Liver disease decompensated

Table 4.3 summarises the potential extent of change in each individual LFT for an example patient with compensated chronic liver disease, decompensated chronic liver disease, hepatitis, hyperacute liver failure and cholestasis. This is a snapshot of the changes that may occur in these conditions however, if each patient s results were observed over time a range of results would be seen. 

Patient 4 Alcoholic liver disease Decompensated cirrhosis... 

Ascites is the accumulation of fluid in the peritoneal space and is often one of the first signs of decompensated liver disease. Ascites is the most common complication of cirrhosis and portends a dire prognosis.14... 

Contraindications to treatment include autoimmune hepatitis, decompensated liver disease, women who are pregnant or patients whose female partners are pregnant, hemoglobinopathies, creatinine clearance <50 mL/ min, hemodialysis, or ischemic cardiovascular or cerebrovascular disease. 

Decompensated liver disease is complicated by jaundice, refractory ascites, bacterial peritonitis, coagulopathy, and variceal bleeding and may require liver transplantation. The number of liver transplants for decompensated cirrhosis doubled from 1990 to 2004, when 5845 cadaveric (orthotopic) liver transplants were performed (65). 

Peginterferon alfa-2b Hypersensitivity to peginterferon alfa-2b or any component of the product autoimmune hepatitis decompensated liver disease. 

Peginterferon alfa-2a treatment results in more sustained responses than simple interferon alpha, although relapse is not uncommon. Such treatment should generally be avoided in those receiving immunosuppressants and those with decompensated liver disease. Lamivudine, a reverse transscriptase inhibitor is often used in initial treatment and in decompensated liver disease. 

The most common adverse effects of lamivudine seen at doses used to treat HBV are mild they include headache, malaise, fatigue, fever, insomnia, diarrhea, and upper respiratory infections. Elevated alanine aminotransferase (ALT), serum lipase, and creatine kinase may also occur. The safety and efficacy of lamivudine in patients with decompensated liver disease have not been established. Dosage adjustment is required in individuals with renal impairment. Coadministration of trimethoprim-sulfamethoxazole decreases the renal clearance of lamivudine. 

Perrillo, R., C. Tamburro, P. Regenstein, et al., Low-dose titratable interferon alfa in decompensated liver disease caused by chronic infection with hepatitis B virus. Gastroenterology, 1995.109 908-16. 

Oral bioavailability of adefovir dipivoxil is about 59% and is unaffected by meals it is rapidly and completely hydrolyzed to the parent compound by intestinal and blood esterases. Protein binding is low (< 5%). The intracellular half-life of the diphosphate is prolonged, ranging from 5 to 18 hours in various cells this makes once-daily dosing feasible. Adefovir is excreted by a combination of glomerular filtration and active tubular secretion and reguires dose adjustment for renal dysfunction however, it may be administered to patients with decompensated liver disease. 

The pharmacokinetics of lamivudine are described earlier in this chapter (see section, Nucleoside and Nucleotide Reverse Transcriptase Inhibitors). The more prolonged intracellular half-life in HBV cell lines (17-19 hours) than in HIV-infected cell lines (10.5-15.5 hours) allows for lower doses and less ffeguent administration. Lamivudine can be safely administered to patients with decompensated liver disease. 

Typical side effects are constitutional in nature, including a flu-like syndrome within 6 hours after dosing in more than 30% of patients that tends to resolve upon continued administration. Other potential adverse effects include thrombocytopenia, granulocytopenia, elevation in serum aminotransferase levels, induction of autoantibodies, nausea, fatigue, headache, arthralgias, rash, alopecia, anorexia, hypotension, and edema. Severe neuropsychiatric side effects may occur. Absolute contraindications to therapy are psychosis, severe depression, neutropenia, thrombocytopenia, symptomatic heart disease, decompensated cirrhosis, uncontrolled seizures, and a history of organ transplantation (other than liver). Alfa interferons are abortifacient in primates and should not be administered in pregnancy. 

VecchiM, FolliC, Donato MF, Formenti S, Arosio E, deFranchisR. High rate of positive anti-tissue transglutaminase antibodies in chronic liver disease. Role of liver decompensation and of the antigen source. Scand J Gastroenterol 2003 38 50-54. 

Hemoglobinopathy (such as thalassemia major and sickle-ceU anemia) Decompensated liver disease Autoimmune diseases Renal function impairment... 

In chronic liver disease, PT may increase over a period of weeks or months to values up to about 30 seconds as the liver decompensates. In patients with acute liver failure the values may increase to over 100 seconds within a few hours. 

In most cases the onset of ascites is a sign of decompensated severe chronic liver disease and impaired liver function. However, it can also be present in non-liver conditions such as malnutrition, heart failure and nephrotic syndrome. 

Malnutrition is found in 80-100% of patients with decompensated liver disease, and in up to 40% of those with compensated disease. As the disease progresses patients become malnourished. Dry weight decreases, as they often reduce their food intake due to anorexia, malabsorption. 

This is helpful because it gives you clues as to what sort of liver picture you should expect to see in your patient. For example, if they have autoimmune hepatitis they will have a hepatic picture of liver dysfunction, which could range from mild fibrosis with fairly normal liver function to cirrhosis which may be decompensated - you can look for signs and symptoms to help yon decide how advanced their liver disease is. 

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]. 

Based on their pharmacokinetic profile alone, the safest statins in chronic compensated liver disease and a history of decompensation are prohahly pravastatin and rosnvastatin. However, clinical experience with rosnvastatin in liver disease is lacking, and so it cannot be recommended. In addition, the true rate of post-marketing adverse drug reactions is not yet clear. Pravastatin is therefore the drug of choice in these patients, where treatment is deemed necessary. It should, however, be avoided in acute episodes until liver function or transaminases stabilise/return to normal. 

In 2006 the National Lipid Association s Statin Safety Assessment Task Force concluded that chronic liver disease and compensated liver disease are not contraindications to the use of statins, but that they are contraindicated in decompensated disease or liver failure [2, 3] see Hepatic Adverse Effects. 

Niacin and acipimox should be relatively safe to use in the absence of varices, gastritis, coagulopathy, thrombocytopenia or a history of decompensation. Both can cause pruritus, which is common in cholestatic liver disease. The extended release formulation of niacin (Niaspan Prolonged Release) may cause hepatitis and LFTs should be monitored. 

A 2006 review by the National Lipid Association s Statin Safety Assessment Task Force concluded that hepatic function does not appear to be compromised by statin use and that there was no apparent link between elevations in LFTs and the development of liver toxicity. They noted that TFT monitoring may itself be of little value in the absence of other symptoms of liver toxicity, but should be performed for medicolegal reasons, as it is recommended in the product SPCs. The expert group concluded that the use of statins is not contraindicated in chronic and compensated liver disease, but that it is contraindicated in decompensated disease or liver failure [2, 3]. 

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