Change in Health-Related Quality of Life in Youth with Chronic Hepatitis B Living in North America: A 5-Year Cohort Study.

BACKGROUND: Greater hepatitis-related symptomology is associated with lower health-related quality-of-life (HRQoL) among untreated youth with chronic hepatitis B (CHB). How HRQoL changes over time in this population is unknown. METHODS: Children from 7 hepatology centers in North America positive for hepatitis B surface antigen, not taking anti-viral therapy, were enrolled in the Hepatitis B Research Network. A validated self-report HRQoL measure, the Child Health Questionnaire Child Report (CHQ-CF87), was completed annually by participants 10-17 years, with demographic variables, liver disease symptoms, and laboratory tests. Linear mixed-effects models were used to evaluate the 10 CHQ-CF87 subscale scores over 5 years among participants who completed the CHQ-CF87 at least twice. RESULTS: Participants (N = 174) completed the CHQ-CF87 a median of 4 times. Median age was 12 years (interquartile range: 10-14) at baseline; 60% were female, 79% Asian, and 47% adopted. The CHQ-CF87 subscale scores were high at baseline (median range: 75.4-100) and did not differ by time point, except for the Family Activities subscale (mean [95% CI]: 82.3 [79.8-84.8] at baseline; 90.8 [86.1-94.6] week 240). Most subscale scores lacked sufficient individual-level variability in change over time to evaluate predictors. Being White versus Asian predicted a more favorable change in Behavior (6.5 [95% CI: 2.0-11.0]). Older age predicted less favorable change in Mental Health (-0.8 [95% CI: -1.36 to -0.23] per year). Changes in liver enzymes and hepatitis B antigens, DNA, or symptom count were not related to changes in these subscale scores. CONCLUSION: HRQoL was generally good and consistent across 5 years in youth with CHB.

The Epidemiology of Biliary Atresia: Exploring the Role of Developmental Factors on Birth Prevalence.

OBJECTIVE: To identify key epidemiologic factors relevant to fetal development that are associated with biliary atresia. STUDY DESIGN: This population-based registry study examined infants born in Texas between 1999 and 2014. Epidemiologic data relevant to fetal development were compared between cases of biliary atresia identified in the Texas Birth Defects Registry (n = 305) vs all live births (n = 4 689 920), and Poisson regression was used to calculate prevalence ratios (PRs) and 95% CIs. RESULTS: The prevalence of biliary atresia over the study period was 0.65 per 10 000 live births. Biliary atresia was positively associated with female sex (adjusted PR, 1.68; 95% CI, 1.33-2.12), delivery before 32-37 weeks of gestation (adjusted PR, 1.64; 95% CI, 1.18-2.29), delivery before 32 weeks of gestation (adjusted PR, 3.85; 95% CI, 2.38-6.22), and non-Hispanic Black vs non-Hispanic White maternal race/ethnicity (adjusted PR, 1.54, 95% CI, 1.06-2.24), while biliary atresia was inversely associated with season of conception in the fall relative to spring (adjusted PR, 0.62; 95% CI, 0.45-0.86). In addition, biliary atresia was associated with maternal diabetes (adjusted PR, 2.34; 95% CI, 1.57-3.48), with a stronger association with pregestational diabetes compared with gestational diabetes. In subgroup analyses, these associations were present in isolated biliary atresia cases that do not have any additional birth defects. CONCLUSIONS: Biliary atresia is associated with multiple factors related to fetal development, including pregestational maternal diabetes, female sex, and preterm birth. These associations also were observed in isolated cases of biliary atresia without other malformations or laterality defects. Our results are consistent with early life events influencing the pathogenesis of biliary atresia, and support further studies investigating in utero events to better understand etiology and time of onset.

The Inflammatory Cytokine Profile Associated With Liver Damage Is Broader and Stronger in Patients With Chronic Hepatitis B Compared to Patients With Acute Hepatitis B.

