Regino P. Gonzalez-Peralta

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).

: Chronic hepatitis C virus (HCV) infection is usually asymptomatic in children, but significant liver disease may occur. We evaluated the efficacy, safety, and pharmacokinetics of interferon alfa-2b and ribavirin in children with chronic HCV. We determined the optimal ribavirin dose in an initial cohort of a phase 1 study and then subsequently used it, in combination with interferon alfa-2b, in a second cohort of this study and a phase 3 trial. The primary efficacy endpoint in all studies was sustained virological response, defined by undetectable serum HCV RNA 24 weeks after completion of therapy. All efficacy and safety analyses were performed on the intent-to-treat population. Children receiving interferon alfa-2b plus ribavirin 15 mg/kg/d in the phase 1 study had the maximum reduction in serum HCV RNA at treatment weeks 4 and 12 with an acceptable safety profile. This ribavirin dose was selected as optimal and used in all subsequent studies. In all, 46% (54/118) of optimally treated children achieved sustained virological response. Sustained virological response was significantly higher in children with HCV genotype 2/3 (84%) than in those with HCV genotype 1 (36%). Adverse events led to dose modification in 37 (31%) and discontinuation in 8 (7%). Multiple-dose interferon alfa-2b and ribavirin peak and trough concentrations and area-under-the-curve were similar between children and adults. In conclusion , interferon alfa-2b in combination with ribavirin is effective and safe in children with chronic hepatitis C virus. (Hepatology 2005;42:1010–1018.)

Since the discovery of hepatitis C virus (HCV) in 1989, significant advances have been made in our understanding of this important viral pathogen. Children at risk for HCV infection include recipients of potentially contaminated blood products and organ transplants, and infants born to HCV-infected mothers. Chronic HCV infection is usually asymptomatic in children but active hepatitis, cirrhosis and hepatocellular carcinoma can occur. The development of treatment strategies for chronic hepatitis C in children has directly evolved from clinical trials in adults. Sustained virologic response, defined by undetectable HCV RNA in serum 24 wk after completion of treatment, occurs in approximately 36% of children treated with conventional interferon alone and in about 50% of those given conventional interferon in combination with ribavirin. Pegylated interferon-based treatment regimens are better than those based on conventional interferon in adults but little is known about pegylated interferon in children. Factors associated with a favorable response to antiviral therapy in children are similar to those in adults and include infection with HCV genotype 2 or 3 and low pretreatment serum HCV RNA levels. Treatment related adverse events in children include 'flu-like' syndrome, fatigue, anorexia, weight loss, depression, anemia, leukopenia and thrombocytopenia.