Nonalcoholic steatohepatitis and cryptogenic cirrhosis within kindreds

Abstract

Purpose: Familial forms of cryptogenic cirrhosis have been described. We have cared for families in which several members were afflicted with cryptogenic cirrhosis as well as the more recently recognized entity of nonalcoholic steatohepatitis. To examine the familial patterns of these disorders, we reviewed patients with nonalcoholic steatohepatitis, with and without cirrhosis, or cryptogenic cirrhosis to assess how frequently their relatives were afflicted with these disorders.

Subjects and methods: Eighteen members of eight kindreds containing 2 or more afflicted members were studied. Diagnoses were based on histology in all but 3 patients (2 elderly women with liver atrophy and severe cirrhotic ascites diagnosed clinically with cryptogenic cirrhosis and 1 adult man with abnormal serum aminotransferase levels and hepatomegaly that was diagnosed as fatty liver by ultrasound). Other forms of liver disease were excluded by extensive serologic testing.

Results: There were 8 index patients (1 man, 7 women; 2 with cryptogenic cirrhosis, 4 with nonalcoholic steatohepatitis with cirrhosis, and 2 with nonalcoholic steatohepatitis without cirrhosis) and 10 relatives (4 men, 6 women; 2 with cryptogenic cirrhosis and 8 with nonalcoholic steatohepatitis). Nonalcoholic steatohepatitis and nonalcoholic steatohepatitis with cirrhosis coexisted within four kindreds, one of which also had an afflicted member with cryptogenic cirrhosis. Nonalcoholic steatohepatitis and cryptogenic cirrhosis coexisted within three additional kindreds. Patterns of afflicted patients included mother-daughter, sister-sister, sister-brother, father-daughter, and male-female cousins. Fifteen (83%) of the 18 subjects were obese, and 11 (61%) had type 2 diabetes mellitus.

Conclusions: The coexistence of nonalcoholic steatohepatitis with and without cirrhosis and cryptogenic cirrhosis within these kindreds suggests a common pathogenesis and possible genetic risk. These disorders were frequently but not invariably associated with female sex, obesity, and type 2 diabetes.