Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate the features of various hepatitis virus infection in intravenous drug users (IVDU), we conducted an epidemiological survey of hepatitis viruses including hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV) and hepatitis G virus (HGV) in IVDU. The correlation of TH lymphocyte cytokine and hepatitis virus infection was examined. A study population of 406 IVDU consisted of 383 males and 23 females. HBV-DNA and HCV-RNA were detected by fluorescence quantitative polymerase chain reaction. HBsAg, HBeAg, anti-HBc, anti-HCV, HDV-Ag and anti-HGV were assayed by ELISA. The levels of cytokines of TH1 and TH2 were measured by ELISA. The similar indices taken from 102 healthy persons served as controls. The infection rate of each virus among IVDU was 36.45 % for HBV, 69.7 % for HCV, 2.22 % for HDV, and 1.97 % for HGV, respectively. The co-infection rate of HBV and HCV was detected in 113 of 406 (27.83 %). In contrast, among controls, the infection rate was 17.65 % for HBV and 0 % for the other hepatitis viruses. The levels of PHA-induced cytokines (IFN-gamma and IL-4) and the level of serum IL-2 were obviously decreased in IVDU. On the other hand, the level of serum IL-4 was increased. The IFN-gamma level was continuously decreased when the IVDU was infected with HBV/HCV. In conclusion, HBV and HCV infection were common in this population of IVDU and they had led to a high incidence of impaired TH1 cytokine levels.
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PMID:Epidemiology of hepatitis B, C, D and G viruses and cytokine levels among intravenous drug users. 1685 Jul 52

Pediatric solid organ transplantation is so successful that >80% of children will survive to become teenagers and adults. Therefore, it is essential that these children maintain a good quality life, free of significant long-term side effects. While intensive immunosuppressive regimens (containing CsA, tacrolimus, MMF, and steroids) effectively reduce acute or chronic rejection, they can produce long-term side effects including viral infection, renal dysfunction, hypertension, and stunting. The development of effective methods of diagnosis, prevention, and treatment of CMV means that this is no longer a significant cause of mortality, but morbidity remains high. In contrast, infection rates of EBV remain high in EBV-negative pre-transplant patients. However, pre-emptive reduction of immunosuppression or treatment with rituximab or adoptive T-cell therapy is effective in preventing/treating post-transplant lymphoproliferative disease. Recent protocols have concentrated on reducing CsA immunosuppression, to prevent unacceptable cosmetic effects, and to reduce the hypertension, hyperlipidemia, and nephrotoxicity. Both CsA and tacrolimus cause a 30% reduction in renal function, with 4-5% of patients developing severe chronic renal failure. The use of IL-2 inhibitors for induction therapy with low-dose calcineurin inhibitors, in combination with renal-sparing drugs such as MMF or sirolimus for maintenance immunosuppression, should prevent significant renal dysfunction in the future. The concept of steroid-free immunosuppression with IL-2 inhibitors, tacrolimus, and MMF is an attractive option, which may reduce stunting and renal dysfunction. However, these regimens may be associated with the increased development of de-novo autoimmune hepatitis in 2-3% of children. The most important challenge to long-term survival in transplanted children is the management of non-adherence and other adolescent issues, particularly when transferring to adult units, as this is the time when many successful transplant survivors lose their grafts.
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PMID:Current issues in pediatric transplantation. 1691 96

Fulminant hepatic failure of unknown origin is the most common cause of fulminant hepatitis with high incidence of aplastic anaemia. Furthermore, the association of liver failure and aplastic anaemia has an increased mortality rate. In this report we describe a 16-month-old boy who presented with aplastic anaemia preceding a non-A, non-B, non-C fulminant liver failure. He developed severe graft versus host disease (GvHD) after liver transplantation, proven by the presence of donor cells in the peripheral blood and in the skin biopsy. He received conventional therapy (steroids, mycophenolate, anti-IL-2 monoclonal antibodies, anti-thymocyte globulin) without success. In an attempt to obtain T cell depletion and reduce the GvHD, he was treated with Alemtuzumab, a first time use for this indication. Aplastic anaemia was extensively investigated, especially exploring the possibility of primary immunodeficiency and reticular dysgenesis which were excluded based on clinical history. However, another form of primary immunodeficiency could be the cause of the uncontrollable proliferation of the donor lymphocytes derived from the liver transplant. Despite aggressive treatment GvHD progressed and the patient died of multiorgan failure. The majority of authors mention aplastic anaemia as a secondary event post liver transplant, whereas in our view this might be a haematopoietic stem cell disorder preceding fulminant hepatic failure. These patients also need to be evaluated extensively in order to exclude a primary immunodeficiency. The underlying disease will determine the choice of immunosuppressive treatment, especially in case of development of GvHD caused by the transplanted lymphocytes inhabiting the donor liver.
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PMID:Fatal GvHD as a complication of liver transplantation for undetermined fulminant hepatic failure and associated aplastic anemia. 1705 30

After liver transplantation for hepatitis-B-related diseases, patients currently receive lifelong treatment with hepatitis B immunoglobulin to prevent endogenous reinfection with hepatitis B virus (HBV). Active immunization with hepatitis B vaccine would be a preferable alternative; however, most attempts to immunize these patients with standard vaccine have failed. A recent study with a new adjuvanted hepatitis B vaccine was exceptionally successful, leading to a high-titered long-lasting antibody response in 80% of all vaccinees. To identify the immunological mechanisms behind these unexpected results, the successfully vaccinated participants were tested for hepatitis B surface antigen (HBsAg)-specific T and B cells, and their cellular responses to revaccination with conventional vaccine were studied. HBsAg-specific CD4(+) T lymphocytes could be detected in 13 of 16 patients after immunization with the new vaccine. Unexpectedly, these T cells produced almost exclusively interleukin (IL)-10 and had a CD4(+)/CD25(+) phenotype. They were functionally active, suppressing cytokine secretion in HBsAg-specific (Th1) cells, thus representing antigen-specific regulatory T cells (T(Reg)). Following a booster dose with conventional vaccine 22-31 months after completion of the initial vaccination series, the T-cell pattern in the revaccinated individuals changed substantially: 7 days after revaccination 9 of 11 individuals showed a switch to a Th1-type immune response with HBsAg-specific T cells secreting IL-2, interferon gamma and tumor necrosis factor alpha as observed in healthy controls. Four weeks after the booster, 4 patients still showed a Th1-type cytokine pattern, whereas in 5 patients only IL-10-secreting cells were detectable. After 1 year, in 3 of 4 revaccinated individuals only IL-10-secreting cells could be found, whereas the specific T cells of the fourth patient still showed a Th1-type of response. HBsAg-specific T(Reg) cells could be demonstrated in HBV-positive liver transplant recipients successfully immunized with a new adjuvanted vaccine. Revaccination led to immediate disappearance of the these cells and the appearance of HBsAg-specific T cells with a Th1-type cytokine profile, which in most cases were replaced by the IL-10-secreting regulatory cells during the following months. The specific induction of T(Reg) cells could contribute to the poor response of liver transplant recipients to conventional vaccine. In conclusion,, for successful vaccination of these patients, a vaccine with a strong inhibitory effect on T(Reg) cells would be desirable.
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PMID:Vaccination against hepatitis B in liver transplant recipients: pilot analysis of cellular immune response shows evidence of HBsAg-specific regulatory T cells. 1731 60

After the initial dramatic effects, observed in a Lewis lung carcinoma animal model, using a combination of thymosin alpha 1 (Talpha1) and interferon (IFN) after cyclophosphamide, a number of other preclinical models in mice (Friend erythroleukemia and B16 melanoma) and in rats (DHD/K12 colorectal cancer liver metastasis) have confirmed the efficacy of the combination therapy with Talpha1 and either IFN or IL-2 plus chemotherapy. These results provided the scientific foundation for the first clinical trials using Talpha1 in combination with BRMs and/or chemotherapy. Pivotal trials in advanced non-small cell lung cancer (NSCLC) and melanoma with Talpha1 and IFN-alpha low doses after cis-platinum or dacarbazine produced the first evidence of the high potentiality of this approach in the treatment of human cancer. The combination of Talpha1 and IFN-alpha was also used in patients affected by chronic B and C hepatitis including IFN-nonresponders and infected by precore mutants or genotype 1b. Further studies demonstrated additional biological activities clarifying the mechanism of action of Talpha1, partially explaining the synergism with IFN. It has been shown the capacity of activating infected dendritic cells through Toll-like receptor signaling, thus influencing the inflammation balance, and of increasing the expression of tumor, viral, and major histocompatibility complex (MHC) I antigens. Dose-response studies suggested the possibility of improving the efficacy of this molecule reducing the overall toxic. Based on these information two clinical trials are ongoing: a large phase II on advanced melanoma patients treated with Talpha1 at different doses after dacarbazine and a phase III one, on IFN-resistant hepatitis C virus (HCV) patients treated with a triple combination (IFN, ribavirin, and Talpha1).
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PMID:Thymosin alpha 1: from bench to bedside. 1760 Feb 90

The purpose of the work was to study the levels of interleukin-1beta (IL-1beta), IL-2, IL-4, IL-6, tumor necrosis factor a (TNF-alpha), interferon alpha (IF-alpha), interferon gamma (IF-gamma), and the parameters of T-cell immunity in 70patients with acute hepatitis C (AHC). The content of cytokines in peripheral blood was determined by immune-enzyme technique using test systems produced by Proteinovy Kontur (Saint-Petersburg). Evaluation of T-cell reacting (CD4, CD8, CD16, and CD20) was done using a kit of mono- and polyclonal antibodies for human T-lymphocyte, B-lymphocyte, T-helper, T-killer-suppressor, and NK-lymphocyte detection with immunofluorescence technique, produced by Sorbent, Podolsk. Assessment of cytokine spectrum was of a prognostic value. Primary examination revealed high levels of IL-2, IFgamma, CD4, and CD16 and normal levels of IL-4 in most patients who recovered later. These changes characterized a more pronounced activity of Th1 lymphocytes and suppression of Th2 mediator synthesis, which favored the formation of a strong immune response and led to viral elimination. Primary examination usually did not find a significant elevation of pro-inflammatory mediators level, but found high levels of IL-4, CD8, and CD20 in AHC patients whose disease later acquired a chronic form. These features of the spectrum of immune response mediators reflected a more prominent activity of Th2-lymphocytes, suppressing Th1-effector mechanisms, which favored active viral replication and the formation of chronic C hepatitis.
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PMID:[Indices of cell immunity and immune system mediators in patients with acute HCV infection]. 1768 96

We describe a 26-year-old female referred to us because of recurrent bacterial pneumonia. Her immunoglobulin profile on admission was; IgG 1920 mg/l, IgA 60 mg/l, IgM 260 mg/l, IgD below 20 mg/l, IgE below 1 kU/l. Antinuclear antibodies, EBV VCA IgM, anti-parvovirus B19 IgM antibodies and hepatitis infection markers were all negative. Bone marrow aspiration revealed normal cellularity without abnormal cells, especially plasma cell proliferation. No rearrangement for IgH and TCR was observed as determined by Southern blot analysis. By the given data, a diagnosis of common variable immunodeficiency (CVID) was made. The genesis of this disease remained unclear. In this study, proliferation and immunoglobulin production with or without several stimulators were examined. Proliferation stimulated by PHA, Con-A, LPS, or IL-2 was decreased compared to that of healthy individuals. Immunoglobulin production after stimulation with several agents was quite low. Interestingly, however, IL-2 or IL-4 could increase IgM production on 6 days culture significantly. These results indicate that IL-2 or IL-4 possibly restore T cell responses to several antigens and induce B cell differentiation.
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PMID:Partial restoration of immunoglobulin production by cytokines in common variable immunodeficiency. 1782 53

The authors studied the levels of cytokines (interleukin (IL)-1, IL-2, IL-4, IL-6, and interferon-gamma (IFN-gamma)) and cell response to HBV and HCV in the dynamics in patients with acute mixed hepatitis (B+C) who recovered or became chronically ill, as well as before and after treatment of hepatitis C. Patients who later recovered had high levels of IL-2 and IFN-gamma during the acute phase of the disease, and displayed T-lymphocyte sensitization to HbeAg, Hbcore Ag, and the non-structural protein HCV NS3. A significant elevation of IL-2 level and, especially, IFN-gamma level, as well as the appearance of T-lymphocyte response to HCV NS3, HCVcore Ag, and HCV NS4 was observed during antiviral therapy.
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PMID:[Clinical significance of cytokine level and T-cell lymphocyte response to B and C hepatic viral antigens in patients with type C and B+C hepatitis receiving antiviral therapy]. 1788 15

