Dataset Information

Current evidence on posthepatectomy liver failure: comprehensive review.

ABSTRACT:

Introduction

Despite important advances in many areas of hepatobiliary surgical practice during the past decades, posthepatectomy liver failure (PHLF) still represents an important clinical challenge for the hepatobiliary surgeon. The aim of this review is to present the current body of evidence regarding different aspects of PHLF.

Methods

A literature review was conducted to identify relevant articles for each topic of PHLF covered in this review. The literature search was performed using Medical Subject Heading terms on PubMed for articles on PHLF in English until May 2022.

Results

Uniform reporting on PHLF is lacking due to the use of various definitions in the literature. There is no consensus on optimal preoperative assessment before major hepatectomy to avoid PHLF, although many try to estimate future liver remnant function. Once PHLF occurs, there is still no effective treatment, except liver transplantation, where the reported experience is limited.

Discussion

Strict adherence to one definition is advised when reporting data on PHLF. The use of the International Study Group of Liver Surgery criteria of PHLF is recommended. There is still no widespread established method for future liver remnant function assessment. Liver transplantation is currently the only effective way to treat severe, intractable PHLF, but for many indications, this treatment is not available in most countries.

SUBMITTER: Sparrelid E

PROVIDER: S-EPMC9681670 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Publications

Current evidence on posthepatectomy liver failure: comprehensive review.

Sparrelid Ernesto E Olthof Pim B PB Dasari Bobby V M BVM Erdmann Joris I JI Santol Jonas J Starlinger Patrick P Gilg Stefan S

BJS open 20221101 6

<h4>Introduction</h4>Despite important advances in many areas of hepatobiliary surgical practice during the past decades, posthepatectomy liver failure (PHLF) still represents an important clinical challenge for the hepatobiliary surgeon. The aim of this review is to present the current body of evidence regarding different aspects of PHLF.<h4>Methods</h4>A literature review was conducted to identify relevant articles for each topic of PHLF covered in this review. The literature search was perfor ...[more]

PMID: 36415029

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Project description:ObjectivesEffective and non-invasive biomarkers to predict and avoid posthepatectomy liver failure (PHLF) are urgently needed. This systematic review aims to evaluate the efficacy of gadoxetic acid-enhanced MRI-derived parameters as an imaging biomarker in preoperative prediction of PHLF.MethodsA systematic literature search was performed in the databases of PubMed/Medline, Web of Science, Embase, and Cochrane Library up to 11 December 2020. Studies evaluating the incidence of PHLF on patients who underwent hepatectomy with preoperative liver function assessment using gadoxetic acid-enhanced MRI were included. Data was extracted using pre-designed tables. The Quality In Prognostic Studies (QUIPS) tool was adopted to evaluate the risk of bias.ResultsA total of 15 studies were identified for qualitative synthesis and most studies were marked as low to moderate risk of bias in each domain of QUIPS. The most commonly used parameter was relative liver enhancement or its related parameters. The reported incidence of PHLF ranged from 3.9 to 40%. The predictive sensitivity and specificity of gadoxetic acid-enhanced MRI parameters varied from 75 to 100% and from 54 to 93% in ten reported studies. A majority of the studies revealed that the gadoxetic acid-enhanced MRI parameter was a predictor for PHLF.ConclusionsGadoxetic acid-enhanced MRI showed a high predictive capacity for PHLF and represents a promising imaging biomarker in prediction of PHLF. Multicenter, prospective trials with large sample size and reliable, unified liver function parameters are required to validate the efficacy of individual liver function parameters.Key points• There is an obvious heterogeneity of the published studies, not only in variance of MRI liver function parameters but also in indication and extent of the liver resection. • Signal intensity (SI)-based parameters derived from gadoxetic acid-enhanced MRI are the commonly used method for PHLF prediction. • Gadoxetic acid-enhanced MRI-derived parameters showed high predictive efficacy for PHLF and can potentially serve as a predictor for the incidence of PHLF.

Project description:ObjectivesPosthepatectomy liver failure (PHLF) is a severe complication of liver resection. We aimed to develop and validate a model based on extracellular volume (ECV) and liver volumetry derived from computed tomography (CT) for preoperative predicting PHLF in resectable hepatocellular carcinoma (HCC) patients.MethodsA total of 393 resectable HCC patients from two hospitals were enrolled and underwent multiphasic contrast-enhanced CT before surgery. A total of 281 patients from our hospital were randomly divided into a training cohort (n = 181) and an internal validation cohort (n = 100), and 112 patients from another hospital formed the external validation cohort. CT-derived ECV was measured on nonenhanced and equilibrium phase images, and liver volumetry was measured on portal phase images. The model is composed of independent predictors of PHLF. The under the receiver operator characteristic curve (AUC) and calibration curve were used to reflect the predictive performance and calibration of the model. Comparison of AUCs used the DeLong test.ResultsCT-derived ECV, measured future liver remnant (mFLR) ratio, and serum albumin were independent predictors for PHLF in resectable HCC patients. The AUC of the model was significantly higher than that of the ALBI score in the training cohort, internal validation cohort, and external validation cohort (all p < 0.001). The calibration curve of the model showed good consistency in the training cohort and the internal and external validation cohorts.ConclusionsThe novel model contributes to the preoperative prediction of PHLF in resectable HCC patients.Critical relevance statementThe novel model combined CT-derived extracellular volume, measured future liver remnant ratio, and serum albumin outperforms the albumin-bilirubin score for predicting posthepatectomy liver failure in patients with resectable hepatocellular carcinoma.Key points• CT-derived ECV correlated well with the fibrosis stage of the background liver. • CT-derived ECV and mFLR ratio were independent predictors for PHLF in HCC. • The AUC of the model was higher than the CT-derived ECV and mFLR ratio. • The model showed a superior predictive performance than that of the ALBI score.

