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 possible correlation between HLA system and liver cirrhosis secondary to HBV infection has been studied in 102 hospitalized elderly patients affected by liver cirrhosis (histologically proven) and 749 elderly health controls. Increased frequencies of HLA-A2, Cw4, Cw5, DR4, DR5 and DR7 have been observed in patients with liver cirrhosis and previous HBV infection, while a lower frequency of HLA-A2 and higher frequencies of HLA-A3, B35, Cw4, DR3 have been observed in patients without previous HBV infection when compared with controls.
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PMID:HLA-A, B, C and DR in hepatitis B virus (HBV)-related liver cirrhosis: a study of 851 elderly subjects. 818 18

Hepatitis C virus (HCV) is a widespread infectious disease in humans with the negative implication of becoming chronic in most persons. Patients infected with HCV are at risk of liver cirrhosis or hepatocellular carcinoma at later stages. In contrast to hepatitis A and hepatitis B, there is no immunization yet available, neither prophylactic nor therapeutic. Thus, there is an urgent need to develop a safe, protective vaccine against this fatal disease. Developing countries are even more at risk for HCV. There are currently a number of scientific approaches aimed towards solving this problem. Taking both risks and costs of immunization into consideration, a peptide-based vaccine may be a reasonable prophylactic protection. Also, it might be of therapeutic use in already infected patients by increasing a specific CTL response against HCV. In our lab, we are focusing on immunopotentiating reconstituted influenza virosomes (IRIVs) as carriers for immunogenic HLA-A2-restricted core epitopes to induce peptide-specific cytotoxic T lymphocytes (CTLs). The IRIVs are similar to liposomes, but in addition contain influenza-derived hemagglutinin and neuraminidase on their outer surface which makes them fusogenic, thus, permitting antigen delivery to host cells. So far, virosomes have been successfully used for vaccine development and as a result a virosomal vaccine against both influenza virus (Inflexal) BERNA) and hepatitis A virus (HAV) (Epaxal) BERNA) already exist on the market. This paper focuses on the importance of development of a successful vaccine against HCV and, more specifically, we discuss the use, advantages and disadvantages of a peptide-based vaccine. A brief report of our latest findings will be included.
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PMID:Perspectives: towards a peptide-based vaccine against hepatitis C virus. 1174 97

The HBx-derived, HLA-A2.1 restricted peptides, XEP-3, XEP-4, and XEP-6, induced activation of specific CTLs from patients with HBV in vitro. XEP-6 peptide induced the strongest response among the three peptides in CTLs from the blood samples of patients that were HBsAg positive. It was not clear whether the stage of disease (chronic infection, cirrhosis or hepatoma) was related to the responsiveness of the CTLs to each peptide. We vaccinated HLA-A2/K(b) transgenic mice with these peptides encapsulated in pH-sensitive liposomes at various concentrations and tested their ability to protect against challenge with rVV-HBx. Mice immunized with encapsulated peptides were protected against viral challenge whereas those immunized with empty liposomes were not. In general, 5 micro g of each peptide per head inoculation was sufficient to give protection after 2 weeks. After 3 weeks, this protective effect was increased. This effect of time was more important on the level of protection than the initial dose of the peptide. To explain the protective effect, IFN-gamma secreting CD8(+) cells isolated from mice 3 weeks after immunization were analyzed ex vivo. There was little dose dependency of peptide on IFN-gamma secretion except for XEP-3. The variations in the results may reflect the chemical properties of the peptides, such as solubility and binding affinity. In conclusion, epitope peptides derived from HBx can induce specific CTL activation and lead to cellular immunity in vitro and in vivo by inducing the peptide-specific CD8(+) CTLs. Thus, pH-sensitive liposomes increase the immune response following immunization with a peptide vaccine. This could be used for the treatment of HBV-related disease.
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PMID:HLA-A2 1 restricted peptides from the HBx antigen induce specific CTL responses in vitro and in vivo. 1239 8

Hepatitis C virus (HCV) is a single-strand RNA virus. Approximately 170 million people around the world are persistently infected and are at risk of liver cirrhosis or cancer. There is an urgent need to develop both therapeutic and diagnostic modalities of HCV. One approach to achieve these goals would be to determine highly immunodominant HCV peptides which are recognized by both cellular and humoral immunities. This study reports one such peptide, HCV-core protein at positions 35-44, having HLA-A2 binding motifs. IgG specific to this CTL-epitope peptide is consistently detectable in a majority of the patients with HCV infection regardless of the different HLA types, different disease conditions, and different HCV-genotypes tested. The sequence LPRR at positions 37-40 is considered to be the fine epitope recognized by the IgG. These results may provide new insights for the development of both therapeutic and diagnostic modalities of HCV at lower costs.
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PMID:Antibody reactive to a hepatitis C virus (HCV)-derived peptide capable of inducing HLA-A2 restricted cytotoxic T lymphocytes is detectable in a majority of HCV-infected individuals without HLA-A2 restriction. 1527 96

