Liver stiffness is associated with all-cause mortality in patients with NAFLD: A systematic review and meta-analysis

Background and Aims: Several studies reported an association between liver stiffness measurement (LSM) obtained through vibration-controlled transient elastography (VCTE) and all-cause mortality in patients with nonalcoholic fatty liver disease (NAFLD). The objective of this systematic review and meta-analysis was to summarize available evidence on the nature and magnitude of this association. Methods: We systematically searched PubMed-MEDLINE and Scopus up to April 2023 for observational cohort studies in which LSM was measured with VCTE in patients with NAFLD or in general population settings, with a follow-up ≥1 year and with available data on all-cause mortality. Measures of association from individual studies were meta-analysed using random effects models. Of the 517 titles initially scrutinized, we included seven studies with data on 18 771 participants (47.1% male) and a mean follow-up of 3.6 years. We included effect estimates obtained in the models with the highest degree of adjustment for potential confounders available in each study. Results: When analysed as a categorical variable based on specific LSM cut-offs, liver fibrosis was associated with an increased risk of all-cause death (HR 2.10, 95% CI 1.56–2.83; test for overall effect z = 4.919, p < 0.001). Results were consistent when LSM was considered as a continuous variable (HR for 1 kPa increase: 1.03, 95% CI 1.01–1.05; test for overall effect z = 3.341, p = 0.001). There was borderline significant heterogeneity among the studies (I2 = 50.2% and I2 = 66.7% in the two analyses, respectively). No significant publication bias was detected by funnel plot analysis and Egger's and Begg's tests. Conclusion: The present meta-analysis indicates that LSM, as a proxy of liver fibrosis, is independently and directly associated with a higher mortality risk in patients with NAFLD.