Liver damage in hepatitis B is immune driven and correlates with inflammatory markers in patient serum. There is no comparison of these markers to determine if inflammatory profiles are distinct to different types of liver damage across patients at different stages of disease. We measured 25 inflammatory markers in patients with acute hepatitis B and chronic hepatitis B with hepatitis B e antigen seroconversion and chronic patients stopping nucleoside analogue therapy. Myeloid markers dominated the inflammatory profile in all stages of hepatitis B. More inflammatory markers were detectable in chronic patients, including elevated concentrations of cytotoxic effectors Fas ligand, TRAIL, and TNF-α.

Chronic Hepatitis Is Common and Often Untreated Among Children with Hepatitis B Infection in the United States and Canada.

OBJECTIVE: To determine the outcomes of chronic hepatitis B virus (HBV) infection in a large, prospectively studied cohort of children in the US and Canada. STUDY DESIGN: This was a prospective, observational study of children with chronic HBV enrolled in 7 clinical centers and evaluated at baseline, weeks 24 and 48, and annually thereafter, with analysis of demographic, clinical, physical examination, and blood test data. RESULTS: Among 362 children followed for a median of 4.2 years, elevated alanine aminotransferase (ALT) levels (>1 upper limit of normal) were present in 72% at last evaluation, including in 60% of children with loss of hepatitis B e antigen during follow-up and 70% of those who were hepatitis B e antigen negative at baseline. Significant ALT flares (male patients ≥400 U/L, female patients ≥350 U/L) occurred in 13 children. Of 129 children who fulfilled the American Association for the Study of Liver Diseases treatment criteria during follow-up, anti-HBV treatment was initiated in only 25. One child died (unrelated to liver disease), 1 developed cirrhosis, but no episodes of cirrhotic decompensation or hepatocellular carcinoma were observed. Decline in platelet count was inversely associated with ALT elevations. CONCLUSIONS: In a cohort of children with chronic HBV infection in the US and Canada, many children remained at risk of progressive liver disease due to active hepatitis, but major clinical outcomes such as cirrhosis, cancer, and death were rare. Many children who met criteria for treatment remained untreated.

Highly multiplexed 2-dimensional imaging mass cytometry analysis of HBV-infected liver.

Studies of human hepatitis B virus (HBV) immune pathogenesis are hampered by limited access to liver tissues and technologies for detailed analyses. Here, utilizing imaging mass cytometry (IMC) to simultaneously detect 30 immune, viral, and structural markers in liver biopsies from patients with hepatitis B e antigen+ (HBeAg+) chronic hepatitis B, we provide potentially novel comprehensive visualization, quantitation, and phenotypic characterizations of hepatic adaptive and innate immune subsets that correlated with hepatocellular injury, histological fibrosis, and age. We further show marked correlations between adaptive and innate immune cell frequencies and phenotype, highlighting complex immune interactions within the hepatic microenvironment with relevance to HBV pathogenesis.

Impact of COVID-19 on Pediatric Gastroenterology Fellow Training in North America.

BACKGROUND: The COVID-19 pandemic has drastically changed healthcare systems and training around the world. The Training Committee of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition sought to understand how COVID-19 has affected pediatric gastroenterology fellowship training. METHODS: A 21 question survey was distributed to all 77 pediatric gastroenterology fellowship program directors (PDs) in the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition program director database via email on April 7. Responses collected through April 19, 2020 were analyzed using descriptive statistics. RESULTS: Fifty-one of 77 (66%) PDs from the United States, Canada, and Mexico responded to the survey. Forty-six of 51 (90%) PDs reported that they were under a "stay-at-home" order for a median of 4 weeks at the time of the survey. Two of the 51 (4%) programs had fellows participating in outpatient telehealth before COVID-19 and 39 of 51 (76%) at the time of the survey. Fellows stopped participating in outpatient clinics in 22 of 51 (43%) programs and endoscopy in 26 of 51 (52%) programs. Changes to inpatient care included reduced fellow staffing, limiting who entered patient rooms, and rounding remotely. Fellows in 3 New York programs were deployed to adult medicine units. Didactics were moved to virtual conferences in 47 of 51 (94%) programs, and fellows used various online resources. Clinical research and, disproportionately, bench research were restricted. CONCLUSIONS: This report provides early information of the impact of COVID-19 on pediatric fellowship training. Rapid adoption of telehealth and reduced clinical and research experiences were important changes. Survey information may spur communication and innovation to help educators adapt.

