Postoperative Liver Dysfunction Research Articles

Using Machine Learning to Predict Postoperative Liver Dysfunction After Aortic Arch Surgery

The study compared machine-learning models with traditional logistic regression to predicting liver outcomes after aortic arch surgery. Retrospective review from January 2013 to May 2017. Fuwai Hospital. The study comprised 672 consecutive patients who had undergone aortic arch surgery. Three machine-learning methods were compared with logistic regression with regard to the prediction of postoperative liver dysfunction (PLD) after aortic arch surgery. The perioperative characteristics, including the patients' baseline medical condition and intraoperative data, were analyzed. The performance of the models was assessed using the area under the receiver operating characteristic curve. Naïve Bayes had the best discriminative ability for the prediction of PLD (area under the receiver operating characteristic curve = 0.77) compared with random forest (0.76), support vector machine (0.73), and logistic regression (0.72). The primary endpoint of PLD was observed in 185 patients (27.5%). The cardiopulmonary bypass time, long surgery time, long aortic clamp time, high preoperative bilirubin value, and low rectal temperature were strongly associated with the development of PLD after aortic arch surgery. The machine-learning method of naïve Bayes predicts PLD after aortic arch surgery significantly better than traditional logistic regression.

Is it necessary to measure hepatic venous pressure gradient before liver resection in cirrhotic patients? A single center audit.

To determine whether routine preoperative hepatic venous pressure gradient measurements are necessary in child's-A cirrhotic patients undergoing liver resection for hepatocellular carcinoma, and to assess immediate post-operative liver dysfunction and 30-day mortality in such cases. The 3-year audit was done at Shuakat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, and comprised data from January 1, 2015, to December 31, 2017, of all Child's class "A" patients with hepatocellular carcinoma without any clinical signs of portal hypertension who had preoperative hepatic venous pressure gradient measurements done. A proforma was used to collect the required data from patient files. Data was analysed using SPSS 21. Of the 20 patients, 11(55%) were males. The overall mean age was 60.6±7.4 years. Only 2(10%) patients had raised hepatic venous pressure gradient. Of the total, 14(70%) patients underwent surgery. Mean duration of surgery was 222±82.5 minutes and mean hospital stay was 6.8±3.2 days. None of the patients had deranged prothrombin-time or bilirubin on postoperative day 5. The incidence of subclinical portal hypertension was very low. Hepatic venous pressure gradient measurement can be avoided in early stage hepatocellular carcinoma for child's A cirrhotic patients undergoing liver resection.

Combined APRI/ALBI score to predict mortality after hepatic resection.

BackgroundAspartate aminotransferase/platelet ratio index (APRI) and albumin–bilirubin grade (ALBI) are validated prognostic indices implicated as predictors of postoperative liver dysfunction after hepatic resection. The aim of this study was to evaluate the relevance of the combined APRI/ALBI score for postoperative clinically meaningful outcomes.MethodsPatients undergoing hepatectomy were included from the American College of Surgeons National Surgical Quality Improvement Program database. The association between APRI/ALBI score and postoperative grade C liver dysfunction, liver dysfunction-associated and overall 30-day mortality was assessed.ResultsA total of 12 055 patients undergoing hepatic resection from 2014 to 2017 with preoperative blood values and detailed 30-day postoperative outcomes were included (exploration cohort: January 2014 to December 2016; validation cohort: 2017). In the exploration cohort (8538 patients), the combination of both scores (APRI/ALBI) was significantly associated with postoperative grade C liver dysfunction, 30-day mortality, and liver dysfunction-associated 30-day mortality, and was superior to either score alone. The association with postoperative 30-day mortality was confirmed in multivariable analysis. A predictive model was generated using the exploration cohort. The predicted incidence of events closely followed the observed incidence in the validation cohort (3517 patients). Subgroup analyses of tumour types were used to generate disease-specific risk models to assess risk in different clinical scenarios. These findings informed development of a smartphone application (https://tellaprialbi.37binary.com).ConclusionThe predictive potential of the combined APRI/ALBI score for clinically relevant outcomes such as mortality was demonstrated. An evidence-based smartphone application will allow clinical translation and facilitation of risk assessment before hepatic resection using routine laboratory parameters.

Risk Factors for Postoperative Liver Enzyme Elevation After Laparoscopic Gastrectomy for Gastric Cancer.

