First-in-class MKK4 inhibitors enhance liver regeneration and prevent liver failure.

Diminished hepatocyte regeneration is a key feature of acute and chronic liver diseases and after extended liver resections, resulting in the inability to maintain or restore a sufficient functional liver mass. Therapies to restore hepatocyte regeneration are lacking, making liver transplantation the only curative option for end-stage liver disease. Here, we report on the structure-based development and characterization (nuclear magnetic resonance [NMR] spectroscopy) of first-in-class small molecule inhibitors of the dual-specificity kinase MKK4 (MKK4i). MKK4i increased liver regeneration upon hepatectomy in murine and porcine models, allowed for survival of pigs in a lethal 85% hepatectomy model, and showed antisteatotic and antifibrotic effects in liver disease mouse models. A first-in-human phase I trial (European Union Drug Regulating Authorities Clinical Trials [EudraCT] 2021-000193-28) with the clinical candidate HRX215 was conducted and revealed excellent safety and pharmacokinetics. Clinical trials to probe HRX215 for prevention/treatment of liver failure after extensive oncological liver resections or after transplantation of small grafts are warranted.

Rapid Self-Assembly Mini-Livers Protect Mice Against Severe Hepatectomy-Induced Liver Failure.

The construction of bioartificial livers, such as liver organoids, offers significant promise for disease modeling, drug development, and regenerative medicine. However, existing methods for generating liver organoids have limitations, including lengthy and complex processes (taking 6-8 weeks or longer), safety concerns associated with pluripotency, limited functionality of pluripotent stem cell-derived hepatocytes, and small, highly variable sizes (typically ≈50-500 µm in diameter). Prolonged culture also leads to the formation of necrotic cores, further restricting size and function. In this study, a straightforward and time-efficient approach is developed for creating rapid self-assembly mini-livers (RSALs) within 12 h. Additionally, primary hepatocytes are significantly expanded in vitro for use as seeding cells. RSALs exhibit consistent larger sizes (5.5 mm in diameter), improved cell viability (99%), and enhanced liver functionality. Notably, RSALs are functionally vascularized within 2 weeks post-transplantation into the mesentery of mice. These authentic hepatocyte-based RSALs effectively protect mice from 90%-hepatectomy-induced liver failure, demonstrating the potential of bioartificial liver-based therapy.

Liver remnant volume to body weight ratio of 0.65% as a lower limit in right hepatic trisectionectomy with bile duct resection.

BACKGROUND: Previous studies have suggested the utility of an indocyanine green plasma clearance rate of the future liver remnant (FLR) (ICGK-F) ≥0.05 in hepatobiliary resection to reduce the surgical risk. The present study aimed to verify whether future liver remnant size rather than ICGK-F matters in extended hepatobiliary resection. METHODS: Between 2004 and 2021, patients who underwent right hepatic trisectionectomy with bile duct resection were included. The effect of the FLR volume-to-body weight ratio (FLR/BW) and ICGK-F on posthepatectomy liver failure was evaluated along with other parameters. RESULTS: Among 91 study patients, the median ICGK-F, FLR, and FLR/BW were 0.057 (range, 0.027-0.099), 392 mL (145-705), and 0.78% (0.40-1.37), respectively. Posthepatectomy liver failure occurred in 23 patients. The incidence was 10 (40%) in 25 patients with an ICGK-F <0.05 and 12 (18%) in 65 patients with an ICGK-F ≥0.05 (P = .053); 13 (52%) in 25 patients with a FLR/BW <0.65% and 10 (15%) in 66 patients with a FLR/BW ≥0.65% (P = .001). Multivariate analysis showed that a FLR/BW <0.65% (odds ratio, 11.7; P = .005), age ≥65 years (odds ratio, 31.7; P < .001), and blood loss ≥25 mL/kg (odds ratio, 22.1; P = .004) were independent predictors of posthepatectomy liver failure, but ICGK-F <0.05 was not (P = .499). According to the meeting number of 3 factors, posthepatectomy liver failure incidence was 0 of 22 (0%) in patients with 0 factors, 6 of 43 (14%) in patients with 1, and 17 of 26 (65%) in patients with 2 or 3 (P < .001). CONCLUSION: A FLR/BW ≥0.65% may serve as a volumetric basis to reduce posthepatectomy liver failure after extended hepatobiliary resection.