Hepatic Histology in Treatment-naïve Children With Chronic Hepatitis B Infection Living in the United States and Canada.

OBJECTIVES: Chronic hepatitis B virus infection is a major cause of morbidity and mortality. The aim of the study is to describe the hepatic histology in children chronically infected with hepatitis B virus living in the United States and Canada. METHODS: Liver biopsies of 134 treatment-naïve children with chronic hepatitis B virus infection were scored for inflammation, fibrosis, and other histological features, and correlated with clinical and laboratory data. RESULTS: Sixty percentage of subjects acquired the infection vertically, 51% were male, and 69% were hepatitis B e antigen-positive at the time of the biopsy. Hepatitis B DNA levels were generally high (mean 7.70 log IU/mL), as was serum alanine aminotransferase (median 120 U/L). Using the Ishak-modified histology activity index scoring system, interface hepatitis was mild in 31%, moderate in 61%, and severe in 6%. Lobular inflammation was mild in 54%, moderate in 29%, and marked in 7%. Portal inflammation was mild in 38% and moderate in 62% of subjects. Eighteen percentage had no fibrosis, 59% had portal expansion without bridging fibrosis, 19% had bridging fibrosis, and 4% had cirrhosis. Alanine aminotransferase positively correlated with inflammation and fibrosis. Neither age, duration of infection, nor Hepatitis B virus DNA levels correlated with fibrosis. Fibrosis-4 index did not correlate with fibrosis but correlated with inflammation. Aspartate aminotransferase/platelet ratio index correlated with both inflammation and fibrosis. CONCLUSIONS: Chronic hepatitis B virus infection results in significant inflammation and fibrosis during childhood. Serum alanine aminotransferase is a strong indicator of the severity and extent of hepatic inflammation and fibrosis.

Phenotypes of Chronic Hepatitis B in Children From a Large North American Cohort.

OBJECTIVE: The aim of the study was to define chronic HBV phenotypes in a large, cohort of United States and Canadian children utilizing recently published population-based upper limit of normal alanine aminotransferase levels (ULN ALT), compared with local laboratory ULN; identify relationships with host and viral factors. BACKGROUND: Chronic hepatitis B virus (HBV) infection has been characterized by phases or phenotypes, possibly associated with prognosis and indications for therapy. METHODS: Baseline enrollment data of children in the Hepatitis B Research Network were examined. Phenotype definitions were inactive carrier: HBeAg-negative with low HBV DNA and normal ALT levels; immune-tolerant: HBeAg-positive with high HBV DNA but normal ALT levels; or chronic hepatitis B: HBeAg-positive or -negative with high HBV DNA and abnormal ALT levels. RESULTS: Three hundred seventy-one participants were analyzed of whom 274 were HBeAg-positive (74%). Younger participants were more likely be HBeAg-positive with higher HBV DNA levels. If local laboratory ULN ALT levels were used, 35% were assigned the immune tolerant phenotype, but if updated ULN were applied, only 12% could be so defined, and the remaining 82% would be considered to have chronic hepatitis B. Among HBeAg-negative participants, only 21 (22%) were defined as inactive carriers and 14 (14%) as HBeAg-negative chronic hepatitis B; the majority (61%) had abnormal ALT and low levels of HBV DNA, thus having an indeterminant phenotype. Increasing age was associated with smaller proportions of HBeAg-positive infection. CONCLUSIONS: Among children with chronic HBV infection living in North America, the immune tolerant phenotype is uncommon and HBeAg positivity decreases with age.

