Changes in Serum Levels of HBV DNA and Alanine Aminotransferase Determine Risk for Hepatocellular Carcinoma

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 141; no. 4; pp. 1240 - 1248.e2
• Main Authors: Chen, Chuen–Fei, Lee, Wen–Chung, Yang, Hwai–I., Chang, Hung–Chuen, Jen, Chin–Lan, Iloeje, Uchenna H., Su, Jun, Hsiao, Chuhsing K., Wang, Li–Yu, You, San–Lin, Lu, Sheng–Nan, Chen, Chien–Jen
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2011
• Subjects: Adult; Alanine Transaminase - blood; Biomarkers - blood; Carcinoma, Hepatocellular - diagnosis; Carcinoma, Hepatocellular - epidemiology; Carcinoma, Hepatocellular - virology; Chronic Hepatitis B; Disease Progression; DNA, Viral - blood; Female; Gastroenterology and Hepatology; Hepatitis B virus - genetics; Hepatitis B, Chronic - complications; Hepatitis B, Chronic - diagnosis; Hepatitis B, Chronic - epidemiology; Humans; Incidence; Liver Cirrhosis - diagnosis; Liver Cirrhosis - epidemiology; Liver Cirrhosis - virology; Liver Disease; Liver Neoplasms - diagnosis; Liver Neoplasms - epidemiology; Liver Neoplasms - virology; Long-term Follow-up Study; Male; Middle Aged; Predictive Value of Tests; Proportional Hazards Models; Registries; Risk Assessment; Risk Factors; Taiwan - epidemiology; Time Factors; Taiwan; Long-term Follow-up Study; ALT; Chronic Hepatitis B; Liver Disease; HBV; HBeAg; hepatitis B virus; alanine aminotransferase; hepatitis B e antigen
• ISSN: 0016-5085; 1528-0012; 1528-0012
• DOI: 10.1053/j.gastro.2011.06.036

It is not clear whether risk for hepatocellular carcinoma can be accurately determined from long-term changes in serum levels of hepatitis B virus (HBV) DNA or alanine aminotransferase (ALT). We measured serum levels of HBV DNA and ALT at enrollment and during follow-up analysis of 3160 participants in the REVEAL-HBV study. Development of hepatocellular carcinoma was determined from follow-up examinations and computerized linkage with National Cancer Registry and National Death Certification profiles. Multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models. During 38,330 person-years of follow-up, 81 participants developed hepatocellular carcinoma (incidence rate, 211.3/100,000 person-years). The risk for hepatocellular carcinoma was only slightly higher for participants whose follow-up levels of HBV DNA spontaneously decreased to <10,000 copies/mL compared with those with baseline levels of HBV DNA <10,000 copies/mL (control group; HR, 2.25; 95% CI, 0.68–7.37). Compared with the control group, the HRs (95% CI) for long-term levels of HBV DNA that persisted at 10,000 to 100,000 copies/mL, decreased to/persisted at 100,000 to 1,000,000 copies/mL, or decreased to/persisted at 1,000,000 to 10,000,000 copies/mL were 3.12 (1.09–8.89), 8.85 (3.85–20.35), and 16.78 (7.33–38.39), respectively. A gradient in ALT level was significantly associated with hepatocellular carcinoma risk: from all low-normal, to ever high-normal, to transient abnormal, to persistent abnormal ( P trend < .001). Long-term changes in serum levels of HBV DNA and ALT are independent predictors of risk for hepatocellular carcinoma. Regular monitoring of levels of HBV DNA and ALT is important in clinical management of chronic carriers of HBV.