The aim of this study was to assess the health-related quality of life (HRQL) of children with chronic hepatitis C (CHC) at 1 year after the effective treatment with sofosbuvir/velpatasvir (SOF/VEL).

All 50 patients treated for CHC with a fixed dose SOF/VEL in the noncommercial, nonrandomized, open-label PANDAA-PED study achieved sustained virologic response at 12 weeks after the end of treatment. Evaluation of HRQL at 1-year posttreatment was compared with the baseline (before the treatment) assessment. KIDSCREEN-27 questionnaires, which included 5 dimensions of HRQL, for child self-reporting and parent proxy reporting were used. The normal range for the population was set to T values of 40-60 points. Child-parent agreement was analyzed using the intraclass correlation coefficient (ICC).

Mean T values were within the normal range for all HRQL dimensions. A significant improvement in "autonomy & parent relation" in children's self-assessment (from 48.3 to 51.5, P = 0.03) was observed. In parent proxy assessment, a significant decrease occurred in "school" dimension (from 49.5 to 45.8, P = 0.03), which was not revealed at 3-month posttreatment. Older age was associated with worse HRQL scores in all dimensions. Evaluation of the ICC for child self-reports versus parent proxy reports revealed poor-to-moderate agreement for most single measures, lower than at 3-month posttreatment analysis.

This is the first study to present the long-term influence of treatment with direct-acting antivirals on patient-reported outcomes in children. At 1 year after effective treatment with SOF/VEL, an improvement in some areas of children's well-being was revealed, which may indicate also some patient-reported outcomes benefits of direct-acting antiviral therapy. Despite the improvement in the child self-report of "autonomy & parent relation," there was a more pronounced discrepancy between children self-reports and parents proxy reports in all dimensions of HRQL. Older patients' age correlated with worse HRQL assessment. If this finding is mediated by the duration of hepatitis C virus infection, it would support recommendation for the treatment of younger children.

Glecaprevir/Pibrentasvir (GLE/PIB) has been approved by the European Medicine Agency (EMA) and by the US Food and Drug Administration (US-FDA) for the treatment of children and adolescents from 3 years of age with chronic hepatitis C virus (CHC) infection. The aim of this study was to confirm the real-world effectiveness and safety of GLE/PIB in children and adolescents (3 to < 18 years old) with CHC.

This prospective, multicentre study involved 11 Italian centres. Children and adolescents (from 3 to < 18 years of age) received a weight-based dose (up to 300/120 mg) of GLE/PIB once daily for 8 weeks. The effectiveness endpoint was sustained virological response 12 weeks after the end of treatment (SVR12). Safety was assessed by adverse events (AE) and clinical/laboratory data.

Sixty-one patients (median age 12 years, interquartile range 5) were enrolled and treated between June 2020 and October 2023. Genotype distribution was as follows: 24/61 genotype 1 (39.4%), 13/61 genotype 2 (21.3%), 18/61 genotype 3 (29.5%) and 6/61 genotype 4 (9.8%). Sixty (98.4%) patients completed treatment and follow-up. SVR12 was obtained by 60/61 patients (98.4%). One patient died because of an oncological illness while on treatment. AE occurred in 13.1% of the patients, were mild and no patients prematurely stopped treatment.

This study confirmed the real-life effectiveness and safety of the 8-week therapy with GLE/PIB for treatment of CHC in children and adolescents.

Glecaprevir/pibrentasvir (GLE/PIB) has been approved by the European Medicines Agency and by US Food and Drug Administration for the treatment of children and adolescents aged 3 to 12 years with chronic hepatitis C (CHC) virus infection. The aim of this study was to confirm the real-world effectiveness and safety of GLE/PIB pediatric formulations in children aged 3 to 12 years with CHC.

This case series describes a pediatric population (3 to ≤12 years of age) treated with a weight-based dose of GLE/PIB pediatric formulation once daily for 8 weeks. The effectiveness end point was a sustained virologic response 12 weeks after the end of treatment. Safety was assessed on adverse events and clinical/laboratory data.

Six patients (median age 6 years; interquartile range, 3 years) were enrolled and treated between March 2023 and December 2023. Genotype distribution was as follows: 4 of 6 genotype 1 (60%), 1 of 6 genotype 2 (20%), and 1 of 6 genotype 3 (20%). Median viral load at baseline was 541,000 IU/mL (interquartile range, 641,000 IU/mL). All (100%) patients completed treatment. Sustained virologic response (SVR) 12 weeks after the end of treatment was 100%. No virologic relapse or breakthrough was observed. No adverse events occurred.

This study confirmed the real-life effectiveness and safety profile of an 8-week treatment with GLE/PIB for CHC in children aged 3 to 12 years.

Hepatitis C virus (HCV) infections continue to steadily increase in the United States and remain a major public health challenge. This review aims to provide a comprehensive overview of HCV infection in children, focusing on recent advancements in screening, diagnosis, and treatment.

Effective screening strategies, including universal screening of pregnant women and nucleic acid testing for all perinatally exposed infants at 2 to 6 months of age, have been implemented to identify infected individuals early. Direct-acting antiviral agents have revolutionized treatment, offering high cure rates for children of all ages. Despite significant progress, challenges remain in achieving HCV elimination. These include the need for improved access to testing and treatment, as well as ongoing efforts to develop a preventive vaccine. Continued research and implementation of effective strategies are essential to reduce the burden of HCV infection.

