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 a form of chronic liver disease characterized by progressive hepatocellular inflammation, which usually responds to treatment with corticosteroids. However, 10% of patients with autoimmune hepatitis are refractory to corticosteroids and develop progressive liver disease and cirrhosis. We describe five patients with autoimmune hepatitis who did not respond to conventional corticosteroids and azathioprine therapy who were then treated with cyclosporine A. Cyclosporine A was started at 2-3 mg/kg/day and induced biochemical remission in four of five patients within 3 months. One of the four responders relapsed within 1 month of discontinuing cyclosporine on two occasions. Each time, liver tests promptly normalized after reinitiation of cyclosporine. Two responders were managed with cyclosporine alone. The single patient who did not respond to cyclosporine developed progressive liver failure, underwent orthotopic liver transplantation, and subsequently died of disseminated cytomegalovirus infection. Cyclosporine was generally well tolerated and none of the patients developed renal insufficiency. These data and review of 11 cases in the literature show that cyclosporine can induce remission of liver disease in patients with autoimmune hepatitis who are refractory to corticosteroids.
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PMID:Cyclosporine therapy in patients with steroid resistant autoimmune hepatitis. 993 64

We characterized 70 consecutive patients with cryptogenic cirrhosis to assess major risks for liver disease. Each patient was reevaluated for past alcohol exposure, scored by the International Autoimmune Hepatitis (IAH) score and assessed for viral hepatitis risks and risks for nonalcoholic steatohepatitis (NASH). The results were compared with 50 consecutive NASH patients, 39 nonalcoholic patients age 50 and over with cirrhosis from hepatitis C, and 33 consecutive patients with cirrhosis caused by primary biliary cirrhosis (PBC). Among the cryptogenic group, 49 (70%) were female, and the mean age was 63 +/- 11 years. Although ascites and variceal bleeding were common, almost one half lacked major signs of complicated portal hypertension. A history of Type 2 diabetes mellitus and/or obesity was present in 51 (73%). Nineteen (27%) patients had a history of blood transfusions antedating the diagnosis of cirrhosis. No clinical or histological features distinguished this group from the other patients, and 14 (74%) of these had a history of obesity and/or diabetes. Nineteen of the remaining nontransfused patients had indeterminant IAH scores but were histologically and biochemically indistinguishable from the others. Twelve of these (63%) also had a history of obesity and/or diabetes. Both diabetes and obesity were significantly more common in the cryptogenic cirrhotic patients compared with the cirrhotic patients with PBC or hepatitis C. In contrast, the prevalence of obesity and diabetes was similar to the NASH patients who were, on average, a decade younger. Although there is some diversity that indicates more than one cause, our findings suggest that NASH plays an under-recognized role in many patients with cryptogenic cirrhosis, most of whom are older, type 2 diabetic and obese females.
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PMID:Cryptogenic cirrhosis: clinical characterization and risk factors for underlying disease. 1005 66

We examined the clinical characteristics of 89 patients with autoimmune hepatitis (AIH) in Nagasaki Prefecture, Japan, and assessed the usefulness of a provisional scoring system for the diagnosis of AIH proposed by the International Autoimmune Hepatitis Group in 1993. The majority of patients were middle-aged women in their fifties. All patients showed a hepatitic picture. Forty-three patients (48%) had an insidious or chronic onset, while 34 (38%) had an acute onset, and 12 (14%) had liver cirrhosis at presentation. Seventy-nine patients (89%) were positive for antinuclear antibody (ANA), and 5 (6%) were positive for antibody to the hepatitis C virus (anti-HCV). The prognosis was good, with 90% 3-year survival, and most patients responded well to treatment with corticosteroids. The international scoring system was useful for the diagnosis of AIH in most of our patients; the percentages of patients with definite and probable AIH were 48% and 47%, respectively. However, certain factors, such as negative ANA, positive antimitochondrial antibody, concurrent infection with hepatitis B or C virus, and insufficient response to treatment precluded the diagnosis of AIH in some patients. Whether these patients were indeed "true" AIH patients is not clear at present, and further investigation of such patients may be useful for a better understanding of AIH.
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PMID:Clinical features of 89 patients with autoimmune hepatitis in Nagasaki Prefecture, Japan. 1021 22

