Liver disease severity

Absolute contraindications to warfarin include active bleeding, hemorrhagic tendencies, pregnancy, and a history of warfarin-induced skin necrosis. It should be used with great caution in patients with a history of GI bleeding, recent neurosurgery, alcoholic liver disease, severe renal... 

Albumin has a molecular mass of approximately 66 000 and is synthesized at a rate of about 12 g, equal to 3% of total body albumin, per day to replace that which is degraded or lost. Impaired albumin synthesis and therefore a low plasma albumin concentration, is a hallmark of chronic liver disease. Several functions can be ascribed to albumin including osmotic (oncotic) pressure regulation of the plasma and a non-specific transport protein for ligands such as calcium, fatty acids, drugs and bilirubin. 

Liver disease, severe thrombocytopenia, obstructive cardiomyopathy. Acute phase of myocardial infarction. 

SAH hydrolase deficiency CBS deficiency Tyrosinemia type 1 Liver disease Severe protein malnutrition... 

Principles of drug use in liver disease Severity of liver disease... 

TABLE 7.4 Pugh Modification of Child s Classification of Liver Disease Severity ... 

FIGURE 7.4 Relationship between Child-Pugh stages of liver disease severity and extent of impairment in antipyrine breath test (ABT), galactose elimination capacity (GEC), sorbitol clearance, and indocyanine green clearance (ICG). (Adapted from data published by Herold C, Heinz R, Niedobitek G et al. Liver 2001 21 260-5.)... 

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 . 

Similarly, in various liver diseases, thought should be given to the presence of HE if neuropsychiatric disturbances occur. This is true for acute liver diseases (severe acute viral hepatitis, acute liver failure) and for severe (particularly alcohol-related) fatty liver, Wilson s disease, severe chronic hepatitis, severe infectious or parasitic liver diseases such as schistosomiasis, metastatic liver, nodular regenerative hyperplasia, and liver cirrhosis. (1,16,17, 22, 24,28,29, 67,76,78,95,104) The diagnosis of HE can prove difficult if the liver disease is (still) unknown. 

Another physicochemical parameter with some clinical correlation is the relative lipophilicity of different agents. Propranolol is by far the most lipophilic of the available P-blockers, and it enters the CNS far better than the less lipophilic agents, such as atenolol or nadolol. Lipophilicity as measured by octanol-water partitioning also correlates with the primary site of clearance, as seen in Table 13.8. The more lipophilic drugs are primarily cleared by the liver, whereas the more hydrophilic agents are cleared by the kidney. This could influence the choice of agents in cases of renal failure or liver disease. Several of the p-blockers must be dose adjusted in patients with impaired renal function, as indicated in Table 13.7. 

Current withdrawal fits or DTs (Ch.77) or seriously ill, e.g. decompensated liver disease, severe malnutrition... 

Vitamin K, preparations are preferred for the treatment of such medical conditions as liver disease, severe malabsorption syndromes, and anticoagulant overdosage. 

Apart from these two Vertex compounds, only one other caspase inhibitor, BDN-6556, has been used in clinical trials. This compound belongs to the class of oxamyl dipeptides and was originally developed by Idun Pharmaceuticals (taken over by Pfizer). It is the only pan-caspase inhibitor that has been evaluated in humans. BDN-6556 displays inhibitory activity against all tested human caspases. It is also an irreversible, caspase-specific inhibitor that does not inhibit other major classes of proteases, or other enzymes or receptors. The therapeutic potential of BDN-6556 was first evaluated in several animal models of liver disease because numerous publications suggested that apoptosis contributes substantially to the development of some hepatic diseases, such as alcoholic hepatitis, hepatitis B and C (HBV, HCV), non-alcoholic steato-hepatitis (NASH), and ischemia/reperfusion injury associated with liver transplant. Accordingly, BDN-6556 was tested in a phase I study. The drug was safe and... 