Hot-melt extrusion (HME) has emerged as a versatile and efficient technique in pharmaceutical formulation development, particularly for enhancing the solubility and bioavailability of poorly water-soluble drugs. This review delves into the fundamental principles of HME, exploring its application in drug delivery systems. A comprehensive analysis of polymers utilized in HME, such as hydroxypropyl methylcellulose, ethyl cellulose, hydroxypropyl cellulose, and polyvinylpyrrolidone, is presented, highlighting their roles in achieving controlled drug release and improved stability. The incorporation of plasticizers, such as triacetin, poly(propylene glycol), glycerol, and sorbitol, is critical in reducing the glass transition temperature (Tg) of polymer blends, thereby enhancing the processability of HME formulations. A comparison of Tg values for various polymer-plasticizer combinations is discussed using different predictive models. For researchers and industry professionals looking to optimize drug formulation strategies, this article offers valuable insights into the mechanisms through which HME enhances drug solubility and bioavailability two critical factors in oral drug delivery. Furthermore, by reviewing recent patents and marketed formulations, the article serves as a comprehensive resource for understanding both the technical advancements and commercial applications of HME. Readers will gain a deep understanding of the role of polymers and additives in HME, alongside future perspectives on how emerging materials and techniques could further revolutionize pharmaceutical development. This review is essential for those aiming to stay at the forefront of pharmaceutical extrusion technologies and their potential to improve therapeutic outcomes. The review concludes that meticulous material selection is vital for advancing pharmaceutical manufacturing processes and ensuring optimal outcomes in HME applications, thereby enhancing the overall efficacy of drug delivery systems.

The aim of this study was to evaluate the influence of treatment of hepatitis C with sofosbuvir and velpatasvir (SOF/VEL) on children's growth.

Fifty children 6-18 years of age were successfully treated for hepatitis C with a 12-week course of SOF/VEL fixed dose adjusted to the body weight in the PANDAA-PED (Treatment of chronic hepatitis C in children 6-18 years of age using a pangenotypic direct-acting antiviral sofosbuvir/velpatasvir) project. Growth parameters were compared at 1 year after treatment with baseline (at the start of treatment) and 12-week-posttreatment values. Body mass index (BMI), weight and height Z scores adjusted to sex and age were calculated according to the World Health Organization reference data.

Forty-nine participants (23 boys and 26 girls) completed all the visits. The mean age at 1 year after treatment was 10.9 ± 2.5 years, and all children had undetectable hepatitis C virus RNA at this point. Significant weight and height gains were observed after treatment irrespective of the patients' age and sex. Height Z scores did not vary significantly both at 12 weeks and 1 year after treatment, confirming a normal increase in participants' height. Weight Z scores for 16 children below 10 years of age decreased at 1 year after treatment. BMI Z score values decreased at 12 weeks after treatment compared to the baseline in boys, but no difference was found between 1-year posttreatment and baseline BMI Z scores in both girls and boys.

Results of the PANDAA-PED study showed normal growth up to 1 year after successful treatment with SOF/VEL in children 6-18 years of age. Despite the decrease in BMI Z score in boys observed at 12 weeks after treatment, no differences were found between baseline and 1-year posttreatment values. Our observations confirm the long-term safety of the SOF/VEL treatment in children 6-18 years of age.

Hepatitis C virus (HCV) testing is recommended for all adults 18 years and older to increase identification of those with infection and facilitate prompt referral for curative antiviral therapy. While critical to promote elimination, this strategy excludes a key demographic group who are clearly at risk of undetected HCV infection and who could benefit from early treatment: adolescents. In this paper, we review the available data on the burden of HCV and the close association with injection drug use, discuss the rationale of universal testing in adolescents and, finally, present data from a quality improvement project implementing HCV testing into routine adolescent health visits.

To analyse the main evidence and recommendations for the management of hepatitis co-infection in children living with HIV.

We analysed available data pertaining to the natural history of liver disease and treatment of co-infected children.

Viral hepatitis co-infection in people living with HIV (PLHIV) is a global problem owing to the shared routes of transmission, particularly in areas of high endemicity for the three viruses. Viral hepatitis co-infection can accelerate liver disease progression and increase morbidity and mortality, even in patients on suppressive antiretroviral treatment (ART). Viral hepatitis should be routinely screened in PLHIV and, once diagnosed with viral hepatitis, PLHIV should be closely monitored for liver disease progression and complications. Children living with HIV-HBV co-infection should be treated with ART containing agents which are active against both viruses. Children living with HIV-HCV co-infection should receive directly acting antivirals (DAA) to eradicate HCV infection. Prevention measures to reduce vertical and horizontal transmission of HBV and HCV (anti-HBV vaccination and immunoglobulins, anti-HBV treatment in pregnancy, anti-HCV DAAs in people of childbearing age, avoiding blood contact, sexual barrier precautions) should be adopted and encouraged, particularly in high endemicity countries.

Since the discovery of hepatitis C virus (HCV) in 1989, we now have curative treatment options with direct-acting antiviral therapies. By increasing the rate of treatment and reducing transmission, the eradication of HCV is potentially achievable. Nonetheless, the feasibility and implementation of this goal remains challenging. This article sums up the approach to managing children with HCV in the Asia-Pacific region and lists some of the difficulties and complexities surrounding this issue.

The Hepatitis C Virus (HCV) is a significant public health challenge in European countries. Historically, healthcare-related procedures were the primary source of HCV infection in Europe. However, with the implementation of blood safety programs, injection drug use has become the main transmission route. The infection's distribution and genotype prevalence vary widely across the continent. Even with the availability of highly effective direct-acting antiviral (DAA) therapies, HCV infection is far from being controlled. A significant proportion of patients remain undiagnosed, contributing to the ongoing transmission of the virus. Additionally, several barriers hinder the widespread use of DAAs, including high treatment costs, stigma, poor linkage to care, and considerable geographical variations in prevalence and transmission routes. The World Health Organization has set ambitious targets to reduce liver-related deaths, decrease new viral hepatitis infections, and ensure that 90% of infected individuals are diagnosed by 2030. However, most European countries face challenges, highlighting the need for screening programs, funding mechanisms, and public health strategies to effectively control HCV infection in Europe.

