Affiliation:
1. Division of Hepatogastroenterology
2. Department of Internal Medicine, Graduate Institute of Clinical Medical Sciences
3. Chang Gung University, Department of Pathology, Kaohsiung Chang Gung Memorial Hospital, 123 Ta Pei Road, Kaohsiung, Taiwan
Abstract
ABSTRACT
To assess the prevalence and clinical significance of hepatitis B virus (HBV) genotypes and precore and core promoter mutations in Taiwan, a cohort of 200 Taiwanese chronic hepatitis B patients was analyzed. The HBV genotypes and sequences of the precore and the core promoter regions were determined in 66 asymptomatic carriers and 134 patients who had liver biopsy-verified chronic hepatitis and liver cirrhosis. The HBV e-antigen (HBeAg)-negative patients had a higher frequency of mutations at core promoter nucleotides 1753 and 1773 and precore nucleotides 1846, 1896, and 1899 than HBeAg-positive patients. Among the 200 patients, the frequencies of genotype C, T1762 and A1764, C1753, T1766 and A1768, and A1896 mutations increased and the frequencies of T or G1752, T1773, G1799, and C1858 mutations decreased with advancing liver diseases. These factors were different between those with HBeAg-positive status and those with HBeAg-negative status. Based on multiple logistic regression analysis, the risk factors of liver cirrhosis for 200 patients were the presence of T1762 and A1764 mutations (odds ratio [OR] = 11.11; 95% confidence interval [CI] = 3.91 to 31.25;
P
< 0.001), age ≥35 years (OR = 3.42; 95% CI = 1.33 to 8.77;
P
= 0.011), and genotype C (OR = 2.87; 95% CI = 1.21 to 6.81;
P
= 0.017). Further categorical analysis found that 62.1% of patients with genotype C, T1762 and A1764 mutations and age ≥35 years had liver cirrhosis. None of the 55 patients infected with the genotype B, A1762 and G1764 wild type and age <35 years showed liver cirrhosis. In conclusion, our data suggest that pathogenic differences between HBeAg-positive and -negative patients may exist. In Taiwan, HBV genotype C and the T1762 and A1764 mutations may play a role in HBV-related liver cirrhosis, and these could serve as molecular markers for prediction of the clinical outcomes of chronic HBV patients.
Publisher
American Society for Microbiology
Reference42 articles.
1. Akahane, Y., T. Yamanaka, H. Suzuki, Y. Sugai, F. Tsuda, S. Yotsumoto, S. Omi, H. Okamoto, Y. Miyakawa, and M. Mayumi. 1990. Chronic active hepatitis with hepatitis B virus DNA and antibody against e antigen in the serum. Disturbed synthesis and secretion of e antigen from hepatocytes due to a point mutation in the precore region. Gastroenterology99:1113-1119.
2. Akarca, U. S., S. Greene, and A. S. F. Lok. 1994. Detection of precore hepatitis B virus mutants in asymptomatic HBs-positive family members. Hepatology19:1366-1370.
3. Baumert, T. F., S. A. Rogers, K. Hasegawa, and T. J. Liang. 1996. Two core promoter mutations identified in a hepatitis B virus strain associated with fulminant hepatitis result in enhanced viral replication. J. Clin. Investig.98:2268-2276.
4. Brunetto, M. R., M. M. Giarin, F. Oliveri, E. Chiaberge, M. Baldi, A. Alfarano, A. Serra, G. Saracco, G. Verme, and H. Will. 1991. Wild-type and e antigen-minus hepatitis B viruses and course of chronic hepatitis. Proc. Natl. Acad. Sci. USA88:4186-4190.
5. Brunetto, M. R., M. Giarin, G. Saracco, F. Oliver, P. Calvo, G. Capra, A. Randone, M. L. Abate, et al. 1993. Hepatitis B virus unable to secret e antigen and response to interferon in chronic hepatitis B. Gastroenterology105:846-850.
Cited by
87 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献