Decisions on futility in patients with cirrhosis and organ failure
Authors: Mark J.W. McPhail, Georg Auzinger, William Bernal, Julia A. Wendon
Journal: Hepatology (2016)

Potential conflict of interest: Nothing to report. Author names in bold designate shared co‐first authorship. To the Editor: We read with interest the article by Gustot et al.1 on prognostication of patients with acute‐on‐chronic liver failure (ACLF). The authors suggest that accelerated assessment for liver transplantation is underused and that futility of further care may be determined using the number of organ failures (OFs) and chronic liver failure (CLIF Consortium [CLIF‐C]) ACLF score after 1 week of medical therapy. We previously reported2 on patients with cirrhosis managed with full organ support in our intensive care unit and sought to validate the findings of Gustot et al. Of 986 (nontransplanted) patients with cirrhosis admitted between 2000 and 2011, 533 (327 [61%] male, median age 51 [range 16‐90]) were still alive and in the intensive care unit at day 7 after admission; 302 (57%) died within 90 days. Of the 533, the median day 7 CLIF Sequential Organ Failure Assessment score was 12 (range 1‐20) and the CLIF‐C ACLF score was 54 (range 6‐87); 244 patients were ACLF grade 3, 192 (78%) of whom died within 90 days; 137 patients had a CLIF‐C ACLF score >64 at day 7, of whom 126 (92%) died (compared with 100% for Gustot et al.). For patients with four or more OFs at day 7, 88% did not survive. The CLIF‐C ACLF score area under the receiver operating characteristic curve was 0.839 (95% confidence interval 0.805‐0.872, sensitivity 68%, and specificity 85%) for predicting mortality. We agree that ACLF‐3 alone is an inappropriate futility marker, but while four or more OFs may be more useful, in our series 10% of patients survived to 90 days without transplantation (0% survived in the Gustot et al. data set with four or more OFs or CLIF‐C ACLF >64). Within the group perceived to have a futile outlook, those who died had higher median CLIF‐C ACLF than the Gustot et al. cutoff (68 [range 30‐84] versus 56 [range 36‐75] in survivors, P < 0.001). Of the patients with five or more OFs, 11% (4/35) survived. In multivariable logistic regression of patients with a futile prognosis only CLIF Sequential Organ Failure Assessment (not CLIF‐C ACLF) retained independent predictive accuracy of mortality (odds ratio = 1.39, 95% confidence interval 1.01‐1.93; P = 0.043). When withdrawing care due to perceived futility it is important to recognize that this decision is irrevocable and small survival probabilities can be perceived differently between caregivers and patient families. Balancing these aspects while maintaining patient life, dignity, and wishes is fraught with statistical and ethical difficulties, and a single score is an unlikely final arbiter. Exceptionally high degrees of confidence in mortality risk are a prerequisite, and our assessment suggests that mortality may not be as reliably predicted as described by Gustot et al. Recent evidence suggests that more complex algorithms may be required in determining the optimal time limitation.3 Withdrawal of care should be decided from knowledge of local and national survival rates, OF reversibility, and qualitative factors such as frailty and patient wishes. We invite other authors to validate Gustot et al.'s findings while providing care for patients with cirrhosis in the intensive care unit beyond 7 days pending further outcome‐related research.