Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heptral (S-adenosine-L-methionine) was given to 32 patients with chronic diffuse diseases of the liver and intrahepatic cholestasis. 16 of them had primary biliary cirrhosis (PBC). Phase I of the treatment lasted 16 days when the drug was injected intravenously in a dose 800 mg/day. It was followed by phase 2--1600 mg/day taken for 16 days. A response was registered in the majority of patients. They had relieved symptoms of asthenia, skin pruritus, jaundice. The patients with liver cirrhosis and chronic hepatitis exhibited a statistically significant fall in ALT, AST and GGTP. PBS patients showed insignificant lowering of cholesterol, bilirubin. No resistance was noted in repeated courses. Heptral tolerance was satisfactory.
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PMID:[Clinical trial of heptral in patients with chronic diffuse liver disease with intrahepatic cholestasis syndrome]. 986 18

We have shown, in animal models as well as in retrospective human study, that some degree of decreased thyroid function is beneficial for subjects with liver damage of various etiologies. Therefore, we herein present the results of a cohort population study. Between 1991 and 1994, 18 patients (12 women and 6 men; mean age, 59 +/- 24 years) with both biopsy-proven active cirrhosis (5 hepatitis C virus, 4 hepatitis B virus, 1 immunocompromised host, 2 primary biliary cirrhosis, 1 alcoholic, and 5 cryptogenic; Child's-Pugh criteria: A-8, B-8, C-2) and primary or induced (by either drug or surgery) thyroxine-treated hypothyroidism were prospectively followed. Each patient was examined at least twice yearly and served as their own control. The thyroid of the profiled patients ranged between euthyroidism and subclinical hypothyroidism. Liver function tests were evaluated and compared in states of normal versus increased thyroid-stimulating hormone (TSH) blood levels. A significant improvement in alanine aminotransferase (p < 0.001), alkaline phosphatase (p < 0.0001), albumin (p < 0.001), and bilirubin (p < 0.01) was found in the increased TSH group. Prothrombin time was also found to be significantly better (p < 0.001). We conclude that euthyroid patients with liver cirrhosis might benefit from a controlled hypothyroidism.
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PMID:The effects of hypothyroidism on liver status of cirrhotic patients. 1099 36

As a part of the defense mechanism of the host to viral infection, interferons induce the transcription of several genes. These interferon-inducible genes contribute to the eradication of the viruses. Whereas some studies suggested the participation of a dsRNA-dependent protein kinase in the host reaction to hepatitis C virus infection, the involvement of other interferon-inducible genes has not been evaluated. Furthermore, there has been no analysis on the expression profile of multiple interferon-inducible genes. The aim of this study was to clarify the hepatic mRNA expression profile of interferon-inducible genes with a special concern to chronic hepatitis C. A total of 76 liver biopsy samples (28 with chronic hepatitis C, 10 with chronic hepatitis B, 9 with alcoholic liver disease, 14 with autoimmune hepatitis, 10 with primary biliary cirrhosis, and 5 of normal liver) were enrolled. The expression of the following genes was quantified by competitive reverse transcription-polymerase chain reaction and was compared according to the etiology; dsRNA-dependent protein kinase (PKR), 2',5'-oligoadenylate synthetase (2,5-AS), latent cellular endoribonuclease (RNase L), RNase L inhibitor, and MxA. As a result, PKR mRNA was significantly overexpressed in the liver of chronic hepatitis C compared with those of other etiologies (P =.0178), and it correlated significantly with serum alanine transaminase values (r =.51, P =.0054). Also, the expression of the RNase L inhibitor showed a significant reduction in chronic hepatitis C (P =.0184). The expressions of 2,5-AS, RNase L, and MxA were not different significantly irrespective to the etiology. In conclusion, hepatic overexpression of PKR and reduced expression of RNase L inhibitor seem to contribute to the anti-HCV mechanism characteristically.
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PMID:Intrahepatic mRNA expression of interferon-inducible antiviral genes in liver diseases: dsRNA-dependent protein kinase overexpression and RNase L inhibitor suppression in chronic hepatitis C. 1105 60

