Extracellular Histones H3 as a Prognostic Blood Marker for Delayed Liver Function Recovery After Donor Hepatectomy

Abstract

Early prediction of liver dysfunction after liver resection remains a challenge. We hypothesized that extracellular histone concentrations are a promising new biomarker for the detection of liver injury after donor hepatectomy. This prospective study considered 93 living donors who underwent hepatectomy. Blood samples of donors were collected on postoperative day 1, and histone levels in the plasma samples of the patients were measured with total histone H3 sandwich ELISA kits. Among 86 right lobe donors, 23 (26.7%) were deemed to have a delayed liver function recovery according to the International Study Group of Liver Surgery's definition of posthepatectomy liver failure, whereas 63 (73.3%) were considered to have an adequate liver function recovery. The area under the receiver operating characteristic (ROC) curve for circulating histones in predicting persistent liver dysfunction was 0.618 ± 0.06 (95% confidence interval [CI], 0.501-0.735; P=.091). The cutoff point value obtained from the analysis of ROC curves was 0.895, with a sensitivity of 95.7% and a specificity of 32.9%, respectively, for examining a delayed liver function recovery (P=.015). The Fisher analysis significantly verified these results empirical influence function % 7.90 (95% CI, 3.91-11.90; P=.006). The univariate analysis determined that postoperative histones were identified as an independent risk factor of delayed liver function recovery (odds ratio, 10.8; 95% CI, 1.4-84.9; P = .024). The circulating histone negatively correlates with liver dysfunctions after donor hepatectomy and had the best value in predicting liver dysfunction within 24 hours after liver resection.