Association Between Fibrosis Stage and Outcomes of Patients with Non Alcoholic Fatty Liver Disease: a Systematic Review and Meta Analysis.
BACKGROUND AIMS Biopsy confirmed liver fibrosis is a prognostic factor for patients with non alcoholic fatty liver disease (NAFLD) We performed a systematic review to quantify the prognostic value of fibrosis stage in patients with NAFLD and the subgroup of patients with non alcoholic steatohepatitis (NASH) and to assess the evidence that change in fibrosis stage is a surrogate endpoint. METHODS We searched the MEDLINE, EMBASE, Cochrane Library, and trial registry databases through August 2018 for prospective or retrospective cohort studies of liver related clinical events and outcomes in adults with NAFLD or NASH. We collected data on mortality (all cause and liver related) and morbidity (cirrhosis, liver cancer, and all liver related events) by stage of fibrosis, determined by biopsy, for patients with NAFLD or NASH. Using fibrosis stage 0 as a reference population, we calculated fibrosis stage specific relative risk (RR) and 95% CI values for mortality and morbidities. We performed fixed effect and random effect model meta analyses. Meta regression was used to examine associations among study design (prospective vs retrospective cohort) overall risk of bias (medium or high) and mean duration of follow up (in years) RESULTS Our meta analysis included 13 studies, comprising 4428 patients with NAFLD; 2875 of these were reported to have NASH. Compared to no fibrosis (stage 0) unadjusted risk increased with increasing stage of fibrosis (stage 0 vs 4) all cause mortality RR, 3.42 (95% CI, 2.63 4.46) liver related mortality RR, 11.13 (95% CI, 4.15 29.84) liver transplantation RR, 5.42 (95% CI, 1.05 27.89) and liver related events RR, 12.78 (95% CI, 6.85 23.85) The magnitude of RR did not differ significantly following adjustment for confounders including age or sex in the subgroup of NAFLD patients with NASH. Three studies examined the effects of increasing fibrosis on quality of life had inconsistent findings. CONCLUSIONS In a systematic review and meta analysis, we found biopsy confirmed fibrosis to be associated with risk of mortality and liver related morbidity in patients with NAFLD, with and without adjustment for confounding factors and in patients with reported NASH. Further studies are needed to assess the association between fibrosis stage and patient quality of life and establish that change in liver fibrosis stage is a valid endpoint for use in clinical trials.
Gastroenterology