Hepatitis: González-Peralta RP

Murray KF, Shah U, Mohan N, Heller S, González-Peralta RP, Kelly D, Chang MH, Mieli-Vergani G, Jara P, Fujisawa T, Anonymous00091. · Hepatobiliary Program, Seattle Children's Hospital and Regional Medical Center, Seattle, WA 98105, USA. · J Pediatr Gastroenterol Nutr. · Pubmed #18664880 No free full text.

This publication has no abstract.

Narkewicz MR, Cabrera R, González-Peralta RP. · Pediatric Liver Center, Section of Pediatric Gastroenterology, Hepatology, and Nutrition, University of Colorado School of Medicine and The Children's Hospital, Denver, Colorado, USA. · Semin Liver Dis. · Pubmed #17682976 No free full text.

Abstract: Chronic hepatitis C virus (HCV) infection is a major global health problem. The incidence of transfusion-related HCV infection has markedly decreased, and perinatal transmission has become the most important route of viral spread in children. Perinatally acquired HCV infection is generally a benign condition, but severe liver disease can occur. Little is known about the risk factors for the progression of liver disease in children, and few well-designed pediatric clinical trials have been conducted. Therefore, the decision to treat (or not) children with this viral pathogen is currently a contentious endeavor. Herein, we describe the virus and its life cycle and summarize our current understanding of the epidemiology and natural history of perinatally acquired infection and review current and future therapy of HCV infection in children.

González-Peralta RP, Langham MR, Andres JM, Mohan P, Colombani PM, Alford MK, Schwarz KB. · Pediatric Hepatology and Liver Transplantation, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, University of Florida College of Medicine, 720 SW 2nd Av, Gainesville, FL 32610-0296, USA. · J Pediatr Gastroenterol Nutr. · Pubmed #19412012 No free full text.

This publication has no abstract.

Shah U, Kelly D, Chang MH, Fujisawa T, Heller S, González-Peralta RP, Jara P, Mieli-Vergani G, Mohan N, Murray KF. · Harvard Medical School Dubai Center, Dubai Health Care City, Dubai, UAE. · J Pediatr Gastroenterol Nutr. · Pubmed #19322053 No free full text.

Abstract: Hepatitis B virus (HBV) infection is a worldwide problem and can cause acute liver failure, acute hepatitis, chronic hepatitis, liver cirrhosis, and liver cancer. In areas of high prevalence such as in Asia, Africa, southern Europe, and Latin America, the hepatitis B surface antigen positive rate ranges from 2% to 20%.In endemic areas, HBV infection occurs mainly during infancy and early childhood. Mother-to-infant transmission accounts for approximately half of the chronic HBV infections. In contrast to infection in adults, HBV infection during early childhood results in a much higher rate of persistent infection and long-term serious complications such as liver cirrhosis and HCC.Three phases of chronic hepatitis B have been identified: the immune-tolerant phase, the immune-active phase, and the inactive hepatitis B phase. These phases of infection are characterized by variations in viral replication, hepatic inflammation, spontaneous clearance, and response to antiviral therapy.The optimal goal of antiviral therapy for chronic HBV infection is to eradicate HBV and to prevent its related liver complications. However, due to the limited effect of available therapies in viral eradication, the goal of treatment is to reduce viral replication, to minimize liver injury, and to reduce infectivity. In this review the current recommendations for monitoring and treating chronic HBV infection in children are reviewed.

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.

Araya CE, Mehta MB, González-Peralta RP, Hunger SP, Dharnidharka VR. · University of Florida College of Medicine, Gainesville, FL, USA. · Pediatr Transplant. · Pubmed #18673359 No free full text.

Abstract: PTLD is an important post-transplant complication. Although PTLD affects kidney allografts after renal transplantation, it has not been reported in native kidneys of other solid organ recipients. Herein, we report a child who underwent an orthotropic liver transplant for cryptogenic cholestatic hepatitis and developed fever, generalized lymphadenopathy, chronic EBV viremia, and lymphatic PTLD. Subsequently, she also developed gross hematuria and nephrotic range proteinuria. Kidney histology revealed EBV-positive mononuclear infiltrates within the renal parenchyma consistent with PTLD. Electron microscopy examination demonstrated subepithelial electron-dense deposits consistent with a membranous glomerulopathy pattern. The PTLD was successfully treated with reduced immunosuppression and cyclic cyclophosphamide, rituximab, and prednisone, but the renal disease progressed to end-stage renal failure within two yr. Repeat kidney histology showed chronic nephropathy and membranous glomerulopathy without PTLD infiltrates or detectable EBV staining, although chronic viremia persisted. To our knowledge, this is the first such child to be reported and highlights the importance of remaining vigilant for renal PTLD even in non-kidney organ recipients.

Murray KF, Rodrigue JR, González-Peralta RP, Shepherd J, Barton BA, Robuck PR, Schwarz KB, Anonymous00127. · Division of Gastroenterology and Nutrition, Department of Pediatrics, University of Washington, Children's Hospital and Regional Medical Center, Seattle, Washington 98105, USA. · Clin Trials. · Pubmed #18042575 No free full text.

Abstract: BACKGROUND: 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. PURPOSE: 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. METHODS: 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. LIMITATIONS: 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. CONCLUSIONS: 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.

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.

González-Peralta RP. · Pediatric Liver Program and Division of Pediatric Gastroenterology, Hepatology and Nutrition, University of Florida, Gainesville, FL 32610-0296, USA. · Pediatr Transplant. · Pubmed #15598340 No free full text.

Abstract: Since the discovery of hepatitis C virus (HCV) in 1989, significant advances have been made in our understanding of this important viral pathogen. Children at risk for HCV infection include recipients of potentially contaminated blood products and organ transplants, and infants born to HCV-infected mothers. Chronic HCV infection is usually asymptomatic in children but active hepatitis, cirrhosis and hepatocellular carcinoma can occur. The development of treatment strategies for chronic hepatitis C in children has directly evolved from clinical trials in adults. Sustained virologic response, defined by undetectable HCV RNA in serum 24 wk after completion of treatment, occurs in approximately 36% of children treated with conventional interferon alone and in about 50% of those given conventional interferon in combination with ribavirin. Pegylated interferon-based treatment regimens are better than those based on conventional interferon in adults but little is known about pegylated interferon in children. Factors associated with a favorable response to antiviral therapy in children are similar to those in adults and include infection with HCV genotype 2 or 3 and low pretreatment serum HCV RNA levels. Treatment related adverse events in children include 'flu-like' syndrome, fatigue, anorexia, weight loss, depression, anemia, leukopenia and thrombocytopenia.

González-Peralta RP, Galasso GJ, Poynard T, Schalm S, Thomas HC, Wright TL. · Department of Pediatrics, University of Florida, Gainesville, USA. · Antiviral Res. · Pubmed #10389652 No free full text.

This publication has no abstract.