Posthepatectomy Liver Failure Research Articles

Preoperative assessment of liver function and perioperative management of posthepatectomy liver failure

Preoperative assessment of liver function and perioperative management of posthepatectomy liver failure

Non-invasive strategies to predict post-hepatectomy liver failure

Non-invasive strategies to predict post-hepatectomy liver failure

Risk predictors of post-hepatectomy liver failure: unraveling complexities and navigating challenges in clinical application

Risk predictors of post-hepatectomy liver failure: unraveling complexities and navigating challenges in clinical application

A Multicenter Exploration of the APRI/ALBI Score in Associating Liver Partition and Portal Vein Ligation for Staged hepatectomy’ (ALPPS)

Abstract Background Perioperative morbidity and mortality remain a point of concern for the Associating Liver Partition and Portal Vein Ligation for Staged hepatectomy (ALPPS) procedure. Post-hepatectomy liver failure (PHLF) after the second step poses the most significant risk factor for futile outcome. Recovery of liver function after the first step of ALPPS is critically important to allow for sufficient liver function after this surgery. The APRI+ALBI score has been proposed as an easily assessable score to monitor liver function and its dynamic recovery. Aims We explored if the APRI+ALBI score was able to assess liver function recovery after the first step of ALPPS and allow for optimal timing of the 2nd step. Methods Based on the ALPPS registry, patients from 2012 to 2020 with available APRI+ALBI score were included. Postoperative outcomes (PHLF A – C, PHLF B + C, 90-day mortality and severe morbidity) were defined as per standard definitions. The APRI/ALBI score was monitored perioperatively. Results Overall, 464 patients from 16 international participating centers in the ALPPS registry were included. Clinically relevant PHLF (B + C) was observed in 7.5 % and of these 63 % of patients ultimately died due to liver failure. The APRI+ALBI score immediately increased after each surgical intervention and continuously decrease thereafter. Failure of the APRI+ALBI score to decrease until the 2nd step of ALPPS predicted PHLF B+C (p = 0.001; AUC 0.78). Particularly patients with high APRI+ALBI scores and short interstage intervals were at risk to develop PHLF B+C. Conclusion The APRI+ALBI score objectifies liver function recovery after the 1st step of ALPPS and failure to sufficiently decreased is associated with a higher risk for PHLF B+C. This might allow for optimized planning of the 2nd step of ALPPS to allow for sufficient liver function recovery to minimize the risk for PHLF B+C and associated futile outcome.

The Interplay between Perioperative Oxidative Stress and Hepatic Dysfunction after Human Liver Resection: A Prospective Observational Pilot Study.

Post-hepatectomy liver failure (PHLF) remains the major contributor to death after liver resection. Oxidative stress is associated with postoperative complications, but its impact on liver function is unclear. This first in-human, prospective, single-center, observational pilot study evaluated perioperative oxidative stress and PHLF according to the ISGLS (International Study Group for Liver Surgery). Serum 8-isoprostane, 4-hydroxynonenal (4-HNE), total antioxidative capacity, vitamins A and E, and intraoperative, sequential hepatic tissue 4-HNE and UCP2 (uncoupling protein 2) immunohistochemistry (IHC) were assessed. The interaction with known risk factors for PHLF and the predictive potential of oxidative stress markers were analyzed. Overall, 52 patients were included (69.2% major liver resection). Thirteen patients (25%) experienced PHLF, a major factor for 90-day mortality (23% vs. 0%; p = 0.013). Post-resection, pro-oxidative 8-isoprostane significantly increased (p = 0.038), while 4-HNE declined immediately (p < 0.001). Antioxidative markers showed patterns of consumption starting post-resection (p < 0.001). Liver tissue oxidative stress increased stepwise from biopsies taken after laparotomy to post-resection in situ liver and resection specimens (all p < 0.001). Cholangiocarcinoma patients demonstrated significantly higher serum and tissue oxidative stress levels at various timepoints, with consistently higher preoperative values in advanced tumor stages. Combining intraoperative, post-resection 4-HNE serum levels and in situ IHC early predicted PHLF with an AUC of 0.855 (63.6% vs. 0%; p < 0.001). This was also associated with grade B/C PHLF (36.4% vs. 0%; p = 0.021) and 90-day mortality (18.2% vs. 0%; p = 0.036). In conclusion, distinct patterns of perioperative oxidative stress levels occur in patients with liver dysfunction. Combining intraoperative serum and liver tissue markers predicts subsequent PHLF. Cholangiocarcinoma patients demonstrated pronounced systemic and hepatic oxidative stress, with increasing levels in advanced tumor stages, thus representing a worthwhile target for future exploratory and therapeutic studies.

