Hepatocellular Carcinoma Risk According to Regimens for Eradication of Hepatitis C Virus; Interferon or Direct Acting Antivirals

Abstract

By pegylated interferon (PegIFN)-free direct-acting antivirals (DAAs) against hepatitis C virus (HCV) infection, a sustained virological response (SVR) rate >95% can be attained with a satisfactory tolerability and shorter treatment duration. However, it remains controversial whether there is any difference in prognosis depending on regimens—PegIFN or DAAs. We compared the probabilities of hepatocellular carcinoma (HCC) development between patients achieving an SVR by PegIFN/ribavirin (PegIFN group, n = 603) and DAAs (DAAs group, n = 479). The DAAs group was significantly older and had a higher proportion of cirrhosis than the PegIFN group. Before adjustment, the DAAs group had a higher HCC incidence than the PegIFN group (p < 0.001). However, by multivariate analyses, the DAAs (vs. PegIFN) group was not associated with HCC risk (adjusted hazard ratio 0.968, 95% confidence interval 0.380–2.468; p = 0.946). Old age, male, higher body mass index, cirrhosis, and lower platelet count were associated with increased HCC risk (all p < 0.05). After propensity score matching (PSM), a similar HCC risk between the two groups was observed (p = 0.372). We also compared HCC incidences according to sofosbuvir (SOF)-based and SOF-free DAAs, showing a similar risk in both groups before adjustment (p = 0.478) and after PSM (p = 0.855). In conclusion, post-SVR HCC risks were comparable according to treatment regimens; PegIFN- vs. DAA-based regimens and SOF-based vs. SOF-free DAA regimens. Further studies with a longer follow-up period are required.

Hepatitis C virus: A critical approach to who really needs treatment

“…Individuals with a high BMI (≥ 25.0 kg/m 2 ) accompanied by low triglyceride levels (< 160 mg/dL) had a significantly increased risk for liver cancer related mortality[ 276 ]. In the DAA era, increase in HCC incidence after treatment has been associated with higher BMI and cirrhosis[ 277 ]. A systematic review demonstrated a significant association between BMI and HCC risk.…”

Viral Manipulation of the Host Epigenome as a Driver of Virus-Induced Oncogenesis

“…Several therapeutic strategies have been developed to eliminate HCV infection. Among these, direct-acting antivirals (DAAs) represent a major breakthrough in viral eradication [50][51][52]. However, these therapies do not eliminate the virus-induced HCC risk, especially in patients with liver cirrhosis [53,54].…”

Persistent epigenetic alterations in transcription factors after a sustained virological response in hepatocellular carcinoma

“…It remains unclear whether there is a difference in risk for hepatocarcinogenesis based on different treatment regimens (IFN or DAA), considering the potential effect of DAAs on angiogenesis and cellular proliferation. 6,7 Challenging clinical questions associated with HCC patients who have achieved an SVR include, why HCC develops and what differences exist between patients who develop HCC after an SVR and those who do not. HCV-induced epigenetic changes associated with hepatocarcinogenesis were found to persist after an SVR in clinical samples 8 and after virus eradication in cell lines.…”

“…Identification of patients at a high risk for developing HCC would improve prognosis and reduce unnecessary medical costs. It remains unclear whether there is a difference in risk for hepatocarcinogenesis based on different treatment regimens (IFN or DAA), considering the potential effect of DAAs on angiogenesis and cellular proliferation 6,7 …”

“…It remains unclear whether there is a difference in risk for hepatocarcinogenesis based on different treatment regimens (IFN or DAA), considering the potential effect of DAAs on angiogenesis and cellular proliferation. 6 , 7 …”