A novel surgical scheme for hepatectomy in hepatocellular carcinoma patients with clinically significant portal hypertension.

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.

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

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

HMGB1-Mediated Cell Death-A Crucial Element in Post-Hepatectomy Liver Failure.

Liver resection (LR) is the primary treatment for hepatic tumors, yet posthepatectomy liver failure (PHLF) remains a significant concern. While the precise etiology of PHLF remains elusive, dysregulated inflammatory processes are pivotal. Therefore, we explored the theragnostic potential of extracellular high-mobility-group-box protein 1 (HMGB1), a key damage-associated molecular pattern (DAMP) released by hepatocytes, in liver recovery post LR in patients and animal models. Plasma from 96 LR patients and liver tissues from a subset of 24 LR patients were analyzed for HMGB1 levels, and associations with PHLF and liver injury markers were assessed. In a murine LR model, the HMGB1 inhibitor glycyrrhizin, was administered to assess its impact on liver regeneration. Furthermore, plasma levels of keratin-18 (K18) and cleaved cytokeratin-18 (ccK18) were quantified to assess suitability as predictive biomarkers for PHLF. Patients experiencing PHLF exhibited elevated levels of intrahepatic and circulating HMGB1, correlating with markers of liver injury. In a murine LR model, inhibition of HMGB1 improved liver function, reduced steatosis, enhanced regeneration and decreased hepatic cell death. Elevated levels of hepatic cell death markers K18 and ccK18 were detected in patients with PHLF and correlations with levels of circulating HMGB1 was observed. Our study underscores the therapeutic and predictive potential of HMGB1 in PHLF mitigation. Elevated HMGB1, K18, and ccK18 levels correlate with patient outcomes, highlighting their predictive significance. Targeting HMGB1 enhances liver regeneration in murine LR models, emphasizing its role in potential intervention and prediction strategies for liver surgery.

Effect of early administration of tolvaptan on pleural effusion post-hepatectomy.

PURPOSE: This study evaluated the efficacy of tolvaptan administration at the early stage after hepatectomy to control pleural effusion and improve the postoperative course. METHODS: Patients were administered tolvaptan (7.5 mg) and spironolactone (25 mg) from postoperative day 1 to postoperative day 5 (tolvaptan group, n = 68) for 13 months. Early administration of tolvaptan was not provided in the control group (n = 68); however, diuretics were appropriately administered according to the patient's condition. The amount of pleural effusion on computed tomography on postoperative day 5 was compared between the two groups. RESULTS: The amount of pleural effusion and increase in body weight on postoperative day 5 showed significant differences in both groups (p < 0.001 and p = 0.019, respectively). However, the rate of pleural aspiration and the duration of postoperative hospitalization were comparable between the groups. The amount of intraoperative blood loss and lack of early administration of tolvaptan were identified as independent risk factors contributing to pleural effusion on multivariate analysis. CONCLUSION: Early administration of tolvaptan to patients after hepatectomy was found to be capable of controlling postoperative pleural effusion and increase in body weight, but it did not reduce the rate of pleural aspiration or the hospitalization period.

The value of intraoperative dynamic liver function test ICG in predicting postoperative complications in patients undergoing staged hepatectomy: a pilot study.

PURPOSE: To assess the predictive value of intraoperative indocyanine green (ICG) test in patients undergoing staged hepatectomy. METHODS: We analyzed intraoperative ICG measurements of future liver remnant (FLR), preoperative ICG, volumetry, and hepatobiliary scintigraphy in 15 patients undergoing associated liver partition and portal vein ligation for staged hepatectomy (ALPPS). Main endpoints were the correlation of intraoperative ICG values to postoperative complications (Comprehensive Complication Index (CCI®)) at discharge and 90 days after surgery, and to postoperative liver function. RESULTS: Median intraoperative R15 (ICG retention rate at 15 min) correlated significantly with CCI® at discharge (p = 0.05) and with CCI® at 90 days (p = 0.0036). Preoperative ICG, volumetry, and scintigraphy did not correlate to postoperative outcome. ROC curve analysis revealed a cutoff value of 11.4 for the intraoperative R15 to predict major complications (Clavien-Dindo ≥ III) with 100% sensitivity and 63% specificity. No patient with R15 ≤ 11 developed major complications. CONCLUSION: This pilot study suggests that intraoperative ICG clearance determines the functional capacity of the future liver remnant more accurately than preoperative tests. This may further reduce the number of postoperative liver failures, even if it means intraoperative abortion of hepatectomy in individual cases.

