No benefit to continue lamivudine therapy after emergence of YMDD mutations.
BACKGROUND
Mutations in the sequence of the conserved tyrosine-methionine-aspartate-aspartate (YMDD) locus of the HBV RNA-dependent DNA polymerase (rt M 204 I/V) may develop after 6-9 months of lamivudine therapy. The current practice of continuing lamivudine therapy has been associated with hepatitis flares or even hepatic decompensation. In addition, experiments have shown that the defective replication competency of rt M 204 I/V restores upon addition of lamivudine.


OBJECTIVE
To evaluate whether continuing lamivudine therapy after emergence of rt M 204 I/V is appropriate.


METHODS
The clinical courses of 66 patients with continuing lamivudine therapy (continued group) and 68 patients who discontinued lamivudine therapy (discontinued group) were monitored monthly or more frequently if condition required. Hepatitis flare, jaundice, hepatic decompensation and hepatitis B e antigen (HBeAg) seroconversion in HBeAg-positive patients were documented as events.


RESULTS
In a 12-month period, hepatitis flares and decompensations occurred in 67 and 11%, respectively, in patients who continued lamivudine therapy, as compared with 54 and 7%, respectively (P>0.05), in those who stopped therapy. HBeAg seroconversion rate was 19% in continued group and 35% in discontinued group (P=0.08). Serum HBV DNA increased in 48 (73%) of the continued group, and the median level increased from 46 pg/ml upon first detection of mutation to 330 pg/ml (P<0.001) at the end of 12 months continuing therapy. In contrast, serum HBV DNA level in the discontinued group increased in 22 (33%) patients but decreased in 39 patients, and median level decreased from 172 to 55 pg/ml at the end of 12 months after stopping lamivudine.


CONCLUSIONS
These results suggest that there is no benefit to continued lamivudine therapy after emergence of rt M 204 I/V.
Liaw
Yun-Fan
YF
Liver Research Unit, Chang Gung Memorial Hospital and University, Taipei, Taiwan. liveryfl@so-net.net.tw
Chien
Rong-Non
RN
Yeh
Chau-Ting
CT
D000293:Adolescent; D000328:Adult; D020816:Amino Acid Motifs; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D006509:Hepatitis B / Q000188:drug therapy* / Q000821:virology; D006515:Hepatitis B virus / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012194:RNA-Directed DNA Polymerase / Q000235:genetics*; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
D000998:Antiviral Agents; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D012194:RNA-Directed DNA Polymerase