Ribavirin In Children Research Articles

M1790 Pegylated Interferon Alpha-2a and Ribavirin in the Treatment of Children with Chronic Hepatitis C

The introduction of pegylated interferons to replace recombinant ones in the treatment of adult chronic hepatitis C (CHC) patients has increased the efficacy of therapy used and improved the patients' quality of life. This study attempts to evaluate the use of pegylated interferon-alpha-2a with ribavirin in children with CHC. The participants in the study were 26 children (11 girls and 15 boys) aged 12-18 (mean age: 14.5 +1.6) infected with HCV, genotype 1 or 4. Presumed infection period varied between 1 and 12 years. 17 of the children (group I) were treated with pegylated interferon-alpha-2a and ribavirin for 48 weeks. In the remaining 9 children (group II), pegylated interferon was introduced into the ongoing therapy, after 2-8 months of treatment with recombinant interferon, and was continued until week 48. The level of HCV RNA prior to the treatment was between 2.66 x 10^4 and 4.74 x 10^6 (mean: 7.73 x 10^5 + 1.20 x 10^6), and the ALAT activity did not exceed 127 IU/mL (mean: 45 +30 IU/mL). The inflammatory activity was not higher than 2p and fibrosis than 1p, according to the modified Scheuer scale. For the assessment of the early and sustained viral response (EVR and SVR), HCV replication was measured with the use of Real-Time Polymerase Chain Reaction, RT-PCR, (TaqMan Roche). Results EVR was observed in 20 out of 26 children, including 12 from group I and 8 from group II. Sustained response to the treatment, defined as no detectable HCV replication 6 months after the end of the treatment, was seen in 16 out of 26 participating children (61%), 8 from each group. No statistically significant differences in the baseline HCV RNA and ALAT activity were observed between the responders (R) and non-responders (NR). Among the parameters analysed, the factor of crucial importance for good prognosis of response to the treatment appeared to be the presumed infection period: 3.5 + 3.4 vs. 6.5 + 3.4 (p < 0.04) for R and NR patients, respectively. In addition, that period was longer in group I as compared to group II: 5.4 + 3.7 vs. 1.6 + 1.8, respectively (p < 0.02). Adverse reactions were observed, with leucopenia being the predominant one, however, there were no cases that would require a discontinuation of the treatment. Conclusions: Pegylated interferon with ribavirin appears to be an effective and safe therapeutic alternative in children with CHC. Shorter HCV infection period seems to be indicative of a higher treatment efficacy. Further studies are needed to assess the efficacy of treatment in children converted from recombinant interferon to pegylated interferon.

Efficacy and Safety of Peginterferon-α2b and Ribavirin Combination Therapy in Children With Chronic Hepatitis C Infection

Interferon (IFN)-alpha2b plus ribavirin is approved for treatment of hepatitis C in children; however, little is known about efficacy and tolerability of pegylated IFN (PEG-IFN)-alpha2b in this population. The objective of this study was to test the efficacy and safety of PEG-IFN-alpha2b plus ribavirin in children with chronic hepatitis C. Thirty children 3-16 years of age who had detectable hepatitis C virus (HCV) RNA for >or=3 years after exposure and elevated alanine aminotransferase values received PEG-IFN-alpha2b 1.0 microg/kg/wk plus ribavirin 15 mg/kg/d for 24 weeks (genotype 2/3) or 48 weeks (genotype 1/4). The primary endpoint was sustained virologic response (SVR), defined as undetectable HCV RNA (<50 IU/mL) at week 24 of follow-up. SVR was achieved in 50% of patients (3/3 genotype 3; 12/27 genotype 1/4). At week 12, 52% of patients were HCV RNA negative and 72% had a >2 log10 decrease in viral load, compared with baseline; 87% and 71% of these patients, respectively, attained an SVR. Therapy was discontinued in 3 patients as a result of adverse events. No patient required ribavirin dose reduction; PEG-IFN-alpha2b dose was reduced in 23% of patients to manage neutropenia. Combination therapy with PEG-IFN-alpha2b and ribavirin treatment was effective in children with chronic hepatitis C. Virologic status at week 12 identified future responders and nonresponders. PEG-IFN-alpha2b and ribavirin were reasonably well tolerated, with no unexpected or permanent adverse effects. Further studies are needed to identify the optimum treatment regimen for this patient population.