Utility of gadoxetate disodium-enhanced magnetic resonance imaging in evaluating liver failure risk after major hepatic resection.

Post-hepatectomy liver failure (PHLF) is still a predominant cause of hepatectomy-related mortality. However, it is difficult to evaluate the remnant liver functional reserve accurately before surgery to prevent PHLF. In this study, we aimed to explore the role of gadoxetate disodium-enhanced magnetic resonance imaging (MRI) in evaluating remnant liver functional reserve. For this cross-sectional study, the sample retrospectively included 56 patients undergoing liver resections of at least three segments between June 2019 and September 2022 at The General Hospital of the Western Theater Command. Pre-surgery assessments involved liver computer tomography (CT), an indocyanine green (ICG) clearance test, the Child-Pugh scoring system, and liver function serum biochemical indicators. Each patient underwent a gadoxetate disodium-enhanced MRI before the hepatectomy, and we measured the remnant hepatocellular uptake index (rHUI) as well as the standard remnant hepatocellular uptake index (SrHUI). We examined the diagnostic utility of rHUI, SrHUI, indocyanine green retention rate of 15 minutes (ICG R15), and Albumin for PHLF. Receiver operating characteristics (ROC) analyses were used to measure the preoperative liver function parameters (namely, rHUI, SrHUI, ICG R15, and Albumin) for predicting PHLF. The areas under the curve (AUCs) were calculated and compared between different preoperative liver function parameters using the Wilson/Brown method. The Pearson or Spearman correlation coefficient was used for correlation analysis between ICG R15, Albumin, and rHUI and between ICG R15, Albumin, and SrHUI, respectively. Twelve patients (21.43%) had complications of PHLF. We found significant differences in rHUI, SrHUI, ICG R15, and Albumin between the non-PHLF and PHLF groups. The pooled r between ICG R15 and rHUI was -0.591 [95% confidence interval (CI): -0.740 to -0.389, P<0.001], and between ICG R15 and SrHUI was -0.534 (95% CI: -0.703 to -0.308, P<0.001). The area under the curve (AUC) values of rHUI, SrHUI, ICG R15, and Ablumin were 0.871 (sensitivity 81.82%; specificity 91.67%), 0.878 (sensitivity 79.55%; specificity 83.33%), 0.835 (sensitivity 99.73%; specificity 66.67%), and 0.782 (sensitivity 88.64%; specificity 58.33%), respectively. We found that the rHUI and SrHUI calculated using the gadoxetate disodium-enhanced MRI reflected a combination of remnant hepatocyte function and liver volume, and these were useful as a quantitative assessment indicator of remnant liver functional reserve and can be a better predictor of PHLF after major hepatic resection.

Multicenter propensity score-matched analysis to compare perioperative morbidity after laparoscopic or robotic complex hepatectomy for solitary hepatocellular carcinoma

BackgroundPostoperative complications are vital factors affecting the prognosis of patients with hepatocellular carcinoma (HCC), especially for complex hepatectomy. The present study aimed to compare perioperative complications between laparoscopic and robotic complex hepatectomy (LCH vs. RCH). MethodsPatients with solitary HCC after complex hepatectomy were collected from a multicenter database. Propensity score-matched (PSM) analysis was adopted to control confounding bias. Multivariable analysis was performed to determine the prognostic factors. Results436 patients were included. After PSM, 43 patients were included in both the LCH and RCH groups. The results showed that compared to LCH, RCH had lower rates of blood loss and transfusion, and lower postoperative 30-day and major morbidity, and post-hepatectomy liver failure (PHLF) (all P < 0.05). Additionally, the length of hospital stay was shorter in the RCH group (P = 0.026). Multivariable analysis showed RCH is an independent protective factor for reducing the 30-day morbidity, major morbidity and PHLF. ConclusionRCH has advantages over LCH in the minimally invasive treatment of complex HCC, as it can reduce the incidence of intraoperative blood loss and postoperative morbidity, especially for major morbidity and PHLF. Therefore, RCH should be considered for patients with HCC who require complex hepatectomy.

Histological and radiological analysis of simultaneous dual hepatic vein embolization for right-sided major hepatectomy.

