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Page 4 of 19 Kornberg et al. Hepatoma Res 2018;4:60 I http://dx.doi.org/10.20517/2394-5079.2018.86

Table 1. Impact of stage of underlying cirrhosis on post-LT HCC recurrence
Ref. n Characterization of cirrhosis severity Impact on post-LT outcome
Ioannou et al. [50] 4453 (lab.) MELD score ≥ 20 Calculated MELD score ≥ 20 was the most important predictor (HR =
1.61; 95%CI 1.3-2.1) of poor post-LT survival, along with AFP level. The
risk of post-LT death was almost doubled in patients with either AFP
level ≥ 455ng/mL or MELD score ≥ 20 (HR = 1.97; 95%CI 1.6-2.5)
Halazun et al. [51] 3519 Pre-LT rising (lab.) MELD score Rising pre-LT MELD score proved to be an independent predictor of
MVI on explant pathology (OR: 1.46, CI 1.13-1.88; P=0.004), which was
the most important factor of poor post-LT outcome
Macdonald et al. [52] 1074 (lab.) MELD score Calculated MELD score was identified as an independent predictor
of HCC recurrence or death after LT (HR = 1.03; 95%CI 1.01-1.05; P =
0.005), along with AFP level and donor risk index
Komorowski et al. [53] 142 (lab.) MELD score Apart from AFP level, pretransplant calculated MELD score turned out
to be an independent and significant predictor of RFS (HR = 1.16)
Foerster et al. [54] 304 (lab.) MELD score ≥ 15 Calculated MELD score ≥ 15 was an independent promoter of poor OS
(HR = 1.028; 95%CI 1.002-1.053: P = 0.033), with HCC relapse to be
the major reason of mortality
Faitot et al. [55] 243 Clinically evident portal PH was an independent predictor of drop out from the waiting list
hypertension due to tumor progression (OR = 2.79; 95%CI 1.02-7.69; P = 0.04). In
an intent-to-treat analysis, post-LT OS was significantly lower in PH
patients when compared to those without PH (P = 0.044). However,
PH had no significant impact on outcome in the transplanted patients
AFP: alpha fetoprotein; HCC: hepatocellular carcinoma; HR: hazard ratio; LT: liver transplantation; lab: laboratory; MELD: model for end-stage liver
disease; MVI: microvascular invasion; OS: overall survival; PH: portal hypertension; RFS: recurrence-free survival

an independent promoter of drop out from the waiting list due to tumor progression. In an intent-to-treat
analysis, post-LT OS was significantly lower in PH patients when compared to those without PH. However,
PH had no significant impact on outcome in the subgroup of transplanted patients [Table 1].

Sarcopenia
Nowadays, it is undoubtedly that recipients’ functional status has a major prognostic impact on liver transplant
recipients [56,57] . In recent years, involuntary loss of muscle mass and strength, referred to “sarcopenia”, was
shown to be an early predictor of frailty and poor outcome. Sarcopenia is a feared complication in consuming
chronic diseases like cancer, sepsis, renal function and liver cirrhosis . The pathogenesis of sarcopenia in
[58]
cirrhotics is multifactorial and not fully understood. It seems to be a response to protein-energy malnutrition,
metabolic catabolism, and patients’ inactivity [59,60] . Although there is currently no worldwide standard
measurement and index of sarcopenia, depletion of skeletal muscle mass and function estimated by cross-
sectional abdominal imaging were demonstrated to be a significant risk factor for wait list mortality, prolonged
intensive care duration, complicated hospital stay, severe infections, metabolic syndrome and overall poor
outcome in liver recipients, independent from underlying indication [57,61-63] .

The pathophysiological mechanisms accounting for such fatal complications are not completely defined.
However, it seems to be quite clear that sarcopenia and in particular sarcopenic obesity negatively affect
immunocompetence via pro-inflammatory cytokines and adipokines, such as IL-1, IL-6, tumor necrosis factor
(TNF)-α and leptin. Apart from that, secretion of the myokin IL-15 is decreased, which has negative effects on
growth and differentiation of B and T lymphocytes, natural killer cells, macrophages and monocytes. Thus, a
persistent state of immunosuppression and inflammation arises, which is not only enhancing morbidity and
mortality, but may also promote cancer development [64-67] . A large retrospective analysis including 1257 HCC
patients following curative and non-curative treatments has recently identified sarcopenia as an independent
promoter of mortality and HCC recurrence .
[68]

Apart from that, several studies on hepatic resection have shown that risk of HCC recurrence is significantly
higher in sarcopenic patients compared to those without muscle waste [69-72] . These data suggest that,
with special regard to high immunosuppressive load early post-LT, sarcopenia-related depression of the