Meta-Analysis
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Aug 27, 2021; 13(8): 949-968
Published online Aug 27, 2021. doi: 10.4254/wjh.v13.i8.949
Non-invasive tests for predicting liver outcomes in chronic hepatitis C patients: A systematic review and meta-analysis
Tanat Yongpisarn, Chanattha Thimphitthaya, Passisd Laoveeravat, Nicha Wongjarupong, Roongruedee Chaiteerakij
Tanat Yongpisarn, Chanattha Thimphitthaya, Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Bangkok 10330, Thailand
Passisd Laoveeravat, Division of Digestive Diseases and Nutrition, Department of Medicine, University of Kentucky, Lexington, KY 40536, United States
Nicha Wongjarupong, Department of Internal Medicine, University of Minnesota, Minneapolis, MN 55455, United States
Roongruedee Chaiteerakij, Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
Roongruedee Chaiteerakij, Center of Excellence for Innovation and Endoscopy in Gastrointestinal Oncology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
Author contributions: Yongpisarn T contributed to acquisition of data, data analysis and interpretation, drafting the article, and final approval; Thimphitthaya C contributed to acquisition of data, analysis and interpretation of data, drafting the article, and final approval; Laoveeravat P contributed to analysis and interpretation of data and final pproval; Wongjarupong N contributed to analysis and interpretation of data and final approval; Chaiteerakij R contributed to study concept, interpretation of data, critical revision, and final approval.
Supported by Research Grant for New Scholar Ratchadaphiseksomphot Endowment Fund Chulalongkorn University, No. RGN_2559_055_10_30.
Conflict-of-interest statement: The authors deny any conflicts of interest.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Roongruedee Chaiteerakij, MD, PhD, Associate Professor, Doctor, Lecturer, Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, 1873 Rama IV Road, Patumwan, Bangkok 10330, Thailand. roon.chaiteerakij@chula.md
Received: March 25, 2021
Peer-review started: March 25, 2021
First decision: June 4, 2021
Revised: June 14, 2021
Accepted: July 13, 2021
Article in press: July 13, 2021
Published online: August 27, 2021
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, I2 = 96%], 4.24 (95%CI: 2.15-8.38, I2 = 20%) and 7.90 (95%CI: 3.98-15.68, I2 = 52%) and AUROCs of 0.81 (95%CI: 0.73-0.89, I2 = 77%), 0.81 (95%CI: 0.75-0.87, I2 = 68%), and 0.79 (95%CI: 0.63-0.96, I2 = 90%), respectively. Pooled adjusted HR with a pre-treatment FIB-4 cutoff of 3.25 was 3.22 (95%CI: 2.32-4.47, I2 = 80%). Pooled adjusted HRs for post-treatment with SVR FIB-4, APRI, and LSM were 3.01 (95%CI: 0.32-28.61, I2 = 89%), 9.88 (95%CI: 2.21-44.17, I2 = 24%), and 6.33 (95%CI: 2.57-15.59, I2 = 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, I2 = 36%). Pooled AUROCs for post-treatment with SVR FIB-4 and LSM were 0.75 (95%CI: 0.55-0.95, I2 = 88%) and 0.84 (95%CI: 0.66-1.03, I2 = 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, I2 = 27%) and 4.04 (95%CI: 2.40-6.80, I2 = 63%), respectively.

CONCLUSION

FIB-4, APRI, and LSM showed potential for risk stratification in CHC patients. Cutoff levels need further validation.

Keywords: Non-invasive tests, Prognosis, Hepatitis C virus, Hepatocellular carcinoma, Mortality, Liver-related outcomes

Core Tip: Previous meta-analyses have evidenced the potential of non-invasive tests (NITs) in determining prognosis. However, these syntheses included studies on chronic liver diseases from various etiologies and did not comprehensively explore all liver-related outcomes. We aimed to assess the importance of validated NITs in risk stratification, specifically in chronic hepatitis C (CHC) patients. Fibrosis-4 (FIB-4) index, aspartate aminotransferase to platelet ratio (APRI) score and liver stiffness measurement (LSM) were found to have prognostic value and can be leveraged to stratify risk for CHC patients, regardless of treatment status or regimen. Further validation of FIB-4, APRI and LSM cutoff levels are needed.