Adefovir dipivoxil treatment of lamivudine-resistant chronic hepatitis B

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Adefovir dipivoxil treatment of lamivudine-resistant chronic hepatitis B

Chia-Yen Daia, b, c, d, Wan-Long Chuanga, b, d, Ming-Yen Hsiehb, Li-Po Leeb,

Jee-Fu Huangb, c, Nai-Jen Houb, c, Zu-Yau Lina, b, Shinn-Cherng Chena, b,

Ming-Yuh Hsieha, b, Liang-Yen Wanga, b, Jun-Fa Tsaia, b, Wen-Yu Changa, b

and Ming-Lung Yua, b, ,

aFaculty of Internal Medicine, College of Medicine, Kaohsiung Medical

University, Kaohsiung, Taiwan

bHepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical

University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

cDepartment of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital,

Kaohsiung Medical University, Kaohsiung, Taiwan

dGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical

University, Kaohsiung, Taiwan

Received 21 November 2006; accepted 21 February 2007. Available online 16

March 2007.

Abstract

Adefovir dipivoxil (ADV)-resistant mutations have been identified in

treating hepatitis B virus (HBV) infection. This study aimed to analyze the

response, the incidence of ADV resistance and the virologic characteristics

of ADV therapy. A total of 29 CHB patients with confirmed lamivudine

(LAM)-resistant HBV were treated with ADV for more than 52 weeks. Serum HBV

DNA, HBV genotypes and sequences of HBV polymerase reverse-transcriptase

domain were determined. Rates for the biochemical response, HBeAg loss,

HBeAg seroconversion and virologic response (<200 copies/mL of HBV DNA) were

82.8, 23.5, 11.8, and 48.3%, respectively, at week 52 of treatment. Lower

pre-treatment mean HBV DNA level was the only significant factor associated

with negative HBV DNA after ADV therapy. Six (20.7%) patients had clearance

of LAM-resistant YMDD variants with replacement by the wild type HBV at week

52. The rtN236T, rtA181V/T and rtI233V were not identified before ADV

therapy and the genotypic mutation of rtN236T was detected in one (3.4%)

patient. In conclusion, the 52-week ADV treatment for patients with

LAM-resistant HBV variants significantly achieved normalization of ALT

levels, reduced serum HBV DNA levels and induced HBeAg loss and

seroconversion. The emergence of ADV-resistant mutations seemed rare at

weeks 52.

Corresponding author at: Hepatobiliary Division, Department of Internal

Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road,

Kaohsiung 807, Taiwan. Tel.: +886 7 312 1101x7475; fax: +886 7 3234553.

Antiviral Research

Volume 75, Issue 2, August 2007, Pages 146-151

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