(HEPATOLOGY 2012;56:943–951) Nonalcoholic fatty liver disease (NAFLD) is the most-common cause of elevated serum alanine aminotransferase in the United States.1 Approximately 1 in every 3 Americans is estimated to have NAFLD.2 Although it is a highly prevalent disease, not all patients with NAFLD develop progressive liver disease.

Based upon the current understanding of the natural history of NAFLD, it is well accepted that only a subset of patients with histologic features of nonalcoholic steatohepatitis (NASH) progress to advanced fibrosis, cirrhosis, and hepatocellular carcinoma (HCC).3 Therefore, improved understanding of risk factors that predict increased risk of presence of NASH and find more fibrosis on liver histology

could help in the risk stratification of patients with NAFLD.4 Previous studies have shown that metabolic traits, such as diabetes, hypertension, dyslipidemia, and obesity, are associated with increased risk of NASH and advanced fibrosis among patients with NAFLD.5, 6 Metabolic traits are known to have both genetic and environmental influences, suggesting a key role of familial risk factors in metabolic diseases,7 including NAFLD and NASH.8, 9 Previous studies have now shown familial clustering of serum gamma-glutamyl transpeptidase (a marker of fatty liver), NAFLD, NASH, and advanced fibrosis.7, 10-13 Recent studies have shown that parental obesity is associated only with increased odds of suspected NAFLD, and there is strong familial clustering of NAFLD, especially in the setting of coexisting insulin resistance (IR).11, 14 Family Z-VAD-FMK clinical trial history is part of routine medical evaluation.15 However,

there are limited data on whether family history of diabetes increases the risk of NASH and fibrosis among patients with NAFLD. We conducted a cross-sectional analysis derived from a prospective, multicenter study of patients with biopsy-proven NAFLD to test the hypothesis that family history of diabetes is associated with increased risk of NASH and fibrosis, after adjusting for multiple metabolic traits as well as personal history of diabetes, in patients with NAFLD who are enrolled in the NASH Clinical Research Network (CRN) studies. ALT, alanine aminotransferase; BMI, body mass index; BP, blood pressure; CI, confidence interval; CRN, NASH Clinical Research Network; DM, diabetes mellitus; HbA1c, glycated hemoglobin; HCC, hepatocellular carcinoma; HDL, high-density lipoprotein; IR, insulin resistance; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; OR, odds ratio; PNPLA3, patatin-like phospholipase domain-containing protein 3; SD, standard deviation; Tg, triglyceride. This was a cross-sectional study utilizing prospectively collected data from the participants of the multicenter NAFLD Database study and PIVENS trial derived from the NASH CRN studies at the baseline visit.