Postoperative Liver Failure: Definitions, Risk factors, Prediction Models and Prevention Strategies.

BACKGROUND: Liver resection is the treatment for a variety of benign and malignant conditions. Despite advances in preoperative selection, surgical technique, and perioperative management, post hepatectomy liver failure (PHLF) is still a leading cause of morbidity and mortality following liver resection. METHODS: A review of the literature was performed utilizing MEDLINE/PubMed and Web of Science databases in May of 2023. The MESH terms "liver failure," "liver insufficiency," and "hepatic failure" in combination with "liver surgery," "liver resection," and "hepatectomy" were searched in the title and/or abstract. The references of relevant articles were reviewed to identify additional eligible publications. RESULTS: PHLF can have devastating physiological consequences. In general, risk factors can be categorized as patient-related, primary liver function-related, or perioperative factors. Currently, no effective treatment options are available and the management of PHLF is largely supportive. Therefore, identifying risk factors and preventative strategies for PHLF is paramount. Ensuring an adequate future liver remnant is important to mitigate risk of PHLF. Dynamic liver function tests provide more objective assessment of liver function based on the metabolic capacity of the liver and have the advantage of easy administration, low cost, and easy reproducibility. CONCLUSION: Given the absence of randomized data specifically related to the management of PHLF, current strategies are based on the principles of management of acute liver failure from any cause. In addition, goal-directed therapy for organ dysfunction, as well as identification and treatment of reversible factors in the postoperative period are critical.

Impact of the Prolonged Intermittent Pringle Maneuver on Post-Hepatectomy Liver Failure: Comparison of Open and Laparoscopic Approaches.

BACKGROUND: The influence of prolonged intermittent Pringle maneuver (IPM) on post-hepatectomy liver failure (PHLF) remains unclear. We evaluated the impact of the prolonged IPM on PHLF in patients undergoing open and laparoscopic hepatectomy. METHODS: We retrospectively included 546 patients who underwent hepatectomy using IPM. The patients were divided into open (n = 294) and laparoscopic (n = 252) groups. Odds ratios for PHLF occurrence were estimated in each group according to cumulative Pringle time (CPT). The cut-off value was set at CPT of 120 min. Risk factors for PHLF were evaluated in the open and laparoscopic groups. Additionally, we analyzed the post-operative outcomes in the open and laparoscopic groups with CPT ≥ 120 min and performed propensity score matching analysis based on PFLF-associated factors. RESULTS: In the open group, the risk of PHLF increased as CPT increased, particularly after 120 min. However, in the laparoscopic group, PHLF did not occur at less than 60 min, and the risk of PHLF was not significantly different at more than 60 min. Multivariate analysis identified CPT ≥ 120 min as an independent risk factor for PHLF in the open group (p < 0.001), but not in the laparoscopic group. Propensity score matching analysis showed that the PHLF rate was significantly lower in the laparoscopic group with CPT ≥ 120 min (p = 0.027). The post-operative transaminase levels were significantly lower in the laparoscopic group with CPT ≥ 120 min. CONCLUSIONS: Laparoscopic hepatectomy may cause less PHLF with prolonged IPM compared with open hepatectomy.

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.

Evolution of care in cirrhosis: Preventing hepatic decompensation through pharmacotherapy.

