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

The chronic alcoholic patient is usually immunosuppressed, but the significance of this phenomenon in terms of bile duct injury is unclear. The immunoreactivity of the bile duct cells was examined in a series of 69 frozen liver biopsy specimens obtained from patients with alcoholic liver disease, comprising 29 cases of cirrhosis, 26 of alcoholic hepatitis, 10 cases of alcoholic fatty liver, and 4 specimens from normal livers. Liver diseases such as primary biliary cirrhosis and human hepatic allograft rejection, known to have an autoimmune basis, share the characteristic feature of damage to the bile duct epithelial cells. In both instances the damage seems to be immune mediated, but the nature of the antigens involved is not established. We used the avidin-biotin-peroxidase complex method to test in alcoholic liver disease for the expression of a battery of surface antigen markers that have been incriminated in tissue injury and are usually present in lymphoid cells but also expressed by epithelium. In this study we investigated the expression of the following molecules: HLA class I (ABC) and class II (HLA-DR, HLA-DP, HLA-DQ), CD29, CD45RA, CD45RO, CD56, interleukin 1 (IL-I), IL-2, IL-4, interferon (IFN-gamma), tumor necrosis factor beta, and transforming growth factor beta1 (TGF-beta1). The bile duct epithelial cells strongly expressed HLA-ABC in all cases, CD56 in 47 of 55, IL-4 in 15 of 41, TGF-beta1 in 14 of 25, and CD29 in 4 of 25 cases. The other markers including IFN-gamma, HLA-DR, HLA-DP, and HLA-DQ were not expressed by bile duct cells. The expression of HLA class I agrees with previous observations while the absence of class II expression does not. The expression by the bile duct epithelium of CD56 confirms our own previous report. A new observation is the finding of molecules such as IL-4, TGF-beta1, and CD29 strongly expressed in the bile ducts cells. The presence of these molecules, taken together with the lack of IFN-gamma expression, contradicts previous speculations that attributed to IFN-gamma a role in the induction of major histocompatibility antigens and adhesion molecules in immune-mediated alcoholic liver disease.
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PMID:The antigenic heterogeneity of the bile duct epithelium in alcoholic liver disease. VA Cooperative Study Group 275. 1023 99

Acute graft-versus-host disease (GVHD) is a frequent complication of bone marrow transplantation but is only rarely observed after solid organ transplantation. We describe a 68-year-old man who developed a maculopapular eruption 7 days following orthotopic liver transplantation for cirrhosis with malignant transformation due to haemochromatosis. At day 20, the patient complained of nausea, vomiting, diarrhoea and fever. Skin biopsy revealed a lymphocytic infiltrate at the dermoepidermal interface, vacuolization of basal cells and epidermal dyskeratosis. Immunohistochemistry showed HLA-DR and intercellular adhesion molecule-1 expression of lesional keratinocytes. HLA-typing of peripheral blood lymphocytes demonstrated circulating lymphocytes of donor origin. Endoscopy revealed extensive erosions of the oesophagus, stomach and duodenum that on histology disclosed multifocal loss of crypts, lymphocytic infiltrates and epithelial cell death. A diagnosis of acute GVHD was made, and high-dose immunosuppressive therapy with azathioprine and methylprednisolone was instituted. The skin and gastrointestinal symptoms subsided within 4 weeks, but the patient died from severe infectious complications 105 days after transplantation. We conclude that acute GVHD is a rare but potentially fatal complication of liver transplantation. Skin lesions are an early sign of acute GVHD and thus represent an important tool for early diagnosis.
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PMID:Cutaneous lesions as the presenting sign of acute graft-versus-host disease following liver transplantation. 1058 55

Hepatitis C virus (HCV) infects more than 180 million of the world's population and causes a persistent infection that over decades can result in cirrhosis and hepatocellular carcinoma. Treatment is only partially effective and control is likely only with the development of effective vaccines. Currently, only chimpanzees can be infected with HCV and alternative animal and tissue culture models are badly needed. We have used mice transgenic for HLA-DR and human CD4 to analyse the specificity of murine responses to the HCV NS3 antigen in an effort to determine whether the epitopes recognized correspond to those recognized by human T cells. Indeed, determinants mapped in transgenic mice overlap with those in a patient exposed to HCV through infection. This result provides hope that such an animal model may be a useful tool with which to analyse particular aspects of immune responses to HCV in vivo.
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PMID:Epitopes of the NS3 protein of hepatitis C virus: recognition in HLA-DR4 transgenic mice. 1186 68

