Long-term tracking of hepatitis B viral load and the relationship with risk for hepatocellular carcinoma in men.
Little is known about the longitudinal course of hepatitis B virus (HBV) load and its relationship with the development of hepatocellular carcinoma (HCC). We conducted a case-cohort study nested within a cohort of 2874 HBV surface antigen-positive male Taiwanese government employees aged 30 years or older. HBV genotype and DNA levels (i.e. viral load) were tested using polymerase chain reaction-based assays on plasma samples from 112 cases and 1031 non-cases. Prediagnostic plasma levels of HBV DNA were measured in multiple samples collected from each man (total 7706 samples), taken over periods of up to 16 years before diagnosis. Baseline viral load influenced HBV genotype-specific HCC risks and predicted the persistence of high viral load (>/=4.39 log copies/ml) that can cause HCC. Moderate to high tracking of viral load was observed within 9 years. Hepatitis B e antigen (P < 0.0001), genotype C HBV infection (P = 0.0369) and longitudinal alanine aminotransferase (ALT) elevation (defined as ALT abnormality in >/=50% of the visits) (P = 0.0005) were positively related to longer duration of persistence for high viral load. After multivariate adjustment, HBV genotype C [odds ratio (OR) = 5.97, 95% confidence interval (CI) = 3.44-10.34], high viral load detected at >/=50% of the visits (compared with sustained low viral load: OR = 5.04, 95% CI = 2.31-11.00) and longitudinal ALT elevation (compared with sustained normal ALT levels: OR = 2.84, 95% CI = 1.46-5.51) accounted for 43.5, 57.2 and 24.9% of HCCs, respectively. The results suggest that maintenance of viral load <4.39 log copies/ml was associated with sustained normalization of ALT levels and decreased risk of HCC.
Wu
Chih-Feng
CF
Research Center for Genes, Environment and Human Health and Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Xuzhou Road Zhongzheng District, Taipei 10055, Taiwan.
Yu
Ming-Whei
MW
Lin
Chih-Lin
CL
Liu
Chun-Jen
CJ
Shih
Wei-Liang
WL
Tsai
Keh-Sung
KS
Chen
Chien-Jen
CJ
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology*; D016022:Case-Control Studies; D015331:Cohort Studies; D004279:DNA, Viral / Q000235:genetics; D006509:Hepatitis B / Q000201:enzymology / Q000821:virology*; D006515:Hepatitis B virus / Q000302:isolation & purification*; D006801:Humans; D008113:Liver Neoplasms / Q000453:epidemiology*; D008297:Male; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology; D019562:Viral Load
D004279:DNA, Viral; D000410:Alanine Transaminase