Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ethanol consumption and/or liver damage may alter liver content of several trace elements, as iron, zinc, copper, and manganese. This alteration may play a role on ongoing liver fibrogenesis. Based on these facts we have determined liver, serum, and urinary Mn, Cu, Zn, and Fe levels in a group of alcoholic cirrhotics and noncirrhotics with normal renal function, comparing them with those of controls. We have observed low liver zinc and high liver copper--this last in relation with histomorphometrically determined total amount of liver fibrosis--and manganese contents in cirrhotics, together with increased excretion of zinc and iron and decreased excretion of manganese. Zinc, iron, and copper excretion kept a relation with data of severity of cirrhosis, including mortality in the case of urinary copper, independently of the use of diuretics. Thus, liver copper and urinary iron, zinc, and copper excretion seem to be related with data of severity of chronic alcoholic liver disease. Low urinary manganese excretion may play a role on liver manganese overload.
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PMID:Zinc, copper, manganese, and iron in chronic alcoholic liver disease. 901 22

Ethanol-inducible cytochrome P4502E1 is the main pathway in the non-alcohol dehydrogenase oxidation of ethanol. Its coding gene, CYP2E1, is polymorphic at the Rsa I restriction site in the 5'-flanking region. The mutant genotype c2c2 has a higher transcriptional activity than the genotype c1c1 or c1c2. Heavy drinkers carrying the c2 allele might be at a higher risk of alcoholic cirrhosis since they might synthesize greater amounts of acetaldehyde, the compound believed responsible for hepatotoxicity of ethanol. With the aim of establishing if the c2 allele increases the risk of cirrhosis in heavy drinkers, we studied 58 (6 female) chronic heavy drinkers with liver cirrhosis and 137 healthy normal controls of the same ethnic (white Spaniards) origin. After extraction of DNA from white blood cells, alleles c1 and c2 of CYP2E1 were identified by restriction fragment length polymorphism (RFLP) with endonuclease Rsa I. Fifty-six patients and 130 controls were classified as homozygous c1c1 and two and seven, respectively, as heterozygous c1c2. No homozygous c2c2 were detected. The c2 allele frequencies were 0.017 in patients and 0.026 in controls (non-significant differences). We conclude that the Rsa I RFLP polymorphism is probably not related to the risk of cirrhosis in Spanish heavy drinkers.
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PMID:Rsa I polymorphism at the cytochrome P4502E1 locus is not related to the risk of alcohol-related severe liver disease. 902 17

Ethanol injection into the focus by means of a thin needle under ultrasonographic guidance has become part of treatment of primary carcinoma of the liver-hepatocellular carcinoma. It is a palliative method suitable for the treatment of small foci of hepatocellular carcinoma in a uniocular or oligolocular form. The limiting factor are in particular the number of foci, their size, depth and stage of hepatic cirrhosis in the remainder of the live parenchyma. Treatment is well tolerated and the survival of patients, if they are properly selected, is similar as in surgical resection.
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PMID:[Treatment of liver tumors with ethanol injection]. 922 82

The present study was done to determine the additional influence of daily ethanol intake (15% in drinking water ad libitum) on long-term toxic effects of a single administration of dibutyltin dichloride (DBTC, 8 mg/kg b.w. i.v.) in pancreas and liver of rats. Pathohistological changes in pancreas, bile duct and liver as well as pathobiochemical parameters of pancreatitis (amylase and lipase activity), liver lesions (alkaline phosphatase activity and bilirubin) and fibrosis (hydroxyproline and hyaluronic acid) were measured 1 day and 1 to 24 weeks after DBTC- and DBTC/ethanol administration. DBTC alone induced in rats an acute interstitial pancreatitis as well as acute bile duct and liver lesions in the early experimental phase. Later on, the acute inflammatory processes in pancreas and liver took a chronic course resulting in pancreatic fibrosis and liver cirrhosis. Ethanol increased the toxic effects of DBTC on pancreas and liver during the acute and chronic course. In the acute phase lasting 1 day to 2 weeks, ethanol enhanced the DBTC toxicity on acinar cell and bilio-pancreatic duct epithelium as well as the formation of obstructive ductal plugs by necrotic cell debris. The obstruction and cholestasis in the DBTC/ethanol-group were significantly stronger as in the DBTC-group. The significant increase of hydroxyproline in urine and hyaluronic acid in serum of the DBTC/ethanol treated rats after 12 to 24 weeks was connected with a more severe chronic inflammatory fibrosis in pancreas and liver in comparison to the DBTC-treated group.
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PMID:The influence of ethanol on long-term effects of dibutyltin dichloride (DBTC) in pancreas and liver of rats. 958 82

