Hepatic disease drug-induced

Many patients have underlying liver disease with liver function abnormalities. It may be difficult to determine superimposed drug-induced liver injury in patients with viral hepatitis, passive congestion of the liver from heart failure, fatty liver... 

The main causes are hepatitis B and C, drug induced damage, metabolic disease (alcohol, haemochro-matosis and Wilsons disease) and autoimmune disease. Management depends upon the diagnosis. 

Autoimmune reactions associated with a-methyldopa treatment include thrombocytopenia and leukopenia. Since a few cases of an a-methyldopa-induced hepatitis have occurred, the drug is contraindicated in patients with active hepatic disease. FluUke symptoms also are known to occur. 

Celecoxib is indicated for the treatment of osteoarthritis and rheumatoid arthritis. Its use is contraindicated in individuals with hypersensitivity to sulfonamides or other NSAIDs. It should be used with caution in persons with hepatic disease. Interactions occur with other drugs that induce CYP2C9 (e.g. ri-... 

Contraindications Anuria, drug-induced or preexisting hyperkalemia, progressive or severe renal disease, severe hepatic disease... 

The biodisposition of sedative-hypnotics can be influenced by several factors, particularly alterations in hepatic function resulting from disease or drug-induced increases or decreases in microsomal enzyme activities (see Chapter 4). 

Biguanide drugs are contraindicated in patients with renal disease, alcoholism, hepatic disease, or conditions predisposing to tissue anoxia (eg, chronic cardiopulmonary dysfunction) because of an increased risk of lactic acidosis induced by biguanide drugs. 

Of 14 cases of suspected drug-induced liver disease presenting to a gastroenterology department over a 3-year period, one was thought to be related to thiamazole, with a hepatitic pattern of liver function tests in a 39-year-old woman 6 days after the start of therapy recovery was swift and complete (48). Delayed cholestatic hepatitis without antineutrophil cytoplasmic antibodies has been reported (49), and there have been fatal cases of hepatic necrosis (SEDA-21, 438) (7). 

A 50-year-old woman with previous autoimmune thyroid disease taking atorvastatin developed acute hepatitis when she also was given ezetimibe (4). Further investigations, including liver biopsy, showed a probable drug-induced autoimmune hepatitis. 

Ishak, K. G., and Zimmerman, H. J. Morphologic spectrum of drug-induced hepatic disease. Gastroenterol. Clin. North Am. 24, 759, 1995. 

A biopsy is often required to make a diagnosis of most types of liver disease. A specimen of liver can be used to identify fibrosis, cirrhosis, cholestasis and hepatitis, both acute and chronic, and tumours. Biochemical measurements can also be taken from a biopsy specimen to determine iron and copper content, virology, microbiology and haematology (e.g. increased numbers of eosinophils in a drug-induced cause). The biopsy can give an indication of the extent of the liver damage. See Chapter 3 for slides of liver biopsies. 

Few drugs exhibit an intermediate extraction ratio. Evaluation of the hepatic clearance of these drugs requires consideration of all of the parameters included in Equation 7.6. Disease-associated or drug-induced alterations in protein binding, hepatic blood flow, or intrinsic clearance may alter hepatic clearance significantly. 

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