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J Clin Oncol. 2013 Oct 10;31(29):3647-55. doi: 10.1200/JCO.2012.48.5896. Epub 2013 Sep 3.

Effect of antiviral treatment with nucleotide/nucleoside analogs on postoperative prognosis of hepatitis B virus-related hepatocellular carcinoma: a two-stage longitudinal clinical study.

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Jianhua Yin, Yifang Han, Yang Deng, Hongwei Zhang, and Guangwen Cao, Second Military Medical University; Nan Li, Jie Xue, Jie Shi, Weixing Guo, Hongyang Wang, and Shuqun Cheng, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, People's Republic of China.

Erratum in

  • J Clin Oncol. 2013 Nov 10;31(32):4167.
  • J Clin Oncol. 2014 May 1;32(13):1386-7.



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.


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).


In the nonrandomized cohort, high viral load (≥ 10(4) 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).


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.

[Indexed for MEDLINE]

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