Disease: Drug-Induced Liver Disease

    What is drug-induced liver disease?

    Drug-induced liver diseases are diseases of the liver that are caused by physician-prescribed medications, over-the-counter medications, vitamins, hormones, herbs, illicit ("recreational") drugs, and environmental toxins.

    What is the liver?

    The liver is an organ that is located in the upper right hand side of the abdomen, mostly behind the rib cage. The liver of an adult normally weighs close to three pounds and has many functions.

    • The liver produces and secretes bile into the intestine where the bile assists with the digestion of dietary fat.
    • The liver helps purify the blood by changing potentially harmful chemicals into harmless ones. The sources of these chemicals can be outside the body (for example, medications or alcohol), or inside the body (for example, ammonia, which is produced from the break-up of proteins; or bilirubin, which is produced from the break-up of hemoglobin).
    • The liver removes chemicals from the blood (usually changing them into harmless chemicals) and then either secretes them with the bile for elimination in the stool, or secretes them back into the blood where they then are removed by the kidneys and eliminated in the urine.
    • The liver produces many important substances, especially proteins that are necessary for good health. For example, it produces proteins like albumin (a protein that carries other molecules through the blood stream), as well as the proteins that cause blood to clot properly.
    Illustration of the Liver

    When drugs injure the liver and disrupt its normal function, symptoms, signs, and abnormal blood tests of liver disease develop. Abnormalities of drug-induced liver diseases are similar to those of liver diseases caused by other agents such as viruses and immunologic diseases. For example, drug-induced hepatitis (inflammation of the liver cells) is similar to viral hepatitis; they both can cause elevations in blood levels of aspartate amino transferase (AST) and alanine aminotransferase (ALT) (enzymes that leak from the injured liver and into the blood) as well as anorexia (loss of appetite), fatigue, and nausea. Drug-induced cholestasis (interference with the flow of bile that is caused by injury to the bile ducts) can mimic the cholestasis of autoimmune liver disease (e.g., primary biliary cirrhosis or PBC) and can lead to elevations in blood levels of bilirubin (causing jaundice), alkaline phosphatase (an enzyme that is leaked from injured bile ducts), and itching.

    What are the symptoms of liver disease?

    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 (symptoms that also can be seen in other disorders) 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 associated with liver disease, 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, due to increased pressure in the vessels going into the liver),
    • mental confusion or coma (from hepatic encephalopathy due to increase in ammonia),
    • kidney failure,
    • vulnerability to bacterial infections, and
    • gastrointestinal bleeding, secondary to varices (enlarged blood vessels in the esophagus or stomach).

    How do drugs cause liver disease?

    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 cause injury 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.).

    Learn more about: Tylenol

    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.

    What types of liver disease do drugs cause?

    Drugs and chemicals can cause a wide spectrum of liver injury. These include:

    • Mild elevations in blood levels of liver enzymes without symptoms or signs of liver disease
    • Hepatitis (inflammation of liver cells)
    • Necrosis (death of liver cells) that often is caused by more severe hepatitis
    • Cholestasis (decreased secretion and/or flow of bile)
    • Steatosis (accumulation of fat in the liver)
    • Cirrhosis (advanced scarring of the liver) as a result of chronic hepatitis, cholestasis, or fatty liver
    • Mixed disease, for example both hepatitis and necrosis of liver cells, hepatitis and fat accumulation, or cholestasis and hepatitis.
    • Fulminant hepatitis with severe, life threatening liver failure
    • Blood clots in the veins of the liver

    Elevated blood levels of liver enzymes

    Many drugs cause mild elevations in blood levels of liver enzymes without symptoms or signs of hepatitis. AST, ALT, and alkaline phosphatase are enzymes that normally reside within the cells of the liver and bile ducts. Some drugs can cause these enzymes to leak from the cells and into the blood, thus elevating the blood levels of the enzymes. Examples of drugs that more commonly cause elevations of liver enzymes in the blood include the statins (used in treating high blood cholesterol levels) some antibiotics, some antidepressants (used in treating depression), and some medications used for treating diabetes, tacrine (Cognex), aspirin, and quinidine (Quinaglute, Quinidex).

    Learn more about: Cognex | aspirin | Quinidex

    Since these patients typically experience no symptoms or signs, the elevations of liver enzymes usually are discovered when blood tests are performed as a part of an annual physical examination, as pre-operative screening, or as a part of periodic monitoring for drug toxicity. Typically, these abnormal levels will become normal shortly after stopping the drug, and there usually is no long-term liver damage. With some drugs, low levels of abnormal liver enzymes are common and don't appear to be associated with important (severe or progressive) liver disease, and the patient may continue taking the drug.

