Folding defects in P‐type ATP 8B1 associated with hereditary cholestasis are ameliorated by 4‐phenylbutyrate

Lieke M. van der Velden, Janneke M. Stapelbroek, Elmar Krieger, Peter V. E. van den Berghe, Ruud Berger, Patricia M. Verhulst, Joost C. M. Holthuis, Roderick H. J. Houwen, Leo W. J. Klomp, Stan F. J. van de Graaf – 23 December 2009 – Deficiency in P‐type ATP8B1 is a severe and clinically highly variable hereditary disorder that is primarily characterized by intrahepatic cholestasis. It presents either as a progressive (progressive familial intrahepatic cholestasis type 1 [PFIC1]) or intermittent (benign recurrent intrahepatic cholestasis type 1 [BRIC1]) disease.

Predictors of response to therapy with terlipressin and albumin in patients with cirrhosis and type 1 hepatorenal syndrome

André Nazar, Gustavo Henrique Pereira, Mónica Guevara, Marta Martín‐Llahi, Marie‐Noëlle Pepin, Marcella Marinelli, Elsa Solá, María Eugenia Baccaro, Carlos Terra, Vicente Arroyo, Pere Ginès – 23 December 2009 – Terlipressin plus albumin is an effective treatment for type 1 hepatorenal syndrome (HRS), but approximately only half of the patients respond to this therapy. The aim of this study was to assess predictive factors of response to treatment with terlipressin and albumin in patients with type 1 HRS.

Mechanisms for increased expression of cholesterol 7α‐hydroxylase (Cyp7a1) in lactating rats

Clavia Ruth Wooton‐Kee, Donna J. Coy, Antony T. Athippozhy, Tianyong Zhao, Brett R. Jones, Mary Vore – 23 December 2009 – Cholesterol 7α‐hydroxylase (Cyp7a1) and the bile acid pool size are increased 2 to 3‐fold in lactating postpartum rats. We investigated the interaction of nuclear receptors with the Cyp7a1 proximal promoter and the expression of regulatory signaling pathways in postpartum rats at day 10 (PPd10) versus female controls to identify the mechanisms of increased expression of Cyp7a1, which is maximal at 16 hours.

Acetaminophen dosing of humans results in blood transcriptome and metabolome changes consistent with impaired oxidative phosphorylation

Rick D. Fannin, Mark Russo, Thomas M. O'Connell, Kevin Gerrish, Jason H. Winnike, Jeffrey Macdonald, Jack Newton, Shahid Malik, Stella O. Sieber, Joel Parker, Ruchir Shah, Tong Zhou, Paul B. Watkins, Richard S. Paules – 23 December 2009 – The diagnosis and management of drug‐induced liver injury (DILI) is hindered by the limited utility of traditional clinical chemistries. It has recently been shown that hepatotoxicants can produce compound‐specific changes in the peripheral blood (PB) transcriptome in rodents, suggesting that the blood transcriptome might provide new biomarkers of DILI.

Major histocompatibility complex class I–related chains A and B (MIC A/B): A novel role in nonalcoholic steatohepatitis

Alisan Kahraman, Martin Schlattjan, Peri Kocabayoglu, Sule Yildiz‐Meziletoglu, Matthias Schlensak, Christian D. Fingas, Inga Wedemeyer, Guido Marquitan, Robert K. Gieseler, Hideo A. Baba, Guido Gerken, Ali Canbay – 23 December 2009 – Stress‐induced soluble major histocompatibility complex class I–related chains A/B (MIC A/B) are increased in chronic liver diseases and hepatocellular malignancy. We investigated the impact of these molecules on liver injury, apoptosis, and fibrosis in nonalcoholic steatohepatitis (NASH).

Impaired expression and function of toll‐like receptor 7 in hepatitis C virus infection in human hepatoma cells

Serena Chang, Karen Kodys, Gyongyi Szabo – 23 December 2009 – Hepatitis C virus (HCV) interferes with interferon (IFN)‐mediated innate immune defenses. Toll‐like receptor (TLR) 7 agonists robustly inhibit HCV infection. We hypothesize that HCV infection may interfere with the expression and/or function of TLR7, a sensor of single‐stranded RNA. We identified reduced TLR7 RNA and protein levels in hepatoma cells expressing HCV (full‐length, BB7‐subgenomic, and JFH‐1 clone) compared with control HCV‐naïve cells.

A peer‐based intervention to educate liver transplant candidates about living donor liver transplantation

Samantha DeLair, Thomas Hugh Feeley, Hyunjung Kim, Juan del Rio Martin, Leona Kim‐Schluger, Dianne LaPointe Rudow, Mark Orloff, Patricia A. Sheiner, Lewis Teperman – 23 December 2009 – The number of liver donors has not measurably increased since 2004 and has begun to decrease. Although many waitlisted patients may be suitable candidates to receive a living donor graft, they are often reticent to discuss living donation with close friends and family, partly because of a lack of knowledge about donor health and quality of life outcomes after donation.

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