Liver cirrhosis causes

Adverse consequences of drinking include a variety of social, legal, medical, and psychiatric problems (Babor et al. 1987, 2003). Alcohol is among the top four causes of mortality in 1988, 107,800 deaths, or about 5% of all deaths in the United States, were attributed to alcohol-related causes (Stinson and DeBakey 1992). Approximately 17% of alcohol-related deaths were directly attributable to alcohol, 38% resulted from diseases indirecdy attributable to alcohol, and 45% were attributable to alcohol-related traumatic injury (U.S. Department of Health and Human Services 1994). Alcohol-related mortality declined during the latter part of the twentieth century. For example, the age-adjusted mortality rate from liver cirrhosis in 1993 (7.9 deaths per 100,000 persons) was just over half the rate in 1970 (14.6 deaths per 100,000) (Saadat-mand et al. 1997), and the proportion of automobile fatalities that was related to the use of alcohol fell to a two-decade low of 33.6% in 1993 (Lane et al. 1997). 

Steatohepatitis A severe form of liver disease caused by fat deposition in the liver, characterized by hepatic inflammation that may rapidly progress to liver fibrosis and cirrhosis. 

Chronic forms of hepatitis (in particular B, C and D) can result in liver cirrhosis and/or hepatocellular carcinoma. This occurs in up to 20 per cent of chronic hepatitis B sufferers and in up to 30 per cent of chronic hepatitis C sufferers. The scale of human suffering caused by hepatitis on a worldwide basis is enormous. Approximately 5 per cent of the global population suffer from chronic hepatitis B. An estimated 50 million new infections occur each year. Over 1.5 million of the 300 million carriers worldwide die annually from liver cirrhosis and hepatocellular carcinoma. 

Liver Methotrexate causes hepatotoxicity, fibrosis, and cirrhosis, but generally only after prolonged use. Acutely, liver enzyme elevations are frequent, usually transient and asymptomatic, and also do not appear predictive of subsequent hepatic disease. Liver biopsy after sustained use often shows histologic changes, and fibrosis and cirrhosis have occurred these latter lesions often are not preceded by symptoms or abnormal liver function tests (see Precautions). For this reason, periodic liver biopsies are usually recommended for psoriatic patients who are under long-term treatment. Persistent abnormalities in liver function tests may precede appearance of fibrosis or cirrhosis in the RA population. 

Two studies were located that reported the occurrence of liver cancer in humans exposed to carbon tetrachloride fumes, both acutely (Tracey and Sherlock 1968) and for longer periods (Johnstone 1948). In the former case, a male died of hepatocellular carcinoma 7 years after acute intoxication with carbon tetrachloride at an age of 59, although he had a history of moderate alcohol consumption (without demonstrable liver cirrhosis). In the second case, a 30- year-old female died of "liver cancer" after 2-3 years of occupational exposure to carbon tetrachloride that was sufficient to produce signs of intoxication. However, this evidence is much too sparse to establish a cause-and-effect relationship. 

Liver disease is the most common medical complication of alcohol abuse an estimated 15-30% of chronic heavy drinkers eventually develop severe liver disease. Alcoholic fatty liver, a reversible condition, may progress to alcoholic hepatitis and finally to cirrhosis and liver failure. In the United States, 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. Concurrent infection with hepatitis or C virus increases the risk of severe liver disease. 

A third type of dose response relationship has been proposed, which is increasingly gaining acceptance, and this is the hormetic kind. This kind of dose response, for which there is experimental evidence, involves opposite effects at low doses, giving rise to a U-shaped or J-shaped curve (Fig. 2.11). That is, there may be positive or stimulatory beneficial effects at low doses. For example, some data indicate that at low doses of dioxin, the incidence of certain cancers in animals exposed is less than occurs in controls. Another example is alcohol (ethanol), for which there is evidence from a number of studies that low to moderate intake in man leads to lower levels of cardiovascular disease. Of course, high levels of intake of alcohol are well established to cause liver cirrhosis, various cancers, and also damage to the cardiovascular system. 

