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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., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objective: This position paper written by the Hepatitis Expert Team of the Federation of International Societies of Pediatric Gastroenterology, Hepatology, and Nutrition aimed to systematically evaluate clinical practice guidelines (CPGs), medical consensus, and position papers on the use of direct-acting antivirals (DAA) to treat chronic hepatitis C virus (HCV) infection in adolescents and children in order to compare recommendations and provide the basis for developing a unified position statement., Methods: MEDLINE, Cochrane-Library, National Guideline Clearinghouse and select websites of relevant societies/organizations were used to identify CPGs, medical consensus and position papers between 2011-2019., Results: A total of 5 documents were analysed: 3 CPGs, 1 medical consensus, and 1 position paper. All publications were consistent in recommending DAA treatment for adolescents (12-17 years old) with chronic HCV infection. Similarly, all of these publications consistently recommended deferring therapy for children between 3 and 11 years of age until DAA became available as standard of care. Finally, none of the included publications recommended treating children younger than 3 years old. By contrast, there was significant discrepancy across the retrieved documents regarding specific DAA regimens and treatment strategies., Conclusions: There is strong consensus on treating all adolescents with chronic HCV infection with DAA and on delaying therapy in younger children until these agents are approved for them. Interferon-based therapies should be avoided. Specific recommendations regarding which DAA regimen to use and treatment duration varied significantly. Key stakeholders need to convene to standardize therapeutic strategies at a global level if we are to eradicate HCV in children.

Background: Childhood cancer survivors treated before 1992, when blood donor screening for hepatitis C virus (HCV) infection was introduced, are at risk of transfusion-transmitted HCV infection. A national HCV screening campaign targeting blood transfusion recipients was launched in Sweden in 2007-2010. The aims of this study were to, among adult childhood cancer survivors in Stockholm County, investigate the prevalence of HCV infection, the natural course of infection, treatment outcome and anti-HCV testing frequency before, during and after the screening campaign and finally to actively screen the untested ones. Material and Methods: This was a combined retrospective register based and prospective screening study of adult childhood cancer survivors ( n  = 686) treated for malignancy in Stockholm before 1992. In the first part, we investigated the prevalence of HCV infection and previous anti-HCV testing, and in the second part, we actively traced and HCV-screened the remaining untested cohort living in Stockholm. Analysis of previous documented anti-HCV tests in medical records, laboratory records, and the national communicable disease registry was performed. In the second part, 231 presumably untested individuals were contacted by mail and offered an anti-HCV test. The natural course of HCV infection and treatment outcome was analyzed for those found to be chronically infected. Results: In total, 235 patients were tested and 11 were HCV-RNA positive. The overall prevalence of chronic HCV infection among the tested childhood cancer survivors was thus 4.7% (95% CI = 2.6-8.2%), which is almost 10 times higher than the national prevalence of 0.5%. Only 12% of the Stockholm cohort were tested during the screening campaign in 2007-2010, while the test uptake using active tracing screening within this study was 40% ( p  < .001). Conclusion: With today's effective treatment options, active tracing and HCV screening of childhood cancer survivors are recommended.

Objectives: The prevalence of hepatitis C virus (HCV) infection in Sweden is estimated to 0.5%. Before 1992, blood transfusion posed a risk of HCV transmission. The primary aim of this study was to estimate anti-HCV prevalence in Stockholm County among individuals receiving blood transfusions 1965-1991. The secondary aim was to study the effect of age at transfusion on the development of liver disease and treatment outcome., Materials and Methods: This is a retrospective analysis of individuals found to be anti-HCV tested positive in Stockholm County during a national screening campaign in Sweden 2008-2010. All anti-HCV-positive individuals were also HCV RNA tested. Data on age at transfusion, age at diagnosis, HCV genotype, viral load, fibrosis score, liver histology and antiviral treatment were recorded., Results: Out of 7473, 134 (1.8%) tested individuals were anti-HCV positive and 102 were HCV RNA positive resulting in a prevalence of chronic hepatitis C (CHC) of 1.4%. The rate of advanced liver damage was 18% (10/56). Patients younger than 19 years of age at transfusion were significantly more often started on antiviral treatment compared to adult patients, 65% vs 29% p < .001. No significant correlation was found between treatment outcome and gender or age at transfusion., Conclusions: In this study, we found an anti-HCV prevalence of 1.8% which is considerably higher than the estimated prevalence in the Swedish general population (0.5%), and patients infected during childhood were more likely to receive antiviral treatment. Additional data on the HCV epidemic in Sweden are needed regarding prevalence and age distribution.

