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Antiviral Treatment Improves Recurrence-Free and Overall Survival in HBV-Related Hepatocellular Carcinoma

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Key Points

  • Nucleoside/nucleotide analog treatment in HBV-positive patients with hepatocellular carcinoma significantly improved relapse-free and overall survival after hepatectomy.
  • Antiviral treatment was associated with reduced early recurrence and improved liver function at 6 months after surgery.

Patients with hepatitis B virus (HBV)-related hepatocellular carcinoma have poor postoperative prognosis. In a study reported in Journal of Clinical Oncology, Jianhua Yin, MD, of the Second Military Medical University in Shanghai, and colleagues assessed the effects of nucleotide/nucleoside analog HBV inhibitor treatment on prognosis. Nucleotide/nucleoside analog treatment was found to significantly improve recurrence-free survival and overall survival.

Study Details

The study included nonrandomized and randomized cohorts of HBV-positive patients with hepatocellular carcinoma who had undergone radical hepatectomy. Patients with hepatitis C virus coinfection and those with disease recurrence within 1 month after surgery were excluded from the studies. The nonrandomized cohort included 617 previously untreated patients with serum HBV DNA > 500 copies/mL; of these, 215 with higher HBV DNA levels received postoperative nucleoside/nucleotide analog treatment. In the open-label randomized cohort, 163 patients with serum HBV DNA of > 500 copies/mL and Child-Pugh class A or B disease were randomly assigned to nucleoside/nucleotide analog treatment (n = 81) or a control group (n = 82). Lamivudine (100 mg/day) was the first choice antiviral; adefovir dipivoxil (10 mg/day) plus lamivudine or entecavir (Baraclude) (0.5 mg/ day) was used in patients with lamivudine resistance. Surgical specimens were examined immunohistochemically for carboxylic acid-terminal truncated HBV X protein (Ct-HBx).

Nonrandomized Cohort

In the nonrandomized cohort, 4-year overall survival (59.6% vs 46.6%, P < .008), 2-year relapse-free survival (44.6% vs 25.5%, P < .001), and 4-year relapse-free survival (37.2% vs 16.6%, P < .001) were significantly greater in the antiviral group. On multivariate analysis, tumor size, incomplete encapsulation, tumor microsatellite, microscopic vascular invasion, tumor differentiation, Barcelona Clinic Liver Cancer stage, abnormal gamma-glutamyl transpeptidase, and high viral load significantly predicted poor prognosis, whereas antiviral treatment significantly reduced hepatocellular carcinoma recurrence (hazard ration [HR] = 0.55, P < .001) and hepatocellular carcinoma–related death (HR = 0.57, P < .001). No serious adverse effects caused by nucleoside/nucleotide analog treatment were reported.

Randomized Trial

In the randomized cohort, 2-year overall survival (93.8% vs 62.2%, P < .001), 4-year overall survival (86.4% vs 47.4%,  P < .001), 2-year relapse-free survival (55.6% vs 19.5%, P < .001), and 4-year relapse-free survival (37.3% vs 12.1%, P < .001) were significantly higher in the antiviral group. Early hepatocellular carcinoma recurrence (within 2 years) was more frequent in the control arm than in the antiviral arm (80.5% vs 44.4%, P < .001).

Nucleoside/nucleotide analog treatment significantly improved relapse-free survival (P < .001) and overall survival (P < .002) in patients with baseline HBV DNA < 104 copies/mL and significantly improved relapse-free survival (P < .004) and overall survival (P < .001) in those with HBV DNA ≥ 104 copies/mL. On multivariate analysis, nucleoside/nucleotide analog treatment significantly reduced risk of recurrence (HR = 0.48, P < .001) and hepatocellular carcinoma–related death (HR = 0.26, P < .001).

Antiviral treatment significantly improved liver function 6 months after surgery compared with the control group (recovered liver function in 51.9% vs 18.3%, P < .001). Patients with recovered liver function had a higher 2-year relapse-free survival than those without (54.4% vs 28.3%, P < .003).

Ct-HBx expression in adjacent hepatic tissues significantly predicted unfavorable relapse-free survival in the antiviral group (P < .001).

The investigators concluded: “Although it might not affect the [hepatocellular carcinoma]– promoting potential of Ct-HBx, [nucleoside/nucleotide analog] treatment is effective in normalizing liver function, decreasing HBV–[hepatocellular carcinoma] recurrence, and improving postoperative survival. This effect should be validated in a multicenter phase III randomized controlled trial.”

The corresponding author for this study is Guangwen Cao, MD, PhD, of the Second Military Medical University in Shanghai.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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