Hepatitis C Virus In Children Research Articles

Updated Clinical Guidelines on the Management of Hepatitis C Infection in Children.

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.

Seroprevalence of hepatitis C virus infection in children: A systematic review and meta-analysis.

Estimates of paediatric hepatitis C virus (HCV) seroprevalence are needed to aid treatment scaling-up, screening and detection approach in this age range, with the ultimate goal of global HCV eradication. The aim of this study was to gather all of the available information on HCV seroprevalence in children all around the world. We searched PubMed, Scopus, Web of Science (WOS), Wiley and EBSCO databases for all studies evaluating HCV seroprevalence in children; however, studies examining seroprevalence in high-risk children or specific groups were excluded. Only 20 articles with 48 963 people met our inclusion criteria, with an overall prevalence of 0.904% and a 95% confidence interval (CI) of 0.543 to 1.355. Seroprevalence was higher in research published prior to 2010 than in those published after 2010 (0.77% vs. 0.53%). Few studies were conducted to assess the seroprevalence of HCV in children worldwide. However, the worldwide pooled seroprevalence of HCV in children in these studies is low (less than 1%).

SNPs of the IFNL favour spontaneous clearance of HCV infection in children.

Both spontaneous and treatment-induced clearance of hepatitis C virus (HCV) in adults have been associated with genetic polymorphisms in the interferon-λ genes. The aim of the present study was to confirm the association between the rs12979860 and evaluate the association between the rs368234815 and the rs4803217 single-nucleotide polymorphisms (SNPs) of the interferon-λ genes and the outcome of the infection in children. Alleles and genotypes frequencies of 32 children, who presented spontaneous clearance of the virus and 135 children, with viral persistence were compared with ethnically matched controls obtained from the 1000 Genomes Project and the International HapMap Project databases. The frequencies of the C/C genotype of rs12979860, the TT/TT of the rs368234815 and the A/C of the rs4803217 were higher in the clearance group than in children with viral persistence (C/C versus T/T + C/T odds ratio (OR): 2.6; 90% confidence intervals (CI): 1.3-5; p = 0.01; TT/TT versus ΔG/TT + ΔG/ΔG OR: 2.8; 90% CI: 1.4-5.5; p = 0.01; and A/A versus A/C OR: 8.3; 90% CI: 1.5-45.9; p = 0.017, respectively) and with the ethnically matched controls. The rs12979860, the rs368234815 and the rs4803217 SNPs are associated with spontaneous clearance of HCV in children. Innate immune system response has a key role in the outcome of vertically acquired HCV infection in children. The rs12979860, the rs368234815 and the rs4803217 SNPs are associated with spontaneous clearance of HCV in children. Interferons-λ activate the Janus kinase-Stat pathway, which in turn induces several interferon-stimulated genes, leading to suppression of HCV replication both in vivo and in vitro.

Cascade of care for children and adolescents with chronic hepatitis C.

Chronic hepatitis C virus (HCV) infection presents a significant global public health burden. In 2015, over 400000 deaths worldwide were attributed to HCV infection. This led the World Health Organization (WHO) in 2016 to set the ambitious goal of eliminating HCV by 2030. Adult-centered guidelines have been established in order to provide direction for healthcare professionals, allowing integration of the newest screening policies and therapeutic strategies into their practices. However, for children and adolescents, HCV is a significant, unrecognized public health problem. HCV infection rates in the United States in women of childbearing age and those who are pregnant have increased in parallel with the rising opioid epidemic. An estimated 29000 women with HCV infection gave birth each year from 2011 to 2014 in the United States, with approximately 1700 of their infants being infected with HCV. Newer HCV-specific therapeutics, namely direct acting antivirals (DAA), has brought a new and highly successful approach to treatment of hepatitis C. Recent studies have confirmed similar levels of effectiveness and safety of DAA therapies in the pediatric population. Thus, an enhanced cascade of care, which should include the population under 18 years of age, can help achieve the WHO goal by focusing on elimination in the youngest populations. This review will present an overview of the natural history, clinical features, and management of HCV in children and adolescents.

