Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

The prevalence of and risk factors for HCV and HBV infections in the general population and the predictive value of ALT screening in identifying anti-HCV positive subjects have been evaluated in a small Sicilian town. A random 1:4 sampling from the census of the general population was performed. Anti-HCV, HCV-RNA, HCV genotype, HBsAg, and anti-HBc were tested. The linkage between HCV infection and potential risk factors was evaluated by multiple logistic regression analysis. Among 721 subjects studied, 75 (10.4%) were anti-HCV positive. The HCV infection rate increased from 0.4% in subjects 10-29 years of age to 34% in those > 60 years of age. Among the 75 anti-HCV positive subjects, 66.7% were HCV-RNA positive and 36% had abnormal ALT, in contrast abnormal ALT levels were found in 4.3% of the 646 anti-HCV negative subjects (P < 0.01). HCV genotype 1b infected the majority (88.0%) of viremic subjects. Exposure to HBV infection (anti-HBc positivity) was found in 11.2% of subjects; HBsAg positivity was 0.7%. At multivariate analysis, two variables were associated with HCV infection: age > or = 45 years (OR 27.8; CI 95% = 11.0-70.2) and previous hospitalization (OR 2.5; CI 95% = 1.3-4.7). ALT testing had low positive predictive value (PPV = 49.1%) for HCV infection. The positive predictive value was good (88%) in people > or = 60 years of age, but minimal (16.7%) in those below 60. These findings indicate that HCV infection is common in the elderly, perhaps as a result of past iatrogenic transmission. The present low rate of HCV infection among the younger generations coupled with the low progression of the viral related liver damage does not support the projection of a future increasing incidence in the next decades of the burden of HCV-related chronic disease. HBV infection, formerly common in this area, is already in sharp decline. In an area of high HCV endemicity, screening of the general population by ALT cannot be used a surrogate marker to detect HCV infection in those susceptible to treatment.
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PMID:Endemic hepatitis C virus infection in a Sicilian town: further evidence for iatrogenic transmission. 1211 24

We describe 8 young dogs with congenital dilatation of the intra- and extrahepatic bile ducts and diffuse cystic kidney disease, compatible with Caroli's disease in humans. The dogs were referred between 1980 and 2000 because of chronic disease at an age of 6 months to 3 years. These dogs included 3 Collies, 2 Frisian Stabyhouns, 2 Jack Russell Terriers, and 1 mixed-breed dog. The most common signs were vomiting (6/6), polyuria and polydipsia (4/6), and anorexia (4/6). Ascites was a common finding (4/6). Clinicopathologic abnormalities were available for 6 dogs. All had increased plasma alkaline phosphatase activity and fasting bile acids: increased alanine aminotransferase activity and urea and creatinine concentrations were present in 50% of dogs. Ultrasound examination of the liver showed severely dilated bile ducts without evidence of obstruction, and calcification in all cases but 1. Postmortem examination revealed severe dilatation of the larger intra- and extrahepatic bile ducts. The common bile duct and gall bladder were normal, and the bile system was patent. The ducts contained a clear viscid fluid often with calcified material. Microscopically, marked portal fibrosis was present, often with abnormally structured dilated bile ducts lined with columnar or cuboid epithelium and regularly small calcifications. The lesion was complicated by ascending cholangitis in 1 dog. The kidneys showed marked cortical and medullary fibrosis with a diffuse radial cystic pattern; only slight renal fibrosis was found in the oldest dog. Seven dogs were euthanized without treatment; the oldest dog was alive and well 5 months after diagnosis and was maintained on a protein-restricted diet.
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PMID:Congenital dilatation of the bile ducts (Caroli's disease) in young dogs. 1256 24

The clinicopathological features of nine acute-onset autoimmune hepatitis (AIH) patients were compared with those of 29 classical AIH patients. The clinical features of acute-onset AIH showed significantly higher serum ALT levels, lower serum IgG levels and AIH score than those of classical AIH, although the type of auto-antibodies, age and gender were not different between the two groups. Pathological features showed that the stages of acute-onset AIH varied from stage 1 to stage 4 and were less advanced compared with those of classical AIH. One patient showed submassive hepatic necrosis. Both centrilobular necrosis and interface hepatitis were observed in 7 and 8 of 9, respectively. Three stage 1 patients with centrilobular necrosis and one patient with submassive hepatic necrosis were suggestive of acute presentation, while patients with stages 2 and 4 fibrosis were suggestive of acute exacerbation of chronic disease. An immunohistochemical study demonstrated that CD8 T cells were predominant at both interface hepatitis and centrilobular necrosis, while CD79alpha-positive B lineage cells were predominant at interface hepatitis. These results suggest that acute-onset AIH includes both acute presentation and acute exacerbation of chronic disease and that centrilobular necrosis might be a prevailing pathological feature.
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PMID:Clinicopathological features of acute-onset autoimmune hepatitis. 1269 47

