Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level.
BACKGROUND
Serum hepatitis B virus (HBV) DNA level is a marker of viral replication and efficacy of antiviral treatment in individuals with chronic hepatitis B.


OBJECTIVE
To evaluate the relationship between serum HBV DNA level and risk of hepatocellular carcinoma.


METHODS
Prospective cohort study of 3653 participants (aged 30-65 years), who were seropositive for the hepatitis B surface antigen and seronegative for antibodies against the hepatitis C virus, recruited to a community-based cancer screening program in Taiwan between 1991 and 1992.


METHODS
Incidence of hepatocellular carcinoma during follow-up examination and by data linkage with the national cancer registry and the death certification systems.


RESULTS
There were 164 incident cases of hepatocellular carcinoma and 346 deaths during a mean follow-up of 11.4 years and 41,779 person-years of follow-up. The incidence of hepatocellular carcinoma increased with serum HBV DNA level at study entry in a dose-response relationship ranging from 108 per 100,000 person-years for an HBV DNA level of less than 300 copies/mL to 1152 per 100,000 person-years for an HBV DNA level of 1 million copies/mL or greater. The corresponding cumulative incidence rates of hepatocellular carcinoma were 1.3% and 14.9%, respectively. The biological gradient of hepatocellular carcinoma by serum HBV DNA levels remained significant (P<.001) after adjustment for sex, age, cigarette smoking, alcohol consumption, serostatus for the hepatitis B e antigen (HBeAg), serum alanine aminotransferase level, and liver cirrhosis at study entry. The dose-response relationship was most prominent for participants who were seronegative for HBeAg with normal serum alanine aminotransferase levels and no liver cirrhosis at study entry. Participants with persistent elevation of serum HBV DNA level during follow-up had the highest hepatocellular carcinoma risk.


CONCLUSIONS
Elevated serum HBV DNA level (> or =10,000 copies/mL) is a strong risk predictor of hepatocellular carcinoma independent of HBeAg, serum alanine aminotransferase level, and liver cirrhosis.
Chen
Chien-Jen
CJ
Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan. cjchen@ha.mc.ntu.edu.tw
Yang
Hwai-I
HI
Su
Jun
J
Jen
Chin-Lan
CL
You
San-Lin
SL
Lu
Sheng-Nan
SN
Huang
Guan-Tarn
GT
Iloeje
Uchenna H
UH
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000821:virology*; D004279:DNA, Viral / Q000097:blood*; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000302:isolation & purification* / Q000472:pathogenicity; D019694:Hepatitis B, Chronic / Q000503:physiopathology*; D006801:Humans; D015994:Incidence; D008103:Liver Cirrhosis; D008113:Liver Neoplasms / Q000453:epidemiology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D013624:Taiwan
D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D000410:Alanine Transaminase