Pathology of chronic hepatitis C in children: Liver biopsy findings in the Peds-C Trial

There is relatively little information in the literature on the histopathology of chronic hepatitis C in children. The Peds-C Trial, designed to test the efficacy and safety of peginterferon alfa-2a and ribavirin in children, provided an opportunity to examine liver biopsies from 121 treatment-naïve children, ages 2 to 16 (mean, 9.8 years) infected with the hepatitis C virus (HCV) and with no other identifiable cause for liver disease, signs of hepatic decompensation, or another significant nonhepatic disease. Liver biopsies were scored for inflammation, fibrosis, steatosis, and other histological features. Inflammation in the biopsy was minimal in 42%, mild in 17%, moderate in 38%, and severe in only 3%. Five had bridging fibrosis, and 2 had cirrhosis. Steatosis was absent in 56%, minimal in 34%, and mild in 10%. Inflammation scores correlated with fibrosis scores, serum alanine aminotransferase levels, and duration of infection, but not with age, body mass index z score, or HCV genotype. Fibrosis scores correlated with inflammation but not with age, HCV genotype, body mass index z score, or steatosis parameters. Steatosis correlated with serum alanine aminotransferase levels and body mass index z scores; overweight children had more fibrosis than the non-overweight. In conclusion, in this cohort of HCV-infected children, inflammation, fibrosis, and steatosis were milder than reported for treatment-naïve adults with chronic hepatitis C, but there were several with bridging fibrosis or cirrhosis. The positive correlation of inflammation with duration of infection and fibrosis and of obesity with fibrosis suggest that children with chronic hepatitis C will be at risk for progressive liver disease as they age and possibly acquire other comorbid risk factors.

Design of the PEDS-C trial: pegylated interferon +/- ribavirin for children with chronic hepatitis C viral infection

PEDS-C is the first multicenter placebo-controlled trial for the treatment of chronic hepatitis C (HCV) in childhood that has ever been conducted in the United States (USA). Establishment of the research team, protocol, administrative infrastructure, and ancillary contributors for the pediatric trial took years of planning. To study the safety and efficacy of pegylated-interferon alpha (PEG-2a) plus ribavirin (RV) with PEG-2a monotherapy in children aged 5 years through 18 years. To assess the health-related quality of life and growth and body composition in children with chronic hepatitis C infection, before, during, and after treatment. Eleven centers of pediatric hepatobiliary clinical research were united in a National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK) funded grant with financial support from the Food and Drug Administration (FDA) and a corporate sponsor to conduct the treatment trial. The most important initial limitation in the design of this complex study was securing the financial support and infrastructural organization, a process that took several years. Challenges faced by the study group included identifying the optimal study design given the limited study population, and determining what ancillary studies could be incorporated into the treatment trial. In this article the process taken to design the study and administrative infrastructure, the lessons learned, and the controversial issues deliberated during the planning process are discussed. The evolution of the study and the considerations taken in the development of the protocol are valuable tools which can be applied to pediatric clinical trials in general.

Adverse effects during the treatment with pegylated interferon and ribavirin in children with chronic hepatitis C

Administration of pegylated interferon-alpha (IFN-alpha) and ribavirin in adults with chronic hepatitis C (CHC) is a recommended therapeutic standard. Nevertheless, this therapeutic regimen rises numerous controversies. The aim of this study was to analyze adverse effects during the treatment with pegylated IFN-alpha and ribavirin in children with CHC. Study group comprised 30 children with CHC, age 8-19 years (mean 13,6 years), 9 girls and 21 boys. All patients were administered two medication therapy with pegylated IFN-alpha-2b in the dose of 1.5 microg/kg of body weight 1x/week subcutaneously and daily oral ribavirin 15 mg/kg of bodyweight for 48 weeks. Blood samples were taken at baseline and every 4 weeks during the whole treatment and 24 weeks of follow-up period. Panel of test included: cellular blood count and smear, ALT activity, bilirubin level. Patients complaints were noticed during every visit. Thyroid hormones and antibodies were checked every 3 months. Children were divided into group A that responded to treatment and group B-nonresponders. Abnormalities in laboratory tests (white blood cells, neutrophils, haemoglobin) were observed mainly during first weeks of treatment. Mean bilirubin level and platelets were normal. Mean ALT normalized during the treatment. After 12-16 weeks of the therapy somatic adverse effects decreased significantly. Administration of pegylated IFN-alpha and ribavirin in children with CHC is related to characteristic adverse effects. Periodical dose reduction was necessary. Although side effects and subjective patient complaints were present, children attended school without difficulties. Constant monitoring is required during the whole treatment.

