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)

We investigated the effects of interferon therapy on hepatocyte human leukocyte antigen class I and class II antigen expression and intrahepatic lymphocyte subsets in patients with chronic viral hepatitis B (n = 11) and C (n = 10). Interferon-alpha was administered intramuscularly in doses ranging from 3 to 18 million international units daily for 4 wk. Liver biopsy specimens were obtained just before and immediately after treatment, and the specimens were stained by the indirect immunoperoxidase method for evaluation of human leukocyte antigen expression and lymphocyte subsets. Before therapy, no significant difference was noted between hepatitis B and C in human leukocyte antigen class I antigen expression on hepatocytes or in the lymphocyte subsets in the intralobular and portal areas. After interferon-alpha treatment, hepatocyte expression of human leukocyte antigen class I antigens and serum beta 2-microglobulin levels were virtually unchanged in chronic viral hepatitis C patients, but both were increased in chronic viral hepatitis B patients. Human leukocyte antigen class II antigens were not expressed during treatment. The mean number of intralobular CD3+ and CD8+ cells and the mean serum ALT level decreased significantly in chronic viral hepatitis C patients (p less than 0.05) but not in chronic viral hepatitis B patients. The mean number of intralobular CD4+ cells was unaffected by interferon therapy in both groups. In all 21 patients, the changes in CD8+ cell numbers paralleled the changes in serum ALT levels. Our findings suggest that T-cell cytotoxicity may play an important role in hepatocyte damage in both chronic viral hepatitis C and chronic viral hepatitis B and that the response to interferon-alpha differs in these two types of hepatitis.
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PMID:Effects of interferon on intrahepatic human leukocyte antigens and lymphocyte subsets in patients with chronic hepatitis B and C. 171 Oct

Human leukocyte antigen-D region-related alleles (human leukocyte antigen DR and DQ) and human leukocyte antigen class I alleles were typed serologically in 31 Japanese patients with autoimmune hepatitis. These patients had increased serum levels of AST and IgG, high titers of autoantibodies, no history of blood transfusion and were negative for HBsAg and antibodies to HBc. Three hundred eighty-six healthy subjects and 30 patients with cryptogenic chronic hepatitis served as control groups. The frequency of DR4 was significantly higher in autoimmune hepatitis patients (90.3%) than in healthy subjects (38.6%) and in cryptogenic chronic hepatitis patients (30%). The frequency of Bw54 was significantly higher in autoimmune hepatitis patients (45.2%) than in healthy subjects (10.9%). The risk to DR4-positive subjects for autoimmune hepatitis was 14.8 relative to healthy subjects. Two of 31 patients (6.5%) with autoimmune hepatitis were positive for antibody to hepatitis C virus; both clearly satisfied criteria for autoimmune hepatitis and both had Bw54 and DR4. This study revealed a highly significant association of autoimmune hepatitis with human leukocyte antigen Bw54 and DR4 in Japanese patients. Among the DR4-positive patients with autoimmune hepatitis, no significant differences were seen between those positive or negative for Bw54 with regard to clinical or laboratory data, relapse of disease or efficacy of prednisolone. Thus human leukocyte antigen class II alleles contribute to susceptibility and resistance to autoimmune hepatitis in Japanese patients, with distinct racial differences from those in white patients.
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PMID:Association of autoimmune hepatitis with HLA-Bw54 and DR4 in Japanese patients. 217 92

We investigated the association of human leukocyte antigen antigens and type 1 chronic active "autoimmune" hepatitis in a population of 65 white Argentinian patients, taking into account the different manifestations of the disease. Standard microlymphocytotoxicity was used for human leukocyte antigen A, B, C, DR and DQ typing. Human leukocyte antigen class 2 alleles were also typed on genomic DNA by means of polymerase chain reaction amplification and hybridization to sequence specific oligonucleotides. A primary association with human leukocyte antigen DR4 was present (human leukocyte antigen DR4: 44% in patients vs. 29% in controls; chi 2, 5.6; p = 0.02, relative risk, 2.1). However, a novel association was observed with human leukocyte antigen A11 (31% in patients vs. 6% in the controls; chi 2, 25.3; corrected p = 0.001; relative risk, 6.8). Moreover, of the 20 human leukocyte antigen A11 patients, 18 had extrahepatic manifestations associated with autoimmune chronic active hepatitis. This represented 60% of the patients bearing this form of the disease (n = 30), conferring a relative risk of 22.2 (chi 2, 46.3; corrected p = 0.00008). In this group, human leukocyte antigen DR3 and DR4 had a weak association. When present together, human leukocyte antigen DR4 and human leukocyte antigen A11 had a synergistic effect, yielding an odds ratio of 357. Statistical analysis and family segregation studies suggest that the two loci products may represent independent risk factors for this form of autoimmune chronic active hepatitis. This synergistic effect was not evident with A11 plus DR3. In autoimmune chronic active hepatitis patients without extrahepatic manifestations, a weak association with human leukocyte antigen DR6 was found.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Two-locus involvement in the association of human leukocyte antigen with the extrahepatic manifestations of autoimmune chronic active hepatitis. 818 67

