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eISSN: 1643-3750

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Apoptosis in liver diseases - detection and therapeutic applications.

Saeid Ghavami, Saeid Ghavami, Mohammad Hashemi, Kamran Kadkhoda, Seyed Moayed Alavian, Graham H Bay, Marek Los

Med Sci Monit 2005; 11(11): RA337-345

ID: 430372


The liver is continuously exposed to a large antigenic load that includespathogens, toxins, tumor cells and dietary antigens. Amongst the hepatitis viruses, only hepatitis Bvirus (HBV) and hepatitis C virus (HCV) cause chronic hepatitis, which can progress to cirrhosis andhepatocellular carcinoma. Of the different antiviral defense systems employed by the tissue, apoptosissignificantly contributes to the prevention of viral replication, dissemination, and persistence. Lossof tolerance to the liver autoantigens may result in autoimmune hepatitis (AIH). This review outlinesthe recent findings that highlight the role and mechanisms of apoptotic processes in the course of liverdiseases. Among factors that contribute to liver pathology, we discuss the role of tumor necrosis factor(TNF)-alpha, HBx, ds-PKR, TRAIL, FasL, and IL-1alpha. Since TNF and FasL-induced hepatocyte apoptosisis implicated in a wide range of liver diseases, including viral hepatitis, alcoholic hepatitis, ischemia/reperfusionliver injury, and fulminant hepatic failure, these items will be discussed in greater detail in thisreview. We also highlight some recent discoveries that pave the way for the development of new therapeuticstrategies by protecting hepatocytes (for example by employing Bcl-2, Bcl-X(L) or A1/Bfl-1, IAPs, orsynthetic caspase inhibitors), or by the induction of apoptosis in stellate cells. The assessment ofthe severity of liver disease, as well as monitoring of patients with chronic liver disease, remainsa major challenge in clinical hepatology practice. Therefore, a separate chapter is devoted to a novelcytochrome c - based method useful for the diagnosis and monitoring of fulminant hepatitis.

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