High serum caspase-3 levels in hepatocellular carcinoma prior to liver transplantation and high mortality risk during the first year after liver transplantation

ABSTRACT

Background: Higher liver caspase-3 activity has been found in patients with different liver diseases. However, there is no published data about circulating caspase-3 levels in patients with hepatocellular carcinoma (HCC) who underwent liver transplantation (LT). Therefore, our objective in this study was to determine whether an association between circulating caspase-3 levels in HCC patients prior to LT and one-year mortality after LT exists.

Methods: In this observational and retrospective study, we included HCC patients who underwent LT. We measured serum levels of caspase-3 (as the main executor of apoptosis) and caspase-cleaved cytokeratin (CCCK)-18 (to estimate apoptosis degree) before LT.

Results: One-year surviving LT patients (n = 129) showed lower serum levels of caspase-3 (p = 0.004) and CCCK-18 (p = 0.001) than non-surviving LT patients (n = 16). Logistic regression analysis showed that serum caspase-3 levels prior to LT were associated with one-year after LT mortality (Odds Ratio = 2.612; 95% CI = 1.519–4.493; p = 0.001). We found a positive association between serum levels of caspase-3 and CCCK-18 (rho = 0.26; p = 0.002).

Conclusions: Our study is the first one reporting data of circulating caspase-3 levels prior to LT for HCC, and an association between high serum caspase-3 levels previously to LT and survival at first year after LT.

KEYWORDS:

• Caspase-3
• hepatocellular carcinoma
• liver transplantation
• mortality
• prognosis

Author contributions

Conception and design: LL

Acquisition of data: LL, STR, PS, JP, DD, AG, MMM, PC, JP and MAB

Determination of serum levels of caspase-3 and CCCK-18: AFGR, APC.

Analysis of data: LL, AJ.

Wrote the paper: LL.

All authors revised the manuscript critically for important intellectual content and made the final approval of the version to be published.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewers disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This study was supported by a grant from Real Academia de Medicina de Santa Cruz de Tenerife 2017. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.