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)

Immunological disturbances with impairment of immune function and a higher incidence of lymphoproliferative disorders and other malignancies have been described in liver cirrhosis patients. To investigate the pathogenetic mechanism(s) involved in such associated we looked for a possible imbalance in peripheral blood T-lymphocyte subpopulations in patients with liver cirrhosis of differing severity. Immunophenotyping and counts of peripheral blood T-lymphocyte subpopulations were carried out using monoclonal antibodies conjugated with different fluorochromes in 31 consecutive cirrhotic patients and 23 matched healthy volunteers. Univariate and multivariate analyses of lymphocyte phenotype counts were performed and odds ratios were computed. Statistically significant associations, according to both univariate and multivariate analyses, were found between case/control status and mean CD3 and CD4 T-lymphocyte counts (P < 0.0001). A strong correlation was found between the Pugh's index and CD3 and CD4 lymphocyte counts, with a clear reduction of these phenotypes with increasing liver cirrhosis. Median CD3 and CD4 values were 2,283 and 1,329/microliters respectively among controls and 896, 801, and 492/microliters and 515, 514, and 307/microliters, respectively in categories A, B, and C of Pugh's classification. Very high odds ratios were found using the median values of CD3 and CD4 as a threshold. There was a statistically significant decrease for each of the T-cell phenotypes studied (CD2, CD3, CD4, CD8, CD16, CD19, CD20, CD56, CD57) between patients and controls (P < 0.0001). The progressive and severity-related decrease in mean peripheral blood CD3 and CD4 counts in liver cirrhosis suggests a progressive impairment of protective immune function and may be a factor facilitating malignancy in cirrhotic patients.
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PMID:Peripheral blood CD3 and CD4 T-lymphocyte reduction correlates with severity of liver cirrhosis. 856 79

Twelve children were included into the protocol, 5 in March 1989 and 7 in April 1993. All of them were HIV 1 positive and had diarrhoea, important adenopathy and opportunistic infections. Seven out of 12 patients had an immunological monitoring. One out of 12 children with B hepatitis died with liver cirrhosis. Eleven children had a clear improvement in their clinical course, during the treatment. Five out of 7 patients had a significant increase of the CD4 lymphocytes at 4 and 7 months follow-up. Four patients had an important and significant increase of the CD8 count at 4 months and 6 out of 7 patients at 7 months. Interestingly, in 4 out of 7 patients after 7 months treatment we observed higher than normal value of the CD8 count. Variations observed for CD8 population compared to CD4 were more important.
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PMID:Augmentation of CD8 and CD4 lymphocytes subsets in AIDS infected children after treatment with a non-toxic chelating agents compound--Rodilemid. 864 93

We describe two cases of pneumonia caused by Sho-saiko-to. Patient 1 was a 61-year-old man with type-C liver cirrhosis. About 50 days after starting to take Sho-saiko-to, he complained of fever and diarrhea, and progressive dyspnea developed. Analysis of arterial blood obtained in the emergency room showed severe hypoxemia:, PaO2 26 Torr. A chest radiograph and a CT scan showed bilateral diffuse fine granular and ground-glass opacities predominantly in the upper lung fields. Despite repeated pulse therapy with methylprednisolone and aggressive medical treatment including mechanical ventilation, the patient remained in respiratory distress, which was later complicated by gastrointestinal bleeding. He died on the 45th hospital day. The bronchoalveolar lavage contained abnormally high fluid percents of lymphocytes and neutrophils. Postmortem examination of the lungs revealed alveolar septal thickening, marked hyperplasia of type 2 pneumocytes, and no hyaline membrane formation. Patient 2 was a 68-year-old man. Eighty days after he began taking Sho-saiko-to, he presented with a 4-day history of shortness of breath accompanied by fewer and progressive coughing. On arrival of the hospital, arterial blood gas analysis showed mild hypoxemia (PaO2, 61 Torr) and a chest radiograph revealed bilateral irregular infiltrates in the lower lung fields. Analysis of bronchoalveolar lavage fluid showed an abnormally high percent of lymphocytes (especially CD8 + lymphocytes), and examination of a biopsy specimen revealed exudates of fibrin and neutrophils in the alveolar spaces and patechy intraluminal organization. The response to prednisolone was good and he was discharged on the 40th hospital day in stable condition. Drug lymphocyte stimulation tests of peripheral blood to Sho-saiko-to were positive in both patients. Patients 2 was though to have a typical case of Sho-saiko-to-induced pneumonia, patient 1 was thought to have fulminating variant of this disease.
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PMID:[Two cases of pneumonia caused by Sho-saiko-to]. 896 2