Predictive value of Gd-EOB-DTPA -enhanced magnetic resonance imaging for post-hepatectomy liver failure: a systematic review and meta-analysis.

BACKGROUND: Accurate preoperative diagnosis of post-hepatectomy liver failure (PHLF) is particularly important to improve the prognosis of patients. PURPOSE: To evaluate the predictive value of Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) for post-hepatectomy liver failure. MATERIAL AND METHODS: A systematic search was performed in the PubMed, Embase, the Cochrane Library, and Web of Science databases to find relevant original articles published up to December 2021. The included studies were assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. The bivariate random-effects model was used to assess the diagnostic authenticity. Meta-regression analyses were performed to analyze the potential heterogeneity. RESULTS: In total, 13 articles were included. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and the area under the summary receiver operating characteristic curves were 88% (95% confidence interval [CI] = 0.80-0.94), 80% (95% CI = 0.73-0.86), 4.4 (95% CI = 3.3-5.9), 0.14 (95% CI = 0.08-0.25), 31 (95% CI = 17-57), and 0.91 (95% CI = 0.89-0.94), respectively. There was no publication bias and threshold effect in our study. CONCLUSION: Gd-EOB-DTPA-enhanced MRI is a potentially useful for the prediction of PHLF after major hepatectomy.

Preoperative Predictive Nomogram Based on Alanine Aminotransferase, Prothrombin Time Activity, and Remnant Liver Proportion (APART Score) to Predict Post-Hepatectomy Liver Failure after Major Hepatectomy.

INTRODUCTION: Post-hepatectomy liver failure (PHLF) is a serious complication associated with major hepatectomies. An accurate prediction of PHLF is necessary to determine the feasibility of major hepatectomy. This study aimed to assess the association between PHLF and preoperative laboratory and computed tomography (CT) findings. METHODS: Medical records of 65 patients who underwent major hepatectomy and preoperative CT were retrospectively reviewed. We evaluated future remnant liver volume evaluation models and remnant liver hemodynamics, which were assessed by arterial enhancement fraction (AEF) by using preoperative CT. Variables, including CT findings, were compared between patients with and without PHLF after major hepatectomy, and the preoperative PHLF-predicting nomogram was constructed using multivariate logistic regression. RESULTS: The PHLF group included 21 patients (32.3%). The AEF was not significantly different between the two groups. In the future remnant liver volume evaluation models, future remnant liver proportion (fRLP) had the highest concordance index (C-index) in the receiver operating characteristic curve analysis (C-index, 0.755). Multivariate analysis of preoperative evaluable factors revealed that alanine aminotransferase levels (p = 0.034), prothrombin time activity (p = 0.021), and fRLP (p = 0.012) were independent predictive factors of PHLF. A nomogram (APART score) was constructed using these three factors, with a receiver operating curve showing a C-index of 0.894. According to the APART score, scores of 51-60 indicated moderate risk (40.0%), and scores over 60 indicated a high risk of PHLF (83.3%) (p < 0.001). DISCUSSION: The APART score may help predict PHLF in patients indicated for major hepatectomies.

Post-hepatectomy liver failure: A timeline centered review.

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/PubMed, 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.

Is metabolic syndrome a risk factor in hepatectomy? A meta-analysis with subgroup analysis for histologically confirmed hepatic manifestations.

