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)

Serum level of osteocalcin (OC) is believed to be a specific biochemical parameter of bone formation. Decreased serum OC has been reported in alcohol-intoxicated subjects, in patients with primary biliary cirrhosis and in patients with chronic alcoholic liver disease. The question was, whether lower OC level could be detected in patients with nonalcoholic and non-cholestatic chronic liver disease. The serum OC was measured by RIA developed in our laboratory. Results were compared to age and sex matched controls. Decreased OC level was found in 35 out of 47 (74%) patients with non-alcoholic and non-cholestatic liver disease as chronic persistent hepatitis, chronic active hepatitis, fatty liver and cirrhosis, in 21 out of 26 (80%) patients with alcoholic liver disease and in 8 out of 15 (53%) primary biliary cirrhosis. None of the patients had elevated value. There was no correlation between the decreased OC level and the duration or severity of the liver disease and the laboratory parameters as bilirubin, AST, ALT, alkaline phosphatase, albumin, prothrombin, and serum 25-OH-D3 vitamin level. Decreased OC was found also in the patients without cirrhosis. The possible causes are discussed. Relying upon these findings it is supposed that chronic liver disease by itself can influence the osteoblast activity also by some unknown mechanism.
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PMID:[Decreased serum osteocalcin level in non-alcoholic and alcoholic chronic liver diseases]. 185 6

Nine women with symptomatic precirrhotic primary biliary cirrhosis have been treated with oral pulse methotrexate, 15 mg/wk, for 12-34 months. Three women had pruritus, two fatigue, and four pruritus and fatigue. Itching disappeared and fatigue lessened or disappeared in all within 4-11 months after starting methotrexate. All who itched were able to discontinue cholestyramine (five) or antihistamines (two). Biochemical tests of liver function improved in all patients and then worsened in three when methotrexate was discontinued or the dose lowered. Mean serum alkaline phosphatase decreased from 471 to 171 U/L (P less than 0.01), serum bilirubin from 0.99 to 0.59 mg/dL (P less than 0.05), and serum alanine aminotransferase from 132 to 61 U/L (P = 0.02), and serum cholesterol fell from 265 to 213 mg/dL (NS). The decrease in serum cholesterol was significant, P = 0.05, if data were used just from the six women whose baseline serum cholesterol levels were elevated. Serum albumin remained normal in all. The serum bilirubin levels became normal in three of four patients with elevated levels. The serum alkaline phosphatase levels became normal in four patients and the alanine aminotransferase levels in three. Liver histology improved in five patients and was stable in the remaining four based on a quantitative evaluation of coded liver biopsy specimens. The improvement in histology was primarily due to decreased portal inflammation and bile duct injury. The titer of antimitochondrial antibody decreased in seven patients. The data suggest that methotrexate may be effective treatment for precirrhotic primary biliary cirrhosis. Controlled trials are needed to evaluate long-term efficacy and toxicity.
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PMID:Treatment of primary biliary cirrhosis with low-dose weekly methotrexate. 193 16

We followed up a group of patients with primary biliary cirrhosis who participated in a 4-yr prospective, double-blind controlled trial of colchicine therapy for 4 additional years. All were placed on open label colchicine (0.6 mg twice daily) after the trial was concluded. Of the original group of 28 patients treated with colchicine, 8 died and 5 received transplants (3 of the 5 died). Of the original placebo control group eight patients died and six received transplants (1 of the 6 died). Surviving patients on long-term colchicine therapy (mean period = 8.1 yr, range = 5.3 to 9.1) showed reduction of mean serum alkaline phosphatase from 5.1 times the upper limit of normal values to 1.9 times (p less than 0.01). Mean ALT fell from 1.8 to 1.2 times the upper limit of normal (p = 0.05), and mean serum total bilirubin remained stable (1.6 mg/dl vs. 1.5 mg/dl). Major complications of cirrhosis developed in four patients in the colchicine group and five patients in the original control group. The only side effect of colchicine was diarrhea, which was noted in three patients. The diarrhea resolved with reduction in the dose of colchicine. Colchicine is a safe and inexpensive drug for the long-term treatment of primary biliary cirrhosis. The biochemical parameters of disease activity (alkaline phosphatase and ALT) remain improved after long-term follow-up, and bilirubin values remain stable. However, complications of cirrhosis, deaths and transplantations were not prevented. The clinical usefulness of colchicine in the treatment of primary biliary cirrhosis seems to be limited.
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PMID:Long-term follow-up of patients with primary biliary cirrhosis on colchicine therapy. 195 87

