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

The effects of ethanol on hepatic cellular metabolism and structure depend mainly on the dose and duration of intake. Following the ingestion of a substantial amount of ethanol, its presence alters a number of hepatic functions in part because of the change in the hepatic redox state (NADH/NAD ratio), resulting for instance in reduction of lipid oxidation. Furthermore, chronic ethanol consumption, at least in its early stages, produces adaptive metabolic changes in the endoplasmic reticulum which result not only in increased metabolism of drugs and accelerated lipoprotein production but also in activation of hepatotoxic compounds. Even more extended periods of ethanol intake result in damage to cell organelles in what can be considered a third stage of the alcohol effect namely that of injury. The injury involves primarily mitochondria, possibly as a consequence of effects of acetaldehyde, the first product of ethanol metabolism. Metabolites of ethanol also alter microtubular function. A defect in protein secretion may be the basis for protein retention and "ballooning" of the hepatocyte. Prolongation of ethanol induced injury eventually culminates in hepatic lesions such as alcoholic hepatitis and cirrhosis. Ethanol can be incriminated as a direct etiologic agent of the liver injury, since liver cirrhosis has been reproduced experimentally in baboons fed alcohol, despite an adequate diet.
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PMID:[Pathogenesis of alcoholic liver injury (author's transl)]. 11 23

Significant liver disease including fatty metamorphosis, alcoholic hepatitis, cirrhosis, and hepatoma occur in two thirds of subjects who consume alcoholic beverages in sufficient quantities to interfere with work and social responsibilities; this is of major importance in the rapidly escalating morbidity and mortality from alcoholism. Chronic alcoholics should be routinely evaluated for the presence of altered liver function and structure. Clearance of indocyanine green using dichromatic ear densitometry and computer and analysis provides a simple and sensitive method for mass screening of such patients. Clinical studies of lymphocyte reactivity to purified alcoholic hyaline may be valuable in recognizing alcoholic hepatitis, the precursor of cirrhosis. Ethanol toxicity, malnutrition and constitutional factors contribute to the development of hepatic fibrosis and cirrhosis in alcoholics. Ethanol and/or acetaldehyde and the supernatant from lymphocytes stimulated by alcoholic hyaline cause a significant increase in the incorporation of proline into collagen of the damaged liver. Abstinence and correction of nutrient deficits are the cornerstones of treatment for alcoholic liver disease; a daily meal and dietary supplements should be provided for those with liver injury who continue to imbibe. Alcoholics with progressive liver disease despite supportive therapy may be aided by pharmacologic agents which suppress immunologic response and reduce fibrogenesis.
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PMID:Liver disease of the alcoholic. 16 41

It is evident that ethanol by itself or one of its metabolites produces alterations in transport, metabolism and disposition of carbohydrates. Ethanol acts via changes in the redox state of co-factors; e.g. ethanol-induced hypoglycemia is due, partly, to the inhibition of hepatic gluconeogenesis by ethanol as a consequence of the increased NADH2/NAD ratio in patients whose glycogen stores are already depleted. On the other hand, hyperglycemia has also been described in patients with alcoholism. Although its mechanism is still obscure, abnormal hormonal secretion of insulin, catecholamines and glucocorticoids has been incriminated. Finally, structural changes of the liver and pancreas such as cirrhosis and pancreatitis produced by chronic alcohol consumption should also be considered as pathogenetic factors in a variety of clinical states involving deranged carbohydrate metabolism.
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PMID:Alcohol induced changes of carbohydrate metabolism [author's transl]. 70 66

