Virological breakthrough and resistance in patients with chronic hepatitis B receiving nucleos(t)ide analogues in clinical practice

Chanunta Hongthanakorn, Watcharasak Chotiyaputta, Kelly Oberhelman, Robert J. Fontana, Jorge A. Marrero, Tracy Licari, Anna S. F. Lok – 24 March 2011 – Virological breakthrough (VBT) is the first manifestation of antiviral drug resistance during nucleos(t)ide analogue (NUC) treatment of chronic hepatitis B (CHB), but not all VBTs are due to drug resistance. This study sought to determine the incidence of VBT and genotypic resistance (GR) in patients with CHB who were receiving NUCs in clinical practice. Records of patients with CHB who were receiving NUCs were reviewed.

Heme oxygenase‐1–mediated autophagy protects against hepatocyte cell death and hepatic injury from infection/sepsis in mice

Evie H. Carchman, Jayashree Rao, Patricia A. Loughran, Matthew R. Rosengart, Brian S. Zuckerbraun – 24 March 2011 – Adaptive responses to sepsis are necessary to prevent organ failure and death. Cellular signaling responses that limit cell death and structural damage allow a cell to withstand insult from sepsis to prevent irreversible organ dysfunction. One such protective pathway to reduce hepatocellular injury is the up‐regulation of heme oxygenase‐1 (HO‐1) signaling.

Macrophage therapy for murine liver fibrosis recruits host effector cells improving fibrosis, regeneration, and function

James A. Thomas, Caroline Pope, Davina Wojtacha, Andrew J. Robson, Timothy T. Gordon‐Walker, Stephen Hartland, Prakash Ramachandran, Marielle Van Deemter, David A. Hume, John P. Iredale, Stuart J. Forbes – 23 March 2011 – Clinical studies of bone marrow (BM) cell therapy for liver cirrhosis are under way but the mechanisms of benefit remain undefined. Cells of the monocyte‐macrophage lineage have key roles in the development and resolution of liver fibrosis. Therefore, we tested the therapeutic effects of these cells on murine liver fibrosis.

Polyinosinic‐polycytidylic acid suppresses acetaminophen‐induced hepatotoxicity independent of type I interferons and toll‐like receptor 3

Amir A. Ghaffari, Edward K. Chow, Shankar S. Iyer, Jane C. Deng, Genhong Cheng – 23 March 2011 – Viral infections are often linked to altered drug metabolism in patients; however, the underlying molecular mechanisms remain unclear. Here we describe a mechanism by which activation of antiviral responses by the synthetic double‐stranded RNA ligand, polyinosinic‐polycytidylic acid (polyI:C), leads to decreased acetaminophen (APAP) metabolism and hepatotoxicity.

Carbon monoxide enhances early liver regeneration in mice after hepatectomy

Kaori Kuramitsu, David Gallo, Myunghee Yoon, Beek Y. Chin, Eva Csizmadia, Douglas W. Hanto, Leo E. Otterbein – 23 March 2011 – Hepatocyte proliferation early after liver resection is critical in restoring liver mass and preserving function as the liver regenerates. Carbon monoxide (CO) generated by heme oxygenase‐1 (HO‐1) strongly influences cellular proliferation and both HO‐1 and CO are accepted hepatoprotective molecules. Mice lacking functional HO‐1 were unable to mount an appropriate regenerative response following partial hepatectomy (PHTx) compared to wildtype controls.

Diclofenac inhibits tumor necrosis factor‐α‐induced nuclear factor‐κB activation causing synergistic hepatocyte apoptosis

Lisa Fredriksson, Bram Herpers, Giulia Benedetti, Quraisha Matadin, Jordi C. Puigvert, Hans de Bont, Sanja Dragovic, Nico P.E. Vermeulen, Jan N.M. Commandeur, Erik Danen, Marjo de Graauw, Bob van de Water – 23 March 2011 – Drug‐induced liver injury (DILI) is an important clinical problem. It involves crosstalk between drug toxicity and the immune system, but the exact mechanism at the cellular hepatocyte level is not well understood. Here we studied the mechanism of crosstalk in hepatocyte apoptosis caused by diclofenac and the proinflammatory cytokine tumor necrosis factor α (TNF‐α).

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