BACKGROUND: Metabolic syndrome (MetS) is a risk factor in surgery. MetS can progress to metabolic (dysfunction)-associated fatty liver disease (MAFLD), a vast-growing etiology of primary liver tumors which are major indications for liver surgery. The aim of this meta-analysis was to investigate the impact of MetS on complications and long-term outcomes after hepatectomy. METHODS: The protocol for this meta-analysis was registered at PROSPERO prior to data extraction. MEDLINE, Web of Science, and Cochrane Library were searched for publications on liver resections and MetS. Comparative studies were included. Outcomes encompassed postoperative complications, mortality, and long-term oncologic status. Data were pooled as odds ratio (OR) with a random-effects model. Risk of bias was assessed using the Quality in Prognostic Studies tool (QUIPS), and the certainty of the evidence was evaluated with GRADE. Subgroup analyses for patients with histopathologically confirmed non-alcoholic fatty liver disease (NAFLD) versus controls were performed. RESULTS: The meta-analyses included fifteen comparative studies. Patients with MetS suffered significantly more overall complications (OR 1.55; 95% CI [1.05; 2.29]; p=0.03), major complications (OR 1.97 95% CI [1.13; 3.43]; p=0.02; I2=62%), postoperative hemorrhages (OR 1.76; 95% CI [1.23; 2.50]; p=0.01) and infections (OR 1.63; 95% CI [1.03; 2.57]; p=0.04). There were no significant differences in mortality, recurrence, 1- or 5-year overall or recurrence-free survivals. Patients with histologically confirmed NAFLD did not have significantly more overall complications; however, PHLF rates were increased (OR 4.87; 95% CI [1.22; 19.47]; p=0.04). Recurrence and survival outcomes did not differ significantly. The certainty of the evidence for each outcome ranged from low to very low. CONCLUSION: Patients with MetS that undergo liver surgery suffer more complications, such as postoperative hemorrhage and infection but not liver-specific complications-PHLF and biliary leakage. Histologically confirmed NAFLD is associated with significantly higher PHLF rates, yet, survivals of these patients are similar to patients without the MetS. Further studies should focus on identifying the tipping point for increased risk in patients with MetS-associated liver disease, as well as reliable markers of MAFLD stages and early markers of PHLF. TRIAL REGISTRATION: PROSPERO Nr: CRD42021253768.

Developmental artificial neural network model to evaluate the preoperative safe limit of future liver remnant volume for HCC combined with clinically significant portal hypertension.

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.

Hepatectomy involves removing the tumor from the liver and is considered the most effective treatment for hepatocellular carcinoma (HCC). Clinically significant portal hypertension is characterized by the presence of gastric and/or esophageal varices and a platelet count <100 × 10⁹/l with the presence of splenomegaly, which would aggravate the risk of post-hepatectomy liver failure, and is therefore regarded as a contraindication to hepatectomy. Over the past few decades, with improvement in surgical techniques and perioperative care, the morbidity of postoperative complications and mortality have decreased greatly. Current HCC guidelines recommend the expansion of hepatectomy to HCC patients with clinically significant portal hypertension. However, determining how to select optimal candidates for hepatectomy remains challenging. The authors' artificial neural network is a mathematical tool developed by simulating the properties of neurons with large-scale information distribution and parallel structure. Here the authors retrospectively enrolled 871 hepatitis B virus-related HCC patients and developed an artificial neural network model to predict the risk of post-hepatectomy liver failure, which could provide a reasonable therapeutic option and facilitate precise surgical decisions for clinicians.

Textbook outcome among voluntary donors undergoing major living donor hepatectomy.

PURPOSE: Textbook outcome (TO) is a composite measure of outcome and provides superior assessment of quality of care after surgery. TO after major living donor hepatectomy (MLDH) has not been assessed. The objective of this study was to determine the rate of TO and its associated factors, after MLDH. METHODS: This was a single center retrospective review of living liver donors who underwent MLDH between 2012 and 2021 (n = 1022). The rate of TO and its associated factors was determined. RESULTS: Among 1022 living donors (of whom 693 [67.8%] were males, median age 26 [range, 18-54] years), TO was achieved in 714 (69.9%) with no donor mortality. Majority of donors met the cutoffs for individual outcome measures: 908 (88.8%) for no major complications, 904 (88.5%) for ICU stay ≤ 2 days, 900 (88.1%) for hospital stay ≤ 10 days, 990 (96.9%) for no perioperative blood transfusion, 1004 (98.2%) for no 30-day re-admission, and 1014 (99.2%) for no post-hepatectomy liver failure. Early donation era (before streamlining of donor operative pathways) was associated with failure to achieve TO [OR 1.4, CI 1.1-1.9, P = 0.006]. TO was achieved in 506/755 (67%) donors in the early donation era versus 208/267 (77.9%) in the later period (P = 0.001). CONCLUSION: Despite zero mortality and low complication rate, TO was achieved in approximately 70% donors. TO was modifiable and improved with changes in donor operative pathway.

An mALBI-Child-Pugh-based nomogram for predicting post-hepatectomy liver failure grade B-C in patients with huge hepatocellular carcinoma: a multi-institutional study.

