Prediction Of Posthepatectomy Liver Failure Research Articles

Intraoperatively measured prehepatectomy portal vein pressure as a useful predictor of posthepatectomy liver failure.

Predicting posthepatectomy liver failure (PHLF) may be a critical requirement for liver disease patients undergoing hepatectomy. This study retrospectively analyzed the impact of the intraoperatively measured portal vein pressure (PVP) prior to hepatectomy on the prediction of PHLF in hepatectomized patients. A total of 334 hepatectomized patients in whom the PVP was intraoperatively measured before resection at our institution were enrolled in the present study. Outcomes were assessed according to the International Study Group of Liver Surgery definition and the severity of PHLF grading. Thirty-nine of the 334 patients (11.6%) developed grade B/C PHLF. The following factors were significantly associated with grade B/C PHLF in a univariate analysis: indocyanine green retention rate after 15min, Child-Pugh score, prehepatectomy PVP, and transfusion (each P < 0.0001). A prehepatectomy PVP value of 19.5 cmH2O was the optimal cutoff value for predicting grade B/C PHLF. In a multivariate analysis, prehepatectomy PVP (≥ 19.5 cmH2O) was selected as the most relevant risk factor for grade B/C PHLF (P = 0.0003, hazard ratio: 5.96, 95% CI: 1.80-19.70). Prehepatectomy PVP can serve as a useful predictor of the risk of PHLF in patients who have undergone hepatectomy. The results emphasize the possibility of reducing the planned extent of hepatic resection when the prehepatectomy PVP value measured intraoperatively exceeds 19.5 cmH2O, and the importance of predicting the PVP before the operation.

Soluble TREM2 reflects liver fibrosis status and predicts postoperative liver dysfunction after liver surgery.

Background & AimsChronic liver disease (CLD) represents a major risk for mortality and, while challenging, early detection is key to improve overall outcome. Triggering receptor expressed on myeloid cells 2 (TREM2)-expressing macrophages and systemic levels of soluble TREM2 (sTREM2) appear critical in the development of CLD and seem relevant in its detection. The aim of this study was to examine sTREM2 as a marker for early CLD and its potential to predict posthepatectomy liver failure (PHLF) in patients undergoing partial hepatectomy. MethodsSTREM2 was assessed in plasma of 108 patients undergoing liver resection. Blood was drawn prior to surgery (preop) and on the first and fifth postoperative day. ResultsPreop sTREM2 levels were similar across different indications for resection (p=0.091). Higher preop sTREM2 levels were associated with advanced hepatic fibrosis (p=0.030) and PHLF (p=0.007). Fibrosis-4 index (FIB-4) (p=0.619) and Model for End Stage Liver Disease (MELD) (p=0.590) did not show a difference between patients grouped by their CLD. Comparing the area under the curve from receiver operating characteristic analysis, sTREM2 (AUC=0.708) outperformed FIB-4 (AUC=0.529), MELD (AUC=0.587), Child-Pugh grading (AUC=0.570) and liver maximum capacity test (LiMAx) (AUC=0.516) in predicting PHLF. Similarly, in uni- and multivariate analysis only sTREM2 proved predictive for PHLF (p=0.023). A high- (p=0.003) and low-risk cutoff (p=0.011) for systemic sTREM2 levels were able to identify patients at risk for adverse outcome after surgery. Finally, high sTREM2 was associated with decreased overall survival after liver surgery (p<0.001). ConclusionsCirculating sTREM2 shows sensitivity for early-stage, asymptomatic liver disease, irrespective of the underlying indication for liver surgery. Assessment of CLD via sTREM2 monitoring could improve early detection of CLD and improve outcome after liver surgery. Impact and ImplicationsSoluble TREM2 (sTREM2) has previously been established to correlate with the degree of chronic liver disease. We found that even in patients undergoing liver resection, who generally do not suffer from end stage liver disease, sTREM2 reflects liver fibrosis status and predicts postoperative development of liver dysfunction. This is especially relevant for liver surgeons and patients, as postoperative liver dysfunction is the main reason for postoperative mortality. Our findings are also important for hepatologists, as early detection of liver fiboris and cirrhosis is paramount for overall patient survival and we can show that even in a cohort with a median MELD of 6, sTREM2 is able to distuinguish patients based on their liver fibrosis status.

