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)

Immunosuppressive treatment with prednisolone and/or azathioprine has been assessed in three chronic liver diseases with immunological features, namely chronic active hepatitis, cryptogenic cirrhosis and primary biliary cirrhosis. In chronic active hepatitis, controlled prospective clinical trials have shown clinical, biochemical and hepatic histological improvement when prednisolone with or without azathioprine is employed. Azathioprine alone has no advantage over placebo tablets. Cirrhosis is probably not prevented. Selection of patients for treatment, the response and therapeutic regimes are discussed. Patients with hepatitis B surface antigen positive chronic active hepatitis have a worse therapeutic response than those patients with chronic active hepatitis who are HBsAg negative. In primary biliary cirrhosis, corticosteroid treatment is contra-indicated on account of bone thinning. Azathioprine has been used in controlled clinical trials and is of only marginal benefit.
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PMID:Immunosuppressive therapy in chronic liver disease. 71 60

Influence of viral liver diseases on the occurrence of azathioprine hepatitis was evaluated in 21 kidney transplant recipients. Diagnosis of azathioprine hepatitis was always based on jaundice, which disappeared after azathioprine withdrawal in 18 patients and after azathioprine dose reduction in 3 patients. Histopathological diagnosis of azathioprine toxicity was ascertained in 14 patients. Rechallenge with azathioprine performed in 4 patients, within 2-4 months after the first jaundice episode, resulted in relapse of jaundice in all cases. Viral hepatitis B virus and hepatitis C markers were present in all 20 tested patients (serum hepatitis B surface antigen in 6 patients and anti-HCV antibodies in 17 patients). Biopsy-proven chronic hepatitis was observed in 18 patients, including 14 chronic active hepatitis, 3 chronic persistent hepatitis and cirrhosis in 1. In kidney transplant recipients, azathioprine hepatitis seems to be facilitated or induced by hepatitis B virus or hepatitis C virus chronic hepatitis. Azathioprine reduction or withdrawal should therefore be combined with the diagnostic evaluation and the treatment of viral liver diseases.
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PMID:Azathioprine hepatitis in kidney transplant recipients. A predisposing role of chronic viral hepatitis. 868 59

Azathioprine is a frequently used immunosuppressant for managing inflammatory bowel disease (IBD). In recent years the hepatotoxic profile of thiopurines has been recognised. We report the case of a 40-year-old man with Crohn's disease treated with azathioprine. After taking azathioprine (2.2 mg/kg daily) for two years, his liver function tests were found to be elevated. Moreover, a myelodepression was established as platelet and leucocytes counts were lowered. The 6-thioguaninenucleotide level was 738 picomoles/8 x 10(8) per red blood cell, which is well above the proposed upper limit of efficacy and associated with an increased risk of developing a myelodepression. Genotyping of the enzyme thiopurine methyltransferase revealed no mutant alleles. The ultrasonography and CT scan showed signs of portal hypertension (spleen 17 cm and widened splenic vein). A liver biopsy was performed and an incomplete septal liver cirrhosis was found. An upper endoscopy revealed oesophageal varices (grade 2 to 3). Autoimmune and viral liver diseases were ruled out by laboratory parameters. After cessation of therapy, all laboratory parameters normalised. Therefore, azathioprine is believed to be the causative factor for inducing the liver cirrhosis. Continuous monitoring of patients taking thiopurines is mandatory. The role of 6-thioguaninenucleotide levels in inducing myelotoxicity and hepatotoxicity is discussed.
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PMID:Myelotoxicity and hepatotoxicity during azathioprine therapy. 1639 13

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

In recent years, the hepatotoxic potential of thiopurines, in particular 6-thioguanine (6-TG) has been discussed in literature. However, cirrhosis was exceptionally reported. We report the case of a 56-year-old woman with ileocaecal Crohn's disease treated with azathioprine. After taking azathioprine (2 mg/kg daily) for four years, she underwent surgical treatment for acute intestinal obstruction. In peroperative, we noticed a cirrhotic liver. A surgical biopsy was performed and the diagnosis of cirrhosis was confirmed. Autoimmune and viral liver diseases were ruled out by laboratory parameters. Therefore, Azathioprine is believed to be the causative actor for inducing liver cirrhosis. Thus, treating inflammatory bowel disease effectively while trying to limit iatrogenic disease is a continuous struggle.
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PMID:Suspected azathioprine induced liver cirrhosis: an unusual side effect. 2539 20

Azathioprine is a cornerstone of the therapy of Crohn's disease. Unfortunately, infections and malignancies are relatively common adverse effects related to this drug; however, cirrhosis is exceptionally reported as a side effect. We report the case of a 49-year-old male patient with ileocolonic steno-penetrating Crohn's disease who developed hepatic cirrhosis while treated with azathioprine. After taking azathioprine for 3 years with regular follow-up, he developed pancytopenia, and liver cirrhosis was diagnosed with ultrasound, abdomen computed tomography scan, transient elastography, and liver biopsy. As all other causes of liver damage were excluded, azathioprine was believed to be the cause of liver injury and therefore was interrupted.
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PMID:Increased Risk of Liver Cirrhosis during Azathioprine Therapy for Crohn's Disease. 3208 51

Azathioprine is widely used for the treatment of Crohn's disease (CD). Few cases from Western countries have reported idiopathic non-cirrhotic portal hypertension (NCPH) related to thiopurine therapy in patients with inflammatory bowel disease. Idiopathic NCPH is a rare hepatic condition with intrahepatic portal hypertension but no evidence of cirrhosis or chronic liver disease. Patients with idiopathic NCPH present with symptoms of portal hypertension such as thrombocytopenia, splenomegaly and esophageal varices. We report a case of idiopathic NCPH in a 51-year-old male patient with CD who had been taking azathioprine for 5 years. He was admitted due to esophageal variceal bleeding along with splenomegaly and thrombocytopenia. Evaluation of cirrhosis or chronic liver disease showed normal-range results as estimated by FibroScan evaluation, laboratory examination for autoimmune hepatitis or viral hepatitis, and liver biopsy. This case may suggest the need for careful monitoring for manifestations of portal hypertension in Asian patients with inflammatory bowel disease receiving thiopurine treatment.
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PMID:A case of non-cirrhotic portal hypertension related to azathioprine therapy in a patient with Crohn's disease. 3261 Aug 90