Background/Aim: Hepatic venography with a positive-contrast medium has been reported as a method for evaluating liver disease. However, the contrast medium used in this method provides insufficient portal vein observation and may cause severe liver injuries. Carbon dioxide (CO(2)), a negative-contrast medium, may be able to depict the portal vein system with minimal hepatic toxicity. The aim of this study was to evaluate the usefulness and side-effects of balloon-occluded hepatic venography with CO(2) (CO(2) venography) and to evaluate the correlation between retrograde portogram and liver function in patients with cirrhosis. Subjects and methods: The subjects consisted of 23 biopsy-proven cirrhotic patients (male:female, 16:7; age, 58+/-12 years, range 34-80). The causes of cirrhosis were alcohol intake in ten, HCV infection in ten, HBV infection in one, primary biliary cirrhosis in one and Budd-Chiari syndrome in one. Of these patients, six were complicated with hepatocellular carcinoma (HCC). CO(2) venography was performed with an occlusion balloon catheter, and 25 ml of CO(2) was infused. CO(2) portograms were scored as follows: 0, no visualization of portal veins; 1, visualization of peripheral portal branches; 2, unilateral first portal branch; 3, bilateral first portal branches; 4, main portal vein; 5, left gastric vein, superior mesenteric vein and splenic vein. Hepatic venous pressure gradient (HVPG), cardiac functions, biochemical analysis, blood gas analysis and oxygen (O(2)) saturation monitoring were measured simultaneously. Arterio-portography was also performed. To evaluate the usefulness of CO(2) venography in patients with HCC accompanied by portal vein tumor thrombus (PVTT), three patients were also examined. Results: No significant changes in ALT, AST, O(2) saturation or blood gas data were observed after CO(2) venography. A statistically significant positive correlation was observed between CO(2) portogram scores and Child-Pugh scores (r=0.68, P=0.003). The correlations between CO(2) portogram scores and HVPG, and the forms of gastroesophageal varices in patients without PVTT and major shunts were not significant. The CO(2) portogram score was significantly higher in patients with alcoholic liver cirrhosis than in those with HCV-positive cirrhosis (P=0.04). Cavernous transformation and peripheral portal branches were demonstrated in patients with HCC accompanied by PVTT. These findings could not be observed by arterio-portography. Conclusion: CO(2) venography to obtain retrograde portogram is a safe and useful method for evaluating the portal vein system and liver function in patients with liver cirrhosis.
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PMID:Evaluation of balloon-occluded hepatic venography with carbon dioxide for portography and correlation between retrograde portogram and liver function in patients with liver cirrhosis. 1105 28

To clarify the role of IP-10 in autoimmune liver diseases, we studied the serum levels of IP-10 in 14 patients with autoimmune hepatitis (AIH), 23 patients with primary biliary cirrhosis (PBC), and 65 patients with chronic viral hepatitis (20 type B and 45 type C). The hepatic expression of IP-10 mRNA and the correlation between the serum levels of IP-10 and clinical parameters were also evaluated. In addition to 20 healthy controls, 16 rheumatoid arthritis (RA) patients were included as an extrahepatic inflammatory disease. The serum level of IP-10 was significantly (P < 0.02) higher in patients with AIH, PBC, and chronic hepatitis B and C than in healthy controls, and it was significantly correlated (P < 0.05) with the serum levels of aspartate aminotransferase and alanine aminotransferase in patients with AIH, PBC, and chronic hepatitis B and C. The serum level of IP-10 was not elevated in RA patients. After successful treatment of AIH and chronic hepatitis C, the serum level of IP-10 decreased to the same level as in healthy volunteers. As we previously showed in cases with chronic hepatitis B or C, in situ hybridization in both AIH and PBC cases demonstrated the expression of IP-10 mRNA in hepatocytes around focal or lobular necrosis surrounded by infiltrating mononuclear cells, whereas IP-10 mRNA was not expressed in areas around the damaged bile ducts in PBC cases. The present results suggest that IP-10 is specifically produced by hepatocytes in inflammatory areas irrespective of the aetiology of hepatitis, and that IP-10 may help to recruit T cells to the hepatic lesions in autoimmune liver diseases as well as in chronic viral hepatitis.
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PMID:Increase of chemokine interferon-inducible protein-10 (IP-10) in the serum of patients with autoimmune liver diseases and increase of its mRNA expression in hepatocytes. 1120 58

