001). This correlation was maintained in patients with CSPH (R=0.85, p<0.001). A validation cohort (n=10) showed this linear model provided a good prediction of HVPG. LSM and ELF score correlated significantly with HVPG in the whole population but the correlation was absent in CSPH. In conclusion, MR parameters related to both hepatic architecture and splanchnic haemodynamics correlate significantly with HVPG. This proposed model, confirmed in a validation

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