Understanding Drug-Induced Liver Injury (DILI)
Jaundice is the yellowing of the skin and whites of the eyes, caused by an excess of bilirubin in the blood. Bilirubin is a yellow pigment produced during the breakdown of red blood cells, and the liver processes this pigment. When medications interfere with the liver's function in processing or excreting bilirubin, drug-induced jaundice can occur. This is a form of drug-induced liver injury (DILI), which can vary from mild enzyme elevation to severe acute liver failure.
Mechanisms by which drugs cause jaundice
Medications can induce jaundice through direct damage to liver cells (hepatocellular injury), obstruction of bile flow (cholestatic injury), or a combination of both (mixed injury). Factors like genetics, age, and existing health conditions influence an individual's susceptibility to DILI. Hepatocellular injury involves damage to hepatocytes, impairing bilirubin processing. Acetaminophen overdose is a notable example, overwhelming detoxification pathways. Cholestatic injury results from blocked bile flow, either within the liver or through interference with bile salt transport, leading to bilirubin accumulation. Some drugs cause a mixed injury pattern involving both mechanisms.
Common drug classes and specific examples
Many medications are linked to DILI and jaundice, with varying levels of risk.
Antibiotics and antifungals
Common culprits include amoxicillin-clavulanate and flucloxacillin, often causing cholestatic jaundice. Isoniazid, used for tuberculosis, can cause severe hepatocellular injury. Macrolides and sulfonamides are also associated with liver injury. Antifungals like ketoconazole and terbinafine have been reported to cause cholestatic or mixed injury.
Pain relievers and NSAIDs
Acetaminophen overdose is a significant cause of acute liver failure, especially with alcohol use. NSAIDs, such as ibuprofen, can also cause liver damage with long-term or high-dose use.
Cardiovascular and cholesterol-lowering drugs
Statins like atorvastatin can elevate liver enzymes and, less often, cause jaundice. Amiodarone is associated with chronic liver injury and cholestasis.
Psychiatric medications
Chlorpromazine is known to cause cholestatic jaundice, particularly in older patients. Tricyclic antidepressants have also been linked to cholestatic hepatitis.
Hormonal therapies and steroids
Anabolic steroids are highly hepatotoxic, causing cholestatic jaundice and sometimes liver tumors. Oral contraceptives can cause cholestasis in susceptible individuals.
Other medications
Anticonvulsants like carbamazepine can cause various DILI patterns. Methotrexate can lead to liver fibrosis and jaundice. Herbal and dietary supplements are also frequent, unregulated causes of DILI.
Comparison of DILI-induced jaundice
| Feature | Hepatocellular Injury | Cholestatic Injury | Mixed Injury |
|---|---|---|---|
| Mechanism | Direct damage to liver cells (hepatocytes). | Blockage of bile flow from the liver. | Combination of both hepatocellular and cholestatic features. |
| Key Laboratory Markers | Significant elevation of ALT and AST (transaminases). | Significant elevation of ALP (alkaline phosphatase) and GGT. | Elevated levels of both transaminases and ALP. |
| Latency Period | Can occur rapidly (e.g., acetaminophen overdose) or weeks to months later. | Onset is often delayed, sometimes occurring weeks after starting or even after stopping the drug. | Varies, depending on the specific drug and individual reaction. |
| Common Drug Examples | Acetaminophen, Isoniazid, Halothane. | Amoxicillin-clavulanate, Anabolic Steroids, Oral Contraceptives. | Sulfa drugs, Tricyclic antidepressants. |
| Associated Symptoms | Fatigue, nausea, abdominal pain, dark urine. | Pruritus (itching), pale or clay-colored stools, fatigue. | A mix of symptoms, potentially including fever and rash. |
| Prognosis | Can be severe, with a risk of acute liver failure in severe cases. | Often slower to resolve but generally better prognosis than severe hepatocellular injury. | Varies depending on severity; chronic issues can occur. |
Symptoms of drug-induced jaundice
Key signs of DILI include yellowing of the skin and eyes (jaundice), dark urine, pale stools, and itching. Fatigue, nausea, vomiting, and upper right abdominal pain are also common. In some cases, fever and rash may indicate an immune reaction.
What to do if you suspect drug-induced jaundice
If DILI is suspected, it is crucial to consult a doctor before stopping the medication. A doctor will evaluate symptoms, conduct blood tests for liver enzymes and bilirubin, and rule out other liver issues. Management involves discontinuing the problematic drug and providing supportive care. N-acetylcysteine is used for acetaminophen overdose. Most DILI cases improve after stopping the drug, though recovery can be slow. Severe liver failure may necessitate a transplant.
Conclusion
Drug-induced jaundice is a significant adverse drug reaction caused by various medications impacting liver function. Awareness of potentially hepatotoxic drugs, including antibiotics, NSAIDs, statins, and others, is vital. Early symptom recognition—such as jaundice, dark urine, and fatigue—and prompt medical evaluation are crucial for diagnosis and management. Always inform your healthcare provider about all medications and supplements to ensure safe treatment and prevent severe liver injury.
Learn more about DILI and liver health from the National Institutes of Health (NIH).