Simultaneous dual hepatic vein embolization (DHVE) has been proposed for safe right-sided hepatectomy, with good results for liver hypertrophy and function. However, the histological and radiological findings of DHVE have not been thoroughly investigated. This study included 14 patients who underwent DHVE before right-sided major hepatectomy. DHVE was performed if the future liver remnant was < 35% or borderline, but with concomitant vascular resection. The liver function was assessed using the signal intensity on Gd-EOB-DTPA-MRI. A histological evaluation of the area of DHVE and portal vein embolization (PVE) were performed. The median pre- and post-functional liver remnants were 363ml and 498ml, respectively (p < 0.001). The median growth rate was 48.6%, and there was no post-hepatectomy liver failure in the patients who underwent DHVE. The signal intensity ratio in the area of DHVE was lower than that in the areas of PVE and the remnant liver (p < 0.01). The degree of congestion and necrosis was greater in the area of DHVE than in the area of PVE alone (p < 0.01 and p = 0.04, respectively). We observed good liver hypertrophy after DHVE and histological and radiological changes in the area of DHVE. Our findings provide a compelling rationale for further investigation of the mechanism of liver hypertrophy in DHVE.

Effects of preoperative biliary drainage on the outcomes of surgical treatment in cholangiocarcinoma: A propensity score matching analysis

BackgroundHyperbilirubinemia is known to increase morbidity and mortality in patients undergoing liver resection for cholangiocarcinoma (CCA). Preoperative biliary drainage (PBD) in patients who have no acute cholangitis or require portal vein embolization is still debatable. The goal of this study is to investigate how PBD affects the surgical results after liver resection. MethodsBetween October 2013 and December 2020, CCA patients presenting with obstructive jaundice who underwent liver resection were retrospectively reviewed. The pre-operative, peri-operative and post-operative characteristics were extracted. To compare the outcomes of the PBD and direct surgery groups, propensity score matching analysis (PSM) and multivariable risk regression analysis were used to analyze. ResultsA total of 355 patients were enrolled, with 99 of them undergoing PBD. At diagnosis, those with PBD showed significantly greater bilirubin levels than those without (20.7 vs 9.6 ​mg/dL, p ​< ​0.001). However, after drainage, the bilirubin level in the PBD group was lower than the direct surgery group (5.5 vs 9.6 ​mg/dL, p ​< ​0.001). Overall postoperative morbidity and mortality were unaffected by PBD in full patient cohort. However, after PSM, PBD was associated with decreased major post-hepatectomy liver failure (PHLF) and 90-day mortality rate, (20.3% vs 39.24%, p ​= ​0.014 and 3.8% vs 22.8%, p ​= ​0.001, respectively). At multivariable analysis of PSM patient cohort, PBD was associated with decreased major post-operative complication (RR 0.64, 95%CI 0.419–0.986), PHLF (RR 0.40, 95%CI 0.227–0.705) and 90-day mortality (RR 0.21, 95%CI 0.086–0.629). ConclusionPBD was associated with decreased post-hepatectomy liver failure and postoperative mortality after liver resection in jaundiced CCA patients.

Impact of clinically relevant posthepatectomy liver failure predicted by preoperative evaluation of functional remnant hepatic reserve

Abstract Background: Few studies have investigated the remnant hepatic functional reserve before hepatectomy by calculating the functional remnant liver rate (RLR) using threedimensional computed tomography (3D-CT)/technetium-99m-diethylenetriaminepentaacetic acid galactosyl human serum albumin (99mTc-GSA) single-photon emission CT (SPECT) fusion imaging. We aimed to preoperatively evaluate the predictive value of functional remnant liver rate (RLR) and indocyanine green (ICG) disappearance rate (KICG) in determining the occurrence of posthepatectomy liver failure (PHLF). Summary of Background Data: The conventional method of volumetric rem-KICG calculated from remnant liver volume and the KICG is difficult to accurately reflect heterogenous remnant liver function. Methods: In total, 106 patients who underwent major hepatectomy were retrospectively analysed. Of these, 24 (22.6%) developed clinically relevant PHLF grades B/C. We examined the ICG retention rate at 15 min (ICGR15) and KICG and constructed a 3DCT/ 99mTc-GSA SPECT fusion image to calculate the volumetric RLR, functional RLR, volumetric rem-KICG, and functional rem-KICG. Results: The multivariate analysis showed functional rem-KICG as the strongest independent risk factor for PHLF grade B/C. The functional-to-volumetric RLR ratios in the patients with portal vein obstruction and/or tumor volume of ≥500 mL was significantly higher. The volumetric rem-KICG determined that hepatectomy was unsafe in 7 patients, whereas the functional rem-KICG determined that it was unsafe in 3 patients. Conclusions: Functional rem-KICG was more reliable than volumetric rem-KICG in predicting clinically relevant PHLF grade B/C, as the resected side’s hepatic status highly influenced the function of the remnant liver. This finding could lead to a wider application of this technique.

