Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
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In the patients with chronic hepatitis C (HHC) there have been found different autoantibodies, some typical for autoimmune hepatitis (AIH) type 1, like: antinuclear antibodies (ANA) in 15-60%, anti-smooth muscle antibodies (ASMA) in 34-60%, or AIH type 2: anti liver/kidney microsomes 1 autoantibodies (LKM 1) in 0-6%. Also, antimitochondrial autoantibodies (AMA), which defines PBC, is discovered in 0.7-1.5% patients with HHC. The purpose of the research was to determine the titr of the serum autoantibodies, which characterise AIH in the patients with HHC and to compare demographical, clinical, biochemical, histological and immunological parameters in the groups of patients: with or without autoantibodies. In 50 patients with HHC are defined clinical (demographical, troubles) facts, laboratorical (the values of complete bilirubin, ALT), histological diagnosis of the liver tissue (PH), and virusological diagnosis (antibodies and antigens of the hepatitis C virus), immunological (autoantibodies, immunoglobulins). The analysis of the results show us that ANA and AMA haven't been present in the patients with HHC in considerable titr (> 1:80), while in 10% of the patients there have been titr of ASMA. In 2 patients were both titrs, ANA (1:40) and ASMA (1:40), as well, which considered important, so there is entirely 7 patients (14%) with detected ANA and ASMA in considerable titr. Autoantibodies, which are characteristic for AIH 2, have not been found in the patients with HHC. Considered the sex, between the group of patients with HHC and autoantibodies, and the group of patients with HHC without autoantibodies, there is no important difference, although the percent of male is a little bit bigger in the second group. Considering the growth, there were no important difference between the patients groups. The fact that appearance of autoantibodies has no correlation with the growth, we can explain with the fact that she most of patients with HHC are persons from 21 to 30 years old, and that the older are no so present. The troubles are present in about the half patients with HHC, and it isn't proved that the appearance of autoantibodies have the influence on this particular clinical parameter. The comparison of activities of the disease, the analysis of the ALT values and the bilirubin, we also didn't get considerable difference between these two groups of patients. Three patients who haven't autoantibodies, but they have the ALT values expended between 5 and 10 times, which we consider the high grade of the necrosis. This high values we can't notice in the patients with autoantibodies. The parameters of grade inflammatory reactions of the extent values of Ig, so as IgG category, also doesn't show we the important difference between the groups. The most patients have normal values both: Ig and IgG. Despite that in both categories of the patients, there is no considerable difference in PH, as well as, in the stage of fibrosis, two patients without autoantibodies have more visible degree of necrosis, manifested like reasonable necrosis, while all the others patients have gently visible necrosis. It is important to say that the patients with autoantibodies have no histological indications for AIH, in the PH sense, and the presence of more important plasmatic infiltrate. All the patients with HHC and autoantibodies have higher values CIC, but the frequency of appearance is not different between the both groups, which show us the variety of becaming autoimmune and immune phenomena in HHC. Based on produced results, we can conclude that: 1. autoantibodies which are characteristic for AIH 1 are visible in 14% of the HHC patients, 2. there are more ASMA in HHC, then ANA; 3. there is no autoantibodies, which caracterize AIH 2, in HHC; 4. the growth and the sex of the patients with HHC have no influence on showing autoantibodies characteristic for AIH; 5. the presence of autoantibodies, characteristic for AIH 1, have no importance of showing the burdens in the patients, degree of PH and the stadium of the diseases, and also on the value of Ig and IgG; 6. discovering the autoantibodies in HHC, no matter there Is no considerable presence on it's symptomatology and the prognosis, oblige us on further following and analysis for starting antivirus therapy, In order to present eventual beginning of AIH.
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PMID:[Autoantibodies characteristic for autoimmune hepatitis found in chronic hepatitis C]. 1511 84