    Acute and chronic hepatitis

    Certain drugs can cause acute and chronic hepatitis (inflammation of liver cells) that can lead to necrosis (death) of the cells. Acute drug-induced hepatitis is defined as hepatitis that lasts less than 3 months, while chronic hepatitis lasts longer than 3 months. Acute drug-induced hepatitis is much more common than chronic drug-induced hepatitis.

    Typical symptoms of drug-induced hepatitis include:

    • loss of appetite,
    • nausea,
    • vomiting,
    • fever,
    • weakness,
    • tiredness, and
    • abdominal pain.

    In more serious cases, patients can develop dark urine, fever, light-colored stool, and jaundice (a yellow appearance to the skin and white portion of the eyes). Patients with hepatitis usually have high blood levels of AST, ALT, and bilirubin. Both acute and chronic hepatitis typically resolve after stopping the drug, but sometimes acute hepatitis can be severe enough to cause acute liver failure (see discussion later in this article), and chronic hepatitis can on rare occasions, lead to permanent liver damage and cirrhosis.

    Examples of drugs that can cause acute hepatitis include acetaminophen (Tylenol), phenytoin (Dilantin), aspirin, isoniazid (Nydrazid, Laniazid), diclofenac (Voltaren), and amoxicillin/clavulanic acid (Augmentin).

    Learn more about: Dilantin | isoniazid | Nydrazid | Voltaren

    Examples of drugs that can cause chronic hepatitis include minocycline (Minocin), nitrofurantoin (Furadantin, Macrodantin), phenytoin (Dilantin), propylthiouracil, fenofibrate (Tricor), and methamphetamine ("ecstasy")..

    Learn more about: Minocin | Furadantin | Macrodantin | Tricor

    Acute liver failure

    Rarely, drugs cause acute liver failure (fulminant hepatitis). These patients are extremely ill with the symptoms of acute hepatitis and the additional problems of confusion or coma (encephalopathy) and bruising or bleeding (coagulopathy). In fact, 70% to 90% of people with fulminant hepatitis die. In the U. S., acetaminophen (Tylenol) is the most common cause of acute liver failure.

    Cholestasis

    Cholestasis is a condition in which the secretion and/or flow of bile is reduced. Bilirubin and bile acids normally secreted by the liver into bile and eliminated from the body via the intestine, collect in the body leading to jaundice and itching, respectively. Drugs causing cholestasis typically interfere with the liver cell's secretion of bile without causing hepatitis or liver cell necrosis (death). Patients with drug-induced cholestasis typically have elevated blood levels of bilirubin but have normal or mildly elevated AST and ALT levels. Blood levels of alkaline phosphate (an enzyme made by bile ducts) increase because the cells of the bile ducts also are dysfunctional and leak the enzyme. Aside from itching and jaundice, patients usually are not as sick as patients with acute hepatitis.

    Examples of drugs that have been reported to cause cholestasis include erythromycin (E-Mycin, Ilosone), chlorpromazine (Thorazine), sulfamethoxazole and trimethoprim (Bactrim; Septra), amitriptyline (Elavil, Endep), carbamazepine (Tegretol), ampicillin (Omnipen; Polycillin; Principen), ampicillin/clavulanic acid (Augmentin), rifampin (Rifadin), estradiol (Estrace; Climara; Estraderm; Menostar), captopril (Capoten), birth control pills (oral contraceptives), anabolic steroids, naproxen (Naprosyn), amiodarone (Cordarone), haloperidol (Haldol), imipramine (Tofranil), tetracycline (Achromycin), and phenytoin (Dilantin).

    Learn more about: Thorazine | Bactrim | Septra | Elavil | Tegretol | Principen | Rifadin | Estrace | Climara | Estraderm | Menostar | Capoten | Naprosyn | Cordarone | Haldol | Tofranil

    Most patients with drug-induced cholestasis will recover fully within weeks after stopping the drug, but in some patients, jaundice, itching, and abnormal liver tests can last months after stopping the drug. An occasional patient can develop chronic liver disease and liver failure. Drug-induced jaundice and cholestasis lasting longer than 3 months is called chronic cholestasis.

    Steatosis (fatty liver)

    The most common causes of accumulation of fat in the liver are alcoholism and non-alcoholic fatty liver disease (NAFLD) associated with obesity and diabetes. Drugs may cause fatty liver with or without associated hepatitis. Patients with drug-induced fatty liver may have only a few symptoms, or none. They typically have mild to moderate elevations in blood levels of ALT and AST, and also may develop enlarged livers. In severe cases, drug-induced fatty liver can lead to cirrhosis and liver failure.

