Impact of Duration of N-Acetylcysteine in Non-Acetaminophen–Induced Acute Liver Failure

OBJECTIVES: Studies of the use of IV N-acetylcysteine in the management of non-acetaminophen-induced acute liver failure have evaluated various dosing regimens. The only randomized trial studying this application described a 72-hour regimen. However, observational studies have reported extended duration until normalization of international normalized ratio. This study seeks to compare differences in patient outcomes based on IV N-acetylcysteine duration. DESIGN: Retrospective cohort study. SETTING: Medical ICU at a large quaternary care academic medical institution and liver transplant center. PATIENTS: Adult patients admitted to the medical ICU who received IV N-acetylcysteine for the treatment of non-acetaminophen-induced acute liver failure. INTERVENTIONS: Patients were divided into cohorts based on duration; standard duration of IV N-acetylcysteine was considered 72 hours, whereas extended duration was defined as continuation beyond 72 hours. MEASUREMENTS AND MAIN RESULTS: The primary outcome was time to normalization of international normalized ratio to less than 1.3 or less than 1.5; secondary outcomes included all-cause mortality and transplant-free survival at 3 weeks. In total, 53 patients were included: 40 in the standard duration cohort and 13 in the extended duration. There were no major differences in baseline characteristics. There was no significant difference in time to international normalized ratio normalization between cohorts. Transplant-free survival was higher with extended duration (76.9% extended vs 41.4% standard; p = 0.03). All-cause mortality at 3 weeks was numerically lower in the extended duration group (0% extended vs 24.1% standard; p = 0.08). CONCLUSIONS: Patients with non-acetaminophen-induced acute liver failure who received extended duration N-acetylcysteine were found to have significantly higher transplant-free survival than patients who received standard duration, although there was no significant difference in time to normalization of international normalized ratio or overall survival. Prospective, randomized, multicenter study is warranted to identify subpopulations of patients with non-acetaminophen-induced acute liver failure who could benefit from extended treatment duration as a bridge to transplant or spontaneous recovery.