Laparoscopic gastrectomy (LG) is more frequently associated with postoperative liver enzyme elevation (PLEE) than open gastrectomy in phase III clinical trials for Japanese gastric cancer patients. The aim of this study was to determine the risk factors for PLEE after LG for gastric cancer. This study enrolled 153 consecutive patients with gastric cancer who underwent LG. The patient characteristics, the liver retraction method [silicone disc (SD) or Nathanson liver retractor (NLR)], and perioperative outcomes were compared between patients with and without PLEE. PLEE was observed in 26 patients (17%). The patients with PLEE exhibited longer operative times (p=0.005) and more frequent use of the NLR for liver retraction (p=0.022). In the multivariate analysis, liver retraction using the NLR (p=0.003) and aberrant left hepatic artery (ALHA) ligation (p=0.042) were independent risk factors of PLEE. Liver retraction with the SD during LG was shown to be the safer method that is less likely to cause postoperative liver dysfunction. ALHA preservation may contribute to avoiding postoperative liver dysfunction.

Von Willebrand factor antigen as a versatile preoperative marker in patients undergoing liver resection for hepatocellular carcinoma

Presenter: Patrick Starlinger MD | Mayo Clinic, Rochester Background: Risk evaluation in patients with hepatocellular carcinoma (HCC) prior to liver resection is an ongoing debate in the field, as long-term outcome is affected by an increased risk for LD and early disease recurrence. Currently available predictors are costly, not broadly available and lack predictive accuracy. Recently, vWF-Ag was established as a marker for postoperative LD. Due to its pleiotropic associations with components of HCC pathology vWF-Ag was further investigated in a variety of malignant diseases. This study aimed to compare routinely available parameters of risk assessment in HCC patients prior to liver resection and investigate the role of von Willebrand factor antigen (vWF-Ag) as a biomarker for postoperative liver dysfunction (LD), disease recurrence and long-term overall survival (OS). Methods: A total of 72 patients suffering from HCC was included out of a prospective trial cohort investigating the predictive potential of vWF-Ag for immediate outcome after liver resection in 223 patients (ClinicalTrials.gov-Identifier:NCT02118545). Patients clinical course was documented and they were followed up for disease recurrence and OS after discharge. Results: Upon logistic regression only vWF-Ag, volumentric assessment of future liver remnant (FLR) and measures of indocyanine green clearance (ICG-C) were able to predict patients risk for development of LD. In direct comparison using ROC-analysis, vWF-Ag was found to be comparable to parameters of ICG-C (area under the curve [AUC] = 0.828, vs 0.894 and 0.880) and more accurate than FLR (AUC = 0.756) and hepatic venous pressure gradient (HVPG, AUC = 0.590). Multivariable Cox-regression further revealed an independent association of vWF-Ag with disease free survival (odds ratio [OR] = 1.004, 95% confidence interval [CI] : 1.000-1.008). Ultimately, prediction of OS according to preoperative vWF-Ag was independent from development of postoperative LD, morbidity and disease recurrence. Given the clinical relevance to identify patients that might not benefit from liver resection and better served with other treatment options we defined a high risk cohort that developed LD in 55.6% of the cases (vs. 12.7% in vWF-AgLOW patients, p = 0.002) and had a 50% risk for postoperative mortality within the first postoperative year (vs. 11.7% in vWF-AgLOW patients, p = 0.006). Conclusion: Preopertive vWF-Ag is comparable to or more accurate than costly methods of preoperative risk evaluation, including volumetric estimation of FLR, ICG-C and HVPG measurement. In addition, preoperative vWF-Ag is associated with OS independent of postoperative outcome. The present data stresses the use of vWF-Ag as a broadly available routine laboratory parameter in preoperative risk evaluation for HCC patients and suggests that it might allow to personalize surgical strategy and treatment plan to the individual patient.

Validation of the APRI+ALBI smart phone application for preoperative risk assessment after liver resection in a routine clinical setting