Tests on 100 alcoholic patients revealed increased lipoprotein levels in 24%. Type IV was the most frequently ecountered (80%), followed by type II or V. The average plasma triglyceride level of the alcoholic group was significantly increased in comparison with a control population. The causal mechanism of alcoholic hyperlipoproteinemia remains poorly understood. The combination of a genetic defect of lipid metabolism, nutritional factors and acute alcohol excess may have an essential bearing on the incidence of hyperlipoproteinemia. Acute excessive intake of alcohol was significantly increased in comparison with alcoholic subjects wihtout hyperlipoproteinemia. The critical dose may be a daily ethanol consumption of about 200 gm. There appeared to be no correlation between acute pancreatic injury or active liver disease and serum lipid elevation. On the other hand, the observation was confirmed that alcoholic patients with hepatic cirrhosis usually do not develop hyperlipoproteinemia. Ethanol-induced hyperlipoproteinemia may be a risk factor for the development of atherosclerosis and pancreatitis.
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PMID:[Alcohol-induced hyperlipoproteinemia]. 91 92

Ethanol-1-14C method for the measurement of intrahepatic shunted blood flow was compared with the method of continuous infusion of D-galactose-1-14C. In controls, in chronic hepatitis, and in hepatic cirrhosis, per cent intrahepatic shunt measured by the ethanol-1-14C- method was about a half or one-third of that measured by the D-galactose-1-14C method. Study of radioactivity-dye concentration ratio of the blood sampled from the inferior vena cava showed that per cent intrahepatic shunt was underestimated by the ethanol-1-14C method because of permeability of ethanol-1-14C through the capillaries. In patients with hepatic carcinoma, in whom the carcinomatous tissue was supplied mainly by the hepatic artery, there was no significant difference in per cent intrahepatic shunt between both methods.
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PMID:Measurement of intrahepatic shunted blood flow by ethanol-1-14C method as compared with D-galactose-1-14C method. 96 99

Zinc deficiency is a concomitant of both alcoholism and cirrhosis, as indicated by plasma and tissue measurements in man. The intracellular sites of zinc distribution, the site-specific nature of alcohol/cirrhosis-related depletion, and the alcohol exposure-zinc depletion time function have not been reported. Spague-Dawley rats (16) at 5 to 6 weeks were given normal chow and 20 per cent ethanol as sole water source. Control animals (14) had tap water. In rats killed at 2, 5, 9, and 14 weeks, zinc levels were measured by atomic absorption spectroscopy in plasma (p); muscle tissue (MT), cell sap (MCS) cell sap-free (MCSF), and mitochondria (MM); liver tissue (LT), cell sap (MCS), cell sap-free fraction (LCSF), And mitochondria (LM). Control zinc levels were stable in all tissues over the 14-week study; p = 108, plus or minus 10 mug per 100 ml., MT = 125 plus or minus 18, MCS = 30.3 plus or minus 3, MCSF = 70 plus or minus 6, MM = 209 plus or minus 17, LT = 198 plus or minus 29, LCS = 125 plus or minus 11.0, LCSF = 79.5 plus or minus 11.2, and LM = 291 plus or minus 30 mug per gram of dry tissue. Ethanol-fed rats showed marked decrease in all liver zinc fractions from the earliest (2 weeks) time, with the greatest depletion in LM to 35 per cent of control. MT and p zinc showed monotonic gradual declines at the rate of 3 per cent per week, becoming statistically different from control at 9 weeks in both tissues. Normal weight gain occurred in control animals: alcohol rats gained 52 per cent of control to 5 weeks, and showed no subsequent gain, weighing 62 per cent of control levels at 14 weeks. Liver mitochondria contain the highest zinc concentration, and are most rapidly depleted. MT and p declines follow hepatic zinc loss.
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PMID:Distribution of zinc in skeletal muscle and liver tissue in normal and dietary controlled alcoholic rats. 117 Feb 68

Rats drank ethanol, on the average 1.20 g/100 g body weight, for various periods up to nearly 300 days. Experimental variables included a high-fat, low-protein diet, administration of additional ethanol by stomach tube, and CCl4 injections instead of ethanol. Growth was retarded by all the variables, especially by the high-fat, low-protein diet. The specific histological finding in the ethanol groups was the presence of Mallory bodies. Significant increase in total liver lipids was caused by ethanol, and rapid fat accumulation, inflammatory changes, and even fibrosis and cirrhosis by the high-fat, low-protein diet and the CCl4 injections. Ethanol raised the concentrations of collagen and soluble protein in the liver; the collagen content was increased also by the high-fat, low-protein diet and the CCl4 injections. The incorporation of proline to collagen was stimulated in incubated liver slices from both ethanol-treated and high-fat, low-protein-fed rats. These treatments also increased the concentration of free proline in the liver, thus augmenting the protein synthesis in fibroblasts.
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PMID:Effect of long-term administration of ethanol to the rat: lipids, collagen and other proteins, and Mallory bodies in the liver. 120 62

