Hepatitis: Rosenthal P

Rook M, Rosenthal P. · Pediatric Gastroenterology, Hepatology and Nutrition, University of California San Francisco, 500 Parnassus Avenue, MU4E, Box 0136, San Francisco, CA 94143, USA. · Curr Gastroenterol Rep. · Pubmed #19166664 No free full text.

Abstract: The etiology of liver disease in childhood varies significantly from its etiology in the adult population. More children with complex diseases are surviving into adulthood, providing challenges to the primary care provider. Adults with pediatric liver disease differ in management, treatment, complications, and extrahepatic considerations. To provide these patients with an optimal transition into the adult health care system, the provider needs a comprehensive knowledge of the common causes of childhood liver disease and their implications and must understand the differences in caring for these patients. This review addresses some of the most common childhood liver diseases, their causes, presentation, evaluation, management, complications, and additional concerns.

Rosenthal P. · University of California, San Francisco, 94143-0136, USA. · J Pediatr Gastroenterol Nutr. · Pubmed #18367947 No free full text.

Abstract: It is becoming increasingly evident that children, like adults, with chronic viral or metabolic liver diseases are at risk for the development of hepatocarcinoma. The aims of this article are to review the risk factors for hepatocarcinoma in chronic viral or metabolic liver disease, outline potential pathogenic mechanisms of hepatocarcinoma, and describe surveillance strategies, clinical evaluation, and management of hepatocarcinoma in children.

Suskind DL, Rosenthal P. · Department of Pediatrics, University of California at San Francisco, 500 Parnassus Avenue, MU E406, Box 0136, San Francisco, CA 94143, USA. · Adolesc Med Clin. · Pubmed #15272262 No free full text.

Abstract: Although less common in childhood, hepatitis B virus (HBV) and hepatitis C virus (HCV) remain the most common causes of chronic hepatitis in the United States and worldwide. Children with chronic HBV or HCV are often asymptomatic, with normal or mildly elevated serum transaminases. Although chronic HBV and HCV are indolent diseases in childhood, they cause significant morbidity and mortality later in life. Because the dreaded complications of chronic HBV and HCV--cirrhosis with liver failure and hepatocellular carcinoma--can be seen in childhood, routine follow-up with a pediatric gastroenterologist or hepatologist is recommended. The most important role of the primary care physician and pediatric gastroenterologist or hepatologist is prevention of chronic viral hepatitis through education and screening programs.

Rosenthal P. · Pediatric Liver Transplant Program, University of California, San Francisco, 94143, USA. · Hepatology. · Pubmed #12500187 No free full text.

Abstract: Hepatitis A is a major public health problem in the United States and other developed countries, largely because decreased natural immunity allows for increased susceptibility. To evaluate the cost-effectiveness of routine vaccination of children, adolescents, and certain high-risk adults against hepatitis A, economic analyses of hepatitis A vaccination were identified through searches of MEDLINE, EMBASE, and BIOSIS (February, 1992, to December, 2001) for studies, reviews, editorials, and letters from peer-reviewed journals published in English, French, German, Italian, or Spanish. Experts were also contacted. Articles conforming to accepted standards of quality for health-economic studies were used to compile data on vaccination of children, and results were synthesized in a narrative review. This review of economic analyses of vaccine use in several developed countries shows cost-effectiveness comparable with that of other vaccines in children and within accepted boundaries for adolescents and high-risk adults.

Comanor L, Minor J, Conjeevaram HS, Roberts EA, Alvarez F, Bern EM, Goyens P, Rosenthal P, Lachaux A, Shelton M, Sarles J, Sokal EM. · Bayer Diagnostics (formerly Chiron Diagnostics), Emeryville, CA 94301, USA. · J Viral Hepat. · Pubmed #10760045 No free full text.

