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Page 8 of 17 Marasco et al. Hepatoma Res 2020;6:32 I http://dx.doi.org/10.20517/2394-5079.2019.54

All the above-mentioned evidence supports the fact that LSM provides valuable prognostic information in
patients undergoing liver resection [102] . Indeed, in the last European guidelines on HCC, LSM was included
among the pre-operative tools to assess liver reserve before surgery. However, most of the prognostic models
including LSM have not been validated externally, the proposed cut-offs differ among studies and differ too,
for the elastosonography technique applied. Therefore, LSM is still not routinely used in pre-operative risk
stratification of patients undergoing surgery.

Noteworthy, in none of these studies was age an independent predictor of PHLF. However, a recent paper
showed that the risk of PHLF development after right hepatectomy rapidly increased in patients over 75
(incidence 35% > 75 years vs. 7% < 75 years, OR = 8.8, 95%CI: 3.6-21) [103] . Considering that older age is a
known risk factor for unreliable LSM measurement [104,105] and that this category of patients might have been
underrepresented in the previously published cohorts, future studies are needed to investigate the prognostic
role of LSM in elderly patients undergoing liver resection.

Computed tomography
Several computed tomography (CT) signatures have been reported in association with PHLF [106,107] . With
regard to liver volumetry, this is performed using CT imaging, preferably utilizing the images obtained
during the venous phase. Liver volumetry is obtained by contouring the liver boundaries and segments,
with semi-automated methods or manually, on dedicated software. PHLF occurrence is closely related to
the volume and functional capacity of the remnant liver. Patients with a small future liver remnant (FLR)
are at higher risk of developing PHLF. Shoup et al. [108] demonstrated that the remnant liver volume (RLV)
correlates with post-operative prothrombin time and bilirubin levels. In their analysis, a RLV < 25% was
more predictive of PHLF than the anatomical extent of resection [108] . There is no consensus about “how much
is enough” but, in general, a FLR of about 20%-30% has been reported as representing the limit of safety in
hepatectomy, in non-cirrhotic livers, by some authors [109-112] .

Remnant liver function, estimated with CT volumetry, is reliable only when liver function is assumed
homogeneous in the entire organ [113] . In cirrhotic patients, the small liver volume suggests the severity of
cirrhosis and poor function of the liver. Indeed, cirrhotic livers have lower levels of hepatocyte growth
factor and slower and less complete regeneration, compared with non-cirrhotic livers [114] . Therefore, in these
patients, the hepatectomy-associated risk cannot be accurately determined with volumetry alone. In different
published series, the critical minimum FLR for a safe hepatectomy was estimated to be approximately 40% in
patients with cirrhosis [115,116] .

Spleen Volume (Sp) can also be a critical factor for the outcome of patients undergoing major liver resection.
An increased Sp/RLV ratio (> 0.199) correlates with PHLF [114] .

Another imaging pre-operative evaluation that should be assessed is the quantification of hepatic steatosis,
which is shown on pre-contrast CT images as lower attenuation of the liver than that of the spleen [117] .
Steatosis contributes to post-operative liver dysfunction, especially in diabetic patients and in patients with
chemotherapy-associated steatohepatitis undergoing major hepatic resection [117] . The effect of steatosis is
explained by the higher incidence of ischemia-reperfusion injury due to altered sinusoidal microcirculation.
A recent study found a significantly higher incidence of hepatic decompensation, 90-day post-operative
morbidity and surgical hepatic complications in patients with steatohepatitis than in patients without [118] .

Among other conditions that could be associated with older age and contribute to the development of
PHLF, it is widely known that primary sarcopenia is strongly associated with age. Therefore, elderly patients
have less skeletal muscle mass than younger patients [119,120] and this loss of muscle mass is accelerated due
to chronic medical illnesses and malnutrition [121] . At the same time, nutritional status is a major concern