The rtL180M Mutation of Hepatitis B Virus Closely Associates with Frequent Virol

StephenW

<http://onlinelibrary.wiley.com/doi/10.1111/j.1440-1746.2011.06853.x/abstract>

The rtL180M Mutation of Hepatitis B Virus Closely Associates with Frequent
Virologic Resistance to Adefovir Dipivoxil Therapy

Yoon-Seon Lee, Young-Hwa Chung, Jeong A. Kim, Young Joo Jin, Won Hyung
Park, Sung Eun Kim, Danbi Lee, Ju Hyun Shim, Kang Mo Kim, Young Suk Lim,
Han Chu Lee, Yung Sang Lee, Dong Jin Suh

DOI: 10.1111/j.1440-1746.2011.06853.x

© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell
Publishing Asia Pty Ltd Issue

Journal of Gastroenterology and Hepatology
Accepted Article (Accepted, unedited articles published online for future
issues)

Abstract

Background/Aim: We intended to investigate the effects of preexisting
mutations at reverse transcriptase region of hepatitis B virus (HBV) on the
occurrence of virologic breakthrough (VB) to adefovir dipivoxil (ADV) in
patients with lamivudine (LAM)-resistant chronic hepatitis B (CHB).

Methods: Ninety-seven patients with LAM-resistant CHB were treated with ADV
at a dose of 10mg daily and followed for a median period of 13 months. Just
before the initiation of ADV therapy, the whole length of reverse
transcriptase region of serum HBV-DNA was sequenced using direct
sequencing.

Results: All patients contained genotype C HBV and mutations in the YMDD
motif, specifically, YIDD (65%), YVDD (28%) or both (7%). The rtL180M and
rtL80V/I mutations were identified in 68% and 69%, respectively. The
cumulative probability of VB was 19% and 27% at 1 and 2 years,
respectively. There was no difference in occurrence of VB with regard to
types of YMDD mutation or rtL80V/I. However, interestingly, patients
containing rtL180M experienced VB during ADV monotherapy more frequently
than those not carrying rtL180M (2-yr cumulative probability of virologic
breakthrough: 37% vs. 3% at 2 years, P < 0.01). On multivariate Cox
proportional-hazards analysis, rtL180M (HR, 8.62; 95% CI, 1.08-69.09; P =
0.042) and decrease in HBV-DNA for 1 year of treatment (HR, 0.69; 95% CI,
0.51-0.95; P = 0.024) are independently associated with VB.

Conclusions: The rtL180M mutation of Hepatitis B virus as well as small
decrease in HBV-DNA after 1 year of treatment may be closely associated
with frequent occurrence of virologic resistance to ADV in patients with
LAM-resistant CHB.



(6.合.彩).足球.篮球...各类投注开户下注

第一投注.现金网:招代理年薪10万以上:6668.cc