Comment on “Antiviral Treatment for Postcurative Hepatitis B Virus-related Hepatocellular Carcinoma”

Chronic Hepatitis B Virus (HBV) infection poses a significant global health burden. Although, effective treatment and vaccinations against HBV are available, challenges still exist, particularly in the development of curative therapies. The dynamic nature and unique features of HBV such as viral variants, integration of HBV DNA into host chromosomes, and extrahepatic reservoirs are considerations towards understanding the virus biology and developing improved anti-HBV treatments. In this review, we highlight the importance of these viral characteristics in the context of treatment and oncogenesis. Viral genotype and genetic variants can serve as important predictive factors for therapeutic response and outcomes in addition to oncogenic risk. HBV integration, particularly in coding genes, is implicated in the development of hepatocellular carcinoma. Furthermore, we will discuss emerging research that has identified various HBV nucleic acids and infection markers within extrahepatic sites (lymphoid cells). Intriguingly, the presence of hepatocellular carcinoma (HCC)-associated HBV variants and viral integration within the lymphoid cells may contribute towards the development of extrahepatic malignancies. Improved understanding of these HBV characteristics will enhance the development of a cure for chronic HBV infection.

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Effect of Antiviral Treatment With Nucleotide/Nucleoside Analogs on Postoperative Prognosis of Hepatitis B Virus–Related Hepatocellular Carcinoma: A Two-Stage Longitudinal Clinical Study

Journal of Clinical Oncology ◽

10.1200/jco.2012.48.5896 ◽

2013 ◽

Vol 31 (29) ◽

pp. 3647-3655 ◽

Cited By ~ 140

Author(s):

Jianhua Yin ◽

Nan Li ◽

Yifang Han ◽

Jie Xue ◽

Yang Deng ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Liver Function ◽

Antiviral Treatment ◽

Phase Iii ◽

Two Stage ◽

Postoperative Prognosis ◽

B Virus ◽

Hcc Recurrence

Purpose Postoperative prognosis of hepatitis B virus (HBV) –related hepatocellular carcinoma (HCC) is poor. The effect of nucleotide/nucleoside analog (NA) treatment on the prognosis has not been fully clarified. Patients and Methods We carried out a two-stage longitudinal study that included a randomized clinical trial (RCT) to evaluate the effect of NA treatment on postoperative prognosis of HBV-HCC. Seven hundred eighty patients (163 in the RCT) were enrolled onto this study following radical hepatectomy. Lamivudine, adefovir dipivoxil, or entecavir were postoperatively administered to antiviral groups. Surgical specimens were examined immunohistochemically for carboxylic acid–terminal truncated HBV X protein (Ct-HBx). Results In the nonrandomized cohort, high viral load (≥ 104 copies/mL) significantly predicted unfavorable overall survival and recurrence-free survival (RFS), whereas antiviral treatment significantly improved both types of survival. In the RCT, antiviral treatment significantly decreased HCC recurrence and HCC-related death, with hazard ratios (HRs) of 0.48 (95% CI, 0.32 to 0.70) and 0.26 (95% CI, 0.14 to 0.50), respectively, in multivariate Cox analyses. Patients who received antiviral treatment had significantly decreased early recurrence (HR, 0.41; 95% CI, 0.27 to 0.62) and improved liver function 6 months after surgery compared with the controls (P < .001). Those with recovered liver function had a higher 2-year RFS rate than those without (P = .003). Ct-HBx expression in adjacent hepatic tissues significantly predicted an unfavorable RFS in the antiviral group (P < .001). Conclusion Although it might not affect the HCC-promoting potential of Ct-HBx, NA treatment is effective in normalizing liver function, decreasing HBV-HCC recurrence, and improving postoperative survival. This effect should be validated in a multicenter phase III RCT.

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