OBJECTIVE: Post-hepatectomy liver failure (PHLF) is a severe complication in patients with hepatocellular carcinoma (HCC) who underwent hepatectomy. This study aims to develop a nomogram of PHLF grade B-C in patients with huge HCC (diameter ≥ 10 cm). METHODS: We retrospectively collected clinical information of 514 and 97 patients who underwent hepatectomy for huge HCC at two medical centers between 2016 and 2021. Univariate and multivariate analysis were carried out to screen the independent risk factors of PHLF grade B-C, which were visualized as a nomogram. RESULTS: Three Hundred Forty Three Thousand One Hundred Seventy One  and 97 HCC patients were included in the training cohort, internal validation cohort, and external validation cohort, with probabilities of PHLF grade B-C of 15.1%, 12.9%, and 22.7%, respectively. Pre-operative modified albumin-bilirubin (mALBI) grade (p < 0.001), Child-Pugh classification (p = 0.044), international normalized ratio (INR) (p = 0.005), cirrhosis (p = 0.019), and intraoperative blood loss (p = 0.004) were found to be independently associated with PHLF grade B-C in the training cohort. All the five independent factors were considered in the establishment of the nomogram model. In the internal validation cohort and external validation cohort, the area under receiver operating characteristic curve for the nomogram in PHLF grade B-C prediction reached 0.823 and 0.740, respectively. Divided into different risk groups according to the optimal cut-off value, patients in the high-risk group reported significantly higher frequency of PHLF grade B-C than those in the low-risk group, both in the training cohort and the validation cohort (p < 0.001). CONCLUSIONS: The proposed noninvasive nomogram based on mALBI-Child-Pugh and three other indicators achieved optimal prediction performance of PHLF grade B-C in patients with huge HCC.

Future liver volume combined with platelet count predicts liver failure after major hepatectomy.

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 × 109/L were at high risk of developing PHLF. CONCLUSION: FLV/eTV combined with preoperative PLT count is effective in predicting PHLF after major hepatectomy.

Hepatectomy risk assessment with functional magnetic resonance imaging (HEPARIM).

BACKGROUND: Post hepatectomy liver failure (PHLF) remains a significant risk in patients undergoing curative liver resection for cancer, however currently available PHLF risk prediction investigations are not sufficiently accurate. The Hepatectomy risk assessment with functional magnetic resonance imaging trial (HEPARIM) aims to establish if quantitative MRI biomarkers of liver function & perfusion can be used to more accurately predict PHLF risk and FLR function, measured against indocyanine green (ICG) liver function test. METHODS: HEPARIM is an observational cohort study recruiting patients undergoing liver resection of 2 segments or more, prior to surgery patients will have both Dynamic Gadoxetate-enhanced (DGE) liver MRI and ICG testing. Day one post op ICG testing is repeated and R15 compared to the Gadoxetate Clearance (GC) of the future liver remnant (FLR-GC) as measure by preoperative DGE- MRI which is the primary outcome, and preoperative ICG R15 compared to GC of whole liver (WL-GC) as a secondary outcome. Data will be collected from medical records, biochemistry, pathology and radiology reports and used in a multi-variate analysis to the value of functional MRI and derive multivariant prediction models for future validation. DISCUSSION: If successful, this test will potentially provide an efficient means to quantitatively assess FLR function and PHLF risk enabling surgeons to push boundaries of liver surgery further while maintaining safe practice and thereby offering chance of cure to patients who would previously been deemed inoperable. MRI has the added benefit of already being part of the routine diagnostic pathway and as such would have limited additional burden on patients time or cost to health care systems. (Hepatectomy Risk Assessment With Functional Magnetic Resonance Imaging - Full Text View - ClinicalTrials.gov , n.d.) TRIAL REGISTRATION: ClinicalTrials.gov, ClinicalTrials.gov NCT04705194 - Registered 12th January 2021 - Retrospectively registered.

Preoperative predictors of liver decompensation after mini-invasive liver resection.

