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Detection of Low Copy Number Integrated Viral DNA Formed by In Vitro Hepatitis B Infection
Published on: November 7, 2018
A case-control study for clinical and molecular biological differences between hepatitis B viruses of genotypes B and
E Orito1, M Mizokami, H Sakugawa
1Second Department of Medicine, Nagoya City University Medical School, Nagoya, Japan.
Insights
Hepatitis B virus (HBV) genotype C is linked to a double core promoter mutation, which is associated with more severe liver disease in older patients. This mutation may worsen chronic hepatitis B progression.
Area of Science:
- Hepatology
- Virology
- Genetics
Background:
- Chronic Hepatitis B (CHB) infection is a global health concern.
- HBV genotypes B and C are prevalent in Asia, with distinct clinical outcomes.
- Understanding molecular differences between genotypes is crucial for managing CHB.
Purpose of the Study:
- To compare clinical and molecular virological differences between Japanese patients with chronic HBV genotypes B and C.
- To investigate the association of specific HBV mutations with clinical parameters and disease severity.
Main Methods:
- A case-control study involving 50 Japanese patients with chronic HBV (genotypes B and C).
- Patients were matched for age, sex, and liver disease severity.
- Analysis included Hepatitis B e antigen (HBeAg), antibody to HBeAg (anti-HBe), precore mutations (A1896), and basic core promoter mutations (T1762/A1764).
Main Results:
- Genotype B patients had lower HBeAg (16% vs. 42%) and higher anti-HBe (84% vs. 56%) compared to genotype C.
- Precore mutation (A1896) prevalence was similar between genotypes and correlated with anti-HBe.
- The double core promoter mutation (T1762/A1764) was significantly more frequent in genotype C (58% vs. 16%) and associated with older age and advanced liver disease.
Conclusions:
- The double core promoter mutation (T1762/A1764) is strongly associated with HBV genotype C.
- This mutation, along with older age and advanced liver disease, may contribute to the aggravation of chronic hepatitis B.
- Genotype C and the double core promoter mutation represent key factors in CHB pathogenesis.
Abstract:
Clinical and molecular virological differences were evaluated in 50 Japanese patients chronically infected with HBV of genotype B and C who were matched for age and sex as well as the severity of liver disease in a case-control study. Hepatitis B e antigen (HBeAg) was significantly less frequent (16% vs. 42%, P <.01), whereas antibody to HBeAg (anti-HBe) was significantly more common (84% vs. 56%, P <. 01) in genotype B than C patients. The predominance of mutants with G-to-A mutation at nucleotide (nt) 1896 in the precore region (A1896) over the wild-type was comparable between genotype B and C patients (60% and 62%, respectively), and it correlated with anti-HBe. The double mutation in the basic core promoter (A-to-T at nt 1762 and G-to-A at nt 1764), however, was significantly more frequent in genotype C than B patients (58% vs. 16%, P <.01), and it did not correlate with anti-HBe or HBeAg. By the multiple logistic regression analysis, the double mutation in the basic core promoter (T1762/A1764) was significantly associated with genotype C [odds ratio (OR), 9.3; 95% confidence interval (CI), 3.4-25.1]], age > or = 35 years (OR, 5.5; CI, 1.5-20.5), and more advanced liver disease (OR, 4.1; CI, 1.6-10.2), but it was not associated with sex, HBeAg, HBV DNA, or the precore mutation (A1896). These results suggest a role of the double mutation in the basic core promoter in association with genotype C and a longer duration of infection in the aggravation of chronic hepatitis B.
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