Early Virological Response in Children with Chronic Hepatitis C Treated with Pegylated Interferon and Ribavirin

Infection with hepatitis C virus (HCV) is widespread worldwide. It is estimated that this problem affects approximately 3% of global population. By introducing weekly doses of pegylated interferon (IFN) alfa in combination with ribavirin, given daily, to chronic hepatitis C (CHC) treatment one can achieve a full inhibition of HCV replication in 54-56% of adult patients. The aim of this study was to examine the relationship between prognostic factors and early virological response (EVR) after combination treatment with peginterferon alfa- 2a or alfa-2b and ribavirin in children with CHC. Twenty-three children with chronic HCV were treated with a combination of peginterferon alfa-2a or alfa-2b once a week and ribavirin twice a day. Assessment included age at the time of infection, the length of infection, HCV genotype, viral load in serum and HCV RNA level in peripheral blood mononuclear cells (PBMCs), alanine aminotransferase (ALT) activity and adherence to therapy. The efficacy endpoint was EVR defined as undetectable HCV RNA in serum or >2 log10 decrease in HCV RNA compared with baseline values. An EVR was achieved in 15 out of 23 patients (65.3%) after 12 weeks of therapy. Lower HCV RNA viral load have positive influence on EVR. HCV RNA presence in PBMCs and lower ALT activity do not influence the achievement of EVR. Oncologic history does not bear any influence on EVR. Adherence to the therapy has an unclear influence on the achievement of EVR in children with CHC.

Response to Pegylated Interferon α-2b and Ribavirin in Children With Chronic Hepatitis C

The purpose of this communication is to report our observations on the treatment of a diverse group of adolescent patients who were chronically infected with hepatitis C and received pegylated interferon and ribavirin. The currently accepted optimal therapy for adults with chronic hepatitis C is weekly injections of pegylated interferon and twice daily oral ribavirin. Information on interferon alone or in combination with ribavirin for chronic hepatitis C in children is limited. There is no published information on pegylated interferon and ribavirin in pediatric patients who previously failed interferon therapy. Ten patients 11 to 18 years old received weekly pegylated interferon and twice daily ribavirin for hepatitis C. Treatment continued for 48 weeks, except for 1 patient with hepatitis C virus type 3a who was treated for 24 weeks and 1 patient who did not complete the course of treatment. The period of observation continued from November 2002 to December 2004. Within this group were 3 pediatric patients who had previously failed interferon therapy for hepatitis C. All but 1 patient had a viral response (no detectable virus) at some time during or after the treatment. Three patients achieved sustained viral response (no detectable virus 6 mo after the therapy). One patient who previously failed interferon therapy was among the sustained responders. In response to treatment with pegylated interferon and ribavirin, children and adolescents with chronic hepatitis C achieve results similar to those seen in adults. Previous antiviral therapy does not preclude positive response to pegylated interferon and ribavirin.

Efficacy and safety of treatment with interferon-α2b plus ribavirin in children with chronic hepatitis C

Efficacy and safety of treatment with interferon-α2b plus ribavirin in children with chronic hepatitis C