The purpose of this study is to determine serum des-gamma-carboxy prothrombin (DCP) levels in benign liver diseases by a new sensitive method, and to demonstrate the elevation of serum DCP in alcoholic liver disease (ALD) without hepatocellular carcinoma (HCC). Median values of serum DCP were 16.2 mAU/ml (range: 3.2 to 1570 mAU/ml) in ALD and 16.7 mAU/ml (1.2 to 75.4 mAU/ml) in viral liver disease (VLD). Using the cut-off value of 40 mAU/ml as a tumor marker for HCC, 21% (11/52) was positive in ALD and 2% (1/57) was positive in VLD (p = 0.0014, Fisher's exact probability test), and 27% (9/33) was positive in alcoholic liver cirrhosis and 3% (1/39) was positive in viral liver cirrhosis (p = 0.0042, Fisher's exact probability test). The positive rate of DCP was significantly (p < 0.001, Spearman's rank correlation test) correlated with the severity of liver disease in ALD. Serum vitamin K level was not decreased in cases with ALD. In a demonstrable case, serum DCP was decreased after abstinence and was increased again after the beginning of ethanol intake, suggesting the involvement of ethanol to the elevation of serum DCP in ALD. In conclusion, serum DCP was significantly elevated in ALD, compared with VLD, although the mechanism of the elevation of DCP was not clarified. Ethanol intake may act, in part, on the increase of serum DCP in ALD.
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PMID:Increase of serum des-gamma-carboxy prothrombin in alcoholic liver disease without hepatocellular carcinoma. 1023 82

Ethanol is one of the few nutrients that is profoundly toxic. Alcohol causes both whole-body and tissue-specific changes in protein metabolism. Chronic ethanol missuse increases nitrogen excretion with concomitant loss of lean tissue mass. Even acute doses of alcohol elicit increased nitrogen excretion. The loss of skeletal muscle protein (i.e., chronic alcoholic myopathy) is one of several adverse reactions to alcohol and occurs in up to two-thirds of all ethanol misusers. There are a variety of other diseases and tissue abnormalities that are entirely due to ethanol-induced changes in the amounts of individual proteins or groups of tissue proteins; for example, increased hepatic collagen in cirrhosis, reduction in myosin in cardiomyopathy, and loss of skeletal collagen in osteoporosis. Ethanol induces changes in protein metabolism in probably all organ or tissue systems. Clinical studies in alcoholic patients without overt liver disease show reduced rates of skeletal muscle protein synthesis though whole-body protein turnover does not appear to be significantly affected. Protein turnover studies in alcohol misusers are, however, subject to artifactual misinterpretations due to non-abstinence, dual substance misuse (e.g., cocaine or tobacco), specific nutritional deficiencies, or the presence of overt organ dysfunction. As a consequence, the most reliable data examining the effects of alcohol on protein metabolism is derived from animal studies, where nutritional elements of the dosing regimen can be strictly controlled. These studies indicate that, both chronically and acutely, alcohol causes reductions in skeletal muscle protein synthesis, as well as of skin, bone, and the small intestine. Chronically, animal studies also show increased urinary nitrogen excretion and loss of skeletal muscle protein. With respect to skeletal muscle, the reductions in protein synthesis do not appear to be due to the generation of reactive oxygen species, are not prevented with nitric oxide synthase inhibitors, and may be indirectly mediated by the reactive metabolite acetaldehyde. Changes in skeletal muscle protein metabolism have profound implications for whole body physiology, while protein turnover changes in organs such as the heart (exemplified by complex alterations in protein profiles) have important implications for cardiovascular function and morbidity.
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PMID:Protein metabolism in alcoholism: effects on specific tissues and the whole body. 1042 97

Alcohol changes the progression of hepatitis C virus (HCV)-related chronic liver disease and may affect the outcome of interferon therapy. The ethanol intake of 245 patients with biopsy-proven chronic hepatitis C with or without cirrhosis, its interaction with laboratory and histological parameters common to alcohol and HCV-mediated liver damage, and its effects on therapy were evaluated. The results show that 60-70% of subjects regularly consumed alcohol (median intake >40 g/day in about 30%). Less than 50% stopped drinking after being diagnosed as having liver disease. Ethanol intake affected: fibrosis, especially in women, HCV RNA levels, which were significantly lower in abstainers than in drinkers (0.6 +/- 0.3 vs 6.9 +/- 5.9 Eq/ml x10(6); P < 0.01), and response to interferon therapy. The number of responders decreased as ethanol intake increased. There were less abstainers than drinkers among non-responders (10.7% vs 63.1% respectively; P < 0.001). Data indicate that alcohol will induce and worsen liver damage and, in subjects with chronic liver disease who continue to drink, adversely affect their response to treatment.
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PMID:Drinking habits of subjects with hepatitis C virus-related chronic liver disease: prevalence and effect on clinical, virological and pathological aspects. 1086 51

