Hepatotoxicity

Hepatotoxicity is liver damage caused by exposure to harmful substances such as medications, chemicals, herbal products, or alcohol. This condition can range from mild symptoms detected only through blood tests to severe, life-threatening liver failure requiring urgent medical attention.

Table of contents

• What Is Hepatotoxicity?
• Alternative Names
• Affected Organ
• Types of Hepatotoxicity
• What Causes Hepatotoxicity?
• Who Is at Higher Risk?
• How Common Is Hepatotoxicity?
• Signs and Symptoms
• How Is Hepatotoxicity Diagnosed?
• Treatment Options
• Recovery and Outlook
• How to Prevent Liver Damage

What Is Hepatotoxicity?

Hepatotoxicity, also known as liver toxicity or toxic hepatitis, is inflammation (swelling) of the liver that occurs when the organ is exposed to harmful substances^[1]. The liver is one of your body’s largest organs, and it plays a vital role in filtering your blood and removing toxins from your system^[3].

When you are exposed to certain chemicals, medications, or other toxic substances, your liver can become inflamed and damaged. This damage can happen quickly—within hours or days—or develop slowly over weeks or months of regular exposure^[1]. Over time, untreated inflammation can cause permanent scarring of the liver, called cirrhosis, which is a buildup of scar tissue that prevents the liver from working properly^[3].

Toxic hepatitis, Liver toxicity, Drug-induced liver injury (DILI), Toxic liver disease, Drug-induced hepatitis, Chemical-induced hepatitis

Affected Organ

• Liver

Your liver is located mainly in the upper right portion of your abdomen, beneath the diaphragm and above the stomach^[1]. It helps clean your blood by filtering out alcohol, drugs, and chemicals, then processes these unwanted substances so you can flush them out through your urine or bile^[7].

Types of Hepatotoxicity

Healthcare providers classify hepatotoxicity in several different ways based on how quickly it develops, what causes it, and how it affects the liver^[2][3].

Acute toxic hepatitis develops suddenly, with symptoms appearing immediately or shortly after exposure to a harmful substance^[3]. Chronic toxic hepatitis takes longer to develop, and you may not notice any symptoms for weeks or months^[3].

Hepatotoxicity can also be classified by the mechanism of injury. Intrinsic hepatotoxicity (also called Type A) is predictable and dose-dependent, meaning higher amounts of the substance cause more damage^[5]. This type of injury occurs shortly after reaching a certain threshold for toxicity. Idiosyncratic hepatotoxicity (Type B) is unpredictable and not related to the dose. It can occur in some people but not others, and has a variable time period before symptoms appear^[5].

Healthcare providers also categorize types based on the cause: chemical-induced hepatitis results from exposure to chemicals through swallowing, breathing, or touching them; drug-induced hepatitis occurs from taking too much of certain medications; and alcohol-induced hepatitis develops from excessive alcohol consumption, especially when combined with recreational drug use^[3].

What Causes Hepatotoxicity?

More than 1,000 medications and herbal compounds are known to cause hepatotoxicity^[2][6]. The substances that most commonly cause liver damage include medications, herbal supplements, chemicals, solvents, and alcohol^[7].

Acetaminophen (also known as paracetamol or Tylenol) is the most common cause of intrinsic liver injury. Taking too much of this over-the-counter pain reliever—more than 4,000 milligrams in one day or using it for more than 10 days in a row—can be dangerous^[3][11]. Acetaminophen overdose is the main cause of acute liver failure in adults in the United States^[6].

Antibiotics are responsible for about 45% of idiosyncratic drug-induced liver injury cases. The antibiotic combination amoxicillin-clavulanate is one of the drugs most commonly responsible for drug-induced liver injury worldwide^[2][6]. Other antibiotics that can cause problems include sulfamethoxazole-trimethoprim, ciprofloxacin, and isoniazid^[2].

Herbal and dietary supplements account for about 16% of drug-induced liver injury cases. Despite being natural, some herbs can cause serious liver damage. Examples include green tea extract, anabolic steroids, multi-ingredient nutritional supplements, aloe vera, black cohosh, cascara, chaparral, comfrey, ephedra, and kava^[2][7].

Other medications that can cause hepatotoxicity include nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen, and naproxen; cardiovascular drugs such as statins and amiodarone; central nervous system agents like valproate and phenytoin; and antineoplastic drugs including tyrosine kinase inhibitors and methotrexate^[2][7].

Taking too much vitamin A—more than 40,000 IU daily—can also cause liver toxicity^[3].

Workplace chemicals can harm your liver if you are exposed to them through your job. Examples include vinyl chloride (used to make plastics), carbon tetrachloride (a dry-cleaning solution), paraquat (a weed killer), and polychlorinated biphenyls^[7].

