Long-term lamivudine therapy for children with HBeAg-positive chronic hepatitis B

Abstract

C hronic hepatitis B is a significant global health care problem that affects more than 350 million people worldwide, resulting in approximately 1 million deaths each year. 1 Despite the widespread availability of an effective vaccine, large numbers of children are infected. People infected early in life who have evidence of ongoing viral replication are at the highest risk for development of progressive liver disease and are a major source of infection in others. 2 Treatment options for children are limited. The goal of treatment is to prevent the progression of chronic hepatitis B to long-term complications, such as cirrhosis and hepatocellular carcinoma, that can result in premature death. 3 Interferon ␣ has demonstrated efficacy in achieving hepatitis B e antigen (HBeAg) loss and seroconversion with HBV DNA suppression in children over 1 year old with active hepatitis B. However, only one third of treated patients will respond, and there are significant side effects associated with interferon therapy, including influenzalike symptoms, gastrointestinal disorders, nausea and vomiting, neutropenia, thrombocytopenia, and transient impairment of growth. 4,5 Treatment with lamivudine, an oral nucleoside analog, has been shown to result in similar response rates as interferon in both adults and children. [6][7][8][9] The drug is well tolerated, but long-term efficacy can be compromised by the emergence of resistance. 10 Treatment with lamivu-

Recent data on treatment of chronic hepatitis B with nucleos(t)ide analogues

“…However, the incidence of YMDD mutations was high at 64%. The durability of response among the responders at year 1 was 89% at month 24 [54]. In a study of longer duration of therapy (median 33, range 14-66 months), response was achieved in the first 2 years and none thereafter.…”

Strategy to Overcome Drug Resistance That Develops during Treatment of Chronic Hepatitis B in Children

“…Most of the children enrolled in these studies had pretreatment baseline ALT ＞ 2×ULN. On the other hand, Sokal et al have revealed that resistance rates were 49% and 64% in 2-year treatment and 3-year treatment, respectively [76]. These were similar or even higher than those of adults.…”

Evaluation of distant results after lamivudine discontinuation in children with chronic hepatitis B.

“…Molecular mechanism of resistance in HBV genome is well known but the optimal length for children's treatment with lamivudine required to achieve a durable virological response has not been established [5].…”