Review for 10.1186/s12876-021-01830-5 (2021)

Title: Creatinine-lactate score predicts mortality in non-acetaminophen-induced acute liver
failure in patients listed for liver transplantation
Version: 2 Date: 19 Apr 2021
Reviewer's report:
Many manuscripts explore the role of prognostic indices to improve the identification of which
patients with ALF will die without a liver transplant. The manuscript by Figueira, et al is different
in that it tries to identify which patients listed for LT will die without being transplanted. A
combination of creatinine and lactate was shown to best predict mortality of wait-listed patients
with non-acetaminophen-induced ALF. This finding is consistent with what is known, that the
primary source of mortality on the LT waitlist in patients with ALF is extrahepatic-systemic
illness and organ failure.
Primary comments.
1. The title could be improved. As it is, the reader will read the title and conclude that this paper
is another index to predict outcome in ALF. I suggest it contain the phrase “in patients with ALF
listed for liver transplantation.” In addition, this patient population is very different than those
in the US and Western Europe in that it includes none with acetaminophen overdose. I think the
phrase “non-acetaminophen-induced ALF” should also be included.
These 2 suggestions, that the authors specify that their patient population is wait-listed and have
non-acetaminophen ALF, should also be inserted in the first few lines of the Introduction.
2. The time on the LT wait list was shown to not predict mortality in univariate analysis in Table
1. Intuitively, this does not make sense, and should be discussed. What happens if time on the
waitlist is forced into the multivariate model?
3. The CL index may be useful to predict mortality in wait-listed patients with ALF. How is the
index to be used? Should patients with high indices be afforded greater Status 1 priority on the
waitlist, or should it be used to identify patients on the waitlist who should not be transplanted
due to excessive mortality? In other words, does the CL index (and the other indices) predict
mortality after LT? What was the CL index in patients who died after LT compared to those
who survived?
The implementation of the CL index in this regard should be added to the Discussion. Consider
giving hypothetical examples of how the CL index might guide clinicians to make decisions
regarding the appropriateness of LT after listing.
4. The cause of death on the waiting list should be added to the manuscript, and discussed, if
appropriate.
5. Ammonia was not used as a variable in the prediction of mortality. Was there a reason for
this? Similarly, the use of vasopressors has been identified as a major predictor of outcome in
patients with ALF, but was not mentioned as a study variable.
6. The year/era of presentation is a major contributor to outcome of ALF, with better survival in
more recent times. The authors need to specify the years of inclusion of their 100 patients, and
examine the effect of year/era in predicting mortality on the LT wait-list (for example, mortality
in the last 10 years vs the era in the 10 years before then).
Minor points.
1. Typos and grammatical errors in manuscript and tables should be corrected.
2. The authors use the word “disease” to describe ALF in multiple places in the MS. ALF is not
really a disease; it’s a syndrome. I’d consider changing the wording.
3. In Introduction line 62, the rate of spontaneous survival of patients with ALF in modern
series that include patients with acetaminophen overdose is much higher than 20%. Assuming
the authors mean non-acetaminophen ALF, I’d specify this patient population.
4. Page 8, lines 178-180 are redundant to lines 161-163, and could be omitted.
5. The Discussion is long. Rather than reviewing literature regarding predicting overall outcome
in patients with ALF, suggest focusing in more detail only on those which address mortality on
the LT waitlist (see #3 in Primary points).