Objectives: Autoantibodies were studied in a well-characterized cohort of children with chronic hepatitis C during treatment with pegylated interferon and ribavirin to assess the relation with treatment and development of autoimmune disease.
Methods: A total of 114 children (5–17 years), screened for the presence of high-titer autoantibodies, were randomized to pegylated interferon with or without ribavirin. Anti-nuclear, anti-liver-kidney-microsomal, anti-thyroglobulin, anti-thyroid peroxidase, insulin, anti-glutamic acid decarboxylase (GAD) antibodies were measured after trial completion using frozen sera.
Results: At baseline, 19% had autoantibodies: anti-nuclear antibodies (8%), anti-liver-kidney-microsomal antibodies (4%), and glutamic acid decarboxylase antibodies (4%). At 24 and 72 weeks (24 weeks after treatment completion), 23% and 26% had autoantibodies (P = 0.50, 0.48 compared with baseline). One child developed diabetes and 2 hypothyroidism during treatment; none developed autoimmune hepatitis. At 24 weeks, the incidence of flu-like symptoms, gastrointestinal symptoms, and headaches was 42%, 8% and 19% in those with autoantibodies versus 52%, 17%, and 26% in those without (P = 0.18, 0.36, and 0.20, respectively). In children with negative hepatitis C virus polymerase chain reaction at 24 weeks, there was no difference in the rate of early virologic response/sustained virologic response, respectively, in those with autoantibodies 76%/69% vs 58%/65% in those without (P = 0.48).
Conclusions: Despite screening, we found autoantibodies commonly at baseline, during treatment for chronic hepatitis C and after. The presence of antibodies did not correlate with viral response, adverse effects, or autoimmune hepatitis. Neither screening nor archived samples assayed for thyroid and diabetes-related antibodies identified the 3 subjects who developed overt autoimmune disease, diabetes (1), and hypothyroidism (2).
*Section of Pediatric Gastroenterology, Hepatology, and Nutrition, Indiana University School of Medicine, Indianapolis, IN
†Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA
‡Department of Pediatrics, Section of Pediatric Gastroenterology, Hepatology, and Nutrition, University of Colorado Denver School of Medicine and The Children's Hospital, Aurora, CO
§Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Medical Center, Cincinnati, OH
||Department of Pediatrics, University of Florida College of Medicine and Shand's Children's Hospital, Gainesville, FL
¶Division of Gastroenterology, Children's Hospital Boston, Boston, MA
#Pediatric Gastroenterology, Hepatology, and Nutrition, Columbia University Medical Center, New York, NY
**Division of Gastroenterology, Hepatology and Nutrition, Children's National Medical Center, Washington, DC
††Division of Gastroenterology and Hepatology, Seattle Children's, Seattle, WA
‡‡Department of Pediatrics, Division of Gastroenterology and Nutrition, Section of Hepatology and Liver Transplantation, Johns Hopkins University School of Medicine, Baltimore, MD
§§Department of Pediatrics, University of California, San Francisco, CA
||||Maryland Medical Research Institute
¶¶Department of Pathology, Division of Immunology, Johns Hopkins University School of Medicine, Baltimore
##Clinical Trials and Surveys Corp, Owings Mills, MD.
Address correspondence and reprint requests to Barbara A. Haber, MD, Merck Hepatology, Upper Gwynedd, Philadelphia, PA 19454 (e-mail: Haber.email@example.com).
Received 9 February, 2012
Accepted 14 August, 2012
www.clinicaltrials.gov registration number: NCT00100659.
This study is supported by a cooperative agreement between the National Institute of Diabetes and Digestive and Kidney Diseases and the Food and Drug Administration, contract number 1UO1DK067767-01.CRC. This project was supported in part by NIH/NCRR Colorado CTSI Grant Number UL1 RR025780 and study sites: MO1-RR-00069, Children's Hospital, Aurora, CO; M01-RR-02172, Children's Hospital, Boston, MA; M01-RR-01271, University of California, San Francisco, CA; 5-M01-RR-020359-01, National Medical Center, Washington, DC; M01-RR-00645, Columbia University Medical Center, New York, NY; M01-RR-00082, University of Florida, Gainesville, FL; M01-RR-00037, University of Washington, Seattle, WA; 5-M01-RR-000240- Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA; U01-DK-067767-02, Johns Hopkins Medical Center, Baltimore, MD; M01-RR-08084, University of Cincinnati, Cincinnati, OH; M01-RR-00750, Indiana University, Indianapolis, IN, the American Autoimmune Related Disease Association, and the Mr and Mrs Joseph Scoby Foundation. Its contents are the authors’ sole responsibility and do not necessarily represent official NIH views. Additional support was provided by Hoffmann-La Roche for study medications and central laboratory costs.
The authors report no conflicts of interest.