Current treatment options and response rates in children with chronic hepatitis C

Vertical transmission has become the most common mode of transmission of hepatitis C virus (HCV) in children.The rate of perinatal transmission from an HCVinfected mother to her child ranges from 2% to 5% and the prevalence of HCV in children in developed countries ranges between 0.1% and 0.4%.Spontaneous viral clearance seems to be dependent on the genotype and has been reported between 2.4%-25%.For chronically infected patients,treatment with recombinant polyethylene glycol (PEG)-interferon α-2b and daily ribavirin has now been approved as standard treatment for children 2-17 years of age.In five large prospective studies,a total of 318 children and adolescents aged 3-17 years were treated either with subcutaneous PEG-interferon α-2b at a dose of 1-1.5 μg/kg or 60 μg/m2 once a week in combination with oral ribavirin (15 mg/kg per day) or PEG-interferon α-2a with ribavirin.Subjects with genotype 1 and 4 received the medication for 48 wk and individuals with genotype 2 and 3 mainly for 24 wk.Overall sustained viral response (SVR) was achieved in 193/318 (60.7%) of treated patients.Stratified for genotype;120/234 (51%) with genotype 1,68/73 (93%) with genotype 2/3,and 6/11 (55%) with genotype 4 showed SVR.Relapse rate was between 7.7% and 17%.Overall,treatment was well tolerated;how-ever,notable side effects were present in approximately 20%.According to recent experiences in the treatment of chronic hepatitis C in children and adolescents,a combination of PEG-interferon α with ribavirin has been found to be well tolerated and highly efficacious,particularly in individuals with genotype 2/3.Thus,this treatment can be recommended as standard of care until more effective treatment options will become available for genotype 1 patients.

Prevalence of autoantibodies and the risk of autoimmune thyroid disease in children with chronic hepatitis C virus infection treated with interferon-α

AIM： To evaluate the prevalence of autoantibodies in chronic hepatitis C virus （HCV）-infected children focusing on thyroid autoimmunity.METHODS： We investigated the prevalence of autoantibodies in 123 chronic HCV-infected children before, during and after monotherapy with interferon-alpha （IFN-α） or combined treatment with interferon-α or peginterferon-α and ribavirin. Besides antibodies against smooth muscle （SMA）, nuclei （ANA）, and liver/kidney microsomes （1KM）, the incidence of antithyroid peroxidase antibodies as well as thyroid function parameters （TSH, FT3 and FT4） were determined.RESULTS： We found that 8% of children had autoantibodies before treatment. During treatment, 18% of children were found positive for at least one autoantibody; 15.5% of children developed pathologic thyroid values during IFN-α treatment compared to only one child before therapy. Six children had to be substituted while developing laboratory signs of hypothyroidism.CONCLUSION： Our data indicate a strong correlation between interferon-α treatment and autoimmune phenomena, notably the emergence of thyroid antibodies. The fact that some children required hormone replacement underlines the need of close monitoring in particularly those who respond to therapy and have to be treated for more than 6 mo.

Prevalence of hepatitis B virus precore stop codon mutations in chronically infected children

AIM： To find out whether there is a significant difference in the prevalence of the precore stop codon mutation between HBeAg positive and anti-HBe positive children. METHODS： We investigated a large pediatric population of 155 European children （mean age 10.9 years） with chronic hepatitis B by PCR and direct sequencing. Ninety were HBeAg positive and 65 had seroconversion to anti-HBe. Additionally genotyping was performed. RESULTS： Seventy-four （48%） of the sequenced HBV strains were attributed to genotype D and 81 （52%） to genotype A. In the group of 90 HBeAg positive patients, 2 （2.2%） 1896-G-to-A transitions leading to precore stop codon mutation were found, and in the group of 65 anti-HBe positive children, 5 （7.7%） were identified harbouring HBeAg-minus mutants. The difference was not statistically significant （P= 0.13）. CONCLUSIONS： HBeAg minus variants as predominant viral HB strains play a minor role in the course of chronic hepatitis B in European children.

Vitamin E treatment for children with chronic hepatitis B:A randomized placebo controlled trial

AIM:To evaluate the safety and efficacy of vitamin E in children with chronic hepatitis B.METHODS:We randomly assigned patients with chronic hepatitis B,positive for hepatitis B e antigen(HBeAg),to receive either vitamin E or placebo once daily for 6 mo in a 3:1 ratio and double-blind manner.The primary end point was HBeAg seroconversion,defined as the loss of HBeAg,undetectable levels of serum hepatitis B virus DNA,and the appearance of antibodies against HBeAg 12 mo after therapy.RESULTS:At baseline visit,49 patients had normal and 43 had increased serum aminotransferase levels.Twenty-nine patients did not respond to previous treatment with interferon-α or lamivudine.Seventy-six children completed the study;16 were non-compliant(n = 7),lost to follow-up(n = 7),or started another antiviral treatment(n = 3).Intention-to-treat analysis showed HBeAg seroconversion in 16 children(23.2%) treated with vitamin E and two(8.7%) in the placebo group(P = 0.13).Vitamin E was well tolerated.CONCLUSION:There is only a tendency that vitamin E may promote HBeAg seroconversion.Therefore larger studies are needed to clarify the role of antioxidants in the therapy of chronic hepatitis B.