Hepatic Encephalopathy in Children With Acute Liver Failure: Utility of Serum Neuromarkers.

BACKGROUND: Pediatric acute liver failure (PALF) is a public heath burden, often requiring prolonged hospitalization and liver transplantation. Hepatic encephalopathy (HE) is a complication of PALF with limited diagnostic tools to predict outcomes. Serum neurological markers (neuron-specific enolase, S100ß, and myelin basic protein) can be elevated in traumatic or ischemic brain injury. We hypothesized that these neuromarkers would be associated with the development of HE in PALF. METHODS: PALF study participants enrolled between May 2012 and December 2014 by 12 participating centers were the subjects of this analysis. Daily HE assessments were determined by study investigators. Neurological and inflammatory markers were measured using enzyme-linked immunosorbent assay and MILLIPLEX techniques, respectively. To model encephalopathy, these markers were log2 transformed and individually examined for association with HE using a generalized linear mixed model with a logit link and random intercept. RESULTS: Eighty-two children had neurological and inflammatory marker levels and HE assessments recorded, with the majority having assessments for 3 days during their illness. An indeterminate diagnosis (29%) was most common and the median age was 2.9 years. Significant associations were observed for HE with S100ß (odds ratio 1.16, 95% confidence interval [1.03-1.29], P = 0.04) and IL-6 (odds ratio 1.24 [1.11-1.38], P = 0.006). CONCLUSIONS: Serum S100ß and IL-6 are associated with HE in children with PALF. Measuring these markers may assist in assessing neurological injury in PALF, impacting clinical decisions.

Combination of Entecavir/Peginterferon Alfa-2a in Children With Hepatitis B e Antigen-Positive Immune Tolerant Chronic Hepatitis B Virus Infection.

The optimal management strategy for children with immune-tolerant chronic hepatitis B virus (HBV) infection remains unknown. The purpose of this clinical trial was to determine the safety and efficacy of therapy with entecavir and peginterferon in a group of children in the immune-tolerant phase of HBV infection. Children with immune-tolerant features of chronic hepatitis B (CHB) received entecavir once-daily in a dose of 0.015 mg/kg (0.5 mg maximum) for 48 weeks; peginterferon alfa-2a (180 µg/1.73m2 subcutaneously) once-weekly was added at the end of week 8 and continued until week 48. The primary endpoint was lack of detectable hepatitis B e antigen (HBeAg) with HBV DNA levels ≤1,000 IU/mL 48 weeks after stopping therapy. Sixty children (75% female), median age 10.9 (range, 3.4-17.9) years, were enrolled. All were positive for hepatitis B surface antigen (HBsAg) and HBeAg and had high levels of HBV DNA with normal or minimally elevated levels of alanine aminotransferase (ALT). Fifty-five children completed the entire 48-week course of therapy. At 48 weeks after treatment ended (week 96), 2 children (3%) achieved the primary endpoint and were also HBsAg negative and anti-hepatitis B surface antigen antibody (anti-HBs) positive. One child was HBeAg positive but HBsAg negative at week 60; another was HBeAg negative but HBsAg positive at week 72, which were their last clinic visits. In the remaining children, serum ALT and HBV DNA levels at week 96 were similar to baseline. Thirty-seven children experienced adverse events (AEs), and 1 had a serious AE (SAE). Conclusion: The combination of entecavir and peginterferon for up to 48 weeks rarely led to loss of HBeAg with sustained suppression of HBV DNA levels in children in the immune-tolerant phase of HBV infection, and treatment was associated with frequent AEs.

A Learning Collaborative Approach Increases Specificity of Diagnosis of Acute Liver Failure in Pediatric Patients.

