Successful N-Acetylcysteine Treatment of Trimethoprim/Sulfamethoxazole-Induced Acute Liver Injury 2235

• Published in: The American journal of gastroenterology Vol. 113; no. Supplement; p. S1269
• Main Authors: Ryan-Fisher, Courtenay, Rawi, Sarah, Sachdev, Rishabh, Vinsard, Daniela G.
• Format: Journal Article
• Language: English
• Published: New York Wolters Kluwer Health Medical Research, Lippincott Williams & Wilkins 01.10.2018
• Subjects: Abdomen; Analgesics; Antibiotics; Drug overdose; Gastroenterology; Liver; Recreational drugs
• DOI: 10.14309/00000434-201810001-02234
• ISSN: 0002-9270

Trimethoprim/Sulfamethoxazole (TMP/SMX) causes hepatotoxicity, defined as a two-fold increase in aminotransferase or total bilirubin.1 TMP/SMX contains propylene glycol, a solvent metabolized in the liver to lactic acid, leading to lactic acidosis.2 A previously healthy 23-year-old female presented to our ED with 24 hours of nausea, vomiting and abdominal pain. She had been taking TMP/SMX for 3 days for a UTI. She was tachycardic, normotensive and afebrile. Her physical exam revealed tenderness to palpation of her right hemi-abdomen. There was no evidence of organomegaly, jaundice, encephalopathy, asterixis or rash. Initial laboratory tests showed total bilirubin 3.6 mg/dL, INR 2.3, albumin 3 g/dL, AST 959, ALT 812, ALP 55, lactate 7 mmol/L, LDH 6494, and WBC 16.2. Acetaminophen levels, urine toxicology, and alcohol levels were all unremarkable and the patient denied ingestion of supplements or recreational drugs. Additional labs included: negative HAV, HBV, HIV, EBV, CMV; negative ANA, ASMA; normal IgG, ceruloplasmin and iron panel. Abdominal US revealed normal hepatobiliary appearance with portal vein patency. The patient's initial treatment consisted of fluid resuscitation. Her lactate resolved to normal within 24 hours, but her liver function tests continued to worsen, peaking at: AST 9958, ALT 8401, INR 4.5; consistent with hepatocellular injury. She was diagnosed with drug-induced liver injury (DILI) secondary to TMP/SMX with a RUCAM (Roussel UCLAF Causality Assessment Method) score3 of 9. N-acetylcysteine (NAC) infusion 100mg/kg was initiated on day 2 and continued for 72 hours with marked clinical improvement, avoiding encephalopathy and liver transplant. To our knowledge, this is the first case report illustrating both elevated lactate and DILI secondary to TMP/SMX. For patients with non-acetaminophen DILI, ACG guidelines support NAC use for earlystage ALF4; however further research into DILI without ALF is needed. Our patient was found to have an expedited recovery, while preventing further liver failure and complications, showing the utility of drug discontinuation with concomitant NAC infusion as an early intervention.