Pre-operative evaluation of spontaneous portosystemic shunts as a predictor of post-hepatectomy liver failure in patients undergoing liver resection for hepatocellular carcinoma

BackgroundPost-hepatectomy liver failure (PHLF) can significantly compromise outcomes, especially in cirrhotic patients. The identification of accurate and non-invasive pre-operative predictors is of paramount importance to appropriately stratify patients according to their estimated risk and select the best treatment strategy. Materials and methodsConsecutive patients undergoing liver resection for HCC on cirrhosis between 1-2015 and 12–2020 at 10 international Institutions were enrolled and their pre-operative CT scans were evaluated for the presence of spontaneous portosystemic shunts (SPSS) to identify predictors of PHLF and develop a nomogram. ResultsThe analysis of the CT scans identified SPSS in 74 patients (17.4 %). PHLF was developed in 27 out of 425 cases (6.4 %), with grades B/C observed in 17 patients (4 %). At the multivariable analysis, the presence of SPSS resulted an independent risk factor for all-grades PHLF (OR 6.83, 95%CI 2.39–19.51, p < 0.001) and clinically significant PHLF development (OR 7.92, 95%CI 2.03–30.85, p = 0.003) alongside a patient's age ≥74 years, a pre-operative platelets count <106x103/μL, a multiple-segments liver resection, and an intraoperative blood loss ≥1200 mL. The 30- and 90-days mortality in patients with and without SPSS resulted 2.7 % vs 0.3 % (p = 0.024) and 5.4 % vs 1.1 % (p = 0.014). The accuracy of SPSS in predicting PHLF development was 0.847 (95%n CI 0.809–0.880). The internally validated nomogram showed excellent performance in predicting grades B/C PHLF (c-statistic = 0.933 (95%CI 0.888–0.979)). ConclusionThe pre-operative presence of SPSS assessed on the pre-operative imaging proved to be a valuable radiological biomarker able to predict PHLF development in patients undergoing liver resection for HCC.

Interaction between the albumin-bilirubin score and nutritional risk index in the prediction of post-hepatectomy liver failure.

Post-hepatectomy liver failure (PHLF) is the most common postoperative complication and the leading cause of death after hepatectomy. The albumin-bilirubin (ALBI) score and nutritional risk index (NRI) have been shown to assess end-stage liver disease and predict PHLF and patient survival. We hypothesized that the ALBI score and NRI interact in the prediction of PHLF. To analyze the interaction between the ALBI score and NRI in PHLF in patients with hepatocellular carcinoma. This retrospective study included 186 patients who underwent hepatectomy for hepatocellular carcinoma at the Affiliated Hospital of Youjiang Medical University for Nationalities between January 2020 and July 2023. Data on patient characteristics and laboratory indices were collected from their medical records. Univariate and multivariate logistic regression were performed to determine the interaction effect between the ALBI score and NRI in PHLF. Of the 186 patients included in the study, PHLF occurred in 44 (23.66%). After adjusting for confounders, multivariate logistic regression identified ALBI grade 2/3 [odds ratio (OR) = 73.713, 95% confidence interval (CI): 9.175-592.199] and NRI > 97.5 (OR = 58.990, 95%CI: 7.337-474.297) as risk factors for PHLF. No multiplicative interaction was observed between the ALBI score and NRI (OR = 0.357, 95%CI: 0.022-5.889). However, the risk of PHLF in patients with ALBI grade 2/3 and NRI < 97.5 was 101 times greater than that in patients with ALBI grade 1 and NRI ≥ 97.5 (95%CI: 56.445-523.839), indicating a significant additive interaction between the ALBI score and NRI in PHLF. Both the ALBI score and NRI were risk factors for PHLF, and there was an additive interaction between the ALBI score and NRI in PHLF.

Soluble suppression of tumourigenicity 2 as a predictor of postoperative hepatic failure.