The immune response in liver cirrhosis and hepatocellular carcinoma is receiving renewed attention in consideration of the possible treatment with biological response modifiers. The aim of this study was to evaluate whether cirrhosis and hepatocellular carcinoma induce any modification in peripheral lymphocyte subsets. Lymphocytes were evaluated (number/percentage) in 61 patients with hepatocellular carcinoma, 35 with cirrhosis and 24 healthy controls. Using flow cytometry, 10 lymphocyte subpopulations were assayed, plus the CD4/CD8 ratio. Results demonstrated no change in the number of lymphocytes; cirrhosis and hepatocellular carcinoma patients had significantly more HLA-DR+ (p = 0.001) and CD3+/HLA-DR+ (activated T) (p = 0.002) and fewer CD3+ (mature T) (p = 0.02) cell than controls; hepatocellular carcinoma patients had significantly more CD3+/CD56+/CD16- (cytotoxic non-MHC restricted T cells) and CD25+ (IL-2 receptor positive cells). If the percentages of all cells with cytotoxic-T activity were pooled, a significant increase (p = 0.03) was seen in hepatocellular carcinoma patients. In conclusion, in contrast to previous data, hepatocellular carcinoma patients reveal an increased number of cytotoxic non-MHC restricted T cells.
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PMID:Activation of cytotoxic and natural killer T-cell system in patients with hepatocellular carcinoma and cirrhosis. 913 93

Chronic alcohol intake is associated with an increased incidence of certain neoplasms. Natural killer (NK) cells have been considered to be involved in control tumor development and growth. The goal of the present study was to contribute to a better understanding of the effects of ethanol (EtOH) per se on the NK-cell population. Both patients with chronic alcoholism without liver disease (AWLD) and subjects with alcohol-induced cirrhosis (ALC) were carefully selected for this study. Immunophenotypical and functional studies of peripheral blood (PB) NK-cells were performed during active EtOH intake and after 3 months of a withdrawal period. In the AWLD group a significant increase in number of NK-cells (CD3-/CD56+) (P < .05) associated with a parallel increase in NK-cell lytic activity (P < .01) was observed. In addition, the number of cytotoxic T cells displaying the CD3+/CD56+ phenotype as well as CD8-/CD57+ NK-cell subset was also increased (P < .01 and P < .001, respectively). By contrast, in ALC patients with active EtOH intake (ALCET group), although a significant increase in the number of NK PB lymphocytes was observed (P < .05), NK lytic activity was depressed (P < .05), suggesting the existence of a decreased lytic activity/NK-cell. After 3 months of EtOH withdrawal, PB mononuclear cells (PBMC) from the AWLD group patients still displayed an increased NK cytolytic activity; in addition, the number of PB NK-cells (CD3-/CD56+ and CD8-/CD57+) and CD3+/CD56+ PB T cells continued to be increased. Independently of the duration of withdrawal period, in ALC patients EtOH withdrawal was followed by a slight decrease in the NK lytic activity of PBMC with respect to the values in active alcoholism phase; slight differences observed in the NK lytic activity in ALC patients who quit drinking could be related to the tendency to decrease of the number of NK-cells toward normal values. Furthermore, although an increase in NK cytotoxic activity after stimulation of PBMC with interleukin-2 (IL-2) was observed in ALC, it did not reach the levels observed in healthy subjects. Overall, our results show that the behavior of PB NK-cell population in chronic alcoholism is different according to both the moment of EtOH consumption and the existence or not of ALC. Alcohol by itself induced an increase in the number and lytic activity of NK-cells. By contrast, the NK cytolytic activity is constantly depressed in the stage of alcoholic cirrhosis, supporting the notion that immunosurveillance mechanisms may be affected in these patients.
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PMID:Decreased natural killer cytotoxic activity in chronic alcoholism is associated with alcohol liver disease but not active ethanol consumption. 914 23