Patients with primary biliary cirrhosis (PBC) may have additional features of autoimmune hepatitis (AIH). Corticosteroids usually contraindicated in PBC have been advocated for these patients. Patients with antimitochondrial antibody (AMA)-positive PBC from two previous randomized, controlled trials were assessed for features of AIH. Their biochemical, immunologic, and histologic responses to ursodeoxycholic acid (UDCA) versus placebo were compared with those without AIH features. The survival of patients testing positive or negative for antinuclear antibodies (ANA) was also examined. Features of AIH were defined by the presence of 2 or more of the following: 1) alanine transaminase (ALT) > 5 x the upper limit of normal (ULN); 2) immunoglobulin G (IgG) > 2 x ULN or positive anti-smooth muscle antibody (ASMA); and 3) moderate to severe lobular inflammation on pretreatment liver biopsy. Testing for AMA, ASMA, and ANA was done by immunofluorescence. The change in serum bilirubin, alkaline phosphatase (ALP), transaminases, IgM, and IgG from baseline to 2 years was compared. Of the 331 patients randomized, 16 (4.8%) had features of AIH (12 UDCA, 4 placebo). The median percent change in serum biochemistry and immunoglobulin values were similar in patients with PBC +/- features of AIH after 2 years of therapy with UDCA. Over 2 years, little change in histologic features of AIH was observed. Survival was similar for patients with PBC with and without ANA. In conclusion, features of AIH in PBC may be transient and response to UDCA therapy similar to patients with PBC without features of AIH.
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PMID:Primary biliary cirrhosis with additional features of autoimmune hepatitis: response to therapy with ursodeoxycholic acid. 1229 61

When rats given D-galactosamine are then treated with the glucogenic amino acid alanine, their alanine aminotransferase (ALT) activity, total bilirubin level, and survival rate improve compared with when other amino acids are used. Here, we report a preliminary study of the clinical and pharmacological effects of alanine given to three patients with primary biliary cirrhosis (PBC). The patients were jaundiced and were in the end-stage of the disease. The treatment they had been receiving was continued while they were given 18 g of alanine per day for a planned 8 weeks. For all three patients, test results for total bilirubin, alkaline phosphatase, and ALT decreased by 25% or more from the base line at some time during treatment. The arterial ketone-body ratio increased. Two of the patients reported that their itching and fatigue lessened. Except for one patient given a second course, who reported nausea, adverse effects were not found. In end-stage PBC, alanine administration decreased the total bilirubin level and improved symptoms, so this compound may decrease jaundice in this disease. A long-term study of a larger group of patients is needed.
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PMID:Effects of alanine in patients with advanced primary biliary cirrhosis: preliminary report. 1264 33

