Pediatr Gastroenterol Hepatol Nutr.  2012 Jun;15(2):63-73.

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

• Hong SJ
• Choe BH

Abstract

Development of antiviral resistance to lamivudine is the most important factor for the treatment failure. It is necessary to establish proper guidelines to overcome drug resistance for children with chronic hepatitis B. Primary treatment with lamivudine should be considered if patients are in immune-clearance phase and have persistently elevated ALT levels more than twice the upper limit of normal value. Before initiating the therapy, careful consideration of the patient's status is required to exclude abnormal liver function tests due to other causes. The treatment option should be carefully decided to suppress the viral replication effectively. To obtain good compliance, clinicians should educate patients and their parents. Appropriate monitoring for virologic breakthrough and genotypic resistance is important in deciding to change the treatment plan. Sequential monotherapy should be avoided and a combination of drugs in other categories is recommended. New antiviral agents, such as entecavir and tenofovir, which have high potency and high genetic barrier, are soon expected to be available for use with children.

Keyword

Chronic hepatitis B; Antiviral agents; Drug resistance; Children

MeSH Terms

Adenine
Antiviral Agents
Child
Compliance
Drug Resistance
Guanine
Hepatitis B, Chronic
Hepatitis, Chronic
Humans
Lamivudine
Liver Function Tests
Organophosphonates
Parents
Reference Values
Treatment Failure
Tenofovir
Adenine
Antiviral Agents
Guanine
Lamivudine
Organophosphonates

Figure

• 

  Fig. 1 The natural course of chronic hepatitis B virus infection. The figure is modified from one presented in reference [78].

• 

  Fig. 2 Recommended flow of initial treatment of chronic hepatitis B in children. The figure has been adapted from reference [4]. ULN denotes upper limits of normal value.

• 

  Fig. 3 Antiviral potency and genetic barrier of antiviral drugs. LAM: lamivudine, ETV: entecavir, TDF: tenofovir, ADF: adefovir.

• 

  Fig. 4 Recommending flow of lamivudine treatment in adults. The figure is modified from reference [2]. Primary non-response is defined as a decrease in serum HBV DNA < 2 log10 (IU/mL) after 6 months of therapy. Virologic breakthrough is defined as an increase in serum HBV DNA of more than 1 log10 (IU/mL) compared to lowest value. Partial virologic response is defined as a decrease in serum HBV DNA of more than 2 log10 (IU/mL) but detectable HBV DNA by real-time PCR assay. Complete virologic response is defined as a decrease in serum HBV DNA to undetectable level by real-time PCR assay.

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