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 relationships among host immune and viral factors and the severity of liver disease due to hepatitis C virus (HCV) are poorly understood. Previous studies have focused on individual components of the immune response to HCV, often in relatively small numbers of patients. We measured HCV-specific lymphoproliferation (LP), intrahepatic cytotoxic T lymphocyte (CTL), and neutralizing antibody (NA) responses and HCV quasispecies (QS) diversity and complexity in a large cohort of subjects with advanced liver fibrosis (Ishak stages 3-6) on entry into the HALT-C (Hepatitis C Antiviral Long-term Treatment against Cirrhosis) trial. We correlated LP, CTL, NA, and QS results with clinical characteristics, including serum alanine aminotransferase (ALT), HCV RNA level, HCV genotype, and hepatic histopathology. LP, CTL, and NA responses were detected in 37%, 22%, and 22% of subjects tested, respectively. The only association that was statistically significant was higher mean serum ALT values in patients with detectable HCV-specific CTL responses (P = .03). In conclusion, immune responses to HCV and viral diversity showed little relationship to clinical or histological features at a single time point in this selected population of patients with advanced chronic hepatitis C for whom prior interferon treatment had failed.
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PMID:Associations among clinical, immunological, and viral quasispecies measurements in advanced chronic hepatitis C. 1572 56

Childhood NAFLD has become an important childhood liver disease, and it is probably highly prevalent. The full of spectrum of NAFLD has been identified in children. It is not currently known whether or not simple hepatic steatosis in children is benign or whether it evolves to NASH over time. In contrast, childhood NASH certainly can have serious consequences. Cirrhosis is apparently rare in children with NAFLD, but it definitely occurs. Childhood NAFLD may occur in very young children, and there is no female predominance in the pediatric age bracket. Children present with vague abdominal pain, if they have any symptoms at all, but frequently hepatic steatosis is found incidentally on abdominal imaging. Laboratory studies show that serum aminotransferase abnormalities are rather moderate, with serum alanine aminotransferase (ALT) more elevated than serum aspartate aminotransferase (AST). Hypertriglyceridemia is the typical blood lipid abnormality, although hypercholesterolemia may occur. NASH may be more severe in children from certain ethnic groups, including Hispanics and Asians, or in association with certain metabolic disorders characterized by abnormalities in insulin receptor structure or signaling, such as lipodystrophy syndromes. Weight loss through dietary redesign and a regimen of regular exercise remains the mainstay for treatment for childhood NAFLD. A dietary strategy to minimize postprandial hyperinsulinemia and overall fat intake, such as a low glycemic index diet, may be the best dietary strategy. The real efficacy of drug treatments in children requires further investigation. The overriding message is that childhood obesity poses important health problems, including but not limited to potentially severe chronic liver disease. Early diagnosis of children who are only overweight is a worthy goal so that strategies to limit obesity can be instituted as early as possible. Identification of genetic risks is important, but management will invariably require changes in environmental factors. In addition to individual treatment, a multifaceted, societal initiative is required for solving the childhood obesity epidemic.
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PMID:Non-alcoholic fatty liver disease (NAFLD) in children. 1597 Apr 96

Lamivudine is effective in suppressing viral replication, normalizing alanine aminotransferase (ALT), and improving histological appearance in HBe positive and negative hepatitis. It is unclear whether hepatitis B virus (HBV) genotype influences the response to lamivudine. We report the long-term response of patients with chronic hepatitis B with and without cirrhosis at baseline treated with lamivudine according to HBV genotype. Retrospective review of charts of all patients treated with lamivudine monotherapy between 1993 and 2002. Response to therapy defined as ALT in the normal range, undetectable HBV DNA, and in the HBeAg positive group loss of HBeAg and/or the development of anti-HBe. HBV DNA measured by the Digene Hybrid capture assay (sensitivity 1.4 x 10(6) copies/mL). YMDD mutation at rtL180M and rtM204V/I measured by restriction digest of amplified products. Genotyping performed by sequencing and phylogenetic tree analysis of the preS region of the virus genome. Seventy-one patients treated with lamivudine for 6 months or more, 53 (75%) were male, average age 47 years, 38 (54%) were HBeAg+ and 33 (46%) HBeAg-. Mean baseline HBV DNA viral titre was 1280.2 copies/mL and 518 copies/mL respectively. Cirrhosis was present in 30 (42%). Sera were examined for YMDD mutations at last patient visit in 61 (86%), and were detected in 45 (74%), there being no association with a particular genotype. Data from up to 5 years on lamivudine indicated no difference in biochemical or virological response between genotypes. Cirrhosis was more prevalent with specific genotypes. We found no influence of HBV genotype on the development of resistance to lamivudine, however liver disease severity was influenced by genotype.
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PMID:Response to long-term lamivudine treatment (up to 5 years) in patients with severe chronic hepatitis B, role of genotype and drug resistance. 1598 11

