Cirrhosis chronic liver disease

Cirrhosis Chronic liver disease caused by chronic ethanol poisoning. Other hepatox-icants may also cause cirrhosis. 

There is very little evidence relating to the role of ROMs in cholestatic liver disease. Serum selenium and glutathione peroxidase activity are decreased in humans with intrahepatic cholestasis of pregnancy (Kauppila et al., 1987). Low levels of vitamin E have been reported in patients with primary biliary cirrhosis, and in children with Alagille s syndrome or biliary atresia (Knight et al., 1986 Jeffrey etal., 1987 Lemonnier etal., 1987 Babin etal., 1988 Kaplan et al., 1988 Sokol etal., 1989). Serum levels of Mn-SOD are increased in patients with all stages of primary biliary cirrhosis compared with patients with other forms of chronic liver disease, although whether this causes or results from the disease process is unclear (Ono etal., 1991). 

Jeffrey, G.P., Muller, D.P.R., Burroughs, A.K., Matthews, S., Kemp, C., Epstein, O., Metcalfe, T.A., Southam, E., Tazir-Melbourcy, M., Thomas, P.K. and McIntyre, N. (1987). Vitamin E deficiency and its clinical significance in adults with primary biliary cirrhosis and other forms of chronic liver disease. J. Hepatol. 4, 307-317. 

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. 

Cirrhosis A liver disease commonly associated with chronic alcohol misuse and characterised by the replacement of once-healthy hepatocytes with abnormal connective tissue. 

Medical indications Chronic pulmonary disease (excluding asthma) chronic cardiovascular diseases, diabetes mellitus chronic liver diseases, including liver disease as a result of alcohol abuse (e.g., cirrhosis) chronic alcoholism, chronic renal failure or nephrotic syndrome functional or anatomic asplenia (e.g, sickle cell disease or splenectomy [if elective splenectomy is planned, vaccinate at least 2 weeks before surgery]) immunosuppressive conditions and cochlear implants and cerebrospinal fluid leaks. Vaccinate as close to HIV diagnosis as possible. 

Most drugs used in anaesthesia are metabolised in the liver by phase I reactions, mediated by cytochrome P-450 enzymes. These are susceptible to destruction by cirrhosis, so that the biotransformation of drugs, such as opioids (except morphine), benzodiazepines, barbiturates, and inhalational agents, may be markedly altered in severe liver disease. These enzymes are found in the centrilobular areas, which are more prone to hypoxia. In contrast, the enzymes responsible for phase II reactions, found predominantly in the peripheral areas, often function normally even in advanced disease. The disposition of benzodiazepines that are eliminated primarily by glucuronidation, e.g. lorazepam and oxazepam, are unaffected by chronic liver disease. For drugs with low hepatic extraction, advanced hepatocytic dysfunction decreases phase I and II biotransformation with a reduced clearance and prolongation of the elimination half-life. This is often partially offset by an increased free fraction due to decreased protein binding. 

Portal hypertension most commonly occurs as a consequence of chronic liver disease. Portal hypertension Is caused by Increased blood flow within the portal venous system and increased resistance to portal flow within the liver. Splanchnic blood flow is increased in patients with cirrhosis due to low arteriolar resistance that is mediated by increased circulating vasodilators and decreased vascular sensitivity to vasoconstrictors. Intrahepatic vascular resistance is increased in cirrhosis due to fixed fibrosis within the spaces of Disse and hepatic veins as well as reversible vasoconstriction of hepatic sinusoids and venules. Among the consequences of portal hypertension are ascites, hepatic encephalopathy, and the development of portosystemic collaterals—especially gastric or esophageal varices. Varices can rupture, leading to massive upper gastrointestinal bleeding. 

A 70-year-old woman with a 2-year history of primary biliary cirrhosis confirmed by histological and immunological criteria took colestyramine sachets twice daily for 2 months and developed lethargy, confusion, and drowsiness (3). She had signs of chronic liver disease, portal hypertension, and hepatic encephalopathy. Laboratory investigations confirmed a metabolic acidosis (pH 7.15) and hyperchloremia. Multiple cultures failed to reveal sepsis, and a urinary pH of 4.85 together with tests of renal acidification excluded renal tubular acidosis. No other cause was found and she responded to 600 mmol of sodium bicarbonate intravenously over 36 hours. 

CIRRHOSIS A chronic liver disease that is caused by alcohol abuse, toxins, nutritional deficiency, or infection. A main symptom of cirrhosis is portal hypertension. 

