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      Liver stiffness: a novel parameter for the diagnosis of liver disease

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          Abstract

          The noninvasive quantitation of liver stiffness (LS) by ultrasound based transient elastography using FibroScan® has revolutionized the diagnosis of liver diseases, namely liver cirrhosis. Alternative techniques such as acoustic radiation impulse frequency imaging or magnetic resonance elastography are currently under investigation. LS is an excellent surrogate marker of advanced fibrosis (F3) and cirrhosis (F4) outscoring all previous noninvasive approaches to detect cirrhosis. LS values below 6 kPa are considered as normal and exclude ongoing liver disease. LS of 8 and 12.5 kPa represent generally accepted cut-off values for F3 and F4 fibrosis. LS highly correlates with portal pressure, and esophageal varices are likely at values >20 kPa. Many other factors may also increase LS such as hepatic infiltration with tumor cells, mast cells (mastocytosis), inflammatory cells (all forms of hepatitis) or amyloidosis. In addition, LS is directly correlated with the venous pressure (eg, during liver congestion) and is increased during mechanic cholestasis. Thus, LS should always be interpreted in the context of clinical, imaging and laboratory findings. Finally, LS has helped to better understand the molecular mechanisms underlying liver fibrosis. The novel pressure-stiffness-fibrosis sequence hypothesis is introduced.

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          Liver fibrosis.

          Liver fibrosis is the excessive accumulation of extracellular matrix proteins including collagen that occurs in most types of chronic liver diseases. Advanced liver fibrosis results in cirrhosis, liver failure, and portal hypertension and often requires liver transplantation. Our knowledge of the cellular and molecular mechanisms of liver fibrosis has greatly advanced. Activated hepatic stellate cells, portal fibroblasts, and myofibroblasts of bone marrow origin have been identified as major collagen-producing cells in the injured liver. These cells are activated by fibrogenic cytokines such as TGF-beta1, angiotensin II, and leptin. Reversibility of advanced liver fibrosis in patients has been recently documented, which has stimulated researchers to develop antifibrotic drugs. Emerging antifibrotic therapies are aimed at inhibiting the accumulation of fibrogenic cells and/or preventing the deposition of extracellular matrix proteins. Although many therapeutic interventions are effective in experimental models of liver fibrosis, their efficacy and safety in humans is unknown. This review summarizes recent progress in the study of the pathogenesis and diagnosis of liver fibrosis and discusses current antifibrotic strategies.
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            Specific aquaporins facilitate the diffusion of hydrogen peroxide across membranes.

            The metabolism of aerobic organisms continuously produces reactive oxygen species. Although potentially toxic, these compounds also function in signaling. One important feature of signaling compounds is their ability to move between different compartments, e.g. to cross membranes. Here we present evidence that aquaporins can channel hydrogen peroxide (H2O2). Twenty-four aquaporins from plants and mammals were screened in five yeast strains differing in sensitivity toward oxidative stress. Expression of human AQP8 and plant Arabidopsis TIP1;1 and TIP1;2 in yeast decreased growth and survival in the presence of H2O2. Further evidence for aquaporin-mediated H2O2 diffusion was obtained by a fluorescence assay with intact yeast cells using an intracellular reactive oxygen species-sensitive fluorescent dye. Application of silver ions (Ag+), which block aquaporin-mediated water diffusion in a fast kinetics swelling assay, also reversed both the aquaporin-dependent growth repression and the H2O2-induced fluorescence. Our results present the first molecular genetic evidence for the diffusion of H2O2 through specific members of the aquaporin family.
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              Shear wave elasticity imaging: a new ultrasonic technology of medical diagnostics.

              Shear wave elasticity imaging (SWEI) is a new approach to imaging and characterizing tissue structures based on the use of shear acoustic waves remotely induced by the radiation force of a focused ultrasonic beam. SWEI provides the physician with a virtual "finger" to probe the elasticity of the internal regions of the body. In SWEI, compared to other approaches in elasticity imaging, the induced strain in the tissue can be highly localized, because the remotely induced shear waves are attenuated fully within a very limited area of tissue in the vicinity of the focal point of a focused ultrasound beam. SWEI may add a new quality to conventional ultrasonic imaging or magnetic resonance imaging. Adding shear elasticity data ("palpation information") by superimposing color-coded elasticity data over ultrasonic or magnetic resonance images may enable better differentiation of tissues and further enhance diagnosis. This article presents a physical and mathematical basis of SWEI with some experimental results of pilot studies proving feasibility of this new ultrasonic technology. A theoretical model of shear oscillations in soft biological tissue remotely induced by the radiation force of focused ultrasound is described. Experimental studies based on optical and magnetic resonance imaging detection of these shear waves are presented. Recorded spatial and temporal profiles of propagating shear waves fully confirm the results of mathematical modeling. Finally, the safety of the SWEI method is discussed, and it is shown that typical ultrasonic exposure of SWEI is significantly below the threshold of damaging effects of focused ultrasound.
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                Author and article information

                Journal
                Hepat Med
                Hepat Med
                Hepatic Medicine: Evidence and Research
                Hepatic Medicine : Evidence and Research
                Dove Medical Press
                1179-1535
                2010
                25 May 2010
                : 2
                : 49-67
                Affiliations
                [1 ]Department of Medicine and Center for Alcohol Research, Liver Disease and Nutrition, Salem Medical Center, University of Heidelberg, Heidelberg, Germany
                [2 ]Echosens, Department of Research and Development, Paris, France
                Author notes
                Correspondence: Sebastian Mueller, Department of Internal Medicine, Salem Medical Center, University of Heidelberg, Zeppelinstraße 11-33, 69121 Heidelberg, Germany, Tel +49 6221 483210, Fax +49 6221 484494, Email sebastian.mueller@ 123456urz.uni-heidelberg.de
                Article
                hmer-2-049
                10.2147/HMER.S7394
                3846375
                24367208
                e3474d18-f525-4797-b4ba-4c93b420aa88
                © 2010 Mueller and Sandrin, publisher and licensee Dove Medical Press Ltd

                This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

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                Categories
                Review

                liver stiffness,fibrosis,liver disease,transient elastography

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