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Abstract Details
Caucasian lean subjects with non-alcoholic fatty liver disease share long-term prognosis of non-lean: time for reappraisal of BMI-driven approach?
Gut. 2021 Feb 4;gutjnl-2020-322564. doi: 10.1136/gutjnl-2020-322564. Online ahead of print.
Ramy Younes123, Olivier Govaere1, Salvatore Petta4, Luca Miele56, Dina Tiniakos17, Alastair Burt1, Ezio David3, Fabio Maria Vecchio58, Marco Maggioni9, Daniela Cabibi10, Duncan McLeod11, Maria Jesus Pareja12, Anna Ludovica Fracanzani13, Rocio Aller14, Chiara Rosso3, Javier Ampuero15, Rocío Gallego-Durán15, Angelo Armandi3, Gian Paolo Caviglia3, Marco Y W Zaki116, Antonio Liguori5, Paolo Francione13, Grazia Pennisi4, Antonio Grieco56, Giovanni Birolo3, Piero Fariselli3, Mohammed Eslam17, Luca Valenti18, Jacob George17, Manuel Romero-Gómez15, Quentin Mark Anstee1920, Elisabetta Bugianesi21
Author information
1The Newcastle Liver Research Group, Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
2Boehringer Ingelheim International GmbH, Ingelheim, Germany.
3Department of Medical Sciences, Division of Gastroenterology and Hepatology, A.O. Città della Salute e della Scienza di Torino, Università degli Studi di Torino, Torino, Italy.
4Sezione di Gastroenterologia, PROMISE, Università di Palermo, Palermo, Italy.
5Dipartimento Universitario Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy.
6Area Medicina Interna, Gastroenterologia e Oncologia Medica, Fondazione Policlinico A. Gemelli IRCCS, Rome, Italy.
7Dept of Pathology, Aretaieion Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
9Department of Pathology, Ca' Granda IRCCS Foundation, Milan, Italy.
10Pathology Institute, PROMISE, University of Palermo, Palermo, Italy.
11Department of Anatomical Pathology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, Sydney, New South Wales, Australia.
12Pathology Unit, Hospital Universitario de Valme, Sevilla, Spain.
13Unit of Medicine and Metabolic Disease Ca' Granda IRCCS Foundation, Policlinico Hospital, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
14Gastroenterology, Hospital Clínico Universitario de Valladolid, Centro de Investigación de Endocrinología y Nutrición, Universidad de Valladolid, Valladolid, Spain.
15UCM Digestive Diseases and SeLiver Group, Virgen del Rocio University Hospital, Institute of Biomedicine of Seville, University of Seville, Seville, Spain.
16Biochemistry Department, Faculty of Pharmacy, Minia University, El Minia, Egypt.
17Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Westmead, New South Wales, Australia.
18Translational Medicine, Department of Transfusion Medicine and Hematology, Fondazione IRCCS C'a Granda Ospedale Maggiore Policlinico, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
19The Newcastle Liver Research Group, Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK elisabetta.bugianesi@unito.it quentin.anstee@newcastle.ac.uk.
20Newcastle NIHR Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
21Department of Medical Sciences, Division of Gastroenterology and Hepatology, A.O. Città della Salute e della Scienza di Torino, Università degli Studi di Torino, Torino, Italy elisabetta.bugianesi@unito.it quentin.anstee@newcastle.ac.uk.
Abstract
Objective: The full phenotypic expression of non-alcoholic fatty liver disease (NAFLD) in lean subjects is incompletely characterised. We aimed to investigate prevalence, characteristics and long-term prognosis of Caucasian lean subjects with NAFLD.
Design: The study cohort comprises 1339 biopsy-proven NAFLD subjects from four countries (Italy, UK, Spain and Australia), stratified into lean and non-lean (body mass index (BMI) 2). Liver/non-liver-related events and survival free of transplantation were recorded during the follow-up, compared by log-rank testing and reported by adjusted HR.
Results: Lean patients represented 14.4% of the cohort and were predominantly of Italian origin (89%). They had less severe histological disease (lean vs non-lean: non-alcoholic steatohepatitis 54.1% vs 71.2% p<0.001; advanced fibrosis 10.1% vs 25.2% p<0.001), lower prevalence of diabetes (9.2% vs 31.4%, p<0.001), but no significant differences in the prevalence of the PNPLA3 I148M variant (p=0.57). During a median follow-up of 94 months (>10 483 person-years), 4.7% of lean vs 7.7% of non-lean patients reported liver-related events (p=0.37). No difference in survival was observed compared with non-lean NAFLD (p=0.069).
Conclusions: Caucasian lean subjects with NAFLD may progress to advanced liver disease, develop metabolic comorbidities and experience cardiovascular disease (CVD) as well as liver-related mortality, independent of longitudinal progression to obesity and PNPLA3 genotype. These patients represent one end of a wide spectrum of phenotypic expression of NAFLD where the disease manifests at lower overall BMI thresholds.
Lay summary: NAFLD may affect and progress in both obese and lean individuals. Lean subjects are predominantly males, have a younger age at diagnosis and are more prevalent in some geographic areas. During the follow-up, lean subjects can develop hepatic and extrahepatic disease, including metabolic comorbidities, in the absence of weight gain. These patients represent one end of a wide spectrum of phenotypic expression of NAFLD.