Antibiotics play a crucial role in our fight against bacterial infections. However, like all medications, they come with potential side effects. The liver is exposed to all kinds of drugs regardless of the administration route (oral, intravenous, or inhalation). The liver contains numerous enzymes to metabolise these drugs. One serious side effect of antibiotics is liver injury. However, the risk of injury to the liver varies with the type of antibiotics, and there are different mechanisms by which the liver is affected. The liver is a crucial organ that detoxifies and metabolises all drugs and chemicals. When it can’t process a drug efficiently or encounters a toxic reaction with a drug, liver injury can occur which ranges from mild to some elevation of liver enzymes to severe liver failure.
Antibiotics that can damage the liver
Amoxicillin-clavulanate (like Augmentin) is a common antibiotic that causes antibiotic-associated liver injury when used excessively, presenting as a cholestatic pattern of hepatitis. Isoniazid (used for tuberculosis) is another drug in India that poses a significant problem in the form of direct hepatotoxicity, particularly in the elderly when combined with other anti-TB medicines like rifampicin. Macrolides, like azithromycin and erythromycin, used for common respiratory infections, also cause cholestatic or hepatocellular liver injury. Drugs like fluoroquinolones can cause severe hepatotoxicity whereas tetracycline causes liver injury — however, their occurrence is quite rare. Contrary to common belief, paracetamol does not cause liver toxicity when used in recommended or less-than-recommended doses but can cause liver injury in overdose — this is a common cause of acute liver failure in the West. In India, paracetamol-induced liver injury is less frequent. A common cause of chemical-induced liver injury and acute liver failure in southern India is the rodenticide (zinc phosphide), although it is used as a pesticide and not as a drug. Off-the-counter preparations, herbal and other “natural medicines” also cause severe liver injury. These drugs haven’t been subjected to the scientific assessment of their efficacy, dosage estimations, and side-effect profile and haven’t been through randomised trials in humans to establish their place in the therapy of illnesses.
Mechanisms of liver injury
The mechanisms of antibiotic-induced liver injury are complex and varied. However, numerous pathways have been identified along with continuous research to understand the mechanisms of liver damage and its prevention measures. Isoniazid causes direct hepatotoxicity. Some antibiotics, like Augmentin, cause immune-mediated liver injury, where the immune system attacks the liver triggered by the drug. Individuals vary in their risk for such drug-induced liver disease depending upon pre-existing liver disease and other co-morbid conditions.
Symptoms of liver disease
Recognising the symptoms of liver injury is crucial. A good patient history is extremely important when treating patients with liver dysfunction or liver failure in any setting (clinic/emergency/ICU). This also helps in identifying the cause of liver problems, including drug exposure — either accidental or intentional. Common symptoms include jaundice (yellowing of the eyes and skin), fatigue, right abdominal pain, dark urine, nausea, vomiting, and itching (especially in cases of cholestatic jaundice).
Treatment & prevention
Treatment generally focuses on maintaining other organ systems while waiting for the liver to recover. Medications can reduce inflammation, but sometimes steroids may be necessary. Severe cases require specific extracorporeal therapies like plasma exchange or liver dialysis. If the liver is irreparably damaged and there is a risk to life due to severe irrecoverable liver failure, a liver transplant might be required. Preventive measures and awareness of drug-related liver issues play an important role in terms of managing and preventing drug-related liver problems. Doctors should inform patients about possible side effects when prescribing such medications and alert them of early symptoms of any damage.
(The author is the lead consultant for HPB, liver transplantation, and robotic surgery at a leading hospital in Bengaluru.)