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)

Autoimmune Hepatitis (AIH), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) represent acute and chronic inflammatory liver diseases in which immune reactions against host antigens are found to be the major pathological mechanism. Only for AIH there is evidence of an autoimmune etiology and humoral and cellular immune reactions are found directed against various liver cell antigens. By diverse autoantibodies several subgroups of autoimmune hepatitis can be distinguished. A very important disease promoting factor seems to be the genetically determined background for autoimmunity characterized by the HLA haplotype A1, B8 and DR3, respectively DR4. Although the histopathology of AIH shows no pathognomonic features distinguishing this type of hepatitis from virus induced chronic hepatitis there are some distinct characteristic morphological lesions. If untreated the prognosis of AIH is unfavourable but the benefit from immunosuppressive therapy with prednisolone and azathioprin is well established. In the last years there was increasing evidence for an overlap syndrome between AIH and PBC and rarely AIH and PSC. These patients are characterized by PBC characteristic bileduct lesions and oftenly antimitochondrial antibodies (AMA). They also show AIH typical inflammatory hepatic lesions in the periportal areas and portal tracts and oftenly the typical genetical background, the HLA haplotype A1, B8, DR3 or DR4. Most of these patients respond probably to a combination therapy containing prednisolon, azathioprine and ursodesoxycholic acid that leads to the reduction of the inflammatory activity.
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PMID:[Autoimmune hepatitis and overlap syndrome: therapy]. 1223 65

Atorvastatin and other members of the statin family are widely used for the treatment of hypercholesterolaemia in order to reduce the risk of atherosclerosis and cardiovascular disease. Atorvastatin-induced adverse events are mostly mild and only a few cases of lupus-like syndrome or severe acute hepatitis have been documented. In this case report we describe a patient who developed an atorvastatin-induced severe autoimmune hepatitis. In addition, this patient presented with a concomitant systemic lupus-like syndrome which has been already described for statins but not in association with severe liver disease. Although the drug was immediately withdrawn the disease persisted and even deteriorated to a fulminant disease with evidence of acute hepatic failure. The patient failed to respond to conventional immunosuppression with corticosteroids and azathioprine. Only the introduction of intense immunosuppressive therapy, as used in solid organ transplantation, led to a complete and sustained recovery of the patient. Interestingly, the patient was HLA DR3- and HLA DR4-positive, which are well-known genetic factors associated with autoimmune diseases. This case is the first report of a drug-induced lupus-likesyndrome concomitant with a severe autoimmune hepatitis in a genetically predisposed patient.
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PMID:Drug-induced lupus-like syndrome associated with severe autoimmune hepatitis. 1276 6

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

We report the case of a 56 year-old woman with post-transfusion chronic hepatitis C who presented with a severe ALT flare up associated with a rapid progression of liver fibrosis during interferon alpha 2b therapy. Several hypotheses were considered to explain the etiology of this ALT flare: there was no viral super infection by other hepatotropic viruses, no toxic hepatitis, no metabolic disease, and no other specific liver diseases could be identified. HLA typing showed a specific profile A1 B8 DR3 (risk factor of auto-immunization during interferon alpha therapy) with antinuclear antibodies and anti smooth muscle antibodies. This case suggests that auto-immunization induced by interferon alpha should be investigated in case of ALT flare that is not followed by an HCV breakthrough.
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PMID:[Autoimmunization induced by interferon alpha therapy in chronic hepatitis C]. 1565 45

