Toxic Drug-Induced Liver Injury

Many medications can harm a normal liver, especially when taken in larger than recommended doses. These medications include prescription drugs, over-the-counter remedies and herbal or other dietary supplements. The liver helps the body break down a wide variety of chemicals, toxins and other substances in the body, including many medicines. Drug-induced liver injury, or DILI, is damage to the liver or impairment of liver function caused by medications that are normally therapeutic.

Types of Drug-induced Liver Injury

There are two main types of DILI:

  • Intrinsic DILI involves drugs known to cause liver injury at sufficiently high doses.
  • Idiosyncratic DILI is a rare, severe, and potentially life-threatening adverse reaction to a drug that develops regardless of the dosage or how the drug was administered.

There are also several categories of DILI, classified by how long the body has been exposed to the offending agent and which tissues have been affected, such as:  

  • acute, which comes on suddenly
  • cholestatic, which impairs the flow of bile
  • chronic, which persists over time
  • hepatitis, which causes liver inflammation  
  • mixed injury types

Causes of Drug-induced Liver Injury

Nearly all classes of medications can cause DILI. According to the National Library of Medicine, some of the most common medications that can cause DILI include:

  • antibiotics such as amoxicillin-clavulanate
  • pain relievers and fever reducers containing acetaminophen
  • nonsteroidal anti-inflammatory drugs, or NSAIDs, such as ibuprofen and naproxen

Other drugs known to cause DILI include: 

  • anabolic steroids 
  • antiepileptic drugs such as carbamazepine 
  • antifungal drugs such as ketoconazole  
  • antimicrobial medications such as didanosine and erythromycin 
  • antineoplastic (cancer) drugs such as flutamide 
  • arrhythmia (irregular heartbeat) drugs such as amiodarone and quinidine 
  • central nervous system drugs, including antidepressants such as iproniazid and nefazodone 
  • cholesterol-lowering drugs such as atorvastatin and simvastatin 
  • heparins, which are blood thinners 
  • immunosuppressive agents such as azathioprine and gold salts 
  • tuberculosis drugs such as isoniazid

Signs and Symptoms of Drug-induced Liver Injury

Early signs of DILI appear in the first 24 hours and may include:

  • malaise, general feeling of being unwell
  • nausea
  • vomiting

After 72 hours without treatment, liver injury begins to set in, causing symptoms including: 

  • abdominal pain 
  • jaundice, a yellowing of your skin and eyes 
  • nausea and vomiting

Symptoms can also include:

  • dark urine
  • diarrhea
  • fatigue
  • fever 
  • headache rash or itchy skin
  • white or clay-colored stool

In the most severe cases of DILI, symptoms may include:

  • coagulopathy, a blood clotting disorder 
  • drug-induced hepatitis, a swelling or inflammation of the liver 
  • hepatic encephalopathy, a loss of brain function due to a buildup of toxins in the liver

The most severe symptom is induced acute liver failure, which can be fatal.

How Is Drug-induced Liver Injury Diagnosed?

In 2014, the American College of Gastroenterology published updated ACG Clinical Guidelines diagnosing and managing DILI, which state that a thorough work-up is required to rule out other possible causes of liver injury. In addition to a physical examination and review of medical history, diagnostic methods for DILI include:

  • blood tests to check for autoimmune diseases, cardiovascular conditions, genetic disorders or infections
  • imaging studies such as computerized tomography (CT) scans, magnetic resonance imaging (MRI) or ultrasound
  • liver biopsies in severe cases or when other tests give inconclusive results

Treatments for Drug-induced Liver Injury

Most cases of DILI can be reversed by discontinuing the offending drug. Treatment depends on the drug ingested, degree of liver injury and any other medical complications and may include:

  • antihistamines 
  • ursodeoxycholic acid (UDCA) 
  • specific therapies tailored to the offending drug, such as n-acetylcysteine (NAC) for acetaminophen overdose

In addition, liver transplant may be considered in cases of liver failure.

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