Hepatitis C virus (HCV): The burden of the beast

Following its formal debut in 1989, HCV (nee “Non-A, Non-B” virus) has come to be recognized as a major cause of morbidity and mortality in adults – accounting for the bulk of liver transplants in the US. This slowly progressive chronic liver injury is a relatively benign disease in children; HCV requires years of ongoing injury before the end stages of cirrhosis or hepatocellular carcinoma develop. But will the impact of infection acquired in childhood be felt in later years?Most studies of the natural history of HCV infection acquired in early life indicate that while abnormal aminotransferase levels may persist, HCV infection acquired early in life is associated with a slow rate of progression and a favorable outcome during long-term follow-up. For example, 58% of a large group of subjects who acquired HCV via mini-transfusions at birth remained anti-HCV positive at follow-up 35 years later (Hepatology 2004;39:90). However, biopsies performed in these subjects showed no fibrosis in most; marked fibrosis was uncommon. The natural history of perinatally acquired HCV infection is similar. However, because of the concern that long-term complications may develop, HCV infected children are serially monitored and many are being treated despite low rate of success. There are no clear guidelines for either strategy.Jhaveri et al generated a projection model of the impact of HCV acquired in childhood. They estimated that by 2016 the costs associated with screening and monitoring would amount to $200 million. If treatment were chosen, the costs would escalate to an estimated additional $50-100 million.Data will soon become available regarding the effectiveness and safety of peg-interferon monotherapy versus peg-interferon plus ribavirin in children (Hepatology 2004;41:421, www.pedsc.org). This may guide our evidence-based decisions regarding the standard of care in childhood HCV infection. What the study of Jhaveri et al indicate is that the burden of HCV acquired in early life is high and this should stimulate continued research efforts: 1) to develop novel strategies for the treatment of HCV in women of child–bearing age to decrease perinatal transmission, 2) to define appropriate evidence-based, cost-effective screening and monitoring strategies, and 3) to develop more effective and reliable treatment options for children infected with HCV. Following its formal debut in 1989, HCV (nee “Non-A, Non-B” virus) has come to be recognized as a major cause of morbidity and mortality in adults – accounting for the bulk of liver transplants in the US. This slowly progressive chronic liver injury is a relatively benign disease in children; HCV requires years of ongoing injury before the end stages of cirrhosis or hepatocellular carcinoma develop. But will the impact of infection acquired in childhood be felt in later years? Most studies of the natural history of HCV infection acquired in early life indicate that while abnormal aminotransferase levels may persist, HCV infection acquired early in life is associated with a slow rate of progression and a favorable outcome during long-term follow-up. For example, 58% of a large group of subjects who acquired HCV via mini-transfusions at birth remained anti-HCV positive at follow-up 35 years later (Hepatology 2004;39:90). However, biopsies performed in these subjects showed no fibrosis in most; marked fibrosis was uncommon. The natural history of perinatally acquired HCV infection is similar. However, because of the concern that long-term complications may develop, HCV infected children are serially monitored and many are being treated despite low rate of success. There are no clear guidelines for either strategy. Jhaveri et al generated a projection model of the impact of HCV acquired in childhood. They estimated that by 2016 the costs associated with screening and monitoring would amount to $200 million. If treatment were chosen, the costs would escalate to an estimated additional $50-100 million. Data will soon become available regarding the effectiveness and safety of peg-interferon monotherapy versus peg-interferon plus ribavirin in children (Hepatology 2004;41:421, www.pedsc.org). This may guide our evidence-based decisions regarding the standard of care in childhood HCV infection. What the study of Jhaveri et al indicate is that the burden of HCV acquired in early life is high and this should stimulate continued research efforts: 1) to develop novel strategies for the treatment of HCV in women of child–bearing age to decrease perinatal transmission, 2) to define appropriate evidence-based, cost-effective screening and monitoring strategies, and 3) to develop more effective and reliable treatment options for children infected with HCV.

Interferon Alfa-2b in Combination With Ribavirin for the Treatment of Chronic Hepatitis C in Children: Efficacy, Safety, and Pharmacokinetics *

Chronic hepatitis C virus (HCV) infection is usually asymptomatic in children, but significant liver disease may occur. We evaluated the efficacy, safety, and pharmacokinetics of interferon alfa-2b and ribavirin in children with chronic HCV. We determined the optimal ribavirin dose in an initial cohort of a phase 1 study and then subsequently used it, in combination with interferon alfa-2b, in a second cohort of this study and a phase 3 trial. The primary efficacy endpoint in all studies was sustained virological response, defined by undetectable serum HCV RNA 24 weeks after completion of therapy. All efficacy and safety analyses were performed on the intent-to-treat population. Children receiving interferon alfa-2b plus ribavirin 15 mg/kg/d in the phase 1 study had the maximum reduction in serum HCV RNA at treatment weeks 4 and 12 with an acceptable safety profile. This ribavirin dose was selected as optimal and used in all subsequent studies. In all, 46% (54/118) of optimally treated children achieved sustained virological response. Sustained virological response was significantly higher in children with HCV genotype 2/3 (84%) than in those with HCV genotype 1 (36%). Adverse events led to dose modification in 37 (31%) and discontinuation in 8 (7%). Multiple-dose interferon alfa-2b and ribavirin peak and trough concentrations and area-under-the-curve were similar between children and adults. In conclusion, interferon alfa-2b in combination with ribavirin is effective and safe in children with chronic hepatitis C virus.