Cirrhosis is a leading cause of morbidity and mortality, impacting more than 120 million people worldwide. Although geographic differences exist, etiologic factors such as alcohol use disorder, chronic viral hepatitis infections, and non-alcoholic fatty liver disease are prevalent in nearly every region. Historically, significant effort has been devoted to modifying these risks to prevent disease progression. Nevertheless, more than 11% of patients with compensated cirrhosis experience hepatic decompensation each year. This transition signifies the most important prognostic factor in the natural history of the disease, corresponding to a decline in median survival to below 2 years. Over the past decade, the need for pharmacotherapies aimed at reducing the risk for hepatic decompensation has been emphasized, and non-selective beta-blockers have emerged as the most effective option to date. However, a critical therapeutic gap still exists, and additional therapies have been proposed, including statins, rifaximin, and sodium-glucose cotransporter-2 inhibitors. Based on the results of innovative retrospective analyses and small-scale prospective trials, these pharmacotherapies represent promising options, but further studies, including randomized controlled trials, are necessary before they can be incorporated into clinical use. This report highlights the potential impact of these agents and others in preventing hepatic decompensation and discusses how this paradigm shift may pave the way for guideline-directed medical therapy in cirrhosis.

Post-hepatectomy liver failure prediction and prevention: Development of a nomogram containing postoperative anticoagulants as a risk factor.

INTRODUCTION AND OBJECTIVES: Posthepatectomy liver failure (PHLF) is a serious complication after hepatectomy, and its effective methods for preoperative prediction are lacking. Here, we aim to identify predictive factors and build a nomogram to evaluate patients' risk of developing PHLF. PATIENTS AND METHODS: A retrospective review of a training cohort, including 199 patients who underwent hepatectomy at the Shanghai Eastern Hepatobiliary Surgery Hospital, was conducted. Independent risk variables for PHLF were identified using multivariate analysis of perioperative variables, and a nomogram was used to build a predictive model. To test the predictive power, a prospective study in which a validation cohort of 71 patients was evaluated using the nomogram. The prognostic value of this nomogram was evaluated by the C-index. RESULTS: Independent risk variables for PHLF were identified from perioperative variables. In multivariate analysis of the training cohort, tumor number, Pringle maneuver, blood loss, preoperative platelet count, postoperative ascites and use of anticoagulant medications were determined to be key risk factors for the development of PHLF, and they were selected for inclusion in our nomogram. The nomogram showed a 0.911 C-index for the training cohort. In the validation cohort, the nomogram also showed good prognostic value for predicting PHLF. The validation cohort was used with similarly successful results to evaluate risk in two previously published study models with calculated C-indexes of 0.718 and 0.711. CONCLUSION: Our study establishes for the first time a novel nomogram that can be used to identify patients at risk of developing PHLF.

Sarcopenia influences the kinetic growth rate after ALPPS.

BACKGROUND: Associating liver partition and portal vein ligation for staged hepatectomy induces rapid and effective hypertrophy of the future liver remnant to prevent postoperative liver failure. The aim of this study was to determine cofactors, including sarcopenia, influencing the kinetic growth rate, and subsequently future liver remnant, in terms of safety, complications, and posthepatectomy liver failure. METHOD: Patients undergoing associating liver partition and portal vein ligation for staged hepatectomy between 2010 and 2020 were included in this study. Kinetic growth rate was defined as the quotient of the degree of hypertrophy and the time interval between the 2 steps. The sarcopenia muscle index was defined as the skeletal muscle area of both psoas major muscles normalized to the patient's height. RESULTS: During the study period, 90 patients underwent associating liver partition and portal vein ligation for staged hepatectomy. The association between kinetic growth rate and posthepatectomy liver failure indicates a significant nonlinear effect (P = .02). The incidence of posthepatectomy liver failure significantly increased at a kinetic growth rate below 7% per week (31%) compared to patients with a kinetic growth rate >7%/wk (7%, P = .02). In patients with a low kinetic growth rate (<7%/wk), the sarcopenia muscle index was significantly lower compared to patients with a high kinetic growth rate (>7%/wk). Furthermore, a low sarcopenia muscle index and a high body mass index turned out to be independent risk factors for a low kinetic growth rate. CONCLUSION: After the first step of the associating liver partition and portal vein ligation for staged hepatectomy procedure, a low kinetic growth rate (<7%/wk) increases the risk of posthepatectomy liver failure. The presence of a low sarcopenia muscle index and a high body mass index are profoundly correlated with clinically substantial impaired liver regeneration, which can result in increased liver dysfunction after associating liver partition and portal vein ligation for staged hepatectomy.

