Clinical significance of hepatitis B virus (HBV) genotypes and precore and core promoter mutations affecting HBV e antigen expression in Taiwan.
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 > or =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 > or =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.
Chen
Chien-Hung
CH
Division of Hepatogastroenterology, Department of Internal Medicine, Kaoshiung Chang Gung Memorial Hospital, 123 Ta Pei Road, Kaohsiung, Taiwan.
Lee
Chuan-Mo
CM
Lu
Sheng-Nan
SN
Changchien
Chi-Sin
CS
Eng
Hock-Liew
HL
Huang
Chao-Min
CM
Wang
Jing-Houng
JH
Hung
Chao-Hung
CH
Hu
Tsung-Hui
TH
D000328:Adult; D002353:Carrier State / Q000821:virology; D005260:Female; D005838:Genotype; D006512:Hepatitis B Core Antigens / Q000235:genetics*; D006513:Hepatitis B e Antigens / Q000378:metabolism*; D006515:Hepatitis B virus / Q000145:classification* / Q000235:genetics / Q000472:pathogenicity*; D019694:Hepatitis B, Chronic / Q000503:physiopathology / Q000821:virology; D006801:Humans; D008103:Liver Cirrhosis / Q000503:physiopathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011498:Protein Precursors / Q000235:genetics*; D013624:Taiwan; D014758:Viral Core Proteins / Q000235:genetics
D006512:Hepatitis B Core Antigens; D006513:Hepatitis B e Antigens; D011498:Protein Precursors; D014758:Viral Core Proteins