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 immunogenicity of hepatitis B vaccine is unknown for patients with chronic hepatitis C, although hepatitis B vaccination is highly recommended in these patients. We therefore studied in a prospective open trial of 59 patients with chronic hepatitis C (mean age 42 years, hepatitis C for >10 years, Child-Pugh score < or = 5) and 58 healthy hospital staff persons the rate of nonresponse (anti-HBs <10 mIU/mL at 9 months) to recombinant hepatitis B vaccine (Gen H-B-Vax(R),10 microg intradeltoidal at month 0, 1, and 6). Nonresponse was observed in 18/59 (31%) patients with chronic hepatitis C and 5/58 (9%) healthy staff persons (P <.005) (vs. 7% in historical controls; P <.005), low response (anti-HBs 10-99 mIU/mL) in 19% of patients with chronic hepatitis C and 17% of staff persons. High-dose booster vaccination led to seroconversion in 12/15 (80%) of primary nonresponders. Primary nonresponse to HB vaccine was related neither to presence of early-stage liver cirrhosis nor magnitude of serum hepatitis C virus (HCV) RNA concentration, nor explained by the presence of human leukocyte antigen (HLA) types (B8 DR3, B44, DR7, DQ2) predisposing to low antibody response to hepatitis B surface antigen. The rate of primary nonresponse to the standard regimen of recombinant hepatitis B vaccine is surprisingly high in patients with longstanding chronic hepatitis C. Therefore, the antibody to HBV surface antigen (anti-HBs) titer response should be determined in these patients. Depending on the response titer, higher booster doses may be required to achieve and maintain seroprotection in these patients.
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PMID:Decreased immunogenicity of recombinant hepatitis B vaccine in chronic hepatitis C. 1096 Feb 83

Autoimmune hepatitis (AIH) is a rare disease, characterized by female predominance, hypergammaglobulinemia, autoantibodies, association with HLA DR3 and HLA DR4 and a good response to immunosuppression. Different subtypes of AIH may be distinguished, based on differences in the autoantibody patterns. AIH type 1 is characterized by anti-nuclear (ANA) and/or anti-smooth muscular (SMA) autoantibodies. AIH type 2 is characterized by liver/kidney microsomal autoantibodies (LKM). AIH type 3 may be distinguished by autoantibodies to soluble liver proteins (SLA) or the liver pancreas antigen (LP). AIH-2 affects predominantly pediatric patients and is characterized by a more severe clinical course, a higher frequency of relapse under immunosuppressive treatment and a more frequent progression to cirrhosis. In contrast, AIH types 1 and 3 show a higher age of onset and a better long-term response to immunosuppressive treatment. At present, the treatment of choice is prednisone alone or a combination with prednisone and azathioprine. Both treatment protocols show high survival rates. However, a rate of 13% of treatment failures and the failure to induce permanent remission in most patients underlines the urgent need to develop additional treatment regimens. A yet unknown genetic predisposition is believed to act as the underlying etiological factor in AIH. This genetic predisposition includes a few known risk factors such as the presence of HLA DR3 or HLA DR4, deletions of C4A alleles and female gender. Furthermore, it has to be postulated that defects in immunoregulatory genes exist. A model for such defects may be the autoimmune polyglandular syndrome type 1 (APS1), which results from the defects in a single gene, the autoimmune regulator type 1 (AIRE-1). Patients with APS1 suffer from mucocutaneous candidiasis and a number of organ-specific autoimmune diseases. Characteristic is a high variability in the number and character of the disease components in APS1, indicating that other genetic and environmental factors may strongly modulate the outcome of disease. Environmental factors may comprise chemical influences, such as nutritional compounds and drugs, or virus infections. Several drugs or chemicals were shown to induce hepatitis with autoimmune involvement, e.g. tienilic acid, dihydralazine and halothane. Adduct formation of an activated metabolite is believed to act as a trigger and to induce a specific immune response. Similarly, viruses were repeatedly shown to trigger autoimmune hepatitis. In virus infections, sequence similarities between viral and self-proteins may trigger autoimmune processes and the simultaneous presence of inflammatory cytokines during virus infection may further increase the risk of developing self-perpetuating autoimmune reactions which overshoot.
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PMID:Autoimmune hepatitis. 1072 4

