Epidemiology and natural history of hepatitis C virus infection among children and young people.

BACKGROUND & AIMS: Chronic hepatitis C virus (HCV) infection is a global health burden. Although HCV infection rarely contributes to morbidity during childhood, most HCV-infected children develop chronic HCV with a lifetime risk of liver disease. Little is known about the development of long-term liver disease and the effect of treatment in patients infected with HCV in childhood. METHOD: This study was a retrospective review of patients infected with HCV in childhood enrolled in HCV Research UK. A total of 1,049 patients were identified and included. RESULTS: The main routes of infection were intravenous drug use (53%), blood product exposure (24%) and perinatal infection (11%). Liver disease developed in 32% of patients, a median of 33 years after infection, irrespective of the mode of infection. Therefore, patients with perinatal exposure developed cirrhosis at an earlier age than the rest of the risk groups. The incidence of hepatocellular carcinoma (HCC) was 5%, liver transplant 4% and death occurred in 3%. Overall, 663 patients were treated (55% with interferon/pegylated interferon and 40% with direct-acting antivirals). Sustained virological response (SVR) was achieved in 406 (75%). There was a higher mortality rate among patients without SVR vs. those with SVR (5% vs. 1%, p = 0.003). Treatment was more effective in patients without cirrhosis and disease progression was less frequent (13%) than in patients with cirrhosis at the time of therapy (28%) p < 0.001. Patients with cirrhosis were more likely to develop HCC, require liver transplantation, or die. CONCLUSION: HCV infection in young people causes significant liver disease, which can now be prevented with antiviral therapy. Early treatment, especially before development of cirrhosis is essential. Detection of HCV should be aimed at relevant risk groups and antiviral therapy should be made available in childhood to prevent long-term liver disease and spread of HCV. LAY SUMMARY: Chronic hepatitis C virus (HCV) infection is a global health problem, which can now be treated with potent direct-acting antiviral drugs. This study demonstrates that HCV infection in childhood causes serious liver disease in 32% of patients, a median of 33 years after infection, irrespective of age, mode and route of infection. Disease outcomes were better in patients treated before the development of advanced liver disease. Antiviral therapy should be made available in childhood to prevent long-term liver disease and the spread of HCV.

Polyethylene Glycol Maintenance Treatment for Childhood Functional Constipation: A Randomized, Placebo-controlled Trial.

OBJECTIVE: The aim of this study was to investigate the long-term efficacy of polyethylene glycol (PEG) during maintenance treatment of childhood functional constipation (FC) in a randomized, double-blinded, placebo-controlled trial. METHODS: Children (2-16 years) with FC according to the Rome III criteria were randomly assigned to maintenance treatment with PEG or placebo for 24 weeks. Children reporting treatment failure before 24 weeks were switched to conventional treatment. Primary outcome was successful treatment, defined as absence of any Rome III criteria with or without use of medication after 24 weeks. RESULTS: A total of 102 children were included: PEG/placebo: 49/53. At 24 weeks, significantly more patients in the PEG group, compared to the placebo group, were successfully treated (33 [67%] vs 19 [36%] hazard ratio (95% confidence intervals) = 3.21 [1.73-5.94]). Significantly fewer children in the PEG group switched to rescue medication (2 [4%] vs 30 [57%], P < 0.001). Time before the change to rescue medication was 13 and 27 days, respectively, for each of the 2 children in the PEG group who required rescue medication. Median time to shift to rescue medication was 27 days (range: 3-64 days) in the placebo group. At 24 weeks after initiation of treatment, 33 children (67%) in the PEG group were successfully treated, compared to 19 children (32%) in the placebo group (hazard ratio (95% confidence intervals) = 3.21 [1.73-5.94]). No serious adverse event related to use of the medication was registered. CONCLUSIONS: Maintenance treatment with PEG is significantly more effective than placebo in preventing relapse of constipation symptoms during long-term maintenance treatment in childhood FC. We therefore recommend that maintenance treatment commence after disimpaction.

Transanal irrigation is effective in functional fecal incontinence.