ALBI score combined with FIB-4 index to predict post-hepatectomy liver failure in patients with hepatocellular carcinoma

Post-hepatectomy liver failure (PHLF) is a potentially life-threatening complication following liver resection. Hepatocellular carcinoma (HCC) often occurs in patients with chronic liver disease, which increases the risk of PHLF. This study aimed to investigate the ability of the combination of liver function and fibrosis markers (ALBI score and FIB-4 index) to predict PHLF in patients with HCC. Patients who underwent hepatectomy for HCC between August 2012 and September 2022 were considered for inclusion. Multivariable logistic regression analysis was used to identify factors associated with PHLF, and ALBI score and FIB-4 index were combined based on their regression coefficients. The performance of the combined ALBI-FIB4 score in predicting PHLF and postoperative mortality was compared with Child–Pugh score, MELD score, ALBI score, and FIB-4 index. A total of 215 patients were enrolled in this study. PHLF occurred in 35 patients (16.3%). The incidence of severe PHLF (grade B and grade C PHLF) was 9.3%. Postoperative 90‐d mortality was 2.8%. ALBI score, FIB-4 index, prothrombin time, and extent of liver resection were identified as independent factors for predicting PHLF. The AUC of the ALBI-FIB4 score in predicting PHLF was 0.783(95%CI: 0.694–0.872), higher than other models. The ALBI-FIB4 score could divide patients into two risk groups based on a cut-off value of − 1.82. High-risk patients had a high incidence of PHLF of 39.1%, while PHLF just occurred in 6.6% of low-risk patients. Similarly, the AUCs of the ALBI-FIB4 score in predicting severe PHLF and postoperative 90-d mortality were also higher than other models. Preoperative ALBI-FIB4 score showed good performance in predicting PHLF and postoperative mortality in patients undergoing hepatectomy for HCC, superior to the currently commonly used liver function and fibrosis scoring systems.

Sarcopenia does not affect liver regeneration and postoperative course after a major hepatectomy. A prospective study on 125 patients using CT volumetry and HIDA scintigraphy

Background & objectivesSarcopenia 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. MethodsFrom 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. ResultsSarcopenic 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_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. ConclusionThis 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.

A combined pre- and intra-operative nomogram in evaluation of degrees of liver cirrhosis predicts post-hepatectomy liver failure: a multicenter prospective study.

Adequate evaluation of degrees of liver cirrhosis is essential in surgical treatment of hepatocellular carcinoma (HCC) patients. The impact of the degrees of cirrhosis on prediction of post-hepatectomy liver failure (PHLF) remains poorly defined. This study aimed to construct and validate a combined pre- and intra-operative nomogram based on the degrees of cirrhosis in predicting PHLF in HCC patients using prospective multi-center's data. Consecutive HCC patients who underwent hepatectomy between May 18, 2019 and Dec 19, 2020 were enrolled at five tertiary hospitals. Preoperative cirrhotic severity scoring (CSS) and intra-operative direct liver stiffness measurement (DSM) were performed to correlate with the Laennec histopathological grading system. The performances of the pre-operative nomogram and combined pre- and intra-operative nomogram in predicting PHLF were compared with conventional predictive models of PHLF. For 327 patients in this study, histopathological studies showed the rates of HCC patients with no, mild, moderate, and severe cirrhosis were 41.9%, 29.1%, 22.9%, and 6.1%, respectively. Either CSS or DSM was closely correlated with histopathological stages of cirrhosis. Thirty-three (10.1%) patients developed PHLF. The 30- and 90-day mortality rates were 0.9%. Multivariate regression analysis showed four pre-operative variables [HBV-DNA level, ICG-R15, prothrombin time (PT), and CSS], and one intra-operative variable (DSM) to be independent risk factors of PHLF. The pre-operative nomogram was constructed based on these four pre-operative variables together with total bilirubin. The combined pre- and intra-operative nomogram was constructed by adding the intra-operative DSM. The pre-operative nomogram was better than the conventional models in predicting PHLF. The prediction was further improved with the combined pre- and intra-operative nomogram. The combined pre- and intra-operative nomogram further improved prediction of PHLF when compared with the pre-operative nomogram. Clinicaltrials.gov Identifier: NCT04076631.