Seroprevalence of Hepatitis C in Children Without Identifiable Risk-Factors: A Systematic Review and Meta-Analysis.

Hepatitis C virus (HCV) remains a major public health burden for >30 years since its discovery. It is estimated that >80 million people have been already infected. Direct-acting antiviral (DAA) treatment is now approved for young children over the age of 3 years. Treating children before the development of high-risk behaviors is optimal. Thus, assessing the current epidemiology of HCV in children becomes important and may promote awareness. Articles describing the prevalence of hepatitis C in children, were systematically reviewed. To assess HCV infection prevalence in the general population, studies discussing high-risk groups alone were excluded. Data from 58 studies were analyzed. National data was scarce. An overall prevalence of HCV in children of 0.87% was found, ranging from 0.34% in Europe to 3.02% in Africa. Prevalence of viremic infection is important and data synthesis from available data indicated that HCV viremia was detected in 56.8% of children. The prevalence of HCV according to sex was described in 25 studies but no difference between sexes was detected. HCV prevalence was significantly higher in children older than 10 years (0.97%) when compared to those ages under 10 years old (0.75%, P < 0.001). Considering probable underdiagnosis of HCV infection in children, this information reveals that prevalence is substantial. One may argue that future strategies aiming towards HCV elimination, may need to include antiviral treatment of pre-adolescent children as well.

Comparison of Recommendations for Treatment of Chronic Hepatitis C Virus Infection in Children and Adolescents: A Position Paper of the Federation of International Societies of Pediatric Gastroenterology, Hepatology, and Nutrition.

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. 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. 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. 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.

High Anti-HCV Seroprevalence and Low Performance of ICT Strip in Diagnosing Hepatitis C Virus Infection in Children in Enugu Metropolis

Background:The lack of a vaccine for Hepatitis C virus (HCV) places children at a high risk of contracting the infection. It becomes necessary to accurately diagnose this infection for proper treatment as well as identifying potential risk factors for effective management.Aim:This study was conceived to assess the test performance of the commonly used Immunochromatographic test (ICT) strip and identify the associated clinical manifestations and risk factors of HCV in children in Enugu Metropolis.Method:A cross-sectional study involving randomly selected 270 children below six years of age was conducted in Enugu Nigeria. The subjects were screened for anti-HCV by ICT and Enzyme-Linked Immunosorbent Assay (ELISA) and the demographic, signs and symptoms and risk factors were collected.Results:A total of 50 out of 270 children were positive for anti-HCV with a seropositivity of 18.5%. ICT strip had a very low sensitivity of 38.00% with an accuracy of 88.52% in detecting anti-HCV. The presence of dark urine was associated (p= 0.01) with HCV infection.Conclusion:A seroprevalence of 18.5% of Anti-HCV was found in children below six years old in Enugu metropolis and the performance of ICT in diagnosing HCV infection was poor compared to ELISA.

Increasing Prevalence of Hepatitis C among Hospitalized Children Is Associated with an Increase in Substance Abuse

To evaluate the impact of substance abuse on pediatric hepatitis C virus (HCV) prevalence, we examined geographic and demographic data on inpatient hospitalizations in children with HCV. We examined hospitalizations in children using the Kids' Inpatient Database, a part of the Healthcare Cost and Utilization Project. We identified cases using the International Classification of Diseases, 9th edition, codes for HCV infection during 2006, 2009, and 2012. Nonparametric tests for trend were used to calculate trend statistics. From 2006 to 2012 nationally, the number of hospitalizations of children with HCV increased 37% (2.69 to 3.69 per 10 000 admissions; P < .001). The mean age of children hospitalized was 17.6 years (95% CI, 17.4-17.8). HCV cases among those 19-20 years of age represented 68% of the total HCV diagnoses, with a 54% increase over the years sampled (P < .001 for trend). The burden of HCV in children was highest in whites, those in the lowest income quartile, and in the Northeast and Southern regions of the US (all P < .0001). The prevalence of substance use among children with HCV increased from 25% in 2006 to 41% in 2012 (P < .001). The increases of HCV in hospitalized children are largely in teenagers, highly associated with substance abuse, and concentrated in Northeast and Southern states. These results strongly suggest that public health efforts to prevent and treat HCV will also need to include adolescents.

