Hepatitis: Brown R

Afdhal N, McHutchison J, Brown R, Jacobson I, Manns M, Poordad F, Weksler B, Esteban R. · Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA. · J Hepatol. · Pubmed #18433919 No free full text.

Abstract: Thrombocytopenia (platelet count <150,000/microL) is a common complication in patients with chronic liver disease (CLD) that has been observed in up to 76% of patients. Moderate thrombocytopenia (platelet count, 50,000/microL-75,000/microL) occurs in approximately 13% of patients with cirrhosis. Multiple factors can contribute to the development of thrombocytopenia, including splenic platelet sequestration, bone marrow suppression by chronic hepatitis C infection, and antiviral treatment with interferon-based therapy. Reductions in the level or activity of the hematopoietic growth factor thrombopoietin (TPO) may also play a role. Thrombocytopenia can impact routine care of patients with CLD, potentially postponing or interfering with diagnostic and therapeutic procedures including liver biopsy, antiviral therapy, and medically indicated or elective surgery. Therapeutic options to safely and effectively raise platelet levels could have a significant effect on care of these patients. Several promising novel agents that stimulate TPO and increase platelet levels, such as the oral platelet growth factor eltrombopag, are currently in development for the prevention and/or treatment of thrombocytopenia. The ability to increase platelet levels could significantly reduce the need for platelet transfusions and facilitate the use of interferon-based antiviral therapy and other medically indicated treatments in patients with liver disease.

Brown R, Emond JC. · Department of Medicine, Columbia University College of Physicians and Surgeons, New York 10032, USA. · Gastroenterology. · Pubmed #17383434 No free full text.

This publication has no abstract.

Alkofer B, Samstein B, Guarrera JV, Kin C, Jan D, Bellemare S, Kinkhabwala M, Brown R, Emond JC, Renz JF. · Center for Liver Disease and Transplantation, New York-Presbyterian Hospital, New York, NY 10032, USA. · Semin Liver Dis. · Pubmed #16850371 No free full text.

Abstract: Extended-donor criteria liver allografts do not meet traditional criteria for transplantation. Although these organs offer immediate expansion of the donor pool, transplantation of extended-donor criteria liver allografts increases potential short- and long-term risk to the recipient. This risk may manifest as impaired allograft function or donor-transmitted disease. Guidelines defining this category of donor, level of acceptable risk, principles of consent, and post-transplantation surveillance have not been defined. This article reviews the utilization, ethical considerations, and outcomes of extended-donor criteria liver allografts.

Brown R, Cable K, Sams R. · Eastland Family Practice, Charlotte, NC, USA. · J Fam Pract. · Pubmed #16009092 No free full text.

This publication has no abstract.

Brown R. · Department of Family Medicine, University of Wisconsin, USA. · WMJ. · Pubmed #15481866 No free full text.

Abstract: Heroin use, particularly injection use, is a problem of great public health importance. The risks associated with heroin dependence, such as HIV and viral hepatitis, and the social costs due to associated crime and poverty exceed those of most other drugs of abuse. Increasing purity and decreasing cost of heroin likely contribute to trends of decreasing age at first use and an increasing rate of initiation into regular use in the United States. Effective treatment is available for heroin dependence, so primary care providers should screen patients for this disorder. This article reviews the epidemiology of heroin use and dependence in the United States and outlines what is known regarding risk factors for initiation of heroin use and for heroin dependence.

Ravikumara M, Hill FG, Wilson DC, Gillett PM, Thomas A, Brown R, Darbyshire PJ, McKiernan PJ. · Department of Hepatology, Birmingham Children's Hospital, Birmingham, UK. · J Pediatr Gastroenterol Nutr. · Pubmed #16707977 No free full text.

Abstract: BACKGROUND: 6-Thioguanine treatment in childhood acute lymphoblastic leukaemia (ALL) has been shown to cause hepatic veno-occlusive disease, but this usually resolved with drug withdrawal. Recent reports suggested that treatment of ALL with 6-thioguanine can lead to chronic hepatotoxicity and portal hypertension. We describe our experience from 2 UK centres of chronic hepatotoxicity in children receiving maintenance 6-thioguanine for ALL in the national leukaemia protocol ALL 97/99. METHODS: Retrospective review of children who were referred with liver disease secondary to 6-thioguanine treatment of ALL was performed. A paediatric pathologist blinded to the clinical features reviewed liver histology slides. RESULTS: Ten of 75 children (13%) treated with 6-thioguanine in both centres were referred at a median of 6 months (range, 2-29) after discontinuation of chemotherapy. In 8 cases, referral was due to persistent thrombocytopenia and splenomegaly. Two children presented with acute variceal bleeding. All had thrombocytopenia at referral, and ultrasonography showed coarse hepatic echo texture and splenomegaly in all. Endoscopy showed oesophageal varices in 7 and gastric varices in 1. Nine underwent liver biopsy that showed features compatible with nodular regenerative hyperplasia in 5 cases. After a median follow-up of 36 months, a further child has had a variceal haemorrhage and all but 2 children remain thrombocytopenic. CONCLUSIONS: 6-Thioguanine-induced chronic hepatotoxicity is a significant complication in children treated with this agent for ALL. Children may present several months to years after discontinuation of 6-thioguanine. All children given maintenance treatment of ALL with this agent should be screened, and affected children require long-term surveillance.

