Increased risk of mortality by fibrosis stage in non-alcoholic fatty liver disease: Systematic Review and Meta-analysis

By P. Dulai, Siddharth Singh, J. Patel, Meera Soni, Larry J Prokop, Z. Younossi, G. Sebastiani, M. Ekstedt, H. Hagstrom, P. Nasr and 5 more. Hepatology, 2017

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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. Through a systematic review and meta‐analysis, we identified five 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 (MRRs) with 95% confidence intervals (CIs) for all‐cause and liver‐related mortality were estimated. The study is reported according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses statement. Included were 1,495 NAFLD patients with 17,452 patient years of follow‐up. 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 increases 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 each 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 of the study include an inability to adjust for comorbid conditions or demographics known to impact fibrosis progression in NAFLD and the inclusion of patients with simple steatosis and nonalcoholic steatohepatitis 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 the utility of each stage and benefits of regression of fibrosis from one stage to another. (Hepatology 2017;65:1557‐1565).

Subfields: Epidemiology, Hepatology

View Paper: https://www.semanticscholar.org/paper/d800fb0ef741e1a59a1abeca3032367b01c74f8b

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Citations in the corpus

Mechanisms and disease consequences of nonalcoholic fatty liver disease (2021, background): “Fibrosis in NASH Fibrosis is the sole histologic feature of NASH that predicts clinical outcomes (Dulai et al., 2017; Sanyal et al., 2019); therefore, it is critical to clarify the mechanisms of fibrogenesis and fibrosis regression in this disease.”
Systematic reviews and meta-analyses (2009, background): “54,55 It therefore is reasonable to focus modeling of the disease on the progression and regression of ﬁ brosis stage rather than the development of NASH vs non-NASH.”
Association Between Fibrosis Stage and Outcomes of Patients with Non-Alcoholic Fatty Liver Disease: a Systematic Review and Meta-Analysis. (2020, background): “IMPACT It is important to monitor liver fibrosis stage in patients with NAFLD.”
Fibrosis stage but not NASH predicts mortality and time to development of severe liver disease in biopsy-proven NAFLD. (2017, background): “In a recent metaanalysis, partly built on these cohorts, also lower stages of fibrosis were associated with overall and liver-specific mortality [24].”
Current and future pharmacological therapies for NAFLD/NASH (2017, methodology): “According to a meta-analysis evaluating five adult NAFLD cohort studies, the presence of advanced fibrosis (stage 2 or more) is the most important predictor of liver-related mortality in NAFLD patients [9].”
Lipotoxicity and the gut-liver axis in NASH pathogenesis. (2018, background): “A critical aspect in the pathogenesis and natural history of NAFLD is the development of hepatic fibrosis, which has been recognized as a factor conditioning liver-related and all-cause mortality [3].”
Global Perspectives on Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis (2019, background): “(6-9) Although NASH is associated with increased liver-related mortality, it is the stage of fibrosis that increases the risk of death in patients with NAFLD.(12) Although cardiovascular disease is the leading cause of death in NAFLD, a recent multicenter study suggests that this is true for noncirr”
Easl Clinical Practice Guidelines (Cpgs) On Non-Invasive Tests For Evaluation Of Liver Disease Severity And Prognosis- 2020 Update. (2021, neutral): “liver-related and global mortality [130] [131].”
Gut microbiome based metagenomic signature for non-invasive detection of advanced fibrosis in human nonalcoholic fatty liver disease (2017, positive): “(Angulo et al., 2015; Dulai et al., 2017; Ekstedt et al., 2015; Younossi et al., 2015) Early identification of the presence of advanced fibrosis using non-invasive modalities is a major unmet need in the field.”
Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A State-of-the-Art Review (2023, background): “19 A prospective study on a cohort of patients with MASLD and baseline liver biopsy found the rate of cardiovascular event to be 2.03 per 100 person-years while the rate of liver-related event was 0.43 per 100 person-years.”