Effect of postoperative administration of nafamostat mesilate on posthepatectomy liver failure.

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

Differences in the safety line of the future liver remnant plasma clearance rate of indocyanine green necessary to prevent post-hepatectomy liver failure associated with underlying diseases.

PURPOSE: To evaluate differences in the safety line of the future liver remnant plasma clearance rate of indocyanine green (RemK) necessary to prevent posthepatectomy liver failure (PHLF) associated with liver tumors and comorbidities. METHODS: The subjects of this retrospective study were patients who underwent trisectionectomy, hemihepatectomy, or sectionectomy, other than left lateral sectionectomy, between 2011 and 2018, at the Shizuoka Cancer Center. We analyzed the risk factors for PHLF grades B and C and then evaluated the RemK in these groups, according to various risk factors. RESULTS: A total of 463 patients were selected for the analyses. Among the patients with PHLF grades B and C, those with diabetes mellitus (DM), liver cirrhosis (LC), or hepatocellular carcinoma (HCC) had significantly higher RemK than those without these diseases. Multivariate analysis identified RemK ≤ 0.078, DM, and creatinine clearance rate < 60 mL/min as independent risk factors for PHLF grades B and C. CONCLUSIONS: Hepatectomy for patients with DM, HCC, or LC requires more functional hepatic reserve than that evaluated by RemK.

Rescue Partial ALPPS for Left Hemihepatectomy with Reconstruction of the Middle Hepatic Vein.

Major hepatectomy in patients with insufficient future liver remnant (FLR) volume and impaired liver functional reserve has considerable risks for posthepatectomy liver failure (PHLF). The patient was a male in his 70s with an intrahepatic cholangiocarcinoma in left hemiliver, involving the middle hepatic vein (MHV). Although FLR volume after left hemihepatectomy was estimated to be 64.4% of the total liver volume, an indocyanine green retention rate at 15 min (ICG-R15) value was 24.2%, thus the patient underwent left portal vein embolization. The FLR volume increased to 71.3%; however, the noncongestive FLR volume was re-estimated as 45.8% after resection of the MHV, the ICG-R15 value was 29.0%, and ICG-Krem was calculated as 0.037. We performed partial rescue Associating Liver Partition and Portal vein occlusion for Staged hepatectomy (ALPPS) for left hemihepatectomy with the MHV reconstruction. On the first stage, partial liver partition was done along Rex-Cantlie's line, preserving the MHV and sacrificing the remaining branches to segment 8. The FLR volume increased to 77.4% on day 14. The ICG-R15 value was 29.6%, but ICG-Krem after MHV reconstruction was estimated to be 0.059. The second-stage operation on day 21 was left hemihepatectomy with the MHV reconstruction using the left superficial femoral vein graft. The usage of rescue partial ALPPS may contribute to preventing PHLF by introducing occlusion of the portal and/or venous branches in the left hemiliver before curative hepatectomy.

Statin therapy in chronic viral hepatitis: a systematic review and meta-analysis of nine studies with 195,602 participants.