Cirrhosis is the irreversible sequel of various disorders that damage liver cells permanently over time. Presently, the use of herbal medicines for prevention and control of chronic liver diseases is in the focus of attention for both the physicians and the patients; the reasons for such shift toward the use of herbals include the expensive cost of conventional drugs, adverse drug reactions, and their inefficacy. In the present study, the efficacy of herbal medicine Liv-52 (consisting of Mandur basma, Tamarix gallica and herbal extracts of Capparis spinosa, Cichorium intybus, Solanum nigrum, Terminalia arjuna and Achillea millefolium) on liver cirrhosis outcomes was compared with the placebo for 6 months in 36 cirrhotic patients referred to Tehran Hepatic Center. The outcome measures included child-pugh score, ascites, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total billirubin, albumin, prothrombin time, platelet and white blood cells counts. The indices were recorded in all patients before and after 6 months of drug or placebo treatment. The results demonstrated that the patients treated with Liv-52 for 6 months had significantly better child-pugh score, decreased ascites, decreased serum ALT and AST. In placebo administered patients all the clinical parameters recorded at beginning of the study were not significantly different than after 6 months. We conclude that Liv-52 possess hepatoprotective effect in cirrhotic patients. This protective effect of Liv-52 can be attributed to the diuretic, anti-inflammatory, anti-oxidative, and immunomodulating properties of the component herbs.
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PMID:The efficacy of Liv-52 on liver cirrhotic patients: a randomized, double-blind, placebo-controlled first approach. 1619 47

Endothelin-1 (ET-1) has been shown to regulate the expression of various genes in addition to its vasoconstrictor role in the liver. Elevated levels of ET-1 during cirrhosis play an important role in the observed microcirculatory dysfunction; however, its role as a transcription regulator remains unclear. This study aimed to determine the role of ET-1 in the hepatic gene expression of vasomediators after cirrhosis in response to LPS. Cirrhosis was induced by bile duct ligation (BDL) for 1 or 3 weeks in male Sprague-Dawley rats. Following 1 or 3 weeks of BDL or sham operation (sham), rats received an intravenous (i.v.) injection of bosentan, a dual-selective ETA/B receptor antagonist (30 mg/kg bw) or saline, and an intraperitoneal (i.p.) injection of LPS (1 mg/kg bw). Plasma alanine aminotransferase (ALT) levels were significantly elevated in 1- and 3-week BDL animals. Six hours following LPS, the elevated ALT levels were markedly exacerbated in 3-week BDL animals, which were significantly ameliorated with bosentan treatment. LPS resulted in increased ET-1, inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX)-2 mRNA expressions in both sham and BDL rats. Bosentan significantly inhibited the up-regulations of ET-1, iNOS, and COX-2 mRNA. Our data strongly suggest that ET-1 plays an important role in up-regulating the expression of iNOS, COX-2, and ET-1 itself in hepatic tissue following LPS challenge, which may contribute to the observed hepatocellular injury during endotoxemia in cirrhosis. Thus, due to significant increases in ET-1 levels during cirrhosis, ET-1 receptor blockade may prove to be of great therapeutic value in the treatment of cirrhotic patients exposed to secondary injuries such as endotoxemia.
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PMID:Inhibition of endothelin-1-mediated up-regulation of iNOS by bosentan ameliorates endotoxin-induced liver injury in cirrhosis. 1655 65