Alcohol is well known to cause liver damage, though the extent of injury varies widely among people who drink heavily. In individuals prone to alcohol-related liver injury—possibly due to genetics—heavy drinking can result in acute liver failure, a life-threatening condition requiring hospitalization^[14].

Who Is at Higher Risk?

Certain factors can increase your chances of developing hepatotoxicity^[2][6][7].

Female sex is associated with a higher risk of drug-induced liver injury, although the reasons are not fully understood^[2][6].

Older age increases your risk because elderly persons often experience decreased clearance of medications, drug-to-drug interactions, reduced blood flow to the liver, and lower liver volume. Poor diet, infections, and multiple hospitalizations also contribute to increased risk in older adults^[6].

Increased body mass index (BMI) or being overweight raises your risk for hepatotoxicity^[2].

Alcohol use makes you more susceptible to drug toxicity because alcohol induces liver injury and causes changes that alter how medications are processed. Alcohol also depletes glutathione (a substance that protects the liver) stores, making you more vulnerable to toxicity from drugs^[6].

Pre-existing liver disease, such as cirrhosis or hepatitis, may not make you more susceptible to injury, but a diminished liver reserve or reduced ability to recover could make the consequences of injury worse^[6].

You may also be at increased risk if you work in a job that uses industrial chemicals, or if you have a gene mutation that affects how well your liver works^[7].

How Common Is Hepatotoxicity?

The true incidence of hepatotoxicity is difficult to determine because it is often underreported^[2]. However, drug-induced liver injury has become the leading cause of acute liver failure in the United States^[2].

In the United States, approximately 2,000 cases of acute liver failure occur each year, and drugs account for over 50% of them. Of these, 39% are due to acetaminophen, while 13% result from idiosyncratic reactions to other medications^[6]. Drugs also account for 2 to 5% of cases of patients hospitalized with jaundice (yellowing of the skin and eyes) and approximately 10% of all cases of acute hepatitis^[6].

The annual incidence of idiosyncratic drug-induced liver injury is estimated to be 14 to 19 per 100,000 people in the U.S. general population, or about 60,000 cases^[6]. Registry studies have found that within six months of onset of idiosyncratic drug-induced liver injury, 10% of patients are at risk for serious outcomes such as acute liver failure, liver transplantation, or death^[6].

Drug-induced liver injury is responsible for 5% of all hospital admissions and 50% of all acute liver failures^[5]. Approximately 75% of idiosyncratic drug reactions result in liver transplantation or death^[6].

Signs and Symptoms

Mild hepatotoxicity might not cause any symptoms and may only be detected through blood tests^[1]. When symptoms do occur, they can include^[1][3][7]:

• Yellowing of the skin and the whites of the eyes (jaundice), which may be easier to see on white skin
• Itching of the skin
• Pain in the upper right part of the abdomen (stomach area)
• Fatigue (feeling very tired)
• Loss of appetite
• Nausea and vomiting
• Rash—small purple dots or splotchy areas may appear on your skin
• Fever
• Weight loss
• Dark or tea-colored urine
• White or gray stool
• Headaches
• Diarrhea

Symptoms may appear within hours after you come in contact with the toxic substance, or you may feel slowly worse over days or weeks of regular exposure^[7].

If you notice yellowing of the skin or eyes, severe abdominal pain, or other worrying symptoms, see a healthcare professional right away^[1].

How Is Hepatotoxicity Diagnosed?

To diagnose hepatotoxicity, a healthcare professional will take a detailed medical history and perform a physical examination^[9]. It is important to bring all medicines you take in their original containers to your appointment. Tell your healthcare provider if you work with industrial chemicals or may have been exposed to pesticides, herbicides, or other environmental toxins^[9].

Blood tests are used to look for high levels of certain liver enzymes and to check how well the liver is working^[9]. In hepatocellular injury (damage to liver cells), blood tests will show elevation in enzymes called aminotransferases. In cholestatic injury (damage to the bile system), an enzyme called alkaline phosphatase (ALP) is elevated^[2].

Imaging tests take pictures of the liver using ultrasound, computerized tomography (CT), or magnetic resonance imaging (MRI)^[9].

A liver biopsy is not mandatory for diagnosis but can help confirm hepatotoxicity and rule out other causes of liver disease^[2][9]. During a liver biopsy, a needle is used to take a small sample of tissue from the liver, which is then examined under a microscope^[9].

Your healthcare provider will also review all your medications, including herbal and dietary supplements, to determine which substance might be causing the liver injury^[7].