We describe the case of a 18-year-old male patient who first presented with decompensated cirrhosis, fever and generalized lymphadenopathy. He had abnormal results for liver biochemical tests, with a hepatitic-like picture and high titre of antinuclear antibodies. According to the scoring system proposed by the International Autoimmune Hepatitis Group he had 'definite' autoimmune hepatitis and responded well to immunosuppressive treatment. One year later he developed pyoderma gangrenosum which was successfully treated with cyclosporine. Two years later he experienced bloody diarrhoea as a first presentation of ulcerative colitis. At that time both the cholestatic biochemical picture and the cholangiographic appearances of the biliary tree were consistent with primary sclerosing cholangitis. Despite the addition of azathioprine and ursodeoxycholic acid to his treatment regime he developed recurrent episodes of cholangitis and intractable pruritus for which he underwent successful liver transplantation.
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PMID:Overlapping syndrome of autoimmune hepatitis and primary sclerosing cholangitis associated with pyoderma gangrenosum and ulcerative colitis. 1065 5

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

Autoimmune hepatitis (AIH) after liver transplantation (LT) may recur and is difficult to diagnose. Our aims were to define the histopathology of and factors related to AIH recurrence. Fourteen of 475 patients received LT for AIH; 2 died perioperatively. Liver specimens (native and post-LT biopsies) from 12 other patients were reviewed and correlated with pre- and post-LT clinical course and outcome. Recurrent AIH was seen in 5 of 12 patients, 35 to 280 days post-LT as lobular hepatitis with acidophil bodies and lymphoplasmacytic infiltrate. Portal/interface hepatitis was seen with disease progression and 2 of 5 patients developed cirrhosis. Of 7 nonrecurrent patients, 1 had acquired hepatitis C with lobular/portal hepatitis and none developed cirrhosis. Histology suggestive of overlap syndrome was seen in 3 of 12 native livers with no effect on post-LT course or pathology. High-grade necroinflammation was present in native livers at LT in 5 of 5 cases with recurrent AIH and in 1 of 7 without recurrence (P <.01). Pre-LT disease duration, donor/recipient gender distribution, HLA studies, and rejection episodes did not correlate with AIH recurrence. We conclude that (1) recurrent AIH is not uncommon and was seen in 42% of patients with lymphoplasmacytic lobular, portal, and interface hepatitis; (2) acidophil bodies with lymphoplasmacytic cells are seen in early recurrent AIH; (3) recurrent AIH appears at variable time periods post-LT, and the progression is slow; and (4) high-grade inflammation in native liver at LT is a strong predictor of recurrent AIH.
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PMID:Liver transplantation for autoimmune hepatitis: a long-term pathologic study. 1091 22

To determine the frequency, risk factors, and consequences of recurrent autoimmune hepatitis after liver transplantation, 41 patients with type 1 disease were monitored after surgery in accordance with a surveillance protocol. Tacrolimus or cyclosporine plus prednisone were administered to each patient, and liver biopsy examinations were performed at least annually according to protocol. Corticosteroid therapy was ultimately discontinued in only 2 patients. Recurrent disease was defined as the presence of lymphoplasmacytic infiltrates in liver tissue in the absence of other causes of allograft dysfunction. Autoimmune hepatitis recurred in 7 patients (17%), and the mean time to recurrence was 4.6 +/- 1 years. Recurrence was asymptomatic in 4 of 7 patients and detected only by surveillance liver biopsy assessment in 2 patients. Histological changes were mild, and there was no progression to cirrhosis during 4.9 +/- 0.9 years of observation. Five-year patient (86% v. 82%; P =.9) and graft (86% v. 67%; P =.5) survival rates were not statistically different between patients with and without recurrent disease. HLA-DR3 or HLA-DR4 occurred more commonly in patients with than without recurrence (100% v. 40%; P =.008) and healthy subjects (100% v. 49%; P =.01). Recurrent disease was unrelated to donor HLA status. In conclusion, recurrence after transplantation for type 1 autoimmune hepatitis is common. Its mild manifestations and favorable prognosis may reflect early detection by a surveillance protocol and/or continuous corticosteroid treatment. HLA-DR3- or HLA-DR4-positive recipients are at risk for recurrence regardless of donor HLA status.
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PMID:Recurrent autoimmune hepatitis after orthotopic liver transplantation. 1130 89

The number of patients with autoimmune hepatitis with histological features of acute hepatitis (AIH-AH) has been increasing recently. Here, the clinical features of patients with AIH-AH have been compared with those of patients with AIH with histological findings of chronic hepatitis (AIH-CH) and liver cirrhosis (AIH-LC). The levels of total serum bilirubin (P<0.05) and serum transaminases (P<0.05) were significantly higher in patients with AIH-AH than in patients with AIH-CH and AIH-LC. However, the serum levels of gamma-globulin (P<0.05) and immunoglobulin G (P<0.05) were significantly lower in AIH-AH than in patients with AIH-CH and AIH-LC. The aggregate score according to the criteria of the International Autoimmune Hepatitis Group in 1999 was also significantly lower in AIH-AH patients than in patients with AIH-CH and AIH-LC (P<0.05). Eleven patients with AIH-AH were treated with corticosteroids, however, the clinical response was insignificant in three patients. In summary, it is difficult to diagnose of patients with AIH-AH using the criteria of the International AIH scoring system. We wish that this scoring system would be modified in the near future.
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PMID:Clinical characteristics of autoimmune hepatitis with histological features of acute hepatitis. 1167 6