Few data on spontaneous clearance rates of cases of mother-to-child transmission of hepatitis C viral (HCV) infection are available in Japan. Furthermore, the treatment courses of interferon-based and direct-acting antiviral agent (DAA) therapies for children are also unclear. Our aim was thus to clarify the long-term natural progression of HCV infection and the treatment outcomes of children in Japan.

We conducted a combined multicenter, observational survey involving 65 pediatric institutions in Japan. Pediatric HCV infection cases with patients born between 1973 and 2021 were collected over the 11-year period from 2012 to 2022. A total of 563 patients were enrolled, with 190 excluded for having insufficient laboratory data or treatment information, resulting in 373 eligible cases.

Of 328 cases of mother-to-child infection, 34 (10.4%) had spontaneous clearance, with a median time to spontaneous clearance of 3.1 years (range 0.9-7.2 years). Of the total 373 eligible cases, 190 received antiviral therapy (interferon-based therapy, 158; DAA therapy, 32). Sustained virologic response rates after first-line treatment were 75.3% (119/158) and 100% (32/32) for interferon-based therapy and DAA therapy, respectively, with the DAA group showing a shorter time from therapy initiation to viral negativity (2.7 vs. 1.0 months; p = 0.0031).

Approximately 10% of Japanese children infected by mother-to-child transmission achieve spontaneous resolution of HCV infection. Our findings indicate that DAA therapy is safe and highly effective in Japanese children, achieving higher sustained virologic response rates and shorter time to clearance of the virus compared with interferon-based therapy.

Since the start of the pandemic, considerable advancements have been made in our understanding of the effects of SARS-CoV-2 infection and the associated COVID-19 on the hepatic system. There is a broad range of clinical symptoms for COVID-19. It affects multiple systems and has a dominant lung illness depending on complications. The progression of COVID-19 in people with pre-existing chronic liver disease (CLD) has also been studied in large multinational groups. Notably, SARS-CoV-2 infection is associated with a higher risk of hepatic decompensation and death in patients with cirrhosis. In this review, the source, composition, mechanisms, transmission characteristics, clinical characteristics, therapy, and prevention of SARS-CoV-2 were clarified and discussed, as well as the evolution and variations of the virus. This review briefly discusses the causes and effects of SARS-CoV-2 infection in patients with CLD. As part of COVID-19, In addition, we assess the potential of liver biochemistry as a diagnostic tool examine the data on direct viral infection of liver cells, and investigate potential pathways driving SARS-CoV-2-related liver damage. Finally, we explore how the pandemic has had a significant impact on patient behaviors and hepatology services, which may increase the prevalence and severity of liver disease in the future. The topics encompassed in this review encompass the intricate relationships between SARS-CoV-2, liver health, and broader health management strategies, providing valuable insights for both current clinical practice and future research directions.

Pharmacotherapy against hepatitis C virus (HCV) infection has tremendously improved since the advent of interferon (IFN)-free direct-acting antivirals (DAAs). Additionally, fixed-dose pangenotypic DAAs, which are safe, potent, easy for use, and can cover a wide spectrum of patients, have been recommended by professional guidelines for DAA-naïve and DAA-experienced patients with HCV.

We review the pharmacokinetics, pharmacodynamics, and potential drug-drug interactions (DDIs) of fixed-dose pangenotypic DAA regimens, including glecaprevir/pibrentasvir (GLE/PIB), sofosbuvir/velpatasvir (SOF/VEL), and sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX). Additionally, we summarize the efficacy and safety of these regimens in clinical trials as well as real-world studies for treating different populations. Lastly, we discuss unmet medical needs in managing HCV in the era of fixed-dose pangenotypic DAAs.

Protease inhibitors (PIs), including GLE and VOX, are prone to have more frequent DDIs, compared to the non-structural (NS) 5A and 5B inhibitors. These regimens are generally well tolerated and can be applied to different populations, except for the contraindicated use of PI-containing DAA regimens in decompensated cirrhosis. Using the first-line GLE/PIB and SOF/VEL can eradicate HCV in more than 95% of DAA-naïve patients across different populations. The viral cure usually exceeds 95% when using the rescue SOF/VEL/VOX regimen for prior DAA failures.

With the introduction of highly effective and safe therapies with next-generation direct-acting antivirals (DAAs), that act without interferon, hepatitis C virus (HCV) infection remains the only treatable chronic infectious disease.

The review aims to provide an overview of the therapy revolution with a description of specific DAAs, their mechanisms of action, a summary of the safety and efficacy of specific regimens, and a discussion of populations requiring special therapeutic approaches.

DAAs are highly effective, safe, and easy to use. However, challenges such as access to health services and loss of patients from the cascade of care, especially in groups disproportionately affected by HCV infection, such as substance abusers, make it difficult to achieve the WHO's goal of HCV elimination. The proposed strategy to combat these difficulties involves a one-step approach to diagnosing and treating the infection, the availability of long-lasting forms of medication, and the development of an effective vaccine. The aforementioned opportunities are all the more important as the world is facing an opioid epidemic that is translating into an increase in HCV prevalence. This phenomenon is of greatest concern in women of childbearing age and in those already pregnant due to treatment limitations.

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.

