Liver Cancer
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Nov 7, 2006; 12(41): 6620-6626
Published online Nov 7, 2006. doi: 10.3748/wjg.v12.i41.6620
Precore/basal core promoter mutants and hepatitis B viral DNA levels as predictors for liver deaths and hepatocellular carcinoma
Myron J Tong, Lawrence M Blatt, Jia-Horng Kao, Jason Tzuying Cheng, William G Corey
Myron J Tong, Jason Tzuying Cheng, William G Corey, The Liver Center, Huntington Medical Research Institutes, Pasadena, California, United States
Myron J Tong, The Pfleger Liver Institute, David Geffen School of Medicine at the University of California in Los Angeles, California, United States
Lawrence M Blatt, Intermune, Inc., Brisbane, California, United States
Jia-Horng Kao, The Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan, China
Correspondence to: Myron J Tong, PhD, MD, Liver Center, Huntington Medical Research Institutes, 660 South Fair Oaks Avenue, Pasadena, California 91105, United States. myrontong@hmri.org
Telephone: +1-626-3975820 Fax: +1-626-3975827
Received: July 27, 2006
Revised: August 12, 2006
Accepted: September 19, 2006
Published online: November 7, 2006
Abstract

AIM: To conduct a retrospective study in 400 chronic hepatitis B patients in order to identify hepatitis B viral factors associated with complications of liver disease or development of hepatocellular carcinoma.

METHODS: The mean follow-up time was 83.6 ± 39.6 mo. Alpha-fetoprotein test and abdominal ultrasound were used for cancer surveillance. Hepatitis B basal core promoter mutants, precore mutants, genotypes, hepatitis B viral DNA (HBV DNA) level and hepatitis B e antigen (HBeAg) were measured. Univariate analysis and logistic regression were used to assess odds ratios for viral factors related to liver deaths and hepatocellular carcinoma development.

RESULTS: During follow-up, 38 patients had liver deaths not related to hepatocellular carcinoma. On multivariate analysis, older age [odds ratio: 95.74 (12.13-891.31); P < 0.0001], male sex [odds ratio: 7.61 (2.20-47.95); P = 0.006], and higher log10 HBV DNA [odds ratio: 4.69 (1.16-20.43); P < 0.0001] were independently predictive for these liver related deaths. Also, 31 patients developed hepatocellular carcinoma. Multivariate analysis showed that older age [odds ratio: 26.51 (2.36-381.47); P = 0.007], presence of precore mutants [odds ratio: 4.23 (1.53-19.58); P = 0.02] and presence of basal core promoter mutants [odds ratio: 2.93 (1.24-7.57); P = 0.02] were independent predictors for progression to hepatocellular carcinoma.

CONCLUSION: Our results show that high levels of baseline serum HBV DNA are associated with non-hepatocellular carcinoma-related deaths of liver failure, while genetic mutations in the basal core promoter and precore regions are predictive for development of hepatocellular carcinoma.

Keywords: Basal core promoter mutants, Precore mutants, Hepatitis B viral genotypes, Hepatitis B viral DNA, Hepatitis B e antigen, Liver failure, Hepatocellular carcinoma