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Primary and metastatic liver cancers are increasing in incidence, and the approaches with the longest survival are resection and transplantation. Posthepatectomy liver failure (PHLF) is the leading cause of mortality following liver resection. PHLF is largely due to liver insufficiency due to the insufficient size of the future liver remnant (FLR). In this review, we will describe portal vein embolization, which is a neoadjuvant therapy used to induce hypertrophy in the FLR before resection., (© 2024 Wiley Periodicals LLC.)

Liver fibrosis progressing to cirrhosis is a major risk factor for liver cancer, impacting surgical treatment and survival. Our study focuses on the role of extracellular nicotinamide adenine dinucleotide (eNAD + ) in liver fibrosis, analyzing liver disease patients undergoing surgery. Additionally, we explore NAD + 's therapeutic potential in a mouse model of extended liver resection and in vitro using 3D hepatocyte spheroids. eNAD + correlated with aspartate transaminase (AST) and bilirubin after liver resection (AST: r = 0.2828, p = 0.0087; Bilirubin: r = 0.2584, p = 0.0176). Concordantly, post-hepatectomy liver failure (PHLF) was associated with higher eNAD + peaks (n = 10; p = 0.0063). Post-operative eNAD + levels decreased significantly (p < 0.05), but in advanced stages of liver fibrosis or cirrhosis, this decline not only diminished but actually showed a trend towards an increase. The expression of NAD + biosynthesis rate-limiting enzymes, nicotinamide phosphoribosyltransferase (NAMPT) and nicotinamide mononucleotide adenylyltransferase 3 (NMNAT3), were upregulated significantly in the liver tissue of patients with higher liver fibrosis stages (p < 0.0001). Finally, the administration of NAD + in a 3D hepatocyte spheroid model rescued hepatocytes from TNFalpha-induced cell death and improved viability (p < 0.0001). In a mouse model of extended liver resection, NAD + treatment significantly improved survival (p = 0.0158) and liver regeneration (p = 0.0186). Our findings reveal that eNAD + was upregulated in PHLF, and rate-limiting enzymes of NAD + biosynthesis demonstrated higher expressions under liver fibrosis. Further, eNAD + administration improved survival after extended liver resection in mice and enhanced hepatocyte viability in vitro. These insights may offer a potential target for future therapies., (© 2024. The Author(s).)

Introduction: Liver transplantation (LT) is a well-established method applied for the treatment of various liver diseases, including primary and secondary malignancies, as well as acute liver failure triggered by different mechanisms. In turn, liver failure (PHLF) is the most severe complication observed after liver resection (LR). PHLF is an extremely rare indication for LT. The aim of the present study was to assess the results of LT in patients with PHLF., Methods: Relevant cases were extracted from the prospectively collected database of all LTs performed in our center. All clinical variables, details of the perioperative course of each patient and long-term follow-up data were thoroughly assessed., Results: Between January 2000 and August 2023, 2703 LTs were carried out. Among them, six patients underwent LT for PHLF, which accounted for 0.2% of all patients. The median age of the patients was 38 years (range 24-66 years). All patients underwent major liver resection before listing for LT. The 90-day mortality after LT was 66.7% (4 out of 6 patients), and all patients experienced complications in the posttransplant course. One patient required early retransplantation due to primary non-function (PNF). The last two transplanted patients are alive at 7 years and 12 months after LT, respectively., Conclusions: In an unselected population of patients with PHLF, LT is a very morbid procedure associated with high mortality but should be considered the only life-saving option in this group., (© 2024. The Author(s).)

Objective: Clinically significant portal hypertension (CSPH) seriously affects the feasibility and safety of surgical treatment for hepatocellular carcinoma (HCC) patients. The aim of this study was to establish a new surgical scheme defining risk classification of post-hepatectomy liver failure (PHLF) to facilitate the surgical decision-making and identify suitable candidates for individual hepatectomy among HCC patients with CSPH., Backgrounds: Hepatectomy is the preferred treatment for HCC. Surgeons must maintain a balance between the expected oncological outcomes of HCC removal and short-term risks of severe PHLF and morbidity. CSPH aggravates liver decompensation and increases the risk of severe PHLF thus complicating hepatectomy for HCC., Methods: Multivariate logistic regression and stochastic forest algorithm were performed, then the independent risk factors of severe PHLF were included in a nomogram to determine the risk of severe PHLF. Further, a conditional inference tree (CTREE) through recursive partitioning analysis validated supplement the misdiagnostic threshold of the nomogram., Results: This study included 924 patients, of whom 137 patients (14.8%) suffered from mild-CSPH and 66 patients suffered from (7.1%) with severe-CSPH confirmed preoperatively. Our data showed that preoperative prolonged prothrombin time, total bilirubin, indocyanine green retention rate at 15 min, CSPH grade, and standard future liver remnant volume were independent predictors of severe PHLF. By incorporating these factors, the nomogram achieved good prediction performance in assessing severe PHLF risk, and its concordance statistic was 0.891, 0.850 and 0.872 in the training cohort, internal validation cohort and external validation cohort, respectively, and good calibration curves were obtained. Moreover, the calculations of total points of diagnostic errors with 95% CI were concentrated in 110.5 (range 76.9-178.5). It showed a low risk of severe PHLF (2.3%), indicating hepatectomy is feasible when the points fall below 76.9, while the risk of severe PHLF is extremely high (93.8%) and hepatectomy should be rigorously restricted at scores over 178.5. Patients with points within the misdiagnosis threshold were further examined using CTREE according to a hierarchic order of factors represented by the presence of CSPH grade, ICG-R15, and sFLR., Conclusion: This new surgical scheme established in our study is practical to stratify risk classification in assessing severe PHLF, thereby facilitating surgical decision-making and identifying suitable candidates for individual hepatectomy., (© 2024. The Author(s).)

Background & Objectives: Sarcopenia is a morbi-mortality risk factor in digestive surgery, though its impact after major hepatectomy (MH) remains unknown. This prospective pilot study investigated whether volume and function of a regenerating liver is influenced by body composition., Methods: From 2011 to 2016, 125 consecutive patients had computed tomography and 99mTc-labelled-mebrofenin SPECT-scintigraphy before and after MH at day 7 and 1 month for measurements of liver volumes and functions. L3 vertebra muscle mass identified sarcopenia. Primary endpoint was the impact of sarcopenia on regeneration capacities (i.e. volume/function changes and post-hepatectomy liver failure (PHLF) rate). Secondary endpoint was 3-month morbi-mortality., Results: Sarcopenic patients (SP; N = 69) were significantly older than non-sarcopenic (NSP), with lower BMI and more malignancies, but with comparable liver function/volume at baseline. Postoperatively, SP showed higher rates of ISGLS&#95;PHLF (24.6 % vs 10.9 %; p = 0.05) but with comparable rates of severe morbidity (23.2 % vs 16.4 %; p = 0.35), overall (8.7 % vs 3.6 %; p = 0.3) and PHLF-related mortality (8,7 % vs 1.8 %; p = 0.075). After matching on the extent of resection or using propensity score, regeneration and PHLF rates were similar., Conclusion: This prospective study using first sequential SPECT-scintigraphy showed that sarcopenia by itself does not affect liver regeneration capacities and short-term postoperative course after MH., Competing Interests: Declaration of competing interest No conflict of interest to disclose, (Copyright © 2024. Published by Elsevier Masson SAS.)

Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht.

Combined liver-kidney transplantation (CLKT) is a surgical procedure that involves transplanting both liver and kidney organs. There are two types of CLKT: simultaneous liver-kidney transplantation (smLKT) and sequential LKT (sqLKT). CLKT accounts for a small percentage of liver transplantations (LTs), particularly in pediatric cases. Nevertheless, the procedure has demonstrated excellent outcomes, with high survival rates and lower rejection rates. The main indications for CLKT in pediatric patients differ somewhat from that in adults, in which end-stage kidney disease after LT is the major indication. In children, congenital diseases are common reason for performing CLKT; the examples of such diseases include autosomal recessive polycystic kidney disease with congenital hepatic fibrosis which equally affects both organs, and primary hyperoxaluria type 1, a primary liver disease leading kidney failure. The decision between smLKT or sqLKT depends on the dominant organ failure, the specific pathophysiology, and available organ sources. However, there remain significant surgical and societal challenges surrounding CLKT. Innovations in pharmacology and genetic engineering have decreased the necessity for CLKT in early-diagnosed cases without portal hypertension or kidney replacement therapy. Nonetheless, these advancements are not universally accessible. Therefore, decision-making algorithms should be crafted, considering region-specific organ allocation systems and prevailing medical environments., (© 2023 Wiley Periodicals LLC.)