We evaluated the effectiveness and safety of pan-genotypic regimens, glecaprevir/pibrentasvir (GLE/PIB), sofosbuvir/velpatasvir (SOF/VEL), and sofosbuvir/daclatasvir (SOF/DCV) and other direct-acting antivirals (DAA) regimens for the treatment of hepatitis C virus (HCV)-infected adolescents (12-18 years), older children (6-11 years), and young children (3-5 years). The purpose of this systematic review and meta-analysis was to inform the World Health Organization (WHO) guidelines.

We included clinical trials and observational studies published up to August 11, 2021, that evaluated DAA regimens in HCV-infected adolescents, older children, and young children. We searched MEDLINE, EMBASE, and CENTRAL databases and key conference abstracts. Sustained virological response 12 weeks after the end of treatment (SVR12), adverse events (AEs), and treatment discontinuation were the outcomes evaluated. Risk of bias was assessed using a modified version of the ROBINS-I tool. Data were pooled using random-effects models, and certainty of the evidence was assessed using the GRADE approach.

A total of 49 studies including 1882 adolescents, 436 older children, and 166 young children were considered. The SVR12 was 100% (95% Confidence Interval: 96-100), 96% (90-100), and 96% (83-100) for GLE/PIB in adolescents, older, and young children, respectively; 95% (90-99), 93% (86-98), and 83% (70-93), for SOF/VEL, respectively; and 100% (97-100) and 100% (94-100) for SOF/DCV in adolescent and older children, respectively. There was a clear trend towards a higher rate of any reported AE from adolescents (50%), older children (53%), to young children (72%). Serious AEs and treatment discontinuations were uncommon in adolescents and older children (<1%) but slightly higher in young children (3%).

All three pan-genotypic DAA regimens were highly effective and well-tolerated and are now recommended by the WHO for use in adults, adolescents, and children down to 3 years, which will simplify procurement and supply chain management. The evidence was based largely on single-arm non-randomized controlled studies. Moreover, there were also missing data regarding key variables such as route of HCV acquisition, presence or absence of cirrhosis, or HIV co-infection that precluded evaluation of the impact of these factors on outcomes.

CRD42020146752.

Children represent only a small proportion of those infected with the hepatitis C virus (HCV) compared to adults. Nevertheless, a substantial number of children have chronic HCV infection and are at risk of complications including cirrhosis, portal hypertension, hepatic decompensation with hepatic encephalopathy, and hepatocellular carcinoma in adulthood. The overall prevalence of the HCV in children was estimated to be 0.87% worldwide. The HCV spreads through the blood. Children born to women with chronic hepatitis C should be evaluated and tested for HCV due to the known risk of infection. The course of treatment for hepatitis C depends on the type of HCV. Currently, there are two pan-genotype HCV treatments (Glecaprevir/pibrentasvir and Sofosbuvir/velpatasvir) for children. We aim to review the updated clinical guidelines on the management of HCV infection in children, including screening, diagnosis, and long-term monitoring, as well as currently published clinical trials and ongoing research on direct acting antiviral hepatitis C treatment in children.

The aim of this study was to assess the effect of treatment with sofosbuvir/velpatasvir (SOF/VEL) on the health-related quality of life (HRQL) of children with chronic hepatitis C.

In the non-commercial, non-randomized, open-label PANDAA-PED study, 50 children aged 6-18 years with chronic hepatitis C were treated with a fixed dose of SOF/VEL. All patients achieved sustained virologic response 12 weeks after the end of treatment (SVR12). Evaluation of HRQL was performed twice: at baseline (before the treatment) and during the SVR12 analysis using the KIDSCREEN-27 questionnaires, which included 5 dimensions of HRQL, for child self-reporting and parent proxy reporting. The normal range for the population was set to T values of 50 ± 10 points. Child-parent agreement was analysed using the intra-class correlation coefficient (ICC) and Bland-Altman test.

Mean T values were within the normal range for all dimensions, both before and after treatment. There was a significant improvement in physical well-being based on the children's self-assessment (from 48.53 to 51.21, p = .03). In addition, a trend towards better scores in the 'social support & peers' part of the parent proxy evaluation (from 45.98 to 48.66, p = .06) was noticed. After the treatment, the proportion of children self-assessing their physical well-being as below normal significantly decreased from 17% to 5% (p = .007). HRQL scores were not associated with patients' sex, but in most cases, younger age correlated with better HRQL. Evaluation of the ICC for child self-reports versus parent proxy reports revealed poor to moderate agreement for most single measures. Bland-Altman analysis showed that in all dimensions, both before and after treatment, the limits of agreement (LoAs) exceeded ±5 points (half of the SD and considered a maximum allowed difference).

A significant proportion of children with chronic hepatitis C have decreased HRQL in all dimensions, but effective treatment with SOF/VEL leads to an improvement in some areas of well-being. As the effect of HCV on HRQL is more pronounced in older patients, treatment of younger children should be indicated to prevent them from experiencing decreased HRQL due to ongoing HCV infection in the future.

The aim of the study was to analyze the effectiveness and safety of anti-HCV treatment based on a pangenotypic direct-acting antiviral (DAA) regimen with glecaprevir/pibrentasvir (GLE/PIB) in children. The multi-center study was conducted in HCV-infected children who were treated in the period from November 2022 to January 2023. The analysis included 23 pediatric patients with a mean (SD) age of 9.61 (3.68) years. The cohort included 13 girls and 10 boys. The most common HCV genotypes were GT1b (n = 9, 39.1%), GT1a (n = 6, 26.1%) and GT3 (n = 5, 21.7%). The SVR was assessed at 12 weeks after the end of treatment and was 100% for both girls and boys. The conducted study showed a very good tolerance of the treatment in the entire analyzed group and confirmed a very high efficacy and safety for 8-week treatment with GLE/PIB in children over three years of age. It seems that our study is the first on the real-world use of an 8-week GLE/PIB pangenotypic therapy in a group of children aged 3-12 years and the first in Europe for adolescents aged 12-17.

