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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Despite the epidemiological evidence of a correlation between ethanol abuse and hepatocellular carcinoma, some of the results of experimental and clinical studies remain controversial. Apart from inducing cirrhosis, which may be viewed as a precancerous liver lesion, ethanol may act as a cocarcinogen. Most investigations on this topic have focused on two aspects: ethanol's capacity to induce the cytochrome P-450-dependent microsomal biotransformation system and its interference with at least one DNA repair mechanism. Ethanol exposure enhances the capacity of mixed function oxidases to activate many chemical carcinogens, such as dimethylnitrosamine (DMN). On the other hand, ethanol exposure fails to influence DMN-induced liver carcinogenesis. The capacity of alcohol to inhibit DMN-demethylase activity has not been clearly demonstrated in experiments carried out with human tissue. In conclusion, both the effects of ethanol and their underlying mechanisms as regards liver carcinogenesis are open to debate. The link between ethanol abuse and hepatocellular carcinoma appears to be mediated mainly by its capacity to induce cirrhosis.
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PMID:Hepatocellular carcinoma, alcohol, and cirrhosis: facts and hypotheses. 165 Jun 91

The results of hepatectomy, percutaneous ethanol injection therapy and transcatheter arterial embolization for small hepatocellular carcinoma (HCC) of 3 cm or less in diameter from the published literature were compared with the authors' experiences with surgical treatment. The survival rates for those treated by hepatectomy and ethanol injection were almost the same, being more than 90% at 1 year and 70% at 3 years. The overall results achieved by embolization were inferior to those achieved by the other two therapeutic modalities, although the 1 year survival rate was not worse. The cancer-free survival rates after hepatectomy and ethanol injection were also similar. Most of the patients with small HCC had associated liver cirrhosis or chronic active hepatitis, but the degree of liver dysfunction and the level of hepatic reserve varied. Anatomically, the number, size, and location of the cancer also varies. Choice of treatment for small HCC should be made based upon the degree of liver function and the anatomic status of the cancer. For example, a patient with multiple (more than four) cancer nodules is a good candidate for embolization. Ethanol injection is indicated for a small HCC, deeply seated in a severely diseased liver. Hepatectomy is the first choice for a small HCC situated near the surface of a liver with relatively good liver function.
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PMID:Choice of treatments for small hepatocellular carcinoma: hepatectomy, embolization or ethanol injection. 165

The pathogenesis of variceal hemorrhage is not well understood. Portal pressure and gastroesophageal collateral (azygous) blood flow are similar in patients with cirrhosis with or without a history of variceal bleeding. However, acute increases in these parameters in individual patients might predispose them to variceal rupture. Fifteen patients with alcoholic cirrhosis and portal hypertension were evaluated to test the hypothesis that ethanol intake acutely increases portal pressure or gastroesophageal blood flow and is a possible risk factor in variceal hemorrhage. A 10% solution of ethanol in 5% dextrose in water was infused intravenously at a rate sufficient to raise the blood-alcohol level to 100 mg/dl over 30 min. Eight patients received ethanol 5% dextrose in water; seven patients received a placebo (5% dextrose in water alone). Ethanol did not produce a significant change in wedged hepatic-vein pressure, free hepatic-vein pressure, azygous blood flow, mean arterial pressure or heart rate compared with the effects of 5% dextrose in water alone. Acute administration of ethanol does not increase portal pressure or gastroesophageal blood flow. It is unlikely that acute ethanol ingestion is a risk factor for variceal hemorrhage.
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PMID:The effects of ethanol administration on portal pressure and gastroesophageal collateral blood flow in patients with alcoholic cirrhosis. 232 59

The ingestion of alcohol, both intermittently and habitually, results in significant patient morbidity and mortality and stresses an already compromised socioeconomic system. Ethanol can interact with normal metabolic pathways to produce a variety of life-threatening abnormalities, particularly in those with underlying poor nutritional status, as is found in many alcohol users. Once identified, the metabolic derangements associated with alcohol use generally respond well to therapeutic interventions. The recurrence rate, however, is extremely high. Any attempt at long-term solutions must involve extensive rehabilitative services. Current research is directed largely toward improving survival from alcohol-related illnesses such as cirrhosis and cardiac disease. We must focus our efforts on the social implications of alcoholism, providing medical support, counseling, and rehabilitation to affected persons. Since alcohol-related problems present most frequently to the Emergency Department, it is appropriate that the emergency physician take the first step in attacking this disease, a step that may be as simple as a referral for detoxification or social services support.
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PMID:Ethanol-associated metabolic disorders. 268 Apr 73