Presenter: David Pereyra MD | Mayo Clinic, Rochester Background: Liver surgery obtains the risk of development of postoperative liver dysfunction (LD) and associated increased morbidity and mortality. In order to mitigate the individual risk for adverse postoperative outcome, predictive markers and scores have been developed. In this context, APRI and ALBI, both based on routine laboratory parameters, and their summative conjunction were previously established as predictive markers for postoperative LD in patients undergoing liver resection after neoadjuvant chemotherapy, as well as in a set of more than 12,000 patients in the NSQUIP database. Here, we aimed to validate APRI+ALBI and our Smart phone application system in a routine clinical set of patients undergoing liver surgery. Methods: We identified 160 patients with available data on preoperative albumin, bilirubin, aspartate aminotransferase and platelet count and postoperative outcome. APRI and ALBI were calculated and prognostic value for postoperative outcome was evaluated. Results: Using receiver operating curve analysis, APRI+ALBI was found to be superior to APRI alone or ALBI alone in prediction of postoperative LD (area under the curve [AUC]=0.717, AUC=0.669, AUC=0.691, respectively). Further, APRI+ALBI was superior to parameters of indocyanine green clearance (plasma disappearance rate: AUC=0.628, retention rate at 15 minutes: AUC=0.669). A preoperative cut-off at -2.46 was able to stratify patients at risk for postoperative LD (6.1% vs 18.0%, p=0.017), morbidity (32.7% vs 63.9%, p<0.001), severe morbidity (11.2% vs 34.4%, p<0.001), and mortality within 90 postoperative days (1.0% vs 8.5%, p=0.028). Utilizing our previously established smart phones application, we were able to validate appropriate classification patients in individual risk groups according to their preoperative APRI/ALBI score. Conclusion: Here, we validate APRI+ALBI as a predictive marker for postoperative adverse outcome in a clinical routine set of patients undergoing liver resection. The detection of multiple with pathophysiological processes , such as for example chemotherapy associated liver injury but also alcoholic liver disease, by the APRI/ALBI score, allowed prediction of outcome after liver resection in an routine clinical setting. Applying this twice validated marker based on routine laboratory parameters allows estimation of individual patient risk prior to liver resection and might ultimately reduce occurrence of postoperative complications. A specific and gradual risk assessment seems to be possible using the APRI/ALBI smart phone application in a routine clinical setting. Until more specific markers are available, this application represents a valuable tool to assess individualized patients risk for postoperative outcome based on routine laboratory parameters.

Simultaneous combined radical surgery for hepatic and renal alveolar echinococcosis: an analysis of 10 clinical cases

Objective: To examine the feasibility, safety and efficacy of simultaneous combined radical surgery for hepatic and renal alveolar echinococcosis (AE). Methods: Clinical dates of consecutive 10 hepatic and renal AE patients who accepted surgical treatment in the First Affiliated Hospital of Xinjiang Medical University during April 2013 to September 2019 were analyzed retrospectively. There were 8 males and 2 females, aged (42.5±10.3) years (range: 27 to 52 years). Seven of them had previously palliative surgical treatment with poor compliance to post-operative medication. All of the patients had hepatic-renal combined AE lesions, and two of them had left lateral and left renal lesions for each, which sized for (726.4±576.1)cm3 (range: 117.0 to 1 998.0 cm3). Extra-hepatic or renal lesions infiltrated to right diaphragm, inferior vena cava, right adrenal gland, abdominal wall, right psoas muscle, duodenum wall and right pulmonary lobe (respectively were 7, 7, 6, 2, 1, 1, 2 cases). Surgery were performed mainly with simultaneous combined surgery and vascular reconstruction techniques for this series. Hemi-hepatectomy or extended right lobectomy was applied in 8 patients, while 2 other patients received ex vivo liver resection and autotransplantation, additionally, one patient had partial hepatectomy for left lateral lobular lesion. Total right nephrectomy, partial right nephrectomy and partial left nephrectomy were respectively performed on 7, 3 and 1 patient(s). Additionally, extra-hepatic or renal lesions were eradicated followed by relevant repairments or reconstructions. Results: Surgeries went well and there was no intra-or post-operative liver or renal dysfunction occurred. During recovery period, 3 cases experienced with hydrothorax and managed well after drainage and supportive treatment, and one patient developed peri-renal urinary leakage and cured by "J" catheter. The subjects were followed-up for 6 to 81 months (median: 21 months), no death, organ dysfunction, chronic or acute kidney diseases occurred. One case encountered with abdominal hernia at post-operative 7th month and was successfully managed with laparoscopic repair with artificial mesh. No disease recurrence in all patients, which reached clinical cure at last. Conclusion: When complied strictly to indications, simultaneous combined radical surgery could be a feasible, safe and efficient approach for patients with hepatic and renal AE, which is primary or relapsed from previous hepatic AE surgery or interventional therapies as well as neighboring organ AE invasions.