Objectives: In 2017, the European Medicines Agency and the Food and Drug Administration approved the use of the fixed-dose combination of ledipasvir/sofosbuvir and of the combination of sofosbuvir and ribavirin for treatment of adolescents (12-17 years or weighing >35 kg) with chronic hepatitis C virus (HCV) genotype 1, 4, 5, and 6 and genotype 2 and 3 infections, respectively. Although trials with direct-acting antivirals are ongoing for younger children, the only available treatment in the United States and Europe for those <12 years is still the dual therapy of pegylated interferon and ribavirin. There is currently a lack of a systematic approach to the care of these patients. The Hepatology Committee of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition developed an evidence-based position paper for the management of chronic HCV infection in children., Methods: A systematic literature search and meta-analysis were performed using MEDLINE and Embase from June 1, 2007 to June 1, 2017. The approach of the Grading of Recommendations Assessment, Development and Evaluation was applied to evaluate outcomes. European Society of Pediatric Gastroenterology, Hepatology and Nutrition Committee members voted on each recommendation, using the nominal voting technique., Results: The efficacy of the different direct-acting antivirals combinations tested was higher, the relapse and the treatment discontinuation rates lower when compared to pegylated interferon and ribavirin., Conclusions: This position paper addresses therapeutic management issues including goals, endpoints, indications, contraindications, and the optimal treatment regimen in children with chronic HCV infection.

Objective: Vertical transmission of hepatitis C virus (HCV) infection is uncommon and occurs in approximately 5% of births from HCV-infected mothers. The reason for the low transmission rate is unclear. We aimed to investigate whether there is evidence of HCV exposure also in the noninfected children born to HCV-infected mothers by the presence of a detectable immune response., Methods: Serum and peripheral blood mononuclear cells from 9 HCV vertically infected children, 32 uninfected children born to HCV infected mothers, and 15 HCV chronically infected mothers, were analyzed. HCV-RNA-negative adults and children were used as controls. HCV-specific T cell responses were analyzed by interferon gamma using an enzyme-linked immunospot assay and 3H-thymidine incorporation assay. HCV antibodies were also analyzed., Results: An HCV-specific T cell response was detected in 73% (11/15) of the HCV-infected mothers, 67% (6/9) of the vertically infected children, 56% (18/32) of the exposed but uninfected children and in 10% and 20% of the control groups, respectively. The 2 groups of HCV-exposed children both had a significantly higher proportion of HCV-specific T cell responders compared to pediatric controls (P = 0.01 and P = 0.02)., Conclusions: HCV-specific immune responses were more common in children born to HCV-infected mothers, regardless of the presence of HCV RNA. We conclude that noninfected children born to HCV-infected mothers may have been exposed to HCV antigens.

There have been no previous reports on the use of interferon-free combinations in pediatric patients with chronic hepatitis C infection. An infected adolescent with severe sickle cell disease underwent stem cell transplantation and subsequent treatment with sofosbuvir and simeprevir during ongoing immunosuppression. Despite the emergence of peripheral edema as a side effect, treatment was continued with sustained antiviral response.

