Chronic hepatitis C in children--review of natural history at a National Centre.

The natural history of hepatitis C virus (HCV) infection in adults has been established, but less is known about outcome in children. We conducted a retrospective review of patients referred to Birmingham Children's Hospital Liver Unit, from 1991 till 2008, with the diagnosis of HCV was undertaken. Only children with documented positive HCV RNA and a minimum duration of follow-up of 6 months were included. One hundred and thirty-three children were identified. The route of transmission was transfusion acquired in 47%, vertically acquired in 49% and transplantation in 2%. Since 2000, most children were infected vertically. The overall rate of spontaneous viral clearance was 17.5% with higher clearance (27%) in the transfusion group compared to the vertically acquired group (9%). Seventy-six had a liver biopsy at diagnosis. There was no evidence of fibrosis in 46%, mild fibrosis in 50% and moderate to severe fibrosis in 4%. None had cirrhosis. There was a statistically significant relationship between fibrosis score and older age at the time of biopsy (P = 0.02) and longer duration of infection (P = 0.05). Eighty children received treatment for HCV. Sustained viral response (SVR) was influenced by viral genotypes, with significantly increased response rates in genotypes (G) 2 and 3 compared to G 1 and 4. Vertical infection is now the major route of HCV infection in children in the UK. Histological changes were mild at diagnosis, but the severity of fibrosis progressed with age. Consideration should be given to improve detection and diagnosis to refer children to specialist centres for management and antiviral therapy before developing fibrosis.

Fecal calprotectin as a measure of disease activity in childhood inflammatory bowel disease.

BACKGROUND: Calprotectin is an abundant neutrophil protein that is extremely stable in feces. The aim of this study was to assess the effectiveness of fecal calprotectin as a noninvasive measure of disease activity in childhood inflammatory bowel disease (IBD) by comparison to a modified Lloyd-Still and Green score and laboratory inflammatory indices. METHODS: Spot fecal samples from 37 children with IBD and 31 control children were sent by ordinary mail to the laboratory. Fecal calprotectin concentration was measured by an in-house enzyme linked immunosorbent assay (ELISA). A modified Lloyd-Still & Green score (mLSS) was calculated for each child with IBD within 10 days of obtaining the fecal sample. RESULTS: Compared with control values (median, range) (2.1, 0.5-6.3 mg/L), fecal calprotectin was increased in 16 children with ulcerative colitis, (11.5, 0.6-272.5 mg/L, P < 0.001) and in 21 children with Crohn disease, (14.0, 0.7-59.7 mg/L, P < 0.001). Twelve "moderately affected" children (mLSS of 35-65) had higher fecal calprotectin concentrations (22.2, 2.7-141.7 mg/L) than 25 "mildly affected" children (mLSS > 65), (10.3, 0.6-272.5 mg/L, P = 0.002). For the total IBD group, fecal calprotectin concentration correlated negatively with the mLSS (r = -0.61, P < 0.001). It also correlated negatively with serum albumin concentration (r = -0.49, P = 0.002) and positively with erythrocyte sedimentation rate (r = 0.40, P = 0.01). CONCLUSIONS: Fecal calprotectin seems to reflect bowel inflammation in children with IBD. As a simple, safe, noninvasive test, it has the potential to reduce the number of invasive investigations performed in these children.

Fecal calprotectin: validation as a noninvasive measure of bowel inflammation in childhood inflammatory bowel disease.

BACKGROUND: Calprotectin is an abundant neutrophil protein, which is extremely stable in feces. This study aimed to validate fecal calprotectin as a marker of bowel inflammation against invasive measures in children with inflammatory bowel disease (IBD), including colitis and small bowel Crohn disease. METHODS: Fecal calprotectin was measured using a simple enzyme-linked immunosorbent assay in 36 spot stool samples from 22 children before colonoscopy and from 14 children before technetium-99 (99Tc) scanning. Using standard scoring systems, the severity of inflammation was assessed macroscopically and histologically at six standard sites in those who underwent colonoscopy and also at six standard sites in those who underwent 99Tc scanning. The subscores from each site were summated to give combined severity and extent scores for macroscopic and for histologic inflammation in the group undergoing colonoscopy and total inflammation in the group undergoing 99Tc scanning. RESULTS: In the 22 children who underwent colonoscopy, median fecal calprotectin was 4.9 mg/L (0.1-272.5 mg/L) (range). Disease groups included six normal cases, nine ulcerative colitis cases, two isolated Crohn colitis cases, two indeterminate colitis cases, and three allergic colitis cases. Fecal calprotectin correlated closely with colonic macroscopic inflammation (r = 0.75, P < 0.001) and histologic inflammation (r = 0.85, P < 0.001). Of the 14 children undergoing 99Tc scanning, 10 had Crohn disease, 3 had ulcerative colitis, and 1 had allergic colitis. Median fecal calprotectin was 9.1 mg/L (0.3-141.7 mg/L), and this correlated closely with the 99Tc scanning score (r = 0.80, P = 0.001). CONCLUSION: Fecal calprotectin correlates closely with the best invasive measures of colonic and small bowel inflammation in childhood inflammatory bowel disease. As a sensitive objective measure of bowel inflammation that is risk-free and noninvasive, fecal calprotectin lends itself particularly to the monitoring of and assessment of therapeutic interventions in children with inflammatory bowel disease.