The transcontinental variability of nonalcoholic fatty liver disease

Aim:To compare the phenotype of lean versus overweight(OW)and obese(OB)subjects with non-alcoholic fatty liver disease(NAFLD)across multiple continents.Methods:A retrospective study of histologically defined subjects from a single center each in France(Fr),Brazil(Br),India(In)and United States(US)was performed.Results:A total of 70 lean[body mass index(BMI)<25 kg/m2]subjects(Fr:Br:In:US:16:19:22:13)with NAFLD were compared to 136 OW(BMI>25 kg/m2,BMI<29 kg/m2)(n=28:33:52:23)and 224 OB subjects(BMI>29 kg/m2)(n=81:11:22:103).Lean French subjects had the lowest incidence of type 2 diabetes while those from Brazil(P<0.01)had the highest.Lean subjects had similar low-density lipoprotein-cholesterol,but higher high-density lipoprotein-cholesterol compared to obese subjects in all regions.In both lean and obese subjects,there were both insulin-sensitive and insulin-resistant subjects.Lean French subjects were most insulin-sensitive while those from Brazil were mostly insulin-resistant.For each weight category,subjects from India were more insulin-sensitive than those from other regions.Disease activity increased from lean to overweight to obese in France but was similar across weight categories in other regions.Conclusion:The phenotype of NAFLD in lean subjects varies by region.Some obese subjects with NAFLD are insulin-sensitive.We hypothesize that genetics and region-specific disease modifiers account for these differences.