Combined loss of orphan receptors PXR and CAR heightens sensitivity to toxic bile acids in mice

Hirdesh Uppal, David Toma, Simrat P.S. Saini, Songrong Ren, Thomas J. Jones, Wen Xie – 23 December 2004 – Efficient detoxification of bile acids is necessary to avoid pathological conditions such as cholestatic liver damage and colon cancer. The orphan nuclear receptors PXR and CAR have been proposed to play an important role in the detoxification of xeno‐ and endo‐biotics by regulating the expression of detoxifying enzymes and transporters.

Elevated prevalence of hepatitis C infection in users of United States veterans medical centers

Jason A. Dominitz, Edward J. Boyko, Thomas D. Koepsell, Patrick J. Heagerty, Charles Maynard, Jennifer L. Sporleder – 23 December 2004 – Several studies suggest veterans have a higher prevalence of hepatitis C virus infection than nonveterans, possibly because of military exposures. The purpose of this study was to estimate the prevalence of anti–hepatitis C antibody and evaluate factors associated with infection among users of Department of Veterans Affairs medical centers.

Cholangiocarcinoma: Molecular targeting strategies for chemoprevention and therapy

Alphonse E. Sirica – 23 December 2004 – Cholangiocarcinomas are devastating cancers that are increasing in both their worldwide incidence and mortality rates. The challenges posed by these often lethal biliary tract cancers are daunting, with conventional treatment options being limited and the only hope for long‐term survival being that of complete surgical resection of the tumor. Unfortunately, the vast majority of patients with cholangiocarcinoma typically seek treatment with advanced disease, and often these patients are deemed poor candidates for curative surgery.

Impact of steatosis on progression of fibrosis in patients with mild hepatitis C

Laetitia Fartoux, Olivier Chazouillères, Dominique Wendum, Raoul Poupon, Lawrence Serfaty – 23 December 2004 – In patients with mild hepatitis C, the usefulness of antiviral therapy is subject of debate, as a low risk for progression of fibrosis is assumed. Several studies have shown that steatosis is a strong and independent predictor of the severity as well as the progression of fibrosis in chronic hepatitis C. Therefore, this study assessed the impact of steatosis on the progression of fibrosis between paired liver biopsies in untreated patients with mild hepatitis on index biopsy.

Quantitative isolation of α1AT mutant Z protein polymers from human and mouse livers and the effect of heat

Jae‐Koo An, Keith Blomenkamp, Douglas Lindblad, Jeffrey H. Teckman – 23 December 2004 – Alpha‐1‐antitrypsin (α1AT) deficiency in its most common form is caused by homozygosity for the α1AT mutant Z gene. This gene encodes a mutant Z secretory protein, primarily synthesized in the liver, that assumes an abnormal conformation and accumulates within hepatocytes causing liver cell injury. Studies have shown that mutant α1ATZ protein molecules form unique protein polymers.

Reconstitution of hepatitis C virus–specific T‐cell–mediated immunity after liver transplantation

Scott J. Weston, Rachel L. Leistikow, K. Rajender Reddy, Maria Torres, Anne M. Wertheimer, David M. Lewinsohn, Sunwen Chou, Michael P. Davey, Christopher Corless, Cliona O'Farrelly, David R. Nelson, Hugo R. Rosen – 23 December 2004 – Hepatitis C virus (HCV)‐related liver failure is the leading indication for liver transplantation worldwide. After transplantation, virological recurrence is the rule, but the spectrum of histological injury is wide, ranging from the development of allograft cirrhosis within a few years to minimal hepatitis despite long‐term follow‐up.

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