The impact of interferon‐free direct‐acting antivirals on clinical outcome after curative treatment for hepatitis C virus–associated hepatocellular carcinoma: Comparison with interferon‐based therapy

Abstract

Background and Aim To examine the effect on recurrence and survival of treatment by interferon (IFN)‐free direct‐acting antivirals (DAA) for patients with hepatitis C virus (HCV)‐associated hepatocellular carcinoma (HCC) who underwent primary curative treatment. Methods This was a retrospective cohort study of 250 patients with HCV who had received curative treatment for primary HCC. As anti‐HCV treatment after HCC treatment, 38 patients received IFN‐free DAA therapy (DAA patients) and 94 received IFN‐based therapy (IFN patients). The recurrence of HCC and overall survival of the patient groups were compared in a case‐control study. Results The cumulative HCC recurrence rates at 1, 3, and 5 years were 5%, 39%, and 39% for DAA patients and 0%, 46%, and 62% for IFN patients, respectively (P = 0.370). Multivariate analysis of the HCC recurrence identified treatment responses (sustained virological response [SVR]: hazard ratio [HR] 2.237; P = 0.003) as an independent predictive factor. The cumulative overall survival rates at 3 and 5 years were 96%, 96% for DAA patients and 93%, 73% for IFN patients, respectively ( P = 0.163). Multivariate analysis identified treatment responses (SVR: HR 8.742; P < 0.001) as independent predictors of overall survival. Propensity score matching analysis showed no significant difference in HCC development rates and overall survival rates in the two groups. Conclusions We found that SVR obtained after curative treatment for primary HCC suppressed recurrence and improved overall survival. And, IFN‐free DAA therapy after curative treatment for primary HCC could predict improving overall survival and suppressed HCC recurrence.

Systematic review with meta‐analysis: effectiveness of direct‐acting antiviral treatment for hepatitis C in patients with hepatocellular carcinoma

“…Study characteristics were summarised in Tables and . Fifty‐six studies were included, with a total of 5522 patients with HCC, while 27 studies enrolled non‐HCC patients as control groups. Fifty‐three (95%) studies were observational cohorts (45 retrospective and eight prospective) and three studies were clinical trials.…”

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

“…In addition, the time-lag bias, i.e., different time frames applied for recurrence analysis, as seen in Table 3, may lead to discrepant result interpretation. When the follow-up period begins from HCC treatment, it consists of a considerable duration prior to the start of antiviral treatment and counts the period lacking antiviral agents, leading to possible underestimation [23,24,26,[28][29][30]. Furthermore, two of these studies [26,30] firstly included untreated patients as a control group and compared it to IFN-based and DAA arms.…”

“…However, a recent meta-analysis concluded that the HCC occurrence and recurrence rates were comparable between DAA-and IFN-treated patients regardless of the higher SVR rate of the DAA regimen [10]. Moreover, several reports with single-arm DAA-treated HCV-HCC patients declared abruptly increased HCC recurrence rate after antiviral treatment [11][12][13][14], while conflicting results have been reported in other studies comparing to the untreated [15][16][17][18][19][20][21][22][23][24][25] or IFN-treated groups [10,21,[26][27][28][29][30]. Concerns have been raised about the benefit and the timing of adjuvant DAA-based therapy.…”

“…Some of these studies consisted of an IFN-containing DAA regimen [27,28] and did not adjust for baseline characteristics before comparison [26,30]. The definition of follow-up duration varies across these studies [10,21,[23][24][25][26][27][28][29][30] and may lead to inconsistent or conflicting comparison results [31]. We therefore conducted this nested case-control study, using propensity score matching (PSM) to adjust for the confounders, and with application of different follow-up time frames to investigate if the tertiary prevention effect is different between the DAA and PegIFN/RBV regimens in curative CHC-HCC patients.…”

Efficacy and safety of glecaprevir and pibrentasvir combination therapy in old-aged patients with chronic hepatitis C virus infection

“…In addition, SVR achieved by IFN-free DAA treatment improved health-related quality of life in patients with chronic HCV infection 9) . Furthermore, SVR achieved by IFN-free DAA treatment suppressed recurrence of HCC and improved overall survival 10) . Thus, increased SVR can provide a lot of benefits for patients with chronic HCV infection, including old-aged patients.…”