Background: This study investigated the volumetric remodeling of the left liver after right hepatectomy looking for factors predicting the degree of hypertrophy and severe post-hepatectomy liver failure (PHLF)., Methods: In a cohort of 121 right hepatectomies, we performed CT volumetrics study of the future left liver remnant (FLR) preoperatively and postoperatively. Factors influencing FLR degree of hypertrophy and severe PHLF were identified by multivariate analysis., Results: After right hepatectomy, the mean degree of hypertrophy and kinetic growth rate of the left liver remnant were 25% and 3%/day respectively. The mean liver volume recovery rate was 77%. Liver remodeling volume was distributed for 79% on segments 2 and 3 and 21% on the segment 4 (p<0.001). Women showed a greater hypertrophy of segments 2 and 3 compared with men (p=0.002). The degree of hypertrophy of segment 4 was lower in case of middle hepatic vein resection (p=0.004). Left liver remnant kinetic growth rate was associated with the standardized future liver remnant (sFLR) (p<0.001) and a two-stage hepatectomy (p=0.023). Severe PHLF were predicted by intraoperative transfusion (p=0.009), biliary tumors (p=0.013), and male gender (p=0.022)., Conclusions: Volumetric remodeling of the left liver after right hepatectomy is not uniform and is mainly influenced by gender and sacrifice of middle hepatic vein. Male gender, intraoperative transfusion, and biliary tumors increase the risk of postoperative liver failure after right hepatectomy., (© 2023. The Society for Surgery of the Alimentary Tract.)

Objective: The study aim was to develop and validate models to predict clinically significant posthepatectomy liver failure (PHLF) and serious complications [a Comprehensive Complication Index (CCI)>40] using preoperative and intraoperative variables., Background: PHLF is a serious complication after major hepatectomy but does not comprehensively capture a patient's postoperative course. Adding the CCI as an additional metric can account for complications unrelated to liver function., Methods: The cohort included adult patients who underwent major hepatectomies at 12 international centers (2010-2020). After splitting the data into training and validation sets (70:30), models for PHLF and a CCI>40 were fit using logistic regression with a lasso penalty on the training cohort. The models were then evaluated on the validation data set., Results: Among 2192 patients, 185 (8.4%) had clinically significant PHLF and 160 (7.3%) had a CCI>40. The PHLF model had an area under the curve (AUC) of 0.80, calibration slope of 0.95, and calibration-in-the-large of -0.09, while the CCI model had an AUC of 0.76, calibration slope of 0.88, and calibration-in-the-large of 0.02. When the models were provided only preoperative variables to predict PHLF and a CCI>40, this resulted in similar AUCs of 0.78 and 0.71, respectively. Both models were used to build 2 risk calculators with the option to include or exclude intraoperative variables ( PHLF Risk Calculator; CCI>40 Risk Calculator )., Conclusions: Using an international cohort of major hepatectomy patients, we used preoperative and intraoperative variables to develop and internally validate multivariable models to predict clinically significant PHLF and a CCI>40 with good discrimination and calibration., Competing Interests: N.R. obtained a grant for postdoctoral fundamental research from the Fund for Scientific Research (FWO)—Flanders Belgium (grant file number: 1260123N). J.W. was supported by the UCSF Noyce Initiative for Digital Transformation in Computational Biology & Health, Computational Innovator Postdoctoral Fellowship Award. The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Liver failure in patients with obstructive jaundice is a significant contributor to mortality within this patient cohort. The exact mechanism and triggers of this occurrence are yet to be fully understood. With this in mind, our study aimed to assess the correlation between the urinary 6 β-OHC/C ratio and various biochemical parameters of liver function. Furthermore, we conducted genotyping of CYP3A4*22 (rs35599367), CYP3A5*3 (rs776746) polymorphic markers to investigate the potential effects of their variants on the probability of liver failure in obstructive jaundice. Our study included 75 patients diagnosed with severe obstructive jaundice. All test subjects underwent functional liver tests, and control blood tests were administered on the seventh day following biliary decompression. Patients were categorized into two groups: group 1 - patients without liver failure (n = 60) and group 2 - patients with liver failure (n = 15). Laboratory indexes such as 6 β -OHC concentration and 6 β- OHC/cortisol ratio can serve as significant predictors of liver failure in patients with moderate and severe degree obstructive jaundice after biliary decompression. Based on the study of "wild" and polymorphic variants of CYP3A4*22 (CC and CT) and polymorphism of CYP3A5*3A6986G (GG, GA, AA), it was discovered that liver failure in the CYP3A4*22 variant may be associated with the CC genotype, and in the CYP3A5*3 variant - with the GA genotype. Hence, the determination of 6β- OHC concentration and 6β- OHC/C ratio, as well as the analysis of polymorphic and "wild" variants of CYP3A4*22 (CC and CT) and CYP3A5*3 polymorphism A6986G (GG, GA, AA), may play a crucial role in predicting liver failure in patients with obstructive jaundice., Competing Interests: Declaration of competing interest The authors declare no conflict of interest. This article does not contain any studies with animals performed by any of the authors., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To compare minimally invasive (MILR) and open liver resections (OLRs) for hepatocellular carcinoma (HCC) in patients with metabolic syndrome (MS)., Background: Liver resections for HCC on MS are associated with high perioperative morbidity and mortality. No data on the minimally invasive approach in this setting exist., Material and Methods: A multicenter study involving 24 institutions was conducted. Propensity scores were calculated, and inverse probability weighting was used to weight comparisons. Short-term and long-term outcomes were investigated., Results: A total of 996 patients were included: 580 in OLR and 416 in MILR. After weighing, groups were well matched. Blood loss was similar between groups (OLR 275.9±3.1 vs MILR 226±4.0, P =0.146). There were no significant differences in 90-day morbidity (38.9% vs 31.9% OLRs and MILRs, P =0.08) and mortality (2.4% vs 2.2% OLRs and MILRs, P =0.84). MILRs were associated with lower rates of major complications (9.3% vs 15.3%, P =0.015), posthepatectomy liver failure (0.6% vs 4.3%, P =0.008), and bile leaks (2.2% vs 6.4%, P =0.003); ascites was significantly lower at postoperative day 1 (2.7% vs 8.1%, P =0.002) and day 3 (3.1% vs 11.4%, P <0.001); hospital stay was significantly shorter (5.8±1.9 vs 7.5±1.7, P <0.001). There was no significant difference in overall survival and disease-free survival., Conclusions: MILR for HCC on MS is associated with equivalent perioperative and oncological outcomes to OLRs. Fewer major complications, posthepatectomy liver failures, ascites, and bile leaks can be obtained, with a shorter hospital stay. The combination of lower short-term severe morbidity and equivalent oncologic outcomes favor MILR for MS when feasible., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Our objective was to investigate the impact of albumin-bilirubin (ALBI) score at the time of post-hepatectomy hepatocellular carcinoma (HCC) recurrence on survival after recurrence (SAR). We further explored the perioperative factors associated with the ALBI score at recurrence., Methods: Patients who underwent primary hepatectomy for HCC between 2007 and 2018 and developed recurrence were included in the study. Cox regression models were used to assess the association between the ALBI score at recurrence and SAR. Linear regression models were used to explore factors associated with ALBI score at recurrence., Results: Of the 233 patients analyzed, 158 developed recurrence within the Milan criteria (RWM) and 76 developed recurrence beyond the Milan criteria (RBM). Multivariable cox regression analysis demonstrated that higher ALBI scores at recurrence were associated with poorer SAR in both RWM and RBM groups (hazard ratios 4.5, 5.0; 95% confidence intervals 2.3-8.8, 2.2-11.6, respectively). In addition, multivariable linear regression analysis revealed that higher ALBI scores at hepatectomy and post-hepatectomy liver failure (PHLF) ≥ grade B were associated with higher ALBI scores at recurrence (β = 0.21, 0.11; 95% confidence intervals 0.15-0.26, 0.06-0.17, respectively)., Conclusions: The ALBI score at recurrence was a significant prognostic factor for SAR, and the ALBI scores at hepatectomy and PHLF ≥ Grade B were independently associated with the ALBI score at recurrence. Prevention of PHLF and consequent preservation of liver function at recurrence may be paramount to achieving better survival after HCC recurrence., (© 2023. The Society for Surgery of the Alimentary Tract.)

