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)

The removal of pathogens from the circulation is achieved primarily by cells of the mononuclear phagocyte system, also known as the reticuloendothelial system. The tissue macrophage is the most important component of this system. The phagocytic activity of macrophages is regulated by opsonins on pathogenic materials and by endogenous cytokines. A number of diseases are caused by qualitative or quantitative disorders of phagocytosis by four major mechanisms: a decrease in the flow of blood to organs which contain macrophages (e.g. congestive heart failure and portal hypertension); a decrease in the quantity of tissue which contains macrophages (e.g. hepatic cirrhosis and splenectomy); a decrease in the effective opsonization of pathogens because of a deficiency of complement or IgG; and qualitative dysfunction of macrophages due to a deficiency of regulatory cytokines (e.g. gamma interferon and tuftsin) or a direct inhibitory effect on the macrophage (e.g. viral infections). New approaches for selective regulation of the phagocytic activity of macrophages are emerging.
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PMID:Regulation of macrophage phagocytosis. 308 38

We investigated the role of the interferon system in the pathogenesis of chronic liver disease. Interferon-gamma production by peripheral blood mononuclear cells was measured with an ELISA. While concanavalin A-stimulated and recombinant interleukin 2-stimulated production of interferon-gamma in patients with chronic active hepatitis and liver cirrhosis was significantly decreased when compared with that of controls (518 +/- 189 and 729 +/- 195 units per ml, mean +/- S.D.), there was also a lot of overlap. Addition of indomethacin to the cultures partially restored interferon-gamma production in patients with chronic active hepatitis and liver cirrhosis, indicating that suppressor function of monocytes was, in part, responsible for the diminished interferon-gamma production. Serial studies showed that interferon-gamma production rose during acute deterioration of illness, during treatment with interleukin 2 and with the improvement of clinical course. Interferon-gamma production was not different among hepatitis B e antigen or antibody positive, and non-A, non-B patients with chronic active hepatitis and liver cirrhosis. Our findings suggest that diminished interferon-gamma production is associated with disease severity in chronic liver disease, irrespective of the hepatitis B virus carrier state. It would be interesting to compare the efficacy of treatment with interferon-gamma or interferon-gamma inducers such as interleukin 2 in chronic hepatitis B patients with and without decreased in vitro interferon-gamma production.
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PMID:Interferon-gamma production by peripheral blood mononuclear cells of patients with chronic liver disease. 310 84

Hepatic cirrhosis is characterized by the replacement of normal liver parenchyma by collagenous fibrous tissue. Although hepatocytes in the adult retain the ability to divide, under certain circumstances hepatocyte death leads to replacement with fibroblasts and collagen. Whether a particular form of hepatocyte injury leads to cirrhosis is dependent upon the stimulus for the injury and is also highly variable between individuals. It has recently been shown that gamma interferon inhibits collagen synthesis in vitro and fibrosis in vivo. I suggest that individuals who are prone to hepatic cirrhosis from a given stimulus are low producers of gamma interferon while high gamma interferon producers are relatively protected from cirrhosis. I also hypothesize that exogenous gamma interferon administration may halt or slow the progression of cirrhosis in patients with early progressive cirrhosis. Alternatively, endogenous gamma interferon production could be stimulated in these patients with progressive cirrhosis. One agent which may be useful for inducing endogenous gamma interferon is GE-132, an organogermanium.
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PMID:Endogenous gamma interferon production may protect against hepatic cirrhosis and administration of exogenous gamma interferon may protect individuals prone to cirrhosis. 310 36

The HBsAg carrier state may present as chronic active hepatitis which may proceed to cirrhosis of the liver and to primary liver cell carcinoma. The large scale production of interferons made these substances available for long-term treatment. A deficiency in interferon production in chronic type B hepatitis presented the rational to treat this disease with interferon alpha-A. In this phase II-trial 3/31 patients eliminated HBsAg and 14/31 HBeAg. This was followed by normalisation of liver function tests and probably an improved prognosis. Efficiency of treatment was dependent on the interferon dose, the level of viral replication, the level of liver enzymes before treatment and concurrent infections (e. g. HIV infection). Reactivation occurred in five patients suggesting that the treatment period was too short in some individuals. Future studies will potentially improve efficiency by the modification of the interferon schedule and a better understanding of the mode of action of interferon.
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PMID:[Treatment of hepatitis B surface antigen (HBsAg)-positive chronic hepatitis with recombinant alpha-A-interferon. Results of a phase II study]. 322 6

The Hepatitis Delta Virus (HDV), a defective ribonucleic acid virus dependent on the Hepatitis B Virus (HBV) is a cause of severe liver disease that often leads to cirrhosis and death. Since the HDV finds in the HBV infection a biological niche in which to thrive indefinitely, the major victims of its infection are the carriers of HBsAg. Spontaneous resolution of chronic HDV hepatitis has been observed rarely and therapeutic attempts with steroids or azathioprine and levamisole have been discouraging. With the advent of recombinant DNA technologies several human alpha-interferons (IFNs) have been synthesized by genetic engineering and the availability of large amounts of the drug has dramatically altered the therapeutic prospects of viral hepatitis. In view of the wide range of biological activities of IFN, including inhibition of viral nucleic acid replication, we have tested the tolerance and the efficacy of this drug in chronic HDV hepatitis. The preliminary results of this study are reported.
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PMID:Treatment of chronic delta hepatitis with alpha-2 recombinant interferon. 329 10

