Chronic hepatitis C remains a global health concern despite substantial advances in antiviral therapy. In Europe, the prevalence of chronic hepatitis C virus (HCV) infection in adults is estimated at approximately 0.5-1% [1], although marked regional variations exist: the Czech Republic is a country with low prevalence (0.5%) [2]. In contrast, epidemiological data in children are limited, and the true prevalence is probably underestimated, as many infected children remain asymptomatic and therefore undiagnosed [3]. In the Czech Republic, in recent years, anti-HCV positivity has been reported in 30-50 children each year, according to the Information System of Infectious Diseases [2, 4].

In the paediatric population, vertical transmission from mother to child represents the predominant route of infection. Available data indicate that approximately 7-12% of children born to mothers with chronic HCV infection acquire the virus through vertical transmission [5]. Parenteral transmission may occur, particularly among adolescents with high-risk behaviour [6]. Most children with chronic HCV infection have a mild clinical course, often presenting with minimal biochemical abnormalities and little or no evidence of advanced fibrosis [3]. As a result, diagnosis frequently relies on targeted screening rather than clinical suspicion.

The introduction of direct-acting antivirals (DAAs) into routine clinical practice has fundamentally changed the management of HCV infection. This represents a major step toward the World Health Organization’s goal of eliminating HCV as a public health threat by 2030 [7]. In children aged ≥ 3 years, approved DAA regimens are well tolerated, achieve sustained virological response (SVR) rates exceeding 95%, and require only short treatment courses [8]. Nevertheless, real-world paediatric data, particularly from Central and Eastern Europe, remain limited.

Beyond clinical considerations, paediatric HCV infection may be associated with significant social challenges. Misconceptions regarding infectivity, concerns about transmission in community settings, and barriers to foster care placement may complicate management and affect the well-being of affected children and their families [9].

The aim of this study was to describe the clinical characteristics, routes of transmission, treatment outcomes, and selected social aspects in a cohort of children with chronic HCV infection managed at a tertiary care centre in the Czech Republic.

This was a single-centre retrospective cohort study including paediatric patients with HCV infection treated between 2019 and 2025. Inclusion criteria were patients aged ≤ 18 years at the time of diagnosis with confirmed HCV infection who received DAA therapy.

Demographic data, presumed route of infection, HCV genotype, laboratory parameters, liver stiffness measurements, social status, treatment regimen and outcomes were collected from medical records. Baseline laboratory evaluation included alanine aminotransferase (ALT), HCV RNA levels, and HCV genotype.

Sustained virological response (SVR12) was defined as undetectable HCV RNA by polymerase chain reaction 12 weeks after completion of therapy. HCV RNA and HCV genotype were assessed by the Roche cobas system (Roche Molecular Systems Inc., Branchburg, NJ, USA) at baseline, at the end of therapy and 12 weeks after the end of treatment.

Liver stiffness measurement (LSM) was performed using vibration-controlled transient elastography (VCTE; FibroScan, Echosens, France) according to the manufacturer’s recommendations to assess liver fibrosis stage. Liver stiffness was expressed in kilopascals (kPa), and fibrosis stages were categorised according to established cut-offs (F2 ≥ 7.1 kPa, F3 ≥ 9.5 kPa, and F4 ≥ 12.5 kPa) [10, 11]. Controlled Attenuation Parameter (CAP, FibroScan, Echosens, France) values were used to assess hepatic steatosis [12, 13].

Patients were treated with either the glecaprevir/pibrentasvir (GLE/PIB) or sofosbuvir/velpatasvir (SOF/VEL) combination. Treatment regimen selection was based on patient age, body weight, and the availability of the drugs on the market at the time of diagnosis. Treatment duration was 8 or 12 weeks, according to contemporary paediatric treatment recommendations [8]. As both regimens used in our cohort are pangenotypic, genotype did not influence treatment selection.

Statistical analysis and ethical statement

Descriptive statistics were used to summarise patient characteristics. Numerical variables are presented as medians and ranges, and categorical data as counts and percentages.

The study was approved by the Ethics Committee of the Institute of Clinical and Experimental Medicine and Thomayer University Hospital in Prague, Czech Republic (ERB approval number 11767/26; G-26-33), and was conducted in accordance with the Declaration of Helsinki. Informed consent was not required under local law because the study was retrospective and used data from which patients’ identifying information had been removed.