Splenic Enlargement Induced by Preoperative Chemotherapy Is an Useful Indicator for Predicting Liver Regeneration after Resection for Colorectal Liver Metastases

Introduction: Conversion chemotherapy may downsize unresectable colorectal liver metastases (CRLMs), but may cause liver injury and splenic enlargement. The effect of preoperative chemotherapy on liver regeneration after liver resection remains undetermined. The aim of this study was to examine whether splenic enlargement induced by preoperative chemotherapy is an indicator to identify high-risk patients for impaired liver regeneration and liver dysfunction after resection. Methods: We retrospectively reviewed 118 Japanese patients with CRLMs. Fifty one patients had conversion chemotherapy. The other 67 patients underwent upfront liver resection. We clarified effects of conversion chemotherapy on splenic volume, liver function, and postoperative liver regeneration. Perioperative outcome was also analyzed. Results: A ratio of the splenic volume before and after chemotherapy (SP index) in the oxaliplatin-based chemotherapy group was significantly greater than other chemotherapy groups after 9 or more chemotherapy cycles. Patients whose SP index was 1.2 or more had significantly higher indocyanine green retention rate at 15 min (ICG-R15) than patients without chemotherapy. Analyses of covariance showed liver regeneration rate after resection was decreased in patients whose SP index was 1.2 or more. The incidence of postoperative liver dysfunction in patients whose SP index was 1.2 or more was significantly greater than patients without chemotherapy. Multivariate analysis showed SP index was a significant predictive factor of impaired liver regeneration. Conclusion: Splenic enlargement induced by preoperative chemotherapy was a useful evaluation indicator for impaired liver regeneration after resection and a decision-making tool for treatment strategy for unresectable CRLMs.

The AXL/Gas-6 pathway as critical negative regulator of inflammation to orchestrate in human liver regeneration

Presenter: Patrick Starlinger MD | Mayo Clinic, Rochester Background: AXL and its corresponding ligand GAS-6 are critically involved in hepatic immunomodulation. Accumulating evidence further suggests their importance in regenerative processes. Essential might be their pleiotropic inhibitory effect on innate inflammatory responses, mediated by shifting macrophage phenotype from a pro-inflammatory M1 to an anti-inflammatory, pro-regenerative M2 polarization. Given experimental evidence, we aimed to assess the relevance of the AXL-pathway in human liver regeneration and, consequently, its association with clinical outcome after hepatic resection. Methods: Preoperative sAXL, GAS-6 concentrations and postoperative clinical outcome were analyzed in patients undergoing partial hepatectomy. Perioperative dynamics of interleukin (IL)-6 and neutrophil density were assessed as markers of inflammation, and sCD163, reflecting a shift in macrophage polarization. Results: Preoperatively elevated sAXL and GAS-6 levels significantly predicted postoperative liver dysfunction (area under the curve = 0.721 and 0.722; P < 0.005) and worse clinical outcome. These patients were found to be unable to respond with an immediate burst upon induction of liver regeneration. Abolished AXL pathway response interfered with sufficient formation/generation of regeneratory macrophages, as shown by a reduced increase of sCD163, an indicator of M2-polarization. Concomitantly, a distinct association of neutrophil infiltration (δ - GAS-6 and δ - Neutrophils: R = - 0.941 (P = 0.002)) and IL-6 release with an absent increase of TAM-signaling indicated pronounced postoperative inflammation. This was further supported by increased intrahepatic secondary necrosis as reflected by M65. Conclusion: We provided evidence that sAXL and GAS-6 represent not only potent and easily accessible preoperative biomarkers for the postoperative outcome, but that AXL/GAS-6 signaling is of critical relevance for human liver regeneration. Chronic exhaustion of the sAXL/GAS-6 system results in a lack of their immediate release upon induction of liver regeneration, resulting in an overwhelming immune activation, presumably due to absent M2 macrophage polarization.

Preoperative APRI+ALBI Score Allows Risk Stratification Prior to Liver Resection

Background: Preoperative risk assessment for postoperative liver dysfunction (LD) still poses a major challenge in patients undergoing liver resection. Aspartate Aminotransferase/Platelet Ratio Index (APRI) and Albumin-Bilirubin Grade (ALBI) are validated markers in patients suffering from hepatic pathologies. Within this analysis, we aimed to validate our recent exploratory findings in a larger cohort focusing on clinically relevant outcome parameters and subsequently develop a web based application system to facilitate easy clinical translation. Methods: Assessing the National Surgical Quality Improvement Program (NSQIP) database, we identified 13401 patients undergoing liver resection from 2014 to 2017 for preoperative blood values and detailed 30-day postoperative outcomes. Preoperative APRI+ALBI score was calculated from these routine laboratory tests. Results: The scores (APRI and ALBI) significantly predicted postoperative grade C liver dysfunction, 30-days mortality and LD associated 30-days mortality upon receiver operating characteristic analyses (all P < 0.001). The combination of both scores was superior to MELD as well as each individual score. Upon multivariable analysis APRI+ALBI remained an independent predictor of postoperative LD associated 30-day mortality. We further developed a web based application to calculate the APRI+ALBI score to define the specific risk of postoperative grade C LD and more importantly 30-day mortality for the APRI+ALBI score. Conclusion: APRI+ALBI is vital to predict clinically meaningful postoperative outcome after liver resection. Further we developed a web based application to allow clinical translation of these findings and facilitate quick and easy risk assessment prior to liver resection using routine laboratory parameters.