Hepatic fibrosis and cirrhosis are possible consequences of corticosteroid-treated autoimmune hepatitis. Our aims were to determine the frequency of progressive fibrosis and the factors associated with this progression. Two hundred seventy-seven liver tissue specimens that had been obtained from 73 patients were interpreted in batch under code by a single pathologist. Fibrosis scores and histological activity indices were determined using the Ishak scoring system, and worsening fibrosis scores were correlated with clinical features, laboratory findings, and treatment responses. Fibrosis scores increased (2.3 +/- 0.4 points to 4.2 +/- 0.4 points; P <.0001) in 18 patients (25%) during 79 +/- 13 months. Only five patients (7%) developed cirrhosis, and 55 patients (75%) had stable (16 patients) or decreased (39 patients) fibrosis scores. Human leukocyte antigen (HLA) DR3/DR4 occurred more frequently in patients with progressive fibrosis than others (23% vs. 2%; P =.03). Patients with progressive fibrosis had higher histological activity indices at last follow-up than patients with stable or reduced fibrosis (3.2 +/- 0.7 vs. 1.7 +/- 0.2; P =.01), and these indices worsened more commonly during therapy (17% vs. 2%, P =.04). Relapse, treatment failure, and incomplete response did not affect progression of fibrosis. In conclusion, fibrosis progresses in only a minority of patients during corticosteroid therapy. Progression is associated with HLA DR3/DR4 and worsening histological activity. Exacerbations or persistence of disease activity does not increase disease progression after treatment has been instituted.
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PMID:Progressive fibrosis during corticosteroid therapy of autoimmune hepatitis. 1518 4

Human leukocyte antigen (HLA) compatibility has no clinically significant impact in cadaveric liver transplantation. Less is known regarding living-donor liver transplantation (LDLT). Our prior analysis of the Organ Procurement and Transplantation Network (OPTN) database suggested a higher graft failure rate in patients who underwent LDLT from donors with close HLA match. We further investigated the effect of HLA-A, -B, and -DR matching on 5-yr graft survival in adult LDLT by analyzing OPTN data regarding adult LDLT performed between 1998 and 2005. We evaluated associations between 5-yr graft survival and total, locus-specific, and haplotype match levels. Separate analyses were conducted for recipients with autoimmune (fulminant autoimmune hepatitis, cirrhosis secondary to autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis) or nonautoimmune liver disease. Multivariable Cox proportional hazard models were used to evaluate interactions and adjust for potential confounders. Among 631 patients with available donor/recipient HLA data, the degree of HLA match had no significant effect on 5-yr graft survival, even when analyzed separately in recipients with autoimmune vs. nonautoimmune liver disease. To be able to include all 1,838 adult LDLTs, we considered a first-degree related donor as substitute for a close HLA match. We found no difference in graft survival in related vs. unrelated pairs. In conclusion, our results show no detrimental impact of close HLA matching on graft survival in adult LDLT, including in recipients with underlying autoimmune liver disease.
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PMID:Human leukocyte antigen and adult living-donor liver transplantation outcomes: an analysis of the organ procurement and transplantation network database. 1790 26

