title: Hepatitis B virus mutation may play a role in hepatocellular carcinoma recurrence: A systematic review and meta-regression analysis.
abstract: OBJECTIVE
  A number of studies have confirmed that antiviral therapy with nucleotide analogs (NAs) can improve the prognosis of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative therapy. However, what factors affected the prognosis of HBV-HCC after removal of the primary tumor and inhibition of HBV replication? A meta-regression analysis was conducted to explore the prognostic factor for this subgroup of patients.
  
  
  METHODS
  MEDLINE, EMBASE, Web of Science, and Cochrane library were searched from January 1995 to February 2014 for clinical trials evaluating the effect of NAs on the prognosis of HBV-HCC after curative therapy. Data were extracted for host, viral, and intervention information. Single-arm meta-analysis was performed to assess overall survival (OS) rates and HCC recurrence. Meta-regression analysis was carried out to explore risk factors for 1-year OS rate and HCC recurrence for HBV-HCC patients after curative therapy and antiviral therapy.
  
  
  RESULTS
  Fourteen observational studies with 1284 patients met the inclusion criteria. Influential factors for prognosis of HCC were mainly baseline HBeAg positivity, cirrhotic stage, advanced Tumor-Node-Metastasis (TNM) stage, macrovascular invasion, and antiviral agent type. The 1-year OS rate decreased by more than four times (coefficient -4.45, P<0.001) and the 1-year HCC recurrence increased by more than one time (coefficient 1.20, P=0.003) when lamivudine was chosen for HCC after curative therapy, relative to entecavir for HCC.
  
  
  CONCLUSIONS
  HBV mutation may play a role in HCC recurrence. Entecavir or tenofovir, a high genetic barrier to resistance, should be recommended for HBV-HCC patients.
authors.affiliation: Department of Infectious Disease, The Second Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Hua-ying
authors.initials: HY
authors.lastname: Zhou
authors.forename: Yue
authors.initials: Y
authors.lastname: Luo
authors.forename: Wen-dong
authors.initials: WD
authors.lastname: Chen
authors.forename: Guo-zhong
authors.initials: GZ
authors.lastname: Gong
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000628:therapy*; D003131:Combined Modality Therapy; D016206:Databases, Bibliographic; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives / Q000627:therapeutic use; D006509:Hepatitis B / Q000150:complications / Q000188:drug therapy / Q000821:virology*; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D012044:Regression Analysis; D000068698:Tenofovir / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; C413685:entecavir; D006147:Guanine; D000068698:Tenofovir
keywords: HBV; hepatocellular carcinoma; nucleotide analogs