Recent advances in molecular biology have made possible the identification of genetic defects responsible for Wilson's disease, Indian childhood cirrhosis and copper toxicosis in Long Evans Cinnamon rats, toxic milk mice, and Bedlington terriers. The Wilson's disease gene is localized on human chromosome 13 and codes for ATP7B, a copper transporting P-type ATPase. A genetic defect similar to that of Wilson's disease occurs in Long Evans Cinnamon rats and toxic milk mice. Familial copper storage disorders in Bedlington and West Highland white terriers are associated with early subclinical disease, and copper accumulation with subsequent liver injury culminating in cirrhosis. The canine copper toxicosis locus in Bedlington terriers has been mapped to canine chromosome region CFA 10q26. Recently, a mutated MURR1 gene was discovered in Bedlington terriers affected with the disease. Idiopathic childhood cirrhosis is biochemically similar to copper toxicosis in Bedlington terriers, but clinically much more severe. Both conditions are characterized by the absence of neurologic damage and Kayser-Fleisher rings, and normal ceruloplasmin levels. A recent study added North Ronaldsay sheep to the list of promising animal models to study Indian childhood cirrhosis. Morphologic similarities between the two conditions include periportal to panlobular copper retention and liver changes varying from active hepatitis to panlobular pericellular fibrosis, and cirrhosis. Certain copper-associated disorders, such as chronic active hepatitis in Doberman pinschers and Skye terrier hepatitis are characterized by copper retention secondary to the underlying disease, thus resembling primary biliary cirrhosis in humans. Copper-associated liver disease has increasingly being recognized in Dalmatians. Copper-associated liver diseases in Dalmatians and Long Evans Cinnamom rats share many morphologic features. Fulminant hepatic failure in Dalmatians is characterized by high serum activities of alanine aminotransferase and aspartate aminotransferase, and severe necrosis of centrilobular areas (periacinar, zone 3) hepatocytes. Macrophages and surviving hepatocytes contain copper-positive material. Liver disease associated with periacinar copper accumulation has also been described in Siamese cats. Many questions regarding copper metabolism in mammals, genetic background, pathogenesis and treatment of copper-associated liver diseases remain to be answered. This review describes the similarities between the clinico-pathological features of spontaneous copper-associated diseases in humans and domestic animals.
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PMID:Animal models of copper-associated liver disease. 1276 23

A 40-year-old woman with a history of fever and arthralgia since age 17 had received long-term prednisolone (PSL) therapy. She was diagnosed with Takayasu's arteritis in 1980 and given PSL. The symptoms were well controlled until she developed itching in 1998. Laboratory tests showed elevated levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyltranspeptidase, total cholesterol, and immunoglobulin M (IgM). She tested positive for anti-mitochondria antibody and for both IgG and IgM anti-pyruvate dehydrogenases. Liver biopsy findings were typical of primary biliary cirrhosis (PBC). Our patient's clinical course suggested that an adequate amount of PSL to control Takayasu's arteritis does not necessarily prevent the development of PBC.
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PMID:A patient with Takayasu's arteritis treated with corticosteroids who developed primary biliary cirrhosis. 1279 18

Drugs may cause several overlapping syndromes of cholestasis, the pathophysiological syndrome resulting from impaired bile flow. These reactions comprise approximately 17% of all hepatic adverse drug reactions (ADRs) and they may be severe. Causes of 'pure' (bland) cholestasis include oestrogens and anabolic steroids; rarer associations are with antimicrobials and NSAIDs. 'Cholestatic hepatitis' is a common drug reaction in which liver injury and inflammation cause significant elevation of serum alanine aminotransferase (ALT) as well as cholestasis. Chlorpromazine and ketoconazole are classic examples, but it is now exemplified by amoxycillin-clavulanate and other oxy-penicillins. Chronic cholestasis results from small bile duct injury leading to the vanishing bile duct syndrome (VBDS), a disorder mimicking primary biliary cirrhosis, or from injury to larger bile ducts causing secondary sclerosing cholangitis. Whilst there is increasing evidence of a genetic predisposition to cholestatic drug reactions, there are currently no pretreatment tests to predict drug safety. Prevention of severe reactions therefore relies on early detection of liver injury and prompt drug withdrawal. Symptomatic management includes relief of pruritus and correction of fat-soluble vitamin deficiency. In small cohort studies, ursodeoxycholic acid (UDCA) arrested progressive cholestasis in two-thirds of cases, but evidence for use of corticosteroids is anecdotal. This review considers diagnosis, pathogenesis, prevention and management of drug-induced cholestasis, with particular reference to frequently- and newly-described causes.
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PMID:Drug-induced cholestasis. 1290 7


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