Long-term lamivudine therapy for chronic hepatitis B infection in children unresponsive to interferon.
OBJECTIVE
Prolonged lamivudine treatment in adults has been shown to improve hepatitis B e (HBe) seroconversion rates in patients with chronic hepatitis B. This prospective open study reports the results of prolonged lamivudine treatment in a group of children with chronic hepatitis B.


METHODS
Twenty-two children and adolescents age 13.2 years (range, 9.5-18 years), who have been treated with lamivudine for 1 year, continued treatment with lamivudine (3 mg/kg/day, up to 100 mg/d) as long as there was evidence of continued biochemical and virological benefit compared with baseline. We evaluated virological and biochemical responses, the occurrence of YMDD mutants and adverse effects during 4 years of follow-up.


RESULTS
After 4 years on lamivudine, only 4 patients (18%) underwent HBe seroconversion. In addition, in 3 patients (13%), the treatment was stopped when lamivudine's lack of efficacy became evident. During the 4-year study period, we recorded a continuing decline in the participants' number, mostly because of lack of compliance with treatment (9/22, 41%). Only 5 children were still receiving lamivudine and showing benefit after 4 years. In 2 children, treatment termination and YMDD mutant emergence were associated with hepatitis flare. Besides subclinical elevation of creatine phosphokinase, no other adverse events were recorded during the study period.


CONCLUSIONS
Four years after starting lamivudine treatment, most children from this study were off lamivudine, mainly because of lack of compliance and poor HBe seroconversion. These findings suggest that continuing treatment with lamivudine for undefined periods is hard to implement and does not improve HBe seroconversion.
Hartman
Corina
C
Division of Pediatric Gastroenterology and Nutrition, Meyer Children's Hospital of Haifa, Haifa, Israel.
Berkowitz
Drora
D
Eshach-Adiv
Orly
O
Hino
Bian
B
Rimon
Nurit
N
Satinger
Iehudith
I
Kra-Oz
Tzipi
T
Shamir
Raanan
R
D000293:Adolescent; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D002648:Child; D005500:Follow-Up Studies; D006513:Hepatitis B e Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D019259:Lamivudine / Q000627:therapeutic use*; D011446:Prospective Studies; D013997:Time Factors; D017211:Treatment Failure; D016896:Treatment Outcome; D016312:Treatment Refusal; D019562:Viral Load
D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; D019259:Lamivudine; D007372:Interferons; D000410:Alanine Transaminase