Pre-S deletion and complex mutations of hepatitis B virus related to advanced liver disease in HBeAg-negative patients.
OBJECTIVE
This longitudinal study investigated the interactions and roles of hepatitis B virus (HBV) genotypes, pre-S deletions, and core promoter and precore mutations on the progression of liver disease in hepatitis B e antigen (HBeAg)-negative patients.


METHODS
A total of 141 HBeAg-negative patients without liver cirrhosis or hepatocellular carcinoma at study entry were recruited for this study, including 45 inactive HBV carriers and 96 patients with HBeAg-negative chronic hepatitis B. The HBV genotypes and the sequences of pre-S, core promoter, and precore regions were determined.


RESULTS
Compared with patients without developing liver cirrhosis, patients with the development of liver cirrhosis had higher rates of genotype C; pre-S deletions; C or G1753, T1762/A1764, T1766, and/or A1768 mutants; and G1799 variant. Cox regression analysis showed that older age, higher total bilirubin and HBV DNA levels, pre-S deletions, and T1766 and/or A1768 mutants were significantly associated with the development of liver cirrhosis. HBV with a complex mutation pattern (pre-S deletion, T1762/A1764, and T1766 and/or A1768 mutants) rather than a single mutation was associated with the development of liver cirrhosis, and the patterns of mutation combinations differed between HBV genotype B and C. Moreover, pre-S deletion was a significant risk factor for hepatocellular carcinoma.


CONCLUSIONS
This study indicated that pre-S deletion and combined mutations of HBV are useful molecular markers for predicting the clinical outcomes of HBeAg-negative patients.
Chen
Chien-Hung
CH
Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Kaohsiung, Taiwan.
Hung
Chao-Hung
CH
Lee
Chuan-Mo
CM
Hu
Tsung-Hui
TH
Wang
Jing-Houng
JH
Wang
Jyh-Chwan
JC
Lu
Sheng-Nan
SN
Changchien
Chi-Sin
CS
D000328:Adult; D001663:Bilirubin / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000235:genetics / Q000276:immunology; D004279:DNA, Viral / Q000097:blood; D018450:Disease Progression; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D006509:Hepatitis B / Q000150:complications / Q000235:genetics / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000235:genetics*; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008103:Liver Cirrhosis / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D008113:Liver Neoplasms / Q000209:etiology / Q000235:genetics / Q000276:immunology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011237:Predictive Value of Tests; D011498:Protein Precursors / Q000235:genetics*; D012044:Regression Analysis; D014758:Viral Core Proteins / Q000235:genetics*
D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D011498:Protein Precursors; D014758:Viral Core Proteins; C050806:presurface protein 1, hepatitis B surface antigen; D001663:Bilirubin