Hepatitis: Jonas MM

Jonas MM. · No affiliation provided · Arch Pediatr Adolesc Med. · Pubmed #17283308 No free full text.

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Jonas MM. · No affiliation provided · N Engl J Med. · Pubmed #10486425 No free full text.

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Jonas MM. · Children's Hospital Boston, Center for Childhood Liver Disease, Division of Gastroenterology, Boston, MA 02115, USA. · Liver Int. · Pubmed #19207977 No free full text.

Abstract: Hepatitis B infection during pregnancy presents a unique set of management issues. Aspects of care that must be considered include maternal and fetal effects of hepatitis B, effects of pregnancy itself on the course of hepatitis B infection and its complications, treatment of hepatitis B during pregnancy and prevention of perinatal infection. There are insufficient studies to date regarding these concerns; most are from the Far East, and many have important limitations, but some have yielded valuable data. Pregnant women with acute hepatitis B virus (HBV) infection typically have a course not very different from that in the general adult population, but the risk of transmission of HBV to neonates increases the later in gestation the acute infection occurs. Chronic HBV infection is usually mild in pregnant women, but may flare shortly after delivery. The risk of perinatal transmission is highest in women with high levels of viraemia; this may be a factor in the small but reproducible failure rate of current immunoprophylaxis strategies. Obstetrical policies must be assessed with respect to detection of maternal infection and liver disease, as well as with respect to perinatal transmission risk. In addition to the usual issues of drug efficacy and safety in the affected individuals, effects on the developing fetus must be considered. This paper reviews the current experience in each of these areas, and highlights the need for further investigation into this critical but often underestimated topic.

Jonas MM. · Children's Hospital, and Harvard Medical School, Boston, MA 02115, USA. · J Pediatr Gastroenterol Nutr. · Pubmed #16819403 No free full text.

Abstract: Chronic hepatitis B infection remains a significant health problem worldwide, and acquisition during infancy or childhood causes many of the chronic infections that are responsible for the morbidity associated with this disease. Some children with chronic hepatitis B are candidates for treatment. Two medications are currently licensed for use in children, and it is anticipated that others will be available in the next several years. This article describes rationale for treatment, patient selection and pros and cons of the current and expected therapeutic options.

Elisofon SA, Jonas MM. · Division of Gastroenterology, Children's Hospital Boston, Hunnewell Ground, 300 Longwood Avenue, Boston, MA 02115, USA. · Clin Liver Dis. · Pubmed #16376798 No free full text.

Abstract: A large proportion of chronic hepatitis B virus (HBV) infections are acquired during childhood. Fewer chronic hepatitis C virus (HCV) infections occur in children than in adults, but thousands of children worldwide have this serious infection. Optimal treatment strategies for these chronic infections in children have not been determined, because data on the natural history are limited. Few medications are currently approved for use in this population. This article discusses how chronic viral hepatitis differs in children and adults in epidemiology, natural history, progression of disease, and response to treatment. Treatment options are discussed, including patient selection, specific medications, ongoing studies, and future treatment options.

Broderick A, Jonas MM. · Department of Paediatrics, University College, Dublin, Our Lady's Hospital for Sick Children, Crumlin, Dublin 12, Ireland. · Clin Liver Dis. · Pubmed #15481346 No free full text.

Abstract: Children with hepatitis B infection require management by physicians knowledgeable about the natural history of this disorder and experienced in the treatment of children. Selection of appropriate pediatric patients for treatment will prevent some cases of advanced liver disease later in life. New treatments under development for adults may benefit children as well, once they have been rigorously investigated in the pediatric population. Prevention of new HBV infections is an important part of management in children, and working with public health campaigns will hopefully reduce both vertical and horizontal transmission.

Broderick AL, Jonas MM. · Gastroenterology and Nutrition, Division of Gastroenterology, Department of Medicine, Children's Hospital, Boston, Massachusetts, USA. · Semin Liver Dis. · Pubmed #12616451 No free full text.