BACKGROUND: Conflicting data suggest that statins could cause chronic liver disease in certain group of patients, while improving prognosis in those with chronic viral hepatitis (CVH). PURPOSE: To quantify the potential protective role of statins on some main liver-related health outcomes in clinical studies on CVH patients.Data Sources: The search strategy was explored by a medical librarian using bibliographic databases, from January 2015 to April 2020.Data synthesis: The results showed no significant difference in the risk of mortality between statin users and non-users in the overall analysis. However, the risk of mortality significantly reduced by 39% in statin users who were followed for more than three years. Moreover, the risk of HCC, fibrosis, and cirrhosis in those on statins decreased by 53%, 45% and 41%, respectively. Although ALT and AST reduced slightly following statin therapy, this reduction was not statistically significant. LIMITATIONS: A significant heterogeneity among studies was observed, resulting from differences in clinical characteristics between statin users and non-users, study designs, population samples, diseases stage, comorbidities, and confounding covariates. CONCLUSION: Not only long-term treatment with statins seems to be safe in patients affected by hepatitis, but also it significantly improves their prognosis.

Liver resection for perihilar cholangiocarcinoma: Impact of biliary drainage failure on postoperative outcome. Results of an Italian multicenter study.

BACKGROUND: Preoperative biliary drainage may be essential to reduce the risk of postoperative liver failure after hepatectomy for perihilar cholangiocarcinoma. However, infectious complications related to preoperative biliary drainage may increase the risk of postoperative mortality. The strategy and optimal drainage method continues to be controversial. METHODS: This is a retrospective multicenter study including patients who underwent hepatectomy for perihilar cholangiocarcinoma between 2000 and 2016 at 14 Italian referral hepatobiliary centers. The primary end point was to evaluate independent predictors for postoperative outcome in patients undergoing liver resection for perihilar cholangiocarcinoma after preoperative biliary drainage. RESULTS: Of the 639 enrolled patients, 441 (69.0%) underwent preoperative biliary drainage. Postoperative mortality was 8.9% (12.5% after right-side hepatectomy versus 5.7% after left-side hepatectomy; P = .003). Of the patients, 40.5% underwent preoperative biliary drainage at the first admitting hospital, before evaluation at referral centers. Use of percutaneous preoperative biliary drainage was significantly more frequent at referral centers than at community hospitals where endoscopic preoperative biliary drainage was the most frequent type. The overall failure rate after preoperative biliary drainage was 43.3%, significantly higher at community hospitals than that at referral centers (52.7% v 36.9%; P = .002). Failure of the first preoperative biliary drainage was one of the strongest predictors for postoperative complications after right-side and left-side hepatectomies and for mortality after right-side hepatectomy. Type of preoperative biliary drainage (percutaneous versus endoscopic) was not associated with significantly different risk of mortality. CONCLUSION: Failure of preoperative biliary drainage was significantly more frequent at community hospitals and it was an independent predictor for postoperative outcome. Centers' experience in preoperative biliary drainage management is crucial to reduce the risk of failure that is closely associated with postoperative morbidity and mortality.

A novel model for predicting posthepatectomy liver failure based on liver function and degree of liver resection in patients with hepatocellular carcinoma.

BACKGROUND: The permissible liver resection rate for preventing posthepatectomy liver failure (PHLF) remains unclear. We aimed to develop a novel PHLF-predicting model and to strategize hepatectomy for hepatocellular carcinoma (HCC). METHODS: This retrospective study included 335 HCC patients who underwent anatomical hepatectomy at eight institutions between 2013 and 2017. Risk factors, including volume-associated liver-estimating parameters, for PHLF grade B-C were analyzed in a training set (n = 122) via multivariate analysis, and a PHLF prediction model was developed. The utility of the model was evaluated in a validation set (n = 213). RESULTS: Our model was based on the three independent risk factors for PHLF identified in the training set: volume-associated indocyanine green retention rate at 15 min, platelet count, and prothrombin time index (the VIPP score). The areas under the receiver operating characteristic curve of the VIPP scores for severe PHLF in the training and validation sets were 0.864 and 0.794, respectively. In both sets, the VIPP score stratified patients at risk for severe PHLF, with a score of 3 (specificity, 0.92) indicating higher risk. CONCLUSION: Our model facilitates the selection of the appropriate hepatectomy procedure by providing permissible liver resection rates based on VIPP scores.

