Successful orthotopic liver transplantation after trimethoprim–sulfamethoxazole associated fulminant liver failure

Abstract

Trimethoprim-sulfamethoxazole (TMP-SMZ) is one of the most commonly used antibiotics. Although many of its adverse effects are well recognized, TMP-SMZ related hepatotoxicity is considered rare and is usually characterized by cholestasis or mixed hepatocellular-holestatic reactions. In this study, we describe the case of a previously healthy young man with acute fulminant liver failure caused by TMP-SMZ. The patient presented with complaints of 'flu-like' symptoms with myalgia and fever after taking TMP-SMZ for 7 d for otitis externa. The patient subsequently developed fever, worsening jaundice, and a rash on his neck and chest. Liver enzymes peaked on day 3 with alanine aminotransferase (ALT) 11,549, aspartate aminotransferase (AST) 23,289, alkaline phosphatase 245, and total bilirubin 10.3 mg/dL, with a conjugated bilirubin of 8.3 mg/dL, prothrombin time (PT) 60.5 s, partial normalized ratio (PTT) 49 s, and international normalized ratio (INR) 7.5. Of note, acetaminophen level on admission was undetectable. Serology for hepatitis A, B, C, cytomegalovirus, HIV, toxoplasmosis, and blood cultures were all negative. The patient developed hepatic encephalopathy with hallucination on day 4. Laboratory tests revealed a serum ammonia level of 190 U, serum creatinine kinase (CK) 10,466 (42 on admission), serum creatinine 8.2 mg/dL (1.2 on admission), and significant metabolic acidosis. Renal ultrasound was unremarkable. The patient was started on hemodialysis for acute renal failure. Meanwhile, liver transplantation assessment was also initiated. On day 8 post-admission (15 d after taking TMP-SMZ), the patient received a successful orthotopic liver transplant.

Considerations when prescribing trimethoprim-sulfamethoxazole

“…Typical manifestations vary in presentation and severity. They include hematologic abnormalities (most commonly lymphopenia or lymphocytosis, but occasionally eosinophilia), cholestatic or hepatocellular hepatitis (which may progress to fulminant hepatic failure), renal dysfunction (including acute interstitial nephritis), [11][12][13][14][15] Stevens-Johnson syndrome and potentially life-threatening toxic epidermal necrolysis. 16 If there has been no previous exposure to trimethoprim-sulfamethoxazole, these reactions typically begin after at least four or five days of therapy but may occur after several weeks of prolonged therapy.…”

Successful extracorporeal liver dialysis for the treatment of trimethoprim-sulfamethoxazole-induced fulminant hepatic failure

“…(5,6) There may be a genetic predisposition in patients who are slow acetylators, possibly due to impairment in normal elimination of toxic metabolites. (7) In 0.01%-0.1% of patients, TMP-SMZ induces DRESS syndrome with a significant mortality rate of up to 10%. (2,6) DRESS syndrome is characterised by fever, rash, lymphadenopathy, eosinophilia and involvement of one or more organs, (2,6,8) and typically occurs one to five weeks after initiation of the offending drug.…”

“…Although most patients with TMP-SMZ-induced fulminant hepatic failure improve with discontinuation of the drug, some may require resin haemoperfusion or liver transplantation. (1,5,7,8,12) Deaths from TMP-SMZ-induced fulminant hepatic failure have also been reported. (4,5) Table II summarises the reported cases of patients with TMP-SMZ-induced fulminant hepatic failure.…”

Trimethoprim-Sulfamethoxazole-Induced Hepatitis in Mixed Connective Tissue Disease

“…On the other hand, numerous cases of severe hepatic toxicity or fulminant hepatitis caused by TMP-SMZ have been reported [5][6][7][8][9], most of which were complicated by the use of TMP-SMZ as an anti-biotic drug for infectious disease. The mechanism of TMP-SMZ-induced hepatitis remains to be clarified [3], but several possibilities have been put forward.…”