Hepatitis C virus (HCV) is a hepatotropic RNA virus that can cause acute and chronic hepatitis, with progressive liver damage resulting in cirrhosis, decompensated liver disease, and hepatocellular carcinoma. In 2016, WHO called for the elimination of HCV infection as a public health threat by 2030. Despite some progress, an estimated 57 million people were living with HCV infection in 2020, and 300 000 HCV-related deaths occur per year. The development of direct-acting antiviral therapy has revolutionised clinical care and generated impetus for elimination, but simplified and broadened HCV screening, enhanced linkage to care, and higher coverage of treatment and primary prevention strategies are urgently required.

The Infectious Diseases Society of America and the American Association for the Study of Liver Diseases have collaboratively developed evidence-based guidance regarding the diagnosis, management, and treatment of hepatitis C virus (HCV) infection since 2013. A panel of clinicians and investigators with extensive infectious diseases or hepatology expertise specific to HCV infection periodically review evidence from the field and update existing recommendations or introduce new recommendations as evidence warrants. This update focuses on changes to the guidance since the previous 2020 published update, including ongoing emphasis on recommended universal screening; management recommendations for incomplete treatment adherence; expanded eligibility for simplified chronic HCV infection treatment in adults with minimal monitoring; updated treatment and retreatment recommendations for children as young as 3 years old; management and treatment recommendations in the transplantation setting; and screening, treatment, and management recommendations for unique and key populations.

Part 1 of the DORA study, a 2019 international clinical trial of glecaprevir and pibrentasvir (G/P) treatment in adolescents with chronic hepatitis C virus (HCV) infection, demonstrated high efficacy and safety. However, few reports have considered real-world experience with G/P treatment in adolescents with chronic HCV. The present prospective multicenter study assessed real-world efficacy and safety of G/P treatment in Japanese adolescents with chronic HCV.

Subjects between 12 and 17 years old who were treatment-naïve or previously managed with interferon-based regimens were prospectively enrolled and treated with G/P (300 mg/120 mg) once daily for 8 or 12 weeks. The primary efficacy endpoint was sustained virologic response at 12 weeks after treatment completion (SVR12). Adverse effects and laboratory abnormalities were assessed.

Twenty-five Japanese patients (15 female) were enrolled from 13 pediatric centers in Japan. Median age was 13 years (range 12-17). Numbers of patients with genotypes 1b, 2a, 2b, and 2b/1b were 6, 12, 6, and 1, respectively. Twenty-two were treatment-naïve, while three had experienced interferon-based treatments. All patients completed G/P treatment (24 for 8 weeks and 1 for 12). Twenty-four achieved SVR12 (96%). Most adverse events were mild. None were serious. G/P significantly decreased serum alanine aminotransferase, γ-glutamyltransferase, and Wisteria floribunda agglutinin-positive Mac-2-binding protein concentrations. No negative effects on growth or maturation were apparent at 12 weeks.

Under real-world conditions, G/P treatment of Japanese adolescents with chronic HCV was highly efficacious and well tolerated.

Approximately 3.5 million children and adolescents worldwide are chronically infected with HCV. This study uses pharmacokinetic modeling to identify pediatric doses of elbasvir/grazoprevir (EBR/GZR) that achieve plasma concentrations similar to those seen in adults receiving the approved fixed-dose combination regimen of EBR/GZR.

We conducted a nonrandomized, single-arm, multicenter, open-label phase 2b trial in children and adolescents aged 3 to <18 years with chronic HCV genotype 1 or 4 infection (NCT03379506). Pharmacokinetic data were used to bridge efficacy and safety data from adults to children in a stepwise (oldest to youngest) manner. A total of 57 participants were enrolled: cohort 1 (aged 12 to <18 y), n=22; cohort 2 (aged 7 to <12 y), n=17; and cohort 3 (aged 3 to <7 y), n=18.

Steady-state plasma exposures were achieved by week 4 for EBR and GZR in all cohorts and daily dosing achieved geometric mean steady-state area under the concentration-time curve at 0-24 hours that fell within comparability bounds established for adults. All participants achieved sustained virologic response 12 weeks after completing treatment (ie, undetectable HCV RNA 12 wk following completion of treatment). Headache (n=4), fatigue (n=4), and nausea (n=2) were the most common treatment-related adverse events (all mild or moderate); no participant discontinued because of an adverse event.

Pediatric EBR/GZR pharmacokinetic models were successfully developed based on complex adult population pharmacokinetic models. At appropriate age-related doses, EBR/GZR is safe and effective in pediatric and adolescent participants with HCV infection.

Hepatitis C virus (HCV) infection is a global public health problem and also generates a significant case load in children and adolescents. With the introduction of directly acting antivirals (DAA), the treatment and care of HCV-infected patients have progressed significantly. The available treatment options in children are limited, and this review aims to provide an overview of treatment of HCV infection in children and adolescents with the current available DAA regimens.

This comprehensive review was undertaken after searching the PubMed/Medline and Embase databases for the available up-to-date literature on pediatric HCV infection and treatment using hepatitis C virus infection/HCV, directly acting antivirals/DAA, natural history, treatment, pediatrics, children, and adolescents as keywords.