We report a case of primary biliary cirrhosis (PBC)-autoimmune hepatitis (AIH) overlap syndrome with concurrent idiopathic thrombocytopenic purpura (ITP) and Hashimoto's disease with positivity for anticentromere antibody. The patient was a 64-year-old woman with symptoms of jaundice and general fatigue. About 30 years earlier, she had been diagnosed as having ITP and had undergone splenectomy. As part of her present history, she had exhibited liver dysfunction in 1995, during the follow-up of Hashimoto's disease, and a liver biopsy led to the diagnosis of PBC. In March 2000, she was admitted to hospital because of general fatigue and jaundice. Blood tests revealed: total protein (TP), 6.6 g/dl; gamma-globulin (glb), 35.9%; total bilirubin (T-bil), 9.41 mg/dl; direct bilirubin (D-bil), 7.52 mg/dl; aspartate aminotransferase (AST), 957 U/l; alanine aminotransferase (ALT), 651 U/l; alkaline phosphatase (ALP), 595 U/l; gamma-guanosine triphosphate (GTP), 129 U/l; IgG, 2620 mg/dl; IgM, 223 mg/dl; hepatitis B surface antigen (HBsAg), negative; anti-hepatitis C virus (HCV), negative; antinuclear antibody, positive; antimitchondrial antibody (AMA), negative (by the immunofluorescence [IF] method); and anti-pyruvate dehydrogenase complex (PDC)-E2 antibody, positive (by Western blotting). Anticentromere antibody (ACA), which is an alternative diagnostic marker for PBC, was detected in this patient. Prednisolone was administered after admission and liver function test results improved markedly. The liver biopsy in 1995 had revealed infiltration of lymphocytes and plasma cells in the portal areas with fibrous expansion and periportal necrosis. Destructive cholangitis was observed, as well as scattered epitheloid cell granulomas in some portal areas. Liver biopsy after the steroid treatment revealed alleviated necrotic inflammatory responses of hepatocytes, while the destructive cholangitis persisted. This is a very rare case of PBC-AIH overlap syndrome accompanied by ITP and Hashimoto's disease which provides a possible insight into the mechanisms and interplay of autoimmune diseases.
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PMID:PBC-AIH overlap syndrome with concomitant ITP and Hashimoto's disease with positivity for anti-centromere antibody. 1517 50

Background and aim: Alternative splicing of human glucocorticoid receptor (hGR) premessenger RNA (mRNA) generates two highly homogenous isoforms, termed hGRalpha and hGRbeta. hGRalpha is a ligand-activated transcription factor, which, in the hormone-bound state, modulates the expression of glucocorticoid-responsive genes by binding to specific glucocorticoid response element DNA sequences. In contrast, hGRbeta may be an endogenous inhibitor of glucocorticoid action and transcriptionally inactive. hGRbeta protein has been known to correlate with the development of glucocorticoid resistance. Glucocorticoids can effectively relieve autoimmune hepatitis (AIH), but some patients with this disease are refractory even when glucocorticoids are administered. The aim of this study was to determine the incidence of hGRbeta mRNA in patients with AIH by reverse transcription polymerase chain reaction (RT-PCR), and to compare the clinical characteristics of hGRbeta-positive and -negative patients with AIH. Materials and methods: RNA was obtained from peripheral blood mononuclear cells (PBMCs) of 62 patients, consisting of 26 with AIH, 10 with primary biliary cirrhosis (PBC), seven with chronic viral hepatitis (CVH), 10 with ulcerative colitis (UC), six with pemphigus, and three with systemic lupus erythematosus (SLE), and 10 healthy volunteers. The total RNA obtained was reverse transcribed, the resulting complementary DNA amplified using specific primers for hGRalpha and hGRbeta. Results: The hGRalpha mRNA was detected in RNA from PBMCs of all patients and healthy volunteers. The hGRbeta mRNA was detected in 15 (57.6%) patients with AIH. This incidence was significantly higher than that for patients with PBC (0%) or CVH (28.6%) or for healthy volunteers (20.0%) ( [Formula: see text] ). Of the hGRbeta-positive and -negative groups, serum ALT and total bilirubin (TB) levels were significantly higher in the positive group ( [Formula: see text] ). The total dose of glucocorticoid was higher in the positive group, but the difference was not statistically significant. However, the average monthly dose was significantly higher in the positive group ( [Formula: see text] ). The rate of relapse of AIH was significantly higher in the positive group (60.0%) than in the negative (10.0%) ( [Formula: see text] ). The rate of usage of immunosuppressive drugs was higher in the positive group (33.3%) than in the negative (18.2%), but the difference was not statistically significant. Conclusions: These data show that hGRbeta expression in PBMCs of patients with AIH assessed by RT-PCR is closely associated with resistance to glucocorticoids which affects the outcome of therapy with this drug.
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PMID:Expression of human glucocorticoid receptor in lymphocytes of patients with autoimmune hepatitis. 1520 78

