Clinical Characteristics and Long-Term Outcomes of Lean Caucasian Patients with Non- Alcoholic Fatty Liver Disease. A longitudinal International Study.
Ramy Younes1, Olivier Govaere2, Salvatore Petta3, Luca Miele4, Anna Ludovica Fracanzani5, Chiara Rosso1,
Antonio Liguori4, Paolo Francione5, Mohammed Eslam6, Luca Valent5, Jacob George6, Quentn M. Anstee2
and Elisabetta Bugianesi1
(1) Department of Medical Sciences, University ofTurin, Turin, Italy, (2)Insttute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK, (3)Department of Gastroenterology and Hepatology, DI.Bi.M.I.S University of Palermo, (4)Area Gastroenterologia Ed Oncologia medica. Fondazione Policlinico Univ. a. Gemelli Irccs, Universita Cattolica Del Sacro Cuore, Rome, Italy, (5)Department of Pathophysiology and Transplantaton, Ca’ Granda Irccs Foundaton, Policlinico Hospital, University of Milan, (6)Storr Liver Centre, the Westmead Insttute for Medical Research., University of Sydney
Background: NAFLD is commonly associated with obesity. Several studies reported a “lean” phenotype, with controversial clinical characteristcs and no long-term longitudinal studies available, especially in Western countries. We aimed at evaluatng clinical and histological features in additon to long-term outcomes of lean patents with NAFLD in an internatonal Caucasian cohort.
Methods: 1186 Caucasian patents underwent a liver biopsy for clinical suspicion of non-alcoholic fatty liver disease in centres in Italy (Turin, Milan, Rome, Palermo), Australia (Sydney) and the United Kingdom
(Newcastle). Clinical and biochemical data were collected at the tme of biopsy. Patents have then undertaken regular visits for routne care and clinical events were recorded by clinicians.
Results: Lean patents (BMI < 25) represented 18.4% of the cohort (N=218) and were mostly of Italian origin (N=205, 94%). Compared to obese patents, they were younger, with a lower prevalence of diabetes (8.8% vs 34.3%, p<0.001) hypertension (25.8% vs 45.3%, p<0.001) dyslipidaemia (44.2% vs 58.7%, p<0.001), lower levels of insulin (mean 11.9 vs 20.9, p<0.001) and predominantly of male gender. Although lean patents had less severe histological disease, 52% had NASH and 12% exhibited advanced fibrosis. No difference in PNPLA3 C>G polymorphism was detected between the two groups. After a median follow-up of 90 months, both liver and non-liver related events had a significant higher prevalence in the obese group. Nonetheless, a subgroup of lean patents progressed to decompensated cirrhosis with 5% (n=10) developing liver
decompensaton and one patent developing hepatocellular carcinoma. At multvariate analysis, diabetes was an independent predictor of progression, determining a higher risk in lean than in obese individuals (OR 5.8 vs 3.4). Despite a higher number of deaths in obese patents, survival curves did not show a better outcome in the lean group, with no significant difference between the two groups’ survival (Log-Rank-Mantel Cox, p=0.063).
Conclusion: In a Western Caucasian cohort, NAFLD patents who are lean represent a specific group of young individuals, predominantly male and of Mediterranean origins, with less severe features of metabolic syndrome and generally milder histological actvity. Nevertheless, in these patents NAFLD can progress to decompensated cirrhosis and hepatocellular carcinoma, with survival similar to obese NAFLD cases. Funded by Horizon 2020, under grant agreement no. 634413, EPoS