Ursodeoxycholic acid (UDCA) was administered to 10 patients diagnosed as having primary biliary cirrhosis (PBC) after liver biopsy. Eight patients were anicteric, and two were icteric cases. One patient was in stage I, seven were in stage II, one in stage I-III, and one in stage III-IV of Scheuer's classification. Six hundred milligrams of UDCA were administered orally after meals three times daily to all of the patients for more than 1 yr. The period of UDCA administration ranged from 6 to 41 months. The major findings are as follows: 1) in six out of seven patients with pruritus, itching disappeared 1 month after administration of UDCA; 2) both serum alkaline phosphatase and gamma-glutamyltranspeptidase levels began decreasing significantly the first month after the onset of UDCA treatment, and continued decreasing throughout the treatment; 3) GOT and GPT levels also decreased significantly during the administration of UDCA, compared with before-treatment levels; 4) in one icteric patient with portal hypertension, although serum biliary enzyme levels improved after treatment, serum bilirubin level got worse, and the patient died of esophageal variceal hemorrhage. In another icteric case, biliary and bilirubin levels improved slightly after treatment; 5) antimitochondrial antibody titer decreased in four cases, but IgM levels and other immunological parameters were not changed; 6) serum UDCA increased significantly during UDCA treatment; in particular, glyco-UDCA occupied up to 40% of the total bile acid and CDC decreased to 25%; 7) portal inflammation activity decreased in all five patients who had undergone follow-up liver biopsy, more than 1 yr after UDCA administration--bridging fibrosis decreased in three cases; and 8) no side effects were observed in any of the cases. Although large-scale, randomized, controlled, double-blind tests are necessary, it is speculated that the long-term administration of UDCA is a safe and effective treatment for the improvement of biliary enzyme levels and pruritus in anicteric PBC.
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PMID:Improvement of biliary enzyme levels and itching as a result of long-term administration of ursodeoxycholic acid in primary biliary cirrhosis. 196 12

Based on uncontrolled observations, we have proposed ursodeoxycholic acid (UDCA) as a novel therapeutic approach in primary biliary cirrhosis (PBC). To confirm and extend our original findings, we have designed a double-blind multicentre randomized clinical trial. An interim analysis was planned at 6 months, involving all subjects included in the trial, with a final analysis at 2 years. The UDCA-PBC trial began in June 1987 and will be completed in March 1990. Seventy patients were randomized to receive UDCA and 68 a placebo. The two groups were well matched with respect to age, sex, duration and prevalence of symptoms and histologic severity (50% of the UDCA group had stage III-IV disease vs. 37% of the placebo group). During the first 6 months of follow-up, six patients withdrew from the trial. At 6 months, the proportion of patients with jaundice was significantly lower (p less than 0.01) in UDCA recipients than in the placebo group. There was a similar decrease in the proportion of patients with pruritus and fatigue in both groups. The following laboratory test values were significantly lower in UDCA recipients than in the placebo group after 6 months of therapy: serum bilirubin, alkaline phosphatase, alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), gamma-glutamyltranspeptidase activities (p less than 0.001), cholesterol (p less than 0.003) and IgM levels (p less than 0.03). The results of this interim analysis confirm and extend the biochemical data provided by our previous pilot study. However the final analysis of the trial is necessary for a definitive assessment of the safety and efficacy of UDCA therapy in PBC.
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PMID:Ursodeoxycholic acid for the treatment of primary biliary cirrhosis. Interim analysis of a double-blind multicentre randomized trial. The UDCA-PBC Study Group. 197 19

A multi-center double-blind controlled trial of ursodeoxycholic acid (UDCA) for treatment of primary biliary cirrhosis (PBC) was carried out. Twenty two and 23 patients were treated with 600 mg/day UDCA and placebo, respectively, for 24 weeks. In UDCA-treated patients, fall of serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and gamma-glutamyltranspeptidase activities started within 4 weeks after start of the trial and continued throughout the trial period. The serum IgM level fell in 7 UDCA-treated patients examined but not in 10 placebo-treated patients examined. Serum bilirubin concentration showed no significant change at the end of the study in either of UDCA- and placebo-treated group of patients. There was no significant difference between these two groups with respect to the frequency of improvement of pruritus. In UDCA-treated patients, serum bile acid composition changed markedly, though its concentration showed no significant change. The percentage of total bile acid which ursodeoxycholic acid took up increased, whereas those which cholic acid, chenodeoxycholic acid and deoxycholic acid took up were decreased.
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PMID:A multi-center double-blind controlled trial of ursodeoxycholic acid for primary biliary cirrhosis. 198 Jun 54

