Fibrosis progression in nonalcoholic fatty liver vs nonalcoholic steatohepatitis: a systematic review and meta-analysis of paired-biopsy studies

Abstract

Background & aims: Little is known about differences in rates of fibrosis progression between patients with nonalcoholic fatty liver (NAFL) vs nonalcoholic steatohepatitis (NASH). We conducted a systematic review and meta-analysis of all studies that assessed paired liver biopsy specimens to estimate the rates of fibrosis progression in patients with nonalcoholic fatty liver disease (NAFLD) including NAFL and NASH.

Methods: Through a systematic search of multiple databases and author contact, up to June 2013, we identified studies of adults with NAFLD that collected paired liver biopsy specimens at least 1 year apart. From these, we calculated a pooled-weighted annual fibrosis progression rate (number of stages changed between the 2 biopsy samples) with 95% confidence intervals (CIs), and identified clinical risk factors associated with progression.

Results: We identified 11 cohort studies including 411 patients with biopsy-proven NAFLD (150 with NAFL and 261 with NASH). At baseline, the distribution of fibrosis for stages 0, 1, 2, 3, and 4 was 35.8%, 32.5%, 16.7%, 9.3%, and 5.7%, respectively. Over 2145.5 person-years of follow-up evaluation, 33.6% had fibrosis progression, 43.1% had stable fibrosis, and 22.3% had an improvement in fibrosis stage. The annual fibrosis progression rate in patients with NAFL who had stage 0 fibrosis at baseline was 0.07 stages (95% CI, 0.02-0.11 stages), compared with 0.14 stages in patients with NASH (95% CI, 0.07-0.21 stages). These findings correspond to 1 stage of progression over 14.3 years for patients with NAFL (95% CI, 9.1-50.0 y) and 7.1 years for patients with NASH (95% CI, 4.8-14.3 y).

Conclusions: Based on a meta-analysis of studies of paired liver biopsy studies, liver fibrosis progresses in patients with NAFL and NASH.

Keywords: Cirrhosis; Fatty Liver; Fibrosis; Natural History; Nonalcoholic Steatohepatitis.

Figure 1

Pooled fibrosis progression rate in patients with (a) nonalcoholic fatty liver disease, (b) nonalcoholic fatty liver and (c) nonalcoholic steatohepatitis, and baseline stage 0 fibrosis. Effect size represents the annual rate of progression of fibrosis stage.

Figure 2

Differential rate of fibrosis progression in patients with non-alcoholic fatty liver disease (NAFLD), nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH), among patients with progressive fibrosis. Rapid progressors refers to a subset of patients with baseline stage 0 fibrosis who developed rapid progression to advanced fibrosis (stage 3 or 4 fibrosis); slow progressors refers to patients with baseline stage 0 fibrosis who had slow progression by 1-2 stages on follow-up biopsy.

Figure 2

Differential rate of fibrosis progression in patients with non-alcoholic fatty liver disease (NAFLD), nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH), among patients with progressive fibrosis. Rapid progressors refers to a subset of patients with baseline stage 0 fibrosis who developed rapid progression to advanced fibrosis (stage 3 or 4 fibrosis); slow progressors refers to patients with baseline stage 0 fibrosis who had slow progression by 1-2 stages on follow-up biopsy.

Figure 2

Differential rate of fibrosis progression in patients with non-alcoholic fatty liver disease (NAFLD), nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH), among patients with progressive fibrosis. Rapid progressors refers to a subset of patients with baseline stage 0 fibrosis who developed rapid progression to advanced fibrosis (stage 3 or 4 fibrosis); slow progressors refers to patients with baseline stage 0 fibrosis who had slow progression by 1-2 stages on follow-up biopsy.