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

Abstract

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 po...

Efficacy of Serum Ferritin–Zinc Ratio for Predicting Advanced Liver Fibrosis in Patients with Autoimmune Hepatitis

“…Among serum biomarkers, APRI and FIB-4 are the most widely used for chronic liver diseases such as nonalcoholic liver disease (NAFLD) and viral hepatitis including HBV and HCV [ 32 , 33 , 34 ], and meta-analyses have also reported about AIH [ 35 , 36 ]. These two serum indicators are considered versatile because of their good reproducibility and high applicability, and they do not incur additional measurement costs [ 31 , 37 ].…”

Dynamic Changes in Non-Invasive Markers of Liver Fibrosis Are Predictors of Liver Events after SVR in HCV Patients

“…Limited data are available on serological markers assessed after SVR as predictors of portal hypertension decompensation. Boursier et al found that the dynamic course of FIB-4 after SVR was associated with the risk of developing any type of LRE [ 16 ], while Yongpisarn et al also reported FIB-4 after SVR to be a good predictor of the risk of developing LREs [ 27 ].…”

Longitudinal Associations of Risk Factors and Hepatocellular Carcinoma in Patients With Cured Hepatitis C Virus Infection

“…Time-varying factors included cirrhosis diagnosis, duration since cirrhosis diagnosis, fibrosis-4 (FIB-4) score (and individual components of FIB-4), serum albumin, sodium, bilirubin, international normalized ratio, hemoglobin, hepatitis B virus surface antigen, diabetes, body mass index (BMI), hypertension, dyslipidemia, active alcohol use disorder, smoking status, and medical and mental health comorbidity. We defined cirrhosis based on ICD codes for cirrhosis or its complications recorded any time before baseline or the presence of FIB-4 > 3.25 (as defined below) (9). We used the date of first instance of cirrhosis code(s) as cirrhosis diagnosis date and once present they were presumed to have cirrhosis for the remaining follow-up time.…”

“…We defined cirrhosis based on ICD codes for cirrhosis or its complications recorded any time before baseline or the presence of FIB-4 . 3.25 (as defined below) (9). We used the date of first instance of cirrhosis code(s) as cirrhosis diagnosis date and once present they were presumed to have cirrhosis for the remaining follow-up time.…”