    Drugs reported to cause fatty liver include total parenteral nutrition, methotrexate (Rheumatrex), griseofulvin (Grifulvin V), tamoxifen (Nolvadex), steroids, valproate (Depakote), and amiodarone (Cordarone).

    Learn more about: Rheumatrex | Grifulvin V | Nolvadex | Depakote

    In certain situations, fatty liver alone can be life threatening. For example, Reye's syndrome is a rare liver disease that can cause fatty liver, liver failure, and coma. It is believed to occur in children and teenagers with influenza when they are given aspirin. Another example of serious fatty liver is caused by high doses of intravenous tetracycline or amiodarone. Certain herbs (for example, the Chinese herb Jin Bu Huan, used as a sedative and pain reliever) also can cause serious fatty liver.

    Cirrhosis

    Chronic liver diseases such as hepatitis, fatty liver, or cholestasis can lead to the necrosis (death) of liver cells. Scar tissue forms as part of the healing process that is associated with the dying liver cells, and severe scarring of the liver can lead to cirrhosis.

    The most common example of drug-induced cirrhosis is alcoholic cirrhosis . Examples of drugs that can cause chronic liver diseases and cirrhosis include methotrexate (Rheumatrex), amiodarone (Cordarone), and methyldopa (Aldomet). Please read the article on Cirrhosis for more information.

    Learn more about: Aldomet

    Hepatic vein thrombosis

    Normally, blood from the intestines is delivered to the liver via the portal vein, and the blood leaving the liver for the heart is carried via the hepatic veins into the inferior vena cava (the large vein that drains into the heart). Certain drugs can cause blood clots to form (thrombosis) in the hepatic veins and in the inferior vena cava. Thrombosis of the hepatic vein and inferior vena cava can lead to an enlarged liver, abdominal pain, fluid collection in the abdomen (ascites), and liver failure. This syndrome is called the Budd Chiari syndrome. The most important drugs that cause Budd-Chiari syndrome are birth control pills (oral contraceptives). Birth control pills also can cause a related disease called veno-occlusive disease in which blood clots only in the smallest hepatic veins. Pyrrolizidine alkaloids found in certain herbs (e.g., borage, comfrey) also can cause veno-occlusive disease.

    How is drug-induced liver disease diagnosed?

    The diagnosis of drug-induced liver diseases often is difficult. Patients may not have symptoms of liver disease or may have only mild, nonspecific symptoms. Patients may be taking multiple drugs, which makes it difficult to identify the offending drug. Patients also may have other potential causes of liver diseases such as non-alcoholic fatty liver disease (NAFLD) and alcoholism.

    The diagnosis of liver disease is based on a patient's symptoms (such as loss of appetite, nausea, fatigue, itching, and dark urine), findings on the physical examination (such as jaundice, enlarged liver), and abnormal laboratory tests (such as blood levels of liver enzymes or bilirubin and blood clotting times). If a patient has symptoms, signs, and abnormal liver tests, doctors then try to decide whether drug(s) are causing the liver disease by:

    1. Taking a careful history of alcohol consumption to exclude alcoholic liver disease.
    2. Performing blood tests to exclude viral hepatitis B and hepatitis C, and to exclude chronic liver diseases such as autoimmune hepatitis and primary biliary cirrhosis (PBC).
    3. Performing abdominal ultrasound or computerized tomography (CT) scan of the liver to exclude gallbladder disease and tumors of the liver.
    4. Taking a careful history of ingestion-particularly recent initiation--of drugs that are commonly associated with liver disease.

    How do drugs cause liver disease?

    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 cause injury 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.).

    Learn more about: Tylenol

    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.

    What types of liver disease do drugs cause?

    Drugs and chemicals can cause a wide spectrum of liver injury. These include:

    • Mild elevations in blood levels of liver enzymes without symptoms or signs of liver disease
    • Hepatitis (inflammation of liver cells)
    • Necrosis (death of liver cells) that often is caused by more severe hepatitis
    • Cholestasis (decreased secretion and/or flow of bile)
    • Steatosis (accumulation of fat in the liver)
    • Cirrhosis (advanced scarring of the liver) as a result of chronic hepatitis, cholestasis, or fatty liver
    • Mixed disease, for example both hepatitis and necrosis of liver cells, hepatitis and fat accumulation, or cholestasis and hepatitis.
    • Fulminant hepatitis with severe, life threatening liver failure
    • Blood clots in the veins of the liver

    Elevated blood levels of liver enzymes

    Many drugs cause mild elevations in blood levels of liver enzymes without symptoms or signs of hepatitis. AST, ALT, and alkaline phosphatase are enzymes that normally reside within the cells of the liver and bile ducts. Some drugs can cause these enzymes to leak from the cells and into the blood, thus elevating the blood levels of the enzymes. Examples of drugs that more commonly cause elevations of liver enzymes in the blood include the statins (used in treating high blood cholesterol levels) some antibiotics, some antidepressants (used in treating depression), and some medications used for treating diabetes, tacrine (Cognex), aspirin, and quinidine (Quinaglute, Quinidex).

