Proteomic profiling of human liver biopsies: Hepatitis C virus–induced fibrosis and mitochondrial dysfunction

Deborah L. Diamond, Jon M. Jacobs, Bryan Paeper, Sean C. Proll, Marina A. Gritsenko, Robert L. Carithers, Anne M. Larson, Matthew M. Yeh, David G. Camp, Richard D. Smith, Michael G. Katze – 24 August 2007 – Liver biopsies from hepatitis C virus (HCV)‐infected patients offer the unique opportunity to study human liver biology and disease in vivo. However, the low protein yields associated with these small samples present a significant challenge for proteomic analysis.

Mutations in the MPV17 gene are responsible for rapidly progressive liver failure in infancy

Lee‐Jun C. Wong, Nicola Brunetti‐Pierri, Qing Zhang, Nada Yazigi, Kevin E. Bove, Beverly B. Dahms, Michelle A. Puchowicz, Ignacio Gonzalez‐Gomez, Eric S. Schmitt, Cavatina K. Truong, Charles L. Hoppel, Ping‐Chieh Chou, Jing Wang, Erin E. Baldwin, Darius Adams, Nancy Leslie, Richard G. Boles, Douglas S. Kerr, William J. Craigen – 10 August 2007 – MPV17 is a mitochondrial inner membrane protein of unknown function recently recognized as responsible for a mitochondrial DNA depletion syndrome.

Influence of ursodeoxycholic acid on the mortality and malignancy associated with primary biliary cirrhosis: A population‐based cohort study

Hannah Jackson, Masoud Solaymani‐Dodaran, Tim R. Card, Guruprasad P. Aithal, Richard Logan, Joe West – 8 August 2007 – There is debate over the mortality and malignancy risk in people with primary biliary cirrhosis (PBC) and whether this risk is reduced by use of ursodeoxycholic acid. To investigate this issue, we identified 930 people with PBC and 9,202 control subjects from the General Practice Research Database in the United Kingdom. We categorized regular ursodeoxycholic acid as treatment with 6 or more prescriptions and nonregular treatment as less than 6.

Hepatitis B prophylaxis in patients undergoing chemotherapy for lymphoma: A decision analysis model

Sammy Saab, Mamie H. Dong, Tom A. Joseph, Myron J. Tong – 6 August 2007 – Hepatitis B reactivation is a major cause of morbidity and mortality in patients undergoing chemotherapy for lymphomas. These patients may experience direct liver‐related complications or reduced cancer survival because of interruptions in chemotherapy. Our aim was to compare the costs and outcomes of 2 different chronic hepatitis B management strategies.

Hepatitis C treatment in “difficult‐to‐treat” psychiatric patients with pegylated interferon‐alpha and ribavirin: Response and psychiatric side effects

Martin Schaefer, Axel Hinzpeter, Ariane Mohmand, Gesa Janssen, Maurice Pich, Markus Schwaiger, Rahul Sarkar, Astrid Friebe, Andreas Heinz, Michael Kluschke, Marlene Ziemer, Juri Gutsche, Viola Weich, Juliane Halangk, Thomas Berg – 1 August 2007 – We investigated and compared the results of treating the chronic hepatitis C (HCV) infection of different groups of psychiatric‐risk patients and controls with pegylated interferon alpha (pegIFN‐α) plus ribavirin. Seventy patients were prospectively screened for psychiatric disorders.

Suppressor of cytokine signaling 3 (SOCS3) expression and hepatitis C virus–related chronic hepatitis: Insulin resistance and response to antiviral therapy

Marcello Persico, Mario Capasso, Eliana Persico, Monica Svelto, Roberta Russo, Daniela Spano, Lori Crocè, Vincenzo La Mura, Francesco Moschella, Flora Masutti, Roberto Torella, Claudio Tiribelli, Achille Iolascon – 1 August 2007 – The response to antiviral therapy is lower in hepatitis C virus (HCV) patients with genotype 1 than in those with genotype 2. Overexpression of the suppressor of cytokine signaling 3 (SOCS3) gene in liver tissue is associated with a poorer treatment outcome in patients with chronic hepatitis C viral genotype 1.

Features associated with treatment failure in type 1 autoimmune hepatitis and predictive value of the model of end‐stage liver disease

Aldo J. Montano‐Loza, Herschel A. Carpenter, Albert J. Czaja – 1 August 2007 – Autoimmune hepatitis may fail to respond to corticosteroid therapy, but the frequency and bases for this outcome are uncertain. We aimed to determine the frequency and nature of treatment failure in patients with type 1 autoimmune hepatitis, define features associated with its occurrence, and assess if the model for end‐stage liver disease can predict this outcome. Patients failing conventional corticosteroid regimens were compared to patients who responded to similar regimens.

Lack of response to exogenous interferon‐α in the liver of chimpanzees chronically infected with hepatitis C virus

Robert E. Lanford, Bernadette Guerra, Catherine B. Bigger, Helen Lee, Deborah Chavez, Kathleen M. Brasky – 1 August 2007 – The mechanism of the interferon‐alpha (IFNα)–induced antiviral response is not completely understood. We recently examined the transcriptional response to IFNα in uninfected chimpanzees. The transcriptional response to IFNα in the liver and peripheral blood mononuclear cells (PBMCs) was rapidly induced but was also rapidly down‐regulated, with most interferon‐alpha–stimulated genes (ISGs) returning to the baseline within 24 hours.

Aging in rat causes hepatic hyperresposiveness to interleukin‐1β which is mediated by neutral sphingomyelinase‐2

Kristina Rutkute, Alexander A. Karakashian, Natalia V. Giltiay, Aneta Dobierzewska, Mariana N. Nikolova‐Karakashian – 1 August 2007 – The process of aging has recently been shown to substantially affect the ability of cells to respond to inflammatory challenges. We demonstrate that aging leads to hepatic hyperresponsiveness to interleukin 1β (IL‐1β), and we examine the factors that could be responsible for this phenomenon. IL‐1β‐induced phosphorylation of c‐jun N‐terminal kinase (JNK) in hepatocytes isolated from aged rats was 3 times more potent than that in hepatocytes from young rats.

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