Table 1.
An overview of randomized clinical trials reporting on the beneficial effects of N-acetyl cysteine (NAC) administration on liver function in patients with drug-induced liver injury.
| Study | Country | NAC dosage and duration | Main findings |
|---|---|---|---|
| Yip and Dart [87] | United States | Received loading dose of NAC at 140 mg/kg body weight, within 8 h after acetaminophen ingestion. A total of six doses were given in a 20 h period, between 1996 and 1999 | Effective in preventing hepatic injury after an acute acetaminophen overdose when the loading dose was initiated within 8 hours after ingestion, especially in patients with an acetaminophen level below the probable hepatotoxicity line |
| Kerr et al. [96] | Australia | Received loading dose of NAC at 150 mg/kg intravenous over a 15 min versus 60 min period | Did not reduce drug-related adverse outcomes with the 60-minute infusion. However, early treatment with NAC (within 8 hours of ingestion) was more effective than later treatment in patients who presented with acetaminophen poisoning |
| Stewart et al. [94] | United Kingdom | Received NAC at 150 mg/kg followed by 100 mg/kg/day for 1 week, and vitamins A–E, biotin, selenium, zinc, manganese, copper, magnesium, folic acid, and coenzyme Q daily for 6 months | Antioxidant therapy, alone or in combination with corticosteroids, did not improve 6-month survival in patients with a severe alcoholic hepatitis |
| Thorsen et al. [97] | Denmark | Received NAC at 250 mg/kg BW intravenously over 12 h, distributed as 150 mg/kg bolus over 15 min, 50 mg/kg over 4 h, and 50 mg/kg over 8 h | Induced a progressive time-dependent partly reversible depression of plasma factor II+VII+X activity to a plateau at 37°C in vitro. A decrease in temperature below 24°C markedly depresses the effect of NAC on plasma factor II+VII+X activity minimizing a preanalytical additional depression of factor II+VII+X activity by residual reactive NAC |
| Bateman et al. [93] | United Kingdom | Received intravenous NAC regimen at 150 mg/kg for the duration of 20 and 25 h over 15 min. Or a shorter a dose of 100 mg/kg in 200 mL, over 2 h for 12 h; with ondansetron pretreatment (4 mg) | In patients with paracetamol poisoning, a 12 h modified NAC regimen resulted in less vomiting, fewer anaphylactoid reactions, and reduced need for treatment interruption |
| Heard et al. [88] | United States | Received NAC at 140 mg/kg loading dose followed by 70 mg/kg every 4 h for 12 doses | Acetaminophen-overdosed patients treated with NAC had a low rate of hepatotoxicity and few adverse events |
| Nabi et al. [21] | India | Received NAC at 150 mg/kg over 1 h, followed by 12.5 mg/kg/h for 4 h and continuous infusion of 6.25 mg/kg/h for remaining 67 h | Reduced mortality and shortened length of hospital stay in survived patients with on-acetaminophen-induced acute liver failure. Moreover, the survival of patients was improved by NAC. Also, drug-induced acute liver failure showed improved outcome |
| Singh et al. [95] | India | NAC was given at 150, 50, and 100 mg/kg, over 30 min, 4 h, and 16 h, respectively; days 2 through 5: 100 mg/kg/day. Granulocyte colony stimulating factor (GCSF) was given at a dose of 5 μg/kg subcutaneously every 12 h for 5 consecutive days | Administration of GCSF improved liver function and increased survival times in patients with severe alcoholic hepatitis, compared to standard therapy, in patients with alcoholic hepatitis. There was no evidence for benefit of adding NAC to GCSF |
| Morrison et al. [92] | United Kingdom | Received NAC at 100 mg/kg in 200 ml over 2 h. Calmangafodipir, a superoxide dismutase mimetic, was administered at 2, 5, or 10 μmol/kg, depending on a cohort, with different NAC doses | Calmangafodipir was tolerated when combined with NAC and reduced biomarkers of paracetamol toxicity such as alanine aminotransferase (ALT), keratin-18, and circulating caspase-cleaved cytokeratin-18 in patients with paracetamol overdose |
| Pickering et al. [89] | France | Received NAC at 300 mg twice daily, and paracetamol at 1 g ×4 daily for 4 days | Neutralized paracetamol-induced hepatic toxicity. This effect was related to the maintenance of glutathione levels |
| Wong et al. [90, 91] | Australia | Received 12 h NAC regimen (200 mg/kg over 4 h, 50 mg/kg over 8 h) versus the control group subjects administered a 20 h course of NAC (200 mg/kg over 4 h, 100 mg/kg over 16 h) | An abbreviated 12 h NAC regimen for paracetamol overdose had similar circulating metabolite concentrations compared to a 20 h regimen in selected subjects with low risk of hepatotoxicity. Also, there was no observed increased liver injury or any effect on levels of ALT or miR-122 expression |