Entecavir and tenofovir reduce hepatitis B virus‐related hepatocellular carcinoma recurrence more effectively than other antivirals

Abstract

Nucleos(t)ide analogues (NAs) have been shown to decrease the risk of hepatocellular carcinoma (HCC) recurrence. This study evaluated whether high-potency NAs (entecavir and tenofovir disoproxil fumarate [TDF]) reduce the risk of tumour recurrence more potently than low-potency NAs after curative treatment of hepatitis B virus (HBV)-related HCC. This study included 607 consecutive HBV-related HCC patients treated with surgical resection or radiofrequency ablation. The patients were categorized into three groups according to antiviral treatment: group A (no antiviral; n = 261), group B (low-potency NA; n = 90) and group C (high-potency NA; n = 256). The primary end-point was recurrence-free survival (RFS). During the duration of follow-up, the median RFS was 29.4, 25.1, and 88.2 months in groups A, B and C, respectively (P < .001, log-rank test). The multivariate Cox analysis indicated that group C had a significantly longer RFS than both group A (adjusted hazard ratio [HR] = 0.39, P < .001) and group B (adjusted HR = 0.47, P < .001). When baseline characteristics were balanced using inverse probability weighting, group C still had a significantly longer RFS than group A (adjusted HR = 0.46, P < .001) and group B (adjusted HR = 0.59, P = .007). Group C had significantly lower risk of viral breakthrough than group B (HR = 0.19, P < .001). Viral breakthrough was an independent risk factor for shorter RFS among groups B and C (adjusted HR = 2.03, P = .007, time-dependent Cox analysis). Antiviral agents with high genetic barrier to resistance (entecavir and TDF) reduced the risk of HCC recurrence compared with other antivirals and no antiviral treatment, especially in patients with high baseline viral load.

KASL clinical practice guidelines for management of chronic hepatitis B

“…A meta-analysis showed that the antiviral treatment group had significantly lower risk of tumor recurrence (odds ratio [OR], 0.59; 95% confidence interval [CI], 0.35–0.97; P =0.04), liver-related mortality (OR, 0.13; 95% CI, 0.02–0.69; P =0.02), and overall mortality (OR, 0.27; 95% CI, 0.14–0.50; P <0.001), than the no antiviral treatment group [368]. In a retrospective Korean study, antiviral treatment with high-potency NAs (i.e., entecavir and tenofovir) showed significantly longer recurrence-free survival than both antiviral treatment with lowpotency NAs (i.e., lamivudine, clevudine, and telbivudine) and no antiviral treatment [369]. In contrast, a randomized controlled trial reported that adjuvant interferon alfa-2b treatment was not associated with lower risk of post-resection tumor recurrence ( P =0.828) [370].…”

<p>Impact of antiviral therapy with nucleos(t)ide analog on survival of patients with HBV-related small hepatocellular carcinomas</p>

“…Then, Kim et al showed that overall survival and recurrence-free survival were better in the ETV-treated patients than in the LAM treated-patients, indicating that the potent antiviral drug should be the preferred choice in HBV-related HCC patients in 2016 47. Cho et al reported that antiviral agents with high genetic barrier to resistance (ETV and TDF) reduced the risk of HCC recurrence compared with other antivirals and no antiviral treatment, especially in patients with high baseline viral load in 2018 48. However, there are conflicting or ambiguous views on the difference of therapeutic outcomes between nucleoside analogs and HCC.…”

Comparison of clinical practice guidelines for the management of chronic hepatitis B: When to start, when to change, and when to stop

“…23,24 Antiviral therapy using interferons or nucleos(t)ide analogs (NAs) efficiently reduces these risks by suppressing HBV replication. [25][26][27][28][29] Current guidelines recommend treatment initiation with antiviral agents before the accumulation of liver injury or progression of fibrosis. However, intrahepatic covalently closed circular DNA cannot be eradicated, even with long-term treatment.…”

“…Antiviral treatment during the immune active phase decreases the risk of liver cirrhosis, hepatic decompensation, and HCC. [25][26][27][28][29] Therefore, antiviral therapy is recommended for patients in this phase. The criteria for treatment differ slightly among the guidelines ( Table 3).…”

“…Importantly, antiviral therapy reduces both the incidence of de novo HCC and the recurrence of HCC in this population. [25][26][27][28][29][75][76][77] Furthermore, the reactivation of HBV can be effechttp://www.e-cmh.org https://doi.org/10.3350/cmh.2020.0049 tively prevented by prophylactic antiviral therapy during anticancer treatment. 78,79 Therefore, the KASL recommends starting NAs before and during HCC treatment if HBV DNA is detected or prophylactically, even if HBV DNA is not detected.…”