Abstract: Childhood hepatitis B virus (HBV) infection presents both medical and public health challenges. Infants who acquire HBV perinatally have up to 90% risk of developing chronic HBV infection. Many HBV-infected children have normal alanine aminotransferase values and minimal chronic hepatitis. Children with chronic HBV infection are usually asymptomatic but may develop chronic liver disease or hepatocellular carcinoma. Both interferon-alfa and lamivudine are available for the treatment of chronic hepatitis B in children, but the optimal treatment of children with chronic HBV infection is evolving as the indications, timing, efficacy, and side effects of the treatments are better understood. Universal infant vaccination has been shown to decrease the frequency of HBV infection and its sequelae. This article addresses aspects of HBV infection that are either unique to or different in children.

Jonas MM. · Division of Gastroenterology, Children's Hospital Boston, MA 02115, USA. · Hepatology. · Pubmed #12407591 No free full text.

Abstract: 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.

Jonas MM. · Department of Pediatrics, Harvard Medical School, and Children's Hospital, Boston, Massachusetts, USA. · Clin Liver Dis. · Pubmed #11685795 No free full text.

Abstract: Hepatitis C infection in children is associated with a unique set of challenges for clinicians and investigators. Although the prevalence of HCV infection is lower in children than in adults, it is important to identify infected children to monitor progression of liver disease and to make appropriate interventions to minimize factors that may exacerbate progression. Identification requires understanding of risk factors important in children, primarily exposure at or near the time of birth. The natural history of this infection in most children is either more benign or significantly prolonged than that of infection acquired in adulthood. Reasons for this difference in natural history must be explored and possibly even exploited in the care of adult patients with HCV infection. Identification of appropriate pediatric candidates for treatment and definition of optimal therapy for these children require ongoing study. Lastly, as perinatal transmission becomes the primary mode of acquisition for new pediatric infections, factors that increase or decrease the likelihood of this transmission must be identified, and effective preventive interventions must be put into practice. There are important differences in the clinical features, natural history, and response to therapy between pediatric and adult patients with HCV infection. Understanding of these differences will allow optimal care for affected children and perhaps better understanding of the pathophysiology and pure natural history of this disease.

Jonas MM. · Division of Gastroenterology, Department of Medicine, Children's Hospital, Boston, Massachusetts, USA. · Clin Liver Dis. · Pubmed #11291255 No free full text.

Abstract: Although HCV infection in children shares some clinical features with that in adults, it is clearly different in several ways. These differences may have important implications for treatment. Some differences, such as milder disease, less frequent extrahepatic manifestations, and fewer comorbid conditions causing progression, argue against aggressive treatment in childhood. Other factors, such as less severe liver disease, shorter disease duration, possibly higher rates of sustained virologic response, and better tolerance of IFN, may be reasons to pursue treatment before advanced hepatic injury occurs. Given the relatively small number of pediatric patients with HCV infection and the gaps in the current understanding of natural history and effects of therapy in these patients, treatment should be undertaken only in clinical trials, so that careful data collection and monitoring can define more precisely the safety and efficacy of IFN therapy in children.

Jonas MM. · Department of Pediatrics, Harvard Medical School, and the Division of Gastroenterology, Children's Hospital, Boston, Massachusetts, USA. · Clin Liver Dis. · Pubmed #11232361 No free full text.

Abstract: The challenge of viral hepatitis has been acknowledged and confronted in the last decade. Significant progress in prevention of infection with HAV and HBV may eradicate these serious infections from the United States and other parts of the world in the coming decades. Application of prophylactic strategies to children will be a major mechanism in accomplishing this task. The quest for potent antiviral medications continues. The next critically important development will be ways to prevent new HCV infections and to treat the millions of already infected individuals at risk for the serious consequences of this disease. For pediatricians, realizing these goals requires a greater understanding of perinatal HCV transmission, use of vaccines for prevention of viral hepatitis, and identification of HCV-infected children who are likely to benefit from new therapeutic strategies as they become available.