Posthepatectomy liver failure remains a potentially life-threatening complication after hepatectomy. Soluble suppression of tumourigenicity 2 is an injury-related biomarker. The aim of the study was to assess soluble suppression of tumourigenicity 2 elevation after hepatectomy and whether it can predict posthepatectomy liver failure. This was a single-centre retrospective study including all patients who underwent a liver resection between 2015 and 2019. Plasma concentrations of soluble suppression of tumourigenicity 2 were measured before surgery and at postoperative days 1, 2, 5 and 7. Posthepatectomy liver failure was defined according to the International Study Group of Liver Surgery and the morbidity rate was graded according to the Clavien-Dindo classification. A total of 173 patients were included (75 underwent major and 98 minor resection); plasma levels of soluble suppression of tumourigenicity 2 increased from 43.42 (range 18.69-119.96) pg/ml to 2622.23 (range 1354.18-4178.27) pg/ml on postoperative day 1 (P < 0.001). Postoperative day 1 soluble suppression of tumourigenicity 2 concentration accurately predicted posthepatectomy liver failure ≥ grade B (area under curve = 0.916, P < 0.001) and its outstanding performance was not affected by underlying disease, liver pathological status and extent of resection. The cut-off value, sensitivity, specificity, positive predictive value and negative predictive value of postoperative day 1 soluble suppression of tumourigenicity 2 in predicting posthepatectomy liver failure ≥ grade B were 3700, 92%, 85%, 64% and 97% respectively. Soluble suppression of tumourigenicity 2high patients more frequently experienced posthepatectomy liver failure ≥ grade B (64.3% (n = 36) versus 2.6% (n = 3)) and Clavien-Dindo IIIa higher morbidity rate (23.2% (n = 13) versus 5.1% (n = 6)) compared with soluble suppression of tumourigenicity 2low patients. Soluble suppression of tumourigenicity 2 may be a reliable predictor of posthepatectomy liver failure ≥ grade B as early as postoperative day 1 for patients undergoing liver resection. Its role in controlling hepatic injury/regeneration needs further investigation. Registration number: ChiCTR-OOC-15007210 (www.chictr.org.cn/).

Utility of gadoxetate disodium-enhanced magnetic resonance imaging in evaluating liver failure risk after major hepatic resection.

Post-hepatectomy liver failure (PHLF) is still a predominant cause of hepatectomy-related mortality. However, it is difficult to evaluate the remnant liver functional reserve accurately before surgery to prevent PHLF. In this study, we aimed to explore the role of gadoxetate disodium-enhanced magnetic resonance imaging (MRI) in evaluating remnant liver functional reserve. For this cross-sectional study, the sample retrospectively included 56 patients undergoing liver resections of at least three segments between June 2019 and September 2022 at The General Hospital of the Western Theater Command. Pre-surgery assessments involved liver computer tomography (CT), an indocyanine green (ICG) clearance test, the Child-Pugh scoring system, and liver function serum biochemical indicators. Each patient underwent a gadoxetate disodium-enhanced MRI before the hepatectomy, and we measured the remnant hepatocellular uptake index (rHUI) as well as the standard remnant hepatocellular uptake index (SrHUI). We examined the diagnostic utility of rHUI, SrHUI, indocyanine green retention rate of 15 minutes (ICG R15), and Albumin for PHLF. Receiver operating characteristics (ROC) analyses were used to measure the preoperative liver function parameters (namely, rHUI, SrHUI, ICG R15, and Albumin) for predicting PHLF. The areas under the curve (AUCs) were calculated and compared between different preoperative liver function parameters using the Wilson/Brown method. The Pearson or Spearman correlation coefficient was used for correlation analysis between ICG R15, Albumin, and rHUI and between ICG R15, Albumin, and SrHUI, respectively. Twelve patients (21.43%) had complications of PHLF. We found significant differences in rHUI, SrHUI, ICG R15, and Albumin between the non-PHLF and PHLF groups. The pooled r between ICG R15 and rHUI was -0.591 [95% confidence interval (CI): -0.740 to -0.389, P<0.001], and between ICG R15 and SrHUI was -0.534 (95% CI: -0.703 to -0.308, P<0.001). The area under the curve (AUC) values of rHUI, SrHUI, ICG R15, and Ablumin were 0.871 (sensitivity 81.82%; specificity 91.67%), 0.878 (sensitivity 79.55%; specificity 83.33%), 0.835 (sensitivity 99.73%; specificity 66.67%), and 0.782 (sensitivity 88.64%; specificity 58.33%), respectively. We found that the rHUI and SrHUI calculated using the gadoxetate disodium-enhanced MRI reflected a combination of remnant hepatocyte function and liver volume, and these were useful as a quantitative assessment indicator of remnant liver functional reserve and can be a better predictor of PHLF after major hepatic resection.

A combined pre- and intra-operative nomogram in evaluation of degrees of liver cirrhosis predicts post-hepatectomy liver failure: a multicenter prospective study.

