The Impact of Direct-Acting Antiviral Therapy on the Risk of Recurrence after Curative Resection in Patients with Hepatitis-C-Virus-Related Early Stage Hepatocellular Carcinoma.

Yu-Syuan Chen,Kuo-Hsuan Huang,Yen-Po Lin,Chih-Chien Yao,Pao-Yuan Huang,Chee-Chien Yong,Ming-Chao Tsai,Yueh-Wei Liu,Pei-Ming Wang,Ching-Hui Chuang

doi:10.3390/medicina58020259

Abstract

Background and Objectives: The impact of direct-acting antiviral (DAA)-based regimens on the recurrence of hepatocellular carcinoma (HCC) after successful curative hepatectomy is controversial. Aims: This study aimed to assess the association between DAAs treatment and recurrence risk in HCC after resection. Materials and Methods: We retrospectively assessed 152 cases of early stage (BCLC stage 0/A) hepatitis C virus (HCV)-related HCC (HCV-HCC) that underwent resection with curative intent between 2001 and 2019 at Kaohsiung Chang Gung Memorial Hospital; 48 cases achieved a sustained virological response (SVR) by DAA, and 104 cases were not treated with any antiviral therapy (non-treatment group). Recurrence-free survival (RFS) following curative resection was analyzed by using the log-rank test and Kaplan–Meier method. A Cox proportional hazards model was used to analyze the factors that impacted RFS and OS. Results: Five patients (10.4%) experienced HCC recurrence after DAA therapy. The cumulative HCC recurrence rate was significantly lower in the DAA group than the non-treatment group (p < 0.001). Multivariate analysis revealed a significant difference in RFS between the non-treatment group and DAA group (p = 0.001; hazard ratio (HR), 4.978; 95% CI, 1.976–12.542); liver cirrhosis (p = 0.005; HR, 2.062; 95% CI, 1.247–3.410), microvascular invasion (p = 0.001; HR, 2.331; 95% CI, 1.408–3.860) and AFP > 15 ng/mL (p = 0.022; HR, 1.799; 95% CI, 1.089–2.970) were also independent factors for HCC recurrence. ALBI stage II/III (p = 0.005; HR, 3.249; 95% CI, 1.418–7.443) and microvascular invasion (p < 0.001; HR, 4.037 95% CI, 2.071–7.869) were independent factors for OS; no significant difference in OS was observed between the DAA and no DAA treatment groups. Conclusions: DAA treatment could reduce the risk of recurrence after curative treatment for early stage HCC.

Highlights

Hepatocellular carcinoma (HCC) is associated with high rates of mortality worldwide and is more common among males than females [1]
Patients diagnosed with early stage HCC are suitable for curative treatments, such as surgical resection or local ablative therapies; these therapies are restricted by high rates of recurrence
Who underwent curative surgical resection achieved a complete tumor response and who were not treated with any antiviral drugs after curative resection were recruited into this study; 48 patients with hepatitis C virus (HCV)-related HCC who received direct-acting antiviral (DAA) and achieved an sustained virological response (SVR) were enrolled in the DAA group, while the other 104 patients were enrolled as the untreated group

Summary

Introduction

Hepatocellular carcinoma (HCC) is associated with high rates of mortality worldwide and is more common among males than females [1]. Patients diagnosed with early stage HCC are suitable for curative treatments, such as surgical resection or local ablative therapies; these therapies are restricted by high rates of recurrence (50–60%) [2–6]. The tumor size, serum alpha-fetoprotein, presence of cirrhosis, microvascular invasion and administration of antiviral therapies have been identified as prognostic factors for recurrence after resection [7]. Before the first generation of direct-acting antivirals (DAAs) was developed, interferon (IFN)-based regimens were the standard of treatment for HCV and led to a sustained virological response (SVR) rate of approximately 50–60% among treated patients [8]. Achievement of a SVR is associated with a reduced risk of HCC recurrence after curative therapy, as well as need for liver transplantation, a lower risk of hepatic decompensation, and both liver-related and overall mortality [9–13]. IFN is not suitable for older or livercancer patients with a low platelet count, because of the risk of adverse events, such as high fever, general malaise, depression, interstitial pneumonia and decreased platelet count [14]

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