Telaprevir‐based treatment effects on hepatitis C virus in liver and blood

Andrew H. Talal, Rositsa B. Dimova, Eileen Z. Zhang, Min Jiang, Marina S. Penney, James C. Sullivan, Martyn C. Botfield, Ananthsrinivas Chakilam, Rishikesh Sawant, Christine M. Cervini, Marija Zeremski, Ira M. Jacobson, Ann D. Kwong – 8 May 2014 – Understanding hepatitis C virus (HCV) replication has been limited by access to serial samples of liver, the primary site of viral replication. Our understanding of how HCV replicates and develops drug‐resistant variants in the liver is limited.

Alpha‐fetoprotein level > 1000 ng/mL as an exclusion criterion for liver transplantation in patients with hepatocellular carcinoma meeting the Milan criteria

Bilal Hameed, Neil Mehta, Gonzalo Sapisochin, John P. Roberts, Francis Y. Yao – 6 May 2014 – Serum alpha‐fetoprotein (AFP) has been increasingly recognized as a marker for a poor prognosis after liver transplantation (LT) for hepatocellular carcinoma (HCC). Many published reports, however, have included a large proportion of patients with HCC beyond the Milan criteria, and the effects of incorporating AFP as an exclusion criterion for LT remain unclear.

Prosurvival function of the cellular apoptosis susceptibility/importin‐α1 transport cycle is repressed by p53 in liver cancer

Juliane Winkler, Alessandro Ori, Kerstin Holzer, Carsten Sticht, Daniel Dauch, Eva Maria Eiteneuer, Federico Pinna, Robert Geffers, Volker Ehemann, Amparo Andres‐Pons, Kai Breuhahn, Thomas Longerich, Justo Lorenzo Bermejo, Norbert Gretz, Lars Zender, Peter Schirmacher, Martin Beck, Stephan Singer – 6 May 2014 – Proteins of the karyopherin superfamily including importins and exportins represent an essential part of the nucleocytoplasmic transport machinery. However, the functional relevance and regulation of karyopherins in hepatocellular carcinoma (HCC) is poorly understood.

Human drug‐induced liver injury severity is highly associated with dual inhibition of liver mitochondrial function and bile salt export pump

Michael D. Aleo, Yi Luo, Rachel Swiss, Paul D. Bonin, David M. Potter, Yvonne Will – 6 May 2014 – Drug‐induced liver injury (DILI) accounts for 20‐40% of all instances of clinical hepatic failure and is a common reason for withdrawal of an approved drug or discontinuation of a potentially new drug from clinical/nonclinical development. Numerous individual risk factors contribute to the susceptibility to human DILI and its severity that are either compound‐ and/or patient‐specific.

Elevated sensitivity of macrosteatotic hepatocytes to hypoxia/reoxygenation stress is reversed by a novel defatting protocol

Nir I. Nativ, Gabriel Yarmush, Ashley So, Jeffery Barminko, Timothy J. Maguire, Rene Schloss, Francois Berthiaume, Martin L. Yarmush – 6 May 2014 – Macrosteatotic livers exhibit elevated intrahepatic triglyceride (TG) levels in the form of large lipid droplets (LDs), reduced adenosine triphosphate (ATP) levels, and elevated reactive oxygen species (ROS) levels, and this contributes to their elevated sensitivity to ischemia/reperfusion injury during transplantation. Reducing macrosteatosis in living donors through dieting has been shown to improve transplant outcomes.

Prosurvival function of the cellular apoptosis susceptibility/importin‐α1 transport cycle is repressed by p53 in liver cancer

Juliane Winkler, Alessandro Ori, Kerstin Holzer, Carsten Sticht, Daniel Dauch, Eva Maria Eiteneuer, Federico Pinna, Robert Geffers, Volker Ehemann, Amparo Andres‐Pons, Kai Breuhahn, Thomas Longerich, Justo Lorenzo Bermejo, Norbert Gretz, Lars Zender, Peter Schirmacher, Martin Beck, Stephan Singer – 6 May 2014 – Proteins of the karyopherin superfamily including importins and exportins represent an essential part of the nucleocytoplasmic transport machinery. However, the functional relevance and regulation of karyopherins in hepatocellular carcinoma (HCC) is poorly understood.

Continuation of metformin use after a diagnosis of cirrhosis significantly improves survival of patients with diabetes

Xiaodan Zhang, William S. Harmsen, Teresa A. Mettler, W. Ray Kim, Rosebud O. Roberts, Terry M. Therneau, Lewis R. Roberts, Roongruedee Chaiteerakij – 3 May 2014 – The risks and benefits of metformin use in patients with cirrhosis with diabetes are debated. Although data on a protective effect of metformin against liver cancer development have been reported, metformin is frequently discontinued once cirrhosis is diagnosed because of concerns about an increased risk of adverse effects of metformin in patients with liver impairment.

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