Treatment Options

Treatment for hepatotoxicity depends on what is causing the liver damage^[9]. The most important step in managing liver toxicity is to identify and eliminate the substance causing the condition^[2][12].

The first treatment is to stop exposure to the toxin. This may mean stopping a medication (under your doctor’s guidance), quitting alcohol, refraining from taking recreational drugs or herbal supplements, or limiting exposure to toxic substances in the workplace if possible^[12]. In most cases of liver toxicity, people recover immediately without further treatment after stopping the exposure^[12].

Supportive care is provided for people with severe symptoms, usually in a hospital setting. This may include receiving fluids through a vein, taking medicine to relieve nausea and vomiting, and close monitoring of the liver for damage^[9].

For acetaminophen overdose, treatment includes receiving a medicine called acetylcysteine (also called N-acetylcysteine), which can reverse liver damage if given early enough^[9][12].

Depending on the type of drug causing liver toxicity, your doctor may administer other specific antidotes. For example, carnitine is used for valproate poisoning, and glucocorticoids may be used for immune-mediated drug-induced liver injury^[12].

When alcohol is causing liver inflammation, healthcare providers will need to address the underlying substance use disorder. Using a compassionate approach, dedicated addiction experts can help you quit for good^[14].

If hepatotoxicity leads to severe liver damage or liver failure, a liver transplant may be necessary^[3][12]. A liver transplant may be life-saving for patients experiencing a severe idiosyncratic drug reaction that causes massive destruction of liver cells and rapidly developing liver failure^[14].

Recovery and Outlook

Drug-induced liver injury is usually reversible, and most people recover within 3 to 12 months after ending their exposure to the toxin^[12]. The prognosis for recovery is usually favorable after discontinuation of the drug^[2].

The symptoms of toxic hepatitis often go away when contact with the toxin stops^[1]. Medical treatment can sometimes reverse the damage to the liver that has occurred, and a person’s symptoms may improve once exposure to the toxin has stopped^[12].

However, without timely diagnosis and treatment, liver toxicity can lead to an irreversible buildup of scar tissue, causing permanent liver damage or acute liver failure^[12]. Sometimes toxic hepatitis causes liver failure, which can be life-threatening^[1]. Toxic hepatitis can damage the liver, leading to cirrhosis. If it continues for a while, it could cause permanent liver scarring, which can lead to liver failure or even death^[3][7].

Even at the advanced stage of cirrhosis, liver disease from alcohol may show significant improvement with total abstinence from alcohol^[14].

How to Prevent Liver Damage

There are many things you can do to protect your liver and reduce your risk of developing hepatotoxicity^[16][18].

Use medications responsibly. Only take medications that you need and carefully follow dosing recommendations^[1]. Read the label on all over-the-counter medications and follow the directions, unless told otherwise by your medical provider^[3]. Check with your pharmacist about any over-the-counter drugs or non-hepatitis prescription drugs before taking them to make sure they are safe for your liver^[21].

Be cautious with acetaminophen. Most adults should not take more than 4,000 milligrams of acetaminophen in one day or use it for more than 10 days in a row^[3].

Talk to your provider before taking herbal remedies or supplements. Some vitamins and herbal products can be toxic to your liver. Always talk to your healthcare provider about any supplements before taking them^[3][21]. People with liver disease should not use herbs or nutritional supplements without their doctor’s approval^[14].

Avoid or limit alcohol. All alcohol, in any amount, is harmful to your liver. Eliminate all alcohols from your diet, especially if you have liver disease^[16][21]. Do not drink alcohol while taking certain medications or supplements^[7].

Avoid recreational drugs. All illicit drugs are harmful to your liver. It doesn’t make any difference how the drug is used—injecting, smoking, eating, or inhaling—they are all harmful^[16].

Protect yourself from harmful chemicals. Avoid inhaling fumes from paint, paint thinners, glue, household cleaning products, nail polish removers, and other potentially toxic chemicals that could damage your liver^[21]. If you work with industrial chemicals, follow safety protocols to minimize exposure^[7].

Maintain a healthy weight and diet. Eat a healthy diet of fruits, vegetables, whole grains, and lean proteins. Maintaining a healthy weight through diet and exercise can reduce your risk for liver disease^[1][18].

Exercise regularly. Regular physical activity helps your liver work as efficiently as possible and lowers your risk for liver disease^[1].

Get vaccinated. Get the hepatitis A and hepatitis B vaccines to protect yourself from other viruses that attack the liver^[21].

Schedule regular check-ups. Schedule regular visits with your liver specialist or healthcare provider to stay on top of your health and the health of your liver^[21]. If you have liver disease or other medical conditions, it is important to follow care instructions and follow up with your doctor whenever you need help^[19].