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A Competent Hepatocyte Model Examining Hepatitis B Virus Entry through Sodium Taurocholate Cotransporting Polypeptide as a Therapeutic Target
Published on: May 10, 2022
Pediatric hepatitis B treatment
Haruki Komatsu1, Ayano Inui2, Tomoo Fujisawa2
1Department of Pediatrics, Toho University Sakura Medical Center, Chiba, Japan.
Insights
Treating chronic hepatitis B in children is challenging. Antiviral therapy aims for HBeAg seroconversion, but its long-term impact and cost-effectiveness require further study in pediatric HBV infection.
Area of Science:
- Hepatology
- Pediatric Infectious Diseases
- Virology
Background:
- Hepatitis B vaccination reduces carriers, but chronic hepatitis B (CHB) in children remains a challenge.
- HBeAg seroconversion is a primary treatment goal, though spontaneous seroconversion is common in children.
- Identifying children needing antiviral treatment for CHB is crucial for effective management.
Purpose of the Study:
- To review current guidelines and expert opinions on identifying and treating children with chronic hepatitis B.
- To discuss first-line antiviral treatments, including interferon-alpha and nucleos(t)ide analogues (NAs), based on disease severity.
- To highlight the need for clarity on the long-term clinical impact and cost-effectiveness of antiviral therapy in pediatric HBV infection.
Main Methods:
- Review of existing guidelines and expert recommendations for pediatric chronic hepatitis B management.
- Analysis of current antiviral treatment options, including interferon-alpha and various nucleos(t)ide analogues (NAs).
- Consideration of factors like disease progression, drug resistance, and age-appropriateness of treatments.
Main Results:
- Interferon-alpha is a first-line treatment for CHB without decompensated cirrhosis; NAs are used if cirrhosis is present.
- NAs like entecavir and tenofovir are preferred for their high genetic barriers against drug resistance.
- Optimal NA treatment duration and long-term adverse events in children remain unclear.
Conclusions:
- Antiviral treatment strategies for pediatric CHB vary based on cirrhosis presence and drug resistance profiles.
- The financial burden and lack of definitive evidence on preventing liver disease progression necessitate further research.
- Clarifying the clinical impact of antiviral therapy is imperative for optimizing treatment decisions in children with HBV infection.
Abstract:
Although the introduction of hepatitis B vaccine has been contributing to the reduction in the prevalence of hepatitis B virus (HBV) carriers worldwide, the treatment of children with chronic HBV infection is a challenge to be addressed. HBeAg seroconversion, which induces low replication of HBV, is widely accepted as the first goal of antiviral treatment in children with chronic hepatitis B. However, spontaneous HBeAg seroconversion is highly expected in children with chronic HBV infection. Therefore, the identification of children who need antiviral treatment to induce HBeAg seroconversion is essential in the management of chronic HBV infection. Guidelines and experts' opinion show how to identify children who should be treated and how to treat them. If decompensated cirrhosis is absent, interferon-alpha is the first-line antiviral treatment. Nucleos(t)ide analogues (NAs), such as lamivudine, adefovir, entecavir and tenofovir, are also available for the treatment of children, although the approval age differs among them. If decompensated cirrhosis is present, NAs are the first-line antivirals. When the emergence of drug-resistant HBV variants is taken into consideration, entecavir (approved for age 2 years or older) and tenofovir (age 12 years or older), which have high genetic barriers, will play a central role in the treatment of HBV infection. However, the optimal duration of NA treatment and adverse events of long-term NA treatment remain unclear in children. In resource-constrained countries and regions, the financial burden of visiting hospitals, receiving routine blood examination and purchasing antiviral drugs is heavy. Moreover, there is no clear evidence that the induction of HBeAg seroconversion by antiviral treatment prevents the progression of liver disease to cirrhosis and hepatocellular carcinoma in children with chronic HBV infection. It is thus imperative to clarify the clinical impact of antiviral treatment in children with HBV infection.
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