Combination therapies with highly effective DAA regimes, such as sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, glecaprevir/pibrentasvir, sofosbuvir/daclatasvir, sofosbuvir/ribavirin and others, are available for use in children. Most of the DAA regimens have either received or are pending to receive regulatory approval by different medical/drug agencies for use in children and adolescents. Pan-genotypic regimens are also available in children and adolescents, and these regimens can be used while skipping genotype testing.

The literature on different DAA regimens for use in children shows that these regimens have higher cure rates with minimal side effects and shorter duration of therapy.

The World Health Organization envisions the elimination of viral hepatitis by 2030 through reducing prevalence and transmission, increasing diagnostic screening, and expanding treatment coverage. Efforts to micro-eliminate hepatitis in Phetchabun province in Thailand, a region where the prevalence of hepatitis C virus (HCV) infection and liver cancer is higher than elsewhere in the country, began with evaluating the province-wide burden of HCV. Here, we describe a feasibility study to assess active HCV infection by screening Phetchabun residents ages 35 to 69 years for anti-HCV antibodies by using a rapid diagnostic test (RDT) at the point of care. Positive anti-HCV results were further evaluated for active infection using qualitative HCV RNA assay, followed by quantitative HCV viral load determination in a subset of samples. Currently, we have identified 6.2% (10,621/170,163) anti-HCV positive individuals, of whom 74.9% (3,930/5,246) demonstrated detectable viral RNA. Quantitative test found that 97.5% (1,001/1,027) had HCV viral load ≥5,000 IU/mL. Thus, primary screening with anti-HCV RDT followed by qualitative HCV RNA evaluation could identify active and chronic HCV infection in almost all individuals with a viral load ≥5,000 IU/mL, which is the current threshold for treatment dictated by Thailand's National Health Security Office. Our data suggest that qualitative HCV RNA evaluation may obviate the need for the more expensive quantitative HCV viral load test and reduce a significant barrier toward HCV elimination in a middle-income country.

Mothers of children with chronic hepatitis C virus (HCV) infection experience anxiety about the health of their children. In this study we assessed an impact of treating children with chronic HCV infection on the psychological burden of their mothers. This was a multicenter, questionnaire survey conducted at six institutions in Japan. A newly-developed questionnaire for this study was used to assess changes in the mothers' various concerns regarding HCV infection and thoughts about their child's HCV infection. Responses at the time of diagnosis and at the time of the survey were compared between mothers of children who had received treatment and those without treatment. Responses were received from 36 of 37 eligible mothers (11 and 25, non-treatment and treatment groups, respectively). All children in treatment group had successfully eliminated the virus. Mothers in both groups were psychologically stressed in various ways, including concern about their child's health in the present and future at the time of diagnosis, concern about school, employment, and marriage, concern about the behavior of others towards them and infecting others with HCV, and feelings of guilt regarding their child. These concerns were significantly lower in the present compared to at the time of diagnosis in treatment group, and the rate of decrease was significantly higher in treatment group compared to non-treatment group. Successful treatment greatly reduced mothers' concerns about their children's HCV infection, indicating that treatment during childhood is beneficial from the perspective of the mothers' psychological burden.

Direct-acting antiviral (DAA) regimens targeting hepatitis C virus (HCV) are now approved for young children. This review examines recent DAA experience in children, current treatment recommendations and challenges, and potential treatment-as-prevention strategies.

In 2021, the US FDA extended approval of two pan-genotypic DAA regimens, glecaprevir/pibrentasvir and sofosbuvir/velpatasvir, to children as young as age 3 years based on high success rates and reassuring safety profiles in registry trials. Similar performance has been replicated with real-world DAA use in thousands of adolescents and in limited reports of children with high-risk conditions, including cirrhosis, cancer, thalassemia and HIV-coinfection. Treatment without delay is now recommended in the USA for viremic children aged 3 years and up to prevent disease progression and future spread. To date, treatment expansion is limited by high rates of undiagnosed paediatric infection. Universal prenatal screening will aid identification of perinatally exposed newborns, but new strategies are needed to boost testing of exposed infants and at-risk adolescents. Postpartum treatment programmes can prevent subsequent vertical transmission but are hampered by low rates of linkage to care and treatment completion. These challenges may be avoided by DAA use in pregnancy, and this warrants continued study.

Paediatric HCV is now readily curable. Substantial clinical and public health effort is required to ensure widespread uptake of this therapeutic breakthrough.

Amorphous solid dispersions (ASDs) have gained attention as a formulation strategy in recent years, with the potential to improve the apparent solubility and, hence, the oral bioavailability of poorly soluble drugs. The process of formulating ASDs is commonly faced with challenges owing to the intrinsic physical and chemical instability of the initial amorphous form and the long-term physical stability of drug formulations. Numerous research publications on hot-melt extrusion (HME) technology have demonstrated that it is the most efficient approach for manufacturing reasonably stable ASDs. The HME technique has been established as a faster scale-up production strategy for formulation evaluation and has the potential to minimize the time to market. Thermodynamic evaluation and theoretical predictions of drug-polymer solubility and miscibility may assist to reduce the product development cost by HME. This review article highlights robust and established prediction theories and experimental approaches for the selection of polymeric carriers for the development of hot melt extrusion based stable amorphous solid dispersions (ASDs). In addition, this review makes a significant contribution to the literature as a pilot guide for ASD assessment, as well as to confirm the drug-polymer compatibility and physical stability of HME-based formulations.

Three Japanese adolescents with chronic hepatitis C were treated by direct-acting antivirals (DAAs). No adverse events or laboratory abnormalities were observed during and after DAA therapy, and a sustained virological response was achieved in all cases. The emotional functioning of the patients and their mothers were improved after DAA therapy.