The extensive use of alternative medicine products, herbal remedies, and vitamins in large doses has reached an all time high in the general public. Some agents are reported and advertised as immune stimulants and may interfere with patients suffering from immune modification, autoimmune diseases, or transplant recipients. In this report, we will present an investigation into the use of herbal remedies and vitamins in our liver transplant population. We performed an investigation using a questionnaire to determine the use of herbal products and vitamins in our liver transplant population. Medical records were reviewed for each liver transplant recipient that admitted to consuming herbal products or vitamins. Information collected included patient demographics, transplant related information, laboratory tests, outcomes, and herbs or vitamin products used. A total of 290 patients completed and returned the questionnaire. We found 156 admitting to taking more than a standard multivitamin and/or an herbal remedy. All patients were treated with steroids for allograft rejection and experienced a recurrence of amino transaminases following the removal of steroids. Further investigation into dietary supplements using a patient questionnaire form revealed that nearly 50% of patients admitted to using vitamins following transplantation, while 19% used herbal remedies combined with vitamins, most admitting to silymarin. One recipient was ingesting colostrum and required admission for the management of allograft rejection, while 5 patients had consumed large amounts of echinacea or CoEnzyme Q-10 and experienced elevations in their transaminases that resolved with discontinuation of the herb. The review also identified 4 patients with primary biliary cirrhosis and with transaminase elevation (mean values of aspartate aminotransferase and alanine aminotransferase levels of 88 and 95, respectively). All recipients were consuming vitamins, in particular high doses of vitamin E (tocopherol), more than 1 gram per day. All of the transplant recipients were instructed to discontinue all vitamin E products and the amino transaminases resolved over the following 30 to 60 days. In conclusion, this information reveals that a significant proportion of our liver transplant recipients consume herbal remedies. The results of this report suggest that transplant teams need to question each recipient about the use of herbal and vitamin remedies and educate them regarding the potential hazards.
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PMID:Consumption of dietary supplements in a liver transplant population. 1563 45

The availability of serum blood chemistries for screening both symptomatic and asymptomatic patients has resulted in a marked increase in the number of abnormal liver chemistry tests that must be interpreted by physicians. Usually the first step in the evaluation of a patient with elevated liver enzymes is to repeat the test to confirm the result. If the result is still abnormal, it seems wise to differentiate between a predominant "necrotic pattern" of liver chemistry, as indicated by an elevation of ALT- or AST-activity or a predominant "cholestatic pattern", as indicated by elevated activities of g-GT and alkaline phosphatase. In patients with elevated serum amino transferases hepatic diseases should be excluded primarily with non-invasive serologic tests. The most common causes of elevated amino transferase levels are chronic hepatitis B and C, autoimmunhepatitis, non-alcoholic steatohepatitis, hemochromatosis, Wilson-disease and (only recently recognized) celiac sprue. In the case of a dominant "cholestatic pattern", primary biliary cirrhosis, primary sclerosing cholangitis, but also drugs and granulomatose hepatitis must be excluded. If non-invasive serologic studies remain inconclusive, ultrasound, mini-laparoscopy and liver biopsy will help to establish the final diagnoses.
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PMID:[The patient with slightly increased liver function tests]. 1574 78

While autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) usually have distinct clinical manifestations, some patients present with features of both conditions. Using cDNA microarrays, we analyzed and compared gene expression profiles in 8 patients with AIH, 9 with PBC, 8 with chronic hepatitis C (CHC), 8 with non-alcoholic steatohepatitis (NASH) and 9 with normal livers. We subsequently applied this method to a tissue sample from a 61-year-old woman with overlapping features of both AIH and PBC. A 61-year-old woman was admitted to our hospital for evaluation of elevated serum alkaline phosphatase. A liver biopsy showed accumulation of mononuclear cells around the bile duct cells, a feature characteristic of chronic non-suppurative destructive cholangitis (CNSDC). Three years later, her serum alanine aminotransferase (ALT) level had increased, and a liver biopsy demonstrated evidence of a severe form of hepatitis. A cDNA microarray analysis of both biopsies identified the molecular events associated with her altered histology. The expression profile of this patient, which was originally different from that of the other PBC patients, changed to an AIH pattern. Our results suggest that this patient has characteristics of both AIH and PBC.
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PMID:cDNA microarray analysis of autoimmune hepatitis, primary biliary cirrhosis and consecutive disease manifestation. 1615 May 73

A 54-year-old woman was admitted to our hospital because of acute liver injury. Since she had a history of having used a diet product, drug-induced liver injury (DILI) was initially considered. However, the patient was subsequently diagnosed as suffering from primary biliary cirrhosis (PBC) based on the findings of liver histology and serum anti-mitochondrial antibody positivity. Overlap syndrome between PBC and autoimmune hepatitis (AIH) was also suspected, however, serum levels of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase became normal three months later, after treatment with combination therapy comprising ursodeoxycholic acid plus bezafibrate. We therefore concluded that the liver disease in this patient was actually PBC, but that it resembled overlap syndrome or DILI. In cases of PBC, a rapid onset, as frequently seen in the case of DILI, viral hepatitis or AIH, is not common. We herein report a rare case of PBC which resembled DILI.
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PMID:Rapid-onset primary biliary cirrhosis resembling drug-induced liver injury. 1629 9

