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)

Genomic ablation of hepatocyte-specific fibroblast growth factor receptor (FGFR)4 in mice revealed a role of FGF signaling in cholesterol and bile acid metabolism and hepatolobular restoration in response to injury without effect on liver development or hepatocyte proliferation. Although the potential role of all 23 FGF polypeptides in the liver is still unclear, the most widely studied prototypes, FGF1 and FGF2, are present and have been implicated in liver cell growth and function in vitro. To determine whether FGF1 and FGF2 play a role in response to injury and fibrosis, we examined the impact of both acute and chronic exposure to carbon tetrachloride (CCl(4)) in the livers of FGF1- and FGF2-deficient mice. After acute CCl(4) exposure, FGF1(-/-)FGF2(-/-) mice exhibited an accelerated release of serum alanine aminotransferase similar to FGFR4 deficiency, but no effect on overall hepatolobular restoration or bile acid metabolism. FGF1(-/-)FGF2(-/-) mice exhibited a normal increase in alpha-smooth muscle actin and desmin associated with activation and migration of hepatic stellate cells to damage, but a reduced level of hepatic stellate cell-derived matrix collagen alpha1(I) synthesis. Liver fibrosis resulting from chronic CCl(4) exposure was markedly decreased in the livers of FGF1/FGF2-deficient mice. These results suggest an agonist role for FGF1 and FGF2 in specifically insult-induced liver matrix deposition and hepatic fibrogenesis and a potential target for the prevention of hepatic fibrosis.
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PMID:Role of fibroblast growth factor type 1 and 2 in carbon tetrachloride-induced hepatic injury and fibrogenesis. 1450 72

To clarify the clinical significance of prior hepatitis B virus (HBV) infection in the development of C-viral hepatocellular carcinoma (HCC), we conducted two studies: (1) Two hundred thirty-four patients with C-viral HCC and 320 patients with C-viral chronic liver disease without HCC admitted to our hospital between 1990 and 1994 were analyzed for the association of hepatitis B core antibody (HBcAb) positivity with HCC by multivariate logistic regression analysis, and this revealed HBcAb positivity as an independent risk factor for development of HCC adjusted for age and sex. (2) Four hundred fifty-nine patients with biopsy-proven hepatitis C virus-related chronic liver disease between 1986 and 1998 were enrolled in the cohort study and followed for the development of HCC. During an average follow-up of 6.6 +/- 3.3 years, HCC developed in 63 patients, 37 of 160 patients positive for HBcAb and 26 of 299 patients negative for HBcAb. Multivariate Cox proportional regression analysis showed that the incidence of HCC increased by age, advanced stage of liver fibrosis, mean alanine aminotransferase value of more than 80 IU/liter, and positivity of HBcAb. Sustained virological responders after interferon therapy revealed a reduced risk for HCC development. In conclusion, prior HBV infection was shown to be one of the independent risk factors for development of HCC in C-viral chronic liver disease.
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PMID:Significance of prior hepatitis B virus infection in the development of hepatocellular carcinoma in patients with chronic hepatitis C. 1456 Oct 2

A study was performed in 10 European health care centers in which 914 patients coinfected with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) who had elevated serum alanine aminotransferase (ALT) levels underwent liver biopsy during the period of 1992 through 2002. Overall, the METAVIR liver fibrosis stage was F0 in 10% of patients, F1 in 33%, F2 in 22%, F3 in 22%, and F4 in 13%. Predictors of severe liver fibrosis (METAVIR stage, F3 or F4) in multivariate analysis were age of >35 years (odds ratio [OR], 2.95; 95% confidence interval [CI], 2.08-4.18), alcohol consumption of >50 g/day (OR, 1.61; 95% CI, 1.1-2.35), and CD4+ T cell count of <500 cells/mm3 (OR, 1.43; 95% CI, 1.03-1.98). Forty-six percent of patients aged >40 years had severe liver fibrosis, compared with 15% of subjects aged <30 years. The use of antiretroviral therapy was not associated with the severity of liver fibrosis. In summary, severe liver fibrosis is frequently found in HCV-HIV-coinfected patients with elevated serum ALT levels, and its severity increases significantly with age. The rate of complications due to end-stage liver disease will inevitably increase in this population, for whom anti-HCV therapy should be considered a priority.
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PMID:Incidence and predictors of severe liver fibrosis in human immunodeficiency virus-infected patients with chronic hepatitis C: a European collaborative study. 1522 29