    Learn more about: Cognex | aspirin | Quinidex

    Since these patients typically experience no symptoms or signs, the elevations of liver enzymes usually are discovered when blood tests are performed as a part of an annual physical examination, as pre-operative screening, or as a part of periodic monitoring for drug toxicity. Typically, these abnormal levels will become normal shortly after stopping the drug, and there usually is no long-term liver damage. With some drugs, low levels of abnormal liver enzymes are common and don't appear to be associated with important (severe or progressive) liver disease, and the patient may continue taking the drug.

    Acute and chronic hepatitis

    Certain drugs can cause acute and chronic hepatitis (inflammation of liver cells) that can lead to necrosis (death) of the cells. Acute drug-induced hepatitis is defined as hepatitis that lasts less than 3 months, while chronic hepatitis lasts longer than 3 months. Acute drug-induced hepatitis is much more common than chronic drug-induced hepatitis.

    Typical symptoms of drug-induced hepatitis include:

    • loss of appetite,
    • nausea,
    • vomiting,
    • fever,
    • weakness,
    • tiredness, and
    • abdominal pain.

    In more serious cases, patients can develop dark urine, fever, light-colored stool, and jaundice (a yellow appearance to the skin and white portion of the eyes). Patients with hepatitis usually have high blood levels of AST, ALT, and bilirubin. Both acute and chronic hepatitis typically resolve after stopping the drug, but sometimes acute hepatitis can be severe enough to cause acute liver failure (see discussion later in this article), and chronic hepatitis can on rare occasions, lead to permanent liver damage and cirrhosis.

    Examples of drugs that can cause acute hepatitis include acetaminophen (Tylenol), phenytoin (Dilantin), aspirin, isoniazid (Nydrazid, Laniazid), diclofenac (Voltaren), and amoxicillin/clavulanic acid (Augmentin).

    Learn more about: Dilantin | isoniazid | Nydrazid | Voltaren

    Examples of drugs that can cause chronic hepatitis include minocycline (Minocin), nitrofurantoin (Furadantin, Macrodantin), phenytoin (Dilantin), propylthiouracil, fenofibrate (Tricor), and methamphetamine ("ecstasy")..

    Learn more about: Minocin | Furadantin | Macrodantin | Tricor

    Acute liver failure

    Rarely, drugs cause acute liver failure (fulminant hepatitis). These patients are extremely ill with the symptoms of acute hepatitis and the additional problems of confusion or coma (encephalopathy) and bruising or bleeding (coagulopathy). In fact, 70% to 90% of people with fulminant hepatitis die. In the U. S., acetaminophen (Tylenol) is the most common cause of acute liver failure.

    Cholestasis

    Cholestasis is a condition in which the secretion and/or flow of bile is reduced. Bilirubin and bile acids normally secreted by the liver into bile and eliminated from the body via the intestine, collect in the body leading to jaundice and itching, respectively. Drugs causing cholestasis typically interfere with the liver cell's secretion of bile without causing hepatitis or liver cell necrosis (death). Patients with drug-induced cholestasis typically have elevated blood levels of bilirubin but have normal or mildly elevated AST and ALT levels. Blood levels of alkaline phosphate (an enzyme made by bile ducts) increase because the cells of the bile ducts also are dysfunctional and leak the enzyme. Aside from itching and jaundice, patients usually are not as sick as patients with acute hepatitis.

    Examples of drugs that have been reported to cause cholestasis include erythromycin (E-Mycin, Ilosone), chlorpromazine (Thorazine), sulfamethoxazole and trimethoprim (Bactrim; Septra), amitriptyline (Elavil, Endep), carbamazepine (Tegretol), ampicillin (Omnipen; Polycillin; Principen), ampicillin/clavulanic acid (Augmentin), rifampin (Rifadin), estradiol (Estrace; Climara; Estraderm; Menostar), captopril (Capoten), birth control pills (oral contraceptives), anabolic steroids, naproxen (Naprosyn), amiodarone (Cordarone), haloperidol (Haldol), imipramine (Tofranil), tetracycline (Achromycin), and phenytoin (Dilantin).

