Background Liver fibrosis is the most important predictor of mortality in nonalcoholic fatty liver disease (NAFLD). Quantitative risk of mortality by fibrosis stage has not been systematically evaluated. We aimed to quantify the fibrosis stage-specific risk of all-cause and liver-related mortality in NAFLD. Methods Through a systematic review and meta-analysis, we identified 5 adult NAFLD cohort studies reporting fibrosis stage specific mortality (0–4). Using fibrosis stage 0 as a reference population, fibrosis stage-specific mortality rate ratios (MRR) with 95% confidence intervals (CI), for all-cause and liver-related mortality, were estimated. The study is reported according to the PRISMA statement. Results 1,495 NAFLD patients with 17,452 patient years of follow-up were included. Compared to NAFLD patients with no fibrosis (stage 0), NAFLD patients with fibrosis were at an increased risk for all-cause mortality and this risk increased with increase in the stage of fibrosis: stage 1, MRR, 1.58 (95% CI 1.19–2.11); stage 2, MRR, 2.52 (95% CI 1.85–3.42); stage 3, MRR, 3.48 (95% CI 2.51–4.83), and stage 4, MRR, 6.40 (95% CI 4.11–9.95). The results were more pronounced as the risk of liver-related mortality increased exponentially with increase in the stage of fibrosis: stage 1, MRR, 1.41 (95% CI 0.17–11.95); stage 2, MRR, 9.57 (95% CI 1.67–54.93); stage 3, MRR, 16.69 (95% CI 2.92–95.36); and stage 4, MRR, 42.30 (95% CI 3.51–510.34). Limitations Inability to adjust for co-morbid conditions or demographics known to impact fibrosis progression in NAFLD, and the inclusion of patients with simple steatosis and NASH without fibrosis in the reference comparison group. Conclusion The risk of liver-related mortality increases exponentially with increase in fibrosis stage. These data have important implications in assessing utility of each stage and benefits of regression of fibrosis from one stage to another.

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