N-acetyl cysteine in Treatment of Transaminitis
N-acetyl cysteine (NAC) is strongly recommended for acetaminophen-induced transaminitis and acute liver failure, but should only be used in the context of clinical trials for non-acetaminophen-related transaminitis. 1
Effectiveness Based on Etiology
Acetaminophen-Induced Transaminitis
- NAC is highly effective in preventing and treating acetaminophen-induced liver injury when administered early 1
- The American Gastroenterological Association (AGA) provides a strong recommendation for NAC use in acetaminophen-associated acute liver failure (ALF), despite the very low quality of evidence 1
- NAC improves mortality in acetaminophen-induced liver injury (relative risk 0.65,95% CI 0.43-0.99) 1
- NAC should be initiated immediately without waiting for acetaminophen level results if acetaminophen overdose is suspected 1, 2
Non-Acetaminophen-Induced Transaminitis
- For non-acetaminophen-related transaminitis, the AGA recommends NAC use only in the context of clinical trials 1
- Post-hoc analysis of one study showed mortality benefit in patients with stage 1 or 2 hepatic encephalopathy, but not in overall non-acetaminophen ALF patients 1
- Some evidence suggests NAC may be beneficial in post-transarterial chemoembolization transaminitis in hepatocellular carcinoma patients 3
Mechanism of Action
- NAC works through multiple mechanisms to protect the liver: 4, 5
- Replenishes glutathione stores depleted during acetaminophen metabolism 2
- Acts as a direct free radical scavenger 5, 6
- Serves as an alternate substrate for conjugation with toxic metabolites 2
- Modulates inflammatory cytokines like TNF-alpha and IL1-beta 5
- Has immunomodulatory effects that reduce oxidative stress 4, 5
Dosing and Administration
For Acetaminophen Overdose
- Oral loading dose: 140 mg/kg followed by maintenance doses 2
- Intravenous regimen: 150 mg/kg for 1 hour, then 12.5 mg/kg/h for 4 hours, followed by 6.25 mg/h for 67 hours 1, 3
- Treatment should be initiated as soon as possible, ideally within 8-10 hours of ingestion 1, 7
For Transaminitis Management
- For post-TACE transaminitis: IV NAC for 72 hours has shown significant reduction in AST and ALT levels 3
- For patients with severe transaminase elevation, paracetamol should be avoided if possible 8
- If paracetamol is necessary in patients with elevated transaminases, limit dose to 2g/day with daily monitoring 8
Timing and Efficacy
- Treatment timing is critical for effectiveness: 1, 7
- NAC should be started as early as possible and within 24 hours of acetaminophen ingestion 2
Special Considerations and Pitfalls
- NAC should be administered to patients with hepatic failure thought to be due to acetaminophen, even without confirmed levels 1, 9
- In cases of ALF of indeterminate cause, NAC can be considered as some cases may be related to unrecognized acetaminophen toxicity 1
- Patients may underreport their actual paracetamol intake, making clinical assessment challenging 8
- Patients may present with elevated transaminases despite being stratified as "no risk" on the Rumack-Matthew nomogram due to inaccurate history or increased susceptibility 9
Adverse Effects
- Oral administration may cause nausea, vomiting, and other gastrointestinal symptoms 2
- IV administration may cause anaphylactic reactions and cutaneous adverse events 7
- Rash with or without mild fever has been observed rarely 2
- Overall, NAC has a favorable safety profile with relatively rare side effects 6