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D’Arcangelo et al. Hepatoma Res 2021;7:4 I http://dx.doi.org/10.20517/2394-5079.2020.109 Page 9 of 12
[29]
There is a lack of agreement on how to assess skeletal muscle abnormalities in patients with cirrhosis .
Per our protocol, sarcopenia was defined by direct quantification of skeletal muscle mass at cross-sectional
imaging (CT scan), which is currently considered the gold standard in patients with cirrhosis due to its
objective and reproducible measurements. In addition, among the different CT scores that can be used to
assess sarcopenia, we specifically choose L3 SMI because of its good correlation with whole body skeletal
muscle mass [3,30] .

In addition, we used sex-specific cut-offs previously proposed for the diagnosis of sarcopenia in patients
[3]
with cirrhosis awaiting LT , and we included only patients with a radiological assessment within the
6 months prior to transplantation. Because the muscle mass in patients with cirrhosis may significantly
change over a 6 months period, we have assessed the impact of sarcopenia in decompensated patients
with CT scan within 3 months prior to LT and in patients with CT scan between 3 months and 6 months
prior to LT separately. Interestingly, we found that sarcopenia was associated with lower survival in
decompensated but not in compensated patients in both groups; however, the difference in patients with
CT scan between 3 months and 6 months was not as evident as in those with CT scan within 3 months,
which would suggest that to evaluate the impact of sarcopenia on post-transplant outcomes the evaluation
of muscle mass should be performed as close as possible to transplantation.

[3]
In line with previous data , we confirm the high prevalence of sarcopenia in patients with cirrhosis
awaiting LT as well as the positive correlation between sarcopenia and increasing severity of liver
[6]
dysfunction (Child C > Child A), particularly in males . Interestingly enough, however, approximately
50% of patients with Child A included in our study were sarcopenic, which indicates that sarcopenia
should be actively screened in all patients with cirrhosis evaluated for transplantation, independent of
liver dysfunction severity. On the same note, we found no association between prevalence of sarcopenia
and patient sex (60% in male and 50% in female patients), aetiology of liver disease (i.e., patients with
HCV, alcoholic, and metabolic-related liver disease), or presence of HCC. This further suggests that
the assessment of sarcopenia should be performed in any patient evaluated for LT, independent of sex,
aetiology, and indication for transplant [31-33] ; however this would need confirmation due to the relatively
small sample size in our study.

Since the majority of patients included in our analysis had HCC, we also sought to determine the role of
sarcopenia in this patient population. In our center, evaluation of transplantability and wait-list priority
in candidates with HCC is not based on morphological criteria, such as Milan criteria, but on other
factors that would reflect tumour behaviour and aggressiveness, including response to downstaging/
[34]
bridging treatments and characteristics and timing of HCC recurrence after treatment . Thus, we were
able to include patients transplanted with HCC beyond MC and to evaluate in these patients the impact of
sarcopenia.

We found a weak association between tumour size, as defined by Milan criteria, and prevalence of
sarcopenia (being higher in patients with HCC beyond vs. within Milan criteria).

On the same note, we noticed that sarcopenia was associated with worse post-LT survival only in patients
who underwent transplantation with HCC beyond Milan criteria. It has been suggested that sarcopenia
and alterations of body composition may be associated with increased risks of HCC recurrence and
death after transplantation [28,35,36] . Our data would further suggest that the impact of sarcopenia in this
patient population may vary according to the tumour size, and that patients with more advanced HCC are
probably the most at risk.

Among secondary outcomes, we found that sarcopenia was associated with a higher rate of early bacterial
infection after transplantation, with as many as 50% of sarcopenic recipients having at least one infection