Safety, efficacy, and pharmacokinetics of interferon alfa-2B plus ribavirin in children with chronic hepatitis C: Deirdre A Kelly Dr, Su K Bunn, Liver Unit, Birmingham Children's Hospital, Birmingham Uk; David Apelian, Andrew Baczkowski, Samir Gupta, Mark Laughlin, Marielle Cohard, Schering Plough Research Institute, Kenilworth, NJ

Safety, efficacy, and pharmacokinetics of interferon alfa-2B plus ribavirin in children with chronic hepatitis C: Deirdre A Kelly Dr, Su K Bunn, Liver Unit, Birmingham Children's Hospital, Birmingham Uk; David Apelian, Andrew Baczkowski, Samir Gupta, Mark Laughlin, Marielle Cohard, Schering Plough Research Institute, Kenilworth, NJ

Peds‐C†

Hepatitis C is a major cause of morbidity and mortality from liver disease in adults, but it is fortunately a rare cause of liver disease in children. In population-based surveys the prevalence of antibody to hepatitis C virus (HCV) in children was found to be 0.2% to 0.4%, from which it is estimated that 60,000 to 100,000 children in the United States are chronically infected with HCV. As in adults, hepatitis C in children occurs largely in high-risk groups. The major risk factor for HCV infection in young children is perinatal exposure from an infected mother. Among adolescents, risk factors also include injection drug use and receipt of blood transfusions or blood products before 1992. Hepatitis C is often mild and minimally progressive during childhood; cases of cirrhosis from hepatitis C have been reported but are rare. Chronic hepatitis C is an uncommon reason for liver transplantation in the pediatric age group, and several prospective as well as cross-sectional studies of hepatitis C in children have documented the rarity of progressive liver disease in this population. Nevertheless, hepatitis C is a concern in pediatrics. While the disease tends to be mild, it is likely to be lifelong, raising concerns about long-term survival and health. In addition, therapy for hepatitis C is most likely to be successful in patients with early disease, before the onset of significant fibrosis or appearance of co-morbid conditions. A child with hepatitis C also must face concerns about infectivity and the possibility of spreading the infection to loved ones and future children. Complicating the issues surrounding hepatitis C in children is the lack of information on the safety and efficacy of current therapies for hepatitis C in the pediatric age group. The combination of standard interferon alfa and ribavirin was recently approved for use in children with chronic hepatitis C who are 3 years and older. However, studies of more current regimens of therapy using peginterferon and ribavirin have not been conducted in adequate numbers of children to make rational decisions regarding therapy. In response to these needs, the National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) in collaboration with the Food and Drug Administration's Office of Orphan Products Development have funded a multicenter, randomized, controlled trial of peginterferon with or without ribavirin in children with chronic hepatitis C (Peds-C). William Balistreri, Children's Hospital Medical Center, Cincinnati, OH Regino Gonzalez-Peralta, University of Florida, Gainesville, FL Barbara Haber, Children's Hospital of Philadelphia, Philadelphia, PA Maureen Jonas, Children's Hospital, Boston, MA Parvathi Mohan, George Washington University, Washington, DC Jean P. Molleston, Indiana University, Indianapolis, IN Karen F. Murray, Children's Hospital and Regional Medical Center, Seattle, WA Michael R. Narkewicz, Children's Hospital, Denver, CO Philip Rosenthal, University of California, San Francisco, CA Lesley Smith, Columbia University Medical Center, New York, NY Zachary Goodman (Pathologist), Armed Forces Institute of Pathology, Washington, DC Patricia Robuck (Project Scientist), NIDDK, Bethesda, MD The design of the study is for 112 children with chronic hepatitis C (ages 5-18 years) to be randomized to receive a 48-week course of peginterferon alfa-2a with either ribavirin or placebo. The dose of peginterferon will be 180 μg/1.73 m2 and that of ribavirin will be 15 mg/kg/d in two divided doses. Therapy will be discontinued at 24 weeks in nonresponders, defined as the persistence of HCV RNA. The primary endpoint is the absence of detectable HCV RNA in serum at least 24 weeks after completion of therapy. Children will have a liver biopsy before treatment, but follow-up biopsies are not planned. Children will be closely monitored. Major ancillary studies in this trial will focus on health-related quality of life, cognitive function, and psychosocial functioning before, during, and after therapy, with plans for long-term follow-up. Also included are measures of growth and development, diet, physical activity, and body composition. Thus, this trial will allow for a careful analysis of both short- and long-term safety and efficacy of peginterferon and ribavirin in children with hepatitis C. Referral of patients for enrollment is encouraged.

