Putting flesh and polish on autoimmune hepatitis and moving the disease of exclusion to inclusion

Albert J. Czaja – 29 July 2010 – Autoimmune hepatitis emerged during an era when concepts of neonatal immune tolerance, clonal selection of lymphocytes, and “forbidden clones” of activated immune cells were forming. The diagnosis had to be deduced from circumstantial evidence and by exclusion of other conditions. The goals of this review are to demonstrate how a clinician nonscientist can contribute to the maturation of autoimmune hepatitis and to illustrate the principles of clinical investigation that can be applied broadly to other projects.

Risk factors for infection during treatment with peginterferon alfa and ribavirin for chronic hepatitis C

Robert Roomer, Bettina E. Hansen, Harry L. A. Janssen, Robert J. de Knegt – 29 July 2010 – Neutropenia during treatment with peginterferon alfa and ribavirin for chronic hepatitis C virus (HCV) infection is a common cause of dose reductions of peginterferon alfa. These reductions are performed to prevent bacterial and fungal infections, which are common during HCV treatment and can be attributed to neutropenia. The aims of this study were to investigate the occurrence of infections and their relation to neutropenia and to identify potential risk factors for infections during HCV treatment.

Potential role for Interleukin‐28B genotype in treatment decision‐making in recent hepatitis C virus infection

Jason Grebely, Kathy Petoumenos, Margaret Hellard, Gail V. Matthews, Vijayaprakash Suppiah, Tanya Applegate, Barbara Yeung, Phillipa Marks, William Rawlinson, Andrew R. Lloyd, David Booth, John M. Kaldor, Jacob George, Gregory J. Dore, for the ATAHC Study Group – 29 July 2010 – Polymorphisms in the IL28B (interleukin‐28B) gene region are important in predicting outcome following therapy for chronic hepatitis C virus (HCV) infection. We evaluated the role of IL28B in spontaneous and treatment‐induced clearance following recent HCV infection.

Prediction of sustained response to peginterferon alfa‐2b for hepatitis B e antigen–positive chronic hepatitis B using on‐treatment hepatitis B surface antigen decline

Milan J. Sonneveld, Vincent Rijckborst, Charles A. B. Boucher, Bettina E. Hansen, Harry L. A. Janssen – 29 July 2010 – Serum hepatitis B surface antigen (HBsAg) levels may reflect the immunomodulatory efficacy of pegylated interferon (PEG‐IFN). We investigated within a large randomized trial whether quantitative HBsAg levels predict response to PEG‐IFN in patients with hepatitis B e antigen (HBeAg)‐positive chronic hepatitis B.

Programmed death‐1/B7‐H1 negative costimulation protects mouse liver against ischemia and reperfusion injury

Haofeng Ji, Xiuda Shen, Feng Gao, Bibo Ke, Maria Cecilia S. Freitas, Yoichiro Uchida, Ronald W. Busuttil, Yuan Zhai, Jerzy W. Kupiec‐Weglinski – 29 July 2010 – Programmed death‐1 (PD‐1)/B7‐H1 costimulation acts as a negative regulator of host alloimmune responses. Although CD4 T cells mediate innate immunity‐dominated ischemia and reperfusion injury (IRI) in the liver, the underlying mechanisms remain to be elucidated. This study focused on the role of PD‐1/B7‐H1 negative signaling in liver IRI.

Type 1 T Helper Cells Induce the Accumulation of Myeloid‐Derived Suppressor Cells in the Inflamed Tgfb1 Knockout Mouse Liver

James G. Cripps, Jing Wang, Ann Maria, Ian Blumenthal, James D. Gorham – 29 July 2010 – Immune‐mediated liver injury in hepatitis is due to activated T cells producing interferon‐γ (IFN‐γ). It is important to identify negative feedback immune mechanisms that can regulate T cell activity.

Activation of interleukin‐6–induced glycoprotein 130/signal transducer and activator of transcription 3 pathway in mesenchymal stem cells enhances hepatic differentiation, proliferation, and liver regeneration

Shuk Pik Lam, John M. Luk, Kwan Man, Kevin T. P. Ng, Cindy K. Cheung, Stefan Rose‐John, Chung Mau Lo – 29 July 2010 – Adult bone marrow–derived mesenchymal stem cells (MSCs) exist in all living species and are capable of differentiating into different types of specific cells. In this study, we demonstrate the therapeutic effectiveness of rat MSC transplantation in D‐galactosamine (GalN)‐induced acute liver injury and identified the novel pathways which are involved in hepatic differentiation of MSCs.

Portal vein thrombosis and liver transplant survival benefit

Michael J. Englesbe, Douglas E. Schaubel, Shijie Cai, Mary K. Guidinger, Robert M. Merion – 27 July 2010 – Portal vein thrombosis (PVT) complicates the liver transplant operation and potentially affects waiting list survival. The implications on calculations of survival benefit, which balance both waiting list and posttransplant survival effects of PVT, have not been determined. The objective of this study is to describe the effect of PVT on the survival benefit of liver transplantation.

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