Autoimmune hepatitis (AIH) is a chronic necroinflammatory disease of the liver characterized by hypergammaglobulinemia, characteristic autoantibodies, association with HLA DR3 or DR4 and a favorable response to immunosuppressive treatment. The etiology is unknown. The detection of non-organ and liver-related autoantibodies remains the hallmark for the diagnosis of the disease in the absence of viral, metabolic, genetic, and toxic etiology of chronic hepatitis or hepatic injury. The current classification of AIH and the several autoantibodies/target-autoantigens found in this disease are reported. Current aspects on the significance of these markers in the differential diagnosis and the study of pathogenesis of AIH are also stated. AIH is subdivided into two major types; AIH type 1 (AIH-1) and type 2 (AIH-2). AIH-1 is characterized by the detection of smooth muscle autoantibodies (SMA) and/or antinuclear antibodies (ANA). Determination of antineutrophil cytoplasmic autoantibodies (ANCA), antibodies against the asialoglycoprotein receptor (anti-ASGP-R) and antibodies against to soluble liver antigens or liver-pancreas (anti-SLA/LP) may be useful for the identification of patients who are seronegative for ANA/SMA. AIH-2 is characterized by the presence of specific autoantibodies against liver and kidney microsomal antigens (anti-LKM type 1 or infrequently anti-LKM type 3) and/or autoantibodies against liver cytosol 1 antigen (anti-LC1). Anti-LKM-1 and anti-LKM-3 autoantibodies are also detected in some patients with chronic hepatitis C (HCV) and chronic hepatitis D (HDV). Cytochrome P450 2D6 (CYP2D6) has been documented as the major target-autoantigen of anti-LKM-1 autoantibodies in both AIH-2 and HCV infection. Recent convincing data demonstrated the expression of CYP2D6 on the surface of hepatocytes suggesting a pathogenetic role of anti-LKM-1 autoantibodies for the liver damage. Family 1 of UDP-glycuronosyltransferases has been identified as the target-autoantigen of anti-LKM-3. For these reasons the distinction between AIH and chronic viral hepatitis (especially of HCV) is of particular importance. Recently, the molecular target of anti-SLA/LP and anti-LC1 autoantibodies were identified as a 50 kDa UGA-suppressor tRNA-associated protein and a liver specific enzyme, the formiminotransferase cyclodeaminase, respectively. Anti-ASGP-R and anti-LC1 autoantibodies appear to correlate closely with disease severity and response to treatment suggesting a pathogenetic role of these autoantibodies for the hepatocellular injury. In general however, autoantibodies should not be used to monitor treatment, predict AIH activity or outcome. Finally, the current aspects on a specific form of AIH that may develop in some patients with a rare genetic syndrome, the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) are also given. Autoantibodies against liver microsomes (anti-LM) are the specific autoantibodies detected in AIH as a disease component of APECED but also in cases of dihydralazine-induced hepatitis. Cytochrome P450 1A2 has been identified as the target-autoantigen of anti-LM autoantibodies in both APECED-related AIH and dihydralazine-induced hepatitis. The latter may indicate that similar autoimmune pathogenetic mechanisms can lead to liver injury in susceptible individuals irrespective of the primary defect. Characterization of the autoantigen-autoantibody repertoire continues to be an attractive and important tool to get access to the correct diagnosis and to gain insight into the as yet unresolved mystery of how hepatic tolerance is given up and AIH ensues.
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PMID:Autoantibodies and autoantigens in autoimmune hepatitis: important tools in clinical practice and to study pathogenesis of the disease. 1567 7

Autoimmune hepatitis (AIH) is characterised histologically by interface hepatitis, and serologically by the presence of non-organ and liver specific autoantibodies and increased levels of immunoglobulin G. Its onset is often ill-defined, frequently mimicing acute hepatitis. AIH usually responds to immunosuppressive treatment, which should be instituted as soon as diagnosis is made. Two types of AIH are recognized according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1 AIH) or liver kidney microsomal type 1 antibody (LKM1, type 2 AIH). There is a female predominance in both. LKM1 positive patients tend to present more acutely, at a younger age and commonly have immunoglobulin A deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment and long-term prognosis are similar in the 2 groups. Susceptibility to AIH type 1 is conferred by possession of HLA DR3 and DR4, while to AIH type 2 by possession of HLA DR7. Liver damage is likely to derive from an immune reaction to liver cell antigens, possibly triggered by a mechanism of molecular mimicry, where immune responses to external pathogens, e.g. viruses, become directed towards structurally similar self-components. In AIH this process would be perpetuated by impairment in immune regulation.
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PMID:Autoimmune hepatitis. 1572 81

Autoimmune hepatitis is classically a disease of young women. Our aims were to determine its occurrence, clinical phenotype, and outcome in elderly patients and contrast findings to young adults. Two-hundred-and-five white North American adults with definite type 1 autoimmune hepatitis were grouped according to age at presentation and the groups compared. Forty-seven patients (23%) were aged > or = 60 years (median age, 68 years), and 31 patients (15%) were aged < or = 30 years (median age, 25 years). The patients > or = 60 years had a higher frequency of cirrhosis at presentation than the patients < or = 30 years (33% versus 10%, P = .03). They also had thyroid or rheumatic diseases more commonly (42% vs. 13%, P = .006). HLA DR3 occurred more frequently in the patients < or = 30 years than in those > or = 60 years (58% vs. 23%, P = .004), and HLA DR4 occurred more often in the patients > or = 60 years (47% vs. 13%, P = .003). Patients aged > or = 60 years failed corticosteroid treatment less commonly than those aged < or = 30 years (5% vs. 24%, P = .03). Autoimmune hepatitis occurred in patients aged 18-30 years (15%), 31-39 years (15%), 40-49 years (21%), 50-59 years (25%), and > or = 60 years (23%). Differences in age distribution, HLA frequencies, and treatment outcome occurred after age > or = 40 years. In conclusion, elderly patients have a greater frequency of cirrhosis at presentation and HLA DR4 than patients < or = 30 years, and they have a lower occurrence of treatment failure. Transitions in clinical and genetic phenotypes occur after age > or = 40 years. Genetic susceptibilities may favor etiologic factors that are age-related.
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PMID:Distinctive clinical phenotype and treatment outcome of type 1 autoimmune hepatitis in the elderly. 1649 38