BACKGROUND & AIMS: Many pediatric patients with acute liver failure (PALF) do not receive a specific diagnosis (such as herpes simplex virus or Wilson disease or fatty acid oxidation defects)-they are left with an indeterminate diagnosis and are more likely to undergo liver transplantation, which is contraindicated for some disorders. Strategies to facilitate complete diagnostic testing should increase identification of specific liver diseases and might reduce liver transplantation. We investigated whether performing recommended age-specific diagnostic tests (AS-DTs) at the time of hospital admission reduces the percentage PALFs with an indeterminate diagnosis. METHODS: We performed a multinational observational cohort study of 658 PALF participants in the United States and Canada, enrolled at 10 medical centers, during 3 study phases from December 1999 through December 2014. A learning collaborative approach was used to implement AS-DT using an electronic medical record admission order set at hospital admission in phase 3 of the study. Data from 10 study sites participating in all 3 phases were compared before (phases 1 and 2) and after (phase 3) diagnostic test recommendations were inserted into electronic medical record order sets. RESULTS: The percentage of subjects with an indeterminate diagnosis decreased significantly between phases 1-2 (48.0%) and phase 3 (to 30.8%) (P = .0003). The 21-day cumulative incidence rates for liver transplantation were significantly different among phase 1 (34.6%), phase 2 (31.9%), and phase 3 (20.2%) (P = .030). The 21-day cumulative incidence rates for death did not differ significantly among phase 1 (17.9%), phase 2 (11.9%), and phase 3 (11.3%) (P = .20). CONCLUSIONS: In a multinational study of children with acute liver failure, we found that incorporating diagnostic test recommendations into electronic medical record order sets accessed at time of admission reduced the percentage with an indeterminate diagnosis that may have reduced liver transplants without increasing mortality. Widespread use of this approach could significantly enhance care of acute liver failure in children.

Health-related Quality of Life in Pediatric Patients With Chronic Hepatitis B Living in the United States and Canada.

OBJECTIVES: The aim of the study was to determine whether selected sociodemographic and hepatitis B virus (HBV)-specific clinical factors are associated with health-related quality of life (HRQoL) among pediatric patients chronically infected with HBV. METHODS: Children with chronic HBV enrolled in the Hepatitis B Research Network completed the Child Health Questionnaire at study entry. Caregivers of children 5 to <10 years completed the parent-reported form (CHQ-Parent Report Form); youth 10 to <18 years completed the child-reported CHQ-Child Report Form. We examined univariable associations of the Child Health Questionnaire scores with selected independent variables: sex, adoption status, maternal education, alanine aminotransferase (U/L), aspartate aminotransferase-to-platelet ratio index, and HBV-specific symptom count. RESULTS: A total of 244 participants (83 young children 5-<10 years, 161 youth 10-<18 years) were included, all HBV treatment-naïve. Among young children, increased alanine aminotransferase level was negatively associated with CHQ-Parent Report Form psychosocial summary t score (r = -0.28, P = 0.01). No other subscale comparisons for young children were statistically significant. Among youth, adoption was associated with better physical functioning and general health (P < 0.01). Higher maternal education was associated with better role/functioning-physical and -emotional scores (P < 0.05). Maternal education and adoption status were linked with adoption associated with higher maternal education. Increased symptom count in youth was associated with worse HRQoL in subscales measuring bodily pain, behavior, mental health, and self-esteem (P < 0.01). CONCLUSIONS: Although overall HRQoL is preserved in children with chronic HBV, some sociodemographic and HBV-related clinical factors were associated with impaired HRQoL in our pediatric patients at baseline. Measurement of HRQoL can focus resources on education and psychosocial support in children and families most in need.

Long-Term Follow-Up of Children Treated With Peginterferon and Ribavirin for Hepatitis C Virus Infection.