Background: The aim of this study was to investigate if neonatal transfusions could underlie chronic hepatitis C in adults for whom the disease transmission route was previously unknown., Study Design and Methods: Questionnaires were sent to 255 patients with chronic hepatitis C born in Sweden in 1960 to 1975. The medical records of 230 of the patients, of whom 98 (43%) had unknown transmission route, were studied regarding the occurrence of neonatal blood transfusions. The clinical, virologic, and histopathologic characteristics of those found to have received transfusions as neonates were also studied., Results: Four of 230 (1.7%; 95% confidence interval, 0.5%-4.4%) patients with hepatitis C had received blood products as neonates. Three of them had reported unknown transmission route. One had cirrhosis, while two had mild histopathologic findings on liver biopsy. Three out of four patients in the transfused group, including the patient with liver cirrhosis, had undergone treatment for hepatitis C, all of them with a sustained viral response., Conclusion: Previously unidentified neonatal blood transfusions explain only a small fraction of chronic hepatitis C cases with unknown transmission route. Individual patients infected early in life can develop progressive liver damage as young adults and may benefit from antiviral treatment. The finding suggests that efforts are needed to actively trace and test adults who have been subjected to neonatal blood product transfusion before 1992., (© 2013 American Association of Blood Banks.)

Background & Aims: This multi-center study aimed to prospectively evaluate the safety and efficacy of a genotype-based Pegylated Interferon alfa-2a/Ribavirin therapy in treatment-naïve hepatitis C virus (HCV), positive HCV serology, and quantifiable HCV RNA, infected children., Methods: Eighteen children with genotypes 2 and 3 patients (group A) were assigned to medication for 24weeks, and 47 children with genotypes 1, 4, 5 and 6 patients (group B) for 48weeks., Results: Early response at week 12 was observed in 83% of group A patients and in 57% of group B patients (p<0.05). End of treatment response was achieved in 94% of patients in group A and in 57% in group B (p<0.001). Sustained virologic response was maintained in 89% of patients in group A and in 57% of patients in group B (p<0.01). Ten patients stopped prematurely the treatment, 2 for serious adverse event (acute hepatitis and thyrotoxicosis), and 8 because of no virologic response at week 24. Peginterferon alfa-2a and Ribavirin dose was adjusted in 15 patients (23%), 11 for neutropenia (17%), and 3 patients (5%), for anemia, respectively. Treatment-related adverse events included fever and flu-like symptoms (54%), irritability-depression-change of mood (34%), vomiting (23%), abdominal pain (38%), loss of appetite (21.5%) and dermatitis (29%). No influence on height growth was observed., Conclusions: Pegylated inteferon alfa-2a and Ribavirin treatment allowed to achieve SVR in 57% of pediatric patients with genotypes 1, 4, 5 and 6, and in 94% of genotypes 2 and 3. These results show an improved SVR as compared to reference series in adults with similar regimen., (Copyright 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

In 1999 a Swedish national expert panel published recommendations for the treatment of chronic hepatitis C (HCV) infection. Recently, pegylated interferon (peg-IFN) products have been introduced, and an increased knowledge concerning treatment of acute HCV and HCV-human immunodeficiency virus (HIV) coinfection has been gained. As a result of this, an update of the Swedish recommendations was developed following an expert meeting in October 2002. The panel now recommends the use of peg-IFN together with ribavirin as the standard treatment. Owing to the excellent response rates in HCV genotype 2 and 3 infections, these patients can be treated for 24 weeks without preceding liver biopsy. For patients with genotype 1 infection (with a slightly below 50% sustained response rate after 48 weeks treatment) and only mild histological disease, treatment can be postponed until future better treatment options become available. In patients who fail to achieve a 99% reduction (2 log drop) in viral titre after 12 weeks of treatment, discontinuation of therapy is recommended. Patients previously treated with IFN monotherapy and not having achieved a sustained virological response are recommended the same combination treatment as treatment-naive patients. IFN monotherapy is recommended in patients with acute hepatitis C. For children with chronic HCV infection, combination treatment is mainly recommended in clinical trials. For HCV-HIV coinfected patients, combination treatment is recommended and preferably given when blood CD4 counts are above 350/ml and before antiretroviral treatment (ART) is needed. Concurrent ART or prominent liver fibrosis requires frequent monitoring because of the increased risk for mitochondrial toxicity and liver failure.

The mother of an HCV-infected child had been subjected to neonatal exchange transfusion. It is likely that she contracted a chronic HCV infection which was later transmitted to her daughter. A similar route of infection is suggested in other HCV-infected patients lacking obvious risk factors.