This is a chronic lesion resulting from repeated injury and subsequent repair. It may result from either hepatocyte damage or cholestatic damage, each giving rise to a different kind of cirrhosis. Thus, carbon tetrachloride will cause liver cirrhosis after repeated exposure, but also compounds, which do not cause acute necrosis, such as ethionine and alcohol may cause cirrhosis after chronic exposure. 

Carbon tetrachloride is a hepato toxic solvent, which causes centrilobular necrosis and fatty liver, liver cirrhosis, and tumors and kidney damage after chronic exposure. It is metabolized... 

Carbon tetrachloride causes centrilobular liver necrosis and steatosis after acute exposure, and liver cirrhosis, liver tumors, and kidney damage after chronic administration. The mechanism underlying the acute toxicity to the liver involves metabolic activation by cytochrome P-450 to yield a free radical (trichloromethyl free radical). This reacts with unsaturated fatty acids in the membranes of organelles and leads to toxic products of lipid peroxidation including malondialdehyde and hydroxynonenal. This results in hepatocyte necrosis and inhibition of various metabolic processes including protein synthesis. The latter leads to steatosis as a result of inhibition of the synthesis of lipoproteins required for triglyceride export. 

Several metal ions are essential or beneficial to life while others, such as lead, cadmium or mercury, are highly detrimental. Many diseases have been associated in a way or another to altered metal ion concentrations in the body. Deficiencies can be as damaging as overloads. Copper deficiency has been associated to anemia while excess copper can lead to Wilson s disease (liver cirrhosis). Anemia may also be caused by a lack of iron and overload of this same metal ion is connected to thalassemia and siderosis [122]. In vivo determination of metal ion distribution is thus highly desirable and progresses have been made towards the design of MRI contrast agents sensitive to the concentration of metal ions. 

The option to remove the toxin from the environment of susceptible persons is taken in hemochromatosis, a common disorder of iron metabolism(101) that affects 1 in 300 persons of northern European descent. Most cases of hereditary hemochromatosis are attributed to a polymorphism of HFE, which results in substitution of tyrosine for cysteine at codon 282. The disease, untreated, causes liver cirrhosis, heart failure, diabetes and arthritis and leads to early death treatment by phlebotomy to remove excess iron allows affected persons to live a normal life span. 

Liver cirrhosis is among the top 10 causes of death in the Western world. The disease occurs after chronic damage to hepatic cells, mainly hepatocytes, which can be caused by viral hepatitis, chronic alcohol abuse or toxic injury, biliary disease, and metabolic liver disorders [64], Liver cirrhosis is characterized by an abnormal deposition of connective tissue in the liver, which hampers the normal functions of the liver. Other features of the disease are general tissue damage, chronic inflammation, and the conversion of normal liver architecture into structurally abnormal nodules. Secondary to these anatomical changes are disturbances in the liver function and in the hemodynamics leading to portal hypertension and intrahepatic shunting [39, 64, 103],... 

Exposure to the dichlorobenzenes is also most likely to occur through inhalation or contact. These compounds are irritants and tend to damage the same organs as monochlorobenzene. The 1,4- isomer has been known to cause profuse rhinitis (running nose), nausea, weight loss associated with anorexia, jaundice, and liver cirrhosis. The di- and tetrachlorobenzenes are considered to be moderately toxic by inhalation and ingestion. 

Progressive fibro-proliferative diseases (e.g. liver cirrhosis, pulmonary fibrosis, rheumatoid arthritis) result in a dramatic increase in collagen synthesis [227], This is preceded by inflammation that correlates with an increased activity of proline and lysine hydroxylase [228], Although they are unlikely to be the primary initiators of these diseases the increased activities of these enzymes may cause other problems. For example, in vitro the enzyme can turn over in the absence of a peptide substrate (but the presence of the 2-oxoglutarate cofactor). In this case stoichiometric amounts of ascorbate are required, probably to reduce the ferryl ion back to ferrous [229]. In vivo, lower concentrations of ascorbate are utilised [229,230], possibly to reactivate the enzyme after a non-productive activation (for example in the presence of a peptide that can bind to the active site, but cannot be hydroxylated). As the amount of proline-hydroxylase activity increases in the fibro-proliferative diseases, the concentration of ascorbate might not be sufficient to reduce these inactive complexes, resulting in the formation of potentially reactive ferryl intermediates. 

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