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Detection of Low Copy Number Integrated Viral DNA Formed by In Vitro Hepatitis B Infection
Published on: November 7, 2018
HBV PreS/S gene mutations in patients with chronic hepatitis B
Bülent Çakal1,2, Bilger Çavuş3, Alp Atasoy3
1Department of Medical Microbiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey. bulentcakal@yahoo.com.
Insights
Hepatitis B virus (HBV) PreS/S gene variations are linked to progressive liver disease. Specific mutations, particularly S207R/N/I/T and in the PreS2 region, are independently associated with advanced liver fibrosis in chronic hepatitis B patients.
Area of Science:
- Hepatology
- Virology
- Molecular Biology
Background:
- Progressive liver disease in chronic hepatitis B (CHB) is a significant health concern.
- Hepatitis B virus (HBV) PreS/S gene variants are implicated in CHB pathogenesis.
- Understanding the relationship between HBV genetic variations and liver histopathology is crucial for predicting disease progression.
Purpose of the Study:
- To investigate the association between HBV PreS/S gene variations and liver histopathology.
- To identify specific HBV PreS/S mutations linked to advanced liver fibrosis in CHB patients.
Main Methods:
- Genomic DNA was extracted from 109 CHB patients.
- The HBV PreS/S gene was amplified using PCR and sequenced via Sanger sequencing.
- Amino acid substitutions, nonsense mutations, and deletions were analyzed against liver fibrosis stages.
Main Results:
- A high mutation rate (14.9%) was observed across the HBV PreS/S gene, with the PreS2 region showing the highest frequency (27.27%).
- Mutations L54P (PreS1), F130L/S (PreS2), S207R/N/I/T, and I208T (S gene) were significantly more common in patients with advanced fibrosis (F≥3).
- The S207R/N/I/T mutation was identified as an independent risk factor for liver fibrosis, and PreS2 mutations correlated with higher fibrosis scores.
Conclusions:
- The S207R/N/I/T mutation in the HBV S protein is independently associated with liver fibrosis progression in CHB.
- PreS/S gene variations, particularly within the PreS2 region, play a role in the development and progression of liver fibrosis in chronic hepatitis B.
Abstract:
Variants in the hepatitis B virus (HBV) PreS/S gene have been suggested to contribute to the development of progressive liver disease. This study aimed to evaluate the association between HBV PreS/S variations and liver histopathology in patients with chronic hepatitis B. A total of 109 patients under clinical follow-up for chronic hepatitis B were included. The HBV PreS/S gene was amplified by PCR and sequenced using the Sanger method. Amino acid substitutions, nonsense mutations, and deletions were analyzed in relation to liver fibrosis stage. Overall, 58 of 389 amino acid sites (14.9%) in the HBV PreS/S gene showed substitutions, with the highest mutation rate observed in the PreS2 region (27.27%). Mutations L54P (PreS1), F130L/S (PreS2), and S207R/N/I/T and I208T (S gene) were significantly more frequent in patients with advanced fibrosis (F ≥ 3) (p < 0.05). Multivariable analysis identified S207R/N/I/T as an independent risk factor for liver fibrosis. Patients with PreS2 mutations had higher fibrosis scores (p < 0.05). The S207R/N/I/T mutation in the C-terminal region of the HBV S protein is independently associated with liver fibrosis, while PreS2 mutations may contribute to fibrosis progression in chronic hepatitis B.
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