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Review
. 2021 Apr 15;10(8):1694.
doi: 10.3390/jcm10081694.

Hepatocellular Carcinoma Recurrence after Hepatitis C Virus Therapy with Direct-Acting Antivirals. A Systematic Review and Meta-Analysis

Leonardo Frazzoni  1   2 , Usama Sikandar  2 , Flavio Metelli  2 , Sinan Sadalla  2 , Giuseppe Mazzella  2 , Franco Bazzoli  1   2 , Lorenzo Fuccio  1   2 , Francesco Azzaroli  1   2
Affiliations
Review

Hepatocellular Carcinoma Recurrence after Hepatitis C Virus Therapy with Direct-Acting Antivirals. A Systematic Review and Meta-Analysis

Leonardo Frazzoni et al. J Clin Med. .

Abstract

Background: Hepatocellular carcinoma (HCC) is a major cause of morbidity and mortality among patients with cirrhosis. The risk of HCC recurrence after a complete response among patients treated with direct-acting antivirals (DAAs) has not been fully elucidated yet.

Aim: To assess the risk of HCC recurrence after DAA therapy for hepatitis C virus (HCV).

Methods: A systematic review across PubMed, Scopus and Scholar up to November 2020, including full-text studies that assessed the pattern of HCC recurrence after DAA therapy for HCV. Random-effect meta-analysis and univariable metaregression were applied to obtain pooled estimates for proportions and relative risk (RR) and variables influential for the outcome, respectively.

Results: Thirty-one studies with 2957 patients were included. Overall, 30% (CI, 26-34%) of the patients with a history of HCC experienced HCC recurrence after DAA therapy, at mean time intervals ranging from 4 to 21 months. This result increased when going from European studies (23%, CI, 17-28%) to US studies (34%, CI, 30-38%), to Egyptian studies (37%, CI, 27-47%), and to Asian studies (33%, CI, 27-40%). Sixty-eight percent (CI, 45-91%) of recurrent HCCs developed within 6 months of follow-up since DAA treatment, among the eight studies providing stratified data. Among the studies providing head-to-head comparisons, the HCC recurrence risk was significantly lower after DAA therapy than IFN (RR, 0.64; CI, 0.51-0.81), and after DAA therapy than no intervention (RR, 0.68; CI, 0.49-0.94).

Conclusions: The recurrence of HCC after DAA is not negligible, being higher soon after the end of treatment and among non-European countries. DAA therapy seems to reduce the risk of HCC recurrence compared to an IFN regimen and no intervention.

Keywords: direct-acting antivirals (DAAs); hepatitis C virus (HCV); hepatocellular carcinoma (HCC).

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Conflict of interest statement

There are no conflicts of interest, either personal or financial, to declare by any of the authors.

Figures

Figure 1
Figure 1
Flow-chart describing the process of study selection.
Figure 2
Figure 2
Proportion of patients developing hepatocellular carcinoma recurrence following direct-acting antiviral therapy.
Figure 3
Figure 3
Recurrence rate for hepatocellular carcinoma stratified by time elapsed from direct-acting antiviral therapy. (A) Within 6 months; (B) Between 6 and 12 months.
Figure 4
Figure 4
Relative risk of developing recurrent hepatocellular carcinoma according to strategy. (A) Direct-acting antivirals vs. interferon; (B) Direct-acting antivirals vs. no intervention.
Figure 5
Figure 5
Funnel plot describing publication bias for the primary outcome.
See this image and copyright information in PMC

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