OBJECTIVES: The aim of the study was to describe the 5-year follow-up of children who received peginterferon and ribavirin in a global, open-label study. METHODS: A 5-year follow-up study of 107 children and adolescents ages 3 to 17 years with chronic hepatitis C virus infection who received peginterferon and ribavirin for 24 or 48 weeks. No drugs were administered during follow-up. RESULTS: Ninety-four patients were enrolled in the long-term follow-up portion of the study; the median duration of follow-up was 287 weeks (range, 73-339). Of 63 patients with sustained virologic response who were enrolled, 54 completed 5 years of follow-up; none had relapse in the 5-year follow-up period. Significant decreases in height z scores were observed during treatment. The effect of treatment on height z score was larger in patients treated for 48 weeks compared with those treated for 24 weeks (mean change from baseline to the end of treatment was -0.13 [P < 0.001] and -0.44 [P < 0.001] in the 24- and 48-week treatment groups, respectively). Among patients treated for 24 weeks, full recovery of height z scores to baseline was observed by 1 year of follow-up, whereas only partial recovery was observed during 5 years of follow-up in patients treated for 48 weeks (mean change from baseline to the final follow-up visit was -0.16 (P = NS) and -0.32 (P < 0.05) in the 24- and 48-week treatment groups, respectively). Similar patterns were observed for weight and body mass index z scores. CONCLUSIONS: Impairment of growth should be considered when assessing the risk-benefit profile of peginterferon/ribavirin therapy in children with hepatitis C virus infection. In deciding to treat children with chronic hepatitis C virus, considerations should include both deferring treatment in patients during optimal growth periods, and the possibility that interferon-free regimens may be available to children in the next 5 to 10 years.

Children with Chronic Hepatitis B in the United States and Canada.

OBJECTIVES: To test the hypothesis that children with chronic hepatitis B living in the US and Canada would have international origins and characteristic hepatitis B virus (HBV) genotypes and laboratory profiles. STUDY DESIGN: Clinical characteristics of children enrolled in the Hepatitis B Research Network were collected from 7 US and Canadian centers. RESULTS: Children (n = 343) with an age range of 1.0-17.8 years were enrolled; 78% of the children were Asian, 55% were adopted, and 97% had international origins with either the child or a parent born in 1 of 31 countries. The majority had HBV genotype B (43%) or C (32%), and the remainder had genotype A (5%), D (16%), E (4%), or multiple (<1%). Children with genotype B or C were more likely to be Asian (98% and 96%), more consistently hepatitis B envelope antigen positive (95% and 82%), had higher median HBV DNA levels (8.2 and 8.3 log10 IU/mL), and less frequently had elevated alanine aminotransferase values (43% and 57%) compared with children with other genotypes. The percentage of hepatitis B envelope antigen positivity and of those with HBV DNA ≥6 log10 IU/mL declined with age. CONCLUSIONS: The majority of children in the Hepatitis B Research Network have HBV genotypes that reflect their international origins. Clinical and laboratory data differ substantially by patient age and HBV genotype. Use of these data can help drive the development of optimal strategies to manage and treat children with chronic hepatitis B.

Analysis of viral testing in nonacetaminophen pediatric acute liver failure.

OBJECTIVE: Viral infections are often suspected to cause pediatric acute liver failure (PALF), but large-scale studies have not been performed. We analyzed the results of viral testing among nonacetaminophen PALF study participants. METHODS: Participants were enrolled in the PALF registry. Diagnostic evaluation and final diagnosis were determined by the site investigator and methods for viral testing by local standard of care. Viruses were classified as either causative viruses (CVs) or associated viruses (AVs). Supplemental testing for CV was performed if not done clinically and serum was available. Final diagnoses included "viral," "indeterminate," and "other." RESULTS: Of 860 participants, 820 had at least 1 test result for a CV or AV. A positive viral test was found in 166/820 (20.2%) participants and distributed among "viral" (66/80 [82.5%]), "indeterminate" (52/420 [12.4%]), and "other" (48/320 [15.0%]) diagnoses. CVs accounted for 81/166 (48.8%) positive tests. Herpes simplex virus (HSV) was positive in 39/335 (11.6%) who were tested 26/103 (25.2%) and 13/232 (5.6%) among infants 0 to 6 and >6 months, respectively. HSV was not tested in 61.0% and 53% of the overall cohort and those 0 to 6 months, respectively. Supplemental testing yielded 17 positive, including 5 HSV. CONCLUSIONS: Viral testing in PALF occurs frequently but is often incomplete. The evidence for acute viral infection was found in 20.2% of those tested for viruses. HSV is an important viral cause for PALF in all age groups. The etiopathogenic role of CV and AV in PALF requires further investigation.

