Removing a large part of the liver (major hepatectomy) can cure primary and secondary liver cancers, but it carries the risk of post-hepatectomy liver failure (PHLF), a serious complication in which the liver left behind - the future liver remnant (FLR) - cannot meet the body's metabolic needs. PHLF occurs after roughly 5% to 15% of major hepatectomies and is the leading cause of postoperative death.
Before surgery, surgeons routinely use CT scans to measure how much liver will remain (CT volumetry). Volume alone does not tell the whole story. After a large resection the remaining liver can rotate and shift into the empty space left behind, kinking or compressing the veins that drain it. The resulting congestion can make an apparently adequate remnant fail.
This prospective, multicenter, observational cohort study tests whether adding two elements to standard CT volumetry improves the preoperative prediction of liver failure:
1. Hepatic vascular deformation mapping (VDM), a three-dimensional image-analysis technique that quantifies the geometry and displacement of the hepatic veins and the portal vein; and 2. A set of simple, reproducible measurements that any radiologist can make on a standard CT scan (hepatic vein diameters, congestion index, spleen volume, liver attenuation, and the distances from the veins to the planned resection plane).
Consecutive adults undergoing major hepatic resection (three or more Couinaud segments) at several tertiary hepatobiliary centers will be enrolled. The preoperative CT scans already performed as part of routine care are analyzed centrally by a core imaging laboratory. There is no additional imaging, no extra hospital visit, and no study-specific intervention: every patient receives standard surgical care. Participants are followed for at least 30 days after surgery to record liver failure (International Study Group of Liver Surgery criteria, operationalized by the "50-50" rule on postoperative day 5) and radiologic evidence of hepatic congestion.
Three nested prediction models are compared - volumetry alone; volumetry plus VDM; and volumetry plus VDM plus the simple radiology parameters - and the best-performing model is converted into a practical risk score. Because the study runs across several centers, the model can be validated by leaving one center out at a time, which gives an honest estimate of how well it would perform at a new hospital. The goal is a generalizable, easy-to-use tool that tells surgeons, before the operation, which patients are genuinely at risk of post-hepatectomy liver failure.
Age 18 years or older
Scheduled to undergo major hepatic resection, defined as the removal of three or more Couinaud segments, at a participating center
Availability of a preoperative multiphasic contrast-enhanced CT of the liver of quality sufficient for central core-laboratory analysis
Willing and able to complete postoperative clinical and laboratory follow-up for at least 30 days
Minor hepatic resection (fewer than three Couinaud segments)
Significant pre-existing vascular anomaly or vascular pathology (for example, portal vein thrombosis)
Emergency hepatic resection for trauma
Preoperative imaging that fails central quality control
Consecutive adult patients undergoing elective major hepatic resection (three or more Couinaud segments) for benign or malignant liver disease at participating tertiary hepatobiliary referral centers in Egypt. Each center enrolls consecutive eligible patients, in order to minimize selection bias, until the overall target sample size is reached.
Cohort
Prospective
Preoperative CT volumetry with hepatic vascular deformation mapping (VDM)
Diagnostic testCentral, non-invasive core-laboratory analysis of the multiphasic contrast-enhanced CT already acquired in routine preoperative work-up; no additional imaging is performed. Images are pseudonymized at source and sent through a secure de-identified pipeline. Using specialized 3D software and one standardized protocol, three sets are extracted: (1) volumetry - total liver volume, future liver remnant (FLR) volume, FLR ratio, FLR-to-body-weight ratio, resection volume; (2) hepatic vascular deformation mapping - hepatic vein angles to the IVC, confluence-to-ostium distance, vascular displacement index, portal vein angulation; and (3) simple radiology parameters on standard CT - hepatic vein, portal, aortic and IVC diameters, congestion index, spleen volume, liver and liver-to-spleen attenuation, remnant attenuation homogeneity, vein-to-resection-plane distances, remnant artery diameter, remnant perfusion index. At least 10% of studies per center are double-read for reliability.
Change in discrimination (delta AUC-ROC) for preoperative prediction of post-hepatectomy liver failure: CT volumetry plus vascular deformation mapping (Model 2) minus CT volumetry alone (Model 1)
One value is reported: delta AUC-ROC = AUC-ROC (Model 2) minus AUC-ROC (Model 1), with a 95% confidence interval. Unit of measure: AUC units (dimensionless). AUC-ROC ranges from 0.5 (no discrimination) to 1.0 (perfect discrimination); delta AUC-ROC therefore ranges from -0.5 to +0.5, and a positive value indicates that vascular deformation mapping improves prediction. Measurement tool: two nested mixed-effects logistic regression models, each with center as a random intercept, fitted in the same participants. Model 1 (volumetry) = total liver volume, future liver remnant (FLR) volume, FLR ratio, FLR-to-body-weight ratio, resection volume. Model 2 = Model 1 plus vascular deformation mapping parameters (right, middle and left hepatic vein angle to the IVC, hepatic vein confluence-to-IVC-ostium distance, vascular displacement index, portal vein angulation). Post-hepatectomy liver failure (PHLF) is defined and centrally adjudicated as specified in Outcome Measure 2.
Incidence of post-hepatectomy liver failure (PHLF)
Number and percentage of participants developing PHLF, defined according to the International Study Group of Liver Surgery (ISGLS) criteria - an impaired ability of the liver to maintain its synthetic, excretory, and detoxifying functions - and operationalized by the "50-50" rule: prothrombin time with INR greater than 1.7 together with serum bilirubin greater than 50 micromol/L on or after postoperative day 5. Events are adjudicated centrally by two independent radiologists and a hepatobiliary surgeon, blinded to the center of origin and to the candidate VDM and radiology parameter values. This is the event on which the sample size is based (100 events at 10 events per candidate predictor).
Discrimination (AUC-ROC) of the full model: CT volumetry plus VDM plus simple radiology parameters
AUC-ROC of the third nested mixed-effects logistic regression model (volumetry + VDM + simple radiology parameters) for the prediction of PHLF, with center as a random intercept, reported with a 95% confidence interval and compared with Model 1 (volumetry alone) and Model 2 (volumetry + VDM).
Calibration of the final prediction model
Agreement between predicted and observed PHLF risk, assessed by the calibration slope, calibration-in-the-large, a calibration plot, and the Hosmer-Lemeshow goodness-of-fit test. A calibration slope of 1.0 and calibration-in-the-large of 0 indicate perfect calibration.
Incidence of radiologic postoperative hepatic congestion
Number and percentage of participants with radiologic evidence of postoperative hepatic congestion on postoperative imaging, defined as areas of delayed enhancement, mosaic attenuation, or periportal edema, adjudicated centrally by two independent radiologists and a hepatobiliary surgeon blinded to the center of origin and to the candidate imaging parameter values.
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Minia University
Lead sponsor
National Liver Institute, Egypt
Collaborator
Maadi Armed Forces Medical Compound, Ministry of Defence
Collaborator
