Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis

Abstract

Nonalcoholic steatohepatitis (NASH) may present with increased hepatic fibrosis progressing to end‐stage liver disease. No factors that determine increasing fibrosis and histologically advanced disease have been recognized, thus, liver biopsy is recommended in all patients for diagnosis and prognosis. Our aim was to identify independent predictors of severe hepatic fibrosis in patients with NASH. One hundred and forty‐four patients were studied. All patients underwent liver biopsy. Clinical and biochemical variables were examined with univariate and multivariate analysis. Thirty‐seven (26%) patients had no abnormal fibrosis, 53 (37%) had mild fibrosis, 15 (10%) had moderate fibrosis, 14 (10%) had bridging fibrosis, and 25 (17%) had cirrhosis. In multivariate analysis, older age (P = .001), obesity (P = .002), diabetes mellitus (P = .009), and aspartate transaminase/alanine transaminase (AST/ALT) ratio greater than 1 (P = .03) were significant predictors of severe liver fibrosis (bridging/cirrhosis). Body mass index (P = .003) was the only independent predictor of the degree of fat infiltration. Increased transferrin saturation correlated positively with the severity of fibrosis (P = .02) in univariate analysis, and there was a trend for more female patients among those with more advanced fibrosis (P = .09). However, iron studies or gender were not significant when controlled for age, obesity, diabetes, and AST/ALT ratio. In conclusion, older age, obesity, and presence of diabetes mellitus help identify those NASH patients who might have severe liver fibrosis. This is the subgroup of patients with NASH who would be expected to derive the most benefit from having a liver biopsy and considering investigational therapies.

Relationship of steatosis grade and zonal location to histological features of steatohepatitis in adult patients with non-alcoholic fatty liver disease

“…As it was recently demonstrated that degree of steatosis quantified by imaging correlates significantly with histological grading of steatosis (5,6), we propose that radiologically-evident severe steatosis should be explored as another variable increasing the risk for the presence of NASH and zone 3 fibrosis in patients with NAFLD. Previous studies have shown that diabetes, older age, and morbid obesity increase the likelihood of NASH in patients with NAFLD (7,8). Future studies should evaluate the role of steatosis severity (as assessed by imaging) in non-invasive prediction of NASH in patients with NAFLD.…”

Role of free radicals in liver diseases

“…However, most studies do not [134][135][136][137][138]. On the contrary, 30% of the patients with NAFLD have elevated ferritin levels [139][140][141], and there is an association between insulin resistance and liver iron [142,143].…”

Diagnosis and Quantitation of Fibrosis

“…In viral and nonalcoholic steatohepatitis (NASH), an AST/ALT ratio of Ͼ1 is often associated with advanced fibrosis or cirrhosis. 24,49,80,81 ␥GT and prothrombin index are markers of progressive liver fibrosis and can be used to predict more advanced fibrosis. These indirect biomarkers simply reflect abnormalities of hepatic structure or function and do not reflect ECM turnover.…”