The activity of the lysosomal enzyme, beta-hexosaminidase, is increased in plasma of patients with various forms of liver disease as well as in plasma from rats with experimental cholestasis or cirrhosis. In this experimental study in the rat, the effect of porta-caval shunt, ammonia infusion and ethanol feeding on plasma beta-hexosaminidase activity was studied. Porta-caval shunted animals had significantly increased plasma beta-hexosaminidase activity compared to sham-operated animals. Ammonia infusion in porta-caval shunted rats resulted in a further increase of plasma enzyme activity. Ethanol feeding for different periods of time (1 day to 4 weeks) did not have any influence on plasma beta-hexosaminidase activity.
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PMID:The effect of porta-caval shunt, ammonia infusion and alcohol administration on rat plasma beta-hexosaminidase. 296 73

Acute and chronic ethanol consumption alters psychotropic drug pharmacokinetics. An understanding of the processes of drug absorption, distribution, biotransformation, and elimination provide a rational basis for predicting and evaluating drug interactions. Careful application of clinical pharmacokinetic models describing these physiological processes are particularly appropriate for the task of understanding drug and alcohol interactions. Absorption: Acute alcohol inhibits first-pass effect increasing systemic bioavailability. Ethanol inhibits gastric emptying and may delay drug absorption (increase lag time of absorption) and decrease the rate of absorption. The effects of chronic alcohol intake are unknown. Distribution: Hypoalbuminemia may be present in alcoholics with liver disease. Fluctuations in free fractions of drugs may occur in the alcohol withdrawal period. The clinical effects of protein binding changes are dependent on degree of binding, hepatic extraction ratio, and binding protein. Acute low-dose ethanol increases hepatic blood flow while high doses decrease it. The effects of chronic alcohol intake on liver blood flow are unknown. Hepatic blood flow changes show the greatest effects on drugs with high extraction ratios. Metabolism: Acute alcohol ingestion usually inhibits drug metabolism and chronic intake (in the absence of severe liver disease) enhances metabolism. Cirrhosis impairs oxidative metabolism, but spares glucuronidation. Although these generalizations may serve as useful guidelines for predicting alcohol and psychotropic drug interactions, they should be applied with caution as exceptions do exist.
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PMID:Pharmacokinetic mechanisms of ethanol-psychotropic drug interactions. 309 58

The type of cirrhosis was blindly evaluated in follow-up liver biopsies performed on 106 alcoholic men with micronodular cirrhosis. The median time interval from entry to follow-up liver biopsy was 31 mo (range, 3-44 mo). Patients were stratified into four groups according to their maximal registered ethanol consumption during follow-up. Thirty-six patients (34%) abstained from ethanol, 40 patients (38%) consumed a small amount of ethanol (less than 50 g/day), 19 patients (18%) consumed a moderate amount of ethanol (51-100 g/day), and 11 patients (10%) consumed an excessive amount of ethanol (greater than 100 g/day) during follow-up. Follow-up liver biopsy specimens demonstrated micronodular cirrhosis in 54 patients (51%), micronodular cirrhosis with development of hyperplastic nodules in 47 patients (44%), and nonclassifiable macronodular cirrhosis in 4 patients (4%); 1 patient showed portal fibrosis. The cumulative prevalence of patients developing hyperplastic nodules increased significantly (p = 0.014 for trend) with decreasing ethanol consumption, the prevalence being 57% in abstainers, 58% in those who consumed a small amount of ethanol, 32% in those who consumed a moderate amount, and 18% in those who consumed an excessive amount. In conclusion, alcoholic men with micronodular cirrhosis develop hyperplastic nodules during follow-up, the rate and prevalence of which is significantly related to the amount of ethanol consumed during follow-up. Ethanol consumption may inhibit hepatocellular proliferation in alcoholic men with micronodular cirrhosis.
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PMID:Influence of ethanol on development of hyperplastic nodules in alcoholic men with micronodular cirrhosis. 359 60