Background: Liver failure is associated with a high mortality rate, with many patients requiring transplant for definitive treatment. The Molecular Adsorbent Recirculating System (MARS) is a nonbiologic system that provides extracorporeal support. Literature on MARS therapy is mixed: outcomes support MARS therapy for patients with isolated acute liver failure, but data on patients with chronic disease is varied. Several case studies report success using MARS as a bridging treatment for patients awaiting transplant. The purpose of this case series is to present the outcomes of 44 patients who underwent MARS therapy for liver failure, 19 of whom used MARS therapy as a bridging therapy to transplant., Methods: This study retrospectively identified 44 patients who underwent MARS therapy for liver failure at Mayo Clinic, Jacksonville, between January 2014 and April 2021. Variables of interest included changes in laboratory markers of hepatic functioning, number and length of MARS therapy sessions, transplantation status, and mortality., Results: Following MARS therapy, there were improvements in mean serum bilirubin, ammonia, urea, creatinine, International Normalized Ratio, alanine aminotransferase, and aspartate aminotransferase levels. Twenty-seven patients (61.36%) survived the hospital stay; 17 (38.63%) died in the hospital. The majority of surviving patients (n = 19; 73.07%) received liver transplant. Six did not require transplant (22.22%). All but 1 patient who received MARS as a bridging treatment to transplant survived the follow-up period (n = 18; 94.74%)., Conclusions: Outcomes of these 44 cases suggest that MARS improves liver failure-associated laboratory parameters and may be effective therapy as a bridge to liver transplant., Competing Interests: Declaration of Competing Interest All the authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Thanks to the introduction of radiomics, 3d reconstruction can be able to analyse tissues and recognise true hypertrophy from non-functioning tissue in patients treated with major hepatectomies with hepatic modulation.The aim of this study is to evaluate the performance of 3D Imaging Modelling in predict liver failure., Methods: Patients submitted to major hepatectomies after hepatic modulation at Sanchinarro University Hospital from May 2015 to October 2019 were analysed. Three-dimensional reconstruction was realised before and after surgical treatment. The volumetry of Future Liver Remnant was calculated, distinguishing in Functional Future Liver Remnant (FRFx) i.e. true hypertrophy tissue and Anatomic Future Liver Remnant (FRL) i.e. hypertrophy plus no functional tissue (oedema/congestion) These volumes were analysed in patients with and without post hepatic liver failure., Results: Twenty-four procedures were realised (11 ALPPS and 13 PVE followed by major hepatectomy). Post hepatic liver failure grade B and C occurred in 6 patients. The ROC curve showed a better AUC for FRFxV (74%) with respect to FRLV (54%) in prediction PHLF > B. The increase of anatomical FRL (iFRL) was superior in the ALPPS group (120%) with respect to the PVE group (73%) (p = 0,041), while the increase of functional FRFX (iFRFx) was 35% in the ALLPS group and 46% in the PVE group (p > 0,05), showing no difference in the two groups., Conclusion: The 3D reconstruction model can allow optimal surgical planning, and through the use of specific algorithms, can contribute to differential functioning liver parenchyma of the FLR., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: 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)., Methods: 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 (cm 3 ) was obtained from preoperative CT and standardized based on the patient's body surface area (BSA, m 2 )., Results: 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 cm 3 /m 2 ), 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)., Conclusion: 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., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Post-hepatectomy liver failure is a severe complication after major liver resection and is associated with a high mortality rate. Nevertheless, there is no effective treatment for severe liver failure. In such a setting, rescue liver transplantation (LT) is used only in extraordinary cases with unclear results. This systematic review aims to define indication of LT in post-hepatectomy liver failure and post-LT outcomes, in terms of patient and disease-free survivals, to assess the procedure's feasibility and effectiveness., Methods: A systematic review of all English language full-text articles published until September 2022 was conducted. Inclusion criteria were articles describing patients undergoing LT for post-hepatectomy liver failure after liver resection, which specified at least one outcome of interest regarding patient/graft survival, postoperative complications, tumour recurrence and cause of death. A pseudo-individual participant data meta-analysis was performed to analyse data. Study quality was assessed with MINORS system. PROSPERO CRD42022349358., Results: Postoperative complication rate was 53.6%. All patients transplanted for benign indications survived. For malignant tumours, 1-, 3- and 5-year overall survival was 94.7%, 82.1% and 74.6%, respectively. The causes of death were tumour recurrence in 83.3% of cases and infection-related in 16.7% of LT recipients. At Cox regression, being transplanted for unconventional malignant indications (colorectal liver metastasis, cholangiocarcinoma) was a risk factor for death HR = 8.93 (95%CI = 1.04-76.63; P-value = 0.046). Disease-free survival differs according to different malignant tumours (P-value = 0.045)., Conclusions: Post-hepatectomy liver failure is an emergent indication for rescue LT, but it is not universally accepted. In selected patients, LT can be a life-saving procedure with low short-term risks. However, special attention must be given to long-term oncological prognosis before proceeding with rescue LT in an urgent setting, considering the severity of liver malignancy, organ scarcity, the country's organ allocation policies and the resource of living-related donation., Competing Interests: Declaration of Competing Interest Authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Liver-to-spleen signal intensity ratio (LSR) is evaluated by magnetic resonance imaging (MRI) in the hepatobiliary phase and has been reported as a useful radiological assessment of regional liver function. However, LSR is a passive (non-time-associated) assessment of liver function, not a dynamic (time-associated) assessment. Moreover, LSR shows limitations such as a dose bias of contrast medium and a timing bias of imaging. Previous studies have reported the advantages of time-associated liver functional assessment as a precise assessment of liver function. For instance, the indocyanine green (ICG) disappearance rate, which is calculated from serum ICG concentrations at multiple time points, reflects a precise preoperative liver function for predicting post-hepatectomy liver failure without the dose bias of ICG or the timing bias of blood sampling. The aim of this study was to develop a novel time-associated radiological liver functional assessment and verify its correlation with traditional liver functional parameters., Methods: A total of 279 pancreatic cancer patients were evaluated to clarify fundamental time-associated changes to LSR in normal liver. We defined the time-associated radiological assessment of liver function, calculated using information on LSR from four time points, as the "LSR increasing rate" (LSRi). We then investigated correlations between LSRi and previous liver functional parameters. Furthermore, we evaluated how timing bias and protocol bias affect LSRi., Results: Significant correlations were observed between LSRi and previous liver functional parameters such as total bilirubin, Child-Pugh grade, and albumin-bilirubin grade (P < 0.001 each). Moreover, considerably high correlations were observed between LSRi calculated using four time points and that calculated using three time points (r > 0.973 each), indicating that the timing bias of imaging was minimal., Conclusions: This study propose a novel time-associated radiological assessment, and revealed that the LSRi correlated significantly with traditional liver functional parameters. Changes in LSR over time may provide a superior preoperative assessment of regional liver function that is better for predicting post-hepatectomy liver failure than LSR using the hepatobiliary phase alone., (© 2023. The Author(s).)