Project description:BackgroundPosthepatectomy liver failure (PHLF) represents a life-threatening complication with limited therapeutic options. Neutrophils play a critical and dynamic role during regeneratory processes, but their role in human liver regeneration is incompletely understood, especially as underlying liver disease, detectable in the majority of patients, critically affects hepatic regeneration. Here we explored intrahepatic neutrophil accumulation and neutrophil extracellular traps (NETs) in patients with PHLF and validated the functional relevance of NETs in a murine partial hepatectomy (PHx) model.MethodsWe investigated the influx of neutrophils, macrophages, eosinophils, and mast cells and the presence of their respective extracellular traps in liver biopsies of 35 patients undergoing hepatectomy (10 patients with PHLF) before and after the initiation of liver regeneration by fluorescence microscopy. In addition, NET formation and neutrophil activation were confirmed by plasma analysis of 99 patients (24 patients with PHLF) before and up to 5 days after surgery. Furthermore, we inhibited NETs via DNase I in a murine PHx model of mice with metabolically induced liver disease.ResultsWe detected rapid intrahepatic neutrophil accumulation, elevated levels of myeloperoxidase release, and NET formation in regenerating human livers, with a significantly higher increase of infiltrating neutrophils and NETs in patients with PHLF. Circulating markers of neutrophil activation, including elastase, myeloperoxidase, and citrullinated histone H3, correlated with markers of liver injury. In a murine PHx model, we showed that the inhibition of NET accelerated hepatocyte proliferation and liver regeneration.ConclusionsPatients with PHLF showed accelerated intrahepatic neutrophil infiltration and NET formation, which were associated with liver damage. Further, we identified postsurgical myeloperoxidase levels as predictive markers for adverse outcomes and observed that blocking NETs in a murine PHx model accelerated tissue regeneration.

Project description:BackgroundMetabolic regulation is critical during liver regeneration in rodents, but human data are limited. We investigated perioperative dynamics of circulating metabolites and plasma levels of glucagon-like peptide-1 (GLP-1) and GLP-2, in patients undergoing liver resections, exploring their associations with the histological phenotype of metabolic dysfunction-associated steatotic liver disease (MASLD) and posthepatectomy liver failure (PHLF).MethodsEighty-one and 75 patients from two centers between 2012 and 2023 were studied. Targeted quantitative metabolomic assay of 180 circulating metabolites, perioperative GLP-1, GLP-2, and standard lipid parameter level evaluation was employed. An exploratory PHLF prediction model was developed, including GLP-1 as a metabolic parameter.ResultsSignificant alterations of 44 metabolites by postoperative day (POD) 1 and 40 by POD5 were observed, mainly among phospholipid species. Unsupervised clustering identified two metabolic clusters, with one encompassing 93% of PHLF patients by POD5 (P<0.001). Standard plasma lipid parameters displayed consistent decrease after hepatectomy, independent from MASLD phenotype, with the lowest levels in PHLF patients. Postoperative GLP-1 and GLP-2 dynamics displayed a reciprocal pattern, indicating adaptive change in secretion. Preoperative GLP-1 levels were significantly increased in PHLF (P=0.02). Furthermore, incorporation of GLP-1 into the established aspartate aminotransferase to platelet ratio index (APRI) + albumin-bilirubin (ALBI) score, improved PHLF prediction [area under the curve (AUC): 0.833, 95% confidence interval (CI): 0.660-0.964].ConclusionsSignificant metabolic changes occur during human liver resection, particularly in phospholipid metabolism, along with distinct perioperative dynamics of GLP-1 and GLP-2, closely linked to PHLF and independent of the histological phenotype of MASLD. Additionally, we provide exploratory results on the predictive value of GLP-1 for PHLF, emphasizing a holistic model of liver function assessment highlighting the metabolic component of human liver regeneration.

Dataset Information

Current evidence on posthepatectomy liver failure: comprehensive review.

Introduction

Methods

Results

Discussion

Publications

Current evidence on posthepatectomy liver failure: comprehensive review.

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