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Between Scylla and Charybdis:The role of the human immune system in the pathogenesis of hepatitis C

World Journal of Gastroenterology 2013年第44期19卷 7852-7866页

作者： Ulrich Spengler hans dieter nischalke Jacob Nattermann Christian P Strassburg Department of Internal Medicine 1 University of Bonn 53105 Bonn Germany

Hepatitis C virus(HCV)frequently elicits only mild immune responses so that it can often establish chronic *** this case HCV antigens persist and continue to stimulate the immune *** persistence then leads to profound changes in the infected host’s immune responsiveness,and eventually contributes to the pathology of chronic *** topic highlight summarizes changes associated with chronic hepatitis C concerning innate immunity(interferons,natural killer cells),adaptive immune responses(immunoglobulins,T cells,and mechanisms of immune regulation(regulatory T cells).Our overview clarifies that a strong anti-HCV immune response is frequently associated with acute severe tissue *** chronic hepatitis C,however,the effector arms of the immune system either become refractory to activation or take over regulatory *** together these changes in immunity may lead to persistent liver damage and ***,effector arms of the immune system will not only be considered with respect to antiviral defence but also as pivotal mechanisms of inflammation,necrosis and progression to ***,avoiding Scylla-a strong,sustained antiviral immune response with inital tissue damage-takes the infected host to virus-triggered immunopathology,which ultimately leads to cirrhosis and liver cancerthe realm of Charybdis.

关键词： Natural killer cells CD4+ T helper cells Regulatory T cells Interferon Hepatitis C Hepatic stellate cells Hepatocytes Immunoglobulin Retinoic acid inducible gene-I Toll like receptors

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Spontaneous bacterial peritonitis: The clinical challenge of a leaky gut and a cirrhotic liver

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World Journal of Hepatology 2015年第3期7卷 304-314页

作者： Philipp Lutz hans dieter nischalke Christian P Strassburg Ulrich Spengler Department of Internal Medicine I University of Bonn German Center for Infection Research

Spontaneous bacterial peritonitis(SBP) is a frequent, life-threatening bacterial infection in patients with liver cirrhosis and ascites. Portal hypertension leads to increased bacterial translocation from the intestine. Failure to eliminate invading pathogens due to immune defects associated with advanced liver disease on the background of genetic predisposition may result in SBP. The efficacy of antibiotic treatment and prophylaxis has declined due to the spread of multi-resistant bacteria. Patients with nosocomial SBP and with prior antibiotictreatment are at a particularly high risk for infection with resistant bacteria. Therefore, it is important to adapt empirical treatment to these risk factors and to the local resistance profile. Rifaximin, an oral, nonabsorbable antibiotic, has been proposed to prevent SBP, but may be useful only in a subset of patients. Since novel antibiotic classes are lacking, we have to develop prophylactic strategies which do not induce bacterial resistance. Farnesoid X receptor agonists may be a candidate, but so far, clinical studies are not available. New diagnostic tests which can be carried out quickly at the patient's site and provide additional prognostic information would be helpful. Furthermore, we need tools to predict antibiotic resistance in order to tailor first-line antibiotic treatment of spontaneous bacterial peritonitis to the individual patient and to reduce mortality.

关键词： Ascites Cirrhosis Farnesoid X receptor Liver Nucleotide-binding oligomerization domaincontaining 2 Rifaximin Prophylaxis Spontaneousbacterial peritonitis Toll-like receptor 2

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