Background: Post-hepatectomy liver failure (PHLF) represents the major source of mortality after liver resection (LR) in hepatocellular carcinoma (HCC) patients. Child-Pugh (CP) score 5 is always considered to indicate a normal liver function but represents a heterogeneous population with a considerable number suffering from PHLF. The present study aimed to access the ability of liver stiffness (LS) measured by two-dimensional shear wave elastography (2D-SWE) to predict PHLF in HCC patients with a CP score of 5., Methods: From August 2018 to May 2021, 146 HCC patients with a CP score of 5 who underwent LR were reviewed. The patients were randomly divided into training (n = 97) and validation (n = 49) groups. Logistic analyses were conducted for the risk factors and a linear model was built to predict the development of PHLF. The discrimination and calibration were assessed in the training and validation cohorts by the areas under the receiver operating characteristic curve (AUC)., Results: Analyses revealed that the minimum of LS (Emin) higher than 8.05 (p = 0.006, OR = 4.59) and future liver remnant / estimated total liver volume (FLR/eTLV) (p < 0.001, OR < 0.01) were independent predictors of PHLF in HCC patients with CP score 5, and the AUC calculated by the model based on them for differentiation of PHLF in the training and validation group was 0.78 and 0.76, respectively., Conclusion: LS was associated with the development of PHLF. A model combining Emin and FLR/eTLV showed proper ability in predicting PHLF in HCC patients with a CP score of 5., (© 2023. The Society for Surgery of the Alimentary Tract.)

Background: Liver transplantation is a life-saving treatment for end-stage pediatric liver failure. We aimed to present the results of pediatric liver transplants performed in our center in the last 11 years (between 2012 and March 2022) in association with prognostic factors affecting survival., Methods: Demographic characteristics, etiologic reasons, previous operations (Kasai procedure), morbidity, mortality, survival, and bilio-vascular complication rates were determined, and outcomes were evaluated. In the postoperative period, the duration of mechanical ventilation and intensive care unit stay and surgical and other complications were evaluated. Graft and patient survival rates were determined, and univariate and multivariate factors affecting these rates were evaluated., Results: In the last 10 years, 229 pediatric liver transplantaion (Pe-LT)/1513 adult liver taransplantation (Ad-LT) (21.35%) were performed in our center. This ratio (Pe-LT/Ad-LT ratio) is 1741/15,886 (10.95%) for our country. A total of 229 liver transplants were performed in 214 pediatric patients. Retransplantation was performed in 15 patients (6.55%). Cadaveric liver transplantation was performed in 9 patients. Graft survival rates were 87%, 83%, 78%, 78%, 78%, and 78% at <30 days, 30 to 90 days, 91 to 364 days, 1 to 3 years, and >3 years, respectively. Patient survival rates for <30 days, 30 to 90 days, 91 to 364 days, 1 to 3 years, and >3 years were 91.5%, 85.7%, 82%, 81.5%, and 81.5%, respectively. Our 5-year survival rates in metabolic diseases and the acute fulminant failure group are 93.8% and 100%, respectively., Conclusions: The fact that the 1- and 5-year survival rates are the same shows that when patients overcome biliary vascular and infectious problems, their survival is prolonged., Competing Interests: Declaration of Competing Interest All the authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper”., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The upper limit for liver resections in rats is approximately 90%. In the early postoperative phase, mortality increases. The aim of the present study was to validate the rat model of 90% partial hepatectomy (PH) as a model of post-hepatectomy liver failure (PHLF). Further, we wanted to test a quantitative scoring system as a detector of lethal outcomes caused by PHLF in rats., Methods: Sixty-eight rats were randomized to 90% PH, sham operation, or no surgery. Further, block randomization was performed based on time of euthanization: 12, 24, or 48 h after surgery. A general distress score (GDS) ≥10 during the day or ≥6 at midnight prompted early euthanization and classification as nonsurvivor. Animals euthanized as planned were classified as survivors. During euthanization, blood and liver tissue were collected, and liver-specific biochemistry was evaluated., Results: Based on the biochemical results, all animals subjected to 90% PH experienced PHLF. Seventeen rats were euthanized due to irreversible PHLF. The GDS increased for nonsurvivors within 12-18 h after surgery. The mean time for euthanization was 27 h after surgery., Conclusion: Based on the GDS and liver-specific biochemistry, we concluded that the model of 90% PH seems to be a proper model for investigating PHLF in rats. As a high GDS is associated with increased mortality, the GDS appears to be valuable in detecting lethal outcomes caused by PHLF in rats., (© 2023 The Authors. Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.)