Adequate evaluation of degrees of liver cirrhosis is essential in surgical treatment of hepatocellular carcinoma (HCC) patients. The impact of the degrees of cirrhosis on prediction of post-hepatectomy liver failure (PHLF) remains poorly defined. This study aimed to construct and validate a combined pre- and intra-operative nomogram based on the degrees of cirrhosis in predicting PHLF in HCC patients using prospective multi-center's data. Consecutive HCC patients who underwent hepatectomy between May 18, 2019 and Dec 19, 2020 were enrolled at five tertiary hospitals. Preoperative cirrhotic severity scoring (CSS) and intra-operative direct liver stiffness measurement (DSM) were performed to correlate with the Laennec histopathological grading system. The performances of the pre-operative nomogram and combined pre- and intra-operative nomogram in predicting PHLF were compared with conventional predictive models of PHLF. For 327 patients in this study, histopathological studies showed the rates of HCC patients with no, mild, moderate, and severe cirrhosis were 41.9%, 29.1%, 22.9%, and 6.1%, respectively. Either CSS or DSM was closely correlated with histopathological stages of cirrhosis. Thirty-three (10.1%) patients developed PHLF. The 30- and 90-day mortality rates were 0.9%. Multivariate regression analysis showed four pre-operative variables [HBV-DNA level, ICG-R15, prothrombin time (PT), and CSS], and one intra-operative variable (DSM) to be independent risk factors of PHLF. The pre-operative nomogram was constructed based on these four pre-operative variables together with total bilirubin. The combined pre- and intra-operative nomogram was constructed by adding the intra-operative DSM. The pre-operative nomogram was better than the conventional models in predicting PHLF. The prediction was further improved with the combined pre- and intra-operative nomogram. The combined pre- and intra-operative nomogram further improved prediction of PHLF when compared with the pre-operative nomogram. Clinicaltrials.gov Identifier: NCT04076631.

Prediction of post-hepatectomy liver failure by preoperative gadoxetate disodium-enhanced magnetic resonance imaging

BackgroundApproximately 15% of patients experience post-hepatectomy liver failure after major hepatectomy. Poor hepatocyte uptake of gadoxetate disodium, a magnetic resonance imaging contrast agent, may be a predictor of post-hepatectomy liver failure. MethodsA retrospective cohort study of patients undergoing major hepatectomy (≥3 segments) with a preoperative gadoxetate disodium-enhanced magnetic resonance imaging was conducted. The liver signal intensity (standardized to the spleen) and the functional liver remnant was calculated to determine if this can predict post-hepatectomy liver failure after major hepatectomy. ResultsIn 134 patients, low signal intensity of the remnant liver standardized by signal intensity of the spleen in post-contrast images was associated with post-hepatectomy liver failure in multiple logistic regression analysis (Odds Ratio 0.112; 95% CI 0.023–0.551). In a subgroup of 33 patients with lower quartile of functional liver remnant, area under the curve analysis demonstrated a diagnostic accuracy of functional liver remnant to predict post-hepatectomy liver failure of 0.857 with a cut-off value for functional liver remnant of 1.4985 with 80.0% sensitivity and 89.3% specificity. ConclusionFunctional liver remnant determined by gadoxetate disodium-enhanced magnetic resonance imaging is a predictor of post-hepatectomy liver failure which may help identify patients for resection, reducing morbidity and mortality.

Predictive Value of Preoperative ICG-R15 Testing in Post-hepatectomy Liver Failure Following Major Liver Resection: Indian Experience.

Surgical resection stands as the preeminent therapeutic approach for both primary hepatocellular carcinoma and metastatic liver malignancies. Its efficacy is contingent upon the attainment of a comprehensive excision while ensuring a sufficient future liver remnant (FLR). However, post-hepatectomy liver failure (PHLF) remains a significant challenge, particularly in patients with preexisting liver disease. The present study aims to investigate the predictive value of the preoperative indocyanine green retention test at 15min (ICG-R15) in identifying patients at risk of PHLF following major liver resection. This retrospective review focused on patients who underwent the ICG-R15 test before major liver resection between August 2021 and January 2023. All patients underwent standard preoperative evaluation and staging. Patients with primary or metastatic liver cancer planned for major resection and undergoing ICG-R15 were included in the study. Patients with elevated serum bilirubin (> 3mg/dl) and those not undergoing liver resection or minor liver resection (< 3 segments) were excluded from the study. PHLF was defined by the International Study Group of Liver Surgery (ISGLS) criteria. Follow-up was performed to identify 90-day morbidity. Using univariate and multivariate logistic regression analyses, we confirmed independent risk parameters that predicted postoperative major complications and severe PHLF. The study included 72 patients who underwent preoperative ICG-R15 testing prior to major liver resection. PHLF occurred in 28 patients (38.9%), with 24 patients (33.3%) classified as severity score B and 3 patients (4.16%) had severity score C. Univariate analysis revealed future liver remnant (FLR), ICG-R15, and blood transfusion as predictors of PHLF. Multivariate analysis confirmed FLR (p = 0.019) and ICG-R15 (p = 0.032) as significant predictors. Receiver operating characteristic curve analysis yielded an area under the curve of 0.642 for ICG-R15 in predicting PHLF. An optimal cut-point of 7.5 was determined. Our study highlights the importance of preoperative risk assessment of liver function evaluation using the ICG-R15 test, to predict the risk of PHLF following liver resection. Implementing appropriate interventions, especially in patients with borderline FLR, can improve surgical outcomes and enhance patient safety. Further research and prospective studies are essential to refine risk prediction models and improve rates of PHLF after liver resections.

