Poisoned Liver: A Rare Case of Acetazolamide-Induced Liver Injury

Introduction: Drug-induced liver injury (DILI) is a phenomenon where the liver suffers toxic injury in a hepatocellular or cholestatic pattern due to drug exposure. DILI is a diagnosis of exclusion. The following case highlights a rare example of DILI caused by acetazolamide, a carbonic anhydrase inhibitor used as a diuretic and also to limit CSF production. Case Description/Methods: A 66-year old man with a history of stage IV lung adenocarcinoma was admitted to the medicine service with acute nausea and vomiting due to post-lumbar laminectomy CSF leak. He was started on a five-day course of acetazolamide 250 mg twice daily to reduce the severity of the leak. Three days after course completion, his liver function tests (LFTs) were elevated in a hepatocellular pattern (ALT 426 Units/L; AST 251 U/L; Alk. Phos. 278 U/L) despite being within normal limits two days prior to admission. The patient had no apparent jaundice or icterus; liver sonography showed mild hepatomegaly with fatty changes, without any cholelithiasis or ductal dilation. A hepatitis panel and autoimmune workup were both unremarkable. Despite a lack of any intervention, the patient’s LFTs returned to normal after two weeks. An initial investigation failed to identify a cause that could explain his injury timeline and severity. The patient was readmitted to our care 10 days after discharge due to recurrent CSF leak; acetazolamide 250 mg was re-initiated, now thrice daily. On day 1 of readmission, LFTs were within normal limits, however there was a rapid and severe increase of LFTs by day 3 (ALT 1298 U/L; AST 224 U/L; Alk. Phos. 227 U/L). As its inadvertent rechallenge resulted in DILI, we concluded that acetazolamide was the sole offender that could explain this phenomenon. We promptly discontinued the drug and administered a steroid taper; shortly thereafter, LFTs plateaued and then gradually declined. Discussion: There are only 2 documented cases of acetazolamide-induced liver injury. In 1967, a glaucoma patient suffered fatal cholestatic injury; in 2013, a pseudotumor cerebri patient developed hepatocellular injury. In our patient’s example, there was a characteristic severe reoccurrence upon rechallenging the patient with acetazolamide that allowed us to make a prompt diagnosis and discontinue the offending agent. The Naranjo Adverse Drug Reaction Score was 10, implying definite causality. This patient’s case should serve to make clinicians aware of the potential of severe drug-induced liver injury that can occur with acetazolamide.