Fulminant Chemical Hepatitis Possibly Associated with Donepezil and Sertraline Therapy

Abstract

An older woman with Alzheimer's disease was admitted to a dementia care facility because of aggressive behavior. Treatment with sertraline was initiated in February 1998. Sertraline doses were increased gradually to 200 mg daily by May 1998, and some improvement in behavior was seen. Concomitant therapy with donepezil 5 mg qhs was initiated June 26, 1998. Ten days later, confusion and jaundice were noted. Total bilirubin was 5.6 mg/dL, GGTP was 1,208 IU/L, and alkaline phosphatase was 369 IU/L. Computed tomography revealed cholelithiasis without ductal dilation. Liver, spleen, and pancreas seemed normal. Donepezil and sertraline were discontinued. The patient was admitted to our institution and treated for dehydration. A liver biopsy revealed scattered portal eosinophils and prominent cholestasis consistent with acute chemical hepatitis. The GGTP and total bilirubin of this patient peaked at 2,235 IU/L and 22.6 mg/dL, respectively. The patient improved, and her liver function tests normalized over the next 2 months.

Sertraline Hepatotoxicity: Report of a Case and Review of the Literature

“…In the medical literature, we found only six other case reports of possible sertraline-induced hepatotoxicity (Table 3) [1,[3][4][5][6]. The mechanism of sertraline-induced hepatotoxicity is of great debate.…”

“…Here, a case of severe drug-induced hepatitis in a patient receiving sertraline is presented. To the best of our knowledge, this is the seventh case in the medical literature as being associated with severe hepatotoxicity [1,[3][4][5][6].…”

Sertraline Hepatotoxicity: Report of a Case and Review of the Literature

“…In all published cases, the onset of symptoms occurs between the first and ninth week [7], except in the case reported by Verrico [8] in whom the symptoms developed immediately after the association of donepezil, a drug that, like sertraline, is metabolized through cytochrome P-450 2D6.…”

Endoplasmic Reticulum Stress in Drug- and Environmental Toxicant-Induced Liver Toxicity

“…Although it is generally considered safe, acute liver failure due to sertraline use has been documented [91][92][93][94][95][96][97][98][99]. Sertraline was demonstrated to be toxic in primary rat hepatocytes and human HepG2 cells; mitochondrial dysfunction and apoptosis are the underlying mechanisms [100,101].…”