From February 2002, all the consecutive patients referring to the Department of Infectious Diseases, University of Turin, who were diagnosed as having acute HCV hepatitis were included in a prospective cohort study to evaluate if a 3-month course of Peg-Interferon alpha-2b (1.5 microg/kg once weekly) is effective to decrease the risk of progression to chronic disease. ALT and HCV-RNA measurements were scheduled at week 4 and 12 during treatment, and 24 weeks after the end of therapy. As of April 2003, ten patients were enrolled in the study. As to HCV genotype, seven patients had type 1 and 3 type non-1. At entry, median HCV-RNA level was 129500 (range: 3000-3100000 copies/mL) and six patients were symptomatic. Treatment was given within 20 days (range: 8-30) of the ALT peak. All patients completing 4 weeks (n = 9) and 12 weeks of treatment (n = 7) had undetectable HCV-RNA. Five patients who completed the 24-week follow-up after the end of treatment had a sustained viral response with ALT levels within normal range. Therapy was well tolerated in all patients. Even if our data are not definitive, our results show that once-weekly administration of Peg-interferon alfa-2b in patients with acute HCV infection may be an effective and convenient regimen.
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PMID:Is a 3-month course of treatment with Peg-interferon effective in acute HCV hepatitis? 1451 21

Schistosomiasis, a chronic disease with considerable social impact, is an important health problem in many countries. To investigate the possible use of immunomodulators as coadjuvants in the treatment of chronic Schistosoma mansoni infection, we evaluated the effect of dexamethasone on histological, hematological, and biochemical parameters that reflect disease severity and morbidity. Animals treated from the first day or after 35 days of infection, were analyzed. In both groups, dexamethasone: (1) induced a decrease in the number of granulomas in hepatic tissue without affecting the alanine aminotransferase profile, (2) reduced splenomegaly and hepatomegaly associated with disease, and (3) improved hemoglobin concentration, hematocrit values and reduced the percentage of reticulocytes, preventing the development of anemia that occurs in the chronic phase of infection. These data suggest that treatment with dexamethasone results in a mild course of murine schistosomiasis and point to this drug as a promising agent to complement S. mansoni specific treatment.
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PMID:Dexamethasone treatment improves morphological and hematological parameters in chronic experimental schistosomiasis. 1499 68

The hepatitis C virus is a leading cause of chronic liver disease, cirrhosis and hepatocellular carcinoma in western countries. Chronic hepatitis C is highly heterogeneous and many patients present with a mild form of liver disease. Population-based studies have indeed demonstrated that around 50% of hepatitis C virus carriers have persistently normal ALT and two-third have mild histological liver lesions. Studies on the natural history of initially mild chronic disease indicate that the short-term outcome is always benign. However, progression of liver fibrosis can be observed at long-term (>5-7 years) follow-up, particularly in those cases who have elevated and/or fluctuating transaminase levels. Observational prospective studies and outcome modelling projections indicate that the risk of liver disease progression towards severe fibrosis/cirrhosis is minimal at 10-15 years in hepatitis C virus carriers with persistently normal ALT, around 5-10% in patients with elevated ALT and F0 (no fibrosis) in the initial biopsy but >30-40% in chronic carriers with elevated ALT and F1 (portal fibrosis) in the initial biopsy. Cofactors like age at infection, alcohol, coinfections and liver steatosis accelerate disease progression. On the basis of these findings, patients with initially mild chronic hepatitis C and elevated ALT should be proposed for antiviral therapy in the absence of contraindications.
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PMID:Natural history of initially mild chronic hepatitis C. 1550 61

Acute hepatitis C often progresses to chronic infection (70%). In this clinical study, we evaluated if early treatment with peginterferon alfa-2b can prevent acute hepatitis C from developing into a chronic disease. Six patients with acute hepatitis C, based on a well-documented hepatitis C virus (HCV) seroconversion with high alanine aminotransferase (ALT) levels (> 10 x ULN) and persistent HCV RNA titers after 3 months from disease onset, were consecutively treated with peginterferon alfa-2b at 1.5 microg/kg/weekly/sc for 24 weeks. The viral load was quantified by PCR assay. Response was defined as undetectable HCV RNA and normal ALT levels at the end of therapy and after a 6-month follow-up. All patients completed therapy; at the end of therapy, 5/6 patients (83%) responded and no relapses were observed during follow-up. No correlation was found between treatment response and pretreatment viral load, viral genotype, and interval between acute infection diagnosis and start of therapy.
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PMID:Peginterferon alfa-2b treatment for patients affected by acute hepatitis C: presentation of six case reports. 1575 Jul 57

