Efficacy and tolerability of long-term therapy using high lamivudine dosesfor the treatment of chronic hepatitis B

Citation
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
Citations number
49
Categorie Soggetti
Gastroenerology and Hepatology
Journal title
JOURNAL OF GASTROENTEROLOGY
ISSN journal
09441174 → ACNP
Volume
36
Issue
7
Year of publication
2001
Pages
476 - 485
Database
ISI
SICI code
0944-1174(200107)36:7<476:EATOLT>2.0.ZU;2-V
Abstract
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.