Prevalence and significance of Hepatitis B reverse transcriptase mutants in different disease stages of untreated patients

Authors

  • Jinxin Zheng,

    1. Laboratory of Virology, Department of Infectious Diseases, Peking University First Hospital, Beijing, P. R. China
    Search for more papers by this author
    • Both authors contributed equally to the manuscript.
  • Zheng Zeng,

    1. Laboratory of Virology, Department of Infectious Diseases, Peking University First Hospital, Beijing, P. R. China
    Search for more papers by this author
    • Both authors contributed equally to the manuscript.
  • Duyi Zhang,

    1. Laboratory of Virology, Department of Infectious Diseases, Peking University First Hospital, Beijing, P. R. China
    Search for more papers by this author
  • Yanyan Yu,

    1. Laboratory of Virology, Department of Infectious Diseases, Peking University First Hospital, Beijing, P. R. China
    Search for more papers by this author
  • Fang Wang,

    1. Laboratory of Virology, Department of Infectious Diseases, Peking University First Hospital, Beijing, P. R. China
    Search for more papers by this author
  • Calvin Q. Pan

    Corresponding author
    1. Division of Liver Diseases, Department of Medicine, The Mount Sinai Medical Center, Mount Sinai School of Medicine, New York, USA
    2. New Discovery, Flushing, New York, USA
    • Laboratory of Virology, Department of Infectious Diseases, Peking University First Hospital, Beijing, P. R. China
    Search for more papers by this author

Correspondence

Calvin Q. Pan, Director, Division of Liver Diseases, Mount Sinai Hospital,

One Gustave L. Levy Place, New York, NY 10029, USA

Tel: +718-888-7728

Fax: +718-888-7738

e-mail: zeng@bjmu.edu.cn; cpan11355@yahoo.com

Abstract

Aims

Hepatitis B virus (HBV) reverse transcriptase (RT) mutants, which have not been well characterized according to different disease stages. This study aimed to characterize the profiles of naturally occurring mutations in the HBV RT region and their associated clinical outcomes.

Methods

HBV RT region mutations and genotypes were determined by PCR-direct sequencing and compared with p-distance model.

Results

Among 467 consecutive eligible patients (262 chronic hepatitis B patients, 105 cirrhotic patients and 100 hepatocellular carcinoma patients), the nucleos(t)ide analogues-related mutations (rtI169T, rtV173L, rtL180M, rtA181T, rtS202C, rtM204I/V, rtN236T) were found. The p-distance value reached a peak in the age of 20–30 years in the CHB patients and in the age of 40–45 years in the cirrhotic patients and hepatocellular carcinoma patients. The naturally occurring mutation, rtS106C mutation was higher in chronic hepatitis B patients (14/100, 14.0%) and cirrhotic patients (14/100, 14.0%) than that in hepatocellular carcinoma patients (4/100, 4.0%, = 0.013). And the rtD134E/G/N/S mutations were also higher in chronic hepatitis B patients (22/100, 22.0%) and cirrhotic patients (21/100, 21.0%) than that in hepatocellular carcinoma patients (10/100, 10.0%, = 0.021 and = 0.032 respectively). The mutation frequencies in A–B interdomain were higher in cirrhotic patients (101/1900, 5.3%) than that in hepatocellular carcinoma patients (68/1900, 3.6%) (= 0.009).

Conclusions

The nucleos(t)ide analogues-related mutations do exist in treatment naive patients with different disease stages. rtS106C, rtD134E/G/N/S and A–B interdomain mutations may be associated with necro-inflammation, immune response and cirrhosis development at ages older than 40.

Ancillary