Liver transplantation (OLT) for end-stage chronic hepatitis-B-virus (HBV) infection is frequently complicated by HBV recurrence. In the present study we investigated whether human leucocyte antigen (HLA)-matching influences the outcome after OLT. In a retrospective analysis we reviewed 84 recipients of liver transplants for end-stage HBV-cirrhosis and complete HLA-typing for outcome after OLT. Follow-up ranges from 1 to 110 months (median = 55.6 months). Immunosuppression consisted of Cyclosporin A (CsA)-based quadruple induction therapy or Tacrolimus-based induction protocols. Immunoprophylaxis with hepatitis B immunoglobulin was started at OLT and continued long-term. Actuarial 1- and 5-yr graft survival figures were 90.5 and 80.4%, respectively. Hepatitis-B recurrence was responsible for 15 of 20 (75%) graft failures. We observed a significantly improved graft survival in patients with more HLA-A, -B compatibilities (p = 0.02), whereas the degree of HLA-DR compatibilities did not influence the outcome. The occurrence of HBV-reinfection was significantly lower in HLA-A, -B matched grafts (p < 0.05). Additionally, graft survival was prolonged in patients with HBV-reinfection and 1 or 2 HLA-B compatibilities when compared with patients with HBV-reinfection and a complete HLA-B mismatch (p = 0.02). In conclusion, this retrospective analysis shows that more HLA-A, -B compatibilities seems to be associated with an improved graft survival in patients after OLT for end-stage HBV infection.
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PMID:Impact of HLA-compatibilities in patients undergoing liver transplantation for HBV-cirrhosis. 1196 82

Hepatitis B (HB) in haemodialysis patients results in morbidity and mortality, through chronicity, which leads to cirrhosis and liver carcinoma, even after renal transplantation. Hepatitis B vaccination is protective against HB virus infection. Suppressed immunity in renal failure leads to low HB vaccination success rates. Uremia, inadequate dialysis, use of low biocompatibility dialysis material, hyperparathyroidism, anemia, iron overload and malnutrition are all factors contributing to depressed immunity. Renal failure, associated with chronic inflammation, leads to impaired monokine production which results in decreased immunity. This impairment could result from defective HLA-DR B7-2 expression on monocytes. Hepatitis B vaccination non-responders express increased levels of HLA class II alleles (T-cell immune response modulators) DRB1 01 (DR1) and DRB1 15 (DR15). Various methods have been used to enhance the immune response to HB vaccination such as recombinant adjuvants, thymopentine, IL-2, levamisole and GM-CSF: they have produced variable results. Better dialysis biocompatibility and adequacy have also been conducted to overcome this low immune response. Response to conventional intramuscular HB vaccination is considered an index of adequate dialysis and low inflammatory state, both associated with better cardiovascular outcome and survival. HB vaccination reinforcement techniques evolved from an initial intramuscular double/multiple-dosing regimen to more frequent intradermal smaller dose injection. This newer regimen achieves a higher and almost complete seroconversion rate, although frequent boosters shots are necessary to maintain protective levels. Experience with pre-S1/S2, third generation, vaccines is limited and they have not been proven to be more effective than intradermally administered S antigens. Recombinant HB vaccines, intradermally administered, have been shown to elicit an immune response in all renal failure patients. Additionally the use of recombinant erythropoietin treatment to correct anemia contributes to this success.
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PMID:Recombinant hepatitis B vaccination in renal failure patients. 1267 88

Primary effusion lymphoma (PEL) or body cavity-based lymphoma (BCBL) is a unique subgroup of B-cell lymphomas that exhibits exclusive or dominant involvement of serous body cavities without a detectable tumor mass. We present a case of a PEL/BCBL that exclusively involved the peritoneal cavity of a 58-year-old immunocompetent male with hepatitis C virus (HCV)-related liver cirrhosis. The lymphoma cells were large, highly atypical and expressed CD19, CD20, CD22, CD10, HLA-DR, and CD45 with kappa light chain restriction. Unlike typical PEL/BCBL, human herpesvirus type 8/Kaposi sarcoma herpes virus (HHV-8/KSHV) genomic sequence was not present in the lymphoma cells and there was no serologic evidence of human immunodeficiency virus (HIV) infection. This is the fourth reported case of HHV-8 negative, HIV negative PEL/BCBL in a patient with associated HCV-related cirrhosis and review of these cases showed some consistent clinicopathological features, i.e. exclusive involvement of the peritoneal cavity and phenotypic expression of B-cell associated antigens in contrast to the generally null phenotype PEL/BCBL. The occurrence of these cases suggests that HCV may play an etiological role in a subcategory of PEL/BCBL not associated with HHV-8.
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PMID:HIV and HHV-8 negative primary effusion lymphoma in a patient with hepatitis C virus-related liver cirrhosis. 1469 39

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide with a poor prognosis and one for which immunotherapy remains a viable option. Experimental tumor models have shown that regulatory T cells, a functionally unique subset of T cells, can suppress effective antitumor immune responses. This suppression might explain the poor outcome of some of the immunotherapy protocols currently being used. A better understanding of the role of regulatory T cells in HCC is important for design of future immunotherapy-based clinical protocols. We have studied regulatory T cells from 84 patients with HCC and 74 controls, including healthy donors, patients with chronic hepatitis B virus and hepatitis C virus infection and nonviral liver cirrhosis. Regulatory T cells were identified by fluorescence-activated cell sorting using a panel of antibodies and by real-time PCR analysis for Foxp3 expression. Functional studies were done to analyze their inhibitory role. Finally, regulatory T cells were analyzed in tumors and ascites from patients with HCC. Patients with HCC have increased numbers of CD4+CD25+ regulatory T cells in their peripheral blood, which express high levels of HLA-DR, GITR, and low or no CD45RA. These cells were anergic toward T-cell receptor stimulation and, when cocultured with activated CD4+CD25- cells, potently suppressed their proliferation and cytokine secretion. There were also high numbers of regulatory T cells in tumor-infiltrating lymphocytes of HCC patients comparable with the increase in their peripheral blood. Our data suggest that the increase in frequency of regulatory T cells might play a role in modulation of the immune response against HCC and could be important in design of immunotherapeutic approaches.
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PMID:Increased populations of regulatory T cells in peripheral blood of patients with hepatocellular carcinoma. 1578 62