An Efficient Saline-Linked Cautery (SLiC) Method for Robotic Liver Parenchymal Transection Using Simultaneous Activation of Saline-Linked Cautery and Robotic Suctioning: Detailed Technical Aspects and Short-Term Outcomes.

Introduction While there are several advantages to utilizing robotics in liver surgery compared to traditional open and laparoscopic approaches, the most challenging part of robotic liver resection (RLR) remains the liver parenchymal transection. This is primarily due to the constraints of the existing robotic tools and the absence of a standard procedure. This study presents detailed technical aspects of our novel saline-linked cautery (SLiC) method for RLR and assesses the short-term outcomes for both non-anatomical and anatomical RLRs. Methods In this study, 82 cases that underwent RLR utilizing the SLiC method at our hospital from September 2021 to December 2023 were examined. A novel SLiC method is introduced in this study for robotically transecting the liver parenchyma utilizing bipolar cautery or monopolar scissors. The technique involves activating the SLiC and robotic suctioning simultaneously. The included patients were divided into two groups: patients undergoing robotic anatomical hepatectomy (n=39), and those receiving robotic non-anatomical hepatectomy (n=43). Short-term outcomes, including intraoperative and postoperative complications, were assessed in patients receiving both anatomical and non-anatomical hepatectomies. Results In the whole cohort, 74% of patients had performance status 1 or 2, and 24% were classified as Child-Pugh class B. RLR was performed without Pringle's maneuver in more than 80% of cases in patients receiving robotic non-anatomical hepatectomy, and more than 80% of patients undergoing robotic anatomical hepatectomy required only four or fewer 15-minute Pringle's maneuvers. There was no conversion to open hepatectomy, no cases of grade B or C post-hepatectomy liver failure, and no mortality in the entire cohort. Four postoperative complications with CDC IIIa or higher occurred (small bowel obstruction in two cases, intraabdominal hemorrhage in one, and bile leak in another), but no differences in the frequency of complications were found between those undergoing non-anatomical and anatomical hepatectomy (p=0.342). Conclusions The SLiC method, which involves simultaneously activating SLiC and robotic suctioning with either monopolar scissors or bipolar cautery, appears to be a secure and convenient technique for liver parenchymal transection in RLR. This innovative method permits precise access to the major Glissonean and venous structures within the liver, making RLR more standardized and easily applicable in routine patient care.

Effect of early peri-operative arterial lactate concentration level ratios on post-hepatectomy liver failure

BackgroundPost-hepatectomy liver failure (PHLF) is a serious complication after hepatectomy and a major cause of death. The current criteria for PHLF diagnosis (ISGLS consensus) require laboratory data of elevated INR level and hyperbilirubinemia on or after postoperative day 5. This study aims to propose a new indicator for the early clinical prediction of PHLF.MethodsThe peri-operative arterial lactate concentration level ratios were derived from time points within the 3 days before surgery and within POD1, the patients were divided into two groups: high lactate ratio group (≥ 1) and low lactate ratio group (< 1). We compared the differences in morbidity rates between the two groups. Utilized logistic regression analysis to identify the risk factors associated with PHLF development and ROC curves to compare the predictive value of lactate ratio and other liver function indicators for PHLF.ResultsA total of 203 patients were enrolled in the study. Overall morbidity and severe morbidity occurred in 64.5 and 12.8 per cent of patients respectively. 39 patients (19.2%) met the criteria for PHLF, including 15 patients (7.4%) with clinically relevant Post-hepatectomy liver failure (CR-PHLF). With a significantly higher incidence of PHLF observed in the lactate ratio ≥ 1 group compared to the lactate ratio < 1 group (n = 34, 26.8% vs. n = 5, 6.6%, P < 0.001). Multivariable logistic regression analysis revealed that a lactate ratio ≥ 1 was an independent predictor for PHLF (OR: 3.239, 95% CI 1.097–9.565, P = 0.033). Additionally, lactate ratio demonstrated good predictive efficacy for PHLF (AUC = 0.792).ConclusionsEarly assessment of peri-operative arterial lactate concentration level ratios may provide experience in early intervention of complications in patients with hepatocellular carcinoma, which can reduce the likelihood of PHLF occurrence and improve patient prognosis.

