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post-hepatectomy liver failure:A timeline centered review

Hepatobiliary & Pancreatic Diseases International 2023年第6期22卷 554-569页

作者： Mohamed Bekheit Lisa Grundy Ahmed KA Salih Petru Bucur Eric Vibert Mudassar Ghazanfar Department of Surgery NHS GrampianForesterhill Health CampusAshgrove RoadAB252ZN AberdeenUK Institute of Medical Sciences Medical SchoolForesterhill Health CampusAshgrove RoadAB252ZN AberdeenUK Hépatica Integrated Center of HPB CareElite HospitalAgriculture RoadAlexandriaEgypt Department of Surgery University Hospital ToursVal de la Loire 37000France Centre Hépatobiliaire Paul Brousse Hospital12 Paul Valliant Couturier94804 VillejuifFrance

Background: post-hepatectomy liver failure(PHLF) is a leading cause of postoperative mortality after liver surgery. Due to its significant impact, it is imperative to understand the risk stratification and preventative strategies for PHLF. The main objective of this review is to highlight the role of these strategies in a timeline centered way around curative resection. Data sources: This review includes studies on both humans and animals, where they addressed PHLF. A literature search was conducted across the Cochrane Library, Embase, MEDLINE/Pub Med, and Web of Knowledge electronic databases for English language studies published between July 1997 and June 2020. Studies presented in other languages were equally considered. The quality of included publications was assessed using Downs and Black’s checklist. The results were presented in qualitative summaries owing to the lack of studies qualifying for quantitative analysis. Results: This systematic review with 245 studies, provides insight into the current prediction, prevention, diagnosis, and management options for PHLF. This review highlighted that liver volume manipulation is the most frequently studied preventive measure against PHLF in clinical practice, with modest improvement in the treatment strategies over the past decade. Conclusions: Remnant liver volume manipulation is the most consistent preventive measure against PHLF.

关键词： post-hepatectomy liver failure liver neoplasms Prediction Prevention Management

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Hypophosphatemia as a prognostic tool for post-hepatectomy liver failure:A systematic review

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World Journal of Gastrointestinal Surgery 2023年第2期15卷 249-257页

作者： Romualdas Riauka Povilas Ignatavicius Giedrius Barauskas Department of Surgery Lithuanian University of Health SciencesKaunas 50161Lithuania

BACKGROUND post-hepatectomy liver failure(PHLF)is one of the main causes of postoperative mortality and is challenging to predict early in patients after liver resection.Some studies suggest that the postoperative serum phosphorus might predict outcomes in these patients.AIM To perform a systematic literature review on hypophosphatemia and evaluate it as a prognostic factor for PHLF and overall morbidity.METHODS This systematic review was performed according to preferred reporting items for systematic reviews and meta-analyses statement.A study protocol for the review was registered in the International Prospective Register of Systematic Reviews database.PubMed,Cochrane and Lippincott Williams&Wilkins databases were systematically searched up to March 31,2022 for studies analyzing postoperative hypophosphatemia as a prognostic factor for PHLF,overall postoperative morbidity and liver regeneration.The quality assessment of the included cohort studies was performed according to the Newcastle-Ottawa Scale.RESULTS After final assessment,nine studies(eight retrospective and one prospective cohort study)with 1677 patients were included in the systematic review.All selected studies scored≥6 points according to the Newcastle-Ottawa Scale.Cutoff values of hypophosphatemia varied frompostoperative liver regeneration,with reported better postoperative liver regeneration in cases of postoperative hypophosphatemia.In three studies hypophosphatemia was associated with better postoperative outcomes,while six studies revealed hypophosphatemia as a predictive factor for worse patient outcomes.CONCLUSION Changes of the postoperative serum phosphorus level might be useful for predicting outcomes after liver resection.However,routine measurement of perioperative serum p

关键词： Hypophosphatemia post-hepatectomy liver failure liver regeneration Serum phosphorus Literature review

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Non-invasive tests for the prediction of post-hepatectomy liver failure in the elderly

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Hepatoma Research 2020年第6期6卷 41-57页

