hepatotoxicity

Hepatotoxicity refers to liver injury caused by chemicals, drugs, alcohol, or other toxins. It can present with jaundice, fatigue, right upper quadrant pain, nausea, or asymptomatically with abnormal liver tests. Evaluation relies on a careful history, laboratory tests (liver enzymes such as ALT and AST, alkaline phosphatase, bilirubin, and coagulation tests), imaging to exclude obstruction, and exclusion of other causes. Causality assessment tools, such as the RUCAM scale, may aid in identifying drug-induced liver injury (DILI).

Causes are broadly categorized as intrinsic or idiosyncratic. Intrinsic DILI is dose-dependent and predictable, as seen with acetaminophen overdose. Idiosyncratic DILI is unpredictable and can be caused by a wide range of medications, including amoxicillin-clavulanate, isoniazid, methotrexate, valproate, nitrofurantoin, and many herbal supplements. Alcohol-related liver disease, autoimmune hepatitis, viral hepatitis, and exposure to other hepatotoxins also contribute to hepatotoxicity. The resulting injury may be hepatocellular, cholestatic, or mixed in pattern.

Pathophysiology involves mechanisms such as formation of reactive metabolites, oxidative stress, mitochondrial dysfunction, and disruption of bile acid transport, leading to hepatocyte injury and/or cholestasis. Immune-mediated processes may also play a role in idiosyncratic cases.

Management centers on removing the offending agent and providing supportive care. N-acetylcysteine is the specific antidote for acetaminophen toxicity, most effective when given early. Corticosteroids are not routinely recommended for DILI but may be considered in cases with autoimmune-like features. Severe or irreversible injury with acute liver failure may require liver transplantation. Prognosis varies with the cause, pattern and severity of injury, and prompt withdrawal of the offending toxin often leads to improvement. Prevention emphasizes careful medication use, monitoring in high-risk patients, and avoidance of known hepatotoxins.