Harmatz P, Jonas MM, Kwiatkowski JL, Wright EC, Fischer R, Vichinsky E, Giardina PJ, Neufeld EJ, Porter J, Olivieri N, Anonymous00146. · Children's Hospital & Research Center Oakland, 747 52 Street, Oakland, CA 94609, USA. · Haematologica. · Pubmed #18556414 links to  free full text

Abstract: Antiviral treatment of hepatitis C virus in thalassemia has raised concerns of ribavirin-induced hemolysis and increased iron loading. This study examined the change in liver iron concentration, transfusion requirement, virological response, and iron-related toxicities after pegylated interferon alpha-2a/ribavirin treatment in patients with thalassemia. Median transfusions increased by 44%. However, only 29% (4/14) of patients showed an increase of liver iron concentration > 5mg/g dry wt. and overall liver iron remained stable. One of 4 patients with genotype 2 or 3 demonstrated sustained viral response, compared with 50% with genotype 1 (6/12). No patient developed cardiac, liver or endocrine toxicities, although neutropenia occurred in 52%. The molar efficacy of deferoxamine improved with reduction in liver inflammation on biopsy (p=0.001). In conclusion, antiviral treatment is safe if transfusion requirement, iron toxicities and neutropenia are monitored.

Sokal EM, Kelly DA, Mizerski J, Badia IB, Areias JA, Schwarz KB, Vegnente A, Little NR, Gardener SD, Jonas MM. · Département de Pédiatrie, Cliniques Universitaires St. Luc, Université Catholique de Louvain, Brussels, Belgium. · Hepatology. · Pubmed #16440364 No free full text.

Abstract: One year of lamivudine treatment results in increased hepatitis B e antigen (HBeAg) seroconversion and serum hepatitis B virus (HBV) DNA negativity in children with chronic hepatitis B and high serum alanine aminotransferase concentrations. Two hundred seventy-six children who participated in a 1-year randomized, placebo-controlled study of lamivudine were enrolled in a 24-month, open-label extension. Patients were stratified into two groups based on HBeAg status at week 48 of the previous study: 213 HBeAg-positive children were entered into a treatment arm, and 63 HBeAg-negative children were entered into an observation arm to evaluate durability of HBeAg loss. In the treatment arm, 28 of 133 (21%) children previously treated with lamivudine and 23 of 77 (30%) children who previously received placebo achieved the primary end point: virological response (VR) (HBeAg loss and HBV DNA negativity) at month 24. The incidence of YMDD (tyrosine, methionine, aspartate, aspartate) mutations at month 24 was 64% (66/103) in the children previously treated with lamivudine and 49% (34/70) in those previously treated with placebo. The incidence of VR at month 24 was 5% (5/100) for patients with YMDD mutant HBV and 54% (39/72) for patients without. The durability of response in the observation arm was 89% (48/54) at month 24. In conclusion, further clinical response was seen over the 24-month open-label study period in children who had not initially achieved a VR after 12 months of lamivudine treatment. However, the incidence of YMMD mutations increased over time and resulted in lower response rates. VR was maintained in most patients who had initially responded to lamivudine in the first 12 months.

Hom X, Little NR, Gardner SD, Jonas MM. · Division of Gastroenterology, Children's Hospital Boston, Boston, MA, USA. · Pediatr Infect Dis J. · Pubmed #15131468 No free full text.

Abstract: BACKGROUND: Some children with chronic hepatitis B develop advanced liver disease. Lamivudine, an oral nucleoside, is a therapeutic option. A recent large, multicenter study demonstrated that lamivudine was superior to placebo in eliciting loss of hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) DNA from serum in children (2 to 17 years) treated for 52 weeks. OBJECTIVE: To identify pretreatment factors that predict the likelihood of response to lamivudine in children with chronic hepatitis B infection. STUDY DESIGN: Data from the multicenter trial in 297 children (191 lamivudine, 96 placebo) were analyzed for the effects of baseline factors on the likelihood of responses. These responses included virologic response, defined as loss of HBeAg and HBV DNA, and HBeAg seroconversion, defined as loss of HBeAg and development of antibody to HBeAg. Univariate and multivariate analyses examined the effects of lamivudine treatment, age, gender, race, body weight, body mass index, previous interferon treatment and baseline alanine aminotransferase (ALT), histologic activity index (HAI) score and HBV DNA on the virologic responses. RESULTS: In the univariate analysis higher baseline ALT, higher HAI score and lower HBV DNA level predicted a greater likelihood of virologic responses to lamivudine. In the multivariate model only baseline ALT and HAI score were predictive of responses. There was no effect of age or ethnicity on response. CONCLUSIONS: Children with higher pretreatment ALT and HAI scores are most likely to respond to lamivudine. Age, ethnicity and other factors do not significantly influence the frequency of virologic responses in children with chronic hepatitis B infection.

