ArticleTranslational pediatrics2025
Functional cure in a child with chronic hepatitis B with rtM204I mutation through an atypical serological response: a case report.
Article in Translational pediatrics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: rtM204I mutation is commonly associated with resistance to nucleos(t)ide analog (NA) therapy for hepatitis B virus (HBV), often resulting in virological breakthrough and treatment failure. Owing to unique immunological and virological characteristics of HBV, achieving a functional cure in pediatric patients is easier than in adults, and cases involving concurrent drug-resistant mutations are rare. Case Description: A 4-year-old boy infected with HBV through mother-to-child transmission experienced virological rebound (HBV DNA, 4.66×107 IU/mL) after 12 months of lamivudine (LAM) monotherapy. Resistance testing revealed rtM204I mutation. The treatment regimen was adjusted to tenofovir disoproxil fumarate (TDF) combined with pegylated interferon α-2a (PegIFNα-2a). At 12 weeks of treatment, there was a significant decline in hepatitis B surface antigen (HBsAg) levels accompanied by positive antibody to hepatitis B surface antigen (anti-HBs), thus presenting an atypical serological pattern of double positivity for HBsAg and anti-HBs. By week 24, HBsAg was negative, but hepatitis B e antigen (HBeAg) remained positive, demonstrating an atypical serological pattern of response dissociation whereby HBsAg disappeared before HBeAg. TDF combined with PegIFNα-2a was administered until week 36, resulting in persistent HBsAg negativity and a significant increase in anti-HBs levels. PegIFNα-2a was discontinued, and TDF monotherapy was continued for 10 months. During this period, HBsAg negativity and anti-HBs positivity were maintained, HBeAg became negative, and alanine aminotransferase levels remained normal. These results indicate achievement of a functional cure. Conclusions: This case indicated that in children with rtM204I mutation, optimizing antiviral therapy combined with PegIFNα-2a can achieve a functional cure despite atypical serological response patterns. Long-acting interferons have significant therapeutic value in pediatric patients with drug-resistant mutations.
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