BACKGROUND: Post-hepatectomy liver failure (PHLF) represents the most frequent complication after liver surgery, and the most common cause of morbidity and mortality. Aim of the study is to identify the predictors of PHLF after mini-invasive liver surgery in cirrhosis and chronic liver disease, and to develop a model for risk prediction. METHODS: The present study is a multicentric prospective cohort study on 490 consecutive patients who underwent mini-invasive liver resection from the Italian Registry of Mini-invasive Liver Surgery (I go MILS). Retrospective additional biochemical and clinical data were collected. RESULTS: On 490 patients (26.5% females), PHLF occurred in 89 patients (18.2%). The only independent predictors of PHLF were Albumin-Bilirubin (ALBI) score (OR 3.213; 95% CI 1.661-6.215; p < .0.0001) and presence of ascites (OR 3.320; 95% CI 1.468-7.508; p = 0.004). Classification and regression tree (CART) modeling led to the identification of three risk groups: PHLF occurred in 23/217 patients with ALBI grade 1 (10.6%, low risk group), in 54/254 patients with ALBI score 2 or 3 and absence of ascites (21.3%, intermediate risk group) and in 12/19 patients with ALBI score 2 or 3 and evidence of ascites (63.2%, high risk group), p < 0.0001. The three groups showed a corresponding increase in postoperative complications (20.0%, 27.5% and 66.7%), Comprehensive Complication Index (5.1 ± 11.1, 6.0 ± 10.9 and 18.8 ± 18.9) and hospital stay (6.0 ± 4.0, 6.0 ± 6.0 and 8.0 ± 5.0 days). CONCLUSION: The risk of PHLF can be stratified by determining two easily available preoperative factors: ALBI and ascites. This model of risk prediction offers an objective instrument for a correct clinical decision-making.

Post-hepatectomy liver failure after hepatic resection for hepatocellular carcinoma: a single center experience.

PURPOSE: Post-hepatectomy liver failure (PHLF) is one of the most feared morbidities after liver resection (LR) for hepatocellular carcinoma (HCC). We aimed to investigate the incidence and predictors of PHLF after LR for HCC and its impact on survival outcomes. METHODS: We reviewed the patients who underwent LR for HCC during the period between January 2010 and 2019. RESULTS: Two hundred sixty-eight patients were included. Patients were divided into two groups according to the occurrence of PHLF, defined according to ISGLS. The non-PHLF group included 138 patients (51.5%), while the PHLF group included 130 patients (48.5%). Two hundred forty-six patients (91.8%) had hepatitis C virus. Major liver resections were more performed in the PHLF group (40 patients (30.8%) vs. 18 patients (13%), p = 0.001). Longer operation time (3 vs. 2.5 h, p = 0.001), more blood loss (1000 vs. 500 cc, p = 0.001), and transfusions (81 patients (62.3%) vs. 52 patients (37.7%), p = 0.001) occurred in PHLF group. The 1-, 3-, and 5-year Kaplan-Meier overall survival rates for the non-PHLF group were 93.9%, 79.5%, and 53.9% and 73.2%, 58.7%, and 52.4% for the PHLF group, respectively (log rank, p = 0.003). The 1-, 3-, and 5-year Kaplan-Meier disease-free survival rates for the non-PHLF group were 77.7%, 42.5%, and 29.4%, and 73.3%, 42.9%, and 25.3% for the PHLF group, respectively (log rank, p = 0.925). Preoperative albumin, bilirubin, INR, and liver cirrhosis were significant predictors of PHLF in the logistic regression analysis. CONCLUSION: Egyptian patients with HCC experienced higher PHLF incidence after LR for HCC. PHLF significantly affected the long-term survival of those patients.

Issues to be considered to address the future liver remnant prior to major hepatectomy.

An accurate preoperative evaluation of the hepatic function and application of portal vein embolization in selected patients have helped improve the safety of major hepatectomy. In planning major hepatectomy, however, several issues remain to be addressed. The first is which cut-off values for serum total bilirubin level and prothrombin time should be used to define post-hepatectomy liver failure. Other issues include what minimum future liver remnant (FLR) volume is required; whether the total liver volume measured using computed tomography or the standard liver volume calculated based on the body surface area should be used to assess the adequacy of the FLR volume; whether there is a discrepancy between the FLR volume and function during the recovery period after portal vein embolization or hepatectomy; and how best the function of a specific FLR can be assessed. Various studies concerning these issues have been reported with controversial results. We should also be aware that different strategies and management are required for different types of liver damage, such as cirrhosis in hepatocellular carcinoma, cholangitis in biliary tract cancer, and chemotherapy-induced hepatic injury.

Critical Role of LSEC in Post-Hepatectomy Liver Regeneration and Failure.