Treatment of Hepatitis C in Children

The aim of this study is to summarize the state of treatment of hepatitis C virus (HCV) infection in children. The 100 articles on HCV in children from 2011 to 2016 contained only one report of a trial with direct acting antiviral agents (DAAs) and none of these agents are yet FDA-approved for children. Thus, we will focus on issues critical to the understanding of the problem of HCV in the pediatric age group including global epidemiology and natural history, as well as results of treatment with the only agents currently FDA-approved for pediatric use: pegylated interferon alpha 2a or 2b plus ribavirin. In addition, the pediatric trials with DAAs in progress will be described. Standard therapy is indicated for some children with HCV but the majority should await approval of DAAs. An algorithm for management and treatment of subjects <18 years of age at the present time is provided.

Prevalence of hepatitis C Antibody in Human Immunodeficiency Virus infected children

Background: Hepatitis C virus (HCV) is a major public health problem for Human Immunodeficiency virus (HIV) infected population. Both infections share same routes of transmission, and quite often co-exist, with dual infections associated with reciprocal and mutually more rapid progression than either infection alone. Co-infection also adversely impacts on the course and management of both infections. This study was carried out to document the prevalence and determinants of HCV sero-positivity in HIVinfected children.Methodology: A total of 132 HIVinfected children attending the Paediatric Antiretroviral Clinic were recruited as subjects. Another 132 HIV negative children matched for age and sex were recruited as controls. Relevant demographic data was taken from each child. Blood samples were also obtained from each child and from their mothers when available, and assayed for the presence of anti-HCV using a membranebased immune-assay kit.Results: The sero-prevalence of HCV antibodies was 9.8% among HIV-infected children and 3.0% among the controls. This was a statistically significant difference (p = 0.042, Fisher exact). HCV sero-postivity was more frequent in children after 5 years of age in both subjects (92.3%) and controls (100.0%). Injection at patent medicine vendor (PMV) was noted to be the most risky practice leading to HCV in children, with more than thrice the chances of HCV sero-positivity than in those who didn’t receive injections at PMV. Four mothers of the HIV-infected children were co-infected with HCV and none in the control group. All 4 children of these dually infected mothers were also co-infected. Controlling for other factors, children of HIV infected mothers were more than twice as likely to have HCV antibody as children whose mothers were HIV negative (RR = 2.67). Similarly, HCV infected mothers have 12% greater chance of transmitting HCV to their children than noninfected mothers and children delivered vaginally were 1.6 times more likely to have HCV antibody than those delivered via caesarean section.Conclusions: The prevalence of anti-HCV in HIV-infected children is significantly higher than that of HIV uninfected peers. Factors strongly associated with HCV sero -positivity identified are maternal HIV and HCV infections, vaginal delivery and injections at patent medicine vendor.Keywords: HCV; HIV; children

Anti-C1q Antibody as a Predictor of Chronic HCV Genotype 4 Response to Treatment in Egyptian Children

