Hepatitis B Virus Combo Mutations Improve the Prediction and Active Prophylaxis of Hepatocellular Carcinoma: A Clinic-Based Cohort Study.
We aimed to evaluate whether hepatitis B virus (HBV) mutations at the core promoter region could improve the prediction and specific prophylaxis of hepatocellular carcinoma (HCC) in chronic HBV-infected patients. A total of 2,114 HBV-infected patients enrolled between August 1998 and December 2007 were followed-up for 18,406 person-years. Of those, 612 received ≥48 week treatments with nucleos(t)ide analogue (NA) and/or IFNα. Baseline HBV mutations were identified by sequencing. Propensity score matching was applied to reduce baseline differences between antiviral and control cohorts. Multivariate Cox regression analyses, including baseline characteristics of 2,114 patients, showed that age, male, cirrhosis, and HBV mutations (C1653T, T1753V, and A1762T/G1764A) independently increased HCC risk. In control patients carrying A1762T/G1764A, addition of C1653T and/or T1753V significantly increased HCC risk (HR, 1.57; P = 0.038); combo mutations with C1653T, T1753V, and A1762T/G1764A improved the validity of HCC prediction by age, male, and cirrhosis (P = 0.002). In the matched cohorts, antiviral treatment reduced HCC incidence (13.90/1,000 vs. 7.70/1,000 person-years, P = 0.005); NA treatment for ≥60 months was required for the prophylaxis of HCC in cirrhotic patients (P = 0.03); antiviral treatment reduced HCC risk in patients carrying A1762T/G1764A (HR, 0.40; P = 0.002) or C1653T (HR, 0.45; P = 0.04) and in those without T1753V (HR, 0.42; P = 0.005), but could not reduce HCC risk in patients without A1762T/G1764A or C1653T and in those with T1753V. In summary, HBV mutation A1762T/G1764A, C1653T, and T1753V in combination improve HCC prediction in HBV-infected patients. To prevent HCC, patients infected with HBV carrying A1762T/G1764A or C1653T, but not T1753V, should be given priority of receiving antiviral treatments.
Department of Epidemiology, Second Military Medical University, Shanghai, China.
Jianhua
J
Yin
Department of Infectious Diseases, The 2nd Affiliated Hospital, Second Military Medical University, Shanghai, China.
Junxue
J
Wang
Department of Epidemiology, Second Military Medical University, Shanghai, China.
Rui
R
Pu
Department of Infectious Diseases, The 2nd Affiliated Hospital, Second Military Medical University, Shanghai, China.
Haiguang
H
Xin
Department of Epidemiology, Second Military Medical University, Shanghai, China.
Zixiong
Z
Li
Division of Chronic Diseases, Center for Disease Control and Prevention of Yangpu District, Shanghai, China.
Xue
X
Han
Department of Epidemiology, Second Military Medical University, Shanghai, China.
Yibo
Y
Ding
Department of Epidemiology, Second Military Medical University, Shanghai, China.
Yan
Y
Du
Department of Epidemiology, Second Military Medical University, Shanghai, China.
Wenbin
W
Liu
Department of Epidemiology, Second Military Medical University, Shanghai, China.
Yang
Y
Deng
Department of Epidemiology, Second Military Medical University, Shanghai, China.
Xiaowei
X
Ji
Division of Chronic Diseases, Provincial Center for Disease Control and Prevention of Jiangsu, Nanjing, China.
Ming
M
Wu
Division of Chronic Diseases, Provincial Center for Disease Control and Prevention of Zhejiang, Hangzhou, China.
Min
M
Yu
Department of Epidemiology, Second Military Medical University, Shanghai, China.
Hongwei
H
Zhang
International Cooperation Laboratory on Signal Transduction, The 3rd Affiliated Hospital, Second Military Medical University, Shanghai, China.
Hongyang
H
Wang
Department of Genitourinary Medical Oncology-Research, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Timothy C
TC
Thompson
Department of Infectious Diseases, The 2nd Affiliated Hospital, Second Military Medical University, Shanghai, China.
Wu
W
Ni
Department of Epidemiology, Second Military Medical University, Shanghai, China. gcao@smmu.edu.cn.
Guangwen
G
Cao
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000517:prevention & control* / Q000821:virology; D015331:Cohort Studies; D005260:Female; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D015994:Incidence; D008103:Liver Cirrhosis / Q000821:virology; D008113:Liver Neoplasms / Q000453:epidemiology / Q000517:prevention & control* / Q000821:virology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016016:Proportional Hazards Models; D012372:ROC Curve; D012307:Risk Factors
D000998:Antiviral Agents