Disease State Transition Probabilities Across the Spectrum of NAFLD: A Systematic Review and Meta-Analysis of Paired Biopsy or Imaging Studies

Background & Aims: We conducted a meta-analysis to summarize the rates of progression to and regression of nonalcoholic fatty liver (NAFL), nonalcoholic steatohepatitis (NASH), and fibrosis in adults with nonalcoholic fatty liver disease (NAFLD). Methods: We searched PubMed/Medline and 4 other databases from 1985 through 2020. We included observational studies and randomized controlled trials in any language that used liver biopsy or imaging to diagnose NAFLD in adults with a follow-up period ≥48 weeks. Rates were calculated as incident cases per 100 person-years and pooled using the random-effects Poisson distribution model. Heterogeneity was assessed using the I² statistic. Results: We screened 9744 articles and included 54 studies involving 26,738 patients. Among observational studies, 20% of healthy adults developed NAFL (incidence rate, 4.8/100 person-years) while 21% of people with fatty liver had resolution of NAFL (incidence rate, 2.4/100 person-years) after a median of approximately 4.5 years. In addition, 31% of patients developed NASH after 4.7 years (incidence rate, 7.4/100 person-years), whereas in 29% of those with NASH, resolution occurred after a median of 3.5 years (incidence rate, 5.1/100 person-years). Time to progress by 1 fibrosis stage was 9.9, 10.3, 13.3, and 22.2 years for F0, F1, F2, and F3, respectively. Time to regress by 1 stage was 21.3, 12.5, 20.4, and 40.0 years for F4, F3, F2, and F1, respectively. Rates estimated from randomized controlled trials were higher than those from observational studies. Conclusions: In our meta-analysis, progression to NASH was more common than regression from NASH. Rates of fibrosis progression were similar across baseline stage, but patients with advanced fibrosis were more likely to regress than those with mild fibrosis.