Human leukocyte antigen (HLA) class II molecules are associated with host immune responses against hepatitis B virus infection. Male gender is the apparent host factor when someone encounters with the severity of hepatitis. The aim of this study was to investigate the association of the most polymorphic HLA class II allele, human leukocyte antigen-DRB1, with the severity of hepatitis in male carriers of hepatitis B virus. In this prospective cohort study, a total of 204 carriers of hepatitis B virus (131 men and 73 women) who have been followed-up for more than 1 year at the outpatient clinic of a university hospital were collected consecutively. Fifty carriers of hepatitis B virus (group I) with alanine aminotransferase <2x upper limit of normal (mean follow-up 83.6 months) were compared with 154 chronic hepatitis B patients (group II) with alanine aminotransferase >/=2x upper limit of normal (mean follow-up 81.3 months). Alleles of HLA-DRB1 were typed by the polymerase chain reaction-sequence specific oligonucleotide probe hybridization and genotypes of hepatitis B virus by melting curve analysis. HLA-DRB1*1101 was found in 18% of group I versus 8% of group II in male carriers (OR 0.23, P = 0.020, after adjustment for age) and 4% versus 9.4% in female carriers (P = 0.094). In male carriers harboring DRB1*1101, the distribution of hepatitis B viral genotype was comparable between the two groups. HLA-DRB1*1101 correlates with less severe hepatitis in Taiwanese male carriers of hepatitis B virus.
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PMID:Human leukocyte antigen-DRB1*1101 correlates with less severe hepatitis in Taiwanese male carriers of hepatitis B virus. 1923 69

Hepatitis B virus (HBV) infection has a wide variety of clinical outcomes, it could be spontaneouly recovered and also could develop fulminant liver failure or cirrhosis with hepatocellular carcinoma. Human leukocyte antigen (HLA) polymorphism and HBV (sub)genotypes have been speculated to associate with the outcome of HBV infection because the data obtained from various populations who bear different HLA alleles have shown a HLA polymorphism associated outcome of HBV infection. However, as the most important viral and host genetic factors, the impact of HBV (sub)genotypes in combination with HLA polymorphism on the clinical outcomes of HBV infections remains unclear. To demonstrate the association of HLA allele polymorphism in combination with HBV subgenotypes with the outcome of HBV infection in Northeastern Han Chinese population, a total of 230 HBV-infected individuals (Infection group) were compared to 210 random selected controls (Control group) who are negative for HBV infection for their HLA alleles frequency as well as the associations with the virus infection, clearance and persistence in combination with HBV subgenotypes. Of the 230 HBV-infected subjects, 54 were acute self-limited hepatitis (ASH) with HBV subgenotype C2 (ASH-C2), 144 were chronic hepatitis (CH) with HBV subgenotype C2 and B2 (CH-C2 and CH-B2), and 32 were spontaneously recovered (SR) without subgenotype results. When two groups are compared, the results suggest that B*48, B*51 and DRB1*12 carrier may have a high risk for HBV infection, but B*51 is likely association with spontaneous recovery and DRB1*07, 12 may be implied in viral persistence. HLA-B*15, DRB1*11 and 14 associated with viral clearance in the cases of HBV-C2 infection; HLA-B*54 carriers in chronic group are more sensitive to with the infection of HBV subgenotype B2; HLA-B*07 and DRB1*13 may protect subjects from HBV infection. The data presented a link between HLA polymorphism and HBV pathogenesis and suggested potential therapeutic targets for hepatitis B.
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PMID:The influence of HLA alleles and HBV subgenotyes on the outcomes of HBV infections in Northeast China. 2205 47

Human leukocyte antigen-G is involved in immunotolerogenic, inflammatory and carcinogenic process. This study investigated serum soluble HLA-G (sHLA-G) levels in patients with chronic hepatitis B virus (HBV) infection according to the infection phases and clinical diagnoses. The study included 223 patients with chronic HBV infection [phases: 38 immune-tolerant (IT), 83 immune clearance (IC), 30 non/low-replicative (LR) and 72 HBeAg negative hepatitis (ENH); diagnoses: 38 asymptomatic HBV carriers (ASC), 98 chronic hepatitis (CH), 46 cirrhosis (LC) and 41 hepatocellular carcinoma (HCC)], 62 HBV infection resolvers and 66 healthy controls. The sHLA-G levels in patients were elevated compared with resolvers and healthy controls (P < 0.001). According to phases, sHLA-G levels were higher in IC and ENH than in IT (P = 0.017 and P = 0.001, respectively). Serum sHLA-G levels were also higher in ENH than in LR (P = 0.008). According to diagnoses, sHLA-G levels in HCC were significantly increased compared with LC, CH and ASC (P = 0.010, P < 0.001 and P < 0.001, respectively). Serum sHLA-G levels were higher in CH than in ASC (P = 0.039). The sHLA-G levels in IC, ENH and CH were correlated with alanine aminotransferase levels (P = 0.011, P = 0.010 and P < 0.001, respectively). It is concluded that sHLA-G is involved in the pathogenesis of chronic HBV infection and correlates with infection phases and clinical diseases, suggesting the value in evaluating disease activity and defining clinical diagnosis.
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PMID:Association of serum soluble human leukocyte antigen-G levels with chronic hepatitis B virus infection. 2300 26

