Autoantibodies and autoimmune disease during treatment of children with chronic hepatitis C

Jean P Molleston, William Mellman, Michael R Narkewicz, William F Balistreri, Regino P Gonzalez-Peralta, Maureen M Jonas, Steven J Lobritto, Parvathi Mohan, Karen F Murray, Dolores Njoku, Philip Rosenthal, Bruce A Barton, Monica V Talor, Irene Cheng, Kathleen B Schwarz, Barbara A Haber, PEDS-C Clinical Research Network, Jean P Molleston, William Mellman, Michael R Narkewicz, William F Balistreri, Regino P Gonzalez-Peralta, Maureen M Jonas, Steven J Lobritto, Parvathi Mohan, Karen F Murray, Dolores Njoku, Philip Rosenthal, Bruce A Barton, Monica V Talor, Irene Cheng, Kathleen B Schwarz, Barbara A Haber, PEDS-C Clinical Research Network

Abstract

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).

Trial registration: ClinicalTrials.gov NCT00100659.

Figures

Figure 1
Figure 1
The consort diagram shows treatment and decision points during the Peds-C Trial. At baseline, week 24 and week 72 serum was stored and frozen. The stored serum was used for analysis of serum auto-antibodies after completion of the clinical trial.

Source: PubMed

3
Subskrybuj