A Novel Method Using Gadolinium-Ethoxybenzyl Diethylenetriamine Pentaacetate Acid-Enhanced Magnetic Resonance Imaging for Predicting Post-Hepatectomy Liver Failure in Hepatocellular Carcinoma Patients with a Major Portal Vein Tumor Thrombus

Introduction: The usefulness of gadolinium-ethoxybenzyl diethylenetriamine pentaacetate acid-enhanced magnetic resonance imaging (EOB-MRI) in assessing the functional future remnant liver volume (fFRLV) to predict post-hepatectomy liver failure (PHLF) has been previously reported. Herein, we evaluated the efficacy of this technique in patients with hepatocellular carcinoma (HCC) with a major portal vein tumor thrombus (PVTT). Methods: This study included 21 patients with PVTT in the ipsilateral first-order branch (Vp3) and 30 patients with PVTT in the main trunk/contralateral branch (Vp4). To evaluate fFRLV, the signal intensity (SI) of the remnant liver was determined on T1-weighted images, using both conventional and newly developed methods. The fFRLV was calculated using the SI of the remnant liver and muscle, remnant liver volume, and body surface area. Preoperative factors predicting PHLF (≥grade B) in HCC patients with Vp3/4 PVTT were evaluated. Results: In the Vp3 group, we found fFRLV area under the receiver-operating characteristic curves (AUCs) above 0.70 (AUC = 0.875, 0.750) using EOB-MRI results calculated using either the plot or whole method. None of the parameters in the Vp4 group had an AUC greater than 0.70. Conclusion: The fFRLV calculated by EOB-MRI using the whole method can be as useful as the conventional method in predicting PHLF (≥grade B) for HCC patients with Vp3 PVTT.

Evaluation and Prediction of Post-Hepatectomy Liver Failure Using Imaging Techniques: Value of Gadoxetic Acid-Enhanced Magnetic Resonance Imaging.

Despite improvements in operative techniques and perioperative care, post-hepatectomy liver failure (PHLF) remains the most serious cause of morbidity and mortality after surgery, and several risk factors have been identified to predict PHLF. Although volumetric assessment using imaging contributes to surgical simulation by estimating the function of future liver remnants in predicting PHLF, liver function is assumed to be homogeneous throughout the liver. The combination of volumetric and functional analyses may be more useful for an accurate evaluation of liver function and prediction of PHLF than only volumetric analysis. Gadoxetic acid is a hepatocyte-specific magnetic resonance (MR) contrast agent that is taken up by hepatocytes via the OATP1 transporter after intravenous administration. Gadoxetic acid-enhanced MR imaging (MRI) offers information regarding both global and regional functions, leading to a more precise evaluation even in cases with heterogeneous liver function. Various indices, including signal intensity-based methods and MR relaxometry, have been proposed for the estimation of liver function and prediction of PHLF using gadoxetic acid-enhanced MRI. Recent developments in MR techniques, including high-resolution hepatobiliary phase images using deep learning image reconstruction and whole-liver T1 map acquisition, have enabled a more detailed and accurate estimation of liver function in gadoxetic acid-enhanced MRI.

Utility of Machine Learning in the Prediction of Post-Hepatectomy Liver Failure in Liver Cancer.

Posthepatectomy liver failure (PHLF) is a serious complication associated with high mortality rates. Machine learning (ML) has rapidly developed and may outperform traditional models in predicting PHLF in patients who have undergone hepatectomy. This study aimed to predict PHLF using ML and compare its performance with that of traditional scoring systems. The clinicopathological data of 334 patients who underwent liver resection were retrospectively collected. The Pycaret library, a simple, open-source machine learning library, was used to compare multiple classification models for PHLF prediction. The predictive performance of 15 ML algorithms was compared using the mean area under the receiver operating characteristic curve (AUROC) and accuracy, and the best-fit model was selected among 15 ML algorithms. Next, the predictive performance of the selected ML-PHLF model was compared with that of routine scoring systems, the albumin-bilirubin score (ALBI) and the fibrosis-4 (FIB-4) index, using AUROC. The best model was extreme gradient boosting (accuracy:93.1%; AUROC:0.863) among the 15 ML algorithms. As compared with ALBI and FIB-4, the ML PHLF model had higher AUROC for predicting PHLF. The novel ML model for predicting PHLF outperformed routine scoring systems.