    Learn more about: Thorazine | Bactrim | Septra | Elavil | Tegretol | Principen | Rifadin | Estrace | Climara | Estraderm | Menostar | Capoten | Naprosyn | Cordarone | Haldol | Tofranil

    Most patients with drug-induced cholestasis will recover fully within weeks after stopping the drug, but in some patients, jaundice, itching, and abnormal liver tests can last months after stopping the drug. An occasional patient can develop chronic liver disease and liver failure. Drug-induced jaundice and cholestasis lasting longer than 3 months is called chronic cholestasis.

    Steatosis (fatty liver)

    The most common causes of accumulation of fat in the liver are alcoholism and non-alcoholic fatty liver disease (NAFLD) associated with obesity and diabetes. Drugs may cause fatty liver with or without associated hepatitis. Patients with drug-induced fatty liver may have only a few symptoms, or none. They typically have mild to moderate elevations in blood levels of ALT and AST, and also may develop enlarged livers. In severe cases, drug-induced fatty liver can lead to cirrhosis and liver failure.

    Drugs reported to cause fatty liver include total parenteral nutrition, methotrexate (Rheumatrex), griseofulvin (Grifulvin V), tamoxifen (Nolvadex), steroids, valproate (Depakote), and amiodarone (Cordarone).

    Learn more about: Rheumatrex | Grifulvin V | Nolvadex | Depakote

    In certain situations, fatty liver alone can be life threatening. For example, Reye's syndrome is a rare liver disease that can cause fatty liver, liver failure, and coma. It is believed to occur in children and teenagers with influenza when they are given aspirin. Another example of serious fatty liver is caused by high doses of intravenous tetracycline or amiodarone. Certain herbs (for example, the Chinese herb Jin Bu Huan, used as a sedative and pain reliever) also can cause serious fatty liver.

    Cirrhosis

    Chronic liver diseases such as hepatitis, fatty liver, or cholestasis can lead to the necrosis (death) of liver cells. Scar tissue forms as part of the healing process that is associated with the dying liver cells, and severe scarring of the liver can lead to cirrhosis.

    The most common example of drug-induced cirrhosis is alcoholic cirrhosis . Examples of drugs that can cause chronic liver diseases and cirrhosis include methotrexate (Rheumatrex), amiodarone (Cordarone), and methyldopa (Aldomet). Please read the article on Cirrhosis for more information.

    Learn more about: Aldomet

    Hepatic vein thrombosis

    Normally, blood from the intestines is delivered to the liver via the portal vein, and the blood leaving the liver for the heart is carried via the hepatic veins into the inferior vena cava (the large vein that drains into the heart). Certain drugs can cause blood clots to form (thrombosis) in the hepatic veins and in the inferior vena cava. Thrombosis of the hepatic vein and inferior vena cava can lead to an enlarged liver, abdominal pain, fluid collection in the abdomen (ascites), and liver failure. This syndrome is called the Budd Chiari syndrome. The most important drugs that cause Budd-Chiari syndrome are birth control pills (oral contraceptives). Birth control pills also can cause a related disease called veno-occlusive disease in which blood clots only in the smallest hepatic veins. Pyrrolizidine alkaloids found in certain herbs (e.g., borage, comfrey) also can cause veno-occlusive disease.

    How is drug-induced liver disease diagnosed?

    The diagnosis of drug-induced liver diseases often is difficult. Patients may not have symptoms of liver disease or may have only mild, nonspecific symptoms. Patients may be taking multiple drugs, which makes it difficult to identify the offending drug. Patients also may have other potential causes of liver diseases such as non-alcoholic fatty liver disease (NAFLD) and alcoholism.

    The diagnosis of liver disease is based on a patient's symptoms (such as loss of appetite, nausea, fatigue, itching, and dark urine), findings on the physical examination (such as jaundice, enlarged liver), and abnormal laboratory tests (such as blood levels of liver enzymes or bilirubin and blood clotting times). If a patient has symptoms, signs, and abnormal liver tests, doctors then try to decide whether drug(s) are causing the liver disease by:

    1. Taking a careful history of alcohol consumption to exclude alcoholic liver disease.
    2. Performing blood tests to exclude viral hepatitis B and hepatitis C, and to exclude chronic liver diseases such as autoimmune hepatitis and primary biliary cirrhosis (PBC).
    3. Performing abdominal ultrasound or computerized tomography (CT) scan of the liver to exclude gallbladder disease and tumors of the liver.
    4. Taking a careful history of ingestion-particularly recent initiation--of drugs that are commonly associated with liver disease.

    Source: http://www.rxlist.com

    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 cause injury 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.).

    Learn more about: Tylenol

    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: http://www.rxlist.com

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