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

correlated with the degree of portal hypertension and, since it was first proposed, this score has shown good
performance in predicting the development of esophageal varices in cirrhotic patients [69-71] . A recent Chinese
[72]
study evaluated the accuracy of PSR, calculated using platelet count and spleen volume (expressed in
3
mm ), as a diagnostic index for the stage of liver fibrosis in patients with HCC and compared PSR with other
currently-used scores. Among patients with severe fibrosis, AUROC was significantly higher for PSR (0.808)
[12]
than for other NITs, except for APRI (0.739, P = 0.215). Peng et al. , instead, conducted a study on the risk
factors for PHLF in which they used, among various markers, a variant of PSR based on spleen stiffness
measurement (SSM), instead of the spleen diameter or volume. On multivariate analysis, PSR seemed to be
an independent prognostic index for the development of hepatic decompensation (P < 0.001, odds ratio [OR]
= 0.622, 95%CI: 0.493~0.784). The PSR thus represents a promising prognostic index for the post-resection
outcome.

APRI score
The APRI score (aspartate aminotransferase [AST] to platelet ratio index) was introduced in a study
[73]
3
by Wai et al. and can be calculated using the following formula: AST(UI/L) × [100/(platelet count 10 /
3
mm )]. It was developed as a non-invasive predictor for progression of fibrosis in patients with chronic
[74]
viral hepatitis. In 2019, a study by Mai et al. found that the APRI score (AUC 0.743, 95%CI: 0.706-0.780;
P < 0.001) had greater accuracy for predicting PHLF than the Child-Pugh, MELD and ALBI scores in the
entire cohort of patients with HCC. The APRI-score cut-off value of 0.55 was able to reach a sensitivity of
[24]
72.2% and a specificity of 68.0% on PHLF prediction. However, Zhang et al. observed that the APRI score
[45]
showed a predictive significance only in the major hepatectomy subgroup. The Chinese group of Mai et al.
used a new combination of ALBI and APRI scores with the following formula: ALBI-APRI score = 5.280 ×
ALBI + 1.583 × APRI. The AUC of the ALBI-APRI model (AUC 0.766, 95%CI: 0.739-0.791) for predicting
the risk of PHLF was significantly higher than the single ALBI (P < 0.001) or APRI scores (P = 0.047). The
ALBI-APRI score cut-off value of -13.10 had a sensitivity of 78.1% and a specificity of 62.2% for predicting
[45]
the risk of PHLF . Thus, the APRI score in combination with other NITs could represent a good surrogate
of portal hypertension and should be further investigated for predicting PHLF.

LSPS
The LSPS (LSM-spleen to platelet ratio score) is a biochemical index derived from the following formula:
3
3
LSM (kPa) × [spleen diameter (mm)/platelet count (10 /mm )]. This score was first proposed as a predictive
[75]
tool for high-risk esophageal varices in patients with HBV-related cirrhosis . In a study by Chon and
[76]
colleagues , LSPS was found to be an independent risk factor for both HCC (HR = 1.001) and hepatic
decompensation (HR = 1.002) in patients with HBV-related hepatitis. Only a single report on 38 patients
[77]
highlighted a potential predictive role of LSPS on univariate analysis . However, not much is known about
the role of LSPS in predicting PHLF.
Other liver function tests
Over time, other tests for estimating liver function have been developed. These tests use different substrates
such as lidocaine, galactose, aminopyrine, amino acid, and methacetin. However, none have been shown
[55]
to be superior to the ICG clearance test in the prediction of PHLF . Other tests are based on the liver’s
energy production (arterial ketone body ratio; AKBR) and the number of receptors for asialo-glycoprotein
(ASGP-R; technetium-99m-galactosyl human serum albumin; 99mTc-GSA scan) but they are expensive
[55]
and less common than ICG . Of course, in the pre-operative assessment, other well-validated tools such
as the Child-Pugh and MELD scores continue to be considered. Both have been used widely to predict
the outcomes of cirrhotic patients in many different contexts; they showed similar prognostic significance
in most cases, even with slight differences in accuracy due to specific settings, as described in a recent,
[23]
[78]
comprehensive meta-nalysis . However, as described above, nowadays several NITs (such as FIB-4 , APRI
[74]
[8]
score , ALBI score [37,39,41,42] or ICG-r15 ) appear to be better predictors of PHLF, and warrant further study.