Background: Hepatitis C virus (HCV) infection has been reported to be the most common blood born pathogen all over the world. The prevalence of HCV in children in developed countries ranges between 0.1 and 0.4 %, and is generally lower than in adults. Combinedpegylated interferon and ribavirin is still the only standard of care treatment in spite of its side effects, high costs and low sustained virological response (SVR) rates. Hence, this provides a compelling reason for the identification of biomarker predictors of disease response to treatment. Objective: To evaluate anti-C1q antibody as a predictor of chronic HCV response to treatment with combined pegylated interferon alpha-2b and ribavirin in Egyptian children. Methodology: This study was conducted on forty-four chronic HCV-infected children (Male/Female: 30/14; aged 12.02±3.1 years) from the outpatient clinic, Pediatric Hepatology Department, National Liver Institute, Menoufiya University. They were given combined pegylated interferon alpha-2b (Peg-IFN-α-2b) and ribavirin (RBV) for 48 weeks and a quantitative polymerase chain reaction (PCR) for hepatitis C virus Ribonucleic acid was performed at 12, 24, 48 weeks during treatment and after another 24 weeks post-treatment. Anti-HCV antibody and Real-time PCR for HCV-RNA was performed (the detection limit was 15 IU/mL). Anti-C1q antibodies were performed by enzyme-linked immunosorbent assay (ELISA). Results: Serum levels of Anti-C1q antibodies were significantly higher (P = 0.001) in the Non-responders group (mean = 14.61± 6.749ng/ml) compared to the SVR one (mean = 2.27 ± 3.77ng/ml). No statistically significant difference (P > 0.05) had been found between SVR and Non-responders regarding the age, ALT, viral load, or hepatic necroinflammatory activity and liver fibrosis. Anti-C1q at a cutoff value of9.05ng/ml, had sensitivity and specificity of 84.6% and 75% respectively and 92% positive predictive value. No significant correlation between the serum level of anti-C1q antibodies and the age, sex or HCV viral load, liver enzymes, and the degree of fibrosis and necroinflammatory activity was found (P> 0.05) for all parameters. Conclusion: Anti-C1q could be a good predictor for HCV treatment and should be included in pretreatment laboratory assessment for proper choice of chronic HCV children patients who will benefit from combination therapy.

Polymorphisms in the IFNL3/IL28B gene and hepatitis C: from adults to children.

The purpose of the present review is to summarise the current knowledge on the association between single nucleotide polymorphisms (SNPs) in the interferon L3 (IFNL3) gene and hepatitis C virus (HCV) infection in children. Many studies in adults have demonstrated that genetic variation in IFNL3 is a strong predictor of the virological response in treatment-naive patients with HCV genotype 1 who were treated with Pegylated-IFN-α and ribavirin. Genetic variation in IFNL3 is also associated with the spontaneous clearance of HCV. Thus far, few paediatric studies have explored the association between variations in the IFNL3 gene and either spontaneous or treatment-induced clearance of HCV. The CC genotype of the rs12979860 SNP is associated with the spontaneous clearance of HCV in children independently of HCV genotype. Four paediatric studies have shown that both the CC genotype of the rs12979860 SNP and the TT genotype of the rs8099917 SNP are associated with the treatment-induced (IFN monotherapy and Pegylated-IFN-α and ribavirin association) clearance of HCV, while the rs12980275 SNP did not affect the virological response. The possible role of IFNL3 gene variation as a pre-treatment and on-treatment predictor of virological response in children is highly attractive but still undetermined. Further paediatric studies are needed to evaluate if testing for SNPs in IFNL3, either alone or together with other predictors of response to treatment, could be used to direct treatment strategies, including an avoidance of unnecessary protease inhibitor therapy and the duration of treatment.

PGI36 - The Cost Effectiveness of Peginterferon Alfa and Ribavirin for the Treatment of Hepatitis C in Children and Young People

OBJECTIVES: To assess the cost-effectiveness of peginterferon ?-2a and peginterferon ?-2b in combination with ribavirin compared to best supportive care (BSC), for the treatment of chronic hepatitis C virus (HCV) in children and young people aged 3 to 17 years. METHODS: A Markov state-transition economic model of chronic HCV in children and young people was developed that extrapolated the impact of sustained virological response (SVR) on life expectancy, quality-adjusted life expectancy and lifetime costs. The model was adapted from one previously developed for adults. A systematic review was conducted of the clinical effectiveness of the treatments, and the health related quality of life for patients with hepatitis C. Uncertainty was explored through probabilistic and deterministic sensitivity analyses. RESULTS: Seven studies were identified that were relatively small and of generally poor quality. Estimates of SVR were similar for for peginterferon ?-2a (60%) and peginterferon ?-2b (58%) was similar, whilst the SVR for no treatment was assumed to be zero. From this model, peginterferon alfa (?-2a or ?-2b) in combination with ribavirin was more effective and cheaper than BSC. Sensitivity analyses suggest that the results were generally robust to all changes to the structural assumptions and input parameters. The model results were most sensitive to changes to the discount rate, time horizon, SVR and baseline fibrosis of the cohort. CONCLUSIONS: Treatment of children and young people with peginterferon alfa (?-2a or ?-2b) and ribavirin may be an effective therapy. Peginterferon alfa (?-2a or ?-2b) in combination with ribavirin is cost-effective compared with BSC. However, the available evidence is of poor quality. The views expressed in this paper are those of the authors and do not necessarily represent the views or policies of the UK HTA programme or Department of Health.

