Lc. Da Silva et al., Efficacy and tolerability of long-term therapy using high lamivudine dosesfor the treatment of chronic hepatitis B, J GASTRO, 36(7), 2001, pp. 476-485
Purpose. A long-term follow-up study was carried out to evaluate the tolera
bility and efficacy of long-term therapy (1 to 3 years) with high doses (15
0 or 300mg daily) of lamivudine for chronic hepatitis B. Methods. Thirty-tw
o patients were studied, including those who were seronegative for hepatiti
s B e antigen (HBeAg), as well as those with decompensated liver cirrhosis.
Viral DNA clearance was monitored by using end-point dilution polymerase c
hain reaction (PCR), a highly sensitive method. Hepatitis B virus (HBV) pol
ymerase gene mutations associated with resistance were determined by sequen
cing. Results. Response to lamivudine in the sixth month was observed in 19
/32 (59.4%) patients. With one exception, viral DNA. results observed at th
is time were maintained. The YMDD mutation was detected in 12 nonresponder
patients (9 YVDD, 2 YIDD, and 1 mixed population Y(V/I)DD),generally associ
ated with the L528M mutation. Re-takeover by the wild type was observed 6 t
o 18 months after lamivudine withdrawal. Lamivudine response rates:in nonci
rrhotic and cirrhotic patients were 9/18 (50%) and 10/14 (71.4%), respectiv
ely. HBeAg to anti-HBe seroconversion was found after different periods in
all responder patients. Hepatitis B surface antigen (HBsAg) clearance and a
nti-HBs seroconversion were occasionally found. Conclusions. In nonresponde
r patients, resistant mutants appeared up to the second year of lamivudine
therapy. In spite of the presence of resistant mutants, maintenance of ther
apy was usually associated with a lower viral load. In responder patients,
maintenance of therapy was associated with continued absence of detectable
HBV DNA in serum, as monitored by highly sensitive methods. No significant
side effects caused by lamivudine were observed in our patients, even in th
ose with liver cirrhosis.