Liver Diseases - Drug Induced Liver Diseases In The Elderly

Drugs are the fundamental and most common cause of hepatic injury. This is not at all surprising, as the liver is the prime site of drug clearance, biotransformation and excretion. Disorder covers a wide range from minor nonspecific derangements to fulminant hepatic necrosis. However, they are the two most common and acute inflammation and cholestasis, which can closely mimic viral hepatitis and biliary obstruction, respectively. Various other acute and chronic ailment patterns in the liver also occur. Thus drug-induced liver disease is a very intricate, has protean manifestations, and can simulate a wide variety of other hepatic disorders.

The pathogenesis differs with the offending component, and in most cases is poorly understood. Sometimes the injurious drug or one of its metabolites exerts a straight toxic effect on liver membranes. This type of hepatic injury is predictable and dose-related, but is relatively infrequent. Much more generally, the hepatic injury occurs unpredictably in only a tiny fraction of individuals receiving the drug and is independent of dosage. In some cases such instances genetic predilection or idiosyncratic metabolism of the drug may be responsible. Immune reaction is often invoked, but only a minority of cases has associated evidence of an allergic reaction such as a rash, arthralgias or eosinophilia. A number of instances of putative hypersensitivity may actually be due to toxic intermediate drug metabolites in rarely vulnerable individuals. In most of the situations the causes for individual susceptibility are unknown, and the precise pathogenesis of the hepatic injury is equally obscure.

A proper diagnosis needs first and foremost a careful history of drug ingestion, including over-the-counter and illicit agents as well as prescribed medications. A sequential connection is also important in cases of acute dysfunction: injury typically develops within days or a few weeks of starting the drug. Other responses involve chronic insidious injury and therefore need prolonged drug exposure such as, methotrexate fibrosis and oral contraceptive-induced adenomas. Sometimes, liver biopsy provides a vital clue to certain drug injuries, but more commonly the histologic pattern is nonspecific and/or mimics other primary liver disorders. Thus in a number of cases the diagnosis of drug injury remains vague or unproven even after appropriate patient assessment. The prediction is variable. Acute damage in the liver membrane usually resolves when the offending agent is withdrawn, but cases of severe acute necrosis can be fatal or result in postnecrotic scarring. In cases of chronic hepatic injury, further hepatocellular damage and inflammation will generally cease when the drug is stopped, but any concomitant fibrosis will be irreversible. No health professional can know the innumerable drugs capable of producing liver injury. It is rather best to maintain a constant awareness of the possibility, to understand the general types of liver damage, and to learn the most common agents responsible for each.

The most effective treatment for drug-induced liver disease is stopping the drug that is causing the liver disease. In most of the patients, signs and symptoms of liver disease will determine and blood tests will become normal and there will be no long-term liver damage. However, they are exceptions. Some of the common drugs also can cause irreversible liver damage and cirrhosis.

• Cassandra Bagley
• 13/01/2009, 6:59 AM
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