Untreated chronic hepatitis C infection can lead to severe and potentially fatal liver-associated complications. Therefore, every hepatitis C virus (HCV) infection represents an indication for antiviral treatment. In particular, patients with progressive liver disease should be treated urgently. Here, we review indication for treatment as well as goals and basic principles of antiviral therapy. In addition, different treatment regimens and monitoring of the treatment course and outcome are discussed.Today, the treatment of chronic HCV infection is based on interferon-free regimens combining different direct-acting antivirals (DAAs), where the choice of DAA-regimen depends on the viral genotype, previous treatments, and the state of liver fibrosis. With these regimens, equally high virus eradication rates are achievable in patients with compensated liver cirrhosis and in patients without advanced liver disease. In addition, patients with decompensated liver cirrhosis or patients with end-stage renal failure requiring renal replacement therapy, as well as children from an age of 3 years, can be treated safely and highly efficiently with DAA-containing regimens. Physicians should be aware of possible drug interactions of the DAAs with concomitant administered drugs. However, possible interactions can be checked easily online. Although, there is an improvement of prognosis after HCV eradication, patients with advanced liver fibrosis or liver cirrhosis must be included in a lifelong HCC surveillance program.

Viral hepatitis infections are a great burden in children who have received liver transplant. Hepatotropic viruses can cause liver inflammation that can develop into liver graft fibrosis and cirrhosis over the long term. Immunological reactions due to viral hepatitis infections are associated with or can mimic graft rejection, rendering the condition difficult to manage. Prevention strategies using vaccinations are agreeable to patients, safe, cost-effective and practical. Hence, strategies to eliminate viral hepatitis A and B focus mainly on immunization programmes for children who have received a liver transplant. Although a vaccine has been developed to prevent hepatitis C and E viruses, its use is not licensed worldwide. Consequently, eliminating hepatitis C and E viruses mainly involves early detection in children with suspected cases and effective treatment with antiviral therapy. Good hygiene and sanitation are also important to prevent hepatitis A and E infections. Donor blood products and liver grafts should be screened for hepatitis B, C and E in children who are undergoing liver transplantation. Future research on early detection of viral hepatitis infections should include molecular techniques for detecting hepatitis B and E. Moreover, novel antiviral drugs for eradicating viral hepatitis that are highly effective and safe are needed for children who have undergone liver transplantation.

The first guidelines for care of pregnant women carrying the hepatitis C virus (HCV) and their infants were published in 2005 in Japan. Since then, evidence has gradually accumulated worldwide regarding the natural course and treatment of this condition and, especially in recent years, treatment for chronic hepatitis C in adult patients has made great progress. However, the clinical practice policy for children has not been standardized, and new clinical practice guidelines for children with mother-to-child (MTC) transmitted HCV infection have become necessary.

In the development of the current guideline, we requested cooperation from The Japanese Society for Pediatric Infectious Diseases, The Japan Society of Hepatology, and the Japan Society of Obstetrics and Gynecology. The committee members were recommended and approved by each society to participate in developing the guidelines. The guideline was also created in accordance with the Minds Guide for Practice Guideline Development. The statements were prepared by consensus-building using the Delphi method, based on the comprehensively searched academic papers and guidelines. These articles were retrieved through searching the PubMed, Cochrane Library, and the Igaku Chuo Zasshi databases.

Eight clinical questions (CQs) with clinical statements were developed regarding etiology (CQs 1-3), diagnosis (CQs 4 and 5), and treatment (two CQs 6 and 7). In each statement, the consensus rate, evidence level, and recommendation level were determined.

The guidelines will be helpful in the management of children with hepatitis C MTC transmission.

Hepatitis C virus infection is a leading cause of blood-borne hepatitis disease worldwide. Hepatitis C is a silent liver disease that, without treatment, leads to late-onset complications, including chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma, in 10-40% of patients.

This study aimed to review the epidemiology, clinical features, diagnosis, treatment, and prevention of hepatitis C among perinatally exposed children.

Public databases, including MEDLINE and PubMed, and websites from the Centers for Disease Control and Prevention, the Food and Drug Administration, the World Health Organization, and the National Institutes of Health were searched for relevant articles published between 2006 and 2021.

The prevalence of hepatitis C has increased among women of childbearing age in the United States and is associated with risk factors, such as intravenous drug use, health inequities, and low socioeconomic background. Infants born to hepatitis C virus-infected mothers have a 6% risk of vertical transmission, and among those infected, 75% will develop chronic hepatitis C and late complications. However, hepatitis C-exposed infants are frequently lost to follow-up, and those infected have delayed diagnosis and treatment and are at high risk for late-onset complications. Direct- acting antivirals and the establishment of effective treatment guidelines cure hepatitis C virus infections.

Hepatitis C predominantly affects underserved communities. Early screening of mothers and infants is critical for the diagnosis, treatment, and prevention of chronic infections and lateonset complications. New policies are needed to address hepatitis C health care inequities affecting mothers and infants in the United States.

Hepatitis C in children is on the rise due to perinatal transmission from infected mothers, and high-risk practices in adolescents and young adults. Prevalence remains underestimated because children at high risk are often not screened. Treatment has evolved over the past decade with the advent of new drugs, and global elimination is now possible. Direct-acting antiviral combinations are safe and effective, with sustained viral suppression rate >90%, and Food and Drug Administration-approved for children ≥3 years old. Although challenging, efficient screening and treatment of chronic hepatitis C virus early is cost-effective and reduces burden of disease and its complications.

