032). Comparing overall and transplant-free survival in the different etiological groups, ALF caused by DILI ACP-196 or hepatitis B virus infection seemed to have the highest benefit of NAC therapy. Due to the small number of patients,

statistical subgroup analysis was not reasonable and therefore was not performed. Advances in intensive care medicine and supportive therapy have improved the overall outcome of ALF. However, liver transplantation remains the ultimate therapy in those patients who fail to restore functional liver mass. In the present study, 40% of the patients required liver transplantation. The authors demonstrate that organ availability and quality are essential factors determining short-term outcomes of transplantation. In patients with early-stage non–AAF-induced liver failure, they could demonstrate

an improved transplant-free Raf inhibitor survival using NAC. These results indicate that patients with non–AAF-induced ALF could benefit from early NAC therapy. Due to the complexity of ALF and the requirement of vigorous intensive-care therapy, it has been unlikely that a given drug will be the “magic bullet” in improving the outcome of non–AAF-induced ALV. However, because NAC has already been studied before in vitro and in vivo it may give a link to a better understanding of ALV pathophysiology. Treatment with NAC also has some beneficial effects after late administration in AAF toxicity, which indicates

additional mechanisms of cellular protection. Recent data from mouse models imply hepatoprotective effects independent of gluthatione replenishment but rather based on changes in intracellular energy metabolism due to NAC.6 NAC especially favors the formation of hypotaurin (Htau) from its cysteine residue, which has been shown protective in cell injury by acting as radical scavenger.7 However, the hepatoprotective potential of Htau is not completely understood. Moreover, NAC increases flux through pyruvate dehydrogenase, D-malate dehydrogenase a key enzyme for mitochondrial energy metabolism by providing acetyl-coenzyme A for the mitochondrial tricarboxylic acid cycle. These metabolic actions seem interesting because they potentially stabilize the mitochondrial function in these patients. Additionally, NAC has been shown to influence cytokine synthesis and is a free-radical scavenger, hence, it has anti-inflammatory and antioxidant effects and may positively affect liver regeneration.8 Moreover, NAC has inotropic and vasodilatatory effects, which might improve microcirculation and oxygen delivery in multiorgan failure due to ALF of all etiologies.9 In summary, the findings of this study are very relevant not only for the novelty of the results, but also that they provide an additional therapeutic option in selected patients with ALF.