Predictors of Mortality During Initial Liver Transplant Hospitalization and Investigation of Causes of Death.

BackgroundLiver transplant (LT) remains a life-saving procedure with a high mortality rate. The present study investigated the causes of death and sought to identify predictive factors of mortality during the initial LT hospitalization.Material/MethodsWe retrieved data on first-time adult recipients who underwent LT between November 2017 and October 2019 receiving grafts from donation after citizen’s death. The risk factors for mortality during the initial LT hospitalization were confirmed by univariate analysis. We also analyzed the causes of death.ResultsWe enrolled 103 recipients, including 86 males and 17 females, with a mean age of 47.7 years. Thirty-eight (36.9%) recipients were labeled as non-cholestatic cirrhosis-related indications. Approximately 8% of all recipients had diabetes prior to LT. Induction therapy was used in 11 (10.7%) recipients, along with maintenance therapy. The median model for end-stage liver disease score at LT was 32.4 (21.4–38.4). The in-hospital mortality rate of LT recipients was 6.8% (7/103), and infections were responsible for most of the deaths (6/7). The 1 remaining death resulted from primary graft failure. Univariate analysis showed recipients with postoperative pneumonia (p<0.05), acute hepatic necrosis, and intensive care unit (ICU) stay ≥7 days (both p<0.01), postoperative bacteremia, creatinine on day 3 after LT>2 mg/dL, and alanine transaminase on day 1 after LT >1800 μmol/L (all P<0.001) were much more likely to die.ConclusionsIn-hospital mortality of LT recipients was high, due in large part to infections. Acute hepatic necrosis, prolonged post-transplant ICU stays, certain types of postoperative infections, and postoperative liver and kidney dysfunction were potential risk factors for in-hospital mortality of LT recipients.

Clinical usefulness of saphenous vein graft in major arterial reconstruction during extended pancreatectomy.

Extended pancreatectomy for locally advanced pancreatobiliary malignancy often involves combined major arterial resection (AR) and reconstruction (ARc). By limiting candidate inflow for ARc after combined resection of the celiac arterial system over a long distance, we evaluated whether great saphenous vein graft (GSVG) is an alternative conduit for obtaining non-anatomical arterial inflow. ARc with GSVG conduit was undertaken prior to resection. GSVG was harvested and anastomosed end-to-side with the reconstructing artery and then mostly passed via the retroperitoneal para-inferior vena cava route. Side-to-end anastomosis of GSVG inflow was established with the right common iliac artery or abdominal aorta. Among 468 consecutive pancreatobiliary surgeries, ARc with GSVG was undertaken in seven cases. Primary cancers were in the pancreas in six patients and distal bile duct in one. Radical surgery was performed with pancreaticoduodenectomy in six patients and total pancreatectomy in one. Hepatic artery (HA) was concomitantly resected and reconstructed by GSVG in six patients or by the jejunal artery in one patient. Median operative time and intraoperative blood loss were 763min and 350ml, respectively. Serum level of AST, ALT, and LDH in patients with HA reconstruction by GSVG peaked by the second postoperative day and promptly normalized. Postoperative morbidity (CD ≥ III) was encountered in one patient. No surgical mortality was observed. Postoperative serum liver enzymes promptly decreased in ARc patients with GSVG to HA. Arterial reconstruction with GSVG prior to resection was performed securely and might help to reduce postoperative liver dysfunction.

Splenic enlargement induced by preoperative chemotherapy is a useful indicator for predicting liver regeneration after resection for colorectal liver metastases

BackgroundConversion chemotherapy may downsize unresectable colorectal liver metastases (CRLMs), but may cause liver injury and splenic enlargement. The effect of preoperative chemotherapy on liver regeneration after liver resection remains undetermined. The aim of this study was to examine whether splenic enlargement induced by preoperative chemotherapy is an indicator to identify high-risk patients for impaired liver regeneration and liver dysfunction after resection.MethodsWe retrospectively reviewed 118 Japanese patients with CRLMs. Fifty-one patients had conversion chemotherapy. The other 67 patients underwent up-front liver resection. We clarified effects of conversion chemotherapy on splenic volume, liver function, and postoperative liver regeneration. Perioperative outcome was also analyzed.ResultsA ratio of the splenic volume before and after chemotherapy (SP index) in the oxaliplatin-based chemotherapy group was significantly greater than other chemotherapy groups after 9 or more chemotherapy cycles. Patients whose SP index was 1.2 or more had significantly higher indocyanine green retention rate at 15 min (ICG-R15) than patients without chemotherapy. Analyses of covariance showed liver regeneration rate after resection was decreased in patients whose SP index was 1.2 or more. The incidence of postoperative liver dysfunction in patients whose SP index was 1.2 or more was significantly greater than patients without chemotherapy. Multivariate analysis showed SP index was a significant predictive factor of impaired liver regeneration.ConclusionsSplenic enlargement induced by preoperative chemotherapy was a useful indicator for impaired liver regeneration after resection and a decision-making tool of treatment strategy for unresectable CRLMs.

