Heritability of Nonalcoholic Fatty Liver Disease

Abstract

Background & Aims-Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the United States. The etiology is believed to be multi-factorial with a substantial genetic component; however, the heritability of NAFLD is undetermined. Therefore, a familial aggregation study was performed to test the hypothesis that NAFLD is highly heritable.

The diagnosis and management of non-alcoholic fatty liver disease: Practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association

“…61 A small familial aggregation study observed that patients with NAFLD have a significantly higher number of first degree relatives with cirrhosis and a trend towards familial clustering of NAFLD or cryptogenic cirrhosis than matched healthy controls. 62 In another familial aggregation study 63 of overweight children with and without NAFLD, after adjusting for age, gender, race, and BMI, the heritability of MR-measured liver fat fraction was 0.386, and fatty liver was present in 18% of family members of children with NAFLD despite normal ALT and lack of obesity. Recommendation 6.…”

“…Anecdotal experience and some published studies suggest familial clustering and heritability of NAFLD, [60][61][62][63] but conclusive studies are lacking. In a retrospective cohort study, Willner et al observed that 18% of patients with NASH have a similarly affected first degree relative.…”

“…Abdominal adiposity may mask detection of hepatomegaly by palpation during physician examination. As in adults, children with features of metabolic syndrome such as obesity, hypertension, insulin resistance and dyslipidemia 63 are at higher risk for NAFLD and particular histopathological features of NAFLD correlate with components of metabolic syndrome. 187 Thus, identification of children at risk for NAFLD could occur in general health provider settings as well as in specialty clinics for nutrition, gastroenterology, hepatology, endocrinology and bariatric surgery.…”

“…188 Penetrance of NAFLD has been demonstrated in family members of children with NAFLD. 63 The likelihood of first, second and third degree relatives exhibiting abnormally high fat fractions (by MRI estimation) relative to body mass index is much more highly correlated in those related to a child with NAFLD than to those who are related to an age, gender and BMI-matched child without NAFLD.…”

“…189 However, as in adults, positive serum autoantibodies are present in a significant population of children with biopsy-proven NAFLD and on some occasion liver biopsy is required to discriminate between autoimmune hepatitis and NAFLD. 63 Obviously, the confounding factor of alcoholism is much less common in children and standard questionnaires for quantifying alcohol intake are usually unnecessary.…”