Apoptosis plays an important role in the progression of alcohol-induced liver disease to cirrhosis. Oxidative stress is an early event in the development of apoptosis. The major aim of this study was to study the conditions in which oxidative stress occurs in chronic alcoholism and its relationship with apoptosis of hepatocytes. We have found that oxidative stress is associated with chronic ethanol consumption in humans and in rats, in the former independently of the existence of alcohol-induced liver disease. Ethanol or acetaldehyde induces apoptosis in hepatocytes isolated from alcoholic rats, but not in those from control rats. Inhibition of aldehyde dehydrogenase, but not of cytochrome P450 2E1, prevents ethanol-induced cell death. Ethanol-induced apoptosis is caused by increased reactive oxygen species (ROS) driven by increased availability of the reduced form of nicotinamide-adenine dinucleotide (NADH) owing to mitochondrial acetaldehyde metabolism and it is prevented by blocking the opening of mitochondrial permeability transition (MPT) pores with cyclosporine A. Inhibition of nitric oxide (NO) synthase or addition of antioxidant vitamins C and E completely prevented ethanol-induced apoptosis. Mitochondrial oxidative stress, which occurs during chronic alcoholism, renders hepatocytes susceptible to apoptosis. On the other hand, the CD95 ligand expression was up-regulated by acetaldehyde. In conclusion, ethanol induces apoptosis via 2 different pathways: MPT and up-regulation of the expression of CD95-Fas ligand. The overproduction of ROS by mitochondria, driven by acetaldehyde metabolism, is a common trigger of both mechanisms.
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PMID:Mitochondrial oxidative stress and CD95 ligand: a dual mechanism for hepatocyte apoptosis in chronic alcoholism. 1198 71

Ethanol and LPS are immunomodulators, whose actions are associated with the activation of the transcription factor, NF-kappaB, that mediates the expression of a number of rapid response genes involved in the whole body inflammatory response to injury, including transcriptional regulation of iNOS and COX-2. We investigated modulation by acute ethanol (EtOH) intoxication, LPS and LPS tolerance of NF-kappaB activation in hepatocytes, Kupffer cells and sinusoidal endothelial cells (SEC), concurrent regulation of iNOS and COX-2 gene expression and the influence of gender on these mechanisms. In vivo EtOH alone or with LPS significantly activates NF-kappaB in Kupffer cells and SEC. iNOS gene expression in these cells is modulated by LPS+EtOH in a gender- dependent manner. Acute EtOH administration enhanced iNOS mRNA in hepatocytes and Kupffer cells.LPS tolerance decreased LPS-induced NF-kappaB activation in Kupffer cells, but markedly raised iNOS mRNA in all three cell types with gender differences (females being higher). In LPS tolerant rats EtOH decreased elevated iNOS mRNA in all cells studied. LPS tolerance significantly reduced LPS-induced COX-2 mRNA in SEC, but only moderately in Kupffer cells of females, and not at all in males. Since NO is a known scavenger of superoxide and therefore protective against oxidative injury associated with LPS and acute EtOH intoxication, the gender differential effect of LPS+EtOH on iNOS gene expression (reduced only in females) may contribute to the greater susceptibility of females to alcoholic liver disease. Suppression of COX-2 gene expression in SEC may cause detrimental effects in the hepatic microcirculation, associated with cirrhosis.
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PMID:Ethanol and LPS modulate NF-kappaB activation, inducible NO synthase and COX-2 gene expression in rat liver cells in vivo. 1199 8

Our understanding of the mechanisms involved in the development of alcohol-induced liver disease has increased substantially in recent years. Specifically, reactive oxygen and nitrogen species have been identified as key components in initiating and possibly sustaining the pathogenic pathways responsible for the progression from alcohol-induced fatty liver to alcoholic hepatitis and cirrhosis. Ethanol has been demonstrated to increase the production of reactive oxygen and nitrogen species and decrease several antioxidant mechanisms in liver. However, the relative contribution of the proposed sites of ethanol-induced reactive species production within the liver is still not clear. It has been proposed that chronic ethanol-elicited alterations in mitochondria structure and function might result in increased production of reactive species at the level of the mitochondrion in liver from ethanol consumers. This in turn might result in oxidative modification and inactivation of mitochondrial macromolecules, thereby contributing further to mitochondrial dysfunction and a loss in hepatic energy conservation. Moreover, ethanol-related increases in reactive species may shift the balance between pro- and anti-apoptotic factors such that there is activation of the mitochondrial permeability transition, which would lead to increased cell death in the liver after chronic alcohol consumption. This article will examine the critical role of these reactive species in ethanol-induced liver injury with specific emphasis on how chronic ethanol-associated alterations to mitochondria influence the production of reactive oxygen and nitrogen species and how their production may disrupt hepatic energy conservation in the chronic alcohol abuser.
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PMID:A review of the role of reactive oxygen and nitrogen species in alcohol-induced mitochondrial dysfunction. 1286 85


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