Jonas MM, Kelley DA, Mizerski J, Badia IB, Areias JA, Schwarz KB, Little NR, Greensmith MJ, Gardner SD, Bell MS, Sokal EM, Anonymous00077. · of Gastroenterology, Children's Hospital, Boston, MA 02115, USA. · N Engl J Med. · Pubmed #12037150 links to  free full text

Abstract: BACKGROUND: Lamivudine therapy is effective for chronic hepatitis B infection in adults. We evaluated the efficacy and tolerability of lamivudine as a treatment for chronic infection with hepatitis B virus (HBV) in children. METHODS: Children with chronic hepatitis B were randomly assigned in a 2:1 ratio to receive either oral lamivudine (3 mg per kilogram of body weight; maximum, 100 mg) or placebo once daily for 52 weeks. The primary end point was virologic response (defined by the absence of serum hepatitis B e antigen and serum HBV DNA) at week 52 of treatment. RESULTS: Of the 403 children screened, 191 were randomly assigned to receive lamivudine and 97 to receive placebo. The rate of virologic response at week 52 was higher among children who received lamivudine than among those who received placebo (23 percent vs. 13 percent, P=0.04). Lamivudine therapy was well tolerated and was also associated with higher rates of seroconversion from hepatitis B e antigen to hepatitis B e antibody, normalization of alanine aminotransferase levels, and suppression of HBV DNA. CONCLUSIONS: In children with chronic hepatitis B, 52 weeks of treatment with lamivudine was associated with a significantly higher rate of virologic response than was placebo.

Rodrigue JR, Balistreri W, Haber B, Jonas MM, Mohan P, Molleston JP, Murray KF, Narkewicz MR, Rosenthal P, Smith LJ, Schwarz KB, Robuck P, Barton B, González-Peralta RP. · The Transplant Center, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. · J Pediatr Gastroenterol Nutr. · Pubmed #19242286 No free full text.

Abstract: OBJECTIVE: Hepatitis C virus (HCV) infection is associated with decreased quality of life (QOL) and neurocognitive dysfunction in adults, but little is known about its impact on children and their caregivers. PATIENTS AND METHODS: We studied the QOL, behavioral, emotional, and cognitive functioning of 114 treatment-naïve children with HCV enrolled in a placebo-controlled, randomized, multisite clinical trial evaluating peginterferon alpha-2a alone or with ribavirin. Baseline assessment included measures of children's QOL, cognitive functioning, behavioral adaptation, and depression. Caregivers' QOL also was assessed. RESULTS: Relative to published normative data, caregivers were more likely to believe that their children's health was poor and would likely worsen (t = 3.93; P < 0.0001), and reported higher concern about their children's health status (t = 6.63; P < 0.0001) and that this concern limited family activities (t = 2.45; P < 0.01); they also viewed their children as having more internalizing behavioral problems (t = 1.98; P < 0.05). Only 2 (2%) children had a score in the clinically depressed range. Children with HCV had worse cognitive functioning than the normative sample but significantly better functioning than children with attention-deficit/hyperactivity disorder. Caregivers' QOL scores did not differ significantly from the normative sample, but infected mothers had lower QOL than noninfected caregivers. Caregivers were highly distressed about their children's medical circumstances. CONCLUSIONS: Although HCV infection, in its early stages, does not lead to global impairment in QOL, cognitive, behavioral, or emotional functioning in children, it is associated with higher caregiver stress and strain on the family system, and it may be associated with some cognitive changes in children.

