Fibrosis progression in nonalcoholic fatty liver vs nonalcoholic steatohepatitis: a systematic review and meta-analysis of paired-biopsy studies.
OBJECTIVE
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.
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.
Siddharth
S
Singh
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.
Alina M
AM
Allen
Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, Minnesota.
Zhen
Z
Wang
Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, Minnesota.
Larry J
LJ
Prokop
Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, Minnesota.
Mohammad H
MH
Murad
Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of California, San Diego, California. Electronic address: roloomba@ucsd.edu.
Rohit
R
Loomba
D001706:Biopsy; D018450:Disease Progression; D006651:Histocytochemistry; D006801:Humans; D008103:Liver Cirrhosis / Q000175:diagnosis* / Q000473:pathology*; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications*; D012307:Risk Factors
Cirrhosis; Fatty Liver; Fibrosis; Natural History; Nonalcoholic Steatohepatitis