Predicting in‐hospital mortality in patients with cirrhosis: Results differ across risk adjustment methods

Robert P. Myers, Hude Quan, James N. Hubbard, Abdel Aziz M. Shaheen, Gilaad G. Kaplan – 28 January 2009 – Risk‐adjusted health outcomes are often used to measure the quality of hospital care, yet the optimal approach in patients with liver disease is unclear. We sought to determine whether assessments of illness severity, defined as risk for in‐hospital mortality, vary across methods in patients with cirrhosis. We identified 258,731 patients with cirrhosis hospitalized in the Nationwide Inpatient Sample between 2002 and 2005.

Transcription factor 7–like 2 polymorphism modulates glucose and lipid homeostasis, adipokine profile, and hepatocyte apoptosis in NASH

Giovanni Musso, Roberto Gambino, Giovanni Pacini, Gianfranco Pagano, Marilena Durazzo, Maurizio Cassader – 28 January 2009 – Genetic factors underlying the association of NAFLD with diabetes and atherosclerosis are unknown. Recent human studies suggest transcription factor 7–like 2 (TCF7L2) polymorphism predisposes to diabetes through modulation of β‐cell function and modulates lipid levels in familial dyslipidemia. Emerging experimental evidence connects TCF7L2 to adipocyte metabolism and lipid homeostasis, as well.

Missense mutations and single nucleotide polymorphisms in ABCB11 impair bile salt export pump processing and function or disrupt pre‐messenger RNA splicing

Jane A. Byrne, Sandra S. Strautnieks, Gudrun Ihrke, Franco Pagani, A.S. Knisely, Kenneth J. Linton, Giorgina Mieli‐Vergani, Richard J. Thompson – 28 January 2009 – The gene encoding the human bile salt export pump (BSEP), ABCB11, is mutated in several forms of intrahepatic cholestasis. Here we classified the majority (63) of known ABCB11 missense mutations and 21 single‐nucleotide polymorphisms (SNPs) to determine whether they caused abnormal ABCB11 pre‐messenger RNA splicing, abnormal processing of BSEP protein, or alterations in BSEP protein function.

Reduction of hepatic steatosis in rats and mice after treatment with a liver‐targeted thyroid hormone receptor agonist

Edward E. Cable, Patricia D. Finn, Jeffrey W. Stebbins, Jinzhao Hou, Bruce R. Ito, Paul D. van Poelje, David L. Linemeyer, Mark D. Erion – 28 January 2009 – Non‐alcoholic fatty liver disease (NAFLD) is one of the most common forms of chronic liver disease, with a prevalence ranging from 10% to 30%. The use of thyroid hormone receptor (TR) agonists for the treatment of NAFLD has not been considered viable because thyroid hormones increase free fatty acid (FFA) flux from the periphery to the liver, induce hepatic lipogenesis, and therefore could potentially cause steatosis.

Using an immune functional assay to differentiate acute cellular rejection from recurrent hepatitis C in liver transplant patients

Roniel Cabrera, Miguel Ararat, Consuelo Soldevila‐Pico, Lisa Dixon, Jen‐Jung Pan, Roberto Firpi, Victor Machicao, Cynthia Levy, David Nelson, Giuseppe Morelli – 28 January 2009 – In transplant recipients transplanted for hepatitis C, presentation of abnormal transaminases can herald the presentation of recurrent hepatitis C, cellular rejection, or both. Given the sometimes ambiguous histology with these 2 entities, the ability to distinguish them is of great importance because misinterpretation can potentially affect graft survival.

Development and characterization of hepatitis C virus genotype 1‐7 cell culture systems: Role of CD81 and scavenger receptor class B type I and effect of antiviral drugs

Judith M. Gottwein, Troels K. H. Scheel, Tanja B. Jensen, Jacob B. Lademann, Jannick C. Prentoe, Maria L. Knudsen, Anne M. Hoegh, Jens Bukh – 28 January 2009 – Six major hepatitis C virus (HCV) genotypes and numerous subtypes have been described, and recently a seventh major genotype was discovered. Genotypes show significant molecular and clinical differences, such as differential response to combination therapy with interferon‐α and ribavirin. Recently, HCV research has been accelerated by cell culture systems based on the unique growth capacity of strain JFH1 (genotype 2a).

Recruitment of host progenitor cells in rat liver transplants

Zhaoli Sun, Xiuying Zhang, Jayme E. Locke, Qizhi Zheng, Shingo Tachibana, Anna Mae Diehl, George Melville Williams – 28 January 2009 – Despite major histocompatibility complex incompatibility, liver transplants from Lewis rats to dark agouti (DA) rats survive indefinitely without immunosuppression, and the studies we report sought the mechanism(s) responsible for this. At 1 year, most of the liver reacted positively to host anti‐DA antibody. When small (50%) grafts were transplanted, recruitment was more rapid because most of the organ assumed the host phenotype at 3 months.

Serum hyaluronic acid with serum ferritin accurately predicts cirrhosis and reduces the need for liver biopsy in C282Y hemochromatosis

Darrell H. G. Crawford, Therese L. Murphy, Louise E. Ramm, Linda M. Fletcher, Andrew D. Clouston, Gregory J. Anderson, V. Nathan Subramaniam, Lawrie W. Powell, Grant A. Ramm – 28 January 2009 – Diagnosing the presence of cirrhosis is crucial for the management of patients with C282Y hereditary hemochromatosis (HH). HH patients with serum ferritin >1,000 μg/L are at risk of cirrhosis; however, the majority of these patients do not have cirrhosis.

Hepatitis B virus prevention strategies for antibody to hepatitis B core antigen–positive liver donation: A survey of North American, European, and Asian‐Pacific transplant programs

Robert Perrillo – 28 January 2009 – Prophylactic therapy is generally used to prevent reactivated hepatitis B after transplantation of an antibody to hepatitis B core antigen (anti‐HBc)–positive liver. To gain insight into current practice, a questionnaire was e‐mailed to 89 liver transplant physicians in the United States, Europe, and Asia/Australia and 4 hepatitis B experts. Addressees were asked if they prefer lamivudine or other nucleoside analogs and whether these drugs are used indefinitely.

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