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

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

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.