Pre-operative evaluation of spontaneous portosystemic shunts as a predictor of post-hepatectomy liver failure in patients undergoing liver resection for hepatocellular carcinoma

Pre-operative evaluation of spontaneous portosystemic shunts as a predictor of post-hepatectomy liver failure in patients undergoing liver resection for hepatocellular carcinoma

Liver remnant volume to body weight ratio of 0.65% as a lower limit in right hepatic trisectionectomy with bile duct resection

BackgroundPrevious studies have suggested the utility of an indocyanine green plasma clearance rate of the future liver remnant (FLR) (ICGK-F) ≥0.05 in hepatobiliary resection to reduce the surgical risk. The present study aimed to verify whether future liver remnant size rather than ICGK-F matters in extended hepatobiliary resection. MethodsBetween 2004 and 2021, patients who underwent right hepatic trisectionectomy with bile duct resection were included. The effect of the FLR volume-to-body weight ratio (FLR/BW) and ICGK-F on posthepatectomy liver failure was evaluated along with other parameters. ResultsAmong 91 study patients, the median ICGK-F, FLR, and FLR/BW were 0.057 (range, 0.027–0.099), 392 mL (145–705), and 0.78% (0.40–1.37), respectively. Posthepatectomy liver failure occurred in 23 patients. The incidence was 10 (40%) in 25 patients with an ICGK-F <0.05 and 12 (18%) in 65 patients with an ICGK-F ≥0.05 (P = .053); 13 (52%) in 25 patients with a FLR/BW <0.65% and 10 (15%) in 66 patients with a FLR/BW ≥0.65% (P = .001). Multivariate analysis showed that a FLR/BW <0.65% (odds ratio, 11.7; P = .005), age ≥65 years (odds ratio, 31.7; P < .001), and blood loss ≥25 mL/kg (odds ratio, 22.1; P = .004) were independent predictors of posthepatectomy liver failure, but ICGK-F <0.05 was not (P = .499). According to the meeting number of 3 factors, posthepatectomy liver failure incidence was 0 of 22 (0%) in patients with 0 factors, 6 of 43 (14%) in patients with 1, and 17 of 26 (65%) in patients with 2 or 3 (P < .001). ConclusionA FLR/BW ≥0.65% may serve as a volumetric basis to reduce posthepatectomy liver failure after extended hepatobiliary resection.

Balance of Gata3 and Ramp2 in hepatocytes regulates hepatic vascular reconstitution in postoperative liver regeneration

Post-hepatectomy liver failure (PHLF) leads to poor prognosis in patients undergoing hepatectomy, with hepatic vascular reconstitution playing a critical role. However, the regulators of hepatic vascular reconstitution remain unclear. In this study, we aimed to investigate the regulatory mechanisms of hepatic vascular reconstitution and identify biomarkers predicting PHLF in patients undergoing hepatectomy. Candidate genes that were associated with hepatic vascular reconstitution were screened using adeno-associated virus vectors in Alb-Cre-CRISPR/Cas9 mice subjected to partial hepatectomy. The biological activities of candidate genes were estimated using endothelial precursor transfusion and associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) models. The level of candidates was detected in biopsies from patients undergoing ALPPS. Risk factors for PHLF were also screened using retrospective data. Downregulation of Gata3 and upregulation of Ramp2 in hepatocytes promoted the proliferation of liver sinusoidal endothelial cells and hepatic revascularization. Pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor A (VEGFA) played opposite roles in regulating the migration of endothelial precursors from bone marrow and the formation of new sinusoids after hepatectomy. Gata3 restricted endothelial cell function in patient-derived hepatic organoids, which was abrogated by a Gata3 inhibitor. Moreover, overexpression of Gata3 led to higher mortality in ALPPS mice, which was improved by a PEDF-neutralizing antibody. The expression of Gata3/RAMP and PEDF/VEGFA tended to have a negative correlation in patients undergoing ALPPS. A nomogram incorporating multiple factors, such as serum PEDF/VEGF index, was constructed and could efficiently predict the risk of PHLF. The balance of Gata3 and Ramp2 in hepatocytes regulates the proliferation of liver sinusoidal endothelial cells and hepatic revascularization via changes in the expression of PEDF and VEGFA, revealing potential targets for the prevention and treatment of PHLF. In this study, we show that the balance of Gata3 and Ramp2 in hepatocytes regulates hepatic vascular reconstitution by promoting a shift from pigment epithelium-derived factor (PEDF) to vascular endothelial growth factor A (VEGFA) expression during hepatectomy- or ALLPS (associating liver partition and portal vein ligation for staged hepatectomy)-induced liver regeneration. We also identified serum PEDF/VEGFA index as a potential predictor of post-hepatectomy liver failure in patients who underwent hepatectomy. This study improves our understanding of how hepatocytes contribute to liver regeneration and provides new targets for the prevention and treatment of post-hepatectomy liver failure.

