Non-invasive tests for predicting liver outcomes in chronic hepatitis C patients: A systematic review and meta-analysis

BACKGROUND: Liver fibrosis leads to liver-related events in patients with chronic hepatitis C (CHC) infection. Although non-invasive tests (NITs) are critical to early detection of the development of liver fibrosis, the prognostic role of NITs remains unclear due to the limited types of NITs and liver outcomes explored in previous studies. AIM: To determine the prognostic value of NITs for risk stratification in CHC patients. METHODS: The protocol was registered in PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42019128176). The systematic review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Search was performed using MEDLINE and EMBASE databases under a timeframe from the inception of the databases through February 25, 2020. We restricted our search to CHC cohort studies reporting an association between liver fibrosis assessed by NITs and the development of hepatocellular carcinoma, decompensation, or mortality. Pooled hazard ratios (HR) and area under the receiver operating characteristic (AUROC) for each NIT were estimated using a random effects model. Subgroup analyses were performed for NITs assessed at pre-treatment or post-treatment with sustained virologic response (SVR), treatment with either pegylated interferon and ribavirin or direct acting antiviral, Eastern or Western countries, and different cutoff points. RESULTS: The present meta-analysis included 29 cohort studies, enrolling 69339 CHC patients. Fibrosis-4 (FIB-4) index, aspartate aminotransferase to platelet ratio (APRI) score, and liver stiffness measurement (LSM) were found to have hepatocellular carcinoma predictive potential with pooled adjusted HRs of 2.48 [95% confidence interval (CI): 1.91-3.23, I(2) = 96%], 4.24 (95%CI: 2.15-8.38, I(2) = 20%) and 7.90 (95%CI: 3.98-15.68, I(2) = 52%) and AUROCs of 0.81 (95%CI: 0.73-0.89, I(2) = 77%), 0.81 (95%CI: 0.75-0.87, I(2) = 68%), and 0.79 (95%CI: 0.63-0.96, I(2) = 90%), respectively. Pooled adjusted HR with a pre-treatment FIB-4 cutoff of 3.25 was 3.22 (95%CI: 2.32-4.47, I(2) = 80%). Pooled adjusted HRs for post-treatment with SVR FIB-4, APRI, and LSM were 3.01 (95%CI: 0.32-28.61, I(2) = 89%), 9.88 (95%CI: 2.21-44.17, I(2) = 24%), and 6.33 (95%CI: 2.57-15.59, I(2) = 17%), respectively. Pooled adjusted HRs for LSM in patients with SVR following direct acting antiviral therapy was 5.55 (95%CI: 1.47-21.02, I(2) = 36%). Pooled AUROCs for post-treatment with SVR FIB-4 and LSM were 0.75 (95%CI: 0.55-0.95, I(2) = 88%) and 0.84 (95%CI: 0.66-1.03, I(2) = 88%), respectively. Additionally, FIB-4 and LSM were associated with overall mortality, with pooled adjusted HRs of 2.07 (95%CI: 1.49-2.88, I(2) = 27%) and 4.04 (95%CI: 2.40-6.80, I(2) = 63%), respectively. CONCLUSION: FIB-4, APRI, and LSM showed potential for risk stratification in CHC patients. Cutoff levels need further validation.