Hepatitis C virus (HCV) has been reported to elicit B and T cell immunity in infected patients. Despite the presence of antiviral immunity, many patients develop chronic infections leading to cirrhosis, hepatocellular carcinoma, and liver failure that can require transplantation. We have previously described the presence of HLA-A2-restricted, HCV NS3-reactive cytotoxic T lymphocytes (CTL) in the blood of HLA-A2- liver transplantation patients that received an HLA-A2+ liver allograft. These T cells are analogous to the "allospecific" T cells that have been described in hematopoietic stem cell transplantation patients. It has been speculated that allospecific T cells express high-affinity T cell receptors (TCRs). To determine if our HCV-reactive T cells expressed TCRs with relatively high affinity for antigen, we identified and cloned a TCR from an allospecific HLA-A2-restricted, HCV:NS3:1406-1415-reactive CD8+ T cell clone and expressed this HCV TCR in Jurkat cells. Tetramer binding to HCV TCR-transduced Jurkat cells required CD8 expression, whereas antigen recognition did not. In conclusion, based on the reactivity of the TCR-transduced Jurkat cells, we have identified a TCR that transfers anti-HCV reactivity to alternate effectors. These data suggest this high affinity HCV-specific TCR might have potential new immunotherapic implications.
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PMID:Identification of a hepatitis C virus-reactive T cell receptor that does not require CD8 for target cell recognition. 1662 27

The patients with hepatitis B or C based liver cirrhosis are at high risk for developing Hepatocellular carcinoma (HCC), and HCC patients treated surgically or by other therapies are also at high risk for recurrence. As a result, the prognosis of HCC remains poor, and new therapies for the prevention of cancer development and recurrence are urgently needed. We previously reported that glypican 3 (GPC3) was over expressed specifically in HCC. In this report, we found the HLA-A2 or HLA-A24 restricted GPC3 epitope peptide, and investigated whether these peptides could induce GPC3 reactive CTLs from the peripheral blood mononuclear cells (PBMCs) of HLA-A2+ or HLA-A24+ HCC patients. We used HLA-A2.1 (HHD) transgenic mice (Tgm) to identify the HLA-A2-restricted GPC3 epitopes. We found that these epitope peptides could induce peptide-reactive CTLs in about 50% of HLA A2+ or HLA-A24+, and GPC3+ HCC patients. Our study raises the possibility that these GPC3 peptides may therefore be applicable to cancer immunotherapy for prevention of cancer development and recurrence of HCC.
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PMID:[Possibilities of glypican-3-specific immunotherapy for hepatocellular carcinoma]. 1721 93

Glypican-3 (GPC3) is one of carcinoembryonic antigens known to be overexpressed in hepatocellular carcinoma (HCC). It has been suggested that GPC3 may be related to the development of HCC in a background of chronic hepatitis (CH) and liver cirrhosis (LC). Therefore, in an attempt to establish an early diagnostic marker of HCC, we quantified the number of GPC3-specific CTLs in the peripheral blood of CH and LC patients. We selected CH and LC patients who were HCV-RNA (+) or HBs antigen (+) within 6 months prior to the study and had no HCC nodules as detected by imaging. A total of 56 patients with CH and LC, and 45 patients with HLA-A24+ or HLA-A2+ were enrolled for this investigation. After isolation of mononuclear cells from each patient's peripheral blood specimens, we performed ELISPOT assay using HLA-A24- and HLA-A2-restricted GPC3 peptides. In the ELISPOT assay, GPC3-specific CTLs were detected in 10 of the 45 CH and LC cases (22%). In addition, the plasma titers of anti-GPC3 IgG were increased in the CH and LC patients as compared with those in healthy donors. GPC3-specific CTLs were found to be present not only in patients with HCC, but also in patients with CH and LC. This suggests the possibility of GPC3-specific CTLs serving as a marker for the early diagnosis of imaging-invisible HCC.
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PMID:Detection of glypican-3-specific CTLs in chronic hepatitis and liver cirrhosis. 1951 17

We investigated the feasibility of the combined detection of HLA-A2/MAGE-A3 epitope-specific cytotoxic T lymphocytes (CTLs) and serum alpha-fetoprotein (AFP) for specific diagnosis of hepatocellular carcinoma (HCC). We detected the frequency of MAGE-A3 epitopes (p112-120, KVAELVHFL) in spontaneous CTLs in the peripheral blood of HCC patients, liver cirrhosis patients, and healthy subjects with HLA-A2/polypeptide complex (pentamer) detection technology. Eighty-five HCC cases, 38 liver cirrhosis cases, and 50 healthy cases who were HLA-A2-positive were selected from 175 HCC patients, 80 patients with liver cirrhosis, and 105 healthy volunteers, respectively. The frequency of HLA-A2-specific MAGE-A3(+) CTLs in the HCC group was significantly higher than that in the other groups. Combined detection of MAGE-A3(+) CTL frequency and serum AFP value had a higher specificity than either of the two indicators alone. The pentamer technique is helpful in distinguishing benign lesions and malignant lesions in the liver. Combined with serum AFP, it can improve the diagnosis performance for HCC, especially for AFP-negative cancer.
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PMID:Combined analysis of serum alpha-fetoprotein and MAGE-A3-specific cytotoxic T lymphocytes in peripheral blood for diagnosis of hepatocellular carcinoma. 2442 79