Abstract: To develop prognostic models for identifying children with hepatitis B who are likely to respond to interferon-alpha (IFN-alpha) or to spontaneously seroconvert, we evaluated results of a multinational controlled trial comprising 70 children with chronic hepatitis B who received IFN-alpha and 74 children who did not receive therapy. Prognostic models were developed using SMILES (similarity of least squares), which is a data analysis network that incorporates multidimensional relationships in the clinical data of complex diseases. Commonly collected clinical data included age, gender, serum aminotransferase (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) and hepatitis B virus (HBV) DNA levels, and IFN-alpha dose. Additional data included pretreatment directional information (e.g. increases or decreases in serum aminotransferase and HBV DNA levels), liver biopsy results, race and transmission mode. Using data available prior to initiation of treatment, the SMILES models achieved prospective predictions of 89% for responders, 96% for non-responders, 100% for seroconverters and 93% for non-seroconverters. Although not predictive by themselves, the variables that had the greatest impact on predictions for IFN-alpha response were HBV DNA pretreatment direction, baseline HBV DNA, IFN-alpha dose and gender. The variables that had the greatest impact on predictions for spontaneous seroconversion were ALT pretreatment direction, baseline HBV DNA level, age and AST pretreatment direction. Therefore, these models may be useful in determining, in children with hepatitis B, the likelihood of response to IFN-alpha and spontaneous seroconversion.

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.

Davis AR, Rosenthal P. · Division of Pediatric Gastroenterology, Hepatology and Nutrition, University of California, San Francisco, Calif., USA · Pediatr Rev. · Pubmed #18381479 No free full text.

This publication has no abstract.

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.

Van Effelterre TP, Zink TK, Hoet BJ, Hausdorff WP, Rosenthal P. · GlaxoSmithKline Biologicals, Rixensart, B-1330, Belgium. · Clin Infect Dis. · Pubmed #16779741 No free full text.

Abstract: BACKGROUND: US recommendations issued in 1999 for hepatitis A (HA) childhood immunization varied according to regional HA incidences prior to vaccination. Mathematical models of HA transmission, especially those accounting for herd protection, can be useful in formulating new, highly effective recommendations that could lead to disease elimination. METHODS: A mathematical model of HA transmission was designed to assess the impact of different vaccination strategies on the evolution of HA infection over time in the United States. The model represents HA transmission dynamics and is stratified by age and regions defined in the Advisory Committee for Immunization Practices 1999 recommendations. The model accounts for herd protection and HA importation, using an age-dependent "force of infection" varying over time as a function of the prevalence of subjects with infectious HA. RESULTS: The model predicts a clear benefit of vaccinating all US children at as young an age as possible. Nationwide routine immunization at 1 year of age with 70% coverage would prevent 57% of additional cases during the period 1995-2029, compared with the continuation of the regional strategy of vaccinating children at 2 years of age, as recommended by the Advisory Committee for Immunization Practices in 1999. In contrast, the model also predicts that nationwide routine immunization for children 12 years of age only would result in a 14% increase of HA cases during the period 1995-2029, compared with the number of cases predicted with the regional strategy of the immunization of 2-year-olds. CONCLUSIONS: These findings highlight the importance of accounting for herd protection induced by early childhood HA vaccination. They also support the very recent Advisory Committee for Immunization Practices recommendations for universal HA immunization of 1-year-olds.

Sipe WE, Su M, Posselt A, Kim GE, Quiros JA, Rosenthal P. · Department of Pediatrics, UCSF, San Francisco, CA, USA. · Pediatr Transplant. · Pubmed #16712616 No free full text.

Abstract: This case describes a young girl with Graves' disease, who presented with fulminant hepatic failure 9 months into propylthiouracil (PTU) therapy. Her clinical presentation was consistent with 'probable autoimmune hepatitis,' as defined by the International Autoimmune Hepatitis Group scoring system. Despite discontinuation of PTU and high-dose steroid therapy, she required liver transplantation. Subsequent pathology could not definitively rule out autoimmune hepatitis. PTU is an important cause of drug-related liver failure in children, and clinicians should be mindful that it is frequently used in patients who already have an underlying risk of autoimmune liver disease.

Sanchez R, Rosenthal P, Goldsby R. · Department of Pediatrics, University of California, San Francisco, California 94143-0106, USA. · Pediatr Blood Cancer. · Pubmed #16395686 No free full text.

Abstract: Severe aplastic anemia is a well-recognized complication of fulminant non-A, non-B, and non-C hepatitis requiring orthotopic liver transplantation. The first line of therapy for cure in the treatment of aplastic anemia is a histocompatible bone marrow transplant. Immunosuppressive therapy is also effective if a histocompatible donor is not available. We describe two children who developed severe aplastic anemia following orthotopic liver transplant who achieved bone marrow recovery with a single course of anti-thymocyte globulin, solumedrol, and adjustments to their immunosuppressive therapy for prevention of liver allograft rejection.

