Drug-induced Liver Injuries (DILI)
Overview: Drug-induced liver injury (DILI) is a condition where the liver is damaged due to the intake of medications, herbal products, or other chemical substances. It is one of the leading causes of acute liver failure and is a significant reason for the withdrawal of drugs from the market and the cessation of drug development.
Pathogenesis: DILI can be classified into two main types: intrinsic and idiosyncratic.
- Intrinsic DILI:
- Predictable and Dose-Dependent: This type of liver injury is predictable and occurs when a person takes a drug at a dose high enough to cause liver damage. Acetaminophen (paracetamol) overdose is a common example.
- Mechanism: It often involves direct hepatotoxicity or the formation of toxic metabolites that overwhelm the liver’s detoxification pathways, leading to cell damage and death.
- Idiosyncratic DILI:
- Unpredictable and Dose-Independent: This form of liver injury is less common and occurs unpredictably, often without a clear dose-response relationship. It is not related to the drug’s pharmacological action and can vary significantly between individuals.
- Mechanism: It may involve genetic susceptibility, immune-mediated mechanisms, or a combination of both. Certain genetic polymorphisms in drug-metabolizing enzymes or immune response genes may predispose individuals to idiosyncratic DILI.
Clinical Presentation: The clinical manifestations of DILI can range from mild elevations in liver enzymes to severe liver failure. Symptoms may include:
- Jaundice (yellowing of the skin and eyes)
- Fatigue
- Nausea and vomiting
- Abdominal pain
- Dark urine
- Pale stools
- Itching
In severe cases, it can lead to acute liver failure, which is a life-threatening condition requiring immediate medical attention.
Drug Causing Hepatitis:
Certain drugs can cause hepatitis, an inflammation of the liver. This happens when the liver reacts negatively to medications, herbal supplements, or toxins. Symptoms include jaundice (yellowing skin/eyes), fatigue, and abdominal pain. Stopping the drug usually helps, but severe cases might need medical treatment or liver transplantation.
Drug Induced Liver (Hepatitis) Treatment:
Diagnosis: Diagnosing DILI is challenging and involves a thorough medical history, including a detailed review of all medications, supplements, and herbal products taken by the patient. Other causes of liver injury must be excluded, such as viral hepatitis, alcoholic liver disease, and autoimmune liver diseases. Diagnostic tests may include:
- Liver function tests (LFTs)
- Imaging studies (ultrasound, CT, MRI)
- Liver biopsy (in selected cases)
Management: The primary treatment for DILI is the immediate discontinuation of the offending drug or substance. In cases of acetaminophen overdose, N-acetylcysteine (NAC) is used as an antidote. Severe cases of DILI may require hospitalization and, in some instances, liver transplantation.
Prevention: Preventing DILI involves careful prescription practices, including:
- Awareness of drugs with a high risk of causing DILI
- Monitoring liver function in patients on long-term or high-risk medications
- Educating patients about the risks of over-the-counter drugs and herbal supplements
- Reporting and monitoring adverse drug reactions through pharmacovigilance systems
Conclusion
Drug-induced liver injury is a significant public health concern due to its potential to cause severe liver damage and its impact on drug development and safety. Early recognition, prompt discontinuation of the offending agent, and supportive care are crucial in managing DILI. Ongoing research aims to better understand the mechanisms underlying DILI and to identify genetic and environmental factors that may predispose individuals to this condition.
FAQ?
Symptoms can vary widely but may include jaundice, abdominal pain, nausea, vomiting, fatigue, and dark urine.
Diagnosis involves reviewing the patient's medication history, physical examination, blood tests (liver function tests), imaging studies, and sometimes a liver biopsy to confirm the diagnosis.
Treatment depends on the severity and cause of DILI and may include stopping the offending medication, supportive care, and monitoring liver function until recovery.