Type IV collagen 7s domain is an independent clinical marker of the severity of fibrosis in patients with nonalcoholic steatohepatitis before the cirrhotic stage

The changes in nonalcoholic fatty liver disease range over a wide spectrum, extending from simple steatosis to nonalcoholic steatohepatitis (NASH). We investigated the clinical usefulness of the type IV collagen 7s domain and hyaluronic acid for predicting the severity of fibrosis before progression to the cirrhotic stage in NASH patients. The type IV collagen 7s domain and hyaluronic acid were measured in 72 patients with histologically verified NASH. In a univariate analysis, marked elevation of hyaluronic acid and the type IV collagen 7s domain was observed in the NASH patients with advanced fibrosis compared with those with mild fibrosis (P = 0.0028, P = 0.0006, respectively). For detection of NASH with advanced fibrosis, the area under the receiver-operating characteristic curves for type IV collagen 7s domain and hyaluronic acid were 0.767 and 0.754, respectively. However, multiple regression analysis revealed that the type IV collagen 7s domain, but not hyaluronic acid, was significantly elevated in patients with advanced fibrosis even after adjustment for age, sex, platelet count, prothrombin time, aspartate aminotransferase/alanine aminotransferase ratio, body mass index, and presence of underlying type 2 diabetes mellitus, all of which have previously been reported as useful predictors of advanced fibrosis in patients with NASH (P = 0.0127, P = 0.2804, respectively). This is the first report to demonstrate a consistent and profound elevation of the type IV collagen 7s domain in NASH patients with advanced fibrosis (before progression to the stage of cirrhosis) compared with those with mild fibrosis.