Interferon Is Superior to Direct Acting Antiviral Therapy in Tertiary Prevention of Early Recurrence of Hepatocellular Carcinoma

Abstract

The elimination of chronic hepatitis C infection (CHC) by pegylated interferon plus ribavirin (Peg-IFN/RBV) decreases hepatocellular carcinoma (HCC) recurrence rate. However, the tertiary prevention of HCC recurrence by direct acting antiviral agents (DAA) remains controversial. This study aims to compare the tertiary prevention effect between DAA and Peg-IFN/RBV in CHC-HCC patients. Three hundred and one patients who received curative HCC treatment were retrospectively recruited. The recurrence incidence rate (IR) was compared among patients either receiving Peg-IFN/RBV or DAA regimen or untreated by three timeframes (I: from HCC treatment to antiviral therapy; II: during antiviral therapy; III: after antiviral therapy). The prevention effect between Peg-IFN/RBV and DAA were compared in frame II and III after propensity score matching (PSM) with age, tumor staging, HCC treatment modality, and cirrhotic status. Before PSM, the recurrence IRs in three arms were comparable in frame I, while being lower in the Peg-IFN/RBV and DAA arm compared to the untreated arm in frame II. In frame III, the tertiary prevention effect lasted in the Peg-IFN/RBV arm (p < 0.001), but diminished in the DAA arm (p = 0.135) compared to untreated patients. After PSM, the HCC recurrence IR was higher in the DAA arm than the Peg-IFN/RBV arm in frame II (2724 vs. 666 per 10 4 person-years, log-rank p = 0.042) and III (5259 vs. 3278 per 10 4 person-years, log-rank p = 0.048). Preantiviral ALBI grade therapy is the only predictor for postantiviral therapy HCC recurrence. In conclusion, the tertiary prevention effect of HCC recurrence was not durable in DAA-treated patients, but persisted in Peg-IFN/RBV treatment patients.

Impact of direct‐acting antiviral regimens on mortality and morbidity outcomes in patients with chronic hepatitis c: Systematic review and meta‐analysis

“…Of the 49 articles that we included, 39 reported adjusted HRs or IRRs for the outcomes of interest and were included in the primary analysis. The remaining 10 articles reported only crude HRs or IRRs and were considered in sensitivity analyses 23–32 . No relevant articles were identified from the reference lists of review articles or meta‐analysis studies (Figure 1).…”

“…The remaining 10 articles reported only crude HRs or IRRs and were considered in sensitivity analyses. [23][24][25][26][27][28][29][30][31][32] No relevant articles were identified from the reference lists of review articles or meta-analysis studies (Figure 1). The 49 studies were conducted in 14 different countries, with 15 in Europe, 14 in the United States, 9 in Asia, 3 in the United Kingdom and 8 in other countries (Table 1).…”

Risk of Hepatocellular Carcinoma after HCV Clearance by Direct-Acting Antivirals Treatment Predictive Factors and Role of Epigenetics

“…Teng et al [ 57 ] compared the preventive tertiary effect between DAAs and peg-IFN-RBV in 301 patients with HCV-HCC by a propensity score corresponding to age, tumor staging, HCC treatment modality and cirrhotic status. The results showed that the tertiary prevention effect lasted in the Peg-IFN/RBV arm ( p < 0.001), but decreased in the DAA arm ( p = 0.135) compared with untreated patients.…”

Tertiary Prevention of HCC in Chronic Hepatitis B or C Infected Patients

“…In a recent study of 301 CHC-HCC patients with curative HCC treatment which adopted the time-varying exposure of different time frames, the incidence rate of HCC recurrence was higher in the DAA arm than in the Peg-IFN/RBV arm during anti-viral therapy (2724.4 vs. 665.8/104 person-years, log-rank p = 0.042) and for a 2-year period after SVR (5259.4 vs. 3277.6/104 person-years, log-rank p = 0.048) [ 148 ], suggesting that the tertiary prevention effect of DAA was brief during antiviral therapy and reduced/absent after the end of treatment. In contrast, a meta-analysis of 15 studies and 2352 CHC-HCC patients found that adjuvant DAA therapy was not associated with higher HCC recurrence (RR 0.62; 95% CI 0.11–3.45; p = 0.56) after adjustment for host and tumor factors [ 147 ].…”