We present the efficacy and safety of 12 weeks of therapy with a fixed dose of ledipasvir/sofosbuvir in 2 teenagers with HIV/hepatitis C virus coinfection. Patient 1 presented with compensated cirrhosis, whereas patient 2 had evidence of previous hepatitis B virus infection. Both patients achieved a sustained virologic response 12 weeks after the end of treatment. No serious adverse effects were reported.

Viral infections are particularly common among children. They often have a mild course, are self-limiting and do not need any specific treatment. However, in some cases, the disease can be severe and lead to permanent disabilities. A variety of antiviral drugs are available for the treatments of certain infectious agents: for instance, acyclovir is used to treat herpes simplex virus encephalitis. Recommendations for flu treatment may change according to the current epidemiological surveillance data, on the basis of which antiviral sensibility can be forecast: recommended drugs for the 2020-21 flu season are oseltamivir, zanamivir, peramivir and baloxavir. Some drugs are used to treat congenital infections, such as valganciclovir and ganciclovir in congenital cytomegalovirus infection. Antiretroviral prophylaxis in newborns from HIV-1 infected mothers must be initiated as soon as possible, with one or more drugs according to therapeutic regimens based on the baby's risk category. According to the most recent guidelines, antiretroviral therapy must be started at diagnosis. Several antiretroviral drugs are available today and approved for use in children, so several combinations can be made. However, out of the 29 antiretroviral drugs approved for adults, only 38% (11/29) are approved for children under the age of two and about 60% (18/29) for children under the age of twelve. Treatment with direct antiviral agents against hepatitis C virus is approved for children over the age of three; it consists in different therapeutic regimens chosen on the basis of the viral genotype (ledipasvir/sofosbuvir for genotypes 1, 4, 5 and 6, sofosbuvir/ribavirin for genotypes 2 and 3, sofosbuvir/velpatasvir and glecaprevir/pibrentasvir for all genotypes) and it has dramatically changed the course of the illness. Many molecules have been studied in order to treat SARS-CoV-2 infection, but only remdesivir seems to play a role in shortening recovery time, although inclusion criteria are very specific and data on the use in children is limited.

Introduction: Sofosbuvir/velpatasvir is a combination of direct-acting antivirals with pangenotypic activity for treatment of chronic hepatitis C virus infection. It was approved in 2020 for use in children aged 6-17 years and in June 2021 by the United States Food and Drug Administration for the age group 3-5 years.Areas covered: A literature search of PUBMED and EMBASE was conducted on April 30th and updated on June 10th. Other citations were identified in references of available literature and from ClinicalTrials.gov. The aim of the present research was to outline and discuss the pharmacokinetics, clinical efficacy, tolerability and safety of sofosbuvir/velpatasvir, exploring its actual and potential use in children and adolescents with chronic hepatitis C virus infection.Expert opinion: Five combinations of direct-acting antivirals, of whom three with pangenotypic activity, are now approved for children. No major differences in efficacy and safety profile have been described. Limited access to treatment still is a major issue, especially in low and middle-income countries.

Coronavirus 2019 disease (COVID-19) has created major impacts on public health. The virus has plagued a large population requiring hospitalization and resource utilization. Knowledge about the COVID-19 virus continues to grow. It can commonly present with gastrointestinal symptoms; initially, this was considered an atypical presentation, which led to delays in care. The pandemic has posed serious threats to the care of anorectal diseases. Urgent surgeries have been delayed, and the care of cancer patients and cancer screenings disrupted. This had added to patient discomfort and the adverse outcomes on healthcare will continue into the future. The better availability of personal protective equipment to providers and standard checklist protocols in operating rooms can help minimize healthcare-related spread of the virus. Telehealth, outpatient procedures, and biochemical tumor marker tests can help with mitigation of anorectal-disease-related problems. There is limited literature about the clinical management of anorectal diseases during the pandemic. We performed a detailed literature review to guide clinicians around management options for anorectal disease patients. We also highlighted the health challenges seen during the pandemic.

Glecaprevir/pibrentasvir (GLE/PIB) has shown high efficacy and safety in chronic HCV-infected adults and adolescents; data in children were limited. DORA part 2 is a phase 2/3, nonrandomized, open-label study evaluating the pharmacokinetics, efficacy, and safety of a pediatric formulation of GLE and PIB in children ages 3 to < 12 years.

Children with chronic HCV infection, genotype 1-6, with or without compensated cirrhosis, were divided into three cohorts by age-cohort 2 (9 to < 12 years), cohort 3 (6 to < 9 years), and cohort 4 (3 to < 6 years)-and given weight-based doses of GLE and PIB for 8, 12, or 16 weeks. Primary endpoints were sustained virologic response at posttreatment week 12 (SVR12) and steady-state exposure; secondary endpoints were rates of persistent viremia, relapse, and reinfection. Safety and laboratory abnormalities were assessed. Final pediatric dosages determined to be efficacious were 250 mg GLE + 100 mg PIB (in children weighing ≥ 30 to < 45 kg), 200 mg GLE + 80 mg PIB (≥ 20 to < 30 kg), and 150 mg GLE + 60 mg PIB (12 to < 20 kg). Of 80 participants enrolled and dosed, 96% (77/80) achieved SVR12. One participant, on the initial dose ratio, relapsed by posttreatment week 4; no participants had virologic failures on the final dose ratio of GLE 50 mg/PIB 20 mg. Two nonresponders prematurely discontinued the study. Most adverse events (AEs) were mild; no drug-related serious AEs occurred. Pharmacokinetic exposures were comparable to those of adults.

A pediatric formulation of GLE/PIB was highly efficacious and well tolerated in chronic HCV-infected children 3 to < 12 years old.