Liver resection is the first-line treatment for primary liver cancers, providing the potential for a cure. However, concerns about post-hepatectomy liver failure (PHLF), a leading cause of death following extended liver resection, have restricted the population of eligible patients. Here, we engineered a clinical-grade bioartificial liver (BAL) device employing human-induced hepatocytes (hiHeps) manufactured under GMP conditions. In a porcine PHLF model, the hiHep-BAL treatment showed a remarkable survival benefit. On top of the supportive function, hiHep-BAL treatment restored functions, specifically ammonia detoxification, of the remnant liver and facilitated liver regeneration. Notably, an investigator-initiated study in seven patients with extended liver resection demonstrated that hiHep-BAL treatment was well tolerated and associated with improved liver function and liver regeneration, meeting the primary outcome of safety and feasibility. These encouraging results warrant further testing of hiHep-BAL for PHLF, the success of which would broaden the population of patients eligible for liver resection., Competing Interests: Declaration of interests L.H. and L.Z. are among the original inventors of patents filed by the Center for Excellence in Molecular Cell Science on the production of hiHeps., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: This study aimed to analyze the predictive value of Hepatobiliary scintigraphy (HBS) for posthepatectomy liver failure (PHLF) after major liver resection with a comparison to assessment of liver volume in a multicenter cohort., Methods: Patients who underwent liver resection after HBS were included from six centers. Remnant liver volume was calculated from CT images. PHLF was scored and graded according to the grade B/C ISGLS criteria., Results: In 547 patients PHLF incidence was 10% (56/547) and 90-day mortality rate 8% (42/547). Overall predictive value of remnant liver function was 0.66 (0.58-0.74) and similar to that of remnant volume (0.63 (0.72). For biliary tumors, a function cut-off of 2.7%/min/m2 and 30% volume cut-off resulted in a PHLF rate 12% and 13%, respectively. While an 8.5%/min (4.5%/min/m2) function cut-off resulted in 7% PHLF for those with a function above the cutoff while a 40% volume cutoff still resulted in 14% PHLF rate. In the multivariable analyses for PHLF, liver function was predictive but liver volume was not., Conclusion: The current study shows that preoperative liver function assessment using HBS is at least as predictive for PHLF as liver volume assessment, and likely has several advantages, particularly in the high-risk sub-group of biliary tumors., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Technetium-99m-galactosyl human serum albumin scintigraphy is preferred for assessing the liver functional reserve in patients undergoing hepatectomy, but its superiority over computed tomography volumetry after portal vein embolization and subsequent hepatectomy remains elusive. We aimed to compare technetium-99m-galactosyl human serum albumin scintigraphy with conventional computed tomography volumetry for predicting posthepatectomy liver failure in patients after portal vein embolization., Methods: This retrospective study analyzed 152 consecutive patients who underwent hepatobiliary cancer resection after portal vein embolization between 2006 and 2021. Posthepatectomy liver failure was graded according to the International Study Group of Liver Surgery criteria. The predictive abilities for posthepatectomy liver failure were compared between the future remnant uptake (%) by technetium-99m-galactosyl human serum albumin scintigraphy and the future remnant volume (%) by computed tomography volumetry., Results: Future remnant uptake (%) was significantly greater than future remnant volume (%) after portal vein embolization (47.9% vs 40.8%; P < .001), while the values were comparable before portal vein embolization (32.7% vs 31.2%; P = .116). Receiver operating characteristic curve analysis revealed that post-portal vein embolization future remnant volume (%) had a significantly higher area under the curve than post-portal vein embolization future remnant uptake (%) (0.709 vs 0.630; P = .046) for predicting posthepatectomy liver failure. Multivariable analysis revealed that post-portal vein embolization future remnant volume (%) independently predicted posthepatectomy liver failure, but future remnant uptake (%) did not. Although the incidence of posthepatectomy liver failure grade ≥B was 17.8% when indocyanine green-clearance of the future liver remnant based on both future remnant volume (%) and future remnant uptake (%) was ≥0.05, it was higher in other combinations: 55.6% for indocyanine green clearance of the remnant volume ≥0.05/indocyanine green clearance of the remnant uptake ≤0.05; 50.0% for indocyanine green clearance of the remnant volume ≤0.05/indocyanine green clearance of the remnant uptake ≥0.05; and 50% for indocyanine green clearance of the remnant volume ≤0.05/indocyanine green clearance of the remnant uptake ≤0.05., Conclusions: Technetium-99m-galactosyl human serum albumin scintigraphy is not superior to computed tomography volumetry for assessing the future liver remnant in patients undergoing major hepatectomy after portal vein embolization., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Backgroud: The aim was to compare perioperative outcomes of hilar cholangiocarcinoma (HCCA) radical resection performed through the laparoscopic route or by open surgery in single-center cohort study., Methods: A retrospective study included all patients undergoing HCCA radical resection in our center from January 2018 to November 2019. Short-term outcomes of patients with laparoscopic and open surgery were compared demographic characteristics, intraoperative and postoperative parameters and extent of resection., Results: Among 64 patients included, 34 were performed with laparoscopic route and 30 were with open surgery. Laparoscopic versus open group was associated with a longer operation duration [475.50(219.00-630.00) vs. 375.00(220.00-557.00) min, P = 0.031], similar intraoperative bleeding volume [300.00(50.00-3500.00) vs. 350.00(100.00-1500.00) ml, P = 0.426]. No significant differences in tumor diameter [2.00(1.50-3.00) vs. 2.00(1.50-3.00) cm, P = 0.965], the number of lymph nodes retrieved [9.50(6.00-15.00) vs. 8.50(5.00-12.00), P = 0.706], and resection margins (94.1% vs. 86.7%, P = 0.407) between the two approaches were found. The LOS [20.00(10.00-44.00) vs. 21.00(6.00-27.00) d, P = 0.622], bile leakage (23.5% vs. 26.7%, P = 0.781), and liver failure (8.80% vs. 6.70%, P>0.99) were similar in the two groups. There was one patient in open surgery group developing liver failure and finally expired., Conclusion: The safety and radicality of laparoscopic resection for HCCA are similar to open surgery and can be technically improved by rational trocar distribution, total caudate lobectomy and appropriate cholangioenteric anastomosis strategy., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2023 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Surgical liver failure (SLF) develops when a marginal amount of hepatic mass is left after surgery, such as following excessive resection. SLF is the commonest cause of death due to liver surgery; however, its etiology remains obscure. Using mouse models of standard hepatectomy (sHx) (68%, resulting in full regeneration) or extended hepatectomy (eHx) (86%/91%, causing SLF), we explored the causes of early SLF related to portal hyperafflux. Assessing the levels of HIF2A with or without oxygenating agent inositol trispyrophosphate (ITPP) indicated hypoxia early after eHx. Subsequently, lipid oxidation (PPARA/PGC1α) was downregulated and associated with persisting steatosis. Mild oxidation with low-dose ITPP reduced the levels of HIF2A, restored downstream PPARA/PGC1α expression along with lipid oxidation activities (LOAs), and normalized steatosis and other metabolic or regenerative SLF deficiencies. Promotion of LOA with L-carnitine likewise normalized the SLF phenotype, and both ITPP and L-carnitine markedly raised survival in lethal SLF. In patients who underwent hepatectomy, pronounced increases in serum carnitine levels (reflecting LOA) were associated with better recovery. Lipid oxidation thus provides a link between the hyperafflux of O 2 -poor portal blood, the metabolic/regenerative deficits, and the increased mortality typifying SLF. Stimulation of lipid oxidation-the prime regenerative energy source-particularly through L-carnitine may offer a safe and feasible way to reduce SLF risks in the clinic., (Copyright © 2022 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: The aim in this study was to determine the efficacy of shear wave dispersion (SWD) technique for the prediction of post hepatectomy liver failure (PHLF) in patients with hepatocellular carcinoma after hepatectomy and develop an SWD based risk prediction model., Methods & Materials: We prospectively enrolled 205 consecutive patients who were scheduled to undergo hepatectomy for hepatocellular carcinoma (HCC), pre-operative SWD examination, laboratory data and some other clinicopathological tests were collected. The risk factors of PHLF were identified according to univariate and multivariate analysis, a predictive model was established based on logistic regression analyses., Results: SWD examination was successfully performed in 205 patients. PHLF occurred in 51 patients (24.9%), including 37/11/3 patients with Grade A/B/C, respectively. There was a high correlation between SWD value of liver and liver fibrosis stage (r = 0.873, p < 0.05). Patients with PHLF has a higher median SWD value of liver than patients without PHLF [17.4 vs 14.7 (m/s)/kHz, p < 0.05]. The SWD value of liver, total bilirubin (TB), international normalized ratio of prothrombin time (INR) and splenomegaly were significantly related to PHLF based on the multivariate analysis. A new prediction model (PM) for PHLF was established (PM = -12.918 + 0.183× SWD + 6.668× INR +0.100×TB+1.240×splenomegaly). The optimal cutoff value of SWD for predicting PHLF was 16.7 (m/s)/kHz. The area under the curve (AUC) of the PM for PHLF was 0.833, which was higher than that of SWD, INR, Forns, FIB4, APRI (p < 0.005, respectively)., Conclusion: SWD is a promising and reliable method for PHLF prediction in patients with HCC who were undergoing hepatectomy. Compared with SWD, Forns, APRI and FIB-4, PM demonstrate better efficacy for preoperative PHLF prediction.

Objective: To investigate the feasibility and efficacy of real-time 3.0 T magnetic resonance imaging (MRI) guided percutaneous microwave ablation (MWA) in the treatment of multifocal liver cancer., Methods: A total of 76 lesions in 26 patients with multifocal liver cancer who underwent 3.0 T MRI-guided microwave ablation in our hospital from April 2020 to April 2022 were retrospectively analyzed. The technical success rate, average operation time, average ablation time, and complications were evaluated. The upper abdomen was reviewed by pre- and post-contrast enhanced MRI scan every 1 months after the operation. The short-term curative effect was evaluated according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria (2020 version), and the local control rate was calculated., Results: All 76 lesions were successfully operated. The technical success rate was 100%, the average operation time was 103.58 ± 18.57 min, the average ablation time of a single lesion was 11.00 ± 4.05 min, and the average ablation power was 43.03 ± 4.45 W. There were no serious complications such as massive bleeding, liver failure, and infection after the operation, except in one case with a small amount of pleural effusion and one case with right upper abdominal pain. The average follow-up time was 13.88 ± 6.62 months. One patient died due to liver failure, and one lesion developed a local recurrence. The local control rate was 98.7%., Conclusions: MWA of multifocal liver cancer guided by real-time 3.0 T MRI is a safe and feasible technique and has excellent short-term efficacy.

Background: Major hepatectomy is associated with high incidence of post-hepatectomy liver failure (PHLF). This study aimed to evaluate the effect of future remnant liver volume combined with liver function tests on predicting PHLF., Methods: Patients who underwent major hepatectomy from April 2009 to May 2017 were enrolled in the training cohort. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors of PHLF and generate a logistic regression model for the prediction of PHLF. A conditional inference tree was generated based on the optimal cutoff value of independent predictive factors of PHLF. The precedent results were validated in an independent cohort from June 2017 to March 2018., Results: One hundred and eighteen patients were included in the training cohort, while another 34 in the validation cohort. Future remnant liver volume/estimated standard total liver volume (FLV/eTV) and preoperative platelet count were independent predictive factors of PHLF (P = 0.0021 and P = 0.012, respectively). The conditional inference tree showed that patients with FLV/eTV ≤0.56 and PLT count ≤145 × 10 9 /L were at high risk of developing PHLF., Conclusion: FLV/eTV combined with preoperative PLT count is effective in predicting PHLF after major hepatectomy., Competing Interests: Declaration of competing interest Authors declare no conflict of Interest for this article., (Copyright © 2022. Published by Elsevier Ltd.)