Prognostic evaluation is important for the management of patients with autoimmune hepatitis (AIH). Although some autoantibodies have been associated with disease activity and outcomes, the implication of antibodies to soluble liver antigen (anti-SLA) remains controversial. To conduct a meta-analysis of observational studies which addressed differences in clinical characteristics by anti-SLA status in patients with AIH. Three databases PUBMED, EMBASE, and OVID were systemically searched up to January 2015 using the terms "soluble liver antigen" or "liver-pancreas antigen" and "autoimmune hepatitis" with restriction to English-language. Studies were included if at least 50 patients with objective diagnosis of AIH were enrolled, anti-SLA detection was performed for the patients, and prognostic outcomes and/or disease severity were reported. Two investigators independently reviewed retrieved literature and evaluated eligibility. Discrepancy was resolved by discussion and a third investigator. Quality of included studies was evaluated using Newcastle-Ottawa Quality Assessment Scale (NOS). Data were pooled using fixed-effect or random-effect models. Prognostic outcomes included death from hepatic failure or requirement for liver transplantation, and responses to immunosuppressive therapy regarding remission or relapse. Results were combined on the odds ratio (OR) or standardized mean difference (SMD) scales. Eight studies were enrolled in this study, involving a total of 1297 AIH patients among whom 195 with anti-SLA. Pooled serum AST levels tended to be lower in anti-SLA seropositive patients. The presence of anti-SLA conferred 3.1-fold increased risk of hepatic death in AIH patients. The remission rates were comparable between anti-SLA seropositive and seronegative AIH patients, while anti-SLA positivity was associated with nearly 2-fold increased risk of relapse after drug withdrawal. Human leukocyte antigen (HLA) allotype DR3 was positively associated with anti-SLA. Antibodies to SLA may be an indicator of increased risks of hepatic death and treatment relapse for AIH patients. Our findings suggest that the anti-SLA seropositive patients should be maintained indefinitely on individually adjusted medication to improve their prognosis.
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PMID:Prognostic Implications of Antibodies to Soluble Liver Antigen in Autoimmune Hepatitis: A PRISMA-Compliant Meta-Analysis. 2606 26

Chronic hepatitis B virus (HBV) infection occurs in association to a deregulation of immune system. Human leukocyte antigen E (HLA-E) is an immune-tolerant nonclassical HLA class I molecule that could be involved in HBV progression. To measure soluble (s) HLA-E in patients with chronic HBV hepatitis (CHB). We tested the potential association of HLA-E*01:01/01:03 A > G gene polymorphism to CHB. Our cohort consisted of 93 Tunisian CHB patients (stratified in CHB with high HBV DNA levels and CHB with low HBV DNA levels) and 245 healthy donors. Plasma sHLA-E was determined using enzyme-linked immunosorbent assay (ELISA). Genotyping was performed using polymerase chain reaction sequence-specific primer. No association between HLA-E*01:01/01:03 A > G polymorphism and HBV DNA levels in CHB patients was found. G/G genotype is less frequent in CHB patients without significance. sHLA-E is significantly enhanced in CHB patients compared with healthy controls (P = 0.0017). Stratification according to HBV DNA levels showed that CHB patients with low HBV DNA levels have higher sHLA-E levels compared with CHB patients with high HBV DNA levels. CHB patients with G/G genotype have enhanced sHLA-E levels compared with other genotypes (P = 0.037). This significant difference is maintained only for CHB women concerning G/G genotypes (P = 0.042). Finally, we reported enhanced sHLA-E in CHB patients with advanced stages of fibrosis (P = 0.032). We demonstrate, for the first time, the association of sHLA-E to CHB. Owing to the positive correlation of HLA-E*01:01/01:03 A > G polymorphism and the association of sHLA-E to advanced fibrosis stages, HLA-E could be a powerful predictor for CHB progression. Further investigations will be required to substantiate HLA-E role as a putative clinical biomarker of CHB.
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PMID:HLA-E polymorphism and soluble HLA-E plasma levels in chronic hepatitis B patients. 2695 31


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