Hypoxia‐inducible transcription factor 2α promotes steatohepatitis through augmenting lipid accumulation, inflammation, and fibrosis

Aijuan Qu, Matthew Taylor, Xiang Xue, Tsutomu Matsubara, Daniel Metzger, Pierre Chambon, Frank J. Gonzalez, Yatrik M. Shah – 29 April 2011 – Oxygen dynamics in the liver is a central signaling mediator controlling hepatic homeostasis, and dysregulation of cellular oxygen is associated with liver injury. Moreover, the transcription factor relaying changes in cellular oxygen levels, hypoxia‐inducible factor (HIF), is critical in liver metabolism, and sustained increase in HIF signaling can lead to spontaneous steatosis, inflammation, and liver tumorigenesis.

In vivo adaptation of hepatitis C virus in chimpanzees for efficient virus production and evasion of apoptosis

Mohsan Saeed, Masaaki Shiina, Tomoko Date, Daisuke Akazawa, Noriyuki Watanabe, Asako Murayama, Tetsuro Suzuki, Haruo Watanabe, Nobuhiko Hiraga, Michio Imamura, Kazuaki Chayama, Youkyung Choi, Krzysztof Krawczynski, T. Jake Liang, Takaji Wakita, Takanobu Kato – 29 April 2011 – Hepatitis C virus (HCV) employs various strategies to establish persistent infection that can cause chronic liver disease.

Reciprocal interference between insulin and interferon‐alpha signaling in hepatic cells: A vicious circle of clinical significance?

Lisa Franceschini, Stefano Realdon, Moira Marcolongo, Silvia Mirandola, Gladis Bortoletto, Alfredo Alberti – 29 April 2011 – Insulin resistance (IR) is common in chronic hepatitis C (CHC) and associates with reduced virological response to pegylated‐interferon (PEG‐IFN)/ribavirin therapy, but the underlying mechanisms are still unclear. We have previously shown that, in CHC patients, insulin plasma levels are inversely related to antiviral effect induced by PEG‐IFN.

Activating transcription factor 6 plays protective and pathological roles in steatosis due to endoplasmic reticulum stress in zebrafish

Ayca Cinaroglu, Chuan Gao, Dru Imrie, Kirsten C. Sadler – 29 April 2011 – Many etiologies of fatty liver disease (FLD) are associated with the hyperactivation of one of the three pathways composing the unfolded protein response (UPR), which is a harbinger of endoplasmic reticulum (ER) stress. The UPR is mediated by pathways initiated by PRKR‐like endoplasmic reticulum kinase, inositol‐requiring 1A/X box binding protein 1, and activating transcription factor 6 (ATF6), and each of these pathways has been implicated to have a protective or pathological role in FLD.

Contributions of new hepatocyte lineages to liver growth, maintenance, and regeneration in mice

Sonya V. Iverson, Kristin M. Comstock, Jean A. Kundert, Edward E. Schmidt – 29 April 2011 – The contributions that de novo differentiation of new hepatocyte lineages makes to normal liver physiology are unknown. In this study, a system that uniquely marks cells during a finite period following primary activation of a serum albumin gene promoter/enhancer‐driven Cre recombinase (albCre) transgene was used to investigate birthrates of new hepatocyte lineages from albumin (Alb)‐naive precursors in mice.

Genetic ablation or chemical inhibition of phosphatidylcholine transfer protein attenuates diet‐induced hepatic glucose production

Ekaterina Y. Shishova, Janis M. Stoll, Baran A. Ersoy, Sudeep Shrestha, Erez F. Scapa, Yingxia Li, Michele W. Niepel, Ya Su, Linda A. Jelicks, Gregory L. Stahl, Marcie A. Glicksman, Roger Gutierrez‐Juarez, Gregory D. Cuny, David E. Cohen – 29 April 2011 – Phosphatidylcholine transfer protein (PC‐TP, synonym StARD2) is a highly specific intracellular lipid binding protein that is enriched in liver. Coding region polymorphisms in both humans and mice appear to confer protection against measures of insulin resistance.

Hepatic organic anion transporting polypeptide transporter and thyroid hormone receptor interplay determines cholesterol and glucose homeostasis

Henriette E. Meyer zu Schwabedissen, Joseph A. Ware, David Finkelstein, Amarjit S. Chaudhry, Sara Mansell, Matilde Leon‐Ponte, Stephen C. Strom, Hani Zaher, Ute I. Schwarz, David J. Freeman, Erin G. Schuetz, Rommel G. Tirona, Richard B. Kim – 28 April 2011 – The role of organic anion transporting polypeptides (OATPs), particularly the members of OATP1B subfamily, in hepatocellular handling of endogenous and exogenous compounds is an important and emerging area of research.

Hepatitis C virus–infected women have a higher risk of advanced fibrosis and graft loss after liver transplantation than men

Jennifer C. Lai, Elizabeth C. Verna, Robert S. Brown, Jacqueline G. O'Leary, James F. Trotter, Lisa M. Forman, Jeffrey D. Duman, Richard G. Foster, R. Todd Stravitz, Norah A. Terrault, for the Consortium to Study Health Outcomes in HCV Liver Transplant Recipients (CRUSH‐C) – 28 April 2011 – In natural history studies of hepatitis C virus (HCV) infection, women have a lower risk of disease progression to cirrhosis. Whether female sex influences outcomes of HCV in the posttransplantation setting is unknown.

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