Systematic Reviews
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Virol. Mar 25, 2024; 13(1): 88946
Published online Mar 25, 2024. doi: 10.5501/wjv.v13.i1.88946
Outcomes of liver resection in hepatitis C virus-related intrahepatic cholangiocarcinoma: A systematic review and meta-analysis
Feng Yi Cheo, Kai Siang Chan, Vishal G Shelat
Feng Yi Cheo, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
Kai Siang Chan, Vishal G Shelat, Department of General Surgery, Tan Tock Seng Hospital, Singapore 308433, Singapore
Author contributions: Cheo FY conception and design of the study, acquisition of data, analysis and interpretation of data, drafting the article, revising the article, final approval; Chan KS conception and design of the study, acquisition of data, analysis and interpretation of data, drafting the article, critical revision, final approval; Shelat VG interpretation of data, revising the article, critical revision, final approval.
Conflict-of-interest statement: The authors deny any conflict 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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Kai Siang Chan, MBBS, Doctor, Department of General Surgery, Tan Tock Seng Hospital, No. 11 Jalan Tan Tock Seng, Singapore 308433, Singapore. kchan023@e.ntu.edu.sg
Received: October 16, 2023
Peer-review started: October 16, 2023
First decision: November 2, 2023
Revised: November 10, 2023
Accepted: December 28, 2023
Article in press: December 28, 2023
Published online: March 25, 2024
Processing time: 147 Days and 4.9 Hours
ARTICLE HIGHLIGHTS
Research background

Incidence of intrahepatic cholangiocarcinoma (ICC) has been rising over the past decade. Hepatitis C virus (HCV) infection is an important risk factor in the development of ICC. Currently, liver resection (LR) remains the only curative treatment modality for ICC. Our study aims to study the outcomes of LR in ICC patients with HCV-positive (HCV+) compared to HCV-negative (HCV-) ICC patients.

Research motivation

Long-term outcomes of curative LR in ICC can be affected by patient and tumor characteristics. The impact of HCV infection on post-LR outcomes should be reviewed and quantitatively concluded.

Research objectives

We aim to identify HCV+ patients as a high-risk subgroup amongst ICC patients undergoing curative LR. Our analysis concluded that HCV+ patients had worse overall survival compared to HCV- patients following LR. Our findings act as a stepping stone for future studies to validate our findings, to determine a cause for this outcome, as well as to devise strategies to improve outcomes in HCV+ ICC patients undergoing curative LR.

Research methods

Four databases (PubMed, EMBASE, Scopus and The Cochrane Library) were systematically searched for relevant studies, which were subsequently screened for inclusion in our study based on our inclusion criteria. We assessed the quality of included observational studies using the modified Newcastle-Ottawa Scale. There were no randomised controlled trials included in our study. Our primary outcomes were overall survival (OS) and recurrence-free survival. Secondary outcomes include perioperative mortality, operation duration, blood loss, intrahepatic and extrahepatic recurrence. Study variables, primary and secondary outcomes were extracted from included studies. Pooled hazard ratio (HR) was calculated through the inverse-variance method using the natural logarithm of HR [ln (HR)] and standard error. Dichotomous outcomes were pooled and calculated using the Mantel-Haenszel method and expressed as odds ratio (OR) with 95% confidence interval (CI). Continuous outcomes were pooled and calculated using the inverse variance method and expressed as mean difference with 95%CI.

Research results

Our meta-analysis demonstrated significantly worse OS in HCV+ patients with ICC that underwent curative resection compared to HCV- patients (HR 2.05, 95%CI: 1.46, 2.88, P < 0.0001). Our analysis also showed increased incidence of cirrhosis (OR 5.78, 95%CI: 1.38, 24.14, P = 0.02), poorly differentiated tumors (OR 2.55, 95%CI: 1.34, 4.82, P = 0.004), as well as simultaneous hepatocellular carcinoma (HCC) lesions in HCV+ patients (OR 8.31, 95%CI: 2.36, 29.26, P = 0.001) compared with HCV- patients. Our findings identify HCV infection as a significant poor prognostic factor in ICC patients undergoing curative LR and as a significant risk factor of liver cirrhosis, poor tumor differentiation and incidence of simultaneous HCC lesions. However, the presence of increased liver cirrhosis and poor tumor differentiation may be confounding factors for worse OS in HCV+ patients. No statistically significant differences were noted between HCV+ and tumor stage, tumor invasion and metastases in our study.

Research conclusions

Our study concluded that HCV infection is associated with significantly worse OS outcomes in ICC post-LR. This may be confounded by increased incidence of cirrhosis and poorly differentiated tumors with HCV infection. The exact pathophysiology and confirmation of our findings ought to be explored in future well-designed prospective studies. The role of viral eradication therapy and chemotherapy in this subgroup of patients should also be explored.

Research perspectives

Future research should be performed with randomized controlled trials or propensity score matched cohorts to validate our findings. Further studies should also explore the role of adjuncts such as anti-viral therapy and adjuvant chemotherapy in HCV+ ICC patients who underwent curative LR.