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)

Autoimmune hepatitis is an immune cell-mediated chronic liver disease of unknown cause that leads, when untreated, to cirrhosis and liver failure. Importantly, this disease affects not only adults but children as well. Genetic susceptibility is clearly important and the major susceptibility factor identified up to now is the HLA-DRB1 locus, but other genes may play a role as well. HLA-DRB1 alleles present in South American patients differ from those found in patients in other parts of the world. In addition, we have recently identified two chromosomal regions where additional susceptibility factors may be found in Brazilian patients, namely, the class III MHC region and the 5q31 region where the IL-4 and IL-13 genes are located. This review discusses the current knowledge of the pathogenesis of this autoimmune disease occurring in the setting of an immune-privileged organ, the liver, and compares the data on gene polymorphisms studied in Brazil and in other parts of the world.
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PMID:Autoimmune hepatitis in Brazil: an overview. 1763 98

Diagnosis of Autoimmune Hepatitis (AIH) often represents a clinical challenge. The clinical spectrum of disease is quite heterogeneous. AIH can affect patients of all age groups, both sexes, and any race and region. The course may range from subclinical and very mild to acute attacks of hepatitis up to fulminant hepatic failure. Other patients present very late with the picture of cryptogenic cirrhosis. Laboratory features may also differ. Autoantibodies vary, and some patients do not display any autoantibodies at the time of clinical presentation. SLA/LP-autoantibodies are the only antibodies specific for the diagnosis of AIH, but they are only present in about 20% of cases. The most common feature in all patients with AIH is an elevation of IgG levels, usually a selective or highly preferential elevation of IgG in comparison to IgA and IgM. However, in some patients the relative increase in IgG levels may be within the normal limits, because the normal range is quite wide. The diagnosis of AIH should not be made without a liver biopsy showing inflammatory hepatitis. Histology mayshow typical features such as enrichment of plasma cells and piecemeal necroses, but distinction from other inflammatory liver disease including allergic drug reactions may be difficult. The International Autoimmune Hepatitis Group has tried to define diagnostic criteria on the basis of consensus discussions. These were revised in 1999 in the light of some clinical studies. However, the criteria are complicated, and not useful in everyday practise. In addition, the criteria were only designed as a scientific tool in order to create comparable groups in publication from different centres. Therefore, the International Autoimmune Hepatitis Group has re-approached the problem with the aim of defining simplified criteria for everyday use. With the help of various specialised centres in the world we evaluated a number of hypothetical criteria, and found out, that four criteria with two categories are sufficient to either make or exclude the diagnosis of AIH with positive and negative predictive values well over 90%: 1 point2 points1. IgG>16 g/l>18 g/l2. ANA, SMA>1 : 40>1 : 80 or SLA/LP+3. Histologycompatible withtypical for AIH4. Viral markersnegativeA value of 6 or more points makes the diagnosis of AIH very likely, a value of 7 or 8 points demonstrates definite AIH. The simplified criteria should help in the diagnosis of AIH in patients with liver disease, and they seem to be valid world-wide. Prospective data are needed to validate these criteria further.
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PMID:Diagnostic criteria for autoimmune hepatitis. 1793 Dec 12

Autoimmune hepatitis (AIH) is a progressive inflammatory diseases of unknown origin that is characterised by a necro-inflammatory and fibrotic process and may result in liver failure or uncompensated liver cirrhosis. Normally AIH is responsive to immunosuppressive therapy, and treatment aims to alleviate clinical symptoms, and induce biochemical and histological remission. This short review aims to describe standard medical treatment (SMT) and the experience with newer immunosuppressive drugs in patients refractory or intolerant to SMT. In such cases calcineurin inhibitors (i.e, ciclosporine and tacrolimus) might salvage patients from transplantation. Mycophenolate mofetil may also improve liver tests and reduce the requirement for corticosteroids. Besides, sirolimus is effective for treatment of de novo autoimmune hepatitis that sometimes develops after liver transplantation. Initial experience with the sirolimus analog everolimus in non-grafted patients with severe AIH complicated by renal dysfunction seems promising. As the experience with these newer therapeutic agents have only been studied in small numbers of patients, larger and controlled clinical trials are clearly needed to ensure that such therapeutic possibilities are expanding without overlook serious side effects.
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PMID:Treatment of patients with severe autoimmune hepatitis. 1829 68

