Effectiveness of direct acting antiviral agents for hepatitis C virus related recurrent hepatocellular carcinoma patients who had multiple courses of recurrence.

Abstract

Eradication of hepatitis C virus (HCV) using direct acting antiviral agents (DAAs) has been reported to alter liver function and reduce the recurrence rate after curative treatment in naïve hepatocellular carcinoma (HCC) patients. However, it is not well known whether administration of DAAs had favourable effect on HCC patients with multiple courses of recurrence. We retrospectively extracted 146 HCV-related HCC (C-HCC) patients who received curative treatment using radiofrequency ablation (RFA) followed by eradication treatment with DAA between 1 January 2015 and 31 December 2017. We also extracted 184 C-HCC patients who were curatively treated using RFA without HCV eradication treatment between 1 January 2009 and 31 July 2014 as controls. We used propensity score matching method and adjusted following factors between the 2 groups: age, sex, liver function, number of recurrence times, tumour diameter and tumour numbers. We finally enrolled 47 C-HCC patients with eradication of HCV, and 47 C-HCC patients without HCV eradication as controls. Primary end point was time to curative treatment failure. We defined time to curative treatment failure as the interval from curative treatment initiation to premature discontinuation of this type of therapy. Their clinical data, time to curative treatment failure and overall survival were compared. We also assessed the prognostic values of time to curative treatment failure and overall survival using multivariate Cox proportional hazard models. The median age was 74.8years, 60 patients (63.8%) were male, and 81 patients (86.2%) were Child-Pugh class A. The median tumour number was 1, tumour diameter was 20mm, and frequency of recurrence was 3 times. There were no significant differences about patients' backgrounds between the 2 groups. The cumulative time to curative treatment failure rates of patients who received DAA were 93.6% and 73.2% at 1 and 3years, respectively; those of controls were 72.5%, and 37.1% (p<.01). Multivariate analysis indicated that eradication with DAAs (HR 0.23, 95% CI; 0.12-0.43, p<.01) and DCP>50mAU/ml (HR 2.62, 95% CI; 1.45-4.74, p<.01) as independent factors contributed to time to curative treatment failure. The cumulative overall survival rates of patients who received DAAs were 93.6% and 72.6% at 1 and 3years, respectively; those of controls were 72.8% and 37.4% (p<.01). Multivariate analysis indicated that eradication with DAAs (HR 0.32, 95% CI; 0.17-0.60, p<.01) and frequency of recurrence times (HR 1.20 per 1 time, 95% CI; 1.01-1.42, p=.038) as independent factors related to overall survival. Eradication of HCV using DAAs prolonged not only time to curative treatment failure but also overall survival even in C-HCC patients with multiple courses of recurrence.