Between 2019 and 2025, 16 paediatric patients with chronic HCV initiated therapy (Table 1); 7 of them (43.75%) were male. The median age at treatment initiation was 16 years (range 3-18). The predominant mode of transmission was mother-to-child acquisition in 9 patients (56.25%), followed by intravenous drug use in 6 adolescent patients (37.5%) and an unknown route in 1 patient (6.25%).

Three patients (18.75%) were in foster care, and two adolescents (12.5%) with a history of intravenous drug use were in a youth detention centre at the time of treatment initiation. Ten patients (62.5%) were screened and diagnosed with HCV infection at our centre while their mothers (or both parents) were receiving treatment. Two adolescent children (12.5%) were diagnosed in the youth detention centres, two (12.5%) during a stay in a psychiatric hospital, and two (12.5%) were referred by their attending paediatricians.

None of the patients had significant comorbidities. Baseline ALT levels ranged from 30 to 150 IU/l (median 47 IU/l). Body mass index ranged from 12.8 to 30.5 kg/m². Liver stiffness measurement by VCTE was available in 13 of 16 patients (81.25%) and demonstrated fibrosis stages ranging from F0 to F2. The median liver stiffness was 4.8 kPa (range 3.3-8.7 kPa). The majority of patients had absent or mild fibrosis (F0-F1: 53.8% and 23.1%, respectively), with 23.1% at the F2 stage, and no cases of advanced fibrosis (F3-F4) were detected. Controlled attenuation parameter (CAP) values ranged from 108 to 259 dB/m, with no evidence of severe hepatic steatosis.

HCV genotype analysis was available in all patients. Genotype 3 was the most frequent (n = 8, 50%), followed by genotype 1b (n = 5, 31.3%). Genotype 1a was detected in two patients (12.5%). One additional patient (6.25%) was infected with the mixed genotype 1b/2. Among patients with vertical acquisition, genotypes 3 and 1b were equally represented (4/9 each, 44.4%), while genotype 1a was detected in one case (11.1%). In contrast, genotype 3 predominated among patients with intravenous drug use (5/6, 83.3%).

All patients received direct-acting antiviral therapy. GLE/PIB was administered to 12 patients (75.0%) for 8 weeks, while 4 patients (25.0%) received SOF/VEL for 12 weeks.

The body weight of all 4 patients treated with SOF/VEL was more than 30 kg, and all received the standard SOF/VEL dosage (400 mg/100 mg, respectively). The patients weighing less than 45 kg were given the paediatric GLE/PIB formulation (granules) based on body weight (6 patients); the remaining 6 patients weighing more than 45 kg were given GLE/PIB tablets. All patients achieved undetectable HCV RNA at the end of therapy. SVR12 was achieved in all patients (16/16, 100%).

There were three adverse events reported during treatment in three children (18.75%): fatigue, headache, and a brief relapse of drug use. All three events were classified as mild and resolved: fatigue and headache resolved by the end of therapy, while the relapse of drug use resolved after one week. None of the events led to interruption or cessation of antiviral therapy. No treatment discontinuation or serious adverse events were observed.

Our findings are consistent with previously published paediatric cohorts reporting high sustained virological response rates and good tolerability of DAA therapy [14, 15]. Treatment should not be unnecessarily delayed once eligibility criteria are met; in 1 child, the treatment was postponed for 6 months until the child reached 3 years of age.

In our cohort, genotype 3 was predominant among adolescents with a history of intravenous drug use, whereas genotypes 3 and 1b were equally represented in vertically infected children. This distribution is consistent with the known association of genotype 3 with high-risk behaviour in European populations [16, 17].

Notably, most patients were asymptomatic and had only mildly elevated ALT levels or even near-normal levels. Without targeted testing, many of these children would likely have remained undiagnosed. These findings support the need for enhanced screening in high-risk paediatric populations; testing for HCV infection should be considered in the children of all HCV-positive women initiating antiviral therapy [18].

Although vertical transmission was the predominant route of infection, more than one-third of our patients were adolescents with a history of intravenous drug use. Both vertically infected children and adolescents with a history of intravenous drug use represent socially vulnerable populations requiring targeted medical and social support. Several children were living outside their biological families, in foster care or residential facilities. These findings suggest that, in this cohort, paediatric HCV care involved substantial social challenges in addition to the management of infection. Our experience suggests that, in many cases, social stigma may represent a substantial burden for affected children.

