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Meta-Analysis
. 2023 Jul;21(7):1723-1738.e5.
doi: 10.1016/j.cgh.2022.04.013. Epub 2022 May 5.

Fibrosis Stage-specific Incidence of Hepatocellular Cancer After Hepatitis C Cure With Direct-acting Antivirals: A Systematic Review and Meta-analysis

Nicole J Kim  1 , Philip Vutien  2 , Erin Cleveland  2 , Anne Cravero  3 , George N Ioannou  4
Affiliations
Meta-Analysis

Fibrosis Stage-specific Incidence of Hepatocellular Cancer After Hepatitis C Cure With Direct-acting Antivirals: A Systematic Review and Meta-analysis

Nicole J Kim et al. Clin Gastroenterol Hepatol. 2023 Jul.

Abstract

Background & aims: Hepatitis C virus (HCV) eradication with direct-acting antivirals reduces hepatocellular carcinoma (HCC) risk. Pooled HCC incidence rates by cirrhosis status and fibrosis stage have not been estimated using meta-analysis.

Methods: We searched PubMed, Web of Science, Embase, and Cochrane Library from January 1, 2014 to December 31, 2020 to identify studies assessing HCC incidence or outcomes by cirrhosis status, in adults with HCV who achieved sustained virologic response (SVR) after direct-acting antivirals. Pooled estimates were obtained using random-effects modeling. Subgroup, sensitivity, and meta-regression analyses were performed to evaluate heterogeneity.

Results: We included 31 studies involving 27,711 patients with cirrhosis (mean follow-up, 2.1 years) and 11 studies involving 32,123 patients without cirrhosis (mean follow-up, 2.6 years). HCC incidence was 2.99/100 person-years (95% confidence interval [CI], 2.52-3.54; I2 = 75%) in patients with cirrhosis, 0.47/100 person-years (95% CI, 0.32-0.70, I2 = 71%) in patients without cirrhosis, and 0.63/100 person-years (95% CI: 0.34-1.20, I2 = 0%) in stage 3 (F3) fibrosis. Among patients with cirrhosis, HCC incidence was highest in studies with <1 year of follow-up (6.17/100 person-years [95% CI, 3.73-10.19]) and progressively lower in studies with longer follow-up (1-2 years: 2.75/100 person-years [95% CI, 2.48-3.06]; 2-3 years: 2.90/100 person-years [95% CI, 1.90-4.44]; ≥3 years: 1.83/100 person-years [95% CI, 0.88-3.80]).

Conclusion: Pooled HCC incidence after SVR in patients with cirrhosis was very high (2.99/100 person-years) but may be declining as longer time accrues after SVR. In patients without cirrhosis, including F3 fibrosis, HCC incidence was lower than thresholds associated with cost-effective HCC screening. In patients with F3 fibrosis, the lack of between-study heterogeneity provides strong evidence that HCC screening may not be warranted.

Keywords: Cirrhosis; Fibrosis; Incidence; Liver Neoplasms.

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Conflict of interest statement

Disclosures: All authors have nothing to disclose as potential conflicts.

Writing Assistance: No writing assistance was received for this manuscript.

Data Transparency Statement: The protocol for the literature search and analytic methods are available through the PROSPERO database (CRD42021235023).

Figures

Figure 1.
Figure 1.. PRISMA flow diagram of study selection.
HCC: hepatocellular carcinoma; SVR: sustained virologic response.
Figure 2.
Figure 2.. Forest plots of hepatocellular carcinoma incidence rates among patients with HCV following DAA-induced SVR by cirrhosis and fibrosis status.
(A) Cirrhosis (B) Without cirrhosis (C) F3 fibrosis. Heterogeneity considered substantial if I2 ≥50%. DAA: direct-acting antivirals; HCC: hepatocellular carcinoma; HCV: hepatitis C virus; SVR: sustained virologic response.
Figure 2.
Figure 2.. Forest plots of hepatocellular carcinoma incidence rates among patients with HCV following DAA-induced SVR by cirrhosis and fibrosis status.
(A) Cirrhosis (B) Without cirrhosis (C) F3 fibrosis. Heterogeneity considered substantial if I2 ≥50%. DAA: direct-acting antivirals; HCC: hepatocellular carcinoma; HCV: hepatitis C virus; SVR: sustained virologic response.
Figure 2.
Figure 2.. Forest plots of hepatocellular carcinoma incidence rates among patients with HCV following DAA-induced SVR by cirrhosis and fibrosis status.
(A) Cirrhosis (B) Without cirrhosis (C) F3 fibrosis. Heterogeneity considered substantial if I2 ≥50%. DAA: direct-acting antivirals; HCC: hepatocellular carcinoma; HCV: hepatitis C virus; SVR: sustained virologic response.
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