Post hepatectomy liver failure (PHLF) - Recent advances in prevention and clinical management.

BACKGROUND: Posthepatectomy liver failure (PHLF) is a relatively rare but feared complication following liver surgery, and associated with high morbidity, mortality and cost implications. Significant advances have been made in detailed preoperative assessment, particularly of the liver function in an attempt to predict and mitigate this complication. METHODS: A detailed search of PubMed and Medline was performed using keywords "liver failure", "liver insufficiency", "liver resection", "postoperative", and "post-hepatectomy". Only full texts published in English were considered. Particular emphasis was placed on literature published after 2015. A formal systematic review was not found feasible hence a pragmatic review was performed. RESULTS: The reported incidence of PHLF varies widely in reported literature due to a historical absence of a universal definition. Incorporation of the now accepted definition and grading of PHLF would suggest the incidence to be between 8 and 12%. Major risk factors include background liver disease, extent of resection and intraoperative course. The vast majority of mortality associated with PHLF is related to sepsis, organ failure and cerebral events. Despite multiple attempts, there has been little progress in the definitive and specific management of liver failure. This review article discusses recent advances made in detailed preoperative evaluation of liver function and evidence-based targeted approach to managing PHLF. CONCLUSION: PHLF remains a major cause of mortality following liver resection. In absence of a specific remedy, the best approach is mitigating the risk of it happening by detailed assessment of liver function, patient selection and general care of a critically ill patient.

Successful management to prevent early graft loss due to Seventh-day Syndrome after liver retransplantation: A case report and literature review.

Graft loss characterized by sudden deterioration after initial favorable recovery of the allograft function within the first week after liver transplantation was reported as "seventh-day syndrome." The outcome of seventh-day syndrome is extremely poor, and its etiology and management are not still established. We herein reported a seventh-day syndrome case who was successfully managed by immediate desensitization after liver retransplantation and reviewed by English literature. A 19-year-old woman who had underwent the first liver transplantation when she was 2-year-old. She developed graft failure due to chronic rejection and was on the waiting list for retransplantation. An evaluation of panel-reactive antibody showed high positivity, but there were no preformed donor-specific antibodies. Plasma exchange was performed one-time just before retransplantation and the mean fluorescence intensity significantly decreased. The second liver was successfully transplanted, and post-operative course was uneventful. However, on post-operative day 5, her body temperature elevated and thereafter, her liver enzymes dramatically elevated. We immediately started a desensitization consisted of plasma exchange, intravenous immunoglobulin, and anti-CD20 antibody. The peak level of AST and ALT was 5799 IU/L and 3960 IU/L, respectively. The pathological findings of liver biopsy revealed some central venous endotheliitis and massive centrilobular hemorrhagic hepatocellular necrosis. These findings were not typical for antibody-mediated rejection, but the desensitization was effective and liver graft was successfully rescued. The only way to prevent early graft loss due to seventh-day syndrome is thought to be an immediate decision to start intensive desensitization.

Liver regeneration after performing associating liver partition and portal vein occlusion for staged hepatectomy (ALPPS) is histologically similar to that occurring after liver transplantation using a small-for-size graft.

