Comparing the accuracy of prediction models to detect clinically relevant post-hepatectomy liver failure early after major hepatectomy

Abstract

Background: Arterial lactate measurements were recently suggested as an early predictor of clinically relevant post-hepatectomy liver failure (PHLF). This needed to be evaluated in the subgroup of major hepatectomies only.

Method: This observational cohort study included consecutive elective major hepatectomies at Karolinska University Hospital from 2010 to 2018. Clinical risk factors for PHLF, perioperative arterial lactate measurements and routine lab values were included in uni- and multivariable regression analysis. Receiver operating characteristics and risk cut-offs were calculated.

Results: In total, 649 patients constituted the study cohort, of which 92 developed PHLF grade B/C according to the International Study Group of Liver Surgery (ISGLS). Lactate reached significantly higher intra- and postoperative levels in PHLF grades B and C compared to grade A or no liver failure (all P < 0.002). Lactate on postoperative day (POD) 1 was superior to earlier measurement time points in predicting PHLF B/C (AUC 0.75), but was outperformed by both clinical risk factors (AUC 0.81, P = 0.031) and bilirubin POD1 (AUC 0.83, P = 0.013). A multivariable logistic regression model including clinical risk factors and bilirubin POD1 had the highest AUC of 0.87 (P = 0.006), with 56.6% sensitivity and 94.7% specificity for PHLF grade B/C (cut-off ≥0.32). The model identified 46.7% of patients with 90-day mortality and had an equally good discriminatory potential for mortality as the established ISGLS criteria for PHLF grade B/C but could be applied already on POD1.

Conclusion: The potential of lactate to predict PHLF following major hepatectomy was inferior to a prediction model consisting of clinical risk factors and bilirubin on first post-operative day.

Fig. 1

Perioperative lactate dynamics by grade of liver failure Lactate dynamics during 24 h from start of surgery, grouped by post-hepatectomy liver failure (PHLF) grading according to the International Study Group of Liver Surgery. Median lactate levels and interquartile range are demonstrated for each time interval. For patients with several lactate measurements in one 3 h interval, the mean was calculated. Median lactate for patients without PHLF and with grade A followed a nearly identical pattern with increasing intraoperative levels, a peak at 6–9 h and returning to initial levels after 18–21 h. Grades B and C liver failure reached higher maximum lactate levels already during the intraoperative intervals with a continued postoperative increase and later peaks at 9–12 h for grade B and 15–18 h for grade C, and did not return to the baseline levels within 24 h.

Fig. 2

Perioperative lactate levels at prespecified time points Median lactate levels grouped by post-hepatectomy liver failure (PHLF) grading according to the International Study Group of Liver Surgery at five pre-specified time points, last preoperative (Preop), highest intraoperative (Intraop), first postoperative (Postop), closest to 06:00 on postoperative day (POD) 1 and highest within 24 h from start of surgery (Peak 24 h). Lactate differed significantly between patients without PHLF or grade A compared to grades B or C at all time points except preoperatively. **P < 0.010, *** P < 0.001. Whiskers extend to the largest value no further than 1.5 × i.q.r. from the hinge.

Fig. 3

Receiver operating characteristic curves for single predictors and multivariable prediction models for post-hepatectomy liver failure (PHLF) grade B/C Lactate on postoperative day (POD) 1 resulted in an area under the curve (AUC) of 0.75, bilirubin on POD1 in an AUC of 0.83, clinical risk factors in an AUC of 0.81 and the combined model of clinical risk factors and bilirubin POD1 in an AUC of 0.87.