Serum interleukin-6 and tumor necrosis factor-α are associated with early graft regeneration after living donor liver transplantation

Abstract

BackgroundLiver graft regeneration is orchestrated by specific and sequential stimuli, including hepatocyte growth factors, cytokines, and catecholamines. We evaluated the association between preoperative serum cytokines and early liver graft regeneration in human living donor liver transplantation (LDLT).Patients and methodsWe retrospectively reviewed the data of adult patients who underwent LDLT from January 2010 to December 2014. Serum cytokines, including interleukin (IL)-2, 6, 10, 12, 17, interferon (IFN)-γ and tumor necrosis factor (TNF)-α were measured in the recipients 1 day before surgery and on postoperative day (POD) 7. Liver graft volume was estimated using abdominal computed tomography images of the donors and recipients.ResultsIn total, 226 patients were analyzed in this study. Median preoperative levels of serum cytokines were as follows: IL-2, 0.1 (0.1–1.6) pg/mL; IL-6, 7.3 (0.1–30.2) pg/mL; IL-10, 0.5 (0.1–11.0) pg/mL; IL-12, 0.1 (0.1–0.1) pg/mL; IL-17, 2.0 (0.1–16.4) pg/mL; IFN-γ, 3.2 (0.1–16.0) pg/mL; and TNF-α, 9.8 (5.4–17.9) pg/mL. Higher preoperative serum levels of IL-6, IL-10, and TNF-α, dichotomized at the median, were associated with increased relative liver volumes by POD 7. Multivariate analysis revealed that higher levels of serum IL-6 and TNF-α were independently associated with increased graft volume during the first 1 week after LDLT, based on the lower levels of those cytokines.ConclusionsIL-6 and TNF-α were important mediators of the success of early graft regeneration in patients who underwent LDLT.

Cytokine Profiles Associated With Angiotensin II Type 1 Receptor Antibodies

“…In the multivariable models, the relationship between cytokines and AT1R-Ab remained consistent when controlling for other clinical variables, and only IL-6 had other significant predictors (aside from time). The additional association of IL-6 with living donation may be reflective of regenerative processes occurring in the allograft, 44 but this relationship requires further investigation. In addition, the cytokines had varying levels during the early posttransplant time point, which may be partially reflective of a proinflammatory state associated with end-stage renal disease.…”

Portal venous velocity affects liver regeneration after right lobe living donor hepatectomy

“…Sasturkar et al reported that the peak level of IL-6 and TNF-α were observed on POD 1, the roles of TNF-α and IL-6 were necessary for proper human liver regeneration after partial hepatectomy in healthy liver donors [ 22 ]. Chae et al reported that higher serum IL-6 and TNF-α levels were associated with increased early graft regeneration after living donor liver transplantation [ 23 ]. IL-6 and TNF-α were important mediators in early regeneration.…”

Markers of liver regeneration—the role of growth factors and cytokines: a systematic review

“…Serial measurements of TNF-α before and after hepatic resection detected only slight elevations, but no correlations with hepatic regeneration [146]. Based on those data, the monitoring of regeneration by TNF-α cannot be recommended [147].…”

“…Furthermore, a correlation between the peak IL-6 levels and HGF was detected [46]. In the setting of human living donor liver transplantation, higher levels of serum IL-6 were independently associated with increased graft volumes during the first postoperative week [147]. Oyama et al demonstrated that patients with a small graft after living donor liver transplantation showed a higher increase in IL-6 levels postoperatively and a better regeneration rate 2 weeks post-transplant [162].…”