Data mining in time-series medical databases has been receiving considerable attention since it provides a way of revealing useful information hidden in the database; for example relationships between the temporal course of examination results and onset time of diseases. This paper presents a new method for finding similar patterns in temporal sequences based on multiscale matching. Multiscale matching enables us the cross-scale comparison of sequences, namely, it enable us to compare temporal patterns by partially changing observation scales. We examined the usefulness of the method on the chronic hepatitis dataset and found some interesting patterns. On GPT sequences, we found patterns that may represent the effectiveness of interferon (IFN) treatment. On platelet count sequences, we found that, if IFN treatment was ineffective, platelet count kept decreasing following the progress of liver fibrosis, while it started increasing if the treatment was effective.
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PMID:Multiscale analysis of long time-series medical databases. 1472 80

The mechanism(s) determining the progression from fatty liver to steatohepatitis is currently unknown. Our goal was to define the relative impact of iron overload, genetic mutations of HFE, and insulin resistance on the severity of liver fibrosis in a population of subjects with nonalcoholic fatty liver disease (NAFLD) who had low prevalence of obesity and no overt symptoms of diabetes. In a cohort of 263 prospectively enrolled patients with NAFLD, 7.4% of patients had signs of peripheral iron overload and 9% had signs of hepatic iron overload, but 21.1% had hyperferritinemia. The prevalence of C282Y and H63D HFE mutations was similar to the general population and mutations were not associated with iron overload. Although subjects were on average only moderately overweight, insulin sensitivity, measured both in the fasting state and in response to oral glucose, was lower. Univariate analysis demonstrated that the presence of severe fibrosis was independently associated with older age, female sex, overweight, aspartate/alanine aminotransferase ratio, serum ferritin level, fasting glucose and insulin levels, decreased insulin sensitivity, and with histologic features (degree of necroinflammation and steatosis). After adjustment for body mass index (BMI), age, sex, and degree of steatosis, ferritin levels (odds ratio [OR] = 1.77; 95% CI = 1.21- 2.58; P =.0032) and the oral glucose insulin sensitivity (OR = 0.53; CI = 0.33-0.87; P =.0113) were independent predictors of severe fibrosis. In conclusion, the current study indicates that insulin resistance is a major, independent risk factor for advanced fibrosis in patients with NAFLD. Increased ferritin levels are markers of severe histologic damage, but not of iron overload. Iron burden and HFE mutations do not contribute significantly to hepatic fibrosis in the majority of patients with NAFLD.
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PMID:Relative contribution of iron burden, HFE mutations, and insulin resistance to fibrosis in nonalcoholic fatty liver. 1518 21

An AST/ALT ratio > 1 is predictive of liver fibrosis and cirrhosis in patients with chronic hepatitis C virus infection. The aim of this case-control study is to assess AST/ALT ratio in 150 workers exposed to VCM (E) from the beginning of the 1960s to the end of the 1990s. The non-exposed group (NE) consists in 150 male workers employed in the production of a food industry. At least since 1983 exposed subjects worked at VCM environmental concentrations < 3 ppm. All the workers underwent venous blood collection for assessment of AST and ALT. Exposed workers presented mean AST/ALT ratio and frequency of AST/ALT ratio > 1 significantly higher than non-exposed. The mean AST/ALT ratio results significantly higher in the exposed group, also after stratification for alcohol consumption. In exposed workers who consume alcoholic beverages and are operating since before 1983 AST/ALT ratio is significantly and positively influenced only by the working age until 1983. If these results will be confirmed, AST/ALT ratio could be proposed to be included in the periodic medical surveillance of VCM workers.
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PMID:[Aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio in health surveillance of workers exposed to vinyl chloride monomer: preliminary results]. 1497 7

Hepatitis C virus (HCV) infection is common in patients with end-stage renal disease. The severity of liver damage, including fibrosis, in these cases varies widely. Although many investigators have searched for noninvasive alternatives to liver biopsy for evaluating the extent of liver fibrosis, no useful noninvasive predictors have been found. Currently, liver biopsy is essential to assess the degree of fibrosis. The aim of this retrospective study was to investigate a range of clinical and laboratory parameters in HCV-infected hemodialysis (HD) patients and identify possible predictors of fibrosis. Ninety-five consecutive HD patients with HCV infection underwent liver biopsy. Each specimen was evaluated for fibrosis stage. Correlations were sought between the degree of fibrosis and the age, HD duration, time since first possible HCV exposure, body mass index, HCV RNA titer, serum ferritin level, and serum alanine aminotransferase (ALT) level. The analysis revealed no significant correlations between fibrosis stage and the parameters investigated (mean age: r =.017, P =.89; mean HD duration: r =.066, P =.576; body mass index r =.231, P =.152; HCV RNA titer: r =.015, P =.091; serum ferritin: r =.134, P =.32; serum ALT r =.108, P =.927). Links with serum ALT were reevaluated with upper normal levels arbitrarily set at 30 IU/L and 20 IU/L, but these analyses also revealed no correlations between fibrosis stage and ALT level (P =.98 and P =.449, respectively). Therefore liver biopsy is still essential for accurate assessment of liver pathology in HD patients with HCV.
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PMID:Investigation of possible clinical and laboratory predictors of liver fibrosis in hemodialysis patients infected with hepatitis C virus. 1501 98

