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Liver Injury Caused by Drugs

By

Danielle Tholey

, MD, Thomas Jefferson University Hospital

Last full review/revision Jan 2020| Content last modified Jan 2020
Click here for the Professional Version
Topic Resources

Many drugs can affect the way the liver functions, damage it, or do both. (See also Drugs and the Liver.)

Some drugs, such as statins (used to treat high cholesterol levels), can increase the levels of liver enzymes and cause liver damage (usually minor) but no symptoms.

A very few drugs damage the liver enough to cause symptoms, such as a yellow color of the skin and eyes (jaundice), abdominal pain, itching, and a tendency to bruise and bleed.

Doctors use the term drug-induced liver injury (DILI) to refer to any liver damage caused by medications, whether it results in symptoms or not. The term also includes damage caused by recreational drugs, medicinal herbs, plants, and nutritional supplements.

For some drugs, liver damage is predictable. It occurs shortly after the drug is taken and is related to the drug's dose. In the United States, such damage (often caused by acetaminophen poisoning) is one of the most common causes of the sudden appearance of jaundice, liver failure, or both. For other drugs, damage is unpredictable. It is detected some time after the drug is taken and is not related to the dose. Rarely, such damage results in a severe liver disorder.

Medicinal herbs and the liver

Some medicinal herbs (parts of plants used for health benefits) contain substances that can damage the liver. The liver is a prime target for damage because it processes everything that enters the mouth and is swallowed.

Pyrrolizidine alkaloids: Hundreds of herbs contain pyrrolizidine alkaloids, which may damage the liver. These herbs include borage, comfrey, and certain Chinese herbs, such as zi cao (groomwell), kuan dong hua (coltsfoot), qian li guang (liferoot), and pei lan (Eupatorium). Some herbs used to make teas contain pyrrolizidine alkaloids. Sometimes milk, honey, and cereals are contaminated with pyrrolizidine alkaloids, which are then consumed unknowingly.

Pyrrolizidine alkaloids can damage the liver gradually if small amounts are consumed for a long time. Damage can occur more quickly if a large amount is consumed. The hepatic veins may become clogged, blocking blood flow out of the liver.

Affected people have abdominal pain and may vomit. Fluid accumulates in the abdomen and legs. Eventually, scar tissue in the liver (cirrhosis), liver failure, and even death may result.

Other herbs: Liver damage may also result from herbs such as Atractylis gummifera, Camellia sinensis (used to make green and black teas), celandine (in the poppy family), chaparral, germander, jin bu huan, kava, ma huang (Ephedra), mistletoe, pennyroyal oil (used to make teas), and syo-saiko-to (a mixture of herbs).

In general, liver doctors recommend avoiding all herbal supplements because of the lack of safety testing by the US Food and Drug Administration (FDA) and the fact that many of these substances can cause liver damage and even liver failure, even in people who do not have any preexisting liver disease.

Risk factors

Generally, the risk of liver damage by drugs is thought to be increased by the following:

  • Age 18 years or over

  • Obesity

  • Pregnancy

  • Consumption of alcohol

  • A genetic makeup that makes people more susceptible to a drug's effects

Drinking alcohol increases the risk of liver damage because alcohol damages the liver and thus changes the way drugs are metabolized. In addition, alcohol reduces the body's supply of an antioxidant that helps protect the liver.

Classification

Doctors categorize drug-induced liver damage in various ways, such as by how the drug damages the liver, how liver cells are affected, and which liver enzyme abnormalities are detected by blood tests. For example, drugs may damage the liver by directly damaging liver cells (hepatocellular), by blocking the flow of bile out of the liver (cholestatic), or by doing both.

