How soon after acetaminophen overdose do aminotransferases (ALT and AST) elevate?

Timing of Aminotransferase Elevation After Acetaminophen Overdose

Aminotransferases typically begin to rise within 12-24 hours after acetaminophen overdose, with most patients showing elevations above 100 IU/L within 24 hours of ingestion, though the initial rise may be detected as early as 12-15 hours post-ingestion in severely poisoned patients. 1

Early Detection Window (12-24 Hours)

• In patients who develop significant hepatotoxicity (peak AT >1,000 IU/L), the median initial aminotransferase concentration at presentation is already elevated at 211 IU/L when measured at approximately 15 hours post-ingestion. 1

• Almost all patients who will develop hepatotoxicity show aminotransferase levels exceeding 100 IU/L within the first 24 hours after ingestion. 1

• The initial aminotransferase is already elevated in most patients at presentation, even when treatment with N-acetylcysteine is begun within 24 hours of ingestion. 1

Peak Elevation Timing (48-96 Hours)

• Peak serum transaminase activities typically occur 48-96 hours after acute ingestion. 2

• Very high aminotransferases (serum levels exceeding 3,500 IU/L) are highly correlated with acetaminophen poisoning and should prompt consideration of this etiology even when historic evidence is lacking. 3

Rate of Rise in Severe Cases

• Serum aminotransferase concentrations rise rapidly with a doubling time of approximately 9.5 hours (95% CI: 8.7-10.4 hours), especially in patients who develop AT >1,000 IU/L within 48 hours of ingestion. 1

• An abnormal and rapidly doubling aminotransferase at presentation is more typical in severely poisoned patients, as judged by effects on clotting. 1

• Patients with aminotransferase >250 IU/L during the first 12 hours of treatment with acetylcysteine have worse coagulopathy. 1

AST vs ALT Kinetics

• AST and ALT rise in a closely aligned 1:1 ratio initially, but fall at distinctly different rates: AST has a half-life of 15.1 hours (IQR: 12.2-19.4) while ALT has a half-life of 39.6 hours (IQR: 32.9-47.6). 4

• Either AST or ALT can be used for early risk stratification when only one is known, as their release into circulation appears tightly linked and numerically similar except in the sickest patients. 4

• Only patients with an AST:ALT ratio greater than 2:1 at the time of acetylcysteine administration represent the most severely ill, with higher mortality risk. 4

Critical Clinical Implications

• Rising aminotransferases indicate impending or evolving liver injury and mandate prompt initiation of N-acetylcysteine therapy. 3

• Normal aminotransferases at initial presentation (especially if <12 hours post-ingestion) do not exclude the risk of acetaminophen toxicity developing during the subsequent hours. 3

• Patients can present in liver failure days after ingestion with undetectable serum acetaminophen concentrations but markedly elevated aminotransferases. 2

Common Pitfalls

• Do not wait for aminotransferase elevation to initiate NAC therapy—treatment decisions should be based on the Rumack-Matthew nomogram for acute ingestions within 24 hours, not on liver function tests alone. 5

• Patients presenting within the first 12 hours may have normal aminotransferases despite toxic acetaminophen levels, requiring nomogram-based treatment decisions rather than relying on liver enzymes. 3, 5

• The rate of aminotransferase rise (doubling time) provides additional prognostic information beyond the absolute value and should be incorporated into risk assessment. 1