Drug-induced liver injury (DILI) refers to damage to the liver caused by medications, herbal products, or dietary supplements. The liver’s central role in metabolism and detoxification makes it particularly susceptible to harm from certain compounds. DILI can range from mild, temporary liver enzyme elevations to severe liver failure.
Understanding Drug-Induced Liver Injury
Drugs can harm the liver through several mechanisms, leading to a spectrum of injury patterns. One way is direct toxicity, where the drug or its metabolic byproducts directly damage liver cells. This injury is often predictable and dose-dependent, meaning higher doses are more likely to cause damage. Acetaminophen is a well-known example where exceeding recommended doses can lead to severe liver injury.
Another mechanism is an idiosyncratic reaction, which is unpredictable and occurs in a small number of individuals. These reactions are not related to the drug’s dose or duration of use and involve a complex interplay of genetic, environmental, and immune factors.
Immune-mediated injury represents a third pathway, where the body’s immune system mistakenly attacks liver cells in response to a drug. This can involve the production of antibodies or the activation of immune cells that cause inflammation and damage.
Common Medications and Substances Implicated
Many medications and substances have been linked to DILI. Over-the-counter pain relievers, such as acetaminophen, are a common cause, especially when taken in doses exceeding recommended limits. Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen, diclofenac, and naproxen can also cause liver injury.
Antibiotics are frequently implicated in DILI cases, with amoxicillin-clavulanate being a common example. Other antibiotics like erythromycin, sulfamethoxazole-trimethoprim, and ciprofloxacin are also associated with DILI. Anti-tuberculosis drugs, such as isoniazid, are known to cause liver damage in some patients.
Cholesterol-lowering drugs, particularly statins, can lead to DILI, as can certain anti-seizure medications like valproate and phenytoin. Herbal and dietary supplements are also recognized as culprits, with examples including green tea extract, turmeric, kratom, and anabolic steroids. These supplements can cause severe, even fatal, liver injury.
Recognizing the Signs and Diagnosis
The symptoms of drug-induced liver injury can vary widely and often mimic those of other liver conditions. Early, non-specific symptoms may include fatigue, nausea, loss of appetite, and abdominal pain. As liver damage progresses, more specific signs can appear, such as jaundice (yellowing of the skin or eyes), dark urine, light-colored or clay-colored stools, and itching. These symptoms can develop anywhere from a few days to several months after starting the offending medication.
Diagnosing DILI primarily involves blood tests to assess liver function. These tests measure levels of liver enzymes like alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as well as alkaline phosphatase and bilirubin. Elevated levels of these markers can indicate liver cell damage or bile duct obstruction.
A thorough medical history, including all prescription drugs, over-the-counter medications, and herbal supplements taken, is also important for diagnosis. Imaging tests of the liver, such as ultrasound, CT scans, or MRI, may be performed to rule out other causes of liver injury. Liver biopsy might be considered in some cases to further assess the extent and type of liver damage.
Risk Factors and Management
Several factors can increase an individual’s susceptibility to drug-induced liver injury. Age plays a role, with both very young and elderly individuals potentially having a higher risk. Pre-existing liver conditions, such as chronic liver disease, can also make the liver more vulnerable to drug-induced harm. Genetic predispositions, including specific human leukocyte antigen (HLA) haplotypes, have been linked to increased risk for idiosyncratic DILI with certain medications.
Lifestyle factors like alcohol consumption and nutritional status can also influence risk. Taking multiple medications, a practice known as polypharmacy, may also elevate the likelihood of DILI due to potential drug interactions or cumulative liver burden. Women are reported to have a higher incidence of idiosyncratic DILI compared to men, possibly due to hormonal interactions or differing pharmacokinetics.
The primary step in managing DILI is to identify and discontinue the offending medication as quickly as possible. Most people recover fully from DILI after the drug is stopped, although recovery time can vary. Supportive care, such as managing symptoms and closely monitoring liver function through blood tests, is often provided. In severe cases, specialized medical interventions may be necessary to support liver function and prevent further complications.