Clinical features of chronic hepatitis B patients with YMDD mutation after lamivudine therapy.
OBJECTIVE
To study the clinical features of chronic hepatitis B (CHB) patients with tyrosine-methionine-aspartate-aspartate (YMDD) mutation after lamivudine therapy.


METHODS
This investigation was a retrospective study of 63 CHB patients with YMDD mutation during lamivudine therapy. Clinical data, including period and types of YMDD mutation; hepatitis B virus (HBV) DNA levels and alanine aminotransferase (ALT) levels before and after YMDD mutation were measured. YMDD mutation in the HBV DNA polymerase gene was determined using polymerase chain reaction (PCR) and direct sequencing. HBV DNA quantification was determined using real-time PCR. Relevant serum markers of HBV were measured. The follow-up period was 12 months after YMDD mutation.


RESULTS
YMDD mutation occurred 7-44 months (median, 21.5 months) after the start of lamivudine therapy. The majority of the cases (42/63, 66.6%) had YMDD mutants detected between 12 and 24 months. Four types of YMDD mutation were observed in this study, rtL180M/M204V mutation was the predominant type (26/63, 41.3%). A proportion of patients (16/63, 25.4%; 12/63, 19.1%) had higher HBV DNA levels and ALT levels (after mutation vs before mutation), respectively.


CONCLUSIONS
The majority of patients with YMDD mutants had similar or lower HBV DNA levels and ALT levels compared with baseline values. This subset of patients might have benefited from the continued lamivudine therapy. The patients with increased ALT and HBV DNA levels (breakthrough hepatitis) should benefit from the addition of a newer nucleotide analogue (e.g. adefovir).
Liu
Ke-zhou
KZ
Institute of Infectious Diseases, First Affiliated Hospital, School of Medcine, Zhejiang University, Hangzhou 310003, China. liukezhou@zju.edu.cn
Hou
Wei
W
Zumbika
Edward
E
Ni
Qin
Q
D000293:Adolescent; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D015684:Gene Products, pol / Q000097:blood* / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012189:Retrospective Studies; D016896:Treatment Outcome
D019380:Anti-HIV Agents; D015684:Gene Products, pol; C066027:P protein, Hepatitis B virus; D019259:Lamivudine