There have been conflicting reports of the clinical outcome of acute hepatitis A virus (HAV) infection in patients with chronic hepatitis C virus (HCV) infection. A prospective study evaluated 432 patients with chronic hepatitis C (183 with cirrhosis) over a 7-year period. Of the 17 patients with concurrent HAV infection, seven developed fulminant hepatitis and six died. None of these patients had cirrhosis; however, the HLA phenotype (A1; B8:DR3) appeared to be a significant factor in the development of fulminant hepatitis. Patients with this phenotype had high titres of antinuclear antibodies, antismooth muscle antibodies and antiasialoglycoprotein-receptor antibodies, possibly reflecting the induction of autoimmune hepatitis in this group. The high frequency of fulminant hepatitis in patients with HAV/HCV coinfection contrasts with other surveys, although a large Centers for Disease Control and Prevention (CDC) survey demonstrated that HAV infection in patients with pre-existing chronic liver disease (CLD) is associated with increased mortality. It is likely that CLD has some importance as an underlying factor in the development of fulminant hepatitis following HAV infection. Further prospective studies are needed to clarify this issue.
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PMID:Fulminant hepatitis associated with hepatitis A virus superinfection in patients with chronic hepatitis C. 1086 37

To investigate whether sclerosing cholangitis with an autoimmune serology characteristic of autoimmune hepatitis (AIH) and AIH are distinct entities, we studied 55 consecutive children with clinical and/or biochemical evidence of liver disease and circulating antinuclear (ANA), anti-smooth muscle (SMA), and/or liver-kidney-microsomal type 1 (LKM1) autoantibodies. They underwent liver biopsy, direct cholangiography, sigmoidoscopy, and rectal biopsy at presentation. Twenty-eight were diagnosed as AIH in the absence and 27 autoimmune sclerosing cholangitis (ASC) in the presence of radiological features of cholangiopathy. Twenty-six ASC and 20 AIH had ANA and/or SMA; 1 ASC and 8 AIH LKM1 autoantibody. Similarities between the 2 conditions included most clinical and biochemical parameters and a lower frequency of HLA DR4. Inflammatory bowel disease and histological biliary changes were more common in ASC; coagulopathy, hypoalbuminemia, lymphocytic periportal hepatitis, and HLA DR3 were more common in AIH. Histological biliary changes were observed in 65% of ASC and 31% of AIH patients. Eighty-nine percent responded to immunosuppression. Follow-up liver biopsies from 17 ASC and 18 AIH patients had similarly reduced inflammatory activity and no progression to cirrhosis. Sixteen follow-up cholangiograms from AIH patients and 9 from ASC patients were unchanged, while 8 ASC patients showed a progressive cholangiopathy. One child with AIH and ulcerative colitis developed sclerosing cholangitis 8 years after presentation. At 2 to 16 years (median, 7 years) from presentation, all patients are alive, including 4 ASC patients who underwent liver transplantation. In conclusion, ASC and AIH are similarly prevalent in childhood; cholangiography is often needed to distinguish between these 2 entities, which are likely to lie within the same disease process.
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PMID:Autoimmune hepatitis/sclerosing cholangitis overlap syndrome in childhood: a 16-year prospective study. 1123 Jul 33

Whether the host's immune response genes influence the severity of hepatitis C virus (HCV) liver disease is controversial. Human leukocyte antigen (HLA) class II alleles were analyzed in 233 HCV RNA-positive patients with chronic active hepatitis (197 patients with Knodell index of fibrosis F0-F3 and 36 patients with index of F4). The 2 groups did not differ by sex, duration of infection, mode of contamination, alcohol consumption, or HCV genotype. Patients with cirrhosis were older than those without (56+/-12 vs. 46+/-14 years; P<10-4) and had a lower DRB1*11 allele frequency (5.6% vs. 14.5%; P=.037), whereas DRB1*03 and DQB1*0201 frequencies appeared to be higher (DRB1*03, 18.1% vs. 9.6%; DQB1*0201, 37.5% vs. 23.4%; P=.04, corrected P value is not significant). Mean index of fibrosis was higher in DR3-positive than in DR11-positive patients (2.14 vs. 1.58; P=.05). By multivariate analysis, cirrhosis was associated with male sex and age >50 years. HLA class II alleles may weakly contribute to the severity of HCV liver disease. Of persons infected with HCV, only 15%-20% spontaneously clear the virus, and the rest become chronically infected.
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PMID:Human leukocyte antigen class II alleles may contribute to the severity of hepatitis C virus-related liver disease. 1208 69

Primary sclerosing cholangitis is a rare, cholestatic liver disease, most commonly affecting young men. The association of primary sclerosing cholangitis with other autoimmune disorders, although rare, indicates a genetic predisposition for this disease. We describe, for the first time, the association of primary sclerosing cholangitis, ulcerative colitis and coeliac disease in two sisters. Ulcerative colitis was mild and preceded liver disease in both patients. There were no symptoms of coeliac disease, and its silent form was diagnosed on the basis of serological tests. Both patients carried HLA molecules DR3 and DQ2. Although HLA DR4 was not found, there was a rapid progression of liver disease to cirrhosis and cholangiocarcinoma in one patient. The familial occurrence of primary sclerosing cholangitis, ulcerative colitis and coeliac disease supports the hypothesis of genetic predisposition for these diseases.
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PMID:Association of primary sclerosing cholangitis, ulcerative colitis and coeliac disease in female siblings. 1216 91