Clinician overconfidence in visual estimation of the posthepatectomy liver remnant volume: A proximal source of liver failure after major hepatic resection?

BackgroundPost-hepatectomy liver failure is a source of morbidity and mortality after major hepatectomy and is related to the volume of the future liver remnant. The accuracy of a clinician’s ability to visually estimate the future liver remnant without formal computed tomography liver volumetry is unknown. MethodsTwenty physicians in diagnostic radiology, interventional radiology, and hepatopancreatobiliary surgery reviewed 20 computed tomography scans of patients without underlying liver pathology who were not scheduled for liver resection. We evaluated clinician accuracy to estimate the future liver remnant for 3 hypothetical major hepatic resections: left hepatectomy, right hepatectomy, and right trisectionectomy. The percent-difference between the mean and actual computed tomography liver volumetry (mean percent difference) was tested along with specialty differences using mixed-effects regression analysis. ResultsThe actual future liver remnant (computed tomography liver volumetry) remaining after a hypothetical left hepatectomy ranged from 59% to 75% (physician estimated range: 50%–85%), 23% to 40% right hepatectomy (15%–50%), and 13% to 29% right trisectionectomy (8%–39%). For right hepatectomy, the mean future liver remnant was overestimated by 95% of clinicians with a mean percent difference of 22% (6%–45%; P < .001). For right trisectionectomy, 90% overestimated the future liver remnant by a mean percent difference of 25% (6%–50%; P < .001). Hepatopancreatobiliary surgeons overestimated the future liver remnant for proposed right hepatectomy and right trisectionectomy by a mean percent difference of 25% and 34%, respectively. Based on years of experience, providers with <10 years of experience had a greater mean percent difference than providers with 10+ years of experience for hypothetical major hepatic resections, but was only significantly higher for left hepatectomy (9% vs 6%, P = .002). ConclusionA clinician’s ability to visually estimate the future liver remnant volume is inaccurate when compared to computed tomography liver volumetry. Clinicians tend to overestimate the future liver remnant volume, especially in patients with a small future liver remnant where the risk of posthepatectomy liver failure is greatest.

Preclinical efficacy and safety of encapsulated proliferating human hepatocyte organoids in treating liver failure

Alginate-encapsulated hepatocyte transplantation is a promising strategy to treat liver failure. However, its clinical application was impeded by the lack of primary human hepatocytes and difficulty in controlling their quality. We previously reported proliferating human hepatocytes (ProliHHs). Here, quality-controlled ProliHHs were produced in mass and engineered as liver organoids to improve their maturity. Encapsulated ProliHHs liver organoids (eLO) were intraperitoneally transplanted to treat liver failure animals. Notably, eLO treatment increased the survival of mice with post-hepatectomy liver failure (PHLF) and ameliorated hyperammonemia and hypoglycemia by providing liver functions. Additionally, eLO treatment protected the gut from PHLF-augmented permeability and normalized the increased serum endotoxin and inflammatory response, which facilitated liver regeneration. The therapeutic effect of eLO was additionally proved in acetaminophen-induced liver failure. Furthermore, we performed assessments of toxicity and biodistribution, demonstrating that eLO had no adverse effects on animals and remained non-tumorigenic.

Pathobiochemical Features of Posthepatectomy Liver Failure and Prospects for Its Metabolic Correction

We review the current understanding of pathophysiology and pathobiochemistry of conditions following extensive resections of the liver parenchyma and describe potential ways of surgical and metabolic correction, including promising molecular targets for therapy. Reduced residual tissue volume (small-for-size syndrome), parenchymal edema due to hyperperfusion and impaired venous blood outflow, septic complications, organ ischemia-reperfusion, mitochondrial dysfunction, and oxidative stress are considered key pathogenetic factors in liver failure development following extensive resections of the liver parenchyma. Given the above, promising ways of managing posthepatectomy conditions are the use of agents reducing portal pressure (octreotide [somatostatin analogue], terlipressin [vasopressin analogue], and propranolol), energotropic metabolic drugs (combined preparations of succinate and antioxidants, gasotransmitter donors), and antibiotics and synbiotics for prevention of infectious complications. The approaches currently used in clinical practice cannot always effectively manage complications following extensive hepatectomy, so fundamental research should focus on searching and creating effective strategies for prevention and therapy of posthepatectomy liver failure.

