Safety, efficacy and pharmacokinetics of peginterferon alpha2a (40 kd) in children with chronic hepatitis C.

Chronic hepatitis C virus (HCV) infection in children is a problem affecting thousands of children worldwide. Although standard interferon (INF) has better efficacy in pediatric patients than in adults, results in children with genotype 1 are poor; response rates to combination treatment with standard INF and ribavirin are better but the treatment requires thrice-weekly injections. The improved antiviral efficacy of weekly pegylated interferons relative to standard interferons in adults with chronic HCV infection suggests that pegylated interferons may also improve antiviral efficacy in children. We therefore investigated the pharmacokinetics, efficacy and safety of peginterferon alpha2a (pegINF-alpha2a) (40 kd) in 14 children ages 2 to 8 years with chronic hepatitis C (13 genotype 1, 1 non-1 genotype). Drug dose was calculated from each patient's body surface area (BSA) according to the formula BSA (m2)/(1.73 m2) x 180 microg, and patients were administered once-weekly subcutaneous injections for 48 weeks. Viral load and pharmacokinetic parameters were determined from blood drawn throughout the study and during follow-up. At week 24, the mean trough concentration was about 20% below values obtained from adults treated with pegINF-alpha2a, and the area under the curve from 0 to 168 hours was about 20% above adult values, suggesting that drug doses calculated from BSA achieved therapeutically adequate concentrations. Six of 14 patients (43%), all infected with genotype 1, achieved a sustained virological response. Adverse events were those commonly associated with INF-based treatment, and none was deemed serious. In conclusion, our findings provide a basis for larger studies evaluating the efficacy and safety of pegINF-alpha2a as monotherapy as well as in combination with ribavirin in pediatric patients with chronic hepatitis C.

Children with hepatitis C.

Hepatitis C affects thousands of children throughout the world. Most children acquire the virus through vertical transmission, although parenteral routes of acquisition are also common. Hepatitis C progresses slowly, with mild biopsy findings and no symptoms in most children and in many adults. However, significant liver inflammation and fibrosis can occur in childhood. Trials of antiviral therapy with interferon and ribavirin have shown these drugs to be effective in almost half of the children treated. Children tend to tolerate therapy well. Further research on the natural history and treatment of hepatitis C in children is needed because the infection can have serious long-term consequences, including end-stage liver disease and hepatocellular carcinoma.

Comparison of serological markers of inflammatory bowel disease with clinical diagnosis in children.

BACKGROUND: Our purpose was to study the concordance of serological tests for inflammatory bowel disease with clinical diagnosis established by traditional testing in children. METHODS: All children seen in our division who had IBD Diagnostic System (ie, pANCA, ASCA IgA, and ASCA IgG) performed over a 21-month period (June 1998 to February 2000) were identified. Their medical records were reviewed for basic demographics, test results (endoscopy, histology, and radiology), IBD Diagnostic System results, and patient symptoms/medications. Results of the IBD Diagnostic System were compared with several patient characteristics including age, sex, absence/presence of symptoms, medication use, disease activity and duration. RESULTS: One hundred seven patients were divided into 6 groups based on clinical diagnosis and IBD Diagnostic System results. The sensitivity, specificity and +/- predictive values of the IBD Diagnostic System for ulcerative colitis were 69.2, 95.1, 90.0, and 87.1%, respectively, and for Crohn's disease were 54.1, 96.8, 90.9, and 80.8%, respectively. Overall, the results of the IBD Diagnostic System were concordant with the clinical diagnosis in 76 of the 107 (71%) patients. CONCLUSIONS: In our experience, the specificity of IBD Diagnostic System is better than the sensitivity; the sensitivity is better for ulcerative colitis than Crohn's disease (69.2% vs 54.1%). The low sensitivity, especially for Crohn's disease, precludes the possibility that the IBD Diagnostic System can replace traditional studies when evaluating for inflammatory bowel disease. Though we do not exclude inflammatory bowel disease solely by IBD Diagnostic System results, it is reassuring to note that all patients without clinical evidence of inflammatory bowel disease also had negative IBD Diagnostic System results.

The role of esophagogastroduodenoscopy in the initial evaluation of childhood inflammatory bowel disease: a 7-year study.

OBJECTIVES: To assess the role of esophagogastroduodenoscopy in the evaluation of children with suspected inflammatory bowel disease. METHODS: All children with inflammatory bowel disease who underwent esophagogastroduodenoscopy during their initial evaluation at our institution during a 7-year period (December 1993 to November 2000) were included in the study. RESULTS: The study included 115 patients: 81 with Crohn disease (mean age, 11.34 years; 42 males) and 34 with ulcerative colitis (mean age, 11.79 years; 20 males). Abnormal findings on esophagogastroduodenoscopy were noted in 64% of patients with Crohn disease and 50% of children with ulcerative colitis; histologic abnormalities were found in 81.6% and 70.6% of the patients, respectively. Granulomas were found in the upper gastrointestinal tracts of 23 of 81 patients (28.4%), with the most common site being the gastric mucosa. Nine of these 23 patients had granulomas solely in the upper gastrointestinal tract. Additional unsuspected pathology noted included: candidiasis, hiatal hernia, Helicobacter pylori infection, and giardiasis. CONCLUSIONS: Endoscopic and histologic abnormalities were found in the upper gastrointestinal tracts of a significant number of children with inflammatory bowel disease. While the mechanism(s) underlying these abnormalities in patients with ulcerative colitis is unclear, the pathology can contribute to the patient's clinical condition. Pathology in the upper gastrointestinal tract should not exclude a diagnosis of ulcerative colitis. Granulomas, confirming the diagnosis of Crohn disease, were found in the upper gastrointestinal tracts of 28% of our patients with Crohn disease. In some cases, granulomas were found solely in the upper gastrointestinal tracts. Based on our data, esophagogastroduodenoscopy with biopsy should be performed in all pediatric patients with suspected inflammatory bowel disease.