Interleukin 6 and 12, Alanine Aminotransferase Activity, and HCV Viral Load in Children with Chronic Hepatitis C Treated with Interferon and Ribavirin

The response to viral infections is mediated through the co-operation of cellular and humoral mechanisms. The aim of this study was to seek the correlation between IL-6 and IL-12 level, HCV viral load, ALT activity during the 48-week treatment with interferon-alpha-2b (IFN-alpha-2b) combined with ribavirin in children with diagnosed CHC and to search their influence on positive response to treatment. The group of 27 children with CHC was enrolled into this study. The children were treated with interferon-alpha and ribavirin in the course of 48-week therapy. The results show that both ALT activity and the viral load at the time of implementation of treatment with IFN-alpha and ribavirin is an important prognostic tool when treating children. It has been shown that the levels of IL-6 do not bear any significant prognostic importance to the implemented therapy, yet the increase of IL-12 levels in the 24th week of the treatment may be of prognostic value and may point out the possible elimination of HCV-RNA.

Children with hepatitis C

An estimated 240,000 children in the United States have antibody to hepatitis C virus (HCV) and 68,000 to 100,000 are chronically infected with HCV. Acute HCV infection is rarely recognized in children outside of special circumstances such as a known exposure from an HCV-infected mother or after blood transfusion. Most chronically infected children are asymptomatic and have normal or only mildly abnormal alanine aminotransferase levels. Although the natural history of HCV infection acquired in childhood seems benign in the majority of instances, the infection takes an aggressive course in a proportion of cases leading to cirrhosis and end-stage liver disease during childhood; the factors responsible for a more aggressive course are unidentified. An optimal approach to management of hepatitis C in children would be prevention, particularly of perinatal transmission, which is now the major cause of new cases of hepatitis C in children. Obstetrical factors may be important determinants of transmission, which, if confirmed, should lead to changes in the care of infected women. Therapy of HCV infection in children is also not well defined. There have been no large randomized, controlled trials of therapy in children with chronic hepatitis C. Small heterogeneous studies of interferon monotherapy have reported sustained virological response rates of 35% to 40%. There are few data regarding the use of combination therapy with interferon and ribavirin in children and no information on the use of peginterferon. Clearly, there are important needs for future epidemiologic and clinical research on hepatitis C in childhood. (Hepatology 2002;36:S173-S178).

Children with hepatitis C.

An estimated 240,000 children in the United States have antibody to hepatitis C virus (HCV) and 68,000 to 100,000 are chronically infected with HCV. Acute HCV infection is rarely recognized in children outside of special circumstances such as a known exposure from an HCV-infected mother or after blood transfusion. Most chronically infected children are asymptomatic and have normal or only mildly abnormal alanine aminotransferase levels. Although the natural history of HCV infection acquired in childhood seems benign in the majority of instances, the infection takes an aggressive course in a proportion of cases leading to cirrhosis and end-stage liver disease during childhood; the factors responsible for a more aggressive course are unidentified. An optimal approach to management of hepatitis C in children would be prevention, particularly of perinatal transmission, which is now the major cause of new cases of hepatitis C in children. Obstetrical factors may be important determinants of transmission, which, if confirmed, should lead to changes in the care of infected women. Therapy of HCV infection in children is also not well defined. There have been no large randomized, controlled trials of therapy in children with chronic hepatitis C. Small heterogeneous studies of interferon monotherapy have reported sustained virological response rates of 35% to 40%. There are few data regarding the use of combination therapy with interferon and ribavirin in children and no information on the use of peginterferon. Clearly, there are important needs for future epidemiologic and clinical research on hepatitis C in childhood.

Management of chronic hepatitis B and C virus infections.

