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Page 2 of 9 Sioutas et al. Hepatoma Res 2020;6:4 I http://dx.doi.org/10.20517/2394-5079.2019.43

[9]
9%-51% and 0%-42.9%, respectively . Normal aging is associated with a gradual decline in the function of
most organ systems, including the liver. The liver synthetic and metabolic activity, liver volume, and blood
[10]
flow to the liver seem to be significantly affected in the elderly . It is well known that the liver remnant
regenerates after liver resection, and the final liver volume after regeneration does not seem to differ
between younger and older individuals [9,11] . However, this process might be delayed in the elderly due to
[12]
the liver’s decreased proliferative capacity in the early period after the loss of the liver mass . Data have
shown that liver regeneration after living donor liver transplantation can be delayed in older donors when
[13]
compared to younger donors . These findings indicate that physiological deconditioning and remaining
organ function might have a more significant effect on clinical outcomes than the actual chronological
age [14,15] .

Frailty syndrome is defined as the increased vulnerability to stressors, loss of ability to adapt, and
diminished resiliency secondary to an age-related decline in the physiological reserves and function
of multiple organ systems [16,17] . It is essential to distinguish frailty from “comorbidity” and “disability”;
although these three terms overlap to some extent and are often used interchangeably to predict patient
[18]
outcomes, they represent entirely different entities . As described by Feinstein, “comorbidity” is “any
distinct additional entity that has existed or may occur during the clinical course of a patient who has
[19]
the index disease under study” . The term “disability” refers to the abnormal biological functioning
or the defect that renders individuals inferior to the “normal” species around them leading to loss of
[21]
[20]
social stability and survival . Frailty should also not be considered synonymous to aging , but rather
[22]
an intermediate clinical state between normal and pathological aging . Frail patients commonly fail to
return to their prior homeostasis after a stressor, resulting in adverse clinical outcomes [23,24] . Therefore, the
need for developing accurate risk-stratification tools that can potentially identify older patients at risk for
[25]
postoperative complications is apparent .

The aim of the present review is to summarize the impact of age on patient outcomes after liver surgery,
describe the available frailty assessment tools, and discuss the impact of frailty on postoperative outcomes
in patients undergoing liver resection.

LIVER RESECTION AND AGE
[26]
Several studies sought to investigate the outcomes of liver resection in young vs. old patients. Fong et al.
published one of the first studies examining the effect of age on liver surgery. Their study included 133
patients older than 65 years undergoing liver resection for colorectal liver metastases, and they found that
age was an independent risk factor for increased risk of morbidity. According to the authors, major hepatic
resection may be safely performed and result in favorable functional outcomes on appropriately selected
[26]
[2]
older patients . Cho et al. investigated the safety of liver resection in the elderly and reported favorable
outcomes in patients ≥ 70 years. Although most elderly patients were transferred to rehabilitation facilities
postoperatively, there was no difference in terms of severe postoperative complications. The authors also
performed a literature review and included 14 previous studies; only two (14.3%) [27,28] of them reported
a statistically significant difference in severe postoperative complications and only two (14.3%) [28,29]
reported a statistically significant difference in mortality between old and young patients. Additionally,
a large single-center study from France showed that age ≥ 75 years is a risk factor of mortality after liver
[30]
resection , while a multicenter study from the US showed that increasing age is associated with increased
[31]
postoperative sepsis and overall mortality, but not overall morbidity .
As liver resection represents the mainstay of treatment in non-metastatic HCC [32-34] , several studies aimed to
investigate the difference in outcomes between young and old HCC patients. Therefore, data have proven the
safety and feasibility of liver resection in appropriately selected patients aged not only more than 70 years, but,
[39]
in some cases, even more than 80 years [35-38] . A meta-analysis reported that the morbidity and mortality