作者： Giovanni Marasco Antonio Colecchia Matteo Milandri Benedetta Rossini Luigina Vanessa Alemanni Elton Dajti Federico Ravaioli Matteo Renzulli Rita Golfieri Davide Festi Department of Medical and Surgical Sciences(DIMEC) University of BolognaBologna 40138Italy Unit of Gastroenterology Borgo Trento University Hospital of VeronaP.le Aristide Stefani 1Verona 37126Italy Radiology Unit Sant’Orsola Malpighi HospitalBologna 40138Italy

post-hepatectomy liver failure(PHLF)is associated with great morbidity and mortality after resection of hepatocellular carcinoma.Previous studies have underlined that advanced age could be a potential factor influencing post-operative complications and long-term survival.In the past,candidates for resection were based on the Child-Pugh classification,the predictive value of which was rather low.The selection of patients undergoing resection in Western countries is based on the assessment of portal hypertension(PH),which is clinically assessed by measurement of the hepatic venous pressure gradient,an invasive and costly process.Thus,there have been several attempts to identify the best non-invasive test(NIT)to accurately predict PHLF.Most biochemical NITs for the prediction of PHLF are focused on evaluation of underlying liver cirrhosis and PH.Amongst them,FIB-4,which also includes the patient's age,seems to have more robust supporting results.In Europe and the USA.,the most tested and reliable NIT for predicting PHLF is the evaluation of liver stiffness measurement,which is also influenced by age.Imaging parameters are promising tools which are used only in specialized centers however,and when available.liver volume parameters,as well as contrast-enhanced data,demonstrate good accuracy in predicting PHLF.In this scenario,the evaluation of sarcopenia and bone mineral density through contextual imaging allows the delineation of PHLF in at-risk elderly patients.Further studies focused on parameters for the evaluation of PHLF in elderly patients are needed.

关键词： post-hepatectomy liver failure liver resection elderly liver stiffness measurement indocyanine green retention test

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Development and Validation of a Nomogram Based on Perioperative Factors to Predict post-hepatectomy liver failure

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Journal of Clinical and Translational Hepatology 2021年第3期9卷 291-300页

作者： Bin Xu Xiao-Long Li Feng Ye Xiao-Dong Zhu Ying-Hao Shen Cheng Huang Jian Zhou Jia Fan Yong-Jun Chen Hui-Chuan Sun Department of liver Surgery and Transplantation Liver Cancer InstituteZhongshan HospitalFudan UniversityShanghaiChina Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education ShanghaiChina Department of Hepatobiliary Surgery Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina

(PHLF)is a severe complication and main cause of death in patients undergoing hepatectomy.The aim of this study was to build a predictive model of PHLF in patients undergoing hepatectomy.Methods:We retrospectively analyzed patients undergoing hepatectomy at Zhongshan Hospital,Fudan University from July 2015 to June 2018,and randomly divided them into development and internal validation cohorts.External validation was performed in an independent cohort.Least absolute shrinkage and selection operator(commonly referred to as LASSO)logistic regression was applied to identify predictors of PHLF,and multivariate binary logistic regression analysis was performed to establish the predictive model,which was visualized with a nomogram.Results:A total of 492 eligible patients were analyzed.LASSO and multivariate analysis identified three preoperative variables,total bilirubin(p=0.001),international normalized ratio(pliver disease score,albumin-bilirubin score and platelet-albumin-bilirubin score(AUROCs:0.723,0.695 and 0.663,respectively;phepatectomy,which may significantly contribute to the postoperative care of these patients.

关键词： hepatectomy post-hepatectomy liver failure LASSO Nomogram

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Validation of a surgical model for posthepatectomy liver failure in rats

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Animal Models and Experimental Medicine 2023年第3期6卷 266-273页

作者： Andrea Lund Michelle Meier Kasper Jarlhelt Andersen Marie Ingemann Pedersen Anders Riegels Knudsen Jakob Kirkegård Frank Viborg Mortensen Aarhus University Hospital Department of Upper Gastrointestinal and Hepato-Pancreato-Biliary SurgeryAarhus NDenmark

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 sur-gery.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 expe-rienced PHLF.Seventeen rats were euthanized due to irreversible PHLF.The GDS increased for nonsurvivors within 12–18 h after surgery.The mean time for euthaniza-tion 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 detect-ing lethal outcomes caused by PHLF in rats.

关键词： 90%liver resection general distress score liver failure post-hepatectomy liver failure rats

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Model for liver hardness using two-dimensional shear wave elastography,durometer,and preoperative biomarkers

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World Journal of Gastrointestinal Surgery 2021年第2期13卷 127-140页

作者： Bing-Jie Ju Ming Jin Yang Tian Xiang Zhen De-Xing Kong Wei-Lin Wang Sheng Yan Department of Hepatobiliary and Pancreatic Surgery The Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009Zhejiang ProvinceChina Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province Hangzhou 310009Zhejiang ProvinceChina Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province Hangzhou 310009Zhejiang ProvinceChina Clinical Medicine Innovation Center of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease of Zhejiang University Hangzhou 310009Zhejiang ProvinceChina Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province Hangzhou 310009Zhejiang ProvinceChina School of Mathematical Sciences Zhejiang UniversityHangzhou 310027Zhejiang ProvinceChina

