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.

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.

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.

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.

Control of hepatitis B virus replication by innate response of HepaRG cells

Julie Lucifora, David Durantel, Barbara Testoni, Olivier Hantz, Massimo Levrero, Fabien Zoulim – 23 December 2009 – Hepatitis B virus (HBV) is currently viewed as a stealth virus that does not elicit innate immunity in vivo. This assumption has not yet been challenged in vitro because of the lack of a relevant cell culture system. The HepaRG cell line, which is physiologically closer to differentiated hepatocytes and permissive to HBV infection, has opened new perspectives in this respect.HBV baculoviruses were used to initiate an HBV replication in both HepG2 and HepaRG cells.

Pregnancy outcomes among liver transplant recipients in the United States: A nationwide case‐control analysis

Carla S. Coffin, Abdel Aziz M. Shaheen, Kelly W. Burak, Robert P. Myers – 23 December 2009 – Liver transplant recipients and their infants may have an increased risk of obstetric complications. Our objective was to describe pregnancy outcomes in women with a prior transplant from a population‐based perspective. We analyzed the 1993–2005 US Nationwide Inpatient Sample database to identify obstetric hospitalizations among transplant recipients (n = 206) and controls matched by age, hospital, and year (n = 4060).

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