The aim of the present work was to investigate the role of inducible nitric oxide (NO) synthase (iNOS) in CCl(4)-induced cirrhosis by utilizing iNOS knock out mice (iNOS(-/-)). Cirrhosis was produced by i.p. administration of CCl(4) (1 ml kg(-1) of body weight) dissolved in olive oil three times a week for 3 months to iNOS(-/-) or iNOS(+/+) (wild type) mice; appropriate olive oil controls were performed. Nitrite plus nitrate levels were lower in iNOS(-/-) compared with iNOS(+/+) mice, but CCl(4) did not produce a significant effect in any mice. Reduced (GSH) glutathione was increased in iNOS(-/-) mice receiving vehicle and in both groups receiving CCl(4); lipid peroxidation increased significantly in iNOS(+/+) but not in iNOS(-/-) mice. Bilirubins, alanine aminotransferase and collagen (measured as the hepatic hydroxyproline content) were increased significantly by the chronic intoxication with CCl(4) in both iNOS(-/-) and iNOS(+/+) mice; importantly there was no difference between these groups. This study clearly suggests that NO derived from iNOS does not participate in cholestasis, necrosis or fibrosis induced by CCl(4) in the mice. The present results are in disagreement with several studies indicating a beneficial or detrimental effect of this molecule utilizing different experimental approaches and in agreement with some studies indicating that NO does not affect liver damage in some models. It must be pointed out that this is the first report in iNOS knock out mice utilizing the chronic model of intoxication with CCl(4); thus, comparisons with other models or approaches are difficult to reconcile.
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PMID:Inducible nitric oxide synthase is not essential for the development of fibrosis and liver damage induced by CCl4 in mice. 1670 56

Hepatoportal sclerosis (HPS) is one of the causes of noncirrhotic portal hypertension. In general, hepatic synthetic function is preserved and treatment is aimed at relief of the portal hypertension. In this study, we present the clinical and pathologic features of HPS cases who underwent liver transplantation (LT). LT cases with confirmed gross and microscopic diagnosis of HPS are included. Weight of the explanted liver, presence of thrombi in the main blood vessels, and gross and microscopic characteristics were assessed. Clinical information was gathered from chart review. From 1995 to 2004, 8 LT patients were diagnosed with HPS. Cirrhosis resulting from alcohol (2), autoimmune hepatitis (2), and hepatitis B (1), or cryptogenic cirrhosis (3) was the presumed diagnoses pre-LT. Seven patients presented with bleeding varices and 5 had concomitant ascites. At the time of LT, mean values were: prothrombin time of 15.2 seconds, serum albumin 3.2 g/dL, serum bilirubin 3.5 mg/dL, alkaline phosphatase 140 IU/L, aspartate aminotransferase 39.4 IU/L, and alanine aminotransferase 34.7 IU/L. Explanted livers were shrunken, with weights ranging from 715 to 1199 g (mean 934). Nonocclusive portal vein thrombosis was present in 2 patients. On histologic examination, there was dense portal fibrosis, marked phlebosclerosis, and presence of variable degrees of megasinusoid formation. Four livers also had features of incomplete septal cirrhosis. None showed histologic features of the presumed underlying liver disease. In conclusion, HPS can cause hepatic synthetic dysfunction that may necessitate LT. Small liver volume, significant portal fibrosis, and phlebosclerosis may contribute to hepatic parenchymal loss and subsequent synthetic compromise.
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PMID:Liver failure and need for liver transplantation in patients with advanced hepatoportal sclerosis. 1741 9