A 35-year-old female patient presented with the following symptoms of Holmes-Adie syndrome: photophobia,enlargement of the left pupil unresponsive to light, Achilles areflexia. The pilocarpine test was positive. No tumor or other neurological abnormality was found. She had a 19-year history of autoimmune hepatitis. Flares up were observed following each 3 deliveries. At age of 31 she presented with diarrhea and weight loss. Abdominal tumor was detected by ultrasound. The surgically removed tumor was histologically a benign mesenteric multicystic lymphangioma.Simultaneously, celiac disease was diagnosed.Gluten-free diet resulted in a significant improvement of celiac disease,but not of autoimmune hepatitis. Autonomic neuropathy was proven by standard cardiovascular tests. The patient was a homozygous carrier for HLA DQ2 antigen characteristic for celiac disease and heterozygous for HLA DR3 B8 frequent in autoimmune liver diseases. Our novel observation on association of Holmes-Adie syndrome with autoimmune hepatitis and celiac disease is suggestive for a common immunological background for all three entities present in a patient with mesenteric multicystic lymphangioma.
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PMID:Holmes-Adie syndrome, autoimmune hepatitis and celiac disease: a case report. 1655 28

Genetic predisposition is known to be an important etiopathogenic factor of autoimmune hepatitis (AIH). HLA antigens associated with AIH have been well studied in Western countries and Japan, but there is no HLA typing data of AIH patients in Taiwan. We therefore investigated HLA phenotypes and their association with AIH patients and compared the results with those of normal subjects and patients with chronic liver disease. Group 1 consisted of 22 AIH patients. All were born in Taiwan with no history of blood transfusion. Group 2 consisted of 19 chronic liver disease patients. Group 3 consisted of 81 unrelated healthy subjects who were normal blood donors. All three groups were tested for HLA phenotypes (HLAA, B, C, DR, DQ) using the polymerase chain reaction-sequence specific probe method. The statistical method used was Fisher's exact test. We found that HLA-DQ5 was significantly more frequent in the AIH group compared to the control group (RR, 2.03; p = 0.034). Low frequency of A1 (n = 2/22), B8 (n = 1/22) and DR3 (n = 0/22) were noted compared to results from the West; only HLA-DR4 showed a higher rate in our AIH patients (n = 8/22). This is a preliminary report of our study of HLA antigens in AIH patients. Further investigation to characterize AIH patients into HLA allelic subgroups is being done.
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PMID:Significant association of HLA-DQ5 with autoimmune hepatitis in Taiwan. 1840 Jun 15

Autoimmune hepatitis (AIH), initially known as chronic active or active chronic hepatitis (and by various other names), first came under clinical notice in the late 1940s. However, quite likely, chronic active hepatitis (CAH) had been observed prior to this and was attributed to a persistently destructive virus infection of the liver. An earlier (and controversial) designation in 1956 as lupoid hepatitis was derived from associated L.E. cell test positivity and emphasized accompanying multisystem features and immunological aberrations. Young women featured prominently in early descriptions of CAH. AIH was first applied in 1965 as a descriptive term. Disease-characteristic autoantibodies were defined from the early 1960s, notably antinuclear antibody (ANA), smooth muscle antibody (SMA) and liver-kidney microsomal (LKM) antibody. These are still widely used diagnostically but their relationship to pathogenesis is still not evident. A liver and disease specific autoantigen has long been searched for but unsuccessfully. Prolonged immunosuppressive therapy with predisolone and azathioprine in the 1960s proved beneficial and remains standard therapy today. AIH like many other autoimmune diseases is associated with particular HLA alleles especially with the "ancestral" B8, DR3 haplotype, and also with DR4. Looking forwards, AIH is one of the several enigmatic autoimmune diseases that, despite being (relatively) organ specific, are marked by autoimmune reactivities with non-organ-specific autoantigens. New paradigms are needed to explain the occurrence, expressions and pathogenesis of such diseases.
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PMID:Historical reflections on autoimmune hepatitis. 1852 26


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