Albumin-indocyanine green evaluation of future liver remnant predicts liver failure after anatomical hepatectomy for hepatocellular carcinoma: A dual-center retrospective study.

The albumin-indocyanine green evaluation (ALICE) score is a useful predictor of post-hepatectomy liver failure (PHLF); however, its usefulness in combination with future liver remnant (FLR), measured by 3-D volumetry, has not been investigated. This study aimed to investigate the relationship between the ALICE of the FLR (ALICE-FLR) score and severe PHLF. The clinical data of 215 patients who underwent anatomical hepatectomy for hepatocellular carcinoma without portal vein embolization at two institutes between January 2010 and December 2021 were analyzed retrospectively. PHLF occurrence and severity were determined according to the International Study Group of Liver Surgery's definition. Grades B and C PHLF were defined as severe PHLF. The ALICE-FLR, ALICE scores, and indocyanine green clearance of FLR (ICGK-FLR) were evaluated for severe PHLF prediction. Severe PHLF was observed in 40 patients (18.6%). The areas under the curve (AUCs) for the ALICE-FLR, ALICE scores, ICGK-FLR, and FLR were 0.76, 0.64, 0.73, and 0.69, respectively. The AUC of the ALICE-FLR score was significantly higher than that of the ALICE score. The ALICE-FLR score was identified as an independent predictor of severe PHLF (the odds ratio for every 0.01 increment in the ALICE-FLR score was 1.24; 95% confidence interval, 1.070-1.453; p = 0.004). Among patients with severe PHLF, the ALICE-FLR score was significantly higher in the grade C than in the grade B PHLF group. The combination of liver function models, including indocyanine green, albumin, and FLR is considered compatible for predicting severe PHLF.

Tc-99m mebrofenin hepatobiliary scintigraphy to assess future liver remnant function before major liver surgery.

Assessment of liver function is paramount before hepatectomy. This study aimed to assess future liver remnant function (FLR-F) using hepatobiliary scintigraphy (HBS) and to compare it to FLR volume (FLR-V) in the prediction of posthepatectomy liver failure (PHLF). The impact of volume and function gains were also assessed in patients undergoing portal vein embolization (PVE) or liver venous deprivation (LVD). All consecutive patients undergoing major hepatectomy between 02/2018 and 09/2021 with preoperative HBS were included. FLR-V was expressed as percentage of total liver volume and analyzed using preoperative computed tomography. FLR-V and FLR-F gains after embolization were expressed in percentage. Receiver operating characteristic analysis was performed to compare both methods in predicting PHLF. Thirty-six patients were included. PVE and LVD were performed in 4 (11%) and 28 patients (78%), respectively. Overall, PHLF occurred in eight patients (22%). FLR-F gain after embolization showed significant ability to predict PHLF (area under the curve [AUC] = 0.789), with cut-off value of 150% showing a sensitivity of 1.00, a specificity of 0.42, and a negative predictive value of 1.00. Preoperative HBS shows a high sensitivity to predict PHLF when HBS is performed twice to measure the function gain after venous embolization.

Comparing Outcomes of Minimally Invasive and Open Hepatectomy for Primary Liver Malignancies in Patients with Low-MELD Cirrhosis

IntroductionCirrhotic patients with primary liver cancer may undergo curative-intent resection when selected appropriately. Patients with T1 tumors and low-MELD are generally referred for resection. We aim to evaluate whether minimally invasive hepatectomy (MIH) is associated with improved outcomes versus open hepatectomy (OH). MethodsNSQIP hepatectomy database 2014–2021 was used to select patients with T1 Hepatocellular Carcinoma (HCC) or Intra-hepatic Cholangiocarcionoma (IHCC) and low-MELD cirrhosis (MELD ≤ 10) who underwent partial hepatectomy. Propensity score matching was applied between OH and MIH patients, and 30-day postoperative outcomes were compared. Multivariable regression was used to identify predictors of post-hepatectomy liver failure (PHLF) in the selected population. ResultsThere were 922 patients: 494 (53.6%) OH, 372 (40.3%) MIH, and 56 (6.1%) began MIH converted to OH (analyzed with the OH cohort). We matched 354 pairs of patients with an adequate balance between the groups. MIH was associated with lower rates of bile leak (HR 0.37 [0.19–0.72)], PHLF (HR 0.36 [0.15–0.86]), collections requiring drainage (HR 0.30 [0.15–0.63]), postoperative transfusion (HR 0.36 [0.21–0.61]), major (HR 0.45 [0.27–0.77]), and overall morbidity (HR 0.44 [0.31–0.63]), and a two-day shorter median hospitalization (3 vs. 5 days; HR 0.61 [0.45–0.82]). No difference was noted in operative time, wound, respiratory, and septic complications, or mortality. Regression analysis identified ascites, prior portal vein embolization (PVE), additional hepatectomies, Pringle’s maneuver, and OH (vs. MIH) as independent predictors of PHLF. ConclusionMIH for early-stage HCC/IHCC in low-MELD cirrhotic patients was associated with improved postoperative outcomes over OH. These findings suggest that MIH should be considered an acceptable approach in this population of patients.