The overlap syndrome raises several questions. First could these patients have two coincident autoimmune diseases? Such possibility cannot be discarded in particular in the setting of consecutive occurrence of the two conditions (eg, PBC followed by AIH) and this is consistent with the fact that autoimmune diseases are associated with one another in about 5% to 10% of cases. Furthermore, it is presumed that they share similar genetic susceptibility. A second possibility could be that overlap syndrome represents the middle of a continuous spectrum of two autoimmune liver diseases. The systematic study of the relationships between elementary histologic lesions and biochemistries in "pure" PBC patients pleads strongly for such a hypothesis. Pure PBC is characterized by 2 different groups of elementary lesions that are not interrelated: first, florid bile duct lesions and bile duct paucity and second, lymphocytic piecemeal necrosis and lobular necro-inflammatory changes. Furthermore, the first set of lesions is selectively associated with biochemical cholestasis and IgM levels, whereas the second set of lesions is selectively associated with serum transaminase activities and IgG levels. These observations are consistent with the assumption that two main mechanisms are involved in the progression of liver injury in PBC. The first is bile duct destruction leading to chronic cholestasis and fibrosis of biliary pattern. The second is lymphocytic piecemeal necrosis of hepatocytes, which tends to lead to cirrhosis, the pattern of which resembles cirrhosis following various forms of chronic active hepatitis. The author has therefore speculated that the picture of pure PBC results always forms the clinical and biochemical expression of the two main histologic lesions, and combination of these processes might explain why the spectrum of PBC varies from typical PBC to AIH or PBC overlap. A third hypothesis is that an exaggerated hepatitic response in PBC is associated with the HLA haplotype commonly seen in AIH, eg, B8, DR3, DR4. Further studies are obviously needed to confirm such an attractive hypothesis. Other possible explanation for the concurrent occurrence of features of both conditions in the same individual includes the selective modulation of HLA class 1, class 2 expression and Rantes by cholestasis itself and in particular bile acids. It is conceivable that the degree of interface and lobular inflammation in PBC and PSC may be modulated by chemokines, their receptors, and the parenchymal concentrations of individual bile acids that are all, at least in part, genetically determined.
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PMID:Autoimmune overlapping syndromes. 1459 34

Our aim was to investigate whether different human leukocyte antigen (HLA) genes might be associated with hepatitis C virus (HCV) infection. DNA obtained from 141 Spanish patients with HCV infection (48 with alanine aminotransferase levels in the range considered to be normal, 47 with liver cirrhosis, and 46 with hepatocellular carcinomas [HCCs]) and from 116 control subjects were typed for HLA-B, HLA-DRB1, and HLA-DQB1 alleles, as well as for major histocompatibility complex class I chain-related gene A (MICA) transmembrane polymorphism. The frequency of HLA-DR11 was increased in HCV carriers, compared with patients with end-stage liver disease (ESLD) (corrected P value [Pc],.0002) and, especially, with patients who had HCC (Pc=.003). The frequency of the HLA-B18 allele was increased in patients with HCC, and the allele was absent in HCV carriers (Pc=.003). The MICA-A4 allele was overrepresented in patients with HCC, compared with HCV carriers (Pc=.0002). The DR3/MICA-A4/B18 haplotype was associated with HCC (Pc=.01). In conclusion, HLA-DR11 seems to be protective against the development of severe forms of infection, and the DR3/MICA-A4/B18 haplotype may be an important factor in the progression to the most severe HCV-infection status.
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PMID:Extended human leukocyte antigen haplotype EH18.1 influences progression to hepatocellular carcinoma in patients with hepatitis C virus infection. 1499 97

Autoimmune hepatitis (AIH) is a rare and chronic disease which may lead to liver cirrhosis if not correctly treated. Its etiology is unknown, but some progresses have been obtained in the knowledge of damage pathogenesis, its immune mechanisms and genetic predisposition (female gender, presence of HLA DR3 and HLA DR4). It seems that such predisposition favours some agents (e.g. drugs or viruses) to trigger the pathological process. Patients present with variable, often few and unspecific symptoms. Diagnosis is made on the basis of anamnestic (absence of other causes, such as virus infections or alcohol abuse), serological (autoantibodies, high levels of aminotransferases, hypergammaglobulinemia), and histological data (piecemeal necrosis further to bridging necrosis, panlobular and multilobular necrosis); these data are processed by a scoring system which is helpful for the diagnostic definition. Therapy is founded in immunosuppressor drugs, mainly steroids and azathioprine, but a lot of other drugs have been studies for cases of recurrence and of intolerance to the standard treatment.
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PMID:[Autoimmune hepatitis: present knowledge]. 1504 22

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


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