Sustained Viral Response Hematological Markers During The Treatment of Chronic Hepatitis C Infection in Children

Dear Editor, We read with interest the paper by Pawlowska et al. (1) and we would like to add some comments. They conducted a retrospective cohort study of children with chronic hepatitis C (CHC) infection who completed treatment with ribavirin (RBV) plus pegylated IFN (peg-IFN) or recombinant IFN, and concluded that a mild decrease in hemoglobin levels , leukocyte and platelet counts during treatment may be the responsible factors for sustained viral response (SVR) induction. One of the interesting data in this paper is the non-discussed main result: SVR was achieved with a non-statistically significant different rate in the two groups of treated children (RBV plus peg-IFN or IFN). In a previous article by Pawlowska et al. (2), the authors concluded that treatment with peg-IFN and RBV was effective, showing the same SVR percentage that appears in the current article, but without comparing it to another group treated with recombinant IFN and RBV. Manns MP et al. (3) and other adult population studies showed that therapy with peg- IFN and RBV was better than monotherapy with IFN or therapy with IFN plus RBV. Current guidelines recommend children are treated for hepatitis C virus (HCV) using the same principles applied in adults. However, few published studies in the pediatric population for HCV treatment assessed the effectiveness of these two treatments. A systematic review of the literature by Hu J et al. (4) found only four randomized controlled trials (RCTs) and 31 non-randomized studies, all involve IFN, peg-IFN, or combinations of these drugs with RBV. The SVR rate could not be directly compared as the populations and interventions differed across studies. Nevertheless, the results were comparable to studies in adults. The therapy must be avoided in children younger than two years of age because of the risk of neurotoxicity. The decision of start therapy time must account for the estimated or known duration of infection, genotype, and degree of fibrosis. On the other hand, the main question discussed in the paper is if the decrease in hematological parameters could be a response marker or simply a side effect. Agreeing with some previous studies (4, 5), anemia during treatment with peg-IFN and RBV in patients with HCV genotype 1 is associated with superior virologic responses. The results show that hemoglobin value, leukocyte and platelet counts decrease in both groups, but hemoglobin level and leukocyte count decrease more in the peg-IFN one. The authors show that the reduction was lower in children who achieved SVR than in those who did not, and peg-IFN had a more marked influence on the decrease in hemoglobin value and leukocyte count. They also suggest that the amount of this decrease could be a marker of beneficial prognosis in children same as in adults and that it may not be indicator for withholding or reducing the dose of IFN. According to the results of this study, it seems reasonable to recommend a close monitoring of different hematological parameters during treatment of children with CHC including IFN plus RBV, as possible side effects and surrogate markers of treatment response. However, according to (4), we conclude that current guidelines for the treatment of HCV in children are based on limited data and further research is needed to define the optimal therapy for HCV in children.

Are we under-diagnosing Hepatitis C in children in Scotland?

