Chronic alcoholic liver disease

Feher, J., Deak, G., Muezes, G., Lang, I., Niderland, V., Nekam, K., and Karteszi, M. 1989. Hepatoprotective activity of silymarin ligalon therapy in patients with chronic alcoholic liver diseases. Orv. Hetil. 130(51), 2723-2727. 

Feher J, Lang I, Nekam K, Gergely P, Muzes G. Hepaprotective activity of sil)anarin therapy in patients with chronic alcoholic liver disease. Orv Hetil 1990 130 51. 

The patient may appear well-nourished or have coexistent signs of malnutrition and chronic alcoholic liver disease. 

Rodriguez-Moreno, F., Gonz es-Reimers, E., Santolaria-Femandez, F., Galindo-Martin, L., Hemandez-Torres, O., Batista-Lopez, N., and Molina-Perez, M. (1997). Zinc, copper, manganese, and iron in chronic alcoholic liver disease. Alcohol 14, 39-44. 

Rodriguez-Moreno F, Gonzalez-Reimers E, Santolaria-Fernandez F, et al. Zinc, copper, manganese and iron in chronic alcoholic liver disease. Alcohol 1997 14 39-44. 

The incidence of thiamine deficiency in alcoholics is 30-80% (Homewood and Bond, 1999). Factors that promote thiamine deficiency in alcoholics include poor thiamine intake, decreased activation of thiamine to thiamine pyrophosphate(TPP), decreased hepatic storage, decreased intestinal thiamine transport and impairment of thiamine absorption (see Table 14.3) (Breen et al, 1985 Hoyumpa, 1980). Although thiamine is stored in various sites, including skeletal muscles, heart, kidneys and brain, the Uver remains the main storage site. Due to the reasons cited above, hepatic thiamine content may be reduced by 73% in patients with severe, chronic alcoholic liver disease. In addition, ethanol has been shown to promote thiamine release from the liver (Hoyumpa, 1980). 

Carbone DL, Doom JA, Kiebler Z, Ickes B.R, Petersen DR. Modification of heat shock protein 90 by 4-hydroxynonenal in a rat model of chronic alcoholic liver disease. J Pharmacol Exp Ther 2005 315 8-15. 

Cirrhosis is the result of long-term insult to the liver, so damage is typically not evident clinically until the fourth decade of life. Chronic liver disease and cirrhosis combined were the 12th leading cause of death in the United States in 2002. In patients between the ages of 25 and 64, damage from excessive alcohol use accounted for over one-half of the deaths.2 Alcoholic liver disease and viral hepatitis are the most common causes of cirrhosis in the United States and worldwide. 

The main indications for liver transplantation include chronic hepatitis C, alcoholic liver disease, nonalcoholic fatty liver disease, and cryptogenic cirrhosis. 

Patients with psoriasis or RA who have any of the following alcoholism, alcoholic liver disease, or other chronic liver disease overt or laboratory evidence of immunodeficiency syndromes preexisting blood dyscrasias (eg, bone marrow hypoplasia, leukopenia, thrombocytopenia, significant anemia). 

The main acute effect is inebriation, which in turn spawns violence, spousal and child abuse, crime, motor vehicle accidents, workplace and home accidents, drowning, suicide, and accidental death. The chronic effects include alcoholism, liver disease, various forms of cancer, brain disorders, cardiovascular disease and other organ system effects, absence from or loss of work, family dysfunction, and malnutrition. 

Pharmacokinetics Poorly absorbed from the G1 tract. Protein binding greater than 98%. Metabolized in the liver. Minimally eliminated in urine. Plasma levels are markedly increased in chronic alcoholic hepatic disease, but are unaffected by renal disease. Half-life 14 hr. 

Liver disease is the most common medical complication of alcohol abuse it is estimated that 15-30% of chronic heavy drinkers eventually develop severe liver disease. Clinically significant alcoholic liver disease may be insidious in onset and progress without evidence of overt nutritional abnormalities. Alcoholic fatty liver, a reversible condition, may progress to alcoholic hepatitis and finally to cirrhosis and liver failure. In the USA, chronic alcohol abuse is the leading cause of liver cirrhosis and of the need for liver transplantation. The risk of developing liver disease is related both to the average amount of daily consumption and to the duration of alcohol abuse. Women appear to be more susceptible to alcohol hepatotoxicity than men. Another factor that increases the risk of severe liver disease is concurrent infection with hepatitis B or C virus. 