Liver sinusoids are lined by liver sinusoidal endothelial cells (LSEC), which represent approximately 15 to 20% of the liver cells, but only 3% of the total liver volume. LSEC have unique functions, such as fluid filtration, blood vessel tone modulation, blood clotting, inflammatory cell recruitment, and metabolite and hormone trafficking. Different subtypes of liver endothelial cells are also known to control liver zonation and hepatocyte function. Here, we have reviewed the origin of LSEC, the different subtypes identified in the liver, as well as their renewal during homeostasis. The liver has the exceptional ability to regenerate from small remnants. The past decades have seen increasing awareness in the role of non-parenchymal cells in liver regeneration despite not being the most represented population. While a lot of knowledge has emerged, clarification is needed regarding the role of LSEC in sensing shear stress and on their participation in the inductive phase of regeneration by priming the hepatocytes and delivering mitogenic factors. It is also unclear if bone marrow-derived LSEC participate in the proliferative phase of liver regeneration. Similarly, data are scarce as to LSEC having a role in the termination phase of the regeneration process. Here, we review what is known about the interaction between LSEC and other liver cells during the different phases of liver regeneration. We next explain extended hepatectomy and small liver transplantation, which lead to "small for size syndrome" (SFSS), a lethal liver failure. SFSS is linked to endothelial denudation, necrosis, and lobular disturbance. Using the knowledge learned from partial hepatectomy studies on LSEC, we expose several techniques that are, or could be, used to avoid the "small for size syndrome" after extended hepatectomy or small liver transplantation.

Markers of liver regeneration-the role of growth factors and cytokines: a systematic review.

BACKGROUND: Post-hepatectomy liver failure contributes significantly to postoperative mortality after liver resection. The prediction of the individual risk for liver failure is challenging. This review aimed to provide an overview of cytokine and growth factor triggered signaling pathways involved in liver regeneration after resection. METHODS: MEDLINE and Cochrane databases were searched without language restrictions for articles from the time of inception of the databases till March 2019. All studies with comparative data on the effect of cytokines and growth factors on liver regeneration in animals and humans were included. RESULTS: Overall 3.353 articles comprising 40 studies involving 1.498 patients and 101 animal studies were identified and met the inclusion criteria. All included trials on humans were retrospective cohort/observational studies. There was substantial heterogeneity across all included studies with respect to the analyzed cytokines and growth factors and the described endpoints. CONCLUSION: High-level evidence on serial measurements of growth factors and cytokines in blood samples used to predict liver regeneration after resection is still lacking. To address the heterogeneity of patients and potential markers, high throughput serial analyses may offer a method to predict an individual's regenerative potential in the future.

An ordinal model to predict the risk of symptomatic liver failure in patients with cirrhosis undergoing hepatectomy.

BACKGROUND & AIMS: Selection criteria for hepatectomy in patients with cirrhosis are controversial. In this study we aimed to build prognostic models of symptomatic post-hepatectomy liver failure (PHLF) in patients with cirrhosis. METHODS: This was a cohort study of patients with histologically proven cirrhosis undergoing hepatectomy in 6 French tertiary care hepato-biliary-pancreatic centres. The primary endpoint was symptomatic (grade B or C) PHLF, according to the International Study Group of Liver Surgery's definition. Twenty-six preoperative and 5 intraoperative variables were considered. An ordered ordinal logistic regression model with proportional odds ratio was used with 3 classes: O/A (No PHLF or grade A PHLF), B (grade B PHLF) and C (grade C PHLF). RESULTS: Of the 343 patients included, the main indication was hepatocellular carcinoma (88%). Laparoscopic liver resection was performed in 112 patients. Three-month mortality was 5.25%. The observed grades of PHLF were: 0/A: 61%, B: 28%, C: 11%. Based on the results of univariate analyses, 3 preoperative variables (platelet count, liver remnant volume ratio and intent-to-treat laparoscopy) were retained in a preoperative model and 2 intraoperative variables (per protocol laparoscopy and intraoperative blood loss) were added to the latter in a postoperative model. The preoperative model estimated the probabilities of PHLF grades with acceptable discrimination (area under the receiver-operating characteristic curve [AUC] 0.73, B/C vs. 0/A; AUC 0.75, C vs. 0/A/B) and the performance of the postoperative model was even better (AUC 0.77, B/C vs. 0/A; AUC 0.81, C vs. 0/A/B; p <0.001). CONCLUSIONS: By accurately predicting the risk of symptomatic PHLF in patients with cirrhosis, the preoperative model should be useful at the selection stage. Prediction can be adjusted at the end of surgery by also considering blood loss and conversion to laparotomy in a postoperative model, which might influence postoperative management. LAY SUMMARY: In patients with liver cirrhosis, the risk of a hepatectomy is difficult to appreciate. We propose a statistical tool to estimate this risk, preoperatively and immediately after surgery, using readily available parameters and on online calculator. This model could help to improve the selection of patients with the best risk-benefit profiles for hepatectomy.