Soluble HLA-class I and CD8 molecules were determined by sandwich ELISA in patients with viral-induced hepatic disorders. As a whole, the patients with hepatic disorders (acute hepatitis: AH; chronic hepatitis: CH; liver cirrhosis: LC; hepatocellular carcinoma: HCC) showed higher sHLA-class I and sCD8 levels than normal controls (P < 0.001). AH patients had the highest sHLA-class I levels (mean, 3513 +/- 2112 ng/ml), followed by CH (2896 +/- 1290 ng/ml), LC (2293 +/- 1266 ng/ml), and HCC (2221 +/- 1212 ng/ml) sCD8 levels wer highest in AH, followed by HCC, LC, and CH, in that order. Among histologically defined C virus-positive patients, sHLA-I levels were higher in those with chronic active hepatitis (CAH) 2A (3802 +/- 1124 ng/ml) than in those with chronic persistent hepatitis (CPH; 2200 +/- 711 ng/ml; P < 0.01), the levels then decreased as the disease progressed (CAH2B, 3564 +/- 1783 ng/ml, LC, 2376 +/- 1265 ng/ml). In contrast, sCD8 values showed little difference among the disorders. sHLA-class I levels showed a positive correlation with sCD8 values both in whole patients and in patients with AH (P < 0.01), but no correlation was shown, in any patients, with biochemical parameters such as GPT and GOT. These findings, taken together, suggest that hepatic destruction is not the only cause of sHLA-class I production, but that sHLA-class I levels, together with sCD8 levels, may reflect immunological activity in hepatic disorders.
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PMID:Serum concentrations of soluble HLA-class I and CD8 forms in patients with viral hepatic disorders. 921 47

A controlled study was performed in 18 viral cirrhosis patients to evaluate whether immune function, as indicated by natural killer (NK) cell activity, was improved by a branched-chain amino acid-enriched nutrient mixture (nutrient-mixture), Aminoleban EN. Five patients received the nutrient-mixture (100 g/day) for 2 to 6 weeks preceded by control periods. Five additional patients received the nutrient-mixture for 2 to 4 weeks, and the remaining 8 patients did not receive the nutrient-mixture. NK cell activity, CD16, CD8, CD11b, and amino acids were assayed before and after the administration of the drug in the nutrient-mixture-supplemented group, and two times with 1 to 6 month intervals in the control group. In the nutrient-mixture-supplemented group (n = 10), increasing NK cell activity, expressed as the ratio of values of post-treatment to that of baseline (ratio > 1.25) was detected in 7 (70%) patients, whereas in the control group (n = 13), it was detected in only 1 (7.7%) (p < 0.01). While in the affected group (NK cell activity ratio > 1.25, n = 7), all patients had compensated liver cirrhosis, in the unaffected group (NK cell activity ratio < 1.25, n = 3), 2 of 3 patients had decompensated liver cirrhosis (p < 0.02). Laboratory data, indicating severity of liver cirrhosis, such as total bilirubin and albumin, showed better values (p < 0.01, p < 0.05 respectively), and baseline NK cell activity was low (8.7 +/- 7.2% vs 33.3 +/- 13.0%, p < 0.05) in the affected group than unaffected group. NK cell subpopulations such as CD16 (%), CD11b (%) and one of the populations of T cell such as CD8 (%) showed no significant change throughout the study. As for amino acids analysis, Fischer's ratio was increased in the nutrient-mixture-supplemented group compared to the control group (p < 0.05), but none of the amino acids showed significant change. Thus the changes in NK cell activity were not explained by increase in NK cell subpopulations nor changes of amino acids. These results suggest that the branched-chain amino acid-enriched nutrient mixture increases NK cell activity moderately in patients who have compensated liver cirrhosis and shows lower values of baseline NK cell activity.
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PMID:Effects of branched-chain amino acid-enriched nutrient mixture on natural killer cell activity in viral cirrhosis. 968 32

Hepatitis C Virus (HCV) causes most cases of posttransfusion hepatitis. Chronic HCV infection is highly related to chronic hepatitis, cirrhosis and hepatocellular carcinoma. Current therapies are only minimally effective and no vaccine has been developed. DNA-based immunization could be of prophylactic and therapeutic value for HCV infection. By intramuscular inoculation in BALB/c mice with an HCV recombinant plasmid pCI-HCV-C, we found significant levels of IgM antibody, but no significant IgG rise. After boost the immunized mice with recombinant HCV-core protein (cp1-10; 1-164aa), the anticore IgG, verified by Western-blotting, rose rapidly, which was two weeks earlier than that with control plasmid. Spleen cells from pCI-HCV-C immunized mice gave higher proliferation index (PI) than control (P < 0.05). The PI of cp1-10 boosted mice was even higher. Proliferation blocking assay with mAb proved the responding cell to be of CD4+ CD8- phenotype, supporting specific priming of T helper cells. A 51Cr-releasing CTL assay specific for HCV-core was developed, and a specific CTL response against HCV-core was demonstrated in both pCI-HCV-C immunized mice and mice boosted with cp1-10. Strong cytotoxic activity against peptide-pulsed p815 cells (H-2d), but not EL-4 cells (H-2b), suggested MHC class I restriction of the CTL activity. Blocking of CTL with mAb proved the effector cells to be of CD4- CD8+. Three CTL epitopes in HCV-core protein were demonstrated. We failed to detect CTL when immunized only with core protein. The results suggested that vaccination with HCV-core derived DNA sequences could be an effective method to induce humoral and cellular immune responses to HCV.
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PMID:Characterization of the humoral and cellular immune responses against hepatitis C virus core induced by DNA-based immunization. 1046 52

