Journal of Pediatric Gastroenterology & Nutrition:
Liver Diseases Branch, Division of Intramural Research, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
Address correspondence and reprint requests to Dr Theo Heller, Bldg 10, Room 9B16, 10 Center Drive, National Institutes of Health, Bethesda, MD 20892-1800 (e-mail: Heller:TheoH@intra.niddk.nih.gov).
Received 28 September, 2012
Accepted 3 October, 2012
The authors report no conflicts of interest.
See “Autoantibodies and Autoimmune Disease During Treatment of Children With Chronic Hepatitis C” by Molleston et al on page 304.
Autoantibody reactivity is a common occurrence in liver diseases. As in other liver diseases, chronic hepatitis C is associated with the presence of various autoimmune markers and autoimmune disease. This autoantibody reactivity in turn may be a reflection of immune system activation. Molecular mimicry of viral antigens by self-antigens, chronic stimulation of B cells, and a bystander effect are some proposed mechanisms for the development of autoimmune phenomena in hepatitis C (1).
The development of autoantibodies and autoimmune diseases is a recognized adverse effect of interferon therapy in adults (2); however, it is unclear whether interferon unmasks previously unrecognized autoimmune disease or causes de novo autoimmune disease. Interestingly, some studies report an association between baseline autoantibody levels and hepatitis C virus (HCV) treatment response in adults (3).
In this issue of the Journal of Pediatric Gastroenterology and Nutrition, Molleston et al (4) analyzed autoantibodies in stored serum from the PEDS-C (Pegylated Interferon +/− Ribavarin for Children With Hepatitis C) trial. Autoantibodies were present in 19% of the children at baseline, with a nonsignificant upward trend in prevalence during the course of treatment. These autoantibodies were not predictive of treatment outcome, treatment adverse effects, or alanine aminotransferase elevations during treatment.
Because the PEDS-C trial excluded children with evidence of preexisting autoimmune diseases, we cannot determine whether interferon worsened preexisting autoimmune disorders; however, the PEDS-C population was well suited for the assessment of de novo development of autoimmune disease. This occurred in 3 of 114 children, 2 of whom developed autoantibodies while receiving peginterferon.
The scant data that are available suggest the presence of a positive anti-nuclear antibody (ANA) in approximately 6% to 15% of healthy controls (5). This is comparable with the ANA positivity rate in the PEDS-C cohort before treatment.
The present study sheds light on an aspect of pediatric hepatitis C that has been largely unexplored until present. Molleston et al were able to measure changes in autoantibodies during the course of HCV therapy in a well-characterized cohort of children. They determined that autoantibodies did not correlate with alanine aminotransferase, and probably are not mere markers of inflammation. They also did not find a relation between autoantibodies and response to therapy, showing that the prognostic value reported in adults did not hold in this population. In addition, the authors determined the incidence of de novo autoimmune disease with HCV treatment.
Furthermore, these findings are particularly timely. With the advent of new directly acting antivirals, the end of the interferon era may be imminent, making it less feasible to study the effect of exogenous interferon on autoantibody reactivity. Thus, the present study adds to our understanding at an opportune moment in pediatric hepatology. For the practitioner, this article shows that if preexisting autoimmune disease has been excluded, one need not check routinely for autoantibodies during therapy in the absence of symptoms.
The findings reported in this issue of the Journal of Pediatric Gastroenterology and Nutrition are a major contribution, and the area of autoimmunity in pediatric HCV is in its nascent stages. Additional data from large cohorts, advances in immunology, and improved autoantibody tests will enhance our understanding of chronic hepatitis C and its myriad manifestations.
1. Ferri S, Muratori L, Lenzi M, et al. HCV and autoimmunity. Curr Pharm Des
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4. Molleston JP, Mellman W, Narkewicz MR, et al. Autoantibodies and autoimmune disease during treatment of children with chronic hepatitis C. J Pediatr Gastroenterol Nutr
5. Wananukul S, Voramethkul W, Kaewopas Y, et al. Prevalence of positive antinuclear antibodies in healthy children. Asian Pac J Allergy Immunol