Among 30 consecutive patients diagnosed with primary biliary cirrhosis (PBC) in Taiwan, 27 were females and the median age of symptom onset was 54.5 years. Most had similar clinical manifestations to those reported in the Western countries, but ascites and oesophageal varices as commonly found at the late stages of cirrhosis of liver were noted in nine patients (30%) and 13 patients (43%) respectively. Only one patient was asymptomatic. Hyperbilirubinaemia was noted in 21 patients (70%) and hypoalbuminaemia in 8 patients (27%). All patients had elevated serum alkaline phosphatase and alanine aminotransferase and 28 (93%) had antimitochondrial antibodies. Ten out of 21 patients (48%) were positive in antinuclear antibodies, of which most were of speckled type. Sixteen out of 18 patients (89%) had elevated serum IgM levels. Interestingly, only one of 26 patients (3.8%) was positive for hepatitis B surface antigen, in contrast to its high prevalence (15%) in the Taiwan population. Special associated diseases, including systemic lupus erythematosus, scleroderma, malignant lymphoma and hepatocellular carcinoma, were each noted in one patient respectively. Eight patients had a history of gallstones before the diagnosis of PBC. The mean follow-up period was 23.6 +/- 19.8 months, and nine patients died during that period. In conclusion, the clinical manifestations of PBC in Taiwan are similar to those in Western countries, but most of our cases were at later stages.
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PMID:Primary biliary cirrhosis in Taiwan. 212 28

Primary biliary cirrhosis is a progressive disease of the liver characterized by the immunologic destruction of bile ducts; effective therapy is lacking. We therefore evaluated the safety and efficacy of low-dose cyclosporine in 29 patients with primary biliary cirrhosis without evidence of damage to the lobular architecture (precirrhotic disease) or portal hypertension. The patients were randomly assigned to receive either cyclosporine (4 mg per kilogram of body weight per day) or placebo. After one year 17 of the 19 patients assigned to cyclosporine had improvement or stability in their degree of fatigue, and 18 in their degree of pruritus. In contrast, among the 10 patients assigned to placebo, fatigue increased in 4 (P less than 0.06) and pruritus worsened in 6 (P less than 0.001). Those assigned to cyclosporine also had significant decreases in serum levels of bilirubin, alanine aminotransferase, alkaline phosphatase, gamma globulin, and the titer of antimitochondrial antibodies. For the 20 patients who have completed two years in the study, liver biopsies (coded specimens) showed evidence of histologic progression in only 1 of 13 patients in the cyclosporine group, as compared with 5 of 7 in the placebo group (P less than 0.003). No patient has permanently discontinued cyclosporine because of side effects; however, signs of nephrotoxicity developed in 12 of 19, and 9 of 19 had increased blood pressure. We conclude that in patients with precirrhotic primary biliary cirrhosis, immunosuppressive therapy with cyclosporine is promising and deserves further evaluation.
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PMID:A controlled trial of cyclosporine in the treatment of primary biliary cirrhosis. 221 26

Evidence is accumulating that ursodeoxycholic acid (UDCA), an agent widely employed for gallstone dissolution, exerts therapeutic effects in chronic liver disease. UDCA is thought to act mainly by reducing the detergent properties of bile, making it less toxic for the liver cells. Confirming the results of preliminary observations double-blind, placebo-controlled trials have shown that UDCA significantly decreased serum concentrations of liver enzymes such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and gamma-glutamyl transferase in primary biliary cirrhosis and other cholestatic conditions, as well as in chronic active hepatitis. A substantial improvement in liver histology has also been detected in UDCA-treated patients with primary biliary cirrhosis. The effect of UDCA in chronic hepatitis is currently a matter of investigation.
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PMID:Treatment of chronic liver disease with ursodeoxycholic acid. 229 32

Six patients were studied to evaluate the efficacy and safety of plasma exchange (PE) in the treatment of primary biliary cirrhosis (PBC). All patients were affected by PBC at stage III-IV and presented symptoms refractory to pharmacologic therapy. Patients underwent PE for a mean period of 40 weeks (range 10-88). A mean of 33 liters (range 17-64) of plasma per patients was removed. Patients reported less fatigue (4/6), pruritus (5/5), nausea (3/3), Sjogren's syndrome (2/6), and painful neuropathy (2/3). A reduction of xanthomata was noted in one of the three affected patients. Definitive improvement was seen in the patient with Raynaud's phenomenon. A significant reduction was noted for serum cholesterol and gammaglobulins. ALT, AST, gamma-GT, alkaline phosphatase, bilirubin, prothrombin activity, AMA titers were not affected by PE. All patients suffered some mild adverse effects during PE. Two patients (IV stage) developed late edema and ascites after 34 and 44 weeks of treatment. We conclude that PE can be considered effective chronic treatment for advanced symptomatic PBC refractory to pharmacological therapy.
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PMID:Effects of plasma exchange (PE) in primary biliary cirrhosis (PBC). A pilot study. 231 37


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