Inevitability of disease recurrence after liver transplantation for NAFLD cirrhosis

François Villeret (1) , Sébastien Dharancy , Domitille Erard , Armand Abergel , Louise Barbier , Camille Besch , Olivier Boillot , Karim Boudjema (2) , Audrey Coilly (3) , Filomena Conti , Christophe Corpechot , Christophe Duvoux , François Faitot , Stéphanie Faure , Claire Francoz , Emiliano Giostra , Jean Gugenheim , Jean Hardwigsen , Marie-Noëlle Hilleret , Jean-Baptiste Hiriart , Pauline Houssel-Debry (2, 4) , Nassim Kamar , Guillaume Lassailly , Marianne Latournerie , Georges-Philippe Pageaux , Didier Samuel , Claire Vanlemmens , Faouzi Saliba , Jérôme Dumortier (1)

1 HCL - Hospices Civils de Lyon
2 CHU Pontchaillou [Rennes]
3 Physiopathologie et traitement des maladies du foie
4 Irset - Institut de recherche en santé, environnement et travail

Background & aims: 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. Method: 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. Results: 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. Conclusion: 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. Impact and implications: 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.

Keywords: ABM; Agence de la Biomédecine; BS; bariatric surgery; Bariatric surgery; CNI; calcineurin inhibitor; CST; corticosteroid; CV; cardiovascular; CYA; cyclosporine; ESLD; end-stage liver disease; HCC; hepatocellular carcinoma; LT; liver transplantation; MS; metabolic syndrome; NAFLD recurrence; NAFLD; non-alcoholic fatty liver disease; NASH; non-alcoholic steatohepatitis; mTOR-i; mTOR inhibitor

Domains: Life Sciences [q-bio]; Human health and pathology; Hépatology and Gastroenterology

François Villeret, Sébastien Dharancy, Domitille Erard, Armand Abergel, Louise Barbier, et al.. Inevitability of disease recurrence after liver transplantation for NAFLD cirrhosis. JHEP Reports Innovation in Hepatology, 2023, 5 (3), pp.100668. ⟨10.1016/j.jhepr.2022.100668⟩. ⟨hal-04020048⟩