Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatocellular carcinoma (HCC) occurs most commonly secondary to cirrhosis due to chronic hepatitis C or B virus (HCV/HBV) infections. Type I interferon (IFN-alpha) treatment of chronic HCV/HBV infections reduces the incidence of HCC in cirrhotic patients. However, IFN-alpha toxicity limits its tolerability and efficacy highlighting a need for better therapeutic treatments. A recently discovered type III IFN (IFN-lambda) has been shown to possess antiviral properties against HCV and HBV in vitro. In phase I clinical trials, IFN-lambda treatment did not cause significant adverse reactions. Using a gene therapy approach, we compared the antitumor properties of IFN-alpha and IFN-lambda in a transplantable hepatoma model of HCC. BALB/c mice were inoculated with syngeneic BNL hepatoma cells, or BNL cells expressing IFN-lambda (BNL.IFN-lambda cells) or IFN-alpha (BNL.IFN-alpha cells). Despite the lack of antiproliferative activity of IFNs on BNL cells, both BNL.IFN-lambda and BNL.IFN-alpha cells displayed retarded growth kinetics in vivo. Depletion of NK cells from splenocytes inhibited splenocyte-mediated cytotoxicity, demonstrating that NK cells play a role in IFN-induced antitumor responses. However, isolated NK cells did not respond directly to IFN-lambda. There was also a marked NK cell infiltration in IFN-lambda producing tumors. In addition, IFN-lambda and, to a lesser extent, IFN-alpha enhanced immunocytotoxicity of splenocytes primed with irradiated BNL cells. Splenocyte cytotoxicity against BNL cells was dependent on IL-12 and IFN-gamma, and mediated by dendritic cells. In contrast to NK cells, isolated from spleen CD11c+ and mPDCA+ dendritic cells responded directly to IFN-lambda. The antitumor activities of IFN-lambda against hepatoma, in combination with HCV and HBV antiviral activities warrant further investigation into the clinical use of IFN-lambda to prevent HCC in HCV/HBV-infected cirrhotic patients, as well as to treat liver cancer.
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PMID:Antitumor activity of type I and type III interferons in BNL hepatoma model. 2021 81

No specific treatment can reverse the liver injury in cirrhosis. This study aims to characterize immune status and correlations between cirrhosis induced by HBV and HCV. Phenotypes of peripheral blood lymphocyte subsets (T, NK, regulatory T cells) and Th cytokine secretion were analyzed using flow cytometry in 42 HBV-cirrhotic and 40 HCV-cirrhotic patients. Cirrhotic patients had a lower proportion of CD3(+)CD8(+)T cells and NK cells, while the proportion of CD3(+)CD4(+)T cells and Treg cells were higher than those of healthy controls. The levels of Th2 cytokine (IL-6) in cirrhotic patients were increased, while only the Th1 cytokine (IFN-gamma) increased in HBV-cirrhotic patients. These findings show that there is no difference between the cirrhotic groups except in the IFN-gamma level. In cirrhosis, defects in innate, adaptive immune cells are likely regardless of which virus is involved. A cytokine imbalance may play a role in the development of posthepatitic cirrhosis.
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PMID:Immunologic characterization of posthepatitis cirrhosis caused by HBV and HCV infection. 2061 33

Approximately 500 million people worldwide are chronically infected with the hepatitis B virus (HBV) or hepatitis C virus (HCV), and are therefore at an increased risk for developing fatal liver diseases such as cirrhosis and hepatocellular carcinoma. The intracellular antiviral responses induced by interferon (IFN)-alpha/-beta and/or IFN-gamma play critical roles in the pathogenesis of HBV and HCV infection, and the function of IFN-lambda in the host immune response to these viruses is beginning to be revealed. A better understanding of how IFN-lambda influences HBV or HCV persistence is not only important for understanding the mechanisms of chronic virus infection, but also may lead to new approaches for improved antiviral therapies.
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PMID:Interferon-lambda in the immune response to hepatitis B virus and hepatitis C virus. 2064 75

Interferon (IFN)-inducible protein-10 (IP-10) is a proinflammatory chemokine, binding the chemokine (C-X-C motif) receptor 3 (CXCR3), which is found mainly on activated T cells and natural killer (NK) cells, and plays an important role in T helper (Th) 1 type inflammatory disorders (autoimmune, neoplastic, and infectious diseases). Concerning viral hepatitis, IP-10 appears to be involved on the pathogenesis of liver damage as well as on the extra-hepatic manifestations either protecting or promoting infection, depending on host immune status and genetic background. During chronic hepatitis B, IP-10 is specifically produced by hepatocytes in inflammatory areas. Here, IP-10 leads to recruitment of T cells, production of IFN-gamma by activated NK T cells, and then monokine induced by IFN-gamma (MIG) and IP-10 secretion by parenchymal and non-parenchymal cells, with a final positive feedback, perpetuating the immune cascade. The increased levels of IP-10 and IP-10 mRNA in the peripheral blood of patients with cirrhosis are closely correlated with the load of HBV DNA in serum, and seem to play a key role in the progression of post-hepatitic cirrhosis. Higher pre-treatment IP-10 levels, and dynamic down-regulation, are associated with an increased probability of hepatitis B e antigen (HBeAg) loss after Peg-IFN therapy. Hepatitis B surface antigen (HBsAg) drop in patients treated with nucleos(t)ide analogues (NAs) is associated with higher baseline IP-10.
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PMID:Hepatitis B virus infection and interferon-inducible protein-10. 2615 31


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