Four years of treatment with lamivudine: clinical and virological evaluations in HBe antigen-negative chronic hepatitis B.
OBJECTIVE
To evaluate the clinical and virological impact of the prolonged use of lamivudine in 94 patients with HBe antigen-negative chronic hepatitis B.


METHODS
Initial virological and biochemical responses were obtained in 84 (89%) and in 83 (88%) patients respectively.


RESULTS
The virological response peaked within the first 12 months, but diminished to 39% at 48 months because of drug resistance. Overall a virological breakthrough developed in 44 patients (52.4%). After virological breakthrough, the actuarial probability of maintaining biochemical remission diminished to 15% at 24 months and 0% at 29 months. There was no response in 10.6%. Polymerase gene mutations were observed in 82.5% of virological breakthroughs but also in 75% of the non-responders. Overall 7.4% of patients developed a hepatocellular carcinoma.


CONCLUSIONS
Almost 90% of patients responded initially to lamivudine but the emergence of drug resistance progressively reduced the rate of virological remission to 39% at the fourth year of therapy. YMDD mutants explained the 75% of lamivudine resistances and were also selected very early in non-responders. Although the biochemical response is invariably lost within 29 months of the YMDD mutant's duration, the clinical outcome was benign despite severe postvirological breakthrough hepatitic flares in about 12% of cases.
Department of Gastroenterology, Molinette Hospital, Turin, Italy. silvygaia@yahoo.com
S
S
Gaia
A
A
Marzano
A
A
Smedile
V
V
Barbon
M L
ML
Abate
A
A
Olivero
M
M
Lagget
S
S
Paganin
M
M
Fadda
G
G
Niro
M
M
Rizzetto
D000998:Antiviral Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000209:etiology; D004341:Drug Evaluation; D005260:Female; D005500:Follow-Up Studies; D006513:Hepatitis B e Antigens / Q000032:analysis; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000209:etiology; D008297:Male; D008875:Middle Aged; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome
D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine