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)

The hepatotropic viruses, measles, and herpesviruses as well as different drugs were repeatedly shown to act presumably as a trigger in patients with autoimmune hepatitis (AI-H). On the other hand, it is known that viral infections stimulate interferon production, which inactivates the cytochrome P-450 enzymes involved in the metabolism of several endogenous substances and exogenous environmental agents. Moreover, it was reported that several cytokines, including interferons, as well as transforming growth factor beta1 and human hepatocyte growth factor, which are abundantly produced and released in the body during infections, also downregulated expression of major cytochrome P-450 and/or other biotransformation enzymes. It seems that all these factors, in addition to individual immune response and the nature and amount of the neoantigen(s) produced, impair the equilibrium of bioactivation and detoxication pathways, thus leading to the development of AI-H in a genetically predisposed person continually exposed to harmful environmental factor(s). Possible increased/decreased density of lysine residues at position D-related human leukocyte antigen locus (DR)beta71 of the antigen-binding groove may affect the eventual steroid-sparing effect of this critical amino acid at the cellular level. In addition, some food additives, such as monosodium glutamate (MSG) and/or aspartame regularly consumed in excessive amounts, may eventually disturb the delicate balance between a positively charged amino acid residue at position DRbeta71 (lysine or arginine) and a negatively charged amino acid residue at position P4 on the antigenic peptide (glutamic acid or aspartic acid). This may favor formation of a salt bridge between these amino acid residues within the hypervariable region 3 on the alpha-helix of the DRbeta polypeptide and facilitate autoantigen presentation and CD4 T-helper cell activation. MSG and aspartate may also depress serum concentrations of growth hormone, which downregulate the activity of several cytochrome P-450 hepatic and other drug-metabolizing enzymes, thus increasing sensitivity to some environmental agents and possibly influencing efficacy of treatment regimens and final outcome of patients with type 1 AI-H.
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PMID:Possible pathomechanism of autoimmune hepatitis. 1252 21

Immunopathological differences between autoimmune hepatitis (AIH) and chronic hepatitis C (CH-C) have not been well investigated. Therefore, we immunohistochemically examined the expression of various cytokeratins (CKs) not only in liver tissues of AIH but also in those of CH-C at the active stage. Furthermore, to evaluate the immune surveillance system and the susceptibility to apoptosis, immunohistochemical staining of human leukocyte antigen (HLA)-DRalpha, cathepsin D, B cell leukemia-2 (bcl-2), bcl-2-associated X protein (bax) and caspase 3 was also performed. Heterogeneous expression of CK 8 and CK 18 was observed in hepatocytes of AIH, while homogeneous expression was observed in hepatocytes of CH-C. Aberrant expression of CK 7 and CK 19 was observed in hepatocytes of AIH, while it was not in hepatocytes of CH-C. Expression of HLA-DRalpha was observed in hepatocytes of AIH but not in those of CH-C. Furthermore, expression of cathepsin D, bax and caspase 3 was much stronger in hepatocytes of AIH than in those of CH-C. These results indicate that cytoskeletal alterations of hepatocytes in AIH may increase the susceptibility to apoptosis and induce hepatocyte destruction.
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PMID:Aberrant cytokeratin expression and high susceptibility to apoptosis in autoimmune hepatitis. 1269 48

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is caused by mutations in the autoimmune regulator (AIRE) gene, which has a central function in maintaining immunological tolerance. A number of conditions with proven or likely autoimmune pathogenesis occur in APECED: hypoparathyroidism, adrenocortical insufficency, candidiasis, hypogonadism, type 1 diabetes, hypothyroidism, hypophysitis, hepatitis, malabsorption, nail dystrophy, enamel hypoplasia and keratopathy. It is not clear which factors are responsible for variation in clinical picture of APECED, but human leukocyte antigen (HLA) genotype may be important. The authors report the first description of a case of primary pulmonary hypertension (PPH) in patient with APECED, caused by R257X mutation in AIRE. The HLA genotype of the patient (DRB1*01/DRB1*11, DQB1*0301/DQB1*0501) has been previously reported as a predisposing factor to PPH. The findings from this study, provided that other similar cases are reported, suggest that immune deregulation plays a role in the pathogenesis of primary pulmonary hypertension.
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PMID:Fatal primary pulmonary hypertension in a 30-yr-old female with APECED syndrome. 1458 26

The human leukocyte antigen (HLA)-A*2402 is common in Asians. The authors attempted to identify epitopes for HLA-A*2402-restricted, hepatitis C virus (HCV)-specific CD8(+) T cells by an enzyme-linked immunospot (ELISpot) assay using peripheral blood CD8(+) T cells from HLA-A*2402-positive hepatitis C patients and synthetic HCV peptides based on HLA-A*2402-binding motifs and the amino acid sequence of type 1b HCV. Ten novel epitopes were identified in five of seven HLA-A*2402-positive patients with acute or short-term chronic HCV infection (<3 years), but in none of four with longer-term chronic infection (>10 years). Only one of the ten epitopes proved to be definitely HLA-A*2402-restricted. Another epitope was identified in one of two HLA-A*2402-negative acute hepatitis C patients. In two of the six patients with positive CD8(+) T cell responses, the targeted epitopes were multiple. The same epitope was targeted in two patients. When patients with unresolved acute HCV infection were treated with alpha interferon, peripheral blood HCV-specific CD8(+) T cells decreased with resolution of the hepatitis. In conclusion, CD8(+) T cell responses to HCV infection are heterogeneous. One definite HLA-A*2402-restricted and ten probably non-HLA-A*2402-restricted epitopes were identified. Patients with short-term HCV infection are suitable for searching for novel HCV epitopes, but peripheral blood HCV-specific CD8(+) T cells decrease markedly after loss of antigenic stimulation.
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PMID:Identification of novel hepatitis C virus-specific cytotoxic T lymphocyte epitopes by ELISpot assay using peptides with human leukocyte antigen-A*2402-binding motifs. 1516 36

Beta2 microglobulin is one of the domains of the histocompatibility class I human leukocyte antigen (HLA) antigen. In hepatitis infection the presentation of the viral antigen on the hepatocyte in the presence of class I HLA antigens plays a significant role in the elimination of the virus. The aim of the study was to estimate the serum beta2 microglobulin levels in cases of chronic hepatitis B infection. Serum beta2 microglobulin levels were assessed in 65 cases with chronic hepatitis B infection including 29 pediatric and 36 adult patients as the study group and in 30 cases as seronegative control group. Beta2 microglobulin level was found significantly higher in chronic active Hepatitis B virus (HBV) patients compared to the asymptomatic HBV carriers and also in the chronic active HBV patients compared to control group. We are of the opinion that beta2 microglobulin concentration is an indicator for monitoring chronic active HBV infections at the asymptomatic hepatitis B virus carrier patients, thus would lead to early initiation of Interferon (IFN) treatment and to monitor the effectiveness of the therapy.
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PMID:The role of beta2 microglobulin levels in monitoring chronic hepatitis B. 1518 72

Genetic (human leukocyte antigen), disease-related and demographic risk factors for nevirapine reactions were examined in a nevirapine-exposed cohort. Cases involving combinations of hepatitis, fever or rash were associated with an interaction between HLA-DRB1*0101 and the percentage of CD4, whereas no associations were detected for isolated rash. These data suggest that HLA-DRB1*0101 and the CD4 status may determine susceptibility to nevirapine hypersensitivity, consistent with a CD4 T-cell-dependent immune response to nevirapine-specific antigens.
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PMID:Predisposition to nevirapine hypersensitivity associated with HLA-DRB1*0101 and abrogated by low CD4 T-cell counts. 1562 41

A 58-year-old woman complaining of finger tremor was referred to our hospital. The diagnosis of Graves' disease was made based on increased free triiodothyronine (18.88 pg/ml) and free thyroxine (7.47 ng/dl), low TSH (<0.005 microIU/ml) and increased TSH receptor binding antibody activity (70.9%). Serum level of AST (62 U/l) and ALT (93 U/l) were increased and liver biopsy revealed linkage of adjacent portal areas by lymphoplasmacytic infiltrates and fibrosis with piecemeal necrosis. Although antinuclear antibody was negative, these findings indicated that she had autoimmune hepatitis (AIH) according to the criteria of the International Autoimmune Hepatitis Scoring System. Slowly progressive type 1 diabetes mellitus (DM) was confirmed by a diabetic response pattern due to 75 g-oral glucose tolerance test, and seropositivity towards anti-glutamic acid decarboxylase (725 U/ml) and islet cell (80 JDF Units) antibodies. This case exhibited an extremely rare combination of three different autoimmune diseases, including Graves' disease, slowly progressive type 1 DM and AIH, and had no known sensitive human leukocyte antigen (HLA) typing or haplotype for these disorders. Although it is common for patients with Graves' disease to exhibit abnormal liver function, it is important to make an accurate diagnosis of AIH because of this life-threatening disorder.
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PMID:A case of polyglandular autoimmune syndrome type III complicated with autoimmune hepatitis. 1694 65

