title: Is excessive acetaminophen intake associated with transaminitis in adult patients with dengue fever?
abstract: BACKGROUND
  Dengue, an endemic infection causing severe flu-like symptoms and fever, is often treated with high-dose acetaminophen that can exceed recommended daily dosages. This leads to hepatotoxicity, although the underlying mechanism is poorly understood. We hypothesised that excessive acetaminophen causes hepatic toxicity in dengue patients.
  
  
  OBJECTIVE
  To investigate a correlation between elevated serum transaminases and excessive acetaminophen intake, and other aggravating factors of liver injury in dengue cases.
  
  
  METHODS
  This prospective observational study obtained blood samples from 150 participants with acute febrile illness for dengue serological tests, blood counts, and the detection of serum transaminases and acetaminophen levels. Other factors were determined by questionnaire.
  
  
  RESULTS
  Of 150 participants enrolled, 77 had dengue fever. Abnormally high serum aspartate transaminase and alanine transaminase levels were present in 97.0% and 75.3% of dengue cases respectively. Multivariate analysis of cases with increased serum transaminases more than threefold normal upper limits indicated that male gender (odds ratio (OR) = 3.62, 95% confidence interval (CI) 1.38-9.42) and consuming >8 g acetaminophen orally (OR = 4.62, 95% CI 1.37-13.18) correlated with transaminitis. No correlation was found for other factors such as age, fever day at presentation, body mass index, alcohol intake or dengue severity classification (all P > 0.05). Chronic alcohol consumption was higher in non-dengue (2.6%) versus dengue cases (27.8%) (P < 0.01).
  
  
  CONCLUSIONS
  Most dengue patients had mild-to-moderate transaminitis. Male gender and acetaminophen >8 g were associated with increased serum transaminases. Thus, 1000 mg acetaminophen every 8 h or <3000 mg/day is recommended for dengue cases. Chronic alcohol consumption might be protective against dengue infection.
authors.affiliation: Department of Medicine, Division of Ambulatory Medicine, Faculty of Medicine Siriraj Hospital, Bangkok, Thailand.
authors.forename: D
authors.initials: D
authors.lastname: Pandejpong
authors.affiliation: Department of Medicine, Chumphonkhetudomsakdi Hospital, Chumphon, Thailand.
authors.forename: P
authors.initials: P
authors.lastname: Saengsuri
authors.affiliation: Department of Medicine, Siriraj Piyamaharajkarun Hospital, Bangkok, Thailand.
authors.forename: R
authors.initials: R
authors.lastname: Rattarittamrong
authors.affiliation: Department of Dermatology, Samitivej Hospital, Bangkok, Thailand.
authors.forename: T
authors.initials: T
authors.lastname: Rujipattanakul
authors.affiliation: Department of Medicine, Division of Ambulatory Medicine, Faculty of Medicine Siriraj Hospital, Bangkok, Thailand.
authors.forename: C
authors.initials: C
authors.lastname: Chouriyagune
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage* / Q000009:adverse effects*; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood*; D001219:Aspartate Aminotransferases / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D003715:Dengue / Q000097:blood* / Q000188:drug therapy; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D015415:Biomarkers; D000082:Acetaminophen; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: acetaminophen; alcohol consumption; dengue infection; natural killer cell; transaminitis