Intravenous N-acetylcysteine in pediatric patients with nonacetaminophen acute liver failure: a placebo-controlled clinical trial.

UNLABELLED: N-acetylcysteine (NAC) was found to improve transplantation-free survival in only those adults with nonacetaminophen (non-APAP) acute liver failure (ALF) and grade 1-2 hepatic encephalopathy (HE). Because non-APAP ALF differs significantly between children and adults, the Pediatric Acute Liver Failure (PALF) Study Group evaluated NAC in non-APAP PALF. Children from birth through age 17 years with non-APAP ALF enrolled in the PALF registry were eligible to enter an adaptively allocated, doubly masked, placebo-controlled trial using a continuous intravenous infusion of NAC (150 mg/kg/day in 5% dextrose in water [D5W]) or placebo (D5W) for up to 7 days. The primary outcome was 1-year survival. Secondary outcomes included liver transplantation-free survival, liver transplantation (LTx), length of intensive care unit (ICU) and hospital stays, organ system failure, and maximum HE score. A total of 184 participants were enrolled in the trial with 92 in each arm. The 1-year survival did not differ significantly (P = 0.19) between the NAC (73%) and placebo (82%) treatment groups. The 1-year LTx-free survival was significantly lower (P = 0.03) in those who received NAC (35%) than those who received placebo (53%), particularly, but not significantly so, among those less than 2 years old with HE grade 0-1 (NAC 25%; placebo 60%; P = 0.0493). There were no significant differences between treatment arms for hospital or ICU length of stay, organ systems failing, or highest recorded grade of HE. CONCLUSION: NAC did not improve 1-year survival in non-APAP PALF. One-year LTx-free survival was significantly lower with NAC, particularly among those <2 years old. These results do not support broad use of NAC in non-APAP PALF and emphasizes the importance of conducting controlled pediatric drug trials, regardless of results in adults.

High sustained virologic response rates in children with chronic hepatitis C receiving peginterferon alfa-2b plus ribavirin.

BACKGROUND & AIMS: Pegylated interferon (PEG-IFN) alfa-2b plus ribavirin (RBV) is the standard of care for adults with chronic hepatitis C but was not approved for the treatment of children at the time of this study. The aim of this study was to evaluate the efficacy and safety of PEG-IFN alfa-2b plus RBV in children. METHODS: Children and adolescents ages 3-17 years were treated with PEG-IFN alfa-2b (60microg/m(2)/week) plus RBV (15mg/kg/day). The duration of therapy was 24 weeks for genotype (G) 2 and G3 patients with low viral load (<600,000IU/ml) and 48 weeks for G1, G4, and G3 with high viral load (>or=600,000IU/ml). The primary end point was sustained virologic response (SVR), defined as undetectable hepatitis C virus (HCV) RNA 24 weeks after completion of therapy. RESULTS: SVR was attained by 70 (65%) children. Genotype was the main predictor of response: G1, 53%; G2/3, 93%; G4, 80%. SVRs were similar in younger and older children. Baseline viral load was the main predictor of response in the G1 cohort. No new safety signals were identified, and adverse events (AEs) were generally mild or moderate in severity. Dose was modified because of AEs in 25% of children; 1 child discontinued because of an AE (thrombocytopenia). No serious AEs related to study drugs were reported. CONCLUSION: Therapy with PEG-IFN alfa-2b plus RBV in children and adolescents with chronic hepatitis C offers favorable efficacy, reduced injection frequency, and an acceptable safety profile.