Background and Aims: Liver regeneration (LR) is vital for the recovery of liver function after hepatectomy. Limited regeneration capacity, together with insufficient remnant liver volume, is a risk factor for posthepatectomy liver failure (PHLF) resulting from small-for-size syndrome. Although inflammation plays an important role in controlling LR, the underlying mechanisms still remain obscure., Approach and Results: We identified C-C motif chemokine ligand (CCL) 5 as an important negative regulator for LR. CCL5 levels were elevated after partial hepatectomy (PHx), both in healthy donors of living donor liver transplantation (LT) and PHx mouse models. Ccl5 knockout mice displayed improved survival after 90% PHx and enhanced LR 36 h after 70% PHx. However, primary hepatocytes from Ccl5 -/- mice exposed to growth factors in vitro showed no proliferation advantage compared to those from wild-type (WT) mice. Flow cytometry analysis showed that proportions of Ly6C lo macrophages were significantly increased in Ccl5 -/- mice after 70% PHx. RNA-sequencing analysis revealed that sorted macrophages (CD11b + Ly6C lo&hi ) manifested enhanced expression of reparative genes in Ccl5 -/- mice compared to WT mice. Mechanistically, CCL5 induced macrophages toward proinflammatory Ly6C hi phenotype, thereby inhibiting the production of hepatocyte growth factor (HGF) through the C-C motif chemokine receptor (CCR) 1- and CCR5-mediated forkhead box O (FoxO) 3a pathways. Finally, blockade of CCL5 greatly optimized survival and boosted LR in the mouse PHx model., Conclusions: Our findings suggest that inhibition of CCL5 is a promising strategy to improve regeneration restoration by enhancing HGF secretion from reparative macrophages through the FoxO3a pathway, which may potentially reduce the mortality of PHLF., (© 2022 The Authors. Hepatology published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Background: Post-hepatectomy liver failure (PHLF) is associated with high mortality following liver resection. There have been limited studies evaluating predictors of PHLF and clinically significant PHLF in non-cirrhotic patients., Methods: This was a retrospective cohort study using the National Surgical Quality Improvement Program database (NSQIP) to evaluate 8,093 non-cirrhotic patients undergoing hepatectomy from 2014 to 2018. Primary endpoints were PHLF and clinically significant PHLF (PHLF grade B or C)., Results: Among all patients, 4.74% (n = 383) developed PHLF and 2.5% clinically significant PHLF (n = 203). The overall 30-day mortality was 1.35% (n = 109), 11.5% (n = 44) in patients with PHLF, and 19.2% in those with clinically significant PHLF. Factors associated with PHLF were: metastatic liver disease (OR = 1.84, CI = 1.14-2.98), trisectionectomy (OR = 3.71, CI = 2.59-5.32), right total lobectomy (OR = 4.17, CI = 3.06-5.68), transfusions (OR = 1.99, CI = 1.52-2.62), organ/space SSI (OR = 2.84, CI = 2.02-3.98), post-operative pneumonia (OR = 2.43, CI = 1.57-3.76), sepsis (OR = 2.27, CI = 1.47-3.51), and septic shock (OR = 5.67, CI = 3.43-9.36). Patients who developed PHLF or clinically significant PHLF had 2-threefold increased risk of perioperative mortality. Post-hepatectomy renal failure (OR = 8.47, CI = 3.96-18.1), older age (OR = 1.04, CI = 1.014-1.063), male sex (OR = 1.83, CI = 1.07-3.14), sepsis (OR = 2.96, CI = 1.22-7.2), and septic shock (OR = 3.92, CI = 1.61-9.58) were independently associated with 30-mortality in patients with clinically significant PHLF., Conclusion: PHLF in non-cirrhotic patients increased the risk of perioperative mortality and is associated with the extent of hepatectomy and infectious complications. Careful evaluation of the liver remnant, antibiotic prophylaxis, nutritional assessment, and timely management of post-operative infections could decrease major morbidity and mortality following hepatectomy., (© 2022. The Author(s) under exclusive licence to Société Internationale de Chirurgie.)

Introduction: Post hepatectomy liver failure (PHFL) still represents a potentially fatal complication after major liver resection. Indocyanine green (ICG) clearance test represents one of the most widely adopted examinations in the preoperative workup. Despite a copious body of evidence which has been published on this topic, the role of ICG in predicting PHLF is still a matter of debate., Methods: A systematic review of the literature was conducted according to PRISMA-DTA guidelines. The primary outcome was the assessment of diagnostic performance of ICG in predicting PHLF. The secondary outcome was the mean ICG R15 and ICG PDR in patients experiencing PHLF., Results: Seventeen studies, for a total of 4852 patients, were deemed eligible. Sensitivity ranged from 25% to 83%; Specificity ranged from 66.1% to 93.8%. ICG clearance test pooled AUC was 0.673 (95% CI: 0.632-0.713). The weighted mean ICG R15 was 11 (95%CI: 8.3-13.7). The weighted mean ICG PDR was 16.5 (95%CI: 13.3-19.8). High risk of bias was detected in all examined domains., Conclusions: Preoperative ICG clearance test alone may not represent a reliable method to predict post hepatectomy liver failure. Its diagnostic significance should be framed within multiparametric models involving clinical and imaging features., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Estimation of the functional reserve of the remnant liver is important to reduce morbidity and mortality., Aim: To estimate the functional reserve of the remnant liver in patients with hepatocellular carcinoma (HCC)., Methods: We reviewed the medical records of 199 patients who underwent resection of HCC. Hepatic clearance of the remnant liver was calculated using fusion images of 99m Tc-labelled galactosyl-human serum albumin liver scintigraphy and computed tomography. Posthepatectomy liver failure (PHLF) was classified according to the International Study Group of Liver Surgery. Complications was classified according to Clavien-Dindo classification. We analyzed by the risk factors for PHLF, morbidity and mortality with multivariate analysis., Results: Twenty-seven (30%) patients had major complications and 23 (12%) developed PHLF. The incidence of major complications increased with increasing albumin-bilirubin (ALBI) grade. The area under the curve values for hepatic clearance of the remnant liver, liver to heart-plus-liver radioactivity at 15 min (LHL15), and ALBI score predicting PHLF were 0.868, 0.629, and 0.655, respectively. The area under the curve for hepatic clearance of the remnant liver, LHL15, and ALBI score predicting major complications were 0.758, 0.594, and 0.647, respectively. The risk factors for PHLF and major complications were hepatic clearance of the remnant liver and intraoperative bleeding., Conclusion: The measurement of hepatic clearance may predict PHLF and major complications for patients undergoing resection of HCC., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest for this study., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Hepatectomy remains the most important treatment modality for most malignant liver tumors. Vascular involvement stays a reason for unresectability or major parenchymal resection. A possible way to avoid this is parenchymal-sparing hepatectomy (PSHX) with vascular resection and reconstruction (HVRR). In this article, we aim to demonstrate the specific role of this technique in avoiding post-hepatectomy liver failure (PHLF)., Methods: A retrospective analysis of 10 patients who underwent HVRR was conducted. 99m Technetium-mebrofenin hepatobiliary scintigraphy (HBS) was used to predict the future liver remnant function (FLRF). Calculations were made for each patient to compare HVRR and major hepatectomy (with or without portal vein embolization)., Results: In our cohort, there was no perioperative mortality. Two patients suffered a Clavien-Dindo grade 3a complication and none had clinically significant PHLF. Estimated FLRF was significantly higher in HVRR compared to major hepatectomy after portal vein embolization ( p  < .005)., Conclusions: Instead of focusing on inducing liver remnant hypertrophy, preserving parenchyma through HVRR can be an interesting treatment strategy. It can be performed with an acceptable operative risk. Calculations of FLRF (using HBS) suggest that this approach is able to reduce the risk for PHLF and related morbidity or mortality.

