Association of hepatitis B virus mutations in basal core promoter and precore regions with severity of liver disease: an investigation of 793 Chinese patients with mild and severe chronic hepatitis B and acute-on-chronic liver failure
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To investigate the features of hepatitis B virus (HBV) basal core promoter/precore (BCP/PC) mutations and genotypes in a large number of mild/severe chronic hepatitis B (CHB-M/CHB-S), and acute-on-chronic liver failure (ACLF) patients and analyze the clinical implications of the virologic features.
Patients and methods
Sera of 793 (325 CHB-M, 170 CHB-S, and 298 ACLF) patients admitted to or who had visited Beijing 302 Hospital from January 2005 to December 2008 were collected and successfully amplified for the HBV BCP/PC and a 1225-bp-long S/Pol (nt 54–1278) gene regions. Biochemical and serological parameters and HBV DNA level were routinely performed. Viral DNA was extracted and subjected to a nested PCR. Genotypes/subgenotypes were determined based on complete genomic sequence or on analysis of the 1225-bp-long S/Pol-gene sequence. HBV genotyping was performed by direct PCR sequencing followed by molecular evolutionary analysis of the viral sequences. A P value of <0.05 (two-sided) was considered to be statistically significant.
Our findings suggest that CHB patients infected with BCP/PC mutant viruses are more susceptible to severe hepatitis and ACLF than those with the BCP/PC wild-type virus and that ACLF patients with PC mutant viruses have an increased risk of death. As such, the HBV PC mutation is a potential predictive indicator of ACLF outcome.
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Journal of Gastroenterology
Volume 46, Issue 3 , pp 391-400
- Cover Date
- Print ISSN
- Online ISSN
- Springer Japan
- Additional Links
- Hepatitis B virus
- Basal core promoter mutation
- Precore mutation
- Acute-on-chronic liver failure
- Industry Sectors
- Author Affiliations
- 1. Viral Hepatitis Research Laboratory, Beijing Institute of Infectious Diseases, Beijing, 100039, China
- 2. Liver Failure Research Center, Beijing 302 Hospital, Beijing, 100039, China
- 3. Department of Medicine and Therapeutics and Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
- 4. INSERM, U871, 69003, Lyon, France
- 5. Department of Hepatology and Gastroenterology, Hospices Civils de Lyon, Hôtel Dieu Hospital, 69002, Lyon, France