[Determination of the lamivudine-resistant mutants of hepatitis B virus].
BACKGROUND
In addition to interferon, lamivudine is the other widely used antiviral agent in the therapy of chronic hepatitis B. This nucleoside analogue inhibits the RNA-dependent DNA polimerase and the reverse transcription by integrating in the viral DNA, which results in the secondary suppression of viral protein synthesis and replication of HBV. It has numerous advantages such as effective viral inhibition, mild side effects and the possibility of oral administration; on the other hand it poses the problem of time-correlated appearance of lamivudine resistant mutants during therapy.


OBJECTIVE
In the Virusserology Laboratory of the Department I. Internal Medicine, Szent György Hospital, Székesfehérvár, detection and type determination of the therapy resistant mutants in the C and B domains of HBV DNA polimerase gene has been carried out the for one year. In this paper, the authors review the molecular biological background of lamivudine resistance and summarise the applied test methodologies and the early results.


METHODS
Six-month and/or 12-, 18-month samples of 18 chronic hepatitis B patients (4 women/14 men) treated in seven Hepatology Centres in Hungary were analysed.


METHODS
Mutants of codons 528, 552, and 555 in the HBV polimerase gene were determined by nested polimerase chain reaction and reverse hybridisation.


RESULTS
M528, V552, I552 and I555 mutants in different variations could be detected in ten out of 18 patients.


CONCLUSIONS
Nowadays, drug therapy is the only treatment option used for the therapy of early and progressed chronic hepatitis B in Hungary. This new diagnostic technique was introduced to clarify the background of ineffective lamivudine therapy. Therapy resistance can occur due to the lack of reaction or the appearance of the special, therapy resistant mutants of the virus. Detection of these YMDD mutants together with the clinical picture and the biochemical and virological parameters can help in forming a decision about cessation of lamivudine therapy or application of a new drug.
Gervain
Judit
J
Fejér Megyei Szent György Kórház, I. Belgyógyászat, Hepato-Pancreatologiai Részleg és Vírusszerológiai Laboratórium, Székesfehérvár. jgervain@mail.fmkorhaz.hu
Papp
Istvánné
I
Csöndes
Mihály
M
Nemesánszky
Elemér
E
Rácz
István
I
Ribiczey
Pál
P
Telegdy
László
L
Tornai
István
I
Weisz
György
G
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000494:pharmacology*; D003062:Codon; D004279:DNA, Viral / Q000187:drug effects* / Q000378:metabolism; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000188:drug therapy; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*
D000998:Antiviral Agents; D003062:Codon; D004279:DNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine