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Melatonin administration has been associated with different benefits in animals and patients suffering from liver diseases. However, there is no published data about circulating melatonin levels in patients with hepatocellular carcinoma (HCC) who underwent liver transplantation (LT). Thus, the objective of this observational and retrospective study was to determine whether patients with HCC with lower serum melatonin levels prior to LT have a higher risk of one-year mortality after LT. We measured serum levels of melatonin, malondialdehyde (to assess lipid peroxidation), and total antioxidant capacity (to assess antioxidant state) before LT. One-year surviving LT patients ( n = 129) showed higher serum levels of melatonin ( p = 0.001) and total antioxidant capacity ( p = 0.001) and lower serum levels of malondialheyde ( p = 0.01) than non-surviving LT patients ( n = 16). Logistic regression analysis showed that high serum melatonin levels prior to LT were associated with lower one-year LT mortality (odds ratio = 0.525; 95% confidence interval (CI) = 0.331⁻0.834; p = 0.006). We found an association between serum levels of melatonin with serum levels of malondialheyde (rho = -0.22; p = 0.01) and total antioxidant capacity (rho = 0.21; p = 0.01). Thus, the novel findings of our study were the association between high serum melatonin levels prior to LT and survival at first year after LT and the association between serum levels of melatonin with malondialheyde and total antioxidant capacity.

Cytokeratin (CK)-18 is the major intermediate filament protein in the liver and during hepatocyte apoptosis is cleaved by the action of caspases; the resulting fragments are released into the blood as caspase-cleaved cytokeratin (CCCK)-18. Higher circulating levels of CCCK-18 have been found in patients with hepatocellular carcinoma (HCC) than in healthy controls and than in cirrhotic patients. However, it is unknown whether serum CCCK-18 levels before liver transplantation (LT) in patients with HCC could be used as a prognostic biomarker of one-year survival, and this was the objective of our study with 135 patients. At one year after LT, non-survivors showed higher serum CCCK-18 levels than survivors (p = 0.001). On binary logistic regression analysis, serum CCCK-18 levels >384 U/L were associated with death at one year (odds ratio = 19.801; 95% confidence interval = 5.301-73.972; p < 0.001) after controlling for deceased donor age. The area under the receiver operating characteristic (ROC) curve of serum CCCK-18 levels to predict death at one year was 77% (95% CI = 69%-84%; p < 0.001). The new finding of our study was that serum levels of CCCK-18 before LT in patients with HCC could be used as prognostic biomarker of survival., Competing Interests: The authors declare no conflict of interest.

Previous studies have found higher levels of serum malondialdehyde (MDA) in hepatocellular carcinoma (HCC) patients compared to healthy controls and higher MDA concentrations in tumoral tissue of HCC patients than in non-tumoral tissue. However, the association between pre-transplant serum levels of MDA and survival in HCC patients after liver transplantation (LT) has not been described, and the aim of the present study was to determine whether such an association exists. In this observational study we measured serum MDA levels in 127 patients before LT. We found higher pre-LT serum MDA levels in 15 non-surviving than in 112 surviving patients one year after LT (p = 0.02). Exact binary logistic regression analysis revealed that pre-LT serum levels of MDA over 3.37 nmol/mL were associated with mortality after one year of LT (Odds ratio = 5.38; 95% confidence interval (CI) = from 1.580 to infinite; p = 0.007) adjusting for age of the deceased donor. The main finding of our study was that there is an association between serum MDA levels before LT for HCC and 1-year survival after LT.