Drug-induced liver injury (DILI) encompasses a spectrum of clinical disease ranging from mild biochemical abnormalities to acute liver failure. The majority of adverse liver reactions are idiosyncratic, occurring in most instances 5-90 days after the causative medication was last taken. The diagnosis of DILI is clinical, based on history, probability of the suspect medication as a cause of liver injury and exclusion of other hepatic disease. DILI can be hepatocellular (predominant rise in alanine transaminase), cholestatic (predominant rise in alkaline phosphatase) or mixed liver injury. An elevated bilirubin level more than twice the upper limit of normal in patients with hepatocellular liver injury implies severe DILI, with a mortality of approximately 10% and with an incidence rate of 0.7-1.3 per 100,000. Although acute liver failure is rare, 13-17% of all acute liver failure cases are attributed to idiosyncratic drug reactions. Response to drug withdrawal may be delayed up to 1 year with cholestatic liver injury with occasional subsequent progressive cholestasis known as the vanishing bile duct syndrome. Overall, chronic disease may occur in up to 6% even if the offending drug is withdrawn. Antibiotics and NSAIDs are the most common cause of DILI. Statins rarely cause significant liver injury whereas antiretroviral therapy is associated with hepatotoxicity in 10% of treated patients. Multiple mechanisms of DILI have been implicated, including TNF-alpha-activated apoptosis, inhibition of mitochondrial function and neoantigen formation. Risk factors for DILI include age, sex and genetic polymorphisms of drug-metabolising enzymes such as cytochrome P450. In patients with human immunodeficiency virus, the presence of chronic viral hepatitis increases the risk of antiretroviral therapy hepatotoxicity. Over the next decade, the combination of accurate case ascertainment of DILI via clinical networks and the application of genomics and proteomics will hopefully lead to accurate prediction of risk of DILI, so that pharmacotherapy can be optimised with avoidance of adverse hepatic events.
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PMID:Idiosyncratic drug-induced liver injury: an overview. 1796 56

Scrub typhus is a zoonotic disease that is caused by Orientia tsutsugamushi. Although hepatic dysfunction occurred in 77-96.7% of the scrub typhus patients, its mechanism is unknown. IL-17 is a potent proinflammatory cytokine known for its role in several chronic disease conditions. Abundant IL-17 was found in conditions affected by microbial pathogens, including the synovial fluid of patients with Lyme arthritis or Chlamydia-induced reactive arthritis, Helicobacter pylori-infected gastric mucosa, and listeria infection. It is also suggested as a marker of acute hepatic injury. In our study, we postulated that IL-17 might be a cytokine with a role in hepatic dysfunction in scrub typhus. In September-November 2006, our study involved 43 patients with Boryong-type scrub typhus patients and 40 age- and sex-matched control healthy people. Scrub typhus was confirmed on the basis of immunofluorescence and a nested polymerase chain reaction assay. IL-17 was measured using human IL-17 immunoassay. We gathered the clinical and laboratory data by chart reviews. We used an independent t-test, Kolmogorov-Smirnov test, and correlation analysis. The IL-17 levels were significantly higher in scrub typhus patients than in the healthy group. Also, the patients with scrub typhus showed significantly higher aspartate aminotransferase and alanine aminotransferase levels, and lower hemoglobin levels than the healthy group. However, in our correlation analysis, we did not find any correlation between IL-17 and hepatic, kidney, and hemogram panels. The IL-17 level in patients with headaches was higher than in patients without headaches, showing a borderline significance. This suggests that IL-17 level might be a cause of a vasculitis-associated headache. More prospective, large-scale studies are needed about the mechanism of hepatic dysfunction and headaches in scrub typhus patients.
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PMID:Does IL-17 play a role in hepatic dysfunction of scrub typhus patients? 1948 73

The tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) has been studied for chronic disease preventive effects, and is marketed as part of many dietary supplements. However, case-reports have associated the use of green tea-based supplements with liver toxicity. We studied the hepatotoxic effects of high dose EGCG in male CF-1 mice. A single dose of EGCG (1500 mg/kg, i.g.) increased plasma alanine aminotransferase (ALT) by 138-fold and reduced survival by 85%. Once-daily dosing with EGCG increased hepatotoxic response. Plasma ALT levels were increased 184-fold following two once-daily doses of 750 mg/kg, i.g. EGCG. Moderate to severe hepatic necrosis was observed following treatment with EGCG. EGCG hepatotoxicity was associated with oxidative stress including increased hepatic lipid peroxidation (5-fold increase), plasma 8-isoprostane (9.5-fold increase) and increased hepatic metallothionein and gamma-histone 2AX protein expression. EGCG also increased plasma interleukin-6 and monocyte chemoattractant protein-1. Our results indicate that higher bolus doses of EGCG are hepatotoxic to mice. Further studies on the dose-dependent hepatotoxic effects of EGCG and the underlying mechanisms are important given the increasing use of green tea dietary supplements, which may deliver much higher plasma and tissue concentrations of EGCG than tea beverages.
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PMID:Hepatotoxicity of high oral dose (-)-epigallocatechin-3-gallate in mice. 1988 14


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