Relaxin modulates human and rat hepatic myofibroblast function and ameliorates portal hypertension in vivo

Jonathan A. Fallowfield, Annette L. Hayden, Victoria K. Snowdon, Rebecca L. Aucott, Ben M. Stutchfield, Damian J. Mole, Antonella Pellicoro, Timothy T. Gordon‐Walker, Alexander Henke, Joerg Schrader, Palak J. Trivedi, Marc Princivalle, Stuart J. Forbes, Jane E. Collins, John P. Iredale – 19 July 2013 – Active myofibroblast (MF) contraction contributes significantly to the increased intrahepatic vascular resistance that is the primary cause of portal hypertension (PHT) in cirrhosis.

Hepatitis C genotype 1 virus with low viral load and rapid virologic response to peginterferon/ribavirin obviates a protease inhibitor

Brian L. Pearlman, Carole Ehleben – 19 July 2013 – The new standard of care for treatment‐naïve patients with hepatitis C virus (HCV) genotype 1 includes triple therapy with peginterferon, ribavirin, and a protease inhibitor. However, patients who achieve a rapid virologic response after 4 weeks of peginterferon and ribavirin therapy are likely to achieve a sustained virologic response (SVR), and we hypothesized that protease inhibitor therapy may be unnecessary in these patients.

Pretransplant donor‐specific anti‐HLA antibodies as predictors of early allograft rejection in ABO‐compatible liver transplantation

Alexandru I. Musat, Courtney M. Pigott, Thomas M. Ellis, Rashmi M. Agni, Glen E. Leverson, Amy J. Powell, Katelyn R. Richards, Anthony M. D'Alessandro, Michael R. Lucey – 19 July 2013 – The significance of preexisting donor‐specific HLA antibodies (HLA‐DSAs) for liver allograft function is unclear. Our previous studies have shown that humoral alloreactivity frequently accompanies acute cellular rejection (ACR).

Protein kinase C (PKC) participates in acetaminophen hepatotoxicity through c‐jun‐N‐terminal kinase (JNK)‐dependent and ‐independent signaling pathways

Behnam Saberi, Maria D. Ybanez, Heather S. Johnson, William A. Gaarde, Derick Han, Neil Kaplowitz – 19 July 2013 – This study examines the role of protein kinase C (PKC) and AMP‐activated kinase (AMPK) in acetaminophen (APAP) hepatotoxicity. Treatment of primary mouse hepatocytes with broad‐spectrum PKC inhibitors (Ro‐31‐8245, Go6983), protected against APAP cytotoxicity despite sustained c‐jun‐N‐terminal kinase (JNK) activation. Broad‐spectrum PKC inhibitor treatment enhanced p‐AMPK levels and AMPK regulated survival‐energy pathways including autophagy.

Cell entry, efficient RNA replication, and production of infectious hepatitis C virus progeny in mouse liver‐derived cells

Anne Frentzen, Anggakusuma, Engin Gürlevik, Kathrin Hueging, Sarah Knocke, Corinne Ginkel, Richard J.P. Brown, Markus Heim, Michael T. Dill, Andrea Kröger, Ulrich Kalinke, Lars Kaderali, Florian Kuehnel, Thomas Pietschmann – 19 July 2013 – Only humans and chimpanzees are susceptible to chronic infection by hepatitis C virus (HCV). The restricted species tropism of HCV is determined by distinct host factor requirements at different steps of the viral life cycle. In addition, effective innate immune targeting precludes efficient propagation of HCV in nonhuman cells.

Radiologic course of primary sclerosing cholangitis: Assessment by three‐dimensional magnetic resonance cholangiography and predictive features of progression

Ana Ruiz, Sara Lemoinne, Fabrice Carrat, Christophe Corpechot, Olivier Chazouillères, Lionel Arrivé – 15 July 2013 – Magnetic resonance imaging (MRI) with magnetic resonance cholangiography (MRC) has become the radiologic standard of reference for diagnosis of primary sclerosing cholangitis (PSC). However, natural history of radiologic features of PSC is poorly known. In the current study, we aimed at analyzing the course of PSC using three‐dimensional (3D) MRC and liver MRI to find predictive radiologic features of progression.

Radiologic course of primary sclerosing cholangitis: Assessment by three‐dimensional magnetic resonance cholangiography and predictive features of progression

Ana Ruiz, Sara Lemoinne, Fabrice Carrat, Christophe Corpechot, Olivier Chazouillères, Lionel Arrivé – 15 July 2013 – Magnetic resonance imaging (MRI) with magnetic resonance cholangiography (MRC) has become the radiologic standard of reference for diagnosis of primary sclerosing cholangitis (PSC). However, natural history of radiologic features of PSC is poorly known. In the current study, we aimed at analyzing the course of PSC using three‐dimensional (3D) MRC and liver MRI to find predictive radiologic features of progression.

Association of severe intrahepatic cholestasis of pregnancy with adverse pregnancy outcomes: A prospective population‐based case‐control study

Victoria Geenes, Lucy C. Chappell, Paul T. Seed, Philip J. Steer, Marian Knight, Catherine Williamson – 15 July 2013 – Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy‐specific liver disease, characterized by maternal pruritus and raised serum bile acids. Our objectives were to describe the epidemiology and pregnancy complications associated with severe ICP and to test the hypothesis that adverse perinatal outcomes are increased in these women.

MicroRNA/gene profiling unveils early molecular changes and nuclear factor erythroid related factor 2 (NRF2) activation in a rat model recapitulating human hepatocellular carcinoma (HCC)

Annalisa Petrelli, Andrea Perra, Davide Cora, Pia Sulas, Silvia Menegon, Claudia Manca, Cristina Migliore, Marta Anna Kowalik, Giovanna Maria Ledda‐Columbano, Silvia Giordano, Amedeo Columbano – 15 July 2013 – Studies on gene and/or microRNA (miRNA) dysregulation in the early stages of hepatocarcinogenesis are hampered by the difficulty of diagnosing early lesions in humans. Experimental models recapitulating human hepatocellular carcinoma (HCC) are then used to perform this analysis.

Liver transplantation for hepatitis B liver disease and concomitant hepatocellular carcinoma in the United States With hepatitis B immunoglobulin and nucleoside/nucleotide analogues

Jeffrey Campsen, Michael Zimmerman, James Trotter, Johnny Hong, Chris Freise, Robert Brown, Andrew Cameron, Mark Ghobrial, Igal Kam, Ronald Busuttil, Sammy Saab, Curtis Holt, Jean Emond, Jessica Stiles, Thresiamma Lukose, Matthew Chang, Goran Klintmalm – 15 July 2013 – Reinfection with hepatitis B virus (HBV) after liver transplantation (LT) may favor the recurrence of hepatocellular carcinoma (HCC), and combination therapy with hepatitis B immunoglobulin (HBIG) and nucleoside/nucleotide analogues may reduce HBV recurrence after LT.

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