Rosenthal P. · University of California, 500 Parnassus Ave, Box 0136 Muy-East, San Francisco, CA 94143 0136, USA. · IDrugs. · Pubmed #16059798 No free full text.

Abstract: The latest advances in hepatology were presented in oral and poster presentations. In order to cover the varying subspecialties, the sessions were divided into various sections including 'Acute Liver Failure and Artificial Liver Support', 'Biliary Tract and Immunologic Liver Diseases', 'Cellular and Molecular Biology', 'Clinical and Experimental Hepatobiliary Surgery', 'Hepatotoxicity and Cell Death', 'Transport and Biliary Physiology', 'Viral Hepatitis', 'Evaluation and Treatment of Biliary Disease', 'Necrosis/Apoptosis', 'Portal Hypertension', 'Blood Flow and Vascular Disorders of Cirrhosis', 'Liver Transplantation', 'Fibrogenesis', 'Hepatocellular Carcinoma', 'Metabolism and Genetic Disease', and 'Public Policy, Epidemiology and Decision Analysis'. Drug therapy focused on treatments for viral hepatitis, autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis, and recurrent viral disease following liver transplant. High dose interferon therapy or various combinations of interferon/ribavirin (ICN Pharmaceuticals Inc) therapy seem to offer the best current therapy for chronic HCV. PEGylated interferon (F Hoffmann-La Roche Ltd) offers hope for treatment and histologic improvement in patients with chronic HCV. Following liver transplantation, combination interferon/ribavirin therapy may also find success, but caution with new potent immunosuppressant monoclonal antibodies is advised. For HBV, intramuscular H-BIG (NABI) appears to be effective and less costly than iv H-BIG administration following liver transplantation. Percutaneous radiofrequency ablation may hold promise over conventional ethanol injection therapy for small hepatocellular carcinoma. Autoimmune hepatitis may respond to tacrolimus therapy whereas budesonide therapy did not provide any advantage to prednisone therapy. For primary biliary cirrhosis, eicosapentate and ursodeoxycholic acid may provide benefit to some patients while silymarin from milk thistle did not provide any additional benefit. In primary sclerosing cholangitis, high dose ursodeoxycholic acid may provide benefit. Ursodeoxycholic acid may also provide benefit for mothers with intrahepatic cholestasis of pregnancy by decreasing pruritus, lowering laboratory values and allowing deliveries to occur closer to term.

Suskind DL, Rosenthal P, Heyman MB, Kong D, Magrane G, Baxter-Lowe LA, Muench MO. · Department of Pediatrics, University of California, San Francisco, USA. · BMC Gastroenterol. · Pubmed #15285784 links to  free full text

Abstract: BACKGROUND: Biliary atresia (BA) is a neonatal cholestatic disease of unknown etiology. It is the leading cause of liver transplantation in children. Many similarities exist between BA and graft versus host disease suggesting engraftment of maternal cells during gestation could result in immune responses that lead to BA. The aim of this study was to determine the presence and extent of maternal microchimerism (MM) in the livers of infants with BA. METHODS: Using fluorescent in situ hybridization (FISH), 11 male BA & 4 male neonatal hepatitis (NH) livers, which served as controls, were analyzed for X and Y-chromosomes. To further investigate MM in BA, 3 patients with BA, and their mothers, were HLA typed. Using immunohistochemical stains, the BA livers were examined for MM. Four additional BA livers underwent analysis by polymerase chain reaction (PCR) for evidence of MM. RESULTS: By FISH, 8 BA and 2 NH livers were interpretable. Seven of eight BA specimens showed evidence of MM. The number of maternal cells ranged from 2-4 maternal cells per biopsy slide. Neither NH specimen showed evidence of MM. In addition, immunohistochemical stains confirmed evidence of MM. Using PCR, a range of 1-142 copies of maternal DNA per 25,000 copies of patients DNA was found. CONCLUSIONS: Maternal microchimerism is present in the livers of patients with BA and may contribute to the pathogenesis of BA.

Jacobs RJ, Rosenthal P, Meyerhoff AS. · Capitol Outcomes Research Inc., 6188 Old Franconia Road, Alexandria, VA 22310, USA; University of California at San Francisco, San Francisco, CA, USA. · Vaccine. · Pubmed #15003653 No free full text.