T. Sawamura, H. Nakada, H. Hazama, Y. Shiozaki, Y. Sameshima, and Y. Tashiro, Hyperasialoglycoproteinemia in patients with chronic liver diseases and/or liver cell carcinoma. Asialoglycoprotein receptor in cirrhosis and liver cell carcinoma, Gastroenterology 87 1217-1221 (1984). 

Alcohol intake is the most important cause of liver cirrhosis in the Western world [2]. Data from the World Health Organization show that the incidence of chronic liver disease and cirrhosis associated with alcohol in the UK is 10.42 per 100 000 people [3]. Interestingly, only around... 

Depending on the nature of the chronic liver disease, the biliary tract may or may not be affected, and hence bilirubin and alkaline phosphatase may be normal or raised. For example, a patient with primary biliary cirrhosis (PBC) can have an alkaline phosphatase and bilirubin raised to twice ULN. Where there is biliary involvement there is the potential for reduced fat-soluble vitamin absorption. ITence a raised alkaline phosphatase may have occurred over time owing to decreased vitamin D absorption affecting bone development, rather than being associated with the liver. Likewise, the clotting may be abnormal because of vitamin K deficiency. 

Other studies have also demonstrated similar increases in half-life when comparing paracetamol pharmacokinetics in patients with decompensated chronic liver disease to normal subjects. Patients with cirrhosis who have a normal plasma albumin concentration and PT have been shown to have a similar paracetamol half-life and clearance to those of healthy subjects. However, cirrhotic patients with a low plasma albumin and an increased PT were found to have a prolonged paracetamol half-life. Despite this, no accumulation and no evidence of hepatotoxicity was demonstrated when therapeutic doses of paracetamol were given to patients with decompensated liver diseases for three to five days [21]. 

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... 

Portosystemic encephalopathy (PSE) develops in chronic liver diseases and/or in the wake of portosystemic circulation. Liver cirrhosis with its hepatofugal collateral circulatory pathway is thus the focus of interest in this clinical form of disease. The term PSE is identical to exogenous liver coma or liver cell failure coma . PSE can be further subdivided according to its symptomatology and depending on its form and degree of severity. There are three forms of portosystemic encephalopathy (1.) subclinical (or latent) PSE, (2.) acute or acute recurrent (episodic) PSE, and (i.) chronic recurrent or chronic persistent PSE. 

It is not clearly understood why in some cases oedema without ascites and in other cases ascites without oedema as well as ascites together with oedema or even pleural effusion without ascites occur. Ascites develops most frequently during the course of liver disease (= hepatogenic ascites), in particular in chronic liver diseases with portal hypertension (= portal ascites), (s. tab. 16.7) Various mechanical, biochemical and neural disorders overlap in their effects and pathways, depending on the underlying liver disease. Only rarely is ascites found in diseases with presinusoidal localization of portal hypertension (such as portal vein thrombosis) or with minor restrictions in the synthesis of albumin (as in biliary cirrhosis). Formation of ascites occurs in about 50% of all cirrhotic patients within 10 years of... 

Disorders of cerebral functions on the one hand and of the water and electrolyte balance on the other hand are the earliest and most reliable hints of the onset of decompensation in severe liver disease, especially cirrhosis. In clinical terms, they can be easily diagnosed as latent hepatic encephalopathy (by carrying out psychometric tests) and/or latent oedema (by recording the increase in body weight). For this reason, these examination methods are also of fundamental importance in the follow-up of chronic liver disease, (s. fig. 15.3)... 

Latent and compensated forms of consumptive coagulopathy frequently occur in the course of severe acute or chronic liver disease. In 80-85% of cirrhosis patients, the values of at least one basic test (thrombocytes. Quick s value, fibrinogen, AT III, bleeding time) are pathological. In 15-30% of cases, clinically relevant haemorrhagic diathesis evolves. 

Chronic liver insufficiency is due to the progression of an already existing chronic liver disease. This generally tends to be advanced cirrhosis of varied aetiology. Basically, however, any liver disease can be a potential cause of chronic liver insufficiency. Alcohol and infections as well as certain medicaments are also deemed to be common causes. A great number of substances and events can trigger liver insufficiency. 

In 1980 the term non-alcoholic steatohepatitis (NASH) was introduced by J. Ludwig et al. to denote chronic liver disease with increased enzymatic activity and the histological picture of alcohol-induced hepatitis. (60) The histological feature itself was described by H. Thaler as early as 1962 in his paper Fatty liver and its relationship to cirrhosis . (76) Over the following years, transition from a diabetic fatty liver into cirrhosis was reported (S. Iron et al., 1979) as well as from an obesity-induced fatty liver into cirrhosis (M. Adler et al., 1979). 

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