The epidermal growth factor receptor ligand amphiregulin participates in the development of mouse liver fibrosis

Maria J. Perugorria, M. Ujue Latasa, Alexandra Nicou, Hugo Cartagena‐Lirola, Josefa Castillo, Saioa Goñi, Umberto Vespasiani‐Gentilucci, Maria G. Zagami, Sophie Lotersztajn, Jesús Prieto, Carmen Berasain, Matias A. Avila – 26 September 2008 – The hepatic wound‐healing response to chronic noxious stimuli may lead to liver fibrosis, a condition characterized by excessive deposition of extracellular matrix. Fibrogenic cells, including hepatic stellate cells and myofibroblasts, are activated in response to a variety of cytokines, growth factors, and inflammatory mediators.

The hepatotoxic metabolite of acetaminophen directly activates the Keap1‐Nrf2 cell defense system

Ian M. Copple, Christopher E. Goldring, Rosalind E. Jenkins, Alvin J. L. Chia, Laura E. Randle, John D. Hayes, Neil R. Kitteringham, B. Kevin Park – 26 September 2008 – The transcription factor Nrf2 regulates the expression of numerous cytoprotective genes in mammalian cells. We have demonstrated previously that acetaminophen activates Nrf2 in mouse liver following administration of non‐hepatotoxic and hepatotoxic doses in vivo, implying that Nrf2 may have an important role in the protection against drug‐induced liver injury.

Hepatocyte nuclear factor 4α is implicated in endoplasmic reticulum stress–induced acute phase response by regulating expression of cyclic adenosine monophosphate responsive element binding protein H

Jennifer Luebke‐Wheeler, Kezhong Zhang, Michele Battle, Karim Si‐Tayeb, Wendy Garrison, Sodhi Chhinder, Jixuan Li, Randal J. Kaufman, Stephen A. Duncan – 26 September 2008 – Loss of the nuclear hormone receptor hepatocyte nuclear factor 4α (HNF4α) in hepatocytes results in a complex pleiotropic phenotype that includes a block in hepatocyte differentiation and a severe disruption to liver function. Recent analyses have shown that hepatic gene expression is severely affected by the absence of HNF4α, with expression of 567 genes reduced by ≥2.5‐fold (P ≤ 0.05) in Hnf4α−/− fetal livers.

Surveillance for hepatocellular carcinoma in patients with primary biliary cirrhosis

Marina G. Silveira, Ayako Suzuki, Keith D. Lindor – 26 September 2008 – Hepatocellular carcinoma (HCC) occurs with increased frequency in patients with primary biliary cirrhosis (PBC). Effectiveness of surveillance recommendations for HCC is controversial, and data are lacking in patients with PBC. In this study, we attempt to (1) establish the importance of surveillance for HCC in patients with PBC; (2) identify a target population of patients with PBC for HCC surveillance; and (3) propose surveillance recommendations for patients with PBC.

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