Table
icon

Drugs That Can Damage the Liver

Type of Drug

Examples

Antibiotics

Amoxicillin/clavulanate

Clindamycin

Erythromycin

Nitrofurantoin

Rifampin

Sulfonamides

Tetracyclines

Trimethoprim/sulfamethoxazole

Drugs used to treat tuberculosis (isoniazid and pyrazinamide)

Anticonvulsants

Carbamazepine

Phenobarbital

Phenytoin

Valproate

Antidepressants

Bupropion

Fluoxetine

Mirtazapine

Paroxetine

Sertraline

Trazodone

Tricyclic antidepressants such as amitriptyline

Antifungal drugs

Ketoconazole

Terbinafine

Antihypertensive drugs (used to treat high blood pressure or sometimes kidney or heart disorders)

Captopril

Enalapril

Irbesartan

Lisinopril

Losartan

Verapamil

Antipsychotic drugs

Phenothiazines such as chlorpromazine

Risperidone

Heart drugs

Amiodarone

Clopidogrel

Hormones and related drugs

Anabolic steroids

Birth control pills (oral contraceptives)

Estrogens

Pain relievers

Acetaminophen

NSAIDs

Other drugs

Acarbose (used to treat diabetes)

Allopurinol (used to treat gout)

ART drugs (used to treat HIV infection)

Baclofen (a muscle relaxant)

Cyproheptadine (an antihistamine)

Azathioprine (used to prevent rejection of an organ transplant)

Methotrexate (used to treat cancer)

Omeprazole (used to treat gastroesophageal reflux)

Statins (used to treat high cholesterol levels)

Many types of chemotherapy, including immune checkpoint inhibitors

Medicinal herbs

Germander

Green tea extract

Kava

Energy drinks

ART = antiretroviral therapy; HIV = human immunodeficiency virus; NSAID = nonsteroidal anti-inflammatory drug.

Symptoms

Symptoms of liver disease vary from the general (such as fatigue, a general feeling of being unwell, nausea, itching, and loss of appetite) to the more severe (such as jaundice, an enlarged liver, pain in the upper right part of the abdomen, confusion, disorientation, and reduced alertness).

Diagnosis

  • A doctor's evaluation

  • Liver blood tests

After stopping the drug suspected of causing damage, doctors repeat liver tests. A significant decrease in liver enzyme levels further supports the diagnosis of drug-induced liver damage.

Liver damage caused by drugs

If liver damage caused by drugs is identified quickly, people have a better prognosis.

Doctors ask which drugs are being taken to determine whether any can cause liver damage. Doctors also do blood tests to measure levels of specific liver enzymes and to evaluate how well the liver is functioning and whether it is damaged (liver tests). Drug-induced liver injury (DILI) is likely when results of liver tests are typical of the liver damage usually caused by a drug that the person is taking. Drugs sometimes cause damage after they are stopped, even when the dose was not high, and sometimes it can take several months for DILI to improve. Thus, determining that a drug is the cause is sometimes difficult or impossible.

Liver damage from other causes

Because no test can confirm the diagnosis, doctors also check for other causes of liver damage. Blood tests to check for hepatitis, autoimmune disorders, and other causes are done. Pressing on the upper abdomen to determine the size of the liver and doing imaging tests, such as ultrasonography or computed tomography (CT), can also help doctors identify other causes of liver damage.

Prevention

When some drugs that can damage the liver (such as statins) are used, doctors sometimes regularly do blood tests to monitor liver enzyme levels. Such monitoring may detect problems early and may help prevent liver damage. For most drugs, monitoring liver enzyme levels is not done.

Treatment

  • Stopping the drug

  • Administration of antidote if available

  • Sometimes liver transplantation

Usually, stopping the drug results in recovery. Drugs to relieve symptoms such as itching can be used.

Only a few drugs have antidotes. For example, acetylcysteine can be used if people have taken an overdose of acetaminophen.

If the damage is severe, people may be referred to a specialist. Liver transplantation may be required.

More Information

Drugs Mentioned In This Article

Generic Name Select Brand Names
No US brand name
FURADANTIN, MACROBID, MACRODANTIN
ACETADOTE
TEGRETOL
TYLENOL
IMURAN
ERY-TAB, ERYTHROCIN
NIZORAL
OTREXUP
REMERON
AMOXIL
LAMISIL
PLAVIX
CLEOCIN
RISPERDAL
ZYLOPRIM
ZOLOFT
CORDARONE
AVAPRO
PRILOSEC
PAXIL
PROZAC, SARAFEM
PRINIVIL, ZESTRIL
LANIAZID
OLEPTRO
VASOTEC
CALAN
DILANTIN
WELLBUTRIN, ZYBAN
CAPOTEN
PRECOSE
LIORESAL
COZAAR
RIFADIN, RIMACTANE
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