Milk thistle has been used to treat acute and chronic viral hepatitis, alcoholic liver disease, and toxin-induced liver injury in human patients. Milk thistle has most often been studied in the treatment of alcoholic hepatitis and cirrhosis. In both of these disorders, outcomes have been mixed and reports include significant reductions in markers of liver dysfunction and in mortality, as well as no effect. In acute viral hepatitis, studies have generally involved small sample sizes and have shown mixed outcomes of improved liver function (eg, aminotransferase values, bilirubin, prothrombin time) or no effect. Studies in chronic viral hepatitis and toxin-induced injury have also been of small size but have reported mostly favorable results. Parenteral silybin is marketed and used in Europe as an antidote in Amanitaphalloides mushroom poisoning, based on favorable outcomes reported in case-control studies. 

Chronic alcohol consumption can induce CYP450 enzymes, whereas acute alcohol intake can inhibit cytochrome P450 enzymes. Prediction of drug handling in alcoholic liver disease is therefore complicated. 

Cirrhosis occurs most frequently in the setting of alcoholic liver disease and represents the final common pathway of a number of chronic liver diseases. The development of cirrhosis is characterized by the appearance of fibroblasts and collagen deposition. This is accompanied by a reduction in liver size and the formation of nodules of regenerated hepatocytes. As a result, total liver content of cytochrome P450 is reduced in these patients. Initially, fibroblasts deposit collagen fibrils in the sinusoidal space, including the... 

Liver diseases severe acute (necrotic) hepatitis, chronic hepatitis, chronic alcoholic liver damage, liver cirrhosis, cardiac liver, liver abscess, liver tumours and liver metastases, toxic liver damage, etc. A severe and, above all, constant reduction in ChE activity (e. g. < 500 U/1) is usually suggestive of an unfavourable prognosis and the foreseeable moment of liver death . 

When treating alcoholic liver diseases, it should be taken into account that one is generally dealing with chronic alcoholics. Therefore, one should be aware of the fact that a withrawal syndrome might occur, possibly requiring the application of clomethiazole, haloperidol or clonidine. In this complicated phase, the administration of zinc is likewise recommended. (138)... 

Baldi, E., Burra, P., Plebani, M., Salvagnini, M. Serum malondialde-hyde and mitochondrial aspartate aminotransferase activity as markers of chronic alcohol intake and alcoholic liver disease. Ital. J. Gastroenterol. 1993 25 429 - 432... 

Sarin, S.K., Dhingra, N., Bansal, A., Malhotra, S., Guptan, R.C. Dietary and nutritional abnormalities in alcoholic liver disease a comparison with chronic alcoholics without liver disease. Amer. X Gastroenterol. 1997 92 777-783... 

Hertelendy ZI, Mendenhall CL, Rouster SD, et al. Biochemical and clinical effects of aspartame in patients with chronic, stable alcoholic liver disease. Am J Gastroenterol 1993 88(5) 737-43. 

Duration and magnitude of alcohol ingestion. Alcoholic liver disease does not occur in all individuals with chronic ethanol intake, but there is a threshold intake of 40g/day in men and lOg/day in women below which alcoholic hepatitis does not occur. For most individuals, the risk dose is about 80 g of alcohol (200 mL of whiskey or equivalent) per day. Daily drinking appears to be riskier than intermittent drinking. 

While cirrhosis has many causes (Table 37-1), in the United States excessive alcohol intake and chronic viral hepatitis (types B and C) are the most common causes. A breakdown of the indications for liver transplantation (Table 37-2) provides an estimate of the clinical frequency for each of the potential causes of cirrhosis, as transplant represents the deflnitive therapeutic strategy for cirrhosis. These data underestimate alcoholic liver disease, as these patients are often not considered suitable transplant candidates. 

Chronic inflammatory liver diseases Malignancies Carcinoma Lymphoma Leukemia Multiple myeloma Less common causes Alcoholic liver disease Congestive heart failure Thrombophlebitis Chronic obstructive lung disease Ischemic heart disease... 

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