Preoperative exercise protects the liver from surgical stress by altering the immune environment

Abstract Introduction Inflammation after liver surgery can lead to post-operative liver dysfunction, significant morbidity and mortality. Preoperative exercise has been associated with reduced postoperative complications. However, the mechanisms behind remain to be elucidated. We hypothesize that preoperative exercise can alter the hepatic immune microenvironment(HIM) to allow protection from liver injury. Methods 8-week-old mice were randomly divided into exercise and sedentary groups. The exercise group ran on a motorized treadmill at a speed of 12.5 m/min for 60 min/day, 5 days/week for 4 weeks whereas sedentary mice were exposed to the same treadmill but held motionless. Both groups were then subjected to surgical stress as modeled by 70% partial liver ischemia/reperfusion (I/R). Single-cell(SC)RNA sequencing was performed on hepatic CD45+ cells isolated from both groups. Results The exercise group had significantly lower serum alanine transaminase compared to sedentary mice after liver I/R. SC-RNA analysis of the hepatic immune cells revealed distinct macrophage subpopulations that correlated with cells derived from both groups. Among these macrophages, the expression of genes related to anti-inflammatory cytokines were significantly higher in exercised mice compared to sedentary mice, whereas pro-inflammatory cytokines and chemokines were significantly lower suggesting that exercise modulates the transcriptomic change in macrophages towards an anti-inflammatory phenotype. Conclusion Our study showed that preoperative exercise alters the HIM which offers a rationale for preoperative exercise therapy for patients undergoing liver surgery thereby decreasing post-operative inflammation and morbidity.

Von Willebrand Factor Antigen Facilitates Long Term Risk Stratification In Patients Undergoing Liver Resection

Presenter: Patrick Starlinger MD | Mayo Clinic, Rochester Background: Measurement of hepatic vein pressure gradient (HVPG) is frequently used to evaluate portal hypertension in high-risk patients prior to liver resection, specifically in patients with cirrhosis. Von Willebrand Factor-antigen (vWF-Ag) has been described to closely correlate with HVPG measurement and clinical outcome in patients suffering from cirrhosis. We have recently demonstrated vWF-Ag to be a significant predictor for poor postoperative outcome in regards to complications and liver dysfunction (LD). However, direct comparative analyses and long term outcomes in context to these parameters has not been evaluated so far. Methods: HVPG and vWF-Ag were evaluated prior to liver resection in 72 patients with hepatocellular carcinoma (HCC). Postoperatively overall survival (OS) and disease-free survival (DFS) were assessed as well as severe morbidity and LD. Previously defined cut offs were used to define risk groups within the cohort. Results: While both a cut-off for HVPG at 5 mmHg and a cut-off for vWF-Ag at 182% could identify patients at risk for severe morbidity (p=0.038, respectively), only vWF-Ag was able to significantly predict LD prior liver resection (p<0.001). Further, Kaplan-Meier analysis revealed that vWF-Ag allowed stratification of patients in regards to OS (median OS vWF-Ag < 182%=95.6 months vs. median OS vWF-Ag≥182%=40.1 months, p=0.003). In clear contrast, HVPG did not show an association with OS (p=0.486). Intriguingly, vWF-Ag was also able to predict DFS in our cohort (median DFS vWF-Ag < 182%=950 days vs. median DFS vWF-Ag≥182%=648 days, p=0.011), while DFS was not associated with preoperative HVPG levels (p=0.742). Conclusion: These findings clearly demonstrate that vWF-Ag is a valuable predictor of postoperative outcome after liver resection in high risk patients such as patients suffering from HCC. This non-invasive parameter of portal hypertension is not only equally effective but superior in terms of risk assessment as compared to the invasive and costly HVPG assessment. The close association with long term outcome seems to not only be caused by vWF-Ag association with postoperative LD but also its association with oncological outcome such as DFS after HCC resection. Thus, vWF-Ag presents a non-invasive and easily assessible tool for risk assessment in HCC patients undergoing liver resection.