Hepatitis B and C virus (HBV and HCV) infections present an important health problem causing significant morbidity and mortality on a worldwide scale. The younger the subjects infected, the higher the risk predisposing to progression towards chronic infection. Treatment of chronic HBV and HCV infections is aimed at reducing hepatic inflammation and thus improving the symptoms, decreasing the likelihood of long-term sequelae such as hepatocellular carcinoma, and increasing the survival rate. Interferon accelerates the spontaneous course of chronic HBV infection in children with greater disease activity and lower levels of replication. There is limited information on the use of lamivudine and its long-term benefit in children with chronic HBV infection. The response of combination therapy with IFN and ribavirin in children with chronic HCV infection is still under investigation. The long-term clinical and virological effects of various drugs used in chronic HBV and HCV infections on children remain to be evaluated.

Treatment of chronic hepatitis C virus infection in children

Hepatitis C virus (HCV) infection may occur in infants and children, although it is much less common than it is in adults. The main transmission routes include mother-to-infant transmission, use of HCV infected blood products, unsterile needles or syringes and other invasive procedures.The natural course of HCV infection in children is variable: some (20–40%) develop an acute resolving infection and spontaneous regression occurs in approximately one-third of infants of HCV infected mothers before 2 years of age. Approximately 60–80% of HCV infected children develop a chronic infection with varying degrees of activity and fibrosis, mostly mild during childhood. However, the potential risks of liver cirrhosis and hepatoma during later life are obvious.Interferon is the main agent used to treat HCV infection in children. The response to interferon at the end of 4–12 months of therapy ranges from 25–90%. A sustained response was found in 36–56% of children 6–36 months after the end of therapy. The duration of therapy is recommended to be 12 months. At the end of 3 months, an evaluation of the response is indicated in the majority of children, except those with thalassemia, in whom evaluation of response should be conducted at the end of 6 months of therapy.The benefit of other therapies, such as combination therapy with interferon and ribavirin in children with hepatitis C is currently under investigation.

Pediatric critical care physicians' attitudes about guidelines for the use of ribavirin in critically ill children with respiratory syncytial virus pneumonia

To determine the attitude of pediatric critical care physicians concerning the use of ribavirin in children with respiratory syncytial virus lung disease in light of the revised American Academy of Pediatrics practice guidelines. A questionnaire was sent to 145 pediatric critical care doctors in the United States. Seventy-seven percent of questionnaires were returned. The vast majority (91%) of the respondents think that the available literature does not support the Academy's recommendations for the administration of ribavirin to critically ill children with respiratory syncytial virus pneumonia. The largest single group of respondents (42%) does not usually prescribe ribavirin for these patients, but may be persuaded to use it by colleagues or consultants in individual cases. Twenty-six percent of all respondents stated that they do not use ribavirin at any time, even in severely ill patients with documented infection. Twenty-two percent of the respondents say that they will prescribe ribavirin, not because they believe it is efficacious, but because they believe the Academy guidelines compel them to do so as a standard of care. The respondents reported adverse effects of the drug, most notably exacerbations of bronchospasm (92%), far more often than the Academy document asserts. When solicited for general comments, the respondents were frequently concerned that critical care physicians were not involved in the development of the guidelines, the guidelines were based on a paucity of reliable data, and that the guidelines could put them at risk of malpractice litigation should they choose to not use ribavirin. Practice guidelines are increasingly being incorporated into patient care and quality improvement regimens, and it is imperative both that appropriate experts be included in their development, and that they be based on valid scientific data. The pediatric critical care community currently treats most of the severely ill patients with respiratory syncytial virus pneumonia. As a group, they remain unconvinced about the efficacy and safety of this drug, and many pediatricians are concerned about the ramifications of individualizing ribavirin therapy in their patients in light of the revised Academy recommendations.

Safety, tolerance, and pharmacokinetics of systemic ribavirin in children with human immunodeficiency virus infection.

Eleven pediatric patients, aged 1 to 10 years and with symptomatic human immunodeficiency virus infection, were treated with 6 or 10 mg of oral ribavirin per kg of body weight daily for 60 days. Safety and pharmacokinetic parameters were monitored; five children had comprehensive pharmacokinetic evaluations. The children tolerated the drug well, and treatment was not associated with any clinically significant adverse effects. Peak concentrations in plasma of 2.5 and 3.0 microM were reached at 90 min after single oral doses of 6 and 10 mg/kg, respectively. The mean systemic availability of oral ribavirin was 42.3%. After 60 days of ribavirin administration, mean trough concentrations in plasma of 2.6 and 4.1 microM were obtained. Ribavirin penetrated well into the cerebrospinal fluid, achieving 70% of the concentration in plasma at steady state.