title: Effect of antiviral treatment with nucleotide/nucleoside analogs on postoperative prognosis of hepatitis B virus-related hepatocellular carcinoma: a two-stage longitudinal clinical study.
abstract: OBJECTIVE
  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.
  
  
  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 (≥ 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yin
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.forename: Yifang
authors.initials: Y
authors.lastname: Han
authors.forename: Jie
authors.initials: J
authors.lastname: Xue
authors.forename: Yang
authors.initials: Y
authors.lastname: Deng
authors.forename: Jie
authors.initials: J
authors.lastname: Shi
authors.forename: Weixing
authors.initials: W
authors.lastname: Guo
authors.forename: Hongwei
authors.initials: H
authors.lastname: Zhang
authors.forename: Hongyang
authors.initials: H
authors.lastname: Wang
authors.forename: Shuqun
authors.initials: S
authors.lastname: Cheng
authors.forename: Guangwen
authors.initials: G
authors.lastname: Cao
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000401:mortality* / Q000601:surgery / Q000821:virology; D006498:Hepatectomy; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D008113:Liver Neoplasms / Q000401:mortality* / Q000601:surgery / Q000821:virology; D008137:Longitudinal Studies; D009705:Nucleosides / Q000737:chemistry / Q000627:therapeutic use*; D009711:Nucleotides / Q000737:chemistry / Q000627:therapeutic use*; D011379:Prognosis; D016016:Proportional Hazards Models
chemical_list: D000998:Antiviral Agents; D009705:Nucleosides; D009711:Nucleotides