The Predictive Role of Tenascin-C and Cellular Communication Network Factor 3 (CCN3) in Post Hepatectomy Liver Failure in a Rat Model and 50 Patients Following Partial Hepatectomy

Abstract

BackgroundMatricellular proteins of the extracellular matrix (ECM) include tenascin-C (TNC) and cellular communication network factor 3 (CCN3). This study aimed to investigate the role of TNC and CCN3 as prognostic factors for post hepatectomy liver failure (PHLF) in a rat model of partial hepatectomy and 50 patients following partial hepatectomy.Material/MethodsSprague-Dawley rats underwent 85% (n=53) or 90% hepatectomy (n=53) in the partial hepatectomy (PHx) model. TNC and CCN3 mRNA expression in residual liver tissue was evaluated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and enzyme-linked immunoassay (ELISA) determined the serum levels of TNC and CCN3. In 50 patients who underwent partial hepatectomy, TNC and CCN3 serum levels were measured on postoperative day 1 and day 3.ResultsIn the rat partial hepatectomy model, mRNA and serum levels of TNC and CCN3 were significantly increased within the first 24 h, and were higher in the 90% PHx group compared with the 85% PHx group. Fifty patients who underwent partial hepatectomy, included patients with PHLF (n=12) and patients without PHLF (n=38). Multivariate analysis confirmed that serum levels on postoperative day 3 TNChigh+CCN3high was a significant predictor of PHLF, which was associated with more than twice the risk of severe morbidity when compared with the low-risk patients (80% vs. 30%) and a significantly longer hospital stay (17 days vs. 8 days).ConclusionsFurther studies are needed to evaluate the potential role of the matricellular proteins, TNC and CCN3 as early clinical predictors for PHLF.

Significance of CCNs in liver regeneration

“…However, we could not exclude the active roles of Ccn3-Ccn6 genes in hepatocyte damage post PHx. For example, Ccn3 has been considered a potential clinical predictor for postoperative morbidity and mortality after liver resection since severe surgical removal (85-95% PHx) in rat models, and patients with PHx-associated liver failure significantly induce this molecule (Li et al 2019).…”