Susceptibility to hepatitis A in patients with chronic liver disease due to hepatitis C virus infection: Missed opportunities for vaccination

Michael Shim, Inessa Khaykis, James Park, Edmund J. Bini – 15 August 2005 – Hepatitis A virus (HAV) superinfection is associated with a high risk of liver failure and death in patients with underlying chronic liver disease. Although HAV vaccination is recommended for all patients with chronic hepatitis C virus (HCV) infection, little is known about adherence to these recommendations in clinical practice. The aims of this study were to determine the frequency of HAV testing and vaccination among patients with chronic HCV infection.

Recapitulation of in vivo gene expression during hepatic differentiation from murine embryonic stem cells

Yusuke Yamamoto, Takumi Teratani, Hanako Yamamoto, Gary Quinn, Sigenori Murata, Rieko Ikeda, Kenji Kinoshita, Kenichi Matsubara, Takashi Kato, Takahiro Ochiya – 15 August 2005 – Hepatic differentiation at the molecular level is poorly understood, mainly because of the lack of a suitable model. Recently, using adherent monoculture conditions, we demonstrated the direct differentiation of hepatocytes from embryonic stem (ES) cells.

Alpha‐1‐antitrypsin deficiency: A new paradigm for hepatocellular carcinoma in genetic liver disease

David A. Rudnick, David H. Perlmutter – 25 July 2005 – Liver disease in alpha‐1‐antitrypsin (α1AT) deficiency is caused by a gain‐of‐toxic function mechanism engendered by the accumulation of a mutant glycoprotein in the endoplasmic reticulum (ER). The extraordinary degree of variation in phenotypical expression of this liver disease is believed to be determined by genetic modifiers and/or environmental factors that influence the intracellular disposal of the mutant glycoprotein or the signal transduction pathways that are activated.

Proteasome inhibition sensitizes hepatocellular carcinoma cells, but not human hepatocytes, to TRAIL

Tom M. Ganten, Ronald Koschny, Tobias L. Haas, Jaromir Sykora, Min Li‐Weber, Kerstin Herzer, Henning Walczak – 21 July 2005 – TRAIL exhibits potent anti‐tumor activity on systemic administration in mice. Because of its proven in vivo efficacy, TRAIL may serve as a novel anti‐neoplastic drug. However, approximately half of the tumor cell lines tested so far are TRAIL resistant, and potential toxic side effects of certain recombinant forms of TRAIL on human hepatocytes have been described.

VPAC1 expression is regulated by FXR agonists in the human gallbladder epithelium

Nicolas Chignard, Martine Mergey, Véronique Barbu, Laetitia Finzi, Emmanuel Tiret, Annick Paul, Chantal Housset – 21 July 2005 – Vasoactive intestinal peptide receptor‐1 (VPAC1) is the high‐affinity receptor of vasoactive intestinal peptide (VIP), a major regulator of bile secretion. To better define the level at which VPAC1 stimulates bile secretion, we examined its expression in the different cell types participating in bile formation (i.e., hepatocytes, bile duct, and gallbladder epithelial cells).

Spectrum of NAFLD and diagnostic implications of the proposed new normal range for serum ALT in obese women

Sachin S. Kunde, Audrey J. Lazenby, Ronald H. Clements, Gary A. Abrams – 21 July 2005 – The upper limit of normal for ALT activity has been recommended to be lowered to ≤30 U/L in men and ≤19 U/L in women. These changes have been suggested to be diagnostically useful in subjects with nonalcoholic fatty liver disease (NAFLD). Our aim was to investigate the prevalence and spectrum of NAFLD with regard to the new ALT guidelines in 233 women with class II/III obesity. We compared our prior reference range for ALT (ULN ≤ 30 U/L in women) with the new standard.

LKM1 autoantibodies in chronic hepatitis C infection: A case of molecular mimicry?

Gabriel Marceau, Pascal Lapierre, Kathie Béland, Hugo Soudeyns, Fernando Alvarez – 21 July 2005 – Anti‐liver‐kidney microsome type 1 (LKM1) autoantibodies directed against the cytochrome P450 2D6 (CYP2D6) are considered specific markers of type 2 autoimmune hepatitis, but are also found in 5% of sera from patients chronically infected by hepatitis C virus (HCV). Molecular mimicry between HCV proteins and CYP2D6 has been proposed to explain the emergence of these autoantibodies.

Transplantation of hepatitis B surface antigen–positive livers into hepatitis B virus–positive recipients and the role of hepatitis delta coinfection

Alessandro Franchello, Valeria Ghisetti, Alfredo Marzano, Renato Romagnoli, Mauro Salizzoni – 20 July 2005 – The scarcity of liver donors requires consideration of grafts from sources not previously used. Allografts from hepatitis B surface antigen (HBsAg)‐carriers without a significant liver disease have been proposed for liver transplant recipients with hepatitis B virus (HBV)‐related cirrhosis and hepatocellular carcinoma (HCC).

Biliary epithelial cell antibodies induce expression of toll‐like receptors 2 and 3: A mechanism for post–liver transplantation cholangitis?

Xupeng Ge, Mehmet Uzunel, Bo‐Göran Ericzon, Suchitra Sumitran‐Holgersson – 20 July 2005 – Studies to determine the role of preformed antibodies to biliary epithelial cells (BECs) in liver transplant rejections have been initiated. However, the clinical importance of these antibodies in the posttransplantation period still remains to be elucidated. Reactivity to BECs isolated from a normal healthy liver was investigated in sera of 56 patients before and after liver transplantation (LTX) using flow cytometry.

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