The histological hallmark of autoimmune hepatitis (AIH) is a dense portal mononuclear cell infiltrate that invades the surrounding parenchyma and comprises T and B lymphocytes, macrophages, and plasma cells. An unknown but powerful stimulus must be promoting the formation of this massive inflammatory cellular reaction that is likely to initiate and perpetuate liver damage. An autoimmune attack can follow different pathways to inflict damage on hepatocytes. Liver damage is likely to be orchestrated by CD4(+) T lymphocytes recognizing an autoantigenic liver peptide. To trigger an autoimmune response, the peptide must be embraced by an HLA class II molecule and presented to naive CD4(+) T helper (Th0) cells by professional antigen presenting cells, with the co-stimulation of ligand-ligand fostering interaction between the two cells. Th0 cells become activated, differentiate into functional phenotypes according to the cytokines prevailing in the microenvironment and the nature of the antigen, and initiate a cascade of immune reactions determined by the cytokines produced by the activated T cells. Th1 cells, arising in the presence of the macrophage-derived interleukin (IL) -12, secrete mainly IL-2 and interferon-gamma (IFN-gamma), which activate macrophages, enhance expression of HLA class I (increasing liver cell vulnerability to a CD8(+) T cell cytotoxic attack), and induce expression of HLA class II molecules on hepatocytes. Th2 cells, which differentiate from Th0 if the microenvironment is rich in IL-4, produce mainly IL-4, IL-10, and IL-13 which favour autoantibody production by B lymphocytes. Physiologically, Th1 and Th2 antagonize each other. Th17 cells, a recently described population, arise in the presence of transforming growth factor beta (TGF-beta) and IL-6 and appear to have an important effector role in inflammation and autoimmunity. The process of autoantigen recognition is strictly controlled by regulatory mechanisms, such as those exerted by CD4(+)CD25(+) regulatory T cells, which derive from Th0 in the presence of TGF-beta, but in the absence of IL-6. If regulatory mechanisms fail, the autoimmune attack is perpetuated. Over the past three decades different aspects of the above pathogenic scenario have been investigated. In particular, a defect in immunoregulation affecting CD4(+)CD25(+) regulatory T cells (T-regs) has been demonstrated in AIH, particularly at diagnosis or during relapse. Advances in the study of autoreactive T cells have occurred mostly in AIH type 2, since the knowledge that CYP2D6 is the main autoantigen has enabled the characterization of both CD4 and CD8 T cells targeting this cytochrome. CD4 T cells from patients with type 2 AIH positive for the predisposing HLA allele DRB1*0701 recognize seven regions of CYP2D6, five of which are also recognized by CD8 T cells. High numbers of IFN-gamma producing CD4 T cells and CD8 T cells are associated with biochemical evidence of liver damage, suggesting a combined cellular immune attack.
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PMID:Aetiopathogenesis of autoimmune hepatitis. 1852 28

Tumor necrosis factor-alpha (TNF-alpha) is critically involved in a wide variety of inflammatory pathologies, such as hepatitis, via the TNF receptor-1 (TNFR1). To develop TNFR1-targeted anti-inflammatory drugs, we have already succeeded in creating a TNFR1-selective antagonistic mutant TNF-alpha (R1antTNF) and shown that R1antTNF efficiently inhibits TNF-alpha/TNFR1-mediated biological activity in vitro. In this study, we examined the therapeutic effect of R1antTNF in acute hepatitis using two independent experimental models, induced by carbon tetrachloride (CCl(4)) or concanavalin A (ConA). In a CCl(4)-induced model, treatment with R1antTNF significantly inhibited elevation in the serum level of ALT (alanine aminotransferase), a marker for liver damage. In a ConA-induced T-cell-mediated hepatitis model, R1antTNF also inhibited the production of serum immune activated markers such as IL-2 and IL-6. These R1antTNF-mediated therapeutic effects were as good as or better than those obtained using conventional anti-TNF-alpha antibody therapy. Our results suggest that R1antTNF may be a clinically useful TNF-alpha antagonist in hepatitis.
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PMID:The therapeutic effect of TNFR1-selective antagonistic mutant TNF-alpha in murine hepatitis models. 1881 54


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