Autoimmune hepatitis affects all ages, and it is probably under-diagnosed in the elderly. Patients aged >or= 60 years have a higher frequency of cirrhosis at presentation than adults aged <or= 30 years, and they more commonly have HLA DRB1*04. These findings suggest that host factors affect the clinical phenotype by influencing the antigens that are presented to immunocytes and the nature of the immune response. The elderly may have an indolent progressive disease that is asymptomatic or masked by other concurrent rheumatic conditions. An acute, even fulminant, presentation may reflect de novo disease or a spontaneous exacerbation of a pre-existent chronic process. Centrilobular (zone 3) necrosis may reflect an early histological stage that transforms later to classical interface hepatitis. Diagnostic criteria have been codified, and a scoring system allows systemic assessment of all clinical features and quantifies the strength of the diagnosis. Prednisone in combination with azathioprine is the safest effective initial treatment, and all elderly patients with severe disease should be treated vigorously to full resolution of clinical, laboratory and histological features. Adverse effects of treatment occur mainly with protracted treatment (>18 months) and repeated therapies after relapse. Adjustments in the management strategy are warranted for an incomplete response or a need for re-treatment after relapse. Azathioprine (2 mg/kg/day) should be used as a corticosteroid-sparing, long-term maintenance therapy in these instances. Treatment failure is uncommon in the elderly, and age-related changes in the cellular immune response may attenuate the disease and enhance its response to therapy. Concurrent adjuvant therapies must focus on maintenance of bone density.
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PMID:Clinical features, differential diagnosis and treatment of autoimmune hepatitis in the elderly. 1833 Oct 74

Autoimmune hepatitis (AIH) is a chronic hepatitis of unknown etiology which can progress to cirrhosis. Its clinical manifestations are highly variable and sometimes follow a fluctuating course. Diagnosis is based on characteristic histologic, clinical, biochemical and serological findings. Anti-inflammatory/immunosuppressive treatment frequently induces remission but long-term maintenance therapy is often required. Liver transplantation is generally successful in patients with decompensated cirrhosis unresponsive to or intolerant of medical therapy.
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PMID:Clinical features and management of autoimmune hepatitis. 1852 27

A 46-year-old woman presented with arthralgia. She had a history of fluctuating liver function impairment for 6 months. Laboratory investigations revealed elevated liver function test results, positive antinuclear antibodies and elevated serum IgG. The histological findings of a liver biopsy were interface hepatitis accompanied by plasmocytic infiltration with bridging fibrosis. There was no evidence of cirrhosis on pathological examination and no portal hypertension on endoscopic and radiographic studies. Autoimmune hepatitis was diagnosed, and treatment with prednisolone improved the liver dysfunction. After 6 months, she complained of dyspnea. Doppler echocardiography showed a dilated right ventricle, severe tricuspid insufficiency, and systolic pulmonary arterial pressure indicative of pulmonary arterial hypertension. We report this rare case of autoimmune hepatitis with pulmonary arterial hypertension.
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PMID:Autoimmune hepatitis associated with pulmonary arterial hypertension. 1901 10

A 66-year-old female presented with acute illness of severe hepatic dysfunction. She had a past history of chronic hepatitis of low disease activity. After admission and clinical investigation including liver biopsy, it showed an underlying chronic liver disease suggestive of autoimmune hepatitis (AIH) with early liver cirrhosis. Together with other clinical features, this patient was diagnosed as definite AIH type 1 by using the IAIHG (International Autoimmune Hepatitis Group) criteria. During this episode, superinfection by Epstein-Barr virus (EBV) was evidenced by positive PCR (polymerase chain reaction) test, and serial changes of EBV VCA IgM and IgG tests. Severe hepatic impairment was evidenced by markedly elevated AST level 3090 IU/L, high bilirubin level 26.4 mg/dL, and presence of ascites. The patient gradually recovered and liver function improved in agreement with the decline of EBV VCA titers. Immunosuppressive therapy resulted in further improvement of the aminotransferases levels. This is an unusual case of EBV superinfection on pre-existing AIH with early cirrhosis, which caused enhancement of the autoimmune disease process and resulted in severe hepatic decompensation and jaundice. We herein describe the case and briefly review the literature.
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PMID:Chronic autoimmune hepatitis with Epstein-Barr virus superinfection: a case report and review of literature. 1910 93

