DRUG INDUCED LIVER INJURY ( DILI )
Any drugs can affect the way the liver functions, damage it, or do both.
Some drugs, such as statins (used to treat high cholesterol levels), can increase the levels of liver enzymes and cause liver damage (usually minor) but no symptoms.A very few drugs damage the liver enough to cause symptoms, such as a yellow color of the skin and eyes (jaundice), abdominal pain, itching, and a tendency to bruise, bleed and cholestasis.
Doctors use the term drug-induced liver injury (DILI) to refer to any liver damage caused by medications, whether it results in symptoms or not. The term also includes damage caused by recreational drugs, medicinal herbs, plants, and nutritional supplements.
For some drugs, liver damage is predictable. It occurs shortly after the drug is taken and is related to the drug's dose. In the United States, such damage (often caused by acetaminophen poisoning) is one of the most common causes of the sudden appearance of jaundice, liver failure, or both. For other drugs, damage is unpredictable. It is detected some time after the drug is taken and is not related to the dose. Rarely, such damage results in a severe liver disorder.
Specific Examples of DILI
Nearly every class of medication can illicit liver injury; listed below are some examples, but the list is not meant to be conclusive.
Acetaminophen is the classic example of acute, dose-related DILI, and is responsible for the largest number of cases. Acetaminophen is either glucuronidated or sulfa-conjugated to compounds that are excreted in urine.
Anesthetics
Halothane-induced DILI usually occurs after multiple and is thought to be driven by immunologic mechanisms. Clinical history may reveal fever and jaundice after previous administration(s). Hepatocyte destruction is reflected by elevated serum transaminases, while eosinophilia suggests the immune reaction. Biopsy findings may range from leukocyte infiltration to massive hepatic necrosis.
Non-steroidal Anti-inflammatory Drugs (NSAIDs)
Due to their extensive use, non-steroidal anti-inflammatory drugs (NSAIDs) are also an important cause of hepatotoxicity. Diclofenac, the most studied in this class, is glucuronidated and also subjected to cytochrome p450-mediated reactions that result in bioactive products. Both reactive metabolites and immune mechanisms mediate toxicity. Decreased prostaglandin synthesis due to cyclooxygenase (COX) inhibition may also enhance injury. Chronic diclofenac administration may result in elevated ALT levels in the first four–six months of therapy Anti-tuberculosis drugs are reported to be hepatotoxic in up to 35% of patients receiving these medications. The American Thoracic Society has published formal guidelines on how to monitor these patients for DILI.
Other Antibiotics
Beta-lactams, such as penicillins and cephalosporins, are commonly associated with DILI. The presence of beta-lactamase inhibitors (clavulanic acid) significantly increases the frequency of adverse reactions leading to cholestasis or a mixed pattern of liver injury.
Antifungals
Ketoconazole and other azoles are associated with an increased risk of hepatotoxicity. Liver injury generally presents as increased transaminase levels that are usually reversible. Although the hepatitis pattern is the most common, cholestatic and mixed forms have been observed.
HIV Antiretroviral Therapy
Up to 18% of patients treated with highly active antiretroviral therapy (HAART) develop DILI. The risk is increased by alcohol consumption, older age, and female gender. In addition, HBV and HCV co-infection enhances both the frequency and the severity of liver injury. Successful treatment of the HCV infection results in reduced hepatic toxicity of antiretroviral drugs. Drug combinations employed in HAART complicate the attempts to clearly identify the hepatotoxic potential of each individual medication.
Oral Hypoglycemics
The first drug of the thiazolidinedione class, troglitazone, was withdrawn due to its potential to cause severe hepatotoxicity. Rarely, rosiglitazone and pioglitazone have been reported to cause hepatotoxicity, including cases of hepatic failure. Among sulfonylureas, glimepiride is associated with cholestatic DILI.
Lipid-lowering Agents
Statins induce a reversible, dose-dependent rise in aminotransferase levels and very rarely result in liver failure. Monitoring the liver tests at the beginning and during statin therapy is under debate. Autoimmune-like hepatitis has been reported in several cases and may be correlated with HLA-DR3, DR4, or DR5. Interestingly, HCV infection did not significantly increase aminotransferase levels during statin treatment.
Ezetimibe (which inhibits the intestinal absorption of cholesterol) was initially reported to be safe. However, ezetimibe was recently shown to induce cholestatic DILI or an autoimmune-like hepatitis when employed alone or in combination with a simvastatin. Despite these associations, statins can often be safely used in patients with chronic liver disease.
The topic and the drug index is very vast and I have tried my best to concise it, Long term therapies of medication usually damage the liver function, it is important to use vitamins like vitamin-C, B-complex, helps in protecting liver to cause any damage because of drug induced liver injuries.
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