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Page 2 of 17 Marasco et al. Hepatoma Res 2020;6:32 I http://dx.doi.org/10.20517/2394-5079.2019.54

INTRODUCTION
[1]
Hepatocellular carcinoma (HCC) is the most common cause of death in patients with cirrhosis . Despite
[2]
numerous therapeutic options, the only curative treatments are liver transplantation and hepatectomy .
Patients with a single HCC nodule, Child-Pugh class A, normal bilirubin (< 1 mg/dL) and without portal
hypertension have the best prognosis and are ideal candidates for liver resection.

The presence of clinically significant portal hypertension (CSPH) (port-hepatic pressure gradient greater
than 12 mmHg) or clinical manifestation (platelet count < 100,000/mL, associated with splenomegaly
or esophageal varices) appears to be associated with a worse prognosis, but does not preclude resection
[3,4]
in selected patients . Thus, patients with cirrhosis should be carefully selected to reduce the risk of
postoperative liver failure and death. Post-hepatectomy liver failure (PHLF) is still a major concern
[2]
for liver surgeons . In the last few years, there has been an increasing need for a simple and accurate
[5]
tool for evaluating liver function before surgery to minimize PHLF and postoperative mortality . It is
difficult to define PHLF exactly since it manifests with one or more of these features: ascites, jaundice,
coagulopathy or kidney failure. The most commonly used criteria for defining PHLF are the 50-50 Criteria
where PHLF is defined as total serum bilirubin > 50 mmol/L 5 days after surgery or thereafter and an
[6]
international normalized ratio (INR) > 1.7 . Other diagnostic criteria are the peak bilirubin > 7 mg/dL in
any postoperative period, in the absence of cholestasis, and the International Study Group of Liver Surgery
(ISGLS) criteria that define PHLF by an increased INR and concomitant hyperbilirubinemia on or after
[7]
postoperative day 5 .

In the past, the selection of candidates for resection was based on the Child-Pugh classification but its
predictive value has been determined to be insufficient. Japanese groups use the indocyanine green retention
test (ICG), which has proved to be more reliable than Child-Pugh and the Model for End-stage Liver Disease
[8,9]
(MELD) to predict PHLF . In Western countries, the selection of candidates for resection is usually based
on the assessment of portal hypertension, which is clinically assessed by measurement of the hepatic venous
[10]
pressure gradient (HVPG > 10 mmHg) . However, these methods are invasive and costly. Thus, several
authors have tried to evaluate other non-invasive methods including biochemical scores, the measurement of
liver and spleen stiffness (LSM and SSM) and imaging patterns as predictors of PHLF [8,11-14] .

With an increase in life expectancy and improvement in operative safety and efficacy of hepatic resection
[15]
techniques, surgeons should also evaluate the best surgical option in elderly patients . Indeed, previous
studies have implicated older age as a potential factor influencing post-resection complications and survival,
[15]
and are summarized in a recent systematic review and meta-analysis which concluded that age > 70
was associated with increased 30-day and overall mortality when compared with non-elderly cohorts. A
promising factor that also influences post-operative outcomes is patient frailty, defined as a syndrome
characterized by decreased physiological reserves. Only one study has reported a specific association between
[16]
frailty and PHLF . However, frailty assessment is based on a self-reporting questionnaire, which could be
affected by several biases.

Thus, this review aims to summarize the recent advances on objective parameters such as non-invasive tests
(NITs) for predicting PHLF, particularly in elderly patients.

BIOCHEMICAL SCORES
Fibrosis and liver functional reserve scores
FIB-4
[17]
The Fibrosis (FIB)-4 index was first proposed by Sterling and colleagues and is based on four factors
included in the following equation: [age(years) × AST(UI/L)]⁄[platelet count × ALT(UI/L)]. It is a non-