Inevitability of disease recurrence after liver transplantation for NAFLD cirrhosis

• Published in: JHEP reports Vol. 5; no. 3; p. 100668
• Main Authors: Villeret, François, Dharancy, Sébastien, Erard, Domitille, Abergel, Armand, Barbier, Louise, Besch, Camille, Boillot, Olivier, Boudjema, Karim, Coilly, Audrey, Conti, Filomena, Corpechot, Christophe, Duvoux, Christophe, Faitot, François, Faure, Stéphanie, Francoz, Claire, Giostra, Emiliano, Gugenheim, Jean, Hardwigsen, Jean, Hilleret, Marie-Noëlle, Hiriart, Jean-Baptiste, Houssel-Debry, Pauline, Kamar, Nassim, Lassailly, Guillaume, Latournerie, Marianne, Pageaux, Georges-Philippe, Samuel, Didier, Vanlemmens, Claire, Saliba, Faouzi, Dumortier, Jérôme
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2023; Elsevier
• Subjects: Bariatric surgery; Human health and pathology; Hépatology and Gastroenterology; Life Sciences; liver transplantation; metabolic syndrome; NAFLD recurrence; NASH; NAFLD; mTOR-i; CST; ESLD; MS; Bariatric surgery; LT; HCC; CYA; NASH; ABM; metabolic syndrome; BS; CV; NAFLD recurrence; liver transplantation; CNI; CST, corticosteroid; ESLD, end-stage liver disease; LT, liver transplantation; ABM, Agence de la Biomédecine; NASH, non-alcoholic steatohepatitis; MS, metabolic syndrome; mTOR-i, mTOR inhibitor; NAFLD, non-alcoholic fatty liver disease; CV, cardiovascular; BS, bariatric surgery; HCC, hepatocellular carcinoma; CYA, cyclosporine; CNI, calcineurin inhibitor; non-alcoholic fatty liver disease; calcineurin inhibitor; Agence de la Biomédecine; mTOR inhibitor; corticosteroid; hepatocellular carcinoma; cyclosporine; bariatric surgery; cardiovascular; end-stage liver disease; non-alcoholic steatohepatitis
• ISSN: 2589-5559; 2589-5559
• DOI: 10.1016/j.jhepr.2022.100668

Liver transplantation (LT) is the only available treatment for end-stage non-alcoholic fatty liver disease (NAFLD) (related decompensated cirrhosis and/or hepatocellular carcinoma). The aim of our study was to evaluate the risk of disease recurrence after LT and the factors influencing it. This retrospective multicenter study included adults transplanted for NAFLD cirrhosis between 2000 and 2019 in 20 participating French-speaking centers. Disease recurrence (steatosis, steatohepatitis and fibrosis) was diagnosed from liver graft biopsies. We analyzed 150 patients with at least one graft liver biopsy available ≥6 months after transplantation, among 361 patients transplanted for NAFLD. The median (IQR) age at LT was 61.3 (54.4-64.6) years. The median follow-up after LT was 4.7 (2.8-8.1) years. The cumulative recurrence rates of steatosis and steatohepatitis at 5 years were 80.0% and 60.3%, respectively. Significant risk factors for steatohepatitis recurrence in multivariate analysis were recipient age at LT <65 years (odds ratio [OR] 4.214; p = 0.044), high-density lipoprotein-cholesterol <1.15 mmol/L after LT (OR 3.463; p = 0.013) and grade ≥2 steatosis on the graft at 1 year after LT (OR 10.196; p = 0.001). The cumulative incidence of advanced fibrosis (F3–F4) was 20.0% at 5 years after LT and significant risk factors from multivariate analysis were metabolic syndrome before LT (OR 8.550; p = 0.038), long-term use of cyclosporine (OR 11.388; p = 0.031) and grade ≥2 steatosis at 1 year after LT (OR 10.720; p = 0.049). No re-LT was performed for NAFLD cirrhosis recurrence. Our results strongly suggest that recurrence of initial disease after LT for NAFLD is inevitable and progressive in a large proportion of patients; the means to prevent it remain to be further evaluated. Non-alcoholic fatty liver disease (NAFLD) is a growing indication for liver transplantation, but the analysis of disease recurrence, based on graft liver biopsies, has been poorly studied. Cumulative incidences of steatosis, steatohepatitis and NAFLD-related significant fibrosis recurrence at 5 years were 85.0%, 60.3% and 48.0%, respectively. Grade ≥2 steatosis on graft biopsy at 1 year (present in 25% of patients) is highly predictive of recurrence of steatohepatitis and advanced fibrosis: bariatric surgery should be discussed in these patients specifically. [Display omitted] •We analyzed the rate of histological recurrence in 150 patients transplanted for NAFLD cirrhosis.•Median follow-up after liver transplantation was 4.7 years.•Recurrence of the initial disease is frequent and rapid after liver transplantation.•Grade ≥2 steatosis at 1 year is highly predictive of recurrence of NASH and advanced fibrosis.