The aim of this study was to investigate the characteristics of the immune function of monocytes in different stages of the patients with acute on chronic liver failure (ACLF). Human leucocyte antigen (HLA)-DR and Toll-like receptor 4 (TLR-4) expression on monocytes in early and late stages of acute on chronic liver failure were detected by flow cytometry. The secretion function of monocytes was measured by cytometric bead array. Compared with healthy controls, the levels of HLA-DR expression on monocytes in patients with chronic hepatitis B, liver cirrhosis and acute on chronic liver failure were gradually decreased, especially in the late stage of acute on chronic liver failure (P < 0.001). TLR-4 expression on monocytes in patients with liver cirrhosis and acute on chronic liver failure were higher than the healthy controls. The concentrations of interleukin (IL)-1beta, tumour necrosis factor (TNF)-alpha and IL-12p70 in early-stage ACLF were significantly higher compared with healthy controls and lower in late-stage ACLF (P < 0.01, 0.05). However, a significantly lower amount of IL-10 was found on monocytes in early-stage ACLF than that of late-stage ACLF and healthy controls (P < 0.01). Monocyte HLA-DR expression in patients who died was significantly lower compared with patients who survived in the early and late stages of ACLF (P < 0.01). The dynamic detection of HLA-DR expression or cytokines secreted from monocytes could contribute to the estimation of the status of the immune function of patients with acute on chronic liver failure.
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PMID:Altered immune function of monocytes in different stages of patients with acute on chronic liver failure. 1717 78

Tissue factor (TF) is one of the proteins that participate in hemostatic and inflammatory processes. Activated monocytes present in the liver increase expression of TF, and while accumulating in the organ they can intensify inflammation. The aim of the present study was to evaluate the expression of TF on monocytes in advanced liver cirrhosis with regard to other activation markers. The flow cytometric analysis of TF (CD142), CD14, adhesive molecules CD11b and CD11c, costimulatory molecules CD40, CD80 and CD86, and HLA-DR on monocytes was carried out in 45 patients with postalcoholic liver cirrhosis (Child Pugh B, 20 patients; Child Pugh C, 25 patients) and in 25 healthy persons. The positive correlation between monocytic TF expression and monocyte [soluble CD14 (sCD14), CD11b, monocyte aggregates] activation, the expression of costimulatory molecules on monocytes (CD40, CD80), blood platelet (soluble P-selectin, microplatelets) activation, the level of tumor necrosis factor-alpha, biochemical parameters of liver damage (alanine aminotransferase, aspartate aminotransferase, alkaline phosphate, gamma-glutamyltransferase, and bilirubin) as well as coagulation disorders were observed in the study. In conclusion, the study revealed that the activation of monocytes and blood platelets is accompanied by the elevation of monocytic TF expression in advanced liver cirrhosis. The monocytic TF is a significant link connecting clotting processes and inflammatory and immunological phenomena in liver cirrhosis.
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PMID:Increase in expression of monocytic tissue factor (CD142) with monocytes and blood platelet activation in liver cirrhosis. 1798 14

The current curative treatments for hepatocellular carcinoma (HCC) do not effectively prevent tumor recurrence. Dendritic cell (DC)-based immunotherapy can be a novel strategy targeting tumor recurrence. Here, we evaluated the bioactivity and beneficial effects of DC infusion of HCC tissues following transcatheter hepatic arterial embolization (TAE). 5x10(6) of monocyte- derived DCs were administered through an arterial catheter during TAE treatment procedures in patients with hepatitis C virus-related cirrhosis and HCC. In DC preparation, peptide-stimulated DCs [HLA-DR(+)CD86(+)CD14(-)] were phenotypically immature [CD80(low)CD83(low)], while OK-432-stimulated DCs highly expressed the activation marker CD83. Following the transfer, there was no clinical or serological evidence of adverse events in any patients in addition to those due to TAE. Most interestingly, survival analysis indicated that the patients treated with OK-432-stimulated DCs prolonged the recurrence-free survivals when compared with the historical controls treated with TAE alone. Collectively, OK- 432-stimulated DC transfer to HCC tissues following TAE treatment contributes to the induction of beneficial antitumor immune responses and the prolongation of recurrence-free survivals, providing a plausible strategy to reduce the tumor recurrence rates of HCC.
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PMID:[Dendritic cell-based immunotherapy for hepatocellular carcinoma]. 2033 77


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