Jonas MM, Kelly D, Pollack H, Mizerski J, Sorbel J, Frederick D, Mondou E, Rousseau F, Sokal E. · Children's Hospital Boston, Boston, MA 02115, USA. · Hepatology. · Pubmed #18433023 No free full text.

Abstract: This study investigated the efficacy, safety, and pharmacokinetics of adefovir dipivoxil (ADV) in children and adolescents with chronic hepatitis B (CHB). A total of 173 treatment-naive and treatment-experienced children with hepatitis B e antigen (HBeAg)+ CHB were randomized to ADV or placebo. Randomization was stratified by age (2 to <7 years; >7 to <12 years; >12 to <18 years) and prior treatment. Significantly more ADV-treated subjects aged 12 to <18 years achieved the primary efficacy endpoint (serum hepatitis B virus [HBV] DNA <1,000 copies/mL and normal alanine aminotransferase) compared to placebo-treated subjects (23% versus 0%; P = 0.007). In the younger groups, differences between ADV and placebo at the end of blinded treatment were not statistically significant. More ADV-treated subjects had HBeAg seroconversion: 18 of 113 (15.9%) versus three of 57 (5.3%) (but P = 0.051), and more met the combined endpoint of HBeAg seroconversion, HBV DNA <1,000 copies/mL and normal alanine aminotransferase (12/113 versus 0/57; P = 0.009). No subject developed an ADV-associated mutation that has been linked to HBV DNA rebound (that is, mutations rtN236T or rtA181V). ADV plasma concentrations were comparable across groups and within the target range. ADV treatment was well tolerated; no new safety issues were identified. Treatment-related adverse events were reported for 12% of ADV-treated and 10% of placebo-treated subjects. After 48 weeks of ADV treatment, antiviral efficacy in subjects ages 12 to <18 years with HBeAg+ CHB was similar to that observed in a study in adult treatment-naive subjects with HBeAg+ CHB. ADV was not different from placebo in subjects aged 2 to 11 years despite adequate plasma ADV exposure in all three age groups. CONCLUSION: ADV showed significant antiviral efficacy in subjects aged 12 to 17 years with HBeAg+ CHB, but was not different from placebo in subjects aged 2 to 11 years.

Goodman ZD, Makhlouf HR, Liu L, Balistreri W, Gonzalez-Peralta RP, Haber B, Jonas MM, Mohan P, Molleston JP, Murray KF, Narkewicz MR, Rosenthal P, Smith LJ, Robuck PR, Schwarz KB. · Armed Forces Institute of Pathology and Veterans Administration Special Reference Laboratory for Pathology, Washington, DC, USA. · Hepatology. · Pubmed #18167062 No free full text.

Abstract: 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.

Jonas MM, Little NR, Gardner SD, Anonymous00027. · Division of Gastroenterology, Children's Hospital Boston, MA 02115, USA. · J Viral Hepat. · Pubmed #18088241 No free full text.