Change of indocyanine green clearance ability and liver function after transcatheter intra-arterial therapies and its impact on outcomes of resectable hepatocellular carcinoma: a retrospective cohort study.

Indocyanine green (ICG) clearance test is a classical measurement of hepatic reserve, which involves surgical safety and patient recovery of hepatocellular carcinoma (HCC). The authors aim to compare effects of hepatic arterial infusion chemotherapy (HAIC) and transcatheter arterial chemoembolization (TACE) on liver function and outcomes of subsequent hepatectomy. HCC patients receiving HAIC/TACE in SYSUCC with repeated ICG clearance tests were retrospectively enrolled. ICG eliminating rate (ICG-K), ICG retention rate at 15 min (ICG-R15) and ordinary laboratory tests were collected. Peri-therapeutic changes of values were compared between the groups. Propensity score matching (PSM) and inverse probability of treatment weighing (IPTW) were employed to validate findings. Post-hepatectomy liver failure (PHLF), overall survival (OS) and recurrence-free survival (RFS) were analyzed in patients with subsequent curative hepatectomy. Two hundred and four patients treated with HAIC ( n =130) and TACE ( n =74) were included. ΔICG-R15 was greater in the HAIC arm before matching (mean, 3.8% vs. 0.7%, P <0.001), after PSM (mean, 4.7% vs. 1.1%, P =0.014) and IPTW (mean, 2.0% vs. -3.6%, P <0.001). No difference was found for ΔALB, ΔALBI, ΔTBIL, ΔALT, ΔAST and ΔPT-INR. Multivariable analyses revealed elder age, cirrhosis, HAIC, greater ΔTBIL and ΔALBI were associated with deteriorating ICG-R15. Among those (105 for HAIC and 48 for TACE) receiving hepatectomy, occurrence of grade B/C PHLF (4.8% vs. 8.3%, P =0.616), OS (median, unreached vs. unreached, P =0.94) and RFS (median, 26.7 vs. 17.1months, P =0.096) were comparable between the two arms. In subgroup analyses, preoperative HAIC yield superior RFS (median, 26.7 vs. 16.2months, P =0.042) in patients with baseline ICG-R15 less than or equal to 10%. Preoperative FOLFOX-HAIC caused apparent impairment of ICG clearance ability than TACE yet comparable impact on liver function and post-hepatectomy outcomes.

Results of robotic liver surgery in association with IWATE criteria — the first 100 cases

BackgroundAim of the current study was to present the results of the implementation phase of a robotic liver surgery program and to assess the validity of the IWATE difficulty score in predicting difficulty and postoperative complications in robotic liver surgery.MethodsBased on the prospective database of the Interdisciplinary Robotic Center of Ulm University Hospital, the first 100 robotic liver surgeries were identified and analyzed. Perioperative parameters (duration of surgery and blood loss) and postoperative parameters including morbidity, mortality, and length of hospital stay were assessed and the results were compared between different IWATE difficulty categories.ResultsFrom November 2020 until January 2023, 100 robotic liver surgeries were performed (41 female, 59 male; median age 60.6 years, median BMI 25.9 kg/m2). Median duration of surgery was 180 min (IQR: 128.7), and median blood loss was 300 ml (IQR: 550). Ninety-day mortality was 2%, and overall morbidity was 21%, with major complications occurring in 13% of patients (≥ grade 3 according to Clavien/Dindo). A clinically relevant postoperative biliary leakage was observed in 3 patients. Posthepatectomy liver failure occurred in 7% (4 Grade A, 3 Grade B). Duration of surgery (p < 0.001), blood loss (p < 0.001), CCI (p = 0.004), overall morbidity (p = 0.004), and length of hospital stay (p < 0.001) were significantly increased in the IWATE ‘expert’ category compared to lower categories.DiscussionRobotic surgery offers a minimally invasive approach for liver surgery with favorable clinical outcomes, even in the implementation phase. In the current study the IWATE difficulty score had the ability to predict both difficulty of surgery as well as postoperative outcomes when assessing the complexity of robotic liver surgery. Therefore, the role of the IWATE score in predicting these outcomes highlights its importance as a tool in surgical planning and decision-making.