Futility of care in patients with acute‐on‐chronic liver failure
Authors: Filipe S. Cardoso, Rui Pereira, Gonçalo Alexandrino, Luís Bagulho
Journal: Hepatology (2017)

Potential conflict of interest: Nothing to report. Author names in bold designate shared co‐first authorship. To the Editor: In their article on the clinical course of acute‐on‐chronic liver failure (ACLF), Gustot et al.1 proposed that organ support in the intensive care unit (ICU) should be discontinued for patients with four or more organ failures or Chronic Liver Failure Consortium (CLIF‐C) ACLF score >64 at days 3‐7 postinclusion, in the absence of liver transplantation, due to futility. In our ICU, 50 consecutive patients with ACLF were admitted between April 2013 and March 2016; 40 (80%) were male, and median (interquartile range) age was 59 (50‐63) years. The precipitant event of ACLF was infection in 32 (64%) patients. Median (interquartile range) Model for End‐Stage Liver Disease score at ICU admission was 29 (22‐32). ACLF grade 3 was present in 23 (46%) patients at days 3‐7 post–ICU admission, with a median (interquartile range) CLIF‐C ACLF score of 55 (48‐68). All‐cause death occurred in 29 (58%) and 32 (64%) patients at days 28 and 90 post–ICU admission, respectively (Fig. 1). Liver transplantation was performed in 13 (26%) patients during follow‐up (3 of these patients died within 90 days post–ICU admission).Figure 1: Overall cumulative survival following intensive care unit admission for patients with acute‐on‐chronic liver failure at Curry Cabral Hospital, Lisbon, Portugal (April 2013‐March 2016).The number of organ failures at days 3‐7 post ICU admission was associated with 28‐day mortality with an odds ratio of 2.7 (95% confidence interval 1.5‐4.8, P = 0.001). Among 11 patients with four or more organ failures at days 3‐7 post–ICU admission, without liver transplantation, 1 (9%) was alive at day 90 post–ICU admission (0% in Gustot et al.1) (Table 1). Nevertheless, all 7 patients with five or more organ failures at days 3‐7 post–ICU admission were dead at day 28 post–ICU admission. Table 1 - Patients' Characteristics Stratified by Gustot et al.1 Futility‐of‐Care Criteria at Days 3‐7 Post–ICU Admission for Patients With ACLF Without Liver Transplantation at Curry Cabral Hospital, Lisbon, Portugal (April 2013‐March 2016) ≥4 Organ Failures <4 Organ Failures P a CLIF‐C ACLF >64 CLIF‐C ACLF ≤64 P a Age (years) 55 (49‐63) 61 (53‐65) 0.16 61 (50‐66) 59 (51‐63) 0.65 Sex (male) 9/11 (82%) 21/26 (81%) 1.00 10/14 (71%) 20/23 (87%) 0.39 MELD 39 (32‐46) 24 (15‐26) <0.001 35 (23‐43) 25 (15‐26) 0.008 Organ failures NA NA NA 4 (3‐5) 2 (1‐3) <0.001 CLIF‐C ACLF 73 (67‐76) 54 (49‐62) <0.001 NA NA NA 28‐day deathb 10/11 (91%) 16/26 (62%) 0.12 12/14 (86%) 14/23 (61%) 0.15 90‐day deathb 10/11 (91%) 19/26 (73%) 0.39 12/14 (86%) 17/23 (74%) 0.68 aMann‐Whitney or chi‐squared test.bTransplant‐free death (overall n of 50 ‐ 13 = 37).Abbreviations: MELD, Model for End‐Stage Liver Disease score; NA, not applicable. Median CLIF‐C ACLF score at days 3‐7 post–ICU admission was greater among nonsurvivors at day 28 post–ICU admission (62 versus 46, P < 0.001). CLIF‐C ACLF score at days 3‐7 post–ICU admission predicted 28‐day mortality with an area under the curve of 0.79 (95% confidence interval 0.66‐0.92). Among 14 patients with a CLIF‐C ACLF score >64 at days 3‐7 post–ICU admission, without liver transplantation, 2 (14%) were alive at day 90 post–ICU admission (0% in Gustot et al.1) (Table 1). Taking into account our results and those of McPhail et al.,2 Gustot et al.'s1 futility‐of‐care algorithm may be oversimplified and difficult to generalize. For patients with cirrhosis and organ failures, futility of care may be more complex to define than using a single cutoff of overall number of organ failures or the CLIF‐C ACLF score. Furthermore, indications and limitations of liver transplantation in this context remain controversial. The study of futility of care for patients with ACLF could benefit by adding qualitative measures (e.g., comorbidities, performance status, local ICU practice, and transplantation criteria). Finally, each individual's, family's, and community's perceptions of goals of care and life need to be respected.