Chronic bile duct ligation (BDL) is a useful model of cirrhosis. However, its parallel plasma and liver changes in levels of cytokines and nitric oxide (NO), involved in liver damage, remain unknown. The aims of this work were to quantify both the plasma and hepatic levels of five cytokines and NO in cirrhotic rats, 28 days after bile BDL, and to analyze their relationship with liver damage markers. One group of male Wistar rats was bile duct ligated and another group was sham operated, both groups were sacrificed 28 days after BDL. Plasma and liver cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin-6, -1beta, -10 (IL-6, -1beta, -10) and interferon-gamma (IFN-gamma), were measured by ELISA. Plasma and hepatic NO was determined as NO(2)(-)+NO(3)(-) by an enzymatic method. Alkaline phosphatase, gamma-glutamyl transpeptidase, alanine aminotransferase and bilirubins were determined in plasma. Collagen, lipid peroxidation and glycogen were quantified in liver. Two histopathological staining techniques were performed. BDL-induced cirrhosis was corroborated by the elevated liver damage markers and histopathological analysis. Chronic BDL significantly increased (P<0.05) most of plasma and hepatic cytokine levels and diminished the hepatic IFN-gamma amount. NO was increased in both tissues, but such change was only significant in plasma. Biliary cirrhosis produces interesting changes in plasma and hepatic levels of cytokines and NO. This finding in chronic BDL model in rats has not been previously described in both tissues for such cytokines and NO. Cytokines and NO imbalance favor establishment and perpetuation of cirrhosis.
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PMID:Chronic bile duct obstruction induces changes in plasma and hepatic levels of cytokines and nitric oxide in the rat. 1661 7

Liver function tests include biochemical parameters (AST, ALT, GGT or Alkaline phosphatase), bilirubin and albumin levels and coagulation tests as prothrombin activity. These tests are commonly used in the routine screening even in symptomatic as in asymptomatic patients, and the right evaluation of the results is of vital importance. Cytolytic elevation in serum aminotransferases: In mild chronic elevation pharmacological toxicity, viral hepatitis, alcoholic and non-alcoholic fatty liver disease and hemochromatosis, should be excluded. Cholestatic elevation os serum enzymes: The first option should be to establish the origin of the alkaline phosphatase elevation, with the evaluation of the GGT levels to confirm the hepatic origin. The next step should be to distinguish the presence of an extrahepatic (biliary obstruction) or intrahepatic (PBC, PSC, drugs, etc) cholestasis, in these cases the most important test should be the abdominal ultrasound, in order to evaluate the biliary system. Hyperbilirubinemia: Non conjugated hyperbilirubinemia (hemolysis, ineffective erythropoiesis, Gilbert or Criggler-Najjar syndromes) and conjugated hyperbilirubinemia, an unusual situation in which Rotor and Dubin-Johnson Syndromes should be considered. The evaluation of albumin and prothrombin levels evaluates the hepatic function per se, allowing to differentiate between acute and chronic diseases. At present, there are not prospective studies to evaluate the efficacy of the liver function tests. To carry out a complete medical history, an appropriate physical examination and the appropriate application of non-invasive diagnostic tests (serology, iron levels, autoimmunity or abdominal ultrasound) allow to perform a right diagnosis in most patients, making more complex tests, including liver biopsy, secondary.
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PMID:[Utility of analytical parameters in the diagnosis of liver disease]. 1737 60

Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an important inhibitor of T-lymphocyte response. Polymorphisms in the CTLA-4 gene have been reported to be associated with numerous autoimmune diseases. The aim of this study was to determine whether polymorphisms of CTLA-4 exon 1 (+49) genes are associated with susceptibility and clinicolaboratory findings of primary biliary cirrhosis (PBC) in the Japanease population. Blood samples were obtained from 45 patients (6 men and 39 women, aged 23-56 years) with PBC and 73 healthy controls (48 men and 25 women, aged 22-72 years). CTLA-4 exon 1 (+49) polymorphism was defined using a polymerase chain reaction-restriction fragment length polymorphism with Bst71I restriction enzyme. The genotype frequencies of A/A, A/G, and G/G in 45 patients with PBC were 11% (5 patients), 44% (20 patients), and 44% (20 patients), respectively. There was no significant difference between frequencies in PBC patients and healthy controls. PBC patients with G/G genotype had significantly higher serum levels of ALT, GGT, and IgM than those in patients with A/A or A/G genotype. In conclusion, CTLA-4 gene polymorphisms are not associated with susceptibility of PBC in Japan; however, G/G genotype may be associated with liver damage.
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PMID:Possible association of cytotoxic T lymphocyte antigen-4 genetic polymorphism with liver damage of primary biliary cirrhosis in Japan. 1742 59


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