Drug Induced Liver Disease (cont.)

Patients with mild liver disease may have few or no symptoms or signs. Patients with more serious disease develop symptoms and signs that may be nonspecific or specific.

Nonspecific symptoms, that is, symptoms that don't suggest that the liver is their cause, include:

• fatigue,
• weakness,
• vague abdominal pain, and
• loss of appetite.

Symptoms and signs that are specific for liver disease include:

• yellowing of the skin (jaundice) due to the accumulation of bilirubin in the blood,
• itching, and
• easy bruising due to decreased production of blood clotting factors by the diseased liver.

Severe, advanced liver disease with cirrhosis can produce symptoms and signs related to cirrhosis; these symptoms include:

• fluid accumulation in the legs (edema) and abdomen (ascites),
• mental confusion or coma,
• kidney failure,
• vulnerability to bacterial infections, and
• gastrointestinal bleeding.

Drugs can cause liver disease in several ways. Some drugs are directly injurious to the liver; others are transformed by the liver into chemicals that can be injurious to the liver directly or indirectly. (This may seem strange in light of the liver's important role in transforming toxic chemicals into nontoxic chemicals, but it happens.) There are three types of liver toxicity; dose-dependent toxicity, idiosyncratic toxicity, and drug allergy.

Drugs that cause dose-dependent toxicity can cause liver disease in most people if enough of the drug is taken. The most important example of dose-dependent toxicity is acetaminophen (Tylenol) overdose (discussed later in this article.).

Drugs that cause idiosyncratic toxicity cause disease in only those few patients who have inherited specific genes that control the chemical transformation of that specific drug, causing accumulation of the drug or products of their transformation (metabolites) that are injurious to the liver. These inherited idiosyncratic toxicities usually are rare, and depending on the drug, typically occur in less than 1 to10 per 100,000 patients who are taking that drug; however, with some drugs the prevalence of toxicity is much higher. Even though the risk of developing drug-induced idiosyncratic liver disease is low, idiosyncratic liver disease is the most common form of drug-induced liver disease because tens of millions of patients are using drugs, and many of them are using several drugs.

Idiosyncratic drug toxicity is difficult to detect in early clinical trials that usually involve, at most, only a few thousand patients. Idiosyncratic toxicity will surface only after millions of patients begin to receive the drug after the drug is approved by the FDA.

Drug allergy also may cause liver disease, though it is uncommon. In drug allergy, the liver is injured by the inflammation that occurs when the body's immune system attacks the drugs with antibodies and immune cells.

Source: MedicineNet.com
http://www.medicinenet.com/drug_induced_liver_disease/article.htm