27 research outputs found
Durability of Response in Children Treated with Pegylated Interferon alfa-2a +/- Ribavirin for Chronic Hepatitis C
Objectives: No long-term data have been published on the durability of response following pegylated interferon (PegIFN) treatment in children with chronic hepatitis C. This prospective, multicenter, long-term follow-up (LTFU) study aimed to assess long-term durability of sustained virological response (SVR), long-term safety and tolerability, and the association between IL28B genotype and treatment response, in children previously treated with PegIFN alfa-2aâ±âribavirin (RBV) in the PEDS-C trial.
Methods: A total of 93 patients were assessed for enrollment, and 38 enrolled in the study. Patients attended 2 study visits: 5 (mean 5.6, range 4.1â6.6) and 6 (6.6, 5.1â7.7) years after treatment cessation. Standardized medical history, physical examination, and laboratory testing were performed at these visits. Reminder telephone calls were conducted at 4 and 8 months after the initial visit.
Results: The LTFU cohort was the representative of the original PEDS-C cohort because both baseline and treatment characteristics were comparable. Of the 38 participants, 21 achieved SVR (responders) during the PEDS-C trial and 17 had not (nonresponders). All 21 responders maintained undetectable hepatitis C virus RNA during the LTFU (4.4â7.0 years after achieving SVR) in contrast to the nonresponders who demonstrated persistent viremia. IL28B CC genotype was associated with SVR (67% vs 30% in non-CC, Pâ=â0.028).
Conclusion: Long-term durability of SVR is excellent following PegIFN alfa-2a treatment in children with chronic hepatitis C; SVR is higher in those with IL28B CC versus non-CC
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Sofosbuvir and Ribavirin Therapy for Children Aged 3 to <12 Years With Hepatitis C Virus Genotype 2 or 3 Infection.
Currently, the only approved hepatitis C virus (HCV) treatment for children aged <12 years is pegylated interferon plus ribavirin. In an open-label study, we evaluated the safety and efficacy of sofosbuvir plus ribavirin for 12 weeks in children aged 3 to <12 years chronically infected with genotype 2 or for 24 weeks in patients with genotype 3. Patients aged 3 to <6 years weighing <17 kg received sofosbuvir 150 mg, and patients aged 3 to <6 years weighing â„17 kg and all patients aged 6 to <12 years received sofosbuvir 200 mg once daily. Intensive pharmacokinetic sampling conducted in each age group confirmed the appropriateness of sofosbuvir doses. For all patients, ribavirin dosing was determined by baseline weight (up to 1,400 mg/day, two divided doses). The primary efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12). Fifty-four patients were enrolled (41 aged 6 to <12 years and 13 aged 3 to <6 years). Most were treatment naĂŻve (98%) and infected perinatally (94%). All but one patient achieved SVR12 (53/54, 98%; 95% confidence interval, 90%-100%). The patient who did not achieve SVR12 was a 4-year-old who discontinued treatment after 3 days because of "abnormal drug taste." The most commonly reported adverse events in patients aged 6 to <12 years were vomiting (32%) and headache (29%), and those in patients aged 3 to <6 years were vomiting (46%) and diarrhea (39%). One 3-year-old patient had a serious adverse event of accidental ribavirin overdose requiring hospitalization for monitoring; this patient completed treatment and achieved SVR12. Conclusion: Sofosbuvir plus ribavirin was well tolerated and highly effective in children aged 3 to <12 years with chronic HCV genotype 2 or 3 infection
342 Herpes Simplex Virus Hepatitis in Infants: Clinical Outcomes and Correlates of Disease Severity
Asymptomatic presentation of mesalamine-induced lung injury in an adolescent with Crohn disease
The present report describes the case of a 14-year-old boy receiving mesalamine for Crohn disease who was discovered to have incidental pulmonary infiltrates on chest radiograph and CT scan shortly after increasing the dose of this medication. Despite the significant radiographic abnormalities, he had no respiratory symptoms. He had normal oxygenation and normal pulmonary function tests including spirometry, lung volumes and diffusion capacity. Transbronchial biopsies showed patchy interstitial fibrosis with ill-defined non-necrotising granulomas and lymphoid aggregates. Pulmonary infiltrates resolved within 6 weeks of discontinuation of mesalamine and the addition of low-dose daily corticosteroids. This case likely represents an asymptomatic âearly stageâ of mesalamine-induced lung injury preceding the onset of symptoms. Alternatively, mesalamine may induce asymptomatic lung injury more commonly than is presently suspected. To the best of our knowledge this is the first time this complication has been reported without respiratory symptoms
The Challenge of Treating Children with Hepatitis C Virus Infection
The development of oral hepatitis C virus direct acting antivirals has revolutionized the therapeutic field. Nowadays, multiple safe and highly effective antiviral regimens are commercially available to treat adults with hepatitis C infection. These new regimens for the first time, genuinely raise the prospects of eradicating hepatitis C virus. However, many challenges remain: from identifying infected individuals to optimizing treatment and ensuring global access to antiviral therapy to all population groups, including children. The only drugs currently approved for children with chronic hepatitis C virus infection are pegylated interferon and ribavirin. There are four registered ongoing pediatric trials assessing safety and efficacy of direct acting antivirals but their current completion timelines are years away. Herein, we summarize the state of the art of direct acting antivirals development for adult and children and highlight the crucial importance of overcoming barriers to treating children with hepatitis C virus
Correlates of adiponectin in hepatitis C-infected children: the importance of body mass index
Adiponectin is a regulator of cytokines that, in turn, play a vital role in inflammatory and immune responses. Adiponectin is therefore likely to have a contributory role in hepatitis C virus (HCV) infection. We sought to characterize adiponectin levels and examine correlates in a pediatric HCV-infected cohort.
