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Detection of Low Copy Number Integrated Viral DNA Formed by In Vitro Hepatitis B Infection
Published on: November 7, 2018
Core I97L mutation in conjunction with P79Q is associated with persistent low HBV DNA and HBs antigen clearance in
T Honda1, M Ishigami1, Y Ishizu1
1Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Insights
Identifying specific mutations, I97L and P79Q, in chronic hepatitis B (CHB) patients can predict persistent low HBV DNA and hepatitis B surface antigen (HBsAg) clearance, aiding treatment decisions.
Area of Science:
- Hepatology
- Virology
- Molecular Biology
Background:
- Chronic hepatitis B (CHB) requires differentiating patients with low viral load from those with active disease to prevent cirrhosis.
- Identifying predictive markers for sustained low HBV DNA and hepatitis B surface antigen (HBsAg) clearance is crucial for effective CHB management.
Purpose of the Study:
- To identify mutations associated with persistent low HBV DNA and eventual HBsAg clearance in CHB patients.
- To evaluate the predictive value of specific HBV mutations for clinical outcomes in CHB.
Main Methods:
- Serum samples from 33 CHB genotype C patients were analyzed based on HBV DNA and ALT levels over two years.
- HBV sequences were compared, focusing on the I97L and P79Q mutations in 82 CHB patients.
- Kaplan-Meier analysis assessed cumulative incidences of low HBV DNA and HBsAg clearance in relation to mutations.
Main Results:
- The I97L mutation incidence was significantly higher in patients with persistent low HBV DNA and normal ALT (83.3%) compared to other groups (p=0.021).
- Patients with the I97L mutation showed significantly higher cumulative incidences of persistent low HBV DNA (p=0.003) and HBsAg clearance (p=0.016).
- The presence of the P79Q mutation further increased the likelihood of these favorable outcomes.
Conclusions:
- The I97L and P79Q mutations are valuable predictors of persistent low HBV DNA, normal ALT levels, and HBsAg clearance in CHB patients.
- Measuring these mutations can assist clinicians in stratifying CHB patients and optimizing treatment strategies.
- These findings contribute to personalized medicine approaches in managing chronic hepatitis B.
Objectives:
When considering treatment for chronic hepatitis B (CHB), it is important to discriminate between patients with persistent low HBV DNA and patients with active hepatitis, who may proceed to cirrhosis. In this study, we sought to identify mutations in patients expected to have persistent low HBV DNA and ultimately exhibit clearance of hepatitis B surface antigen (HBsAg).
Methods:
Serum samples were obtained from 33 CHB genotype C patients, divided based on HBV DNA and alanine aminotransferase (ALT) levels following observation for >2 years: Group A (n=10), transient HBV DNA ≥5.0 log copies/mL and ALT ≥120 IU/L; Group B (n=11), persistent HBV DNA <5.0 and ALT <60; and Group C (n=12), persistent HBV DNA <4.0 and ALT <30. Full-length HBV sequences were compared among groups. Subsequently, 82 patients with CHB were evaluated for the I97L mutation and the additional mutation P79Q. We compared cumulative incidences of persistent low HBV DNA and HBsAg clearance in patients with or without I97L and P79Q by the Kaplan-Meier method.
Results:
Incidence of Core mutation I97L differed significantly among groups: A, 30% (3/10); B, 36.4% (4/11); C, 83.3% (10/12) (p = 0.021). Cumulative incidences of persistent low HBV DNA and HBsAg clearance were significantly higher in patients with I97L than in those with wild-type I97 (p = 0.003 and p = 0.016, respectively), and even higher in those with P79Q.
Conclusions:
In patients with CHB, measurement of I97L and additional mutation P79Q would be useful for predicting persistent low HBV DNA, normal ALT, and HBsAg clearance.
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