Autoimmune hepatitis is characterized by a continuing hepatocyte necrosis that usually progresses to liver cirrhosis. Autoimmunity is also a feature of chronic infection by Helicobacter pylori, a gram-negative bacterium involved in the pathogenesis of peptic ulcer and upper gastrointestinal bleeding, with both events frequently occurring in patients with chronic liver disease. A newly described pathogenetic mechanism for chronic hepatitis and hepatocellular carcinoma in the mouse is linked to Helicobacter spp. infection. A high prevalence of H. pylori infection was demonstrated in patients with viral-related cirrhosis but never studied in cases of autoimmune hepatitis. In a case-control study, we examined 31 consecutive patients (25 women and 6 men, age range 20-66, mean age 46 +/- 4.3 years) suffering from autoimmune hepatitis and 62 sex- and age-matched blood donors (50 women, 12 men, age range 20-65, mean age 46 +/- 5.4 years) resident in the same area. Antibodies to H. pylori were present in 20 of 31 (64.5%) autoimmune patients compared to 33 of 62 (53.2%) controls (P = 0.3, odds ratio 1.60, 95% CI 0.60-4.28). The difference was not statistically significant either in female or male patients. In conclusion, the prevalence of H. pylori infection in patients and controls was similar in our study of patients with chronic autoimmune hepatitis.
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PMID:Helicobacter pylori seroprevalence in patients with autoimmune hepatitis. 1185 54

Autoimmune hepatitis (AIH) is a rare autoimmune disease (incidence about 5% among all chronic liver disorders) that reflects a loss of tolerance to normal hepatic proteins. AIH is characterized by female preponderance, hypergammaglobulinemia, extrahepatic syndromes and a good response to immunosuppressive treatment. AIH may be subdivided into two or three subtypes. AIH type 1 is characterized by antinuclear autoantibodies (ANA) and/or smooth muscle antibodies (SMA). SMA are actin-specific, can occur without ANA and their presence relates strongly to AIH. AIH type 2 is defined by the presence of anti-liver-kidney microsomal antibodies (LKM-1). Patients with AIH type 2 are typically younger at the time of disease onset, exhibit higher inflammatory activity, suffer more frequent relapses under immunosuppressive treatment and are more likely to progress to cirrhosis. AIH type 3 is characterized by autoantibodies against the soluble liver antigen (SLA) and liver-pancreas antigen (LP), but ANA/SMA are frequently present and, therefore, some authors consider this autoantibody manifestation as belonging to AIH type 1. Antineutrophil cytoplasmic antibodies (ANCA) recognize cytoplasmic or nuclear components of neutrophilic granulocytes and are detected with high prevalence in patients with autoimmune liver diseases. They are associated with AIH type 1 but not with AIH type 2. However, 40-70% of patients with primary sclerosing cholangitis (PSC) also produce these autoantibodies. Autoimmune cholangitis is an idiopathic disorder with mixed hepatocellular and cholestatic findings that typically has antinuclear antibodies (ANA). It may be considered as an atypical form of primary biliary cirrhosis. It has been recognized that some forms of AIH may also occur with variable incidence and severity especially in patients with primary biliary cirrhosis (overlap AIH/PBC) or primary sclerosing cholangitis (AIH/PSC). On the basis of clinical, biochemical, serological, histological and radiological criteria a clear distinction between these conditions can be readily made in the majority of cases. An association of AIH-typical autoantibodies (anti-LKM-1, anti-SLA/LP) in association with antimitochondrial autoantibodies (AMA) almost confirm the overlap syndrome AIH/PBC. In PSC patients expressing typical ERCP findings and suffering from inflammatory bowel disease (IBD), the diagnosis of an overlap syndrome between PSC/AIH can be readily made in the presence of ANCA and AIH relevant autoantibodies. Apart from this kind of overlap syndrome involving different types of autoimmune disorders within the liver AIH can be also associated with other organspecific autoimmune disorders as documented in the autoimmune polyglandular syndrome type 1 (APS-1). In this disease homozygosity for a defect in a single gene (AIRE) leads to a broad spectrum of organ specific autoimmune diseases.
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PMID:[Autoimmune hepatitis and overlap syndrome: diagnosis]. 1223 64


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