Recent studies have shown that gene expression profiles change in the livers of animals treated acutely with toxic chemicals such as carbon tetrachloride (CCl(4)). This study was undertaken to evaluate the changes in gene expression in mouse liver immediately after a long-term treatment with CCl(4) and possible effects of treatment cessation on these changes. Adult 129/Sv(pc)J mice were treated twice a week with CCl(4) at 1 ml/kg in olive oil for 4 weeks. Hepatic pathological changes observed in the CCl(4)-treated mice included necrosis, inflammation, and fibrosis, along with increased serum alanine aminotransferase activities. Consistent with these changes, expression of genes involved in cell death, cell proliferation, metabolism, DNA damage, and fibrogenesis were upregulated as detected by microarray analysis and confirmed by real-time RT-PCR. Four weeks after CCl(4) treatment cessation, the pathological changes were recovered, with the exception of fibrosis, which was not completely reversed. Most of the gene expression profiles also returned to the control level; however, the fibrogenetic genes remained at a high level of expression. These results demonstrate that changes in gene expression profile correlate with pathological alterations in the liver in response to CCl(4) intoxication. Most of these changes are recoverable upon withdrawal of the toxic insult. However, liver fibrosis is a prolonged change both in gene expression and histopathological alterations.
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PMID:Changes in the gene expression associated with carbon tetrachloride-induced liver fibrosis persist after cessation of dosing in mice. 1505 8

In 504 patients with chronic hepatitis C who underwent liver biopsy, the correlation between serum ALT levels and histologic liver inflammation was investigated, and the effects of age, sex, and degree of histologic liver fibrosis on this correlation were analyzed. Serum ALT levels were significantly higher in male than in female patients only when activity of hepatitis was mild. In contrast, ALT levels were significantly higher in younger (< or = 50 years old) than in older patients only when activity of liver inflammation was severe. Fibrosis was closely associated with activity of hepatitis and, also, serum ALT level. More importantly, a significant number of older patients and patients with severe hepatic fibrosis had severe hepatic inflammation even when their serum ALT level was not markedly elevated (< or = 70 IU/L). Age, sex, and degree of liver fibrosis independently influenced serum ALT levels in patients with chronic hepatitis C.
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PMID:Influence of age, sex, and degree of liver fibrosis on the association between serum alanine aminotransferase levels and liver inflammation in patients with chronic hepatitis C. 1510 73

Non-alcoholic steatohepatitis (NASH) can vary from mild hepatic inflammation and steatosis to cirrhosis, and is most frequently associated with obesity, Type 2 diabetes mellitus, hypertension, and the female gender. The prevalence of fatty liver and NASH in the general population is 20% and 3%, respectively. In Western countries, 15-20% of the population is obese and 74-90% of them exhibit fatty changes in liver biopsies. We assessed the prevalence of NASH in morbidly obese patients and evaluated serum TGF-beta1 concentrations in different stages of liver fibrosis. Thirty-five obese patients were evaluated, nine male and 26 female. Their mean body mass index (BMI) was 43.62 +/- 7.92 kg/m2. Liver biopsies were evaluated by light microscopy; graded and staged according to Brunt's system. Serum obtained from patients was used to detect TGF-beta1 concentrations by an ELISA method. Serum alanine transaminase (ALT) levels were elevated in four of the patients and the mean level was 49.98 +/- 94.7 (8-65 IU/L). NASH was diagnosed in 32 (91%) of the biopsies, and the most common pattern seen was mixed, predominantly macrovesicular steatosis. Some degree of fibrosis was seen in 34 (97%) of the biopsies and 22 (63%) were at stage 2 (range 1-3). Serum concentrations of TGF-beta1 had no relationship with the stages of fibrosis. In conclusion, NASH and fibrosis are common in our obese patients, as observed in other studies. TGF-beta1 may play a key role in liver fibrogenesis.
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PMID:Obesity-related non-alcoholic steatohepatitis and TGF-beta1 serum levels in relation to morbid obesity. 1511 94


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