The definite indications for the treatment of chronic hepatitis B are serum hepatitis B virus (HBV) DNA levels greater than 10(5) copies/mL and alanine aminotransferase (ALT) levels more than 2 times the upper limit of normal. If cirrhosis is present, an HBV DNA level greater than 10(5) copies/mL is the sole criterion for treatment. Treatment end points include hepatitis B e antigen (HBeAg) seroconversion for HBeAg-positive patients, reduction of HBV DNA levels to less than 10(5) copies/mL, and normalization of ALT values. These guidelines may apply to patients who acquire the hepatitis B infection during adolescence or adulthood but are less suitable for most hepatitis B carriers, who are infected in early life. Cirrhosis complications, including hepatocellular carcinoma, often occur in this latter group despite HBeAg seroconversion, HBV DNA levels less than 10(4) copies/mL, or ALT levels between 0.5 and 2 times the upper limit of normal. Therefore, HBeAg seroconversion may not be an adequate end point for these patients; the ideal treatment end points are permanent suppression of HBV DNA to levels undetectable by polymerase chain reaction and reduction of ALT levels to less than 0.5 times the upper limit of normal.
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PMID:The natural history and treatment of chronic hepatitis B: a critical evaluation of standard treatment criteria and end points. 1760 63

Herbal products, used for centuries in Far Eastern countries, are gaining popularity in western countries. Surveys indicate that persons with chronic hepatitis C (CHC) often use herbals, especially silymarin (milk thistle extract), hoping to improve the modest response to antiviral therapy and reduce side effects. The Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial, involving persons with advanced CHC, nonresponders to prior antiviral therapy but still willing to participate in long-term pegylated interferon treatment, offered the opportunity to examine the use and potential effects of silymarin. Among 1145 study participants, 56% had never taken herbals, 21% admitted past use, and 23% were using them at enrollment. Silymarin constituted 72% of 60 herbals used at enrollment. Among all participants, 67% had never used silymarin, 16% used it in the past, and 17% used it at baseline. Silymarin use varied widely among the 10 participating study centers; men were more frequent users than women, as were non-Hispanic whites than African Americans and Hispanics. Silymarin use correlated strongly with higher education. No beneficial effect of silymarin was found on serum alanine aminotransferase or hepatitis C virus (HCV) RNA levels. Univariate analysis showed significantly fewer liver-related symptoms and better quality-of-life parameters in users than nonusers, but after reanalysis adjusted for covariates of age, race, education, alcohol consumption, exercise, body mass index, and smoking, only fatigue, nausea, liver pain, anorexia, muscle and joint pain, and general health remained significantly better in silymarin users. In conclusion, silymarin users had similar alanine aminotransferase and HCV levels to those of nonusers but fewer symptoms and somewhat better quality-of-life indices. Because its use among these HALT-C participants was self-motivated and uncontrolled, however, only a well-designed prospective study can determine whether silymarin provides benefit to persons with chronic hepatitis C.
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PMID:Herbal product use by persons enrolled in the hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial. 1850 76

Cirrhosis is a very common disease and its treatment is limited due to lack of effective drugs. Some studies indicate that this disease is associated with oxidative stress. Therefore, we decided to study the effect of trolox, an effective antioxidant, on experimental cirrhosis. Cirrhosis was induced by CCl4 administration (0.4 g/kg, intraperitoneally, three times per week, for 8 weeks) to Wistar male rats. Trolox was administered daily (50 mg/kg, orally). Fibrosis was assessed histologically and by measuring liver hydroxyproline content. Glutathione, lipid peroxidation and glycogen were measured in liver; serum markers of liver damage were also quantified. Transforming growth factor-beta (TGF-beta) was determined by Western blot and quantified densitometrically. Alkaline phosphatase, gamma-glutamyl transpeptidase and alanine aminotransferase increased in the group receiving CCl4; trolox completely or partially prevented these alterations. Glycogen was almost depleted by CCl4 but was partially preserved by trolox. Lipid peroxidation increased while glutathione decreased by CCl4 administration; trolox corrected both effects. Histology showed thick bands of collagen, necrosis and distortion of the hepatic parenchyma in the CCl4 group, such effects were prevented by trolox. Hydroxyproline content increased 5-fold by CCl4, while the group receiving both CCl4 and trolox showed no significant difference compared to the control group. CCl4 increased 3-fold TGF-beta, while trolox completely prevented this increase. We found that trolox effectively prevented cirrhosis induced with CCl4 in the rat. Our results suggest that the beneficial effects of trolox may be associated to its antioxidant properties and to its ability to reduce the profibrogenic cytokine TGF-beta expression.
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PMID:Trolox down-regulates transforming growth factor-beta and prevents experimental cirrhosis. 1881 77


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