Functional fecal incontinence (FFI) is divided into cases related to functional constipation (FC) and cases without concomitant constipation termed functional non-retentive fecal incontinence (FNRFI). Transanal irrigation (TAI) is widely used in children with neurogenic fecal incontinence but is less studied in children with functional defecation disorders. The aim was to evaluate the feasibility and efficacy of TAI in the treatment of FFI. A retrospective study in 72 children (mean age 9.2 ± 2.2 years, 47 males) with treatment-resistant FFI was performed. All children accepted treatment and 35% (n = 25) were titrated to daily sessions. Of the 63 children who fulfilled the Rome III criteria of constipation, 46 (73%) showed full response with complete remission of incontinence episodes. Eleven (17%) showed partial response (≥50% reduction). Of nine children with FNRFI, four (44%) showed full response whereas two (22%) showed partial response. We found no significant difference in the reduction of incontinence episodes between the children with FC (87%) and children with FNRFI (68%) (p = 0.11). CONCLUSION: TAI is an effective, well-tolerated, and safe choice in children with FC. No clinical parameters seemed to predict response to treatment. The number of children with FNRFI was low, but TAI seemed effective in this group of children. What is Known: • Functional fecal incontinence (FFI) is a frequent, chronic condition with significant impact on children's quality of life. • Transanal irrigation (TAI) is used in children with neurogenic bowel dysfunction but less studied in children with functional defecation disorders. What is New: • TAI seems an effective, well-tolerated, and safe choice in children with FFI due to functional constipation. • Albeit the number of children with functional non-retentive fecal incontinence was low in our study, TAI seems effective also in this group of children.

Follow-up in Childhood Functional Constipation: A Randomized, Controlled Clinical Trial.

OBJECTIVES: Guidelines recommend close follow-up during the treatment of childhood functional constipation. Only sparse evidence exists on how follow-up is best implemented. Our aim was to evaluate whether follow-up by phone or self-management through Web-based information improved treatment outcomes. METHODS: In this randomized controlled trial, conducted in secondary care, 235 children, ages 2 to 16 years, who fulfilled the Rome III criteria of childhood constipation, were assigned to 1 of the 3 follow-up regimens: control group (no scheduled contact), phone group (2 scheduled phone contacts), and Web group (access to Web-based information). PRIMARY OUTCOME: number of successfully treated children after 3, 6, and 12 months. SECONDARY OUTCOMES: phone contacts, relapse, fecal incontinence, and laxative use. RESULTS: After 3 and 6 months, significantly more children in the Web group (79.7%/75.9%) were successfully treated compared with the control and phone groups (59.7%/63.6% and 63.3%/64.6%) (P = 0.007/P = 0.03). No difference was found after 12 months (control, 72.7%; phone, 68.4%; Web group, 78.5%; P = 0.40). Extra phone consultations were significantly more frequent in the Web group (44.3%) compared with the control group (28.6%) (P = 0.04). Before 3 months, 45.5% of phone consultations were completed in the Web group versus 28.8% and 25.8% in the control and phone groups (P = 0.05/P = 0.02). Relapses, fecal incontinence, and laxative use were not different between interventions. CONCLUSIONS: Improved self-management behavior caused by access to self-motivated Web-based information induced faster short-term recovery during the treatment of functional constipation. Patient empowerment rather than health care-promoted follow-up may be a step toward more effective treatment for childhood constipation.

Conventional treatment of functional constipation has a positive impact on the behavioural difficulties in children with and without faecal incontinence.

AIM: Constipation studies have only evaluated behavioural difficulties in children with faecal incontinence. This study evaluated changes in behavioural difficulties in childhood with functional constipation (FC) with and without faecal incontinence, based on treatment outcomes. METHODS: Children aged five to 16 years who fulfilled the Rome III criteria for FC received conventional treatment. The Strength and Difficulties Questionnaire was completed at inclusion and at the 12-month follow-up. RESULTS: We included 116 children. The behaviour scores decreased in successfully treated boys (10.3 versus 7.9; p < 0.001) and girls (10.0 versus 7.4; p = 0.0001) with and without faecal incontinence. There was no decrease in the behaviour scores in children with unsuccessful outcomes. Unsuccessfully treated boys had significantly higher behaviour scores than successfully treated boys at inclusion (13.2 versus 10.3; p = 0.006) and after 12 months (11.4 versus 7.9; p = 0.02). No difference was found between unsuccessfully treated and successfully treated girls at inclusion (10.5 versus 10.0; p = 0.77) or after 12 months (10.3 versus 7.4; p = 0.18). CONCLUSION: Our findings indicate that conventional treatment of FC had a positive impact on behavioural difficulties in constipated children with and without faecal incontinence. This study highlights the importance of proactive detection and treatment of FC in paediatric patients.

