Co-medications that modulate liver injury and repair influence clinical outcome of acetaminophen-associated liver injury.
OBJECTIVE
Acetaminophen-induced liver injury is the most common cause of acute liver failure in the United States; it occurs inadvertently in approximately half of all cases. Concomitant use of other medications might impact susceptibility to acetaminophen hepatotoxicity. We investigated its association with administration of drugs that have been shown to modulate liver injury and/or repair in preclinical studies.


METHODS
We analyzed data from 6386 cases of acetaminophen-associated liver injury that were defined in the FDA database of reported adverse events. Data reported in the severe adverse event categories of "died" or "life-threatening" (defined as "fatal" cases, n = 2512) were compared with those of "non-fatal" cases (n = 3874). Potential associations between fatality and concomitant use of 9 drug classes were assessed using multiple logistic regression analyses after adjusting for other variables.


RESULTS
Among female subjects, concomitant use of statins, fibrates or nonsteroidal anti-inflammatory drugs was associated with decreased likelihood of fatality, whereas ethanol use was associated with increased likelihood. Among male subjects, concomitant use of statins was associated with decreased likelihood of fatality, whereas concomitant use of sympathetic stimulants or ethanol was associated with increased likelihood. Concomitant use of angiotensin converting enzyme inhibitors or angiotensin receptor II antagonists was associated with decreased likelihood of fatality among younger subjects.


CONCLUSIONS
Concomitant use of medications that have been shown in preclinical studies to modulate liver injury and/or repair influenced acetaminophen hepatotoxicity. Drugs that reduce injury or increase repair are protective, whereas those that exacerbate injury or reduce repair are detrimental.
Suzuki
Ayako
A
Gastroenterology, Duke University, Durham, North Carolina, USA. suzuk004@mc.duke.edu
Yuen
Nancy
N
Walsh
John
J
Papay
Julie
J
Hunt
Christine M
CM
Diehl
Anna Mae
AM
D000082:Acetaminophen / Q000009:adverse effects*; D000322:Adrenergic Agonists / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury; D002995:Clofibric Acid / Q000627:therapeutic use; D004347:Drug Interactions; D000431:Ethanol / Q000633:toxicity; D005260:Female; D006801:Humans; D008107:Liver Diseases / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult
D000322:Adrenergic Agonists; D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000924:Anticholesteremic Agents; D000082:Acetaminophen; D000431:Ethanol; D002995:Clofibric Acid