Hepatitis following famotidine: a case report

H2 receptor antagonists can rarely cause idiosyncratic drug reactions leading to acute hepatitis. Famotidine, however, is considered a relatively safe drug with regards to hepatotoxicity. We report a case of a 47 year old male with a history of hepatitis C who developed acute hepatitis on the third day of hospitalization with a dramatic rise in his liver enzymes from normal values at the time of admission. The acute rise in liver enzymes made us consider an adverse drug reaction and famotidine was discontinued. Subsequently his liver enzymes came back to normal in seven days. Thus, physicians should consider famotidine induced hepatitis as a possible etiology of acute liver dysfunction

Proteinase Activated Receptor 1 Mediated Fibrosis in a Mouse Model of Liver Injury: A Role for Bone Marrow Derived Macrophages

Published onlineJournal ArticleResearch Support, Non-U.S. Gov'tThis is the final version of the article. Available from Public Library of Science via the DOI in this record.Liver fibrosis results from the co-ordinated actions of myofibroblasts and macrophages, a proportion of which are of bone marrow origin. The functional effect of such bone marrow-derived cells on liver fibrosis is unclear. We examine whether changing bone marrow genotype can down-regulate the liver's fibrotic response to injury and investigate mechanisms involved. Proteinase activated receptor 1 (PAR1) is up-regulated in fibrotic liver disease in humans, and deficiency of PAR1 is associated with reduced liver fibrosis in rodent models. In this study, recipient mice received bone marrow transplantation from PAR1-deficient or wild-type donors prior to carbon tetrachloride-induced liver fibrosis. Bone marrow transplantation alone from PAR1-deficient mice was able to confer significant reductions in hepatic collagen content and activated myofibroblast expansion on wild-type recipients. This effect was associated with a decrease in hepatic scar-associated macrophages and a reduction in macrophage recruitment from the bone marrow. In vitro, PAR1 signalling on bone marrow-derived macrophages directly induced their chemotaxis but did not stimulate proliferation. These data suggest that the bone marrow can modulate the fibrotic response of the liver to recurrent injury. PAR1 signalling can contribute to this response by mechanisms that include the regulation of macrophage recruitment.Funding for YNK SJF came from the MRC Clinical Research Training Fellowship (G0500428), www.mrc.ac.uk. For CJS RCC: Wellcome Trust Programme Grant (071124), www.wellcome.ac.uk. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

FoxO1 regulates Tlr4 inflammatory pathway signalling in macrophages

The transcriptional regulator FoxO1 promotes inflammation by regulating TLR4-mediated signalling in macrophages. TLR4 activation as well as insulin signalling inactivates FoxO1, thereby limiting the inflammatory response