Ethanol metabolism and its influence on serum lactate/pyruvate ratio was studied after intravenous infusion of ethanol in 17 patients: 4 controls, 5 alcoholics with cirrhosis, 4 non-alcoholic cirrhotics and 4 alcoholics without liver disease. All refrained from the use of alcohol and drugs 4 weeks prior to the experiment. After maximal ethanol blood levels were achieved at the end of the infusion, ethanol removal occurred at two different rates. This was probably due to the fact that different volumes of ethanol were distributed with time: a fast period (30 to 60 min) and a slow period (60 to 180 min). The rates of disappearence in the two periods were similar in all groups which suggests that liver cirrhosis, independent of clinical severity and/or chronic alcoholism with previous abstinence from alcohol, does not modify ethanol metabolic rates in the liver. The relation lactate/pyruvate doubled in all cases but it occurred within 30 minutes in the groups without liver disease and within 60 minutes in the cirrhotics. This could account for the decreased liability of cirrhotic patients to alcohol hypoglycemia.
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PMID:Ethanol metabolism in liver cirrhosis and chronic alcoholism. 121 Oct 63

Forty-six patients with cirrhosis and 75 biopsy-proved hepatocellular carcinoma (HCC) nodules underwent percutaneous ethanol injection (PEI) regardless of number (up to five) and size (mean diameter, 3.6 cm) of tumoral lesions and clinical severity of cirrhosis (11 patients in Child's class C were included). Ethanol was injected under sonographic guidance through 20 to 22 gauge needles so as to obtain homogeneous hyperechogenicity of lesions. A total of 271 PEI sessions were carried out, delivering 2 to 14 ml per session. All nodules but one decreased in size, and seven were no longer appreciable on sonography. Recurrence was detected in two patients. The 3 year survival rate of all cases was 86%. Child's classes A and B patients fared better (3 yr survival 100%); 2 year survival of subjects with HCC < or = 3 cm was 92%. Multifocality did not affect survival. Most patients experienced mild pain at the site of injection, but only two major complications were encountered: partial chemical thrombosis of the left portal vein and cholangitis. Both cases were managed conservatively. In conclusion, PEI seems to offer a safe and valuable tool for therapy of HCC, especially in patients with good functional liver reserve and small (< or = 3 cm) tumors.
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PMID:Percutaneous ethanol injection under sonographic guidance of hepatocellular carcinoma in compensated and decompensated cirrhotic patients. 133 95

Cirrhosis was induced in Sprague-Dawley rats via ligation of the common bile duct. Changes in gastric blood flow and mucosal architecture were examined. Using an ex vivo gastric chamber preparation, the susceptibility of the cirrhotic gastric mucosa to injury by 20% ethanol was also examined. The gastric mucosa of cirrhotic animals was abnormal, even before ethanol administration. The macroscopically visible damage in these animals ranged from superficial hyperemia to epithelial sloughing. These gastric lesions were similar in appearance to the gastropathy described in cirrhotic patients, including "cherry-red spots" and areas of generalized erythema. Cirrhotic rats had a lower resting gastric transmucosal potential difference than control rats, and their gastric mucosa was also significantly more susceptible to damage by topical ethanol application. Ethanol administration caused a significant increase in gastric blood flow in control rats, whereas it significantly decreased gastric blood flow in cirrhotic rats. This lack of a reactive hyperemic response in cirrhotic rats may be responsible for the increased susceptibility of the gastric mucosa to ethanol-induced damage.
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PMID:Characterization of spontaneous and ethanol-induced gastric damage in cirrhotic rats. 149 5


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