Systematic investigations into a proposed mechanistic biomarker panel of liver injury for use in liver resection

Presenter: Patrick Starlinger MD | Mayo Clinic, Rochester Background: A proposed panel of mechanistic biomarkers of liver injury has been developed and investigated for utility in drug-induced liver injury. However, applicability of these markers in liver resection (LR) is unexplored. We have investigated the response of this mechanistic biomarker panel in LR, before investigating its potential to predict and report postoperative liver dysfunction (LD) and patient outcomes. Methods: 71 patients were prospectively recruited into a description cohort without control for patient selection. A further 96 patients were selected from a retrospective outcome cohort to investigate marker association to postoperative LD and morbidities. Results: Preoperative ccK18 measurement allowed improved prediction of patients suffering postoperative LD (no LD 184.3 U/L, LD 264.7 U/L, p=0.0012) compared to current routinely used non-invasive parameters. Strength of preoperative ccK18 prediction of LD and poor postoperative outcome was particularly strong in patients subjected to vascular occlusion through the operative procedure. On postoperative day (POD) POD1 miR-122 (no LD 14158 copies/μl, LD 33952 copies/μl, p=0.0147), HMGB1 (no LD 1.89 ng/ml, LD 3.40 ng/ml, p=0.0214) and AST (no LD 351.0 U/L, LD 415.0 U/L, p=0.0480) indicated association of elevated intraoperative hepatic damage with LD, and further suggested a role for ischemic reperfusion injury in the pathogenesis of LD. Conclusion: This is the first systematic assessment of a postulated liver damage marker panel in LR. Preoperative assessment of ccK18 could exhibit important value in allowing preoperative assessment of patient risk of poor postoperative outcome, allowing opportunity for optimisation of surgical and care strategies. Postoperative assessments of miR-122, HMGB1, ccK18 and total-K18 may represent useful new markers for early postoperative assessment of patient risk.

Perioperative use of selective serotonin reuptake inhibitors is associated to poor postoperative outcome in patients undergoing liver resection

Presenter: Patrick Starlinger MD | Mayo Clinic, Rochester Background: Recently, modification of intra-platelet serotonin levels as therapeutic intervention to promote postoperative liver regeneration was proposed. In this context, we previously showed a bivalent effect of serotonin on liver regeneration and early tumour recurrence. We were able to provide exploratory data on the use of selective serotonin reuptake inhibitors (SSRI) within the previous publications. Yet, this data has to be considered exploratory, as the number of patients under SSRI treatment was extremely low. Accordingly, we aimed to evaluate the use of selective serotonin reuptake inhibitors (SSRI) in a large cohort of patients undergoing liver resection. Methods: In total, 755 patients undergoing liver resection were retrospectively included from our prospectively maintained institutional database. Perioperative intake of SSRI was evaluated and patients were followed up for postoperative liver dysfunction (LD) and morbidity. Results: Within this cohort 75 patients (9.9%) with perioperative SSRI therapy could be identified. Of note, patients treated with SSRI showed a higher incidence of severe morbidity (22.9% - no SSRI vs 31.6% - SSRI, p<0.05) and a significantly increased incidence of liver dysfunction (10.7% - no SSRI vs 23.4% - SSRI, p<0.05). On the other hand, patients receiving SSRI therapy were found to suffer from significantly reduced early tumor recurrences at 6 and 12 months after surgery (6 months: 13.0% - no SSRI vs 22.7% - SSRI, p<0.05; 12 months: 26.3% - no SSRI vs 42.1% - SSRI, p<0.05). Conclusion: Within the present study we present solid data on the influence of SSRI on postoperative clinical outcome. Indeed, perioperative SSRI treatment seems to be associated to development of LD most likely via downregulation of intra-platelet serotonin, which was shown to be central for postoperative liver regeneration. However, SSRI therapy also seems to supressearly tumor recurrences and might therefore reflect an attractive adjuvant therapy in patients after liver resection.

Bivalent property of intra-platelet VWF in liver regeneration and HCC recurrence: A prospective multicenter study.