Renz JF, Kin C, Kinkhabwala M, Jan D, Varadarajan R, Goldstein M, Brown R, Emond JC. · Center for Liver Disease and Transplantation, New York Presbyterian Hospital, New York, NY 10032, USA. · Ann Surg. · Pubmed #16192816 links to  free full text

Abstract: OBJECTIVE: The objective of this study was to evaluate the effect of systematic utilization of extended donor criteria liver allografts (EDC), including living donor allografts (LDLT), on patient access to liver transplantation (LTX). SUMMARY BACKGROUND DATA: Utilization of liver allografts that do not meet traditional donor criteria (EDC) offer immediate expansion of the donor pool. EDC are typically allocated by transplant center rather than regional wait-list priority (RA). This single-institution series compares outcomes of EDC and RA allocation to determine the impact of EDC utilization on donor use and patient access to LTX. METHODS: The authors conducted a retrospective analysis of 99 EDC recipients (49 deceased donor, 50 LDLT) and 116 RA recipients from April 2001 through April 2004. Deceased-donor EDC included: age >65 years, donation after cardiac death, positive viral serology (hepatitis C, hepatitis B core antibody, human T-cell lymphotrophic), split-liver, hypernatremia, prior carcinoma, steatosis, and behavioral high-risk donors. Outcome variables included patient and graft survival, hospitalization, initial graft function, and complication categorized as: biliary, vascular, wound, and other. RESULTS: EDC recipients were more frequently diagnosed with hepatitis C virus or hepatocellular carcinoma and had a lower model for end-stage liver disease (MELD) score at LTX (P < 0.01). Wait-time, technical complications, and hospitalization were comparable. Log-rank analysis of Kaplan-Meier survival estimates demonstrated no difference in patient or graft survival; however, deaths among deceased-donor EDC recipients were frequently the result of patient comorbidities, whereas LDLT and RA deaths resulted from graft failure (P < 0.01). EDC increased patient access to LTX by 77% and reduced pre-LTX mortality by over 50% compared with regional data (P < 0.01). CONCLUSION: Systematic EDC utilization maximizes donor use, increases access to LTX, and significantly reduces wait-list mortality by providing satisfactory outcomes to select recipients.

Minuk GY, Orr PS, Brown R, Macdonald S, Chaudhary RK, Temple P. · Liver Diseases Unit, University of Manitoba, Winnipeg, Canada. · J Hepatol. · Pubmed #11097487 No free full text.

Abstract: BACKGROUND/AIMS: Previous cross-sectional data suggested that chronic hepatitis B viral (HBV) infections in the Canadian Inuit were inactive. The aim of this study was to confirm these findings and document the prevalence of the subsequently described "pre-core mutant" variant of HBV in this population. METHODS: We obtained sera from residents of five remote Canadian Inuit communities. Residents were selected if they were known to be hepatitis B surface antigen (HBsAg) positive or had a history of liver disease. HBV serology, HBV-DNA, and pre-core mutant testing were performed by commercially available assays, polymerase chain reaction (PCR) and direct sequencing of the viral genome, respectively. RESULTS: Sera were obtained from 176/266 (66%) of selected individuals. Thirty-eight (22%) were HBsAg positive and 16 (9.1%) anti-HBs positive. Of HBsAg positive carriers 25/38 (66%) were male as compared to 68/138 (49%) of the remaining individuals (p<0.05). Of 37 HBsAg positive carriers, none were HBeAg positive, 36 (97%) anti-HBe positive and one (3%) HBeAg and anti-HBe negative. Liver enzyme and function tests were normal in all cases. 30/37 (81%) HBsAg positive carriers were HBV-DNA positive and 26/30 (87%) were pre-core mutant positive. CONCLUSION: The majority of HBV infections in community-based Canadian Inuit are inactive and the prevalence of pre-core mutant infections is the highest reported to date.