Reply
Authors: Thierry Gustot, Javier Fernandez, Marco Pavesi, Vicente Arroyo
Journal: Hepatology (2016)

Potential conflict of interest: Nothing to report. Author names in bold designate shared co‐first authorship. Reply: We thank McPhail et al. for their comments about our recently published paper "Clinical Course of Acute‐on‐Liver Failure Syndrome and Effects on Prognosis" in Hepatology.1 We would like to raise the following points regarding their comments. The concept of futility of care is a complex issue. Ethically, it is only justified based on the limitations of resources to attend to the medical needs of the general population even in the most developed countries. Methodologically, futility criteria should be based on studies in large cohorts of patients representative of population and specific treatments. The analysis by McPhail et al. was performed in a large cohort of patients with cirrhosis admitted to a highly specialized liver intensive care unit (ICU).2 To mimic our study, clinical assessment was performed 7 days after admission to the ICU to test our futility criteria. The CANONIC study was performed in 1349 hospitalized patients with cirrhosis and acute decompensation from February to September 2011 in 29 liver units from university hospitals in 10 European countries. Of these patients, 302 had acute‐on‐chronic liver failure (ACLF) at the time of study enrollment. The rate of direct admission to ICU of these patients of course depended on the severity of the syndrome (10% in ACLF grade 1, 32% in ACLF grade 2, and 67% in ACLF grade 3). On the other hand, all cases in the McPhail et al. series were treated in an ICU. Consequently, the design of the study by McPhail et al. does not reproduce the current clinical practice in Europe. Another major difference is that 9% of the patients included in the King's College study did not fulfill the CANONIC criteria for ACLF. Based on the CANONIC results, the expected mortality rate of these patients at 90 days after enrollment is 14%, which may account for the observed differences. Moreover, the definitions of organ failures in the two studies were different, making it difficult to compare the observed results. Despite these differences, the results reported by McPhail et al. confirm our data from the CANONIC study. The 90‐day mortality rate observed in King's College patients with a CLIF‐C ACLF score >64 (92%; 95% confidence interval, 86%‐96%) was not statistically different than that observed in the CANONIC study in patients with a CLIF‐C ACLF score >60 (100%; 95% confidence interval, 82%‐100%). In conclusion, we believe that futility criteria for general use should be based on studies that reproduce the real context of the disease treatment. Contrary to our study, which included a general population of hospitalized patients with cirrhosis, the McPhail et al. study and its prognostication are more appropriate for a liver‐specialized ICU. It was surprising to observe such a low rate of admission at ICU (36%) for the CANONIC study patients with ACLF grade 2 and 3 who showed a short‐term (28‐day) mortality rate of 40% and 63%, respectively (the reasons for this low rate are currently unknown). Prompt ICU admission may improve outcomes and question our futility criteria of ACLF patients.