BACKGROUND post-hepatectomy liver failure(PHLF)increases morbidity and mortality after liver resection for patients with advanced liver fibrosis and cirrhosis.Preoperative liver stiffness using two-dimensional shear wave elastography(2D-SWE)is widely used to evaluate the degree of fibrosis.However,the 2D-SWE results were not accurate.A durometer measures hardness by quantifying the ability of a material to locally resist the intrusion of hard objects into its surface.However,the durometer score can only be obtained during surgery.To measure correlations among 2D-SWE,palpation by surgeons,and durometermeasured objective liver hardness and to construct a liver hardness regression model.METHODS We enrolled 74 hepatectomy patients with liver hardness in a derivation cohort.Tactile-based liver hardness scores(0-100)were determined through palpation of the liver tissue by surgeons.Additionally,liver hardness was measured using a durometer.Correlation coefficients for durometer-measured hardness and preoperative parameters were calculated.Multiple linear regression models were constructed to select the best predictive durometer scale.Receiver operating characteristic(ROC)curves and univariate and multivariate analyses were used to calculate the best model’s prediction of PHLF and risk factors for PHLF,respectively.A separate validation cohort(n=162)was used to evaluate the model.RESULTS The stiffness measured using 2D-SWE and palpation scale had good linear correlation with durometer-measured hardness(Pearson rank correlation coefficient 0.704 and 0.729,respectively,P<0.001).The best model for the durometer scale(hardness scale model)was based on stiffness,hepatitis B virus surface antigen,and albumin level and had an R2 value of 0.580.The area under the ROC for the durometer and hardness scale for PHLF prediction were 0.807(P=0.002)and 0.785(P=0.005),respectively.The optimal cutoff value of the durometer and hardness scale was 27.38(sensitivity=0.900,specificity=0.660)and 27.87(sensitivity=0.700,specificity=0.787),resp

关键词： hepatectomy liver Hardness Durometer Two-dimensional shear wave elastography post-hepatectomy liver failure liver failure

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Cyclin-dependent kinase inhibitors p21 and p27 function as critical regulators of liver regeneration following 90%hepatectomy in the rat

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World Journal of Hepatology 2020年第12期12卷 1198-1210页

作者： Nicolas Moniaux Laurence Lacaze Adelie Gothland Alice Deshayes Didier Samuel Jamila Faivre INSERM U1193Paul-Brousse University HospitalHepatobiliary CentreVillejuif 94800France UniversitéParis-Saclay Facultéde Médecine Le KremlinBicêtre 94270France Department of Pôle de Biologie Médicale Laboratoire d’Onco-HématologieAssistance Publique-Hôpitaux de Paris(AP-HP)Paul-Brousse University HospitalVillejuif 94800France

BACKGROUND liver reduction is the main curative treatment for primary liver cancer,but its use remains limited as liver regeneration requires a minimum of 30%functional parenchyma.AIM To study the dynamics of the liver regeneration process and consequent behavior of cell cycle regulators in rats after extended hepatectomy(90%)and postoperative glucose infusions.METHODS post-hepatectomy liver failure was triggered in 84 Wistar rats by reducing their liver mass by 90%.The animals received a post-operative glucose infusion and were randomly assigned to two groups:One to investigate the survival rate and the other for biochemical analyses.Animals that underwent laparotomy or 70%hepatectomy were used as controls.Blood and liver samples were collected on postoperative days 1 to 7.liver morphology,function,and regeneration were studied with histology,immunohistochemistry,and western blotting.RESULTS postoperative mortality after major resection reached 20%and 55%in the first 24 h and 48 h,respectively,with an overall total of 70%7 d after surgery.No apparent signs of apoptotic cell death were detected in the extended hepatectomy rat livers,but hepatocytes displaying a clear cytoplasm and an accumulation of hyaline material testified to changes affecting their functional activities.liver regeneration started properly,as early events initiating cell proliferation occurred within the first 3 h,and the G1 to S transition was detected in less than 12 h.However,a rise in p27(Kip1)followed by p21(Waf1/Cip1)cell cycle inhibitor levels led to a delayed S phase progression and mitosis.Overall,liver regeneration in rats with a 90%hepatectomy was delayed by 24 h and associated with a delayed onset and lower peak magnitude of hepatocellular deoxyribonucleic acid synthesis.CONCLUSION This work highlights the critical importance of the cyclin/cyclin-dependent kinase inhibitors of the Cip/Kip family in regulating the liver regeneration timeline following extended hepatectomy.

关键词： Major hepatectomy liver failure liver regeneration post-hepatectomy liver failure p21 p27

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