Amino acids promote the production of proteins, enhance tissue repair and wound healing, and reduce the rate of protein breakdown. Amino acids are used in certain disease states, such as severe kidney and liver disease, as well as in TPN solutions. (See the last section of this chapter for a more detailed discussion of TPN.) TPN may be used in patients with conditions such as impairment of gastrointestinal absorption of protein, in patients with an increased requirement for protein, as seen in those with extensive bums or infections, and in patients with no available oral route for nutritional intake ... 

Hepatitis C infection has an unpredictable natural history with significant potential for causing severe liver disease and variable response to current therapy based on pretreatment factors. Therefore, HCV is an excellent model to describe the... 

At present, severe ai-antitrypsin deficiency liver disease can be successfully treated by liver transplantation. In the future, introduction of the gene for normal ttj-antitrypsin into hepatocytes may become possible, but this would not stop production of the PiZ protein. Figure 50-7 is a scheme of the causation of this disease. 

The substrate phenyl phosphate, which is hydrolyzed by the serum acid phosphatases originating from many tissues, has been used in most of the published studies. Total serum acid phenylphos-phatase is elevated in diseases of the liver, disease of bone such as Paget s disease, and several blood dyscrasias, especially those involving platelets (99>100). 

Hemophilia or other hemorrhagic tendencies Severe liver disease with elevated baseline PT Severe thrombocytopenia (platelet count less than 20,000) Malignant hypertension... 

Progression of alcoholic liver disease moves through several distinct phases from development of fatty liver to the development of alcoholic hepatitis and cirrhosis. Fatty liver and alcoholic hepatitis may be reversible with cessation of alcohol intake, but cirrhosis itself is irreversible. Although the scarring of cirrhosis is permanent, maintaining abstinence from alcohol can still decrease complications and slow development to end-stage liver disease.22 Continuing to imbibe speeds the advancement of liver dysfunction and its complications. 

Disulfiram works by irreversibly blocking the enzyme aldehyde dehydrogenase, a step in the metabolism of alcohol, resulting in increased blood levels of the toxic metabolite acetaldehyde. As levels of acetaldehyde increase, the patient experiences decreased blood pressure, increased heart rate, chest pain, palpitations, dizziness, flushing, sweating, weakness, nausea and vomiting, headache, shortness of breath, blurred vision, and syncope. These effects are commonly referred to as the disulfiram-ethanol reaction. Their severity increases with the amount of alcohol that is consumed, and they may warrant emergency treatment. Disulfiram is contraindicated in patients who have cardiovascular or cerebrovascular disease, because the hypotensive effects of the disulfiram-alcohol reaction could be fatal in such patients or in combination with antihypertensive medications. Disulfiram is relatively contraindicated in patients with diabetes, hypothyroidism, epilepsy, liver disease, and kidney disease as well as impulsively suicidal patients. 

Biguanides such as metformin are thought to inhibit mitochondrial oxidation of lactic acid, thereby increasing the chance of lactic acidosis occurring. Fortunately, the incidence of lactic acidosis in clinical practice is rare. Patients at greatest risk for developing lactic acidosis include those with liver disease or heavy alcohol use, severe infection, heart failure, and shock. Thus, it is common practice to evaluate liver function prior to initiation of metformin. 

The incidence of liver complications associated with PN ranges from approximately 7% to 84%, and end-stage liver disease develops in as many as 15% to 40% of adult patients on long-term PN.35 Patients often develop a mild increase in liver enzymes within 1 to 2 weeks of initiating PN, but this generally resolves when PN is discontinued. Severe liver complications include hepatic steatosis (fat deposition in liver), steatohepatitis (a severe form of liver disease characterized by hepatic inflammation that may progress rapidly to liver fibrosis and cirrhosis), cholestasis, and cholelithiasis.35... 

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. 

Although as many as 20% of patients with chronic hepatitis C may be coinfected with HGV/GB V-C, coinfection does not appear to influence the severity of liver disease or response to interferon-a therapy (Martinot et al., 1997). 

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