Abstract: Lamivudine has been demonstrated safe and efficacious in the short term in a large cohort of children with chronic hepatitis B (CHB), but optimal duration of treatment has not been elucidated and limited data on the safety of long-term lamivudine administration have been reported. In addition, the durability of favourable therapeutic outcomes after lamivudine therapy in children has not been well characterized. The aim of this study was to examine the safety of lamivudine and the durability of clinical responses in a group of children who received up to 3 years of treatment for CHB. One hundred and fifty-one children from centres in nine countries who had previously received lamivudine in a large prospective trial were enrolled. During the first year, children had been randomized to either lamivudine or placebo treatment. Subsequently, in a separate extension study, those who remained hepatitis B e antigen (HBeAg) positive were given lamivudine for up to 2 years and those who were HBeAg negative were observed for additional 2 years. Results of these studies have been previously reported. In this study, these children were followed for 2 additional years. Data gathered from medical record review included weight, height, signs and symptoms of hepatitis, alanine aminotransferase (ALT) levels, serologic markers, hepatitis B virus (HBV) DNA levels and serious adverse events (SAEs). Other pharmacological treatments for CHB were allowed according to the practices of individual investigators and were documented. Subjects were divided into two groups for analysis, those who had achieved virological response (VR), defined as HBeAg negative and undetectable HBV DNA by the bDNA assay by the end of the extension study at 3 years, and those who had not. In those who had achieved VR by the end of the extension study, long-term durability of HBeAg seroconversion was 82% and >90% in those who had received lamivudine for 52 weeks and at least 2 years respectively. This compares to 75% for those who had achieved seroconversion after placebo. In those who had not achieved VR by the end of the extension study, an additional 11% did so by the end of the study; they had all received lamivudine in the previous trial, and none had received further treatment during the study. Eight children lost hepatitis B surface antigen during the study and all had received lamivudine at some point during the previous trials. Evaluation of safety data revealed no SAEs related to lamivudine. There was no effect of treatment on weight or height z scores. Clinically benign ALT flares (>10 times normal) were seen in 2% of children. Favourable outcomes from lamivudine treatment of CHB in children are maintained for at least several years after completion of treatment. Up to 3 years of lamivudine treatment is safe in children.

González-Peralta RP, Kelly DA, Haber B, Molleston J, Murray KF, Jonas MM, Shelton M, Mieli-Vergani G, Lurie Y, Martin S, Lang T, Baczkowski A, Geffner M, Gupta S, Laughlin M, Anonymous00039. · Division of Pediatric Gastroenterology, Hepatology and Nutrition, University of Florida, Gainesville, FL 32610, USA. · Hepatology. · Pubmed #16250032 No free full text.

Abstract: 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.

Yuan Q, Jonas MM. · Division of Gastroenterology and Nutrition, Children's Hospital, Boston, Massachusetts 02115, USA. · Curr Opin Gastroenterol. · Pubmed #15703569 No free full text.

Abstract: Advances in the field of pediatric hepatobiliary disease have provided insights into disease mechanisms and offered potential tools for early diagnosis or predicting prognosis of devastating diseases. This review summarizes recent major advances in seven areas in the field of pediatric hepatobiliary disease, including extrahepatic biliary atresia, liver disease and transplantation in cystic fibrosis, growth after liver transplantation, predicting acetaminophen hepatotoxicity, treatment of chronic hepatitis B, hepatocellular carcinoma, and liver disease in neonatal lupus erythematosus.

Razvi S, Schneider L, Jonas MM, Cunningham-Rundles C. · The Department of Medicine, Mount Sinai School of Medicine, New York City, New York 10029, USA. · Clin Immunol. · Pubmed #11726220 No free full text.

Abstract: Physicians in the United States who treat patients with primary immunodeficiency were contacted to identify subjects who had been infected with hepatitis C due to exposure to contaminated intravenous immunoglobulin (IVIg) in 1993-1994. From this survey we gathered information on 58 PCR-positive hepatitis C-infected patients; 37 had CVID, 9 had XLA, 5 were IgG subclass deficient, 4 were antibody deficient with normal immunoglobulin levels, 2 had SCID after BMT, and 1 had B cell linker deficiency. Of the 58 subjects, 30 had been treated with IFN-alpha in combination with ribavirin in 5 cases, and 26 other subjects were not treated. Of those who were treated, 11 (37%) resolved the infection and became PCR-negative; of the 26 who were not treated, 5 (19%) have resolved the infection, outcomes not significantly different. Patients 20 years of age or younger had a significantly better outcome compared to those older than age 20 (P = 0.02). Five subjects of the 58 have had a liver transplantation, a sixth has had two transplants, and 10 (17%) of the group have died. This survey demonstrates the heterogeneity of the clinical outcome in subjects with primary immunodeficiency who contracted hepatitis C due to viral contamination of IVIg.

Jonas MM. · No affiliation provided · J Pediatr Gastroenterol Nutr. · Pubmed #12187308 No free full text.

This publication has no abstract.