1. The influence of ethanol on the metabolism of perfused livers from normal rats and rats in various stages of development of dietary cirrhosis was studied. A choline-deficient, low-protein and high-fat diet was used. Results were obtained on oxygen consumption and carbon dioxide production, on glucose release and uptake by the liver and on changes in the concentrations of lactate and pyruvate and of beta-hydroxybutyrate and acetoacetate in the perfusion medium. 2. Oxygen consumption and carbon dioxide production were lower in fatty and cirrhotic livers than in normal livers. Ethanol had no effect on the oxygen consumption of any of the various livers. After addition of ethanol to the perfusion medium carbon dioxide production ceased almost completely in normal livers. Only a slight decrease in the carbon dioxide production occurred in fatty and cirrhotic livers. 3. With every type of liver glucose was released from the liver into the perfusion medium during the initial control period. This release continued after the addition of ethanol to the perfusion medium in experiments with normal and fatty livers, whereas with cirrhotic livers a marked uptake of glucose from the medium was found. A simultaneous release of the glycolytic end products lactate and pyruvate into the medium occurred. 4. The production of ketone bodies was equal in normal and early fatty livers (6 weeks on the fat diet). It was smaller in late fatty livers (3-4 months on the fatty diet) and in cirrhotic livers. 5. The lactate/pyruvate concentration ratio in the perfusion medium increased from 11 to 67 with normal livers, from 12 to 16 with early fatty livers, from 13 to 26 with late fatty livers and from 21 to 55 with cirrhotic livers when the livers were perfused with a medium containing ethanol. The beta-hydroxybutyrate/acetoacetate concentration ratio increased from 1.2 to 8.4 in normal livers, from 2.0 to 2.8 in early fatty livers, from 1.2 to 2.4 in late fatty livers and from 2.1 to 4.0 in cirrhotic livers when ethanol was added to the medium. 6. The effects of ethanol on liver metabolism during the development of dietary cirrhosis are discussed and related to human fatty liver and cirrhosis during chronic ethanol consumption.
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PMID:Influence of ethanol on the metabolism of perfused normal, fatty and cirrhotic rat livers. 596 89

The conversion of alcoholic hepatitis into cirrhosis and the eventual development of hepatocellular carcinoma (HCC) has been documented by serial biopsies in patients with uncomplicated alcoholism. Ethanol toxicity, nutritional deficiency and immunological abnormalities in a genetically predisposed individual appear to account for this sequence which can be accelerated by the hepatitis B virus and other noxious agents. Immune deficiency in malnourished alcoholics with liver disease diminishes response to the hepatitis B vaccine and may contribute to the development of HCC. Antigenic moieties in Mallory bodies appear to contribute directly to cytotoxicity and fibrosis in alcoholics, and may act like proto-oncogens. Available Mallory-body-specific monoclonal antibodies will hopefully facilitate diagnosis and treatment. Studies of DNA and collagen synthesis by in vitro perfusion of percutaneous liver biopsies provide information on precursor lesions of HCC. Abstinence, nutrient therapy and drug-induced anabolism lead to repair of liver damage and correction of immunological abnormalities, both of which may contribute to development of HCC in alcoholics with cirrhosis.
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PMID:Hepatocellular carcinoma in the alcoholic. 610 Feb 66

Ther are several main mechanisms that allow us to understand a number of the hepatic and metabolic effects of ethanol. Ethanol is oxidized in the liver to two products (hydrogen and acetaldehyde), to which many of the effects of ethanol can be attributed. The hydrogen generated alters the redox state, and though this effect is attenuated after chronic ethanol consumption, it may still be sufficient to explain alterations in lipid metabolism, possibly increased collagen deposition, and, under special circumstances, depression of protein synthesis. Acetaldehyde impairs microtubules, decreases protein secretion, and causes protein retention and ballooning of the hepatocyte. Acetaldehyde exerts toxicity also with regard to other key cellular functions, particularly in the mitochondria, and it may promote peroxidation of the cellular membranes. It is noteworthy that after chronic consumption of ethanol, there is increased acetaldehyde, in part because of decreased disposition in the mitochondria and partly because of induction of an alternative pathway of ethanol metabolism, namely the microsomal ethanol-oxidizing system. Indeed, this MEOS increases in activity after chronic ethanol consumption, with cross induction and acceleration of the metabolism of other drugs and increased lipoprotein production with hyperlipemia. There is also increased microsomal activation of hepatotoxic compounds (including drugs and possibly vitamin A). Fibrosis and cirrhosis can develop despite an associated adequate diet and even in the absence of alcoholic hepatitis. They are preceded by myofibroblasts and fibroblast proliferation. What eventually causes the increased number of myofibroblasts and promotes fibrosis is unclear, nor do we know the relative role of hepatocytes or mesenchymal cells in the process of fibroplasis. Possibly selective roles in this process of specific nutritional factors remain to be elucidated.
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PMID:Alcohol, protein nutrition, and liver injury. 634 74


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