Spleen volume is a predictor of posthepatectomy liver failure and short-term mortality for hepatocellular carcinoma.

The study aimed at retrospectively assessing the impact of spleen volume (SpV) on the development of posthepatectomy liver failure (PHLF) in patients who underwent hepatectomy for hepatocellular carcinoma (HCC). 152 patients with primary HCC who underwent hepatectomy (sectionectomy or more) were classified into PHLF and non-PHLF groups, and then the relationship between PHLF and SpV was assessed. SpV (cm3) was obtained from preoperative CT and standardized based on the patient's body surface area (BSA, m2). PHLF was observed in 39 (26%) of the 152 cases. SpV/BSA was significantly higher in the PHLF group, and the postoperative 1-year survival rate was significantly worse in the PHLF group than that in the non-PHLF group (p = 0.044). Multivariable analysis revealed SpV/BSA as a significant independent risk factor for PHLF. Using the cut-off value (160 cm3/m2), the 152 cases were divided into small SpV and large SpV groups. The incidence of PHLF was significantly higher in the large SpV group (p = 0.002), the liver failure-related mortality rate was also significantly higher in the large SpV group (p = 0.007), and the 1-year survival rate was significantly worse in the large SpV group (p = 0.035). These results suggest SpV as a predictor of PHLF and short-term mortality in patients who underwent hepatectomy for HCC. Moreover, SpV measurement is a simple and potentially useful method for predicting PHLF in patients with HCC.

Poresekčná pečeňová nedostatočnosť – skórovacie systémy v klinickej praxi

Summary: Introduction: Posthepatectomy liver failure (PHLF) is still a dreaded disease entity despite medical advances. The primary aim of the work was to retrospectively apply selected scoring systems used to assess the risk of PHLF to a group of patients after major liver resections operated at the authors‘ workplace. We anticipate that the latest scoring systems will provide a more accurate picture of PHLF risk. Methods: Between 2007 and 2016, 82 patients meeting the inclusion criteria (elective removal of three or more liver segments for neoplasm) were identified. Five scoring systems were applied to them, namely: “50-50” criterion, ISGLS classification, Hyder score, ALBI and Liu score. Results: Using the “50-50” criterion, none of the patients reached the diagnosis of PHLF. Applying the ISGLS scoring system, 68 patients (86%) had grade “A” and 11 had grade “B” PHLF on the 5th postoperative day. Hyder‘s score above 11 was achieved by two patients who died on the 14th and 34th postoperative day. In the ALBI score, only one patient achieved a value of more than –1.39 (–0.4), while he died on the second postoperative day. Within the Liu score, 55 patients had a predicted very serious risk of developing PHLF, while 46 patients died with an average survival of 27 months after resection. Of the five applied scoring systems, only in the case of ALBI and Liu scores was a statistically significant difference between subgroups of patients with different degrees of presence or prediction of PHLF. A marginally significant difference in the proportion of genders was also noted within the entire set, with men having a higher chance of death (OR 2.63; 95% CI 0.83–8.32). Discussion: The ALBI scoring system correlates with the literature. It has shown very good prediction in several meta-analyses of cohorts of patients after major liver resection. A significantly positive clinical factor of the use of this system is that it is based on preoperative values of laboratory blood tests and can be proposed as a stable prediction model for short-term results after liver resection. Conclusion: The presented scoring systems still represent a rather heterogeneous view of PHLF. Our work points to the ALBI score as the best scoring system. Consistent stratification of patients and treatment in high-volume centers are key pillars of prevention of PHLF. Key words: hepatectomy – liver failure – liver neoplasm – posthepatectomy liver failure – major liver resection – scoring systems