To investigate mitogen induced helper interleukin 2 (IL-2) production in patients with chronic liver disease (CLD), IL-2 activity was assessed by an IL-2 bioassay using phytohaemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMNC). IL-2 activity was significantly reduced in patients with autoimmune chronic active hepatitis, primary biliary cirrhosis and alcoholic hepatitis with or without cirrhosis (P less than 0.01), and was comparable to controls in those with alcoholic cirrhosis alone. In vitro preincubation of PBMNC with lymphoblastoid alpha-interferon (alpha-IFN) before stimulation with PHA, led to a significant increase in IL-2 activity in all subjects (P less than 0.01), except those with alcoholic hepatitis, but in none of the groups did the levels of IL-2 activity reach those seen in normal subjects. The decrease in IL-2 activity in patients with CLD may be due to low IL-2 production or presence of an IL-2 antagonist(s). Such an abnormality may occur, not only as a result of liver damage, but may also be important in determining immunological disturbances involved in the pathogenesis of the liver disease.
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PMID:Interleukin 2 activity in chronic liver disease and the effect of in vitro alpha-interferon. 348 32

beta 2-Microglobulin display was examined in 131 liver biopsies from patients with acute and chronic type B hepatitis, using an indirect immunoperoxidase method. Enhanced expression of beta 2-microglobulin on hepatocyte membranes was observed in patients with acute hepatitis, chronic active hepatitis with moderate to severe activity and cirrhosis, when compared with normal liver. In acute hepatitis, beta 2-microglobulin-positive hepatocytes were mainly observed in perivenular areas in association with bridging necrosis. In chronic hepatitis, beta 2-microglobulin-positive hepatocytes were observed mainly in periportal zones and in some areas of lobular activity. Diffuse-enhanced display of beta 2-microglobulin on hepatocytes was observed in 5 of 6 patients treated with lymphoblastoid interferon as part of a trial of antiviral therapy. The mechanism by which beta 2-microglobulin display is enhanced on hepatocytes in patients not treated with interferon is uncertain. However, display of beta 2-microglobulin on hepatocytes probably reflects display of HLA-A, B and C antigens and may influence the course of hepatitis B virus infection by increasing susceptibility of the affected cells to T cell-mediated immune attack.
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PMID:Expression of beta 2-microglobulin on hepatocytes in acute and chronic type B hepatitis. 351 Sep 50

Cells expressing alpha 2-interferon were identified by indirect immunofluorescence using both a polyclonal and a monoclonal anti-alpha-interferon antibody reagent. In hepatitis B or delta virus infection, focal clusters of alpha-interferon-positive infiltrating mononuclear cells and (to a lesser extent) fibroblasts were regularly seen in liver sections from patients who had chronic active hepatitis and cirrhosis and evidence of virus replication, but in a minority of patients with chronic persistent hepatitis B and not in nonvirally infected livers. This report provides evidence for local alpha-interferon production near the site of virus replication in hepatitis B infection, identifies mononuclear cells and fibroblasts (but not hepatocytes) as the main cell types producing interferon in this infection and suggests that locally produced alpha-interferon may be a natural regulator of virus replication in HBsAg-positive chronic active hepatitis. Furthermore, serological characterization of the interferon species produced locally may predict which particular interferon species could be of the greatest therapeutic benefit in specific disease states or individual patients.
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PMID:Cellular localization of alpha-interferon in hepatitis B virus-infected liver tissue. 353 Sep 48

Using antibodies directed to beta 2-microglobulin (b2-m) and HLADR antigens, the expression of MHC products by normal and abnormal bile ducts in 90 paraffin-embedded biopsies showing various liver diseases, was studied. Normal and abnormal bile ducts constantly expressed b2-m. Increased b2-m expression was found in 17/19 PBC, and 4/7 chronic aggressive hepatitis or cirrhosis of viral etiology with hepatitic bile duct lesions. Normal bile ducts failed to express HLADR antigens. Aberrant HLADR display was found in 24/26 PBC and 10/16 chronic aggressive hepatitis or cirrhosis of viral etiology with hepatitic bile duct lesions. It is concluded that the pattern of the major histocompatibility complex (MHC) display does not discriminate between PBC and hepatitic bile duct lesions. Enhanced expression of class I MHC products at the surface of medium-sized bile ducts in PBC may render these structures more susceptible to lysis by cytotoxic T-cells, whereas its significance in chronic aggressive hepatitis or cirrhosis remains unknown. Aberrant expression of HLADR antigens by abnormal bile ducts in PBC and chronic aggressive hepatitis or cirrhosis of viral etiology is probably induced by gamma-interferon, liberated by intra-epithelial lymphocytes, and may serve to enhance the immune response, either by attracting HLADR-restricted cytotoxic T-cells or by the presentation of non-self antigens at the surface of bile duct epithelium.
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PMID:Expression of MHC products by normal and abnormal bile duct epithelium. 354 67

Immunoglobulin M antibody to hepatitis B core antigen (IgM anti-HBc) was measured by radioimmunoassay in the sera of 96 HBV carriers. IgM anti-HBc was detected in 17 of 66 patients with chronic active hepatitis and in 4 of 11 with liver cirrhosis. This antibody was not present in asymptomatic carriers or in patients with chronic persistent hepatitis. Testing of sequential samples revealed that the presence of IgM anti-HBc indicated active replication of HBV and at the same time an immune response to the virus. The relationship between IgM anti-HBc and the response to interferon (IFN) therapy was also studied. Results showed that IgM anti-HBc is a useful marker of the efficacy of interferon therapy.
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PMID:Immunoglobulin M antibody to hepatitis B core antigen (IgM anti-HBc) as a marker of interferon therapy in patients with persistent hepatitis B virus infection. 367 47


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