<h3>Aim</h3> Hepatitis C virus (HCV) is a major public health problem in Scotland. Under-diagnosis in adults is well recognised, with almost 60% of HCV-infected persons unaware of their status. The epidemiology of HCV in children in Scotland is not well studied. This study aims to compare predicted prevalence of vertically transmitted HCV to actual number of diagnosed cases in children born in Scotland between January 1991 and December 2008. <h3>Methods</h3> A crude model was used to estimate the prevalence of vertically transmitted HCV infection in children born in Scotland 1991-2008: a. Estimated prevalence of maternal HCV infection 0.29% (95% CI 0.23-0.36%) x number of registered births (Jan 1991- Dec 2008) = Number of infants potentially exposed to HCV b. No of infants potentially exposed to HCV x vertical transmission rate (5%) = Total expected number of vertically transmitted HCV-infected infants in Scotland (1991-2008) Estimated maternal seroprevalence was based on published national Scottish neonatal HCV seroprevalence data from 2000. Vertical transmission rate was based on the European Paediatric HCV Network ‘best estimate’ from large European transmission studies. The Health Protection Scotland (HPS) Blood Borne Virus database was used to identify all cases of HCV in children under 16 years diagnosed between January 1991 and December 2010. <h3>Results</h3> Of 1, 040,219 live births in Scotland from Jan 1991- December 2008 an estimated 3017 (range based on 95% CI 2393-3745) were to HCV infected mothers. 151 (120-187) infants were predicted to be infected with HCV. The predicted prevalence rate of vertically transmitted HCV in Scotland was 1.4/10000 (1.1-1.8/10000) live births. The actual number of diagnosed cases in Scottish children born 1991-2008 identified from the HPS database was 57, an observed HCV prevalence rate of 0.5/10000 live births. There was a 62% (52-70%) deficit between predicted and diagnosed cases. <h3>Conclusions</h3> There is a significant deficit between predicted and diagnosed cases of HCV in children in Scotland. This could indicate under-diagnosis. Targeted antenatal screening could potentially identify undiagnosed women and infants at risk of HCV. Large population based paediatric seroprevalence studies are required to establish the true prevalence of HCV in Scotland.

XVIII Latin American Congress

XVIII Latin American Congress

Current treatment options and response rates in children with chronic hepatitis C

Vertical transmission has become the most common mode of transmission of hepatitis C virus (HCV) in children. The rate of perinatal transmission from an HCV-infected mother to her child ranges from 2% to 5% and the prevalence of HCV in children in developed countries ranges between 0.1% and 0.4%. Spontaneous viral clearance seems to be dependent on the genotype and has been reported between 2.4%-25%. For chronically infected patients, treatment with recombinant polyethylene glycol (PEG)-interferon α-2b and daily ribavirin has now been approved as standard treatment for children 2-17 years of age. In five large prospective studies, a total of 318 children and adolescents aged 3-17 years were treated either with subcutaneous PEG-interferon α-2b at a dose of 1-1.5 μg/kg or 60 μg/m² once a week in combination with oral ribavirin (15 mg/kg per day) or PEG-interferon α-2a with ribavirin. Subjects with genotype 1 and 4 received the medication for 48 wk and individuals with genotype 2 and 3 mainly for 24 wk. Overall sustained viral response (SVR) was achieved in 193/318 (60.7%) of treated patients. Stratified for genotype; 120/234 (51%) with genotype 1, 68/73 (93%) with genotype 2/3, and 6/11 (55%) with genotype 4 showed SVR. Relapse rate was between 7.7% and 17%. Overall, treatment was well tolerated; however, notable side effects were present in approximately 20%. According to recent experiences in the treatment of chronic hepatitis C in children and adolescents, a combination of PEG-interferon α with ribavirin has been found to be well tolerated and highly efficacious, particularly in individuals with genotype 2/3. Thus, this treatment can be recommended as standard of care until more effective treatment options will become available for genotype 1 patients.