Background: Surgical resection, where appropriate, remains one of the best treatment options for hepatocellular carcinoma (HCC), however outcomes can be compromised by the development of liver failure. We reviewed our experience of liver resection for HCC patients to identify factors that may predict the development of post-hepatectomy liver failure (PHLF) and survival., Methods: A single centre retrospective cohort study. Data was collected between 1999 and 2017 from all patients undergoing HCC resection in a tertiary university hospital from electronic medical records. PHLF was defined as per the International Study Group for Liver Surgery criteria. Variables with p < 0.15 on univariate analysis were included in a multivariate binary logistic regression model. Kaplan-Meier analyses were used to determine correlations with overall survival (OS) and disease-free survival (DFS), and variables with p < 0.15 on univariate analysis selected for a step-down Cox proportional hazard regression model., Results: Overall, 120 patients underwent liver resection within the study period, of which 22 (18%) developed PHLF. Patients with normal INR ≤1.20 at day 2 did not develop PHLF whereas patients with INR >1.60 were at significant risk. Resection of multiple tumours (odds ratio 21.63, p = 0.002) and deranged postoperative day 2 INR>1.6 (odds ratio 21.05, p < 0.0001) were identified as independent prognostic markers of PHLF., Conclusion: The use of INR measurement at day 2 predicts PHLF and may enable us to objectively identify and stratify patients who may be eligible for enhanced recovery programs from those who will merit close monitoring in high dependency areas., Competing Interests: Declaration of competing interest Silva ANS reports no conflict of interest. Greensmith M reports no conflict of interest. Praseedom RK reports no conflict of interest. Jah A reports no conflict of interest. Huguet EL reports no conflict of interest. Harper SJF reports no conflict of interest. Liau SS reports no conflict of interest. Basu B reports no conflict of interest. Alexander GJ reports no conflict of interest. Brais R reports no conflict of interest. See TC reports no conflict of interest. Hoare M reports no conflict of interest. Gibbs P reports no conflict of interest. Balakrishnan A reports no conflict of interest., (Crown Copyright © 2022. Published by Elsevier Ltd. All rights reserved.)

Background: Chemotherapy agents for metastatic colorectal cancer can cause liver injury, increasing the risk of post-hepatectomy liver failure after hepatectomy for metastases. The role of noninvasive fibrosis markers in this setting is not well established., Aims: To evaluate the aspartate aminotransferase-to-platelet ratio index (APRI) as a predictor of postoperative liver failure., Methods: The National Surgical Quality Improvement Program database was utilized to identify patients who received preoperative chemotherapy and underwent hepatectomy for colorectal metastases between 2015 and 2017. Concordance index analysis was conducted to determine APRI's contribution to the prediction of liver failure. The optimal cutoff value was defined and its ability to predict post-hepatectomy liver failure and perioperative bleeding were examined., Results: A total of 2374 patients were identified and included in the analysis. APRI demonstrated to be a better predictor of postoperative liver failure than MELD score, with a statistically significant larger area under the curve. The optimal APRI cutoff value to predict liver failure was 0.365. The multivariable logistic regression showed that APRI ≥ 0.365 was independently associated with PHLF, odds ratio (OR) 2.51, 95% confidence interval (CI) 1.67-3.77, P < .0001. Likewise, APRI ≥ 0.365 was independently associated with perioperative bleeding complications requiring transfusions, OR 1.41, 95% CI 1.13-1.77, P = 0.002. MELD score was not statistically associated with PHLF or bleeding complications., Conclusions: APRI was independently associated with post-hepatectomy liver failure and perioperative bleeding requiring transfusions after resection of colorectal metastases in patients who received preoperative chemotherapy. Concordance index showed APRI to add significant contribution as a predictor of postoperative liver failure., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: To investigate whether the administration of nafamostat mesilate (NM) reduces the risk of posthepatectomy liver failure (PHLF) in patients undergoing hepatectomy for hepatocellular carcinoma (HCC)., Methods: We retrospectively reviewed the 1114 patients who underwent hepatectomy for HCC between 2004 and 2020. NM was selectively administered to patients undergoing major hepatectomy with an estimated blood loss of >500 mL. NM group was administered via intravenous of 20 mg of NM from immediately after surgery until postoperative day 4. We performed 1:1 propensity score matching and included 56 patients in each group. PHLF was defined according to the International Study Group of Liver Surgery (ISGLS)., Results: The incidence of PHLF was lower in the NM group than control group (P = 0.018). The mean peak total bilirubin (P = 0.006), aspartate transaminase (P = 0.018), and alanine aminotransferase (P = 0.018) levels postoperatively were significantly lower in the NM group. The mean hospital stays (P = 0.012) and major complication rate (P = 0.023) were also significantly lower in the NM group., Conclusion: Prophylactic administration of NM reduced the risks of complication and decreased the frequency of PHLF after hepatectomy. A further prospective study is needed to verify our findings., (Copyright © 2022 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Post-hepatectomy liver failure (PHLF) is the leading cause of postoperative mortality following major liver resection. Between December 2012 and May 2015, 10 consecutive patients with PHLF (according to the Balzan criteria) following major/extended hepatectomy were included in a prospective treatment study with the molecular adsorbent recirculating system (MARS). Sixty- and 90-day mortality rates were 0% and 10%, respectively. Of the nine survivors, four still had liver dysfunction at 90 days postoperatively. One-year overall survival (OS) of the MARS-PHLF cohort was 50%. The present study aims to assess long-term outcome of this cohort compared to a historical control cohort., Methods: To compare long-term outcome of the MARS-PHLF treatment cohort with PHLF patients not treated with MARS, the present study includes all 655 patients who underwent major hepatectomy at Karolinska University Hospital between 2010 and 2018. Patients with PHLF were identified according to the Balzan criteria., Results: The cohort was split into three time periods: pre-MARS period ( n  = 192), MARS study period ( n  = 207), and post-MARS period ( n  = 256). The 90-day mortality of patients with PHLF was 55% (6/11) in the pre-MARS period, 14% during the MARS study period (2/14), and 50% (3/6) in the post-MARS period ( p  = 0.084). Median OS (95% confidence interval (CI)) was 37.8 months (29.3-51.7) in the pre-MARS cohort, 57 months (40.7-75.6) in the MARS cohort, and 38.8 months (31.4-51.2) in the post-MARS cohort. The 5-year OS of 10 patients included in the MARS study was 40% and the median survival 11.6 months (95% CI: 3 to not releasable). In contrast, for the remaining 21 patients fulfilling the Balzan criteria during the study period but not treated with MARS, the 5-year OS and median survival were 9.5% and 7.3 months (95% CI, 0.5-25.9), respectively ( p  = 0.138))., Conclusions: MARS treatment may contribute to improved outcome of patients with PHLF. Further studies are needed.The initial pilot study was registered at ClinicalTrials.gov (NCT03011424).

Background: The liver-to-spleen signal intensity ratio (LSR) on magnetic resonance imaging with gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid has been used as a parameter to assess liver function. LSR of the future remnant liver region (FR-LSR) is included in preoperative assessment of regional liver function. The aim of this study was to investigate the predictability of post-hepatectomy liver failure (PHLF) by FR-LSR., Methods: Between May 2013 and May 2019, 127 patients underwent standardized EOB-MRI for diagnosis of liver tumor before major hepatectomy. The FR-LSR on EOB-MRI was calculated by a semiautomated three-dimensional volumetric analysis system. The cutoff value of FR-LSR in association with clinically relevant PHLF was determined according to the areas under the receiver operating characteristic curves. Then, FR-LSR and clinical variables were analyzed to assess the risk of clinically relevant PHLF., Results: In patients with preoperative biliary drainage, metastatic liver tumor, estimated future remnant liver volume <50%, biliary reconstruction, operation time ≥ 480 min, estimated blood loss ≥ 1000 g, blood transfusion and a FR-LSR < 2.00 were associated with clinically relevant PHLF ( P < .05 for all) in univariable analysis. The liver-to-spleen signal intensity ratio of the future remnant liver region < 2.00 was the only independent risk factor for clinically relevant PHLF in multivariable risk analysis (OR, 27.90; 95% CI: 7.99-136.40; P < .05)., Discussion: The present study revealed that FR-LSR calculated using a 3-dimensional volumetric analysis system was an independent risk factor for clinically relevant PHLF. The liver-to-spleen signal intensity ratio of the future remnant liver region might be a reliable preoperative parameter in liver functional assessment, enabling safe performance of major hepatectomy.