Abstract: Hepatitis B immunization is provided in many US prison systems. We examined the cost effectiveness of substituting bivalent hepatitis A/B vaccine in this setting, considering regional variation in hepatitis A risks and the potential for disease transmission by former prisoners. Where hepatitis A rates are >200, 100-200, and <100% the national average, declines in hepatitis A treatment costs would offset 137, 88, and 40% of the bivalent vaccine's added cost. In the three regions considered, cost effectiveness would be US$ <0, 2131, and 22,819 per life-year saved, respectively. Prison-based hepatitis A/B immunization would meet accepted standards of cost effectiveness throughout the US.

Rosenthal P. · Division of Pediatric Gastroenterology, Hepatology & Nutrition, University of California, San Francisco, San Francisco, CA, USA. · J Pediatr Gastroenterol Nutr. · Pubmed #12968596 No free full text.

This publication has no abstract.

Renz JF, de Roos M, Rosenthal P, Mudge C, Bacchetti P, Watson J, Roberts JP, Ascher NL, Emond JC. · Department of Surgery, University of California, San Francisco, USA. · Liver Transpl. · Pubmed #11753906 links to  free full text

Abstract: The aim of this retrospective analysis was to evaluate the growth of 96 pediatric liver transplant recipients from February 1988 to June 1999. Inclusion criteria were the following: age younger than 18 years, follow-up longer than 1 year, transplantation for a nontumor indication, and no retransplantation. Linear height and growth velocity SD scores were correlated to age, sex, indication for transplantation, immunosuppression, and graft type. Transplant recipients of all ages and indications and both sexes were growth retarded at transplantation. Recipients aged younger than 24 months showed growth within the first year to achieve a height distribution equal to that of an age-matched population. Posttransplantation growth inversely correlated with height standard score at transplantation. Children older than 2 years at transplantation established new growth curves, but remained growth retarded. As children approached the prepubertal growth acceleration, growth deficits frequently were erased. Transplant recipients with biliary atresia and alpha(1)-antitrypsin deficiency showed increased growth performance compared with those who underwent transplantation for chronic hepatitis or fulminant hepatic failure. Boys were less growth retarded at transplantation and showed improved posttransplantation growth performance versus girls. No correlation to immunosuppression or graft type was identified. We conclude that early transplantation of children who show growth retardation is optimal for restoration of growth potential, whereas delaying transplantation in older children impedes potential growth.

Bahar RJ, Yanni GS, Martín MG, McDiarmid SV, Vargas JH, Gershman GB, Heyman MB, Rosenthal P, Tipton JR, Nanjundiah P, Starr A, Ament ME. · Department of Pediatrics, UCLA School of Medicine, 12-383 MDCC, 10833 Le Conte Avenue, Los Angeles, CA, USA. · Transplantation. · Pubmed #11571445 No free full text.

Abstract: BACKGROUND: Autoimmune hepatitis (AIH) and cryptogenic chronic hepatitis (CCH) are important causes of liver failure in children, frequently necessitating orthotopic liver transplantation (OLT). The aim of this study is to review disease progression and potential differences between subgroups of children with AIH and CCH. METHODS: The medical records of 65 children diagnosed with AIH or CCH between 1980 and 1998 were evaluated. RESULTS: The median age at presentation was 9 years, 8 months (range 4 months-19 years), and the median follow-up period was 8 years (range 3 months-18 years, 10 months). Forty-one patients (63%) were female. Twenty-eight patients were Hispanic, 28 were Caucasian, 8 were African-American, and 1 was Asian. Forty-three patients (66%) were diagnosed with type 1 AIH, 8 (12%) with type 2 AIH, and 14 (22%) with CCH. Forty patients (62%) underwent OLT (51% of those with type 1 AIH, 75% of those with type 2 AIH, and 86% of those with CCH). Thirteen (33%) of the transplanted patients experienced disease recurrence. African-American patients experienced a significantly higher rate of disease recurrence post-OLT than did Hispanic patients. Seven patients (11%) died, two without OLT, and five posttransplantation. CONCLUSIONS: AIH and CCH frequently necessitate OLT in children. CCH is a more aggressive disease than Type 1 AIH among children with these disorders. Ethnicity influences the rate of disease recurrence after liver transplantation.