In children born to HCV-infected mothers, testing should follow recommended guidelines [8, 18], as serological testing in early infancy may be misleading due to the persistence of maternal antibodies [18, 19]. A definitive evaluation can be performed later in childhood, before age 3, when antiviral therapy is already approved and may be initiated.

As the prevalence of hepatitis C in children is low, even the clinical trials enrolled only a limited number of participants [20, 21] and the real-world cohorts are also small. Polish authors report their experience with the glecaprevir/pibrentasvir combination in children based on the data from Epiter-2 study [22]. They enrolled 23 paediatric patients, all of whom achieved an SVR12 of 100% in the per-protocol analysis. Treatment tolerance was excellent, with only 2 adverse events (nausea and fatigue). The safety and efficacy of sofosbuvir-based regimens were reported by Pokorska-Śpiewak et al., who presented the results of a cohort of 90 patients [23]. The efficacy was excellent (100% in the per-protocol analysis); one-third of the patients reported adverse events of mild or moderate intensity, most often headache and fatigue. However, none of the patients interrupted treatment. In both of the above-mentioned studies, the number of children lost to follow-up was negligible and also in our group, SVR12 was assessable in all patients. The frequency of adverse events in our cohort was also comparable.

Advanced liver disease in children with HCV is generally rare. In the POLAC project, 12% of children presented with fibrosis ≥ F2 according to the METAVIR score at treatment initiation; three children had liver cirrhosis [23]. In our study, three children (18.75%) had F2 fibrosis; all patients with F2 fibrosis were adolescents, aged 16, 17 and 18 years, with liver stiffness measurements of 8.7, 8.2 and 7.7 kPa, respectively. All three had normalised ALT levels and maintained normal synthetic liver function. The presence of F2 fibrosis in these adolescents highlights the need for screening of children at risk and early treatment initiation.

In the Czech Republic, anti-HCV assessment is an integral part of screening at baby homes when children are placed in foster care if the mother has a history of intravenous drug use. Adolescents with a history of illicit drug use are regularly screened upon admission to psychiatric hospitals: two children in our cohort underwent the full course of their DAA treatment during their stay in the hospital. Our observations, therefore, highlight the importance of addressing the social aspects of paediatric HCV infection. Misconceptions about the risk of transmission may contribute to stigmatisation and may complicate foster care placement. Educational efforts directed toward caregivers, foster families, and social workers may help to reduce unnecessary concerns and anxiety, as the risk of transmission from an infected child through everyday contact is negligible. Furthermore, DAA treatment is short, well tolerated and highly effective.

The principal limitation of this study is its relatively small sample size, which is attributable to the low prevalence of HCV infection in the Czech Republic, especially among children. The retrospective design of the study did not allow for assessing patient-reported outcomes during treatment and the follow-up period. We were also unable to assess the HCV reinfection rate in adolescent patients with a history of intravenous drug use. Although the sample size is limited, this real-world cohort reflects both the clinical outcomes and the social background of HCV-infected children. Our data may help improve the identification and management of HCV-infected children in the Czech Republic.

In conclusion, DAA therapy is highly effective, feasible and well tolerated in children with chronic HCV infection [8]. However, most paediatric patients are asymptomatic, so active case-finding is needed in high-risk populations [18]. Paediatric HCV infection, therefore, remains closely linked to social vulnerability, including that experienced by children in foster care and adolescents with high-risk behaviour [9]. Effective management requires not only antiviral treatment but also multidisciplinary collaboration, involving paediatricians, hepatologists, addiction specialists and social workers [17].

In addition to targeted screening of at-risk children and adolescents, preventive strategies should include improved awareness and early treatment of HCV in young women of reproductive age to minimise vertical transmission and interrupt the intergenerational cycle of infection [24].

The authors thank referring physicians, foster families and social workers for their support.

The study was supported by the project (Ministry of Health, Czech Republic) for the development of research organisation 00023001 (Institute for Clinical and Experimental Medicine, Prague, Czech Republic) – institutional support.

The study was approved by the Bioethics Committee of the Institute of Clinical and Experimental Medicine and Thomayer University Hospital in Prague, Czech Republic (ERB approval number 11767/26; G-26-33).

S.F. has served as speaker and advisor for AbbVie and Gilead Sciences. J.S. has served as speaker and advisor for AbbVie and Gilead Sciences. The other authors declare no conflict of interest.