Current therapeutic approaches in childhood chronic hepatitis B infection: A multicenter study

Ankara University, Engüri, Ankara, Turkey
Journal of Gastroenterology and Hepatology (Impact Factor: 3.5). 02/2004; 19(2):127-33. DOI: 10.1111/j.1440-1746.2004.03209.x
Source: PubMed


The aim of the present study was to compare the therapeutic efficacy of three different regimens in childhood chronic hepatitis B (CHB) infection.
A total of 182 children with CHB infection were prospectively allocated to three random groups. Sixty-two patients in the first group received high-dose interferon (IFN)-alpha 2b (10 MU/m2) thrice/weekly alone for 6 months. In the second (n = 60) and third groups (n = 60), IFN-alpha was used for 6 months (5 MU/m2) thrice/weekly in combination with lamivudine (LAM) (4 mg/kg, maximum 100 mg/day) for 12 months. Lamivudine was started simultaneously with IFN in the second group, while it was started 2 months prior to IFN injections in the third group.
The initial mean alanine aminotransferase (ALT) values for the first, second and third groups were 109 +/- 93 IU/L, 101 +/- 64 IU/L and 92 +/- 42 IU/L, respectively (P > 0.05). At the end of the therapy, ALT values decreased to 82 +/- 111 IU/L, 38 +/- 41 IU/L and 29 +/- 16 IU/L in groups 1, 2 and 3, respectively. The mean ALT value of the first group was significantly different to the second and third groups (P = 0.046 and P = 0.002, respectively) at the end of the therapy and these differences were found to be sustained after 18 months. However, results in the second and third groups were similar (P > 0.05). There were no significant differences in HBeAg clearance and anti-HBe seroconversion at the initial stage, 12 months and 18 months between the three groups (P > 0.05). Hepatitis B virus (HBV) DNA clearance in the first group was different from the second and third groups, while the second and third groups had similar HBV DNA clearance ratios at 12 and 18 months. No significant difference was found in the complete response (normalization of ALT, clearance of HBV DNA and seroconversion of anti HBe) ratios of all groups (at 12 months: 28.8, 45.5, 35.8% and at 18 months 33.3, 49 and 34% in groups 1, 2 and 3, respectively, P > 0.05).
Although the ALT normalization and HBV DNA clearance ratios of IFN plus LAM combination groups were better than the high-dose IFN-alpha monotherapy group, no significant difference was found in the complete response ratios of all three groups.

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    ABSTRACT: Hepatitis viruses produce significant worldwide morbidity causing acute, fulminant and chronic hepatic disease. Since, the main route of virus transmission is blood and blood products, transfusion dependent population is at greater risk. Viral hepatitis is one of the major causes of liver dysfunction in multiple-transfused children and has become a significant concern in patients with hematological disorders. Prevention has been the mainstay of effort and current therapies for hepatitis B (HBV) virus infection are aimed at viral suppression, while treatment for hepatitis C (HCV) virus can eradicate infection in many treated patients. At the present time, a combination of interferon and lamivudine seem to be the best options for HB infection treatment in the pediatric population, even though they induce the presence of drug-resistant mutations, and new therapies have to be developed to improve reduction and cessation of viral replication and decrease the emergence of mutations. Therapy with interferon and ribavirin seems to offer the best results for children and adolescents. Results from studies on pegylated interferon in pediatric population might lead to better therapeutic responses. ÖZET Hepatit viruslari, akut, fulminan ve kronik hepatite neden olan yaygin ve ciddi enfeksiyon ajanlaridir. Temel bula yolunun kan ve kan ürünleri olmasi tekrarlayan transfüzyon ihtiyaci olan hastalarin risk grubu olmasina yol açar. Çoklu transfüzyon yapilan hastalarda karacier disfonksiyonunun temel nedenlerinden biri viral hepatitlerdir. Temel yaklaim korunma ve ai olmalidir. Günümüzdeki tedavi metodlari ile hepatit B (HBV) virus enfeksiyonu baskilanirken hepatit C (HCV) virus enfeksiyonu eradike edilebilmektedir. Çocukluk ça�i kronik HBV enfeksiyonu tedavisinde interferon+lamivudin kombinasyonu önerilmektedir; ancak direnç geliim sorunu vardir ve yeni terapötik ajanlar ile bu sorun ailmaya çaliilmaktadir. nterferon ile ribavirin kombinasyonu pediatrik kronik HCV tedavisinde en iyi sonuçlarin alindi�i tedavi modelidir. Pegile interferon ile yapilan çali malar çocuklarda HCV infeksiyonunda pegile formun ümit verici olduunu göstermektedir.
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    ABSTRACT: To analyse the most relevant recent information on efficacy, duration and coverage of anti-hepatitis B virus vaccination; correlates of mother-to-child hepatitis C virus transmission; the natural history and outcomes of hepatitis B and C virus infections in children; the efficacy and safety of specific therapies. Insufficient hepatitis B virus vaccine coverage and incomplete or delayed vaccine cycles need improvement in many countries. Hepatitis B virus mutants may explain some fulminant hepatitis in perinatally infected infants and vaccine failures. No interventions to prevent vertical hepatitis C virus transmission have been identified. Spontaneous clearance of hepatitis B is lower in children than in adults, while the rates appear to be similar for hepatitis C. The disease progression is slower for both infections in childhood. Several studies support the efficacy and safety of interferons and lamivudine in chronic hepatitis B or of interferons and ribavirin in chronic hepatitis C in children, but the optimal therapy remains unclear. There are doubts as to the long-term persistence of anti-hepatitis B immunization in low-endemicity areas. Routine hepatitis C virus testing in pregnancy is not recommended as there are no available prophylactic measures. Although hepatitis B and C virus infections are usually asymptomatic or with mild manifestations in childhood, concerns around their long-term clinical impact suggest the need for early treatment. Children should preferably be treated in the context of targeted trials for a better understanding of the efficacy and tolerance of drugs currently used in adults.
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