Iron and its binding proteins have immunoregulatory properties, and shifting of immunoregulatory balances by iron excess or deficiency may produce severe, deleterious physiological effects. Effects of iron overload include decreased antibody-mediated and mitogen-stimulated phagocytosis by monocytes and macrophages, alterations in T-lymphocyte subsets, and modification of lymphocyte distribution in different compartments of the immune system. The importance of iron in regulating the expression of T-lymphocyte cell surface markers, influencing the expansion of different T-cell subsets, and affecting immune cell functions can be demonstrated in vitro and in vivo. The poor ability of lymphocytes to sequester excess iron in ferritin may help to explain the immune system abnormalities in iron-overloaded patients. Iron overload as seen in hereditary hemochromatosis patients enhances suppressor T-cell (CD8) numbers and activity, decreases the proliferative capacity, numbers, and activity of helper T cells (CD4) with increases in CD8/CD4 ratios, impairs the generation of cytotoxic T cells, and alters immunoglobulin secretion when compared to treated hereditary hemochromatosis patients or controls. A correlation has recently been found between low CD8+ lymphocyte numbers, liver damage associated with HCV positivity, and severity of iron overload in beta-thalassemia major patients. Iron overload, with its associated increases of serum iron levels and transferrin saturation, may cause a poor response to interferon therapy. Iron overload with hyperferremia is associated with suppressed functions of the complement system (classic or alternative types). High plasma ferritin content in patients with chronic, diffuse diseases of the liver (cirrhosis, chronic hepatitis), beta-thalassemia major, dyserythropoiesis, and hereditary hemochromatosis may induce the development of anti-ferritin antibodies with the production of circulating immune complexes. Increased body stores of iron in various clinical situations may tip the immunoregulatory balance unfavorably to allow increased growth rates of cancer cells and infectious organisms, and complicate the clinical management of preexisting acute and chronic diseases.
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PMID:Effects of iron overload on the immune system. 1104 59

Since the aetiopathogenesis of primary sclerosing cholangitis (PSC) in humans remains undefined, investigators have studied a variety of animal models to gain insights into immunopathogenetic mechanisms associated with obliterative fibrous cholangitis of intra- and extra-hepatic bile ducts. To date, no animal model has been developed that exhibits all of the attributes of PSC. Rodent models instigated by bacterial cell components or colitis are promising because they may help to explain the strong association between PSC and inflammatory bowel disease (IBD). Other models of direct injury to biliary epithelia, peribiliary vascular endothelia or portal venous endothelia indicate that inflammation, chemokines and cytokines can produce diffuse sclerosis of bile ducts. Models of toxic, infectious or intra-luminal injury of the biliary tract also exhibit focal biliary sclerosis mediated by inflammation and cytokines. The histopathology of several models suggests a sequence of events beginning with secretion of proinflammatory cytokines by activated hepatic macrophages followed by peribiliary infiltration with CD4 and CD8 T cells with a T helper 1 phenotype. These results strongly suggest co-ordinated, pathogenetic roles for both the innate and adaptive immune responses. However, the stimuli that initiate and perpetuate peribiliary fibrosis remain unknown. Interestingly, several models are also associated with the development of anti-neutrophil cytoplasmic antibodies that react in a perinuclear and cytoplasmic pattern similar to that observed in patients with ulcerative colitis and/or PSC. Finally, models of extra-hepatic biliary obstruction continue to provide important information about the pathogenesis of portal fibrosis and secondary biliary cirrhosis that occurs in PSC and other diseases with obstruction of bile flow. Future studies in either existing or new animal models should advance our understanding of the pathogenesis of PSC, the major prerequisite for the development of effective therapies.
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PMID:Animal models for primary sclerosing cholangitis. 1149 70


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