Background: Mesohepatectomy is a viable treatment option for patients diagnosed with centrally located liver tumors (CLLTs). There are several reports from Eastern centers, but few data are available on this topic from Western centers., Study Design: Data of 128 consecutive patients who underwent mesohepatectomy between September 2000 and September 2020 in our center were analyzed from a prospectively collected database. Patient demographic data, liver tumor characteristics, and intraoperative data were collected. In addition, posthepatectomy bile leakage (PHBL), posthepatectomy hemorrhage (PHH), posthepatectomy liver failure (PHLF), and 90-day mortality after mesohepatectomy were assessed. Long-term outcomes were also reported, and factors that may influence disease-free survival were evaluated., Results: Of 128 patients, 113 patients (88.3%) had malignant hepatic tumors (primary and metastatic tumors in 41 [32%] and 72 [56.3%] patients, respectively), and 15 patients suffered from benign lesions (11.7%). Among the relevant surgical complications (grade B or C), PHBL was the most common complication after mesohepatectomy and occurred in 11.7% of patients, followed by PHLF in 3.1% of patients and PHH in 2.3% of patients. Only four patients (3.1%) died within 90 days after mesohepatectomy. The 5-year overall survival and overall recurrence (for malignant lesion) rates were 76.5% and 45.1%, respectively., Conclusion: Mesohepatectomy is a safe and feasible surgical treatment with low morbidity and mortality for patients with CLLT. Long-term outcomes can be improved by increased surgical expertise., (Copyright © 2022 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background & aims: Finding a way to comprehensively integrate the presence and grade of clinically significant portal hypertension, amount of preserved liver function and extent of hepatectomy into the guidelines for choosing appropriate candidates to hepatectomy remained challenging. This study sheds light on these issues to facilitate precise surgical decisions for clinicians. Methods: Independent risk factors associated with grade B/C post-hepatectomy liver failure were identified by stochastic forest algorithm and logistic regression in hepatitis B virus-related hepatocellular carcinoma patients. Results: The artificial neural network model was generated by integrating preoperative pre-ALB, prothrombin time, total bilirubin, AST, indocyanine green retention rate at 15 min, standard future liver remnant volume and clinically significant portal hypertension grade. In addition, stratification of patients into three risk groups emphasized significant distinctions in the risk of grade B/C post-hepatectomy liver failure. Conclusion: The authors' artificial neural network model could provide a reasonable therapeutic option for clinicians to select optimal candidates with clinically significant portal hypertension for hepatectomy and supplement the hepatocellular carcinoma surgical treatment algorithm.

Background: A precise evaluation of liver reserve function in patients with hepatic alveolar echinococcosis (HAE) prior to hepatectomy could substantially increase the success rate of the operation and reduce the incidence of postoperative complications. The present study aimed to investigate the significance of the indocyanine green retention test at 15 min (ICG-R15) and the Albumin-Indocyanine Green Evaluation (ALICE) grading system in predicting severe posthepatectomy liver failure (PHLF) and postoperative mortality in HAE patients undergoing liver resection., Methods: A total of 105 HAE patients undergoing hepatectomy were enrolled in this study. The value of each variable in predicting severe PHLF was evaluated by univariate and multivariate logistic regression analyses. The area under the receiver operating characteristic (ROC) curves (AUC) were calculated to evaluate the predictive ability of the Child-Pugh grade, ICG-R15, and ALICE grading system. Also, patients were classified using the optimal cutoff value for ICG-R15 and different ALICE grades, and the incidence of severe PHLF and postoperative mortality were compared with the predicted values., Results: Out of the 105 HAE patients enrolled in this study, 34 patients (32.4%) developed severe PHLF. The ALICE grade and operative time were identified as independent predictors of severe PHLF. According to ROC analysis, the AUCs of the Child-Pugh grade, ICG-R15, and ALICE grade for predicting severe PHLF were 0.733 (95% confidence interval (CI), 0.637-0.814), 0.823 (95% CI, 0.737-0.891), 0.834 (95% CI, 0.749-0.900). The incidence of severe PHLF and postoperative 90-day mortality in patients with ICG-R15 > 7.2% were significantly higher than those with ICG-R15 ≤ 7.2% (P < 0.001; P = 0.008). Likewise, the incidence of severe PHLF and postoperative 90-day mortality in patients with ALICE grade 2 were higher than those with ALICE grade 1 within the Child-Pugh grade A (P < 0.001; P = 0.083)., Conclusion: ICG-R15 and ALICE grading system are powerful predictors of severe PHLF and postoperative mortality among HAE patients undergoing hepatectomy. Furthermore, a combination of the preoperative Child-Pugh grade and ALICE grading system may provide an even more precise and objective guidance and facilitate surgical decision-making for HAE patients., (© 2022. The Author(s).)

Background: Primary and secondary liver tumors are not always amenable to resection due to location and size. Inadequate future liver remnant (FLR) may prevent patients from having a curative resection or may result in increased postoperative morbidity and mortality from complications related to small-for-size syndrome (SFSS)., Data Sources: This comprehensive review analyzed the principles, mechanism and risk factors associated with SFSS and presented current available options in the evaluation of FLR when planning liver surgery. In addition, it provided a detailed description of specific modalities that can be used before, during or after surgery, in order to optimize the conditions for a safe resection and minimize the risk of SFSS., Results: Several methods which aim to reduce tumor burden, preserve healthy liver parenchyma, induce hypertrophy of FLR or prevent postoperative complications help minimize the risk of SFSS., Conclusions: With those techniques the indications of radical treatment for patients with liver tumors have significantly expanded. The successful outcome depends on appropriate patient selection, the individualization and modification of interventions and the right timing of surgery., (Copyright © 2021. Published by Elsevier B.V.)

Background . Post-hepatectomy liver failure (PHLF) is an important cause of mortality and morbidity. Whether Child-Pugh A patients with varying degrees of cirrhosis are good candidates for hepatectomy is disputed. The purpose of this study was to analyze the impact of portal venous pressure gradient (PVPG) variation during surgery on PHLF. Methods . PVPG, the pressure gradient between the portal vein and central vein, was measured in consecutive patients before and after liver resection. The optimal cutoff of PVPG to predict PHLF was determined by receiver operating characteristic curve analysis. Risk factors for PHLF were subjected to univariate and multivariable analysis. Results . Sixty Child-Pugh A patients were recruited. The mean PVPG was increased from 5.17 ± 4.78 mm of mercury (mmHg) to 6.37 ± 4.44 mmHg after liver resection. The optimal cutoff value of PVPG increments to predict PHLF was 1.5 mmHg. Multivariable analysis showed prothrombin time (PT), post-hepatectomy PVPG increments of 1.5 mmHg or greater, and resected liver segments of 3 or more to be independent predictors of PHLF. Conclusions . Acute PVPG increase after hepatectomy is associated with a higher risk of PHLF in Child-Pugh A patients.

Background/aims: Posthepatectomy liver failure (PHLF) is a major complication that increases mortality in patients with hepatocellular carcinoma after surgical resection. The aim of this retrospective study was to evaluate the utility of magnetic resonance elastography-assessed liver stiffness (MRE-LS) for the prediction of PHLF and to develop an MRE-LS-based risk prediction model., Methods: A total of 160 hepatocellular carcinoma patients who underwent surgical resection with available preoperative MRE-LS data were enrolled. Clinical and laboratory parameters were collected from medical records. Logistic regression analyses were conducted to identify the risk factors for PHLF and develop a risk prediction model., Results: PHLF was present in 24 patients (15%). In the multivariate logistic analysis, high MRE-LS (kPa; odds ratio [OR] 1.49, 95% confidence interval [CI] 1.12 to 1.98, p=0.006), low serum albumin (≤3.8 g/dL; OR 15.89, 95% CI 2.41 to 104.82, p=0.004), major hepatic resection (OR 4.16, 95% CI 1.40 to 12.38, p=0.014), higher albumin-bilirubin score (>-0.55; OR 3.72, 95% CI 1.15 to 12.04, p=0.028), and higher serum α-fetoprotein (>100 ng/mL; OR 3.53, 95% CI 1.20 to 10.40, p=0.022) were identified as independent risk factors for PHLF. A risk prediction model for PHLF was established using the multivariate logistic regression equation. The area under the receiver operating characteristic curve (AUC) of the risk prediction model was 0.877 for predicting PHLF and 0.923 for predicting grade B and C PHLF. In leave-one-out cross-validation, the risk model showed good performance, with AUCs of 0.807 for all-grade PHLF and 0. 871 for grade B and C PHLF., Conclusions: Our novel MRE-LS-based risk model had excellent performance in predicting PHLF, especially grade B and C PHLF.