In the fight against liver cancer, one of the deadliest malignancies in the world, antiviral therapy is grossly underestimated as an important weapon. Hepatocellular carcinoma, the third leading cause of cancer death worldwide, is strongly linked to chronic infection with hepatitis B and C viruses (HBV and HCV). These viruses account for a significant proportion of liver cancer deaths each year. However, despite clear clinical guidelines and antiviral therapies that have been shown to be effective in prolonging life and improving quality of life, a new study reveals a troubling treatment gap in treating patients with virus-induced liver cancer.
This large-scale international study, covering data from 12 sites in the United States, Europe, and Asia-Pacific, investigated the use and impact of antiviral therapy in more than 1,900 patients undergoing surgery for hepatitis B and C virus-associated hepatocellular carcinoma. Recent findings published in the Journal of Clinical Oncology show that although antiviral therapy significantly improves long-term survival, its use is woefully underutilized – particularly in patients with hepatitis B virus-associated hepatocellular carcinoma, whose use has declined over time.
The study is a large-scale, retrospective cohort study of patients with hepatocellular carcinoma who underwent hepatic resection between 1992 and 2022 at nine centers in four countries in the United States and Asia. Data was collected by reviewing patients' medical records and analyzed at Stanford University.
Studies included people aged 18 years and older who were associated with hepatitis B or C virus-associated hepatocellular carcinoma. Patients with other liver diseases such as autoimmune hepatitis were excluded.
Studies focused on the use of antiviral therapy and the impact of this treatment on long-term survival. Survival in treated and untreated patients was compared using statistical tests, and multivariate analyses were performed to identify factors influencing survival.
Basic Characteristics of Participants:
- A total of 2,623 patients with hepatocellular carcinoma who underwent partial hepatic resection, of which 1,906 met the inclusion criteria.
- The average age was 62.1 years, with 73.9% male and 83.9% Asian.
- About 27.1% of participants had type 2 diabetes and 53.8% had cirrhosis.
Use of antiviral therapy:
- Overall, 47% of participants received antiviral therapy during the study.
- The use of antiviral therapy for HBV-associated hepatocellular carcinoma was 57% and decreased over time.
- The use of antiviral therapy for HCV-associated hepatocellular carcinoma was 35% but has increased significantly since July 2015.
Overall survival (OS) and influencing factors:
- Treated participants had significantly improved overall survival compared to non-treated participants. For example, the 5-year and 10-year OS of HBV-associated hepatocellular carcinoma were 78.19% and 61.27%, respectively, and the 5-year and 10-year OS of HCV-associated hepatocellular carcinoma were 91.55% and 81.67%, respectively.
- In multivariate analysis, antiviral therapy was associated with better OS, particularly initiation of treatment before or within 6 months of hepatocellular carcinoma diagnosis.
- Recurrence-free survival (RFS) and factors:
- For HBV-associated hepatocellular carcinoma, the 5-year RFS was 23.14% for treated participants and 21.02% for untreated participants.
- For HCV-associated hepatocellular carcinoma, the 5-year RFS was 20.74% for treated participants and 17.80% for untreated participants.
- Antiviral therapy was associated with improved RFS in multivariate analyses, especially when treatment was initiated within 6 months of diagnosis.
Subgroup analysis:
- HBV-associated hepatocellular carcinoma patients without cirrhosis: patients without cirrhosis on antiviral therapy showed better overall survival.
- Use of high-potency nucleoside analogues in patients with HBV-associated hepatocellular carcinoma: patients using high-potency nucleoside analogues such as tenofovir or entecavir have significantly better long-term survival compared with those who receive other treatments.
- Cirrhosis-free patients with HCV-associated hepatocellular carcinoma: patients without cirrhosis who received antiviral therapy showed a higher trend in overall survival compared with those with cirrhosis, although this difference was not statistically significant.
- Impact of the use of interferon-free regimens in patients with HCV-associated hepatocellular carcinoma: The long-term survival of patients with HCV-associated hepatocellular carcinoma who received interferon-free regimens was significantly better than that of patients receiving interferon-based therapy.
- In this large, multi-country study, researchers explored the efficacy of antiviral therapy in 1,906 patients with HBV or HCV-associated hepatocellular carcinoma who underwent radical liver resection. The results of the study showed that antiviral therapy, especially initiated before or within 6 months of HCC diagnosis, was associated with a significant improvement in overall survival in patients with HBV and HCV-associated HCV-related HCC. However, less than half of the patients received antiviral therapy during the study period.
The study raised several key points:
Survival benefits of antiviral therapy: Antiviral therapy significantly reduced overall mortality, reducing the risk of death from HBV-associated hepatocellular carcinoma by approximately 40% and HCV-associated hepatocellular carcinoma by approximately 82%. This finding suggests that although earlier studies have reported improved survival with antiviral therapy, this study provides data on follow-up of up to 10 years, further reinforcing this conclusion.
Timing of antiviral therapy: The timing of initiation of antiviral therapy is critical. Studies have found that initiation of antiviral therapy before or within 6 months of diagnosis of liver cancer is associated with maximum improvement in OS and RFS. If antiviral therapy was delayed by more than six months, the benefit on OS and RFS was reduced and not statistically significant.
The importance of real-world data: This study provides real-world data on the utilization of antiviral therapy in patients with HBV and HCV-associated hepatocellular carcinoma in the context of radical resection. The use of antiviral therapy for HBV is low in Asian countries and may be related to health insurance reimbursement. Since the introduction of well-tolerated and effective DAA therapy in 2014, the use of antiviral therapy for HCV-associated hepatocellular carcinoma has increased significantly.
Overall, this study highlights the critical role of antiviral therapy in improving long-term survival in patients with HBV and HCV-associated hepatocellular carcinoma, while revealing the inadequacy of antiviral therapy in practical applications.
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Huang DQ, Hoang JK, Kamal R, et al. Antiviral Therapy Utilization and 10-Year Outcomes in Resected Hepatitis B Virus- and Hepatitis C Virus-Related Hepatocellular Carcinoma. J Clin Oncol. 2024; 42(7):790-799. doi:10.1200/JCO.23.00757
Source: International Hepatobiliary Information