Acute liver failure and bioartificial liver support: preventing the former to obviate the latter

We read with interest the paper by Samuel et al. (1) that concluded with a statement on the good tolerance of the bioartificial liver (BAL) HepatAssist 2000 and its therapeutic efficacy on the neurologic condition of patients with acute liver failure (ALF) awaiting emergency liver transplantation (LT). An accompanying editorial by two experts in the field of ALF emphasizes limitations of the study and concludes that BAL cannot be recommended for routine clinical use (2). Thus, Transplantation presents two opposite and confronting opinions. Samuel’s study is an evaluation of “tolerability and safety” (1) that does not allow the authors to make a conclusion on therapeutic efficacy. Moreover, because even a transient improvement in overall liver function was barely detectable, a nonliver-specific, rather than a liver-like, effect of BAL can be contemplated (2). The mean initial serum creatinine (as calculated from data in that article’s Table 1) was lower in the six patients with (100 μmol/L), than in the four patients without (161 μmol/L), improvement in neurologic scores during the first BAL course. Thus, this improvement could be related, at least in part, to a relatively preserved initial renal function. What is noteworthy is that the accuracy of determining serum creatinine is questionable because, although serum bilirubin was above 300 μmol/L in most patients (Table 3), serum creatinine was below 50 μmol/L in two patients (Table 1), which is quite an unexpected finding in adults with ALF. Underevaluation of serum creatinine is common in patients with high levels of bilirubin when the negative interference of bilirubin is not eliminated before creatinine determination by the kinetic Jaffe reaction (3). Samuel’s study also points to serious drawbacks of BAL (2) without considering the risk of overtransplantation and whether it could have been increased by using BAL. Whatever the therapeutic strategy in patients with ALF, this risk is mathematically unavoidable because the criteria for emergency LT, drawn from Beaujon-Paul Brousse as well as King’s College Hospital (4), were established with a 80% to 90% (not 100%) fatality rate. Thus, when patients with both ALF and the above criteria are bridged to emergency LT, as it occurred in the 10 patients managed with BAL, the individual risk of overtransplantation ranges from 10% to 20%. This, as emphasized by the late Dame Sheila Sherlock (5), is not a fully satisfactory therapeutic achievement. In this context, the unusually high 50% rate of serious bleeding complications reported by Samuel et al. might have compromised the 10% to 20% chance of spontaneous recovery in the 10 patients managed with BAL, especially in the 2 patients with favorable prognostic factors (i.e., both a short delay onset jaundice-encephalopathy and initial serum creatinine below 110 μmol/L) (Table 1) (4). Thus, considering BAL’s undetectable liver-like effect and its serious drawbacks, the usefulness of the Paul-Brousse team’s study might essentially be to promote increased efforts in prevention of ALF in patients with acute liver disease and thus reduce the number of those who will need artificial liver support and emergency LT. Jacques R. Bernuau François Durand Dominique C. Valla