Chronic hepatitis C in children is a mild and curable liver disease

Hepatitis C virus (HCV) infection is a major health problem orldwide, but children constitute only a small portion of infected atients. HCV transmission can occur through blood transfusion, nd the incidence of HCV infection was very high in children transused before 1990 for treatment of chronic haematological diseases 1] or other diseases that required blood transfusion [2]. Since he introduction of screening for HCV infection, blood transfusions ave become safe in developed countries, and the residual risk is oday very limited. In developed countries, maternal–fetal transmission has ecome themajor risk factor for HCV in children,with an estimated isk of infection ranging from 2% to 6% [3]. The key questions to anaging children with HCV chronic infection are identifying the vailable methods for the staging of the liver fibrosis in children ith chronic HCV infection, assessing the risk of developing cirhosis, and understanding the therapeutic options for curing HCV hronic hepatitis. Percutaneous liver biopsy is still the standardmethod for definng the grade of liver inflammation, and the stage of fibrosis. The se of liver biopsy in children is limited by the risk of complicaions, and by the reluctance, from both children and their parents, o consent to this procedure. However, in the last year, two studes have been published that included children with chronic HCV nfection who had undergone liver biopsy before starting antiviral reatment. Both reported a very low percentage of children with ignificant liver fibrosis. In the study by Sokal et al. [4], more than 5% of 65 children or adolescents included in a trial of treatment ith peginterferon alpha and ribavirin had no fibrosis, or had mild brosis; none of themhad severe fibrosis or cirrhosis. Anothermulicentre, controlled trial [5] reported that only 3 out of 104 children valuated for antiviral treatmenthadhistological evidenceof portal brosis with septa. Recently, non-invasive methods for assessing iver fibrosis, in place of biopsy, have been developed. Amongst hese methods, transient elastography has been applied and studed, mainly in adult patients with chronic HCV. There are few data n stiffness measurement of the liver by FibroScan in children. A tudy performed on 116 children, with amean age of 10 years, con-

Treatment of hepatitis C in children: a systematic review.

BackgroundCurrent guidelines recommend children be treated for hepatitis C virus (HCV) using the same principles applied in adults. There are however few published studies which assess the efficacy and safety of HCV therapy in children.Methodology/Principal FindingsA systematic review of the literature was completed for studies of any design that evaluated HCV therapy in children. The primary outcome was sustained virologic response (SVR), with sub-group analysis of response rates by genotype. There were 4 randomized controlled trials (RCTs) and 31 non-randomized studies, all involving interferon, pegylated interferon (PEG-IFN), or combinations of these drugs with ribavirin. The SVR rate could not be directly compared as the populations and interventions differed across studies. Genotype was not reported or differed substantially from study to study. The overall SVR rate for PEG-IFN and ribavirin ranged from 30 to 100% which is comparable to the rate in adults. Similar to adults, the SVR rates were significantly higher in children with genotype 2 or 3 compared to genotype 1. Adverse effects were primarily flu-like symptoms and neutropenia. There were insufficient data to assess the applicability of the week 12 stop rule (stopping therapy at week 12 if there is less than a 2 log drop in HCV RNA) or the efficacy of shortening therapy to 24 weeks in children with genotype 2 and 3.Conclusions/SignificanceCurrent guidelines for the treatment of HCV in children are based on limited data. Further research is needed to define the optimal therapy for HCV in children.

Hepatitis B and Hepatitis C Seroprevalence in Children Receiving Antiretroviral Therapy for Human Immunodeficiency Virus-1 Infection in China, 2005-2009

Coinfection of hepatitis B virus (HBV) or hepatitis C virus (HCV) may compromise pediatric antiretroviral therapy (ART) in China. In this study, we evaluated the seroprevalence of HBV and HCV in children receiving ART and associated factors. Patients were selected from HIV-1-infected children under age 16 enrolled in China National Pediatric ART Cohort since July 2005. Medical assessments, hepatitis B surface antigen (HBsAg), and anti-HCV antibody serologies, and transaminase levels were obtained for analysis. A total of 53 of 1082 children tested were HBsAg seropositive [4.9%; 95% confidence interval (CI): 3.6% to 6.2%], and 90 of 938 children tested were anti-HCV antibody positive (9.6%; 95% CI: 7.7% to 11.5%). No other serologic assays were performed for HBV detection. Age was associated with HBV coinfection in univariate analysis; older children were more likely to be HBsAg positive. Multivariate analysis revealed that children infected with HIV through transfusion of contaminated blood or blood products were more likely to be anti-HCV antibody positive than those infected with HIV through other routes (adjusted odds ratio = 6.2; 95% CI: 3.3% to 11.7%). The high prevalence of HBV and HCV coinfection in HIV-infected children in China receiving ART demands routine screening for viral hepatitis coinfection, intensive prevention of childhood HBV and HCV transmission, and modification of the management of pediatric HIV infection.