Autoimmune liver diseases in childhood includes Autoimmune Hepatitis (AIH) and Primary (Autoimmune) Sclerosing Cholangitis (P(A)SC). Both diseases are characterized by a chronic, immune-mediated liver inflammation involving mainly hepatocytes in AIH and bile ducts in PSC. Both diseases, if untreated, lead to liver cirrhosis. AIH could be classified, according to the autoantibodies pattern, into two subtypes: AIH type 1 presents at any age as a chronic liver disease with recurrent flares occasionally leading to liver cirrhosis and liver failure. Characterizing autoantibodies are anti-nuclear (ANA) and anti-smooth muscle (SMA), usually at high titer (>1:100). These autoantibodies are not specific and probably do not play a pathogenic role. AIH type 2 shows a peak of incidence in younger children, however with a fluctuating course. The onset is often as an acute liver failure. Anti-liver kidney microsome autoantibodies type 1 (LKM1) and/or anti-liver cytosol autoantibody (LC1) are typically found in AIH type 2 and these autoantibodies are accounted to have a potential pathogenic role. Diagnosis of AIH is supported by the histological finding of interface hepatitis with massive portal infiltration of mononuclear cells and plasmocytes. Inflammatory bile duct lesions are not unusual and may suggest features of ''overlap'' with P(A)SC. A diagnostic scoring system has been developed mainly for scientific purposes, but his diagnostic role in pediatric age is debated. Conventional treatment with steroids and azathioprine is the milestone of therapy and it is proved effective. Treatment withdrawal however should be attempted only after several years. Cyclosporin A is the alternative drug currently used for AIH and it is effective as steroids. P(A)SC exhibit a peak of incidence in the older child, typically in pre-pubertal age with a slight predominance of male gender. Small bile ducts are always concerned and the histological picture shows either acute cholangitis (bile duct infiltration and destruction) and/or lesions suggesting chronic cholangitis as well (bile duct paucity and/or proliferation, periductal sclerosis). Small bile ducts damage may be associated, at onset or in the following years, with lesions of larger bile ducts with duct wall irregularities, strictures, dilations, and beading resulting in the characteristic ''bead-on-a-string'' appearance. The ''small duct'' (autoimmune) sclerosing cholangitis is also called autoimmune cholangitis. PSC is strictly associated to a particular form of inflammatory bowel disease (IBD) which shows features not typical of ulcerative colitis neither of Crohn's disease. Symptoms related to IBD often are present at onset (abdominal pain, weight loss, bloody stools) but the liver disease is frequently asymptomatic and it may be discovered fortuitously. Treatment of PSC is particularly challenging. In case of ''small duct'' SC or in case of evidence active inflammation on liver biopsy, immunosuppressive treatment is probably useful while in case of large bile ducts non inflammatory sclerosis, immunosuppression is probably uneffective. Ursodeoxycholic acid, however, may leads to an improvement of liver biochemistry even if there's no evidence that it may alter the course of disease. Thus, liver transplantation, is often necessary in the long term follow-up, even with a risk of disease recurrence. In adjunction to these two main disorders, many patients show an''overlap'' disease with features of both AIH and PSC. In such disorders the immune-mediated damage concerns both the hepatocyte and the cholangiocyte with a continuous clinical spectrum from AIH with minimal bile ducts lesions and PSC with portal inflammation and active inflammatory liver damage.
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PMID:Autoimmune diseases of the liver and biliary tract and overlap syndromes in childhood. 1921 8

Autoimmune hepatitis (AIH) can occur in all age groups. AIH affects women more commonly than men (3:1). Clinical presentation may be an acute hepatitis up to fulminant liver failure, but can also be asymptomatic. AIH is characterized by lymphoplasmacellular infiltrates on liver biopsy, elevated liver enzymes in serum and the absence of active viral markers. Patients characteristically present with hypergammaglobulinemia, elevated serum levels of IgG and autoantibodies. Corticosteroids are the drug of choice for induction of remission, azathioprine the drug of choice for maintenance of remission. Rapid response to immunosuppressive treatment supports the diagnosis and leads to a good long-term prognosis.Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are immune mediated diseases affecting bile ducts. While PBC has a slow progression to cirrhosis and complications mostly will be limited to complications of cirrhosis, PSC additionally carries a high risk of developing cholangiocellular carcinoma. The treatment of choice in PBC and PSC is oral ursodeoxycholic acid which may slow progression of liver disease and may ameliorate lab findings.
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PMID:[Autoimmune liver diseases]. 1922 47

Corticosteroid therapy induces clinical, laboratory and histological improvements in 80% of patients with autoimmune hepatitis. Prednisone, alone or at a lower dose in combination with azathioprine, increases the 20-year life expectancy to 80% and prevents or reduces hepatic fibrosis in 79% of patients. The combination regimen is preferred and treatment should be considered in all patients with active disease. The duration of therapy is finite and the medication should be discontinued after resolution of all manifestations of inflammatory activity, including the histological changes. Relapse after drug withdrawal occurs in 50-79% of patients, and it should be treated with long-term azathioprine (2 mg/kg daily). Salvage therapies for individuals intolerant of or refractory to the conventional regimens include high-dose corticosteroids, with or without high-dose azathioprine, 6-mercaptopurine, mycophenolate mofetil, tacrolimus or ciclosporin. Liver transplantation should be considered in patients with hepatic failure unresponsive to corticosteroid treatment, decompensated cirrhosis with a Model for End-Stage Liver Disease score of at least 15 points, or hepatocellular carcinoma that meets transplantation criteria. Autoimmune hepatitis recurs after transplantation in at least 17% of patients, and it typically improves after adjustments in the immunosuppressive regimen. Future therapies are likely to include mesenchymal stem cell transplantation, adoptive transfer of T regulatory cells, and cytokine manipulation. The emergence of new treatments will require the development of a collaborative network of clinical and basic investigators, as the complexity and specificity of current management problems require solutions that exceed the capabilities of single institutions.
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PMID:Current and future treatments of autoimmune hepatitis. 1948 9


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