Natural history of nonalcoholic steatohepatitis: A longitudinal study of repeat liver biopsies

Abstract

Nonalcoholic steatohepatitis may cause severe fibrosis, cirrhosis, and hepatocellular carcinoma, but supporting evidence is based on indirect data. Few publications have examined the results of repeat liver biopsies to evaluate progression of fibrosis. The aims of this study were to assess rate of fibrosis progression in untreated patients with nonalcoholic steatohepatitis and to identify associated variables. Among 106 patients, a second liver biopsy was proposed to those who had undergone their first liver biopsy at least 3 years before. None of them had been given pharmacological therapy. Liver biopsy samples were evaluated blindly. Variables were compared between patients with (group P) and without (group NP) fibrosis progression, using a Wilcoxon rank-sum test for numerical variables and a difference of two binomial proportions for categorical ones. Twenty-two patients (median age, 45 years; age range, 20-69 years; 13 women; diabetes in 8 patients, obesity in 10 patients) underwent a second liver biopsy 4.3 years (range, 3.0-14.3 years) after the first. Fibrosis progression was found in 7 patients in group P (31.8%), no progression was found in 15 patients in group NP. There were no differences between both groups regarding age, gender, diabetes, hyperlipidemia, ALT levels, AST-to-ALT ratio levels, albumin levels, prothrombin activity, steatosis, or inflammation. Obesity was significantly more prevalent in group P (86%) than in group NP (27%; P =.01). Basal body mass index was higher in group P (median, 33.2; range, 29.1-38.2) than in group NP (median, 29.0; range, 24.0-38.1; P =.024). Time between biopsies was not different between groups. In conclusion, progression of liver fibrosis was found in a third of nonalcoholic steatohepatitis patients 4.3 years after the first liver biopsy, and obesity and body mass index were the only associated factors with such progression.

Adipokines in NASH: Postprandial Lipid Metabolism as a Link Between Adiponectin and Liver Disease *

“…The finding that changes in severity of steatosis and inflammation run an independent course from those of fibrosis has been previously reported. 24 Consistently with our data, adiponectin attenuated carbon tetrachloride-induced liver fibrosis in mouse models. 25 The suppressive effect of adiponectin on platelet-derived growth factor-and transforming growth factor-␤1-induced proliferation and migration of cultured hepatic stellate cells provides the molecular basis for the anti-fibrotic effect of this adipokine.…”

Natural history of nonalcoholic fatty liver disease: A prospective follow‐up study with serial biopsies

“…There are few paired biopsy studies with approximately 520 patients in total,7, 8, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 and all but two studies have a median follow‐up time of less than 7 years (range, 3.0‐7.0 years). Albeit, some studies only include patients with NASH, the rate of fibrosis progression does not seem to be affected by the presence of steatohepatitis.…”

Long‐term follow‐up of patients with NAFLD and elevated liver enzymes†‡

“…Published follow-up studies where repeat liver biopsies were performed have either included relatively small numbers of patients, and/or repeat biopsies were obtained after a rather modest length of follow-up. [6][7][8][9][10][11] Our aim was to describe the long-term clinical and histological development of NAFLD in patients originally referred because of chronically elevated liver enzymes.…”