We performed a cross-sectional study in children (5-17 years of age, nâ=â86) in the Pediatric Study of Hepatitis C (PEDS-C) trial. Adiponectin levels were univariately correlated with patient demographics, anthropometrics, and viral and histological measures. Multivariate regression models were used to identify the unique (ie, nonconfounded) associations with adiponectin concentrations.
Body mass index (BMI) had the highest univariate inverse correlation with log(e)âadiponectin (râ=â-0.5, Pâ<â0.0001). In multivariate analysis, BMI remained inversely correlated with log(e)âadiponectin after accounting for age and route of HCV transmission (râ=â-0.38, Pâ=â0.0003). Steatosis and fibrosis were inversely related to log(e)âadiponectin in univariate analysis, but these associations were not statistically significant after multivariate adjustments (Pââ„â0.1827).
High BMI among HCV-infected children is associated with lower adiponectin levels. Practitioners should be cognizant of the possible risks of low adiponectin when managing HCV-infected children who are overweight. Further studies are indicated to determine the impact of having low adiponectin on HCV infection in youth
ESPGHAN recommendations on treatment of chronic hepatitis C virus infection in adolescents and children including those living in resourceâlimited settings
Hepatitis C virus (HCV) infection is a major cause of chronic liver disease worldwide, with more than three million viraemic adolescents and children. Treatment of adults with HCV infection and HCV-related liver disease has advanced considerably thanks to development and improvements in therapy. Direct-acting antiviral regimens are safe and effective. Three regimens with pangenotypic activity (glecaprevir/pibrentasvir, sofosbuvir/velpatasvir and sofosbuvir/velpatasvir/voxilaprevir) and three regimens with genotype-specific activity (sofosbuvir/ribavirin, sofosbuvir/ledipasvir and elbasvir/grazoprevir) have been approved with age-specific limitation for treatment of children with chronic hepatitis C by the European Medicines Agency and the United States Food and Drug Administration. The World Health Organization has set the ambitious target to eliminate hepatitis C as a major public health threat by 2030 and based its actions against HCV on the large use of direct acting antivirals. These updated European Society for Pediatric Gastroenterology, Hepatology and Nutrition recommendations on treatment of hepatitis C describe the optimal therapeutic management of adolescents and children with HCV infection including specific indications for those living in resource-limited settings
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Evaluating progression of liver disease from repeat liver biopsies in children with chronic hepatitis C: A retrospective study
UnlabelledClinical and histologic progression of liver disease in untreated children with chronic hepatitis C virus (HCV) infection is poorly documented. The aim of this retrospective study was to characterize changes in liver histology over time in a cohort of HCV-infected children who had more than one liver biopsy separated by over 1 year. Forty-four untreated children without concurrent liver diseases, who had repeat liver biopsies at eight U.S.-based medical centers, were included. Biopsies were scored by a single pathologist for inflammation, fibrosis, and steatosis and were correlated with demographic data including age at biopsy, time from infection to biopsies, and laboratory values such as serum alanine aminotransferase (ALT). Mode of transmission was vertical in 25 (57%) and from transfusions in 17 children (39%). Genotype 1 was present in 30/35 (84%) children. The mean age at first and final biopsy was 8.6 and 14.5 years, respectively, and the mean interval between biopsies was 5.8 ± 3.5 years. Duration of infection to biopsy was 7.7 and 13.5 years, respectively. Laboratory values did not change significantly between the biopsies. Inflammation was minimal in about 50% at both timepoints. Fibrosis was absent in 16% in both biopsies, limited to portal/periportal in 73% in the first biopsy, and 64% in the final biopsy. Between the two biopsies, the proportion of patients with bridging fibrosis/cirrhosis increased from 11% to 20% (P = 0.005).ConclusionAlthough in aggregate this cohort did not show significant histologic progression of liver disease over 5 years, 29.5% (n = 13) of children showed an increase in severity of fibrosis. These findings may have long-term implications for the timing of follow-up biopsies and treatment decisions
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Evaluating progression of liver disease from repeat liver biopsies in children with chronic hepatitis C- a retrospective study.
UnlabelledClinical and histologic progression of liver disease in untreated children with chronic hepatitis C virus (HCV) infection is poorly documented. The aim of this retrospective study was to characterize changes in liver histology over time in a cohort of HCV-infected children who had more than one liver biopsy separated by over 1 year. Forty-four untreated children without concurrent liver diseases, who had repeat liver biopsies at eight U.S.-based medical centers, were included. Biopsies were scored by a single pathologist for inflammation, fibrosis, and steatosis and were correlated with demographic data including age at biopsy, time from infection to biopsies, and laboratory values such as serum alanine aminotransferase (ALT). Mode of transmission was vertical in 25 (57%) and from transfusions in 17 children (39%). Genotype 1 was present in 30/35 (84%) children. The mean age at first and final biopsy was 8.6 and 14.5 years, respectively, and the mean interval between biopsies was 5.8 ± 3.5 years. Duration of infection to biopsy was 7.7 and 13.5 years, respectively. Laboratory values did not change significantly between the biopsies. Inflammation was minimal in about 50% at both timepoints. Fibrosis was absent in 16% in both biopsies, limited to portal/periportal in 73% in the first biopsy, and 64% in the final biopsy. Between the two biopsies, the proportion of patients with bridging fibrosis/cirrhosis increased from 11% to 20% (P = 0.005).ConclusionAlthough in aggregate this cohort did not show significant histologic progression of liver disease over 5 years, 29.5% (n = 13) of children showed an increase in severity of fibrosis. These findings may have long-term implications for the timing of follow-up biopsies and treatment decisions