Comanor L, Minor J, Conjeevaram HS, Roberts EA, Alvarez F, Bern EM, Goyens P, Rosenthal P, Lachaux A, Shelton M, Sarles J, Sokal EM. · Clinical Research Consultant, Palo Alto, California, USA. · J Viral Hepat. · Pubmed #11264734 No free full text.

Abstract: Interferon-alpha (IFN) has been approved as treatment for children with chronic hepatitis B (CHB). The aims of this study were to assess the impact on children's growth of the disease itself and of IFN treatment. The growth of 142 children with CHB (70 IFN-treated, 72 untreated) was monitored for a minimum of one year. Regression analysis models were used to determine which of the variables most affected children's growth. After adjusting for racial differences, the population of 142 children with CHB had a mean baseline height for age percentile of 39 and a mean baseline weight for age percentile of 38, which were significantly different (P < 0.0001) from the 50th percentiles of their respective reference populations. The height for age Z score of untreated children was inversely correlated with serum hepatitis B virus DNA and aspartate aminotransferase levels, and the weight for age Z score was inversely correlated with serum hepatitis B virus DNA levels. While undergoing IFN therapy, children displayed a "U-shaped" growth pattern, such that height for age and weight for age Z scores at 3 or 6 months were lower than scores at baseline or 12 months. In this study the average child with CHB showed compromised growth even in the absence of IFN therapy. During IFN therapy, children's growth was temporarily disrupted.

Rosenthal P, Lightdale JR. · No affiliation provided · Pediatr Rev. · Pubmed #10790485 No free full text.

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Elkayam O, Hassoba HM, Ferrell LD, Garcia-Kennedy R, Gish RG, Wright TL, Laffler T, Traylor D, Hunt G, Rosenthal P. · Department of Pediatrics, University of California, San Francisco, 94143, USA. · Pediatr Res. · Pubmed #10367767 No free full text.

Abstract: The association of GB virus type C (GBV-C) virus and clinical disease is uncertain. The role of GBV-C and (Envelope) E2 antibody in children with liver transplants has not been determined. This study's aim is to examine the prevalence of GBV-C in children with liver transplants, to assess the relationship of GBV-C to posttransplant hepatitis, and to determine the role of E2 antibodies. Sera from 34 children, preliver and postliver transplant, between 1989-1996 were tested for GBV-C (Ribonucleic acid) RNA by the automated Abbott LCx PCR assay. Anti-E2 antibodies were detected by an Abbott immunoassay. Recent posttransplant liver biopsies were examined for hepatitis. The results of the study determined that pretransplant, four children (12%) were GBV-C RNA positive. Posttransplant, 14 (42%) children were GBV-C RNA positive. The GBV-C RNA positive conversion rate was 33% (CI 17.2-55.7%). Patients received blood products from a mean of 68 +/- 34 donors, which correlated with GBV-C acquisition. There was no difference in the incidence (32%versus 36%; p = 0.726) or severity (grade 2.00 versus 0.68; p = 0.126) of posttransplant hepatitis in the liver biopsies of GBV-C RNA negative and/or positive children, respectively. Pretransplant, nine of 32 children were anti-E2 positive. Posttransplant, eight of 32 children were anti-E2 positive, including five children who were anti-E2 positive pretransplant. Of nine children who were anti-E2 positive and GBV-C RNA negative pretransplant, three became GBV-C RNA positive posttransplant. The results of this study conclude that the prevalence of GBV-C infection in children postliver transplantation is high and that blood product transfusions correlate with GBV-C acquisition. Also, no correlation was found between GBV-C RNA and the incidence or severity of posttransplant hepatitis. Finally, E2 antibody presence before transplantation failed to provide complete protection from GBV-C acquisition.

Rosenthal P. · No affiliation provided · N Engl J Med. · Pubmed #15156595 No free full text.

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Rosenthal P. · No affiliation provided · J Pediatr Gastroenterol Nutr. · Pubmed #12487128 No free full text.

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Huang J, Rosenthal P. · No affiliation provided · J Pediatr Gastroenterol Nutr. · Pubmed #10997359 No free full text.

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Rosenthal P. · No affiliation provided · J Pediatr Gastroenterol Nutr. · Pubmed #10941957 No free full text.

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