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. 2024 Sep 18;16(9):1485.
doi: 10.3390/v16091485.

Hepatocellular Carcinoma Incidences and Risk Factors in Hepatitis C Patients: Interferon versus Direct-Acting Agents

Yu-Ting Kao  1   2 , Yen-Chun Liu  1   2 , Ya-Ting Cheng  1   2 , Yu-Wen Wen  3   4 , Yi-Chung Hsieh  1   2 , Cheng-Er Hsu  1   2 , Chung-Wei Su  1   2 , Jennifer Chia-Hung Tai  1   2 , Yi-Cheng Chen  1   2 , Wen-Juei Jeng  1   2 , Chun-Yen Lin  1   2 , Rong-Nan Chien  1   2 , Dar-In Tai  1   2 , I-Shyan Sheen  1   2
Affiliations

Hepatocellular Carcinoma Incidences and Risk Factors in Hepatitis C Patients: Interferon versus Direct-Acting Agents

Yu-Ting Kao et al. Viruses. .

Abstract

Background: Hepatocellular carcinoma (HCC) remains a significant concern for patients with chronic hepatitis C (HCV), even after achieving a sustained virological response (SVR) with direct-acting antivirals (DAAs) or interferon (IFN)-based therapies. This study compared the risk of HCC in patients with HCV who achieved SVR through the DAA versus IFN regimens.

Methods: A retrospective analysis was conducted on 4806 HCV patients, without coinfection nor prior HCC history, treated at the Chang Gung Memorial Hospital, Taiwan (DAA: 2825, IFN: 1981). Kaplan-Meier and Cox regression analyses with propensity score matching (PSM) were used to adjust for baseline differences.

Results: DAA-treated patients exhibited a higher incidence of HCC than IFN-treated patients before and after PSM (after PSM: annual: 1% vs. 0.5%; 6-year: 6% vs. 3%, p = 0.01). Both DAA and IFN patients had a decreased HCC incidence during follow-up (>3 vs. <3 years from the end of treatment: DAA: 1.43% vs. 1.00% per year; IFN: 0.47% vs. 0.36% per year, both p < 0.05). HCC incidence was higher in the first three years post-SVR in DAA-treated ACLD patients and then decreased (3.26% vs. 1.39% per year, p < 0.01). In contrast, HCC incidence remained constant in the non-ACLD and IFN-treated groups. Multivariate Cox regression identified age ≥ 60, male sex, BMI, AFP ≥ 6 ng/mL, FIB-4, and ACLD status as independent risk factors for HCC, but antiviral regimens were not an independent factor for HCC.

Conclusion: DAA treatment significantly affects HCC risk primarily within three years post-treatment, especially in younger HCV patients with ACLD. HCC incidence was reduced after three years in ACLD patients treated by DAA, but continued surveillance was still necessary. However, patients under 60 without advanced liver disease may require less intensive follow-up.

Keywords: Hepatitis C virus; direct-acting antivirals; hepatocellular carcinoma; interferon-based therapy; sustained viral response.

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Conflict of interest statement

The authors have no financial or personal relationships with other people or organizations that could inappropriately influence (bias) their work.

Figures

Figure 1
Figure 1
The cumulative HCC incidences in interferon (IFN)- and direct-acting antivirals (DAA)-treated patients. (A) before propensity score matching (PSM) (B) after PSM.
Figure 2
Figure 2
The comparisons of the cumulative HCC incidences in interferon (IFN)- and direct-acting antivirals (DAA)-treated patients stratified by liver fibrotic stages and ages before PSM. (A) in advanced chronic liver disease (ACLD) patients with age < 60 years (B) in ACLD patients with age ≥ 60 years (C) in non-ACLD patients with age < 60 years (D) in non-ACLD patients with age ≥ 60 years.
Figure 3
Figure 3
The comparisons of the cumulative HCC incidences in interferon (IFN)- and direct-acting antivirals (DAA)-treated patients stratified by liver fibrotic stages and ages after PSM. (A) in advanced chronic liver disease (ACLD) patients with age < 60 years (B) in ACLD patients with age ≥ 60 years (C) in non-ACLD patients with age < 60 years (D) in non-ACLD patients with age ≥ 60 years.
Figure 4
Figure 4
The comparisons of the HCC risks within three years (early onset) and after three years (late onset). (A) ACLD patients treated by DAA (B) ACLD patients treated by IFN (C) non-ACLD patients treated by DAA (D) non-ACLD patients treated by IFN.
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