Identifying faecal impaction is important for ensuring the timely diagnosis of childhood functional constipation.

AIM: Most research on functional constipation has been carried out at a tertiary level. We focused this study on a secondary-level hospital outpatients' department, assessing the distribution of diagnostic criteria for childhood functional constipation and evaluating the consequences of current diagnostic practice based on current guidelines. METHODS: We enrolled 235 children, aged two to 16 years of age, with functional constipation according to the Rome III criteria and assessed them using medical histories and physical examinations, including rectal examinations and ultrasound measurements of rectal diameter. Faecal impaction was a rectal diameter exceeding 3 cm. RESULTS: The most frequently reported symptom was painful bowel movements (72.3%) and 39.1% had faecal incontinence. Rectal examination identified faecal impaction in 149 children (66.2%), and ultrasound showed a mean rectal diameter of 3.4 ± 0.6 cm, compared to 2.2 ± 0.6 cm in children without impaction (p < 0.001). Of the 149 children with faecal impaction, 19 (12.8%) only had one additional Rome III criterion. The rectal diameter exceeded 3 cm in 79.9% of cases. CONCLUSION: Identifying faecal impaction is important for ensuring the timely diagnosis of childhood functional constipation at the secondary care level. Ultrasound examination proved a reliable alternative to rectal examination or abdominal radiography when identifying faecal impaction.

Transabdominal ultrasound measurement of rectal diameter is dependent on time to defecation in constipated children.

AIM: To study whether diurnal variations and time in relation to defecation has to be taken into account when measurements of rectal diameter are used to determine faecal impaction in constipated children. METHODS: Repeated ultrasound measures of rectal diameter were performed in 28 children (14 constipated/14 healthy, aged between 4 and 12 years) every third hour during 24 h. After defecation, three additional scans were performed at 1-h intervals. RESULTS: No diurnal variation in rectal diameter was found in the healthy group. In the constipated group, mean rectal diameter was significantly larger at 2 pm (P = 0.038) and 5 pm (P = 0.006). There were significant differences between rectal diameter in the healthy group and the constipated group at 2 pm (P = 0.016) and 5 pm (P = 0.027). When we omitted the rectal diameter of five constipated children who had their first bowel movement after 5 pm, there were no difference between groups (2 pm (P = 0.103)/5 pm (P = 0.644) ). Only in the constipated group, rectal diameter exceeded 3 cm without the patients feeling the urge to defecate. CONCLUSION: We found no independent daily variation in either group without relation to defecation. There was a relation between defecation and changes in rectal diameter in both healthy children and constipated children during maintenance treatment.Asking for defecation signals before scanning should be considered a routine question, and a positive answer should cause postponement of the scan.

A Case Series on Genotype and Outcome of Liver Transplantation in Children with Niemann-Pick Disease Type C.

BACKGROUND: To report on clinical presentation and outcomes of children who underwent liver transplantation (LTx) and were subsequently diagnosed to have Niemann-Pick type C (NPC). METHODS: Retrospective, descriptive, multi-centre review of children diagnosed with NPC who underwent LTx (2003-2018). Diagnosis was made by filipin skin test or genetic testing. RESULTS: Nine children were identified (six centres). Neonatal acute liver failure was the most common indication for LTx (seven children). Median age at first presentation: 7 days (range: 0-37). The most prevalent presenting symptoms: jaundice (8/9), hepatosplenomegaly (8/9) and ascites (6/9). 8/9 children had a LTx before the diagnosis of NPC. Genetic testing revealed mutations in NPC1 correlating with a severe biochemical phenotype in 5 patients. All 9 children survived beyond early infancy. Seven children are still alive (median follow-up time of 9 (range: 6-13) years). Neurological symptoms developed in 4/7 (57%) patients at median 9 (range: 5-13) years following LTx. CONCLUSION: Early diagnosis of NPC continues to be a challenge and a definitive diagnosis is often made only after LTx. Neurological disease is not prevented in the majority of patients. Genotype does not appear to predict neurological outcome after LTx. LTx still remains controversial in NPC.