Published online Mar 25, 2024. doi: 10.5501/wjv.v13.i1.88946
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
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.
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.
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.
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.
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.
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.
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.