Lamivudine-Resistance in Patients with Chronic Hepatitis B and/or Cirrhosis and Detection of Mutations in YMDD Motif of Hepatitis B Virus Genome

Korean J Hepatol > Volume 7(1); 2001 > Article

The Korean Journal of Hepatology 2001;7(1): 15-33.

원저 / 만성 B형 간염과 간경변 환자에서 Lamivudine 저항성 B형 간염 바이러스의 출현양상 및 YMDD motif 돌연변이 검출 ( Lamivudine-Resistance in Patients with Chronic Hepatitis B and/or Cirrhosis and Detection of Mutations in YMDD Motif of Hepatitis B Virus G

Lamivudine-Resistance in Patients with Chronic Hepatitis B and/or Cirrhosis and Detection of Mutations in YMDD Motif of Hepatitis B Virus Genome

Sung Ho Kang,Young Min Park,Jong Young Choi,Je Hyun Shin,Tae Wook Park,Si Hyun Bae,Byung Hun Byun,Byung Min Ahn,Chang Don Lee,Sang Bok Cha,Hee Sik Sun,Doo Ho Park,Boo Sung Kim

Department of Internal Medicine, College of Medicine, and WHO Collaborating Center for Reference and Research on Viral Hepatitis, The Catholic University of Korea, Seoul, Korea

ABSTRACT

Background/Aims
Lamivudine is an antiviral nucleoside analogue effective for the treatment of hepatitis B virus (HBV) infection via the inhibition of DNA polymerase activity. The mutations, however, in YMDD motif, such as YVDD and YIDD, have been found to interfere with the therapeutic efficacy of lamivudine. This study was performed to identify the role of such mutant-type HBV among Korean hepatitis B patients with chronic hepatitis or cirrhosis receiving lamivudine treatment. Methods: Serum samples were collected from four groups of patients; patients with breakthrough (group I, n = 8); patients who showed no response after the treatment (group II, n = 6); patients who showed good response (group III, n = 6); patients with chronic hepatitis B without any treatment (group IV, n = 4). Mutations were detected by PCR-cloning and automated sequencing. Results: Mutations in YMDD were found in only 4 (50%) in group I and were negative in group II. No mutations could be identified in the serum samples collected before treatment and from groups III and IV. YVDD mutation was found to be associated with two additional mutations, 'L-to-M' in 528th amino acid and 'L-to-V' in 577th amino acid. Conclusions: Lamivudine resistance appeared in three different patterns: (1) breakthrough related to the mutations in YMDD motif; (2) breakthrough not related to the YMDD mutations; and (3) primary non-responder not related to the YMDD mutations.(Korean J Hepatol 2001;7:15-33)

KeyWords: Lamivudine, Hapatitis/Viral/Chronic Hepatitis B, Lamivudine- resistant , YMDD motif