A striking difference has been observed in structure and functional properties between plasma and platelet von Willebrand factor (VWF). While the existing evidence has revealed a clinical relevance of plasma VWF-Ag in liver regeneration (LR) and different cancers, this study was designed to explore the properties of intra-platelet (IP) and serum VWF-Ag in patients with hepatocellular carcinoma (HCC) undergoing partial hepatectomy. A total of 40 patients undergoing partial hepatectomy were prospectively recruited from 3 institutions. VWF-Ag concentrations were evaluated mainly in serum and platelet extracts. Patients were followed-up for postoperative liver dysfunction and HCC recurrence. We observed a post-resection increase in the concentration of VWF-Ag in serum and platelet. Patients with postoperative liver dysfunction had substantially reduced serum and IP VWF-Ag concentrations. After a 2-year follow-up, patients with higher post-resection serum and IP VWF-Ag concentrations were found to develop early HCC recurrence. Likewise, IP VWF-Ag was able to independently predict post-resection early HCC recurrence. This multicenter, prospective, pilot study demonstrates a bivalent property of IP VWF in LR and oncological outcome; low preoperative VWF appeared to have a negative association on post-resection liver dysfunction, whereas, patients with higher post-resection VWF-Ag concentrations were found to have early HCC recurrence.

Postoperative liver dysfunction after total arch replacement combined with frozen elephant trunk implantation: incidence, risk factors and outcomes.

The authors aimed to clarify the incidence and risk factors of postoperative liver dysfunction (PLD) in patients undergoing total arch replacement combined with frozen elephant trunk implantation and to determine the association of PLD with short-term outcomes. Data from 672 adult patients undergoing total arch replacement with frozen elephant trunk from January 2013 until December 2016 at Fuwai Hospital were analysed retrospectively. A multivariable logistic regression model was used to identify the risk factors for PLD. The overall incidence of PLD was 27.5%, which was associated with higher in-hospital mortality (PLD 4.9% vs No PLD 0.8%, P = 0.002) and 30-day mortality (PLD 9.2% vs No PLD 2.5%, P < 0.001) and a higher incidence of major adverse events (PLD 54.6% vs No PLD 23.4%, P < 0.001). In the multivariable analysis, preoperative hypotension [odds ratio (OR) 1.97, 95% confidence interval (CI) 1.14-3.41; P = 0.02), coronary artery disease (OR 2.64, 95% CI 1.17-5.96; P = 0.02), prolonged cardiopulmonary bypass duration (OR 1.01, 95% CI 1.00-1.01; P < 0.001), increased preoperative alanine transferase (OR 1.01, 95% CI 1.00-1.01; P < 0.001), preoperative platelet count <100 × 109/l (OR 3.99, 95% CI 1.74-9.14; P = 0.001) and increased intraoperative erythrocyte transfusion (OR 1.07, 95% CI 1.01-1.12; P = 0.02) were identified as independent risk factors for PLD. PLD was associated with increased mortality and morbidity. Among the independent risk factors for PLD, cardiopulmonary bypass duration and erythrocyte transfusion could be modifiable. A skilled surgical team and an ideal blood protection strategy may be helpful to protect liver function.

Preoperative Evaluation of Liver Parenchyma of Potential Donors in Living Donor Liver Transplantation

BackgroundHepatic steatosis carries a risk of postoperative liver dysfunction in donors and graft nonfunction in recipients. This article discusses the evaluation of fatty infiltration in donor liver parenchyma on multidetector computed tomography. Materials and methodsThe methods of hepatic fat estimation include measurement of hepatic attenuation in HU and calculation of the liver attenuation index (LAI). Liver attenuation values reflect the degree of steatosis. Average attenuation of liver parenchyma is calculated by placing the circular region of interest of at least 1 cm2 area at multiple places in the liver on noncontrast CT images. Splenic attenuation is measured by placing the circular region of interest at its upper, middle, and lower poles. The LAI is the difference between mean hepatic attenuation and mean splenic attenuation. ResultsA total of 52 donors were evaluated as potential recipients (34 men, 18 women; mean age, 33.2 years; range, 23-55 years). In 34 donors liver attenuation index (LAI) values were from 2 HU to 22 HU. An LAI > 5 HU correctly predicted the absence of significant macrovesicular steatosis. These donors were acceptable for a liver transplant. The LAI values of −10 to 5 HU were suggestive of mild to moderate steatosis (6%-30%); 18 (34.6%) volunteers did not proceed to donation because of negative LAI < −5 HU. In 2 cases with LAI of −7 and LAI of −8 liver biopsy was performed, and 30% steatosis was confirmed in the pathohistologic examination. Unacceptable liver biopsy result was considered as contraindication for donation. The LAI values of < −10 HU were suggestive of moderate to severe hepatic steatosis of 30% or greater. In these cases liver biopsy is not needed, as such donors are not acceptable for liver transplant. ConclusionComputed tomography imaging provides a detailed evaluation of fatty infiltration in donor liver parenchyma.