We describe an unusual case of unexpected dyspnoea following transfusion of fresh frozen plasma (FFP) in a previously-well 72-year-old woman. Our patient was scheduled for an ultrasonographically-guided liver biopsy for work-up for autoimmune hepatitis. She was given FFP to correct a prolonged prothrombin time. Shortly after the transfusion was initiated, she started coughing and became progressively dyspnoeic. Clinically, she was tachypnoeic with diffuse bilateral crepitations, and rapidly went into respiratory failure. She was intubated and placed on mechanical ventilation. Her condition improved and she was extubated by the second day, with no long-term pulmonary sequelae. A diagnosis of transfusion-related acute lung injury (TRALI) was made, based on the rapidity of onset and association with transfusion. This was confirmed by the findings of anti-human leukocyte antigen antibodies in both the patient and recipient blood. Our case highlights this important but under-recognised condition. The incidence, diagnosis and management of TRALI are also discussed.
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PMID:Dyspnoea due to plasma transfusion-related acute lung injury. 1699 Sep 69

Acute cellular graft-vs.-host disease (GVHD) following liver transplantation has an incidence of 1 to 2% and a mortality rate of 85%. Our aim was to identify a patient population at high risk for developing GVHD using a large clinical database to study both recipient and donor factors. We compared our liver transplant patients who developed GVHD to those that did not for recipient and donor factors and combinations of factors. For 2003-2004 we had 205 first-time liver transplant patients surviving >30 days. From this group, 4 (1.9%) developed GVHD. Compared to the control group, there were no significant differences in recipient age, recipient gender, donor age, donor gender, total ischemia time, donor-recipient human leukocyte antigen (HLA) mismatch, or donor-recipient age difference. Percentages of liver disease etiologies among the patients who developed GVHD were as follows: 16% (1/6) autoimmune hepatitis (AIH) (P = 0.003), 5.6% (3/54) alcoholic liver disease (ALD) (P = 0.057), and 7.1% (3/42) hepatocellular carcinoma (HCC) (P = 0.026). The incidence of GVHD in patients with glucose intolerance (either Type I or Type II diabetes mellitus [DM]) was significant (P = 0.022). Focusing on patients only with high-risk factors for GVHD during the years 2003-2005, we had 19 such patients. Four of these high-risk patients developed GVHD. Three of these 4 patients had received a donor liver with steatosis of degree >or=mild compared to only 2 of the 15 high-risk patients who did not develop GVHD (P = 0.037). In conclusion, we have identified liver transplant patients with AIH or the combination of ALD, HCC, and glucose intolerance who receive a steatotic donor liver as being at high risk for developing GVHD.
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PMID:Recipient and donor factors influence the incidence of graft-vs.-host disease in liver transplant patients. 1739 49

1. In hepatitis C virus (HCV)-infected patients undergoing liver transplantation (LT), the virus infects the liver graft immediately after transplantation. The main source of HCV infection is circulating virions. Nevertheless, some data suggest that HCV present in extrahepatic compartments may contribute to HCV infection in some cases of hepatitis C recurrence. 2. Studies on early kinetics have shown that HCV replication starts a few hours after transplantation and that HCV-RNA concentrations increase a few hours or days after the procedure, suggesting that HCV has an enormous ability to adapt to the new environment. 3. The quasispecies population may change significantly after transplantation, most likely because of the need to adapt to a new environment. There are no conclusive data supporting the role of HCV quasispecies composition and disease outcomes. 4. Persistence of HCV infection is the rule after transplantation. This is due to immunosuppression and to the immune exhaustion of the previously exposed immune system. 5. In general, HCV is not thought to be directly cytopathic. Thus, it is believed that the immune response against HCV causes liver damage. However, understanding the mechanisms of liver damage in HCV-infected LT recipients is extremely complex because of the existence of a human leukocyte antigen-mismatched organ, the preexisting virus-specific T cells that may be dysfunctional and/or tolerized, and the immunosuppression. 6. Despite the possible effect of immune-mediated liver damage, it is clear that strong immunosuppression is associated with severe forms of hepatitis C recurrence (cholestatic hepatitis, fibrosing cholestatic hepatitis, and accelerated fibrosis progression). Thus, in the absence of a strong anti-HCV immune response, HCV is able to directly (HCV proteins) or indirectly (cytokines) produce liver damage. 7. The activation of stellate cells and accelerated deposition of fibrosis are the final consequences of HCV infection in the graft. There are several mechanisms that may act synergistically to activate and perpetuate stellate cell activation in the setting of LT: ischemia-reperfusion damage, old donor age, HCV proteins, cholestasis, rejection, infection with other viruses (cytomegalovirus), and immune-mediated injury.
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PMID:Virology and pathogenesis of hepatitis C virus recurrence. 1882 23


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