Source Division of Gastroenterology, Department of Internal Medicine, Buddhist Tzu Chi General Hospital Taipei Branch, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan; School of Medicine, Tzu Chi University, Hualien, Taiwan.
BACKGROUND & AIMS: Patients with chronic hepatitis B virus (HBV) infection have a high risk for developing hepatocellular carcinoma (HCC). Patients with lower levels of hepatitis B surface antigen (HBsAg) have higher chances of losing HBsAg than those with high levels. However, little is known about whether higher levels of HBsAg increase the risk for HCC.
METHODS: We followed 2688 Taiwanese HBsAg-positive patients without evidence of cirrhosis for a mean time period of 14.7 years. In addition to known risk factors of HCC, we investigated association between levels of HBsAg and the development of HCC.
RESULTS: Of the patients followed, 191 developed HCC, with an average annual incidence rate of 0.5%. Baseline levels of HBsAg and HBV were associated with the development of HCC, and risk increased with level. Compared to HBsAg level, by receiver operating characteristic curve analysis, HBV DNA level better predicted the development of HCC over 10-year and 15-year periods (both P<.001). However, when we evaluated hepatitis B e antigen (HBeAg)-negative patients with levels of HBV DNA <2000 IU/mL, factors that determined HCC risk included sex, age, and levels of alanine aminotransferase (ALT) and HBsAg (≧1000 IU/mL), but not level of HBV DNA. Multivariate analysis showed that the adjusted hazard ratio for HCC in patients with levels of HBsAg ≧1000 vs <1000 IU/mL was 13.7 (95% confidence interval, 4.8-39.3).
CONCLUSIONS: Among patients infected with HBV genotypes B or C, determinants of HCC risk include their sex, age, HBeAg status, HBV genotype and levels of ALT and HBV DNA, but not level of HBsAg. Among HBeAg-negative patients with low viral loads, HCC risk is determined by levels of HBsAg and ALT and age, but not HBV DNA.