PURPOSE: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) can achieve marked future liver remnant (FLR) hypertrophy but this procedure is associated with a risk of mortality due to liver failure because of an insufficient FLR functional increase, a situation comparable to small-for-size syndrome (SFSS) after living-donor liver transplantation (LDLT). METHODS: The clinical data, morphologic volume changes, and histopathologic and immunohistochemical findings in hepatocytes and bile ductules were compared between ALPPS (n = 10) and LDLT with a risk for SFSS (n = 12). RESULTS: Although the patient characteristics and short-term outcome differed between the groups, the mean hypertrophy ratios with respect to liver volume for the FLR after performing the first-stage ALPPS procedures resembled those in small-for-size grafts after similar time intervals: 1.702 ± 0.407 in ALPPS vs. 1.948 ± 0.252 in LDLT (P = 0.205). The histologic grades for sinusoidal dilation (P = 0.896), congestion (P = 0.922), vacuolar change (P = 0.964), hepatocanalicular cholestasis (P = 0.969), and ductular reaction (P = 0.728) within the FLR at the second-stage operation during ALPPS or implanted graft were all similar between the groups. CONCLUSIONS: The hepatic regenerative process may be similar in ALPPS and LDLT using a small-for-size graft. Reducing the hepatic vascular inflow that may be excessive for the FLR volume during the first stage of ALPPS might enhance the functional recovery since measures with a similar effect appear to lessen the likelihood of SFSS.

Minimally Invasive Stage 1 to Protect Against the Risk of Liver Failure: Results from the Hepatocellular Carcinoma Series of the Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy Italian Registry.

Introduction: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been described to treat hepatocellular carcinoma (HCC) but burdened, in its pioneering phase, by high morbidity and mortality. With the advent of minimally invasive (MI) techniques in liver surgery, surgical complications, including posthepatectomy liver failure (PHLF), have been dramatically reduced. The primary endpoint of this study was to compare the short-term outcomes of MI- versus open-ALPPS for HCC, with specific focus on PHLF. Methods: Data of patients submitted to ALPPS for HCC between 2012 and 2020 were identified from the ALPPS Italian Registry. Patients receiving an MI Stage 1 (MI-ALPPS) constituted the study group, whereas the patients who received an open Stage 1 (open-ALPPS) constituted the control group. Results: Sixty-six patients were enrolled from 12 Italian centers. Stage 1 of ALPPS was performed in 14 patients using an MI approach (21.2%). MI-ALPPS patients were discharged after Stage 1 at a significantly higher rate compared with open-ALPPS (78.6% versus 9.6%, P < .001). After Stage 2, major morbidity after MI-ALPPS was 8.3% compared with 28.6% reported after open-ALPPS. Mortality was nil after MI-ALPPS. Length of hospital stay was significantly shorter in MI-ALPPS (12 days versus 22 days, P < .001). Univariate logistic regression analysis (Firth method) found that both MI-ALPPS (odds ratio [OR] = 0.05, P = .040) and partial parenchymal transection (OR = 0.04, P = .027) were protective against PHLF. Conclusion: This national multicenter study showed that a less invasive approach to ALPPS first stage was associated with a lower overall risk of PHLF.

[The value of Gd-EOB-DTPA-enhanced MRI in patients with major resection of liver cancer].

Objective: To investigate the value of Gd-EOB-DTPA-enhanced MRI in evaluating liver function and predicting the risk of post-hepatoectomy liver failure in patients with major resection of liver cancer. Methods: A total number of 212 patients were included from June 2016 to June 2019 at Department of General Surgery, Peking University Third Hospital with a retrospectively collected data.All patients underwent Gd-EOB-DTPA-enhanced MRI for diagnosis and preoperative evaluation of liver function.There were 135 males and 77 females, with age of (63.1±10.3) years old (range: 18 to 86 years old) . Relative enhancement ratio (RER) of the region of interest on Gd-EOB-DTPA-enhanced MRI was acquired by two independent researcher and then conducted the comparison of RER among the patients with or without post-hepatoectomy liver failure (PHLF) .Preoperative evaluation demonstrated that 141 cases infected by hepatitis virus, 128 cases with hepatitis B alone and 11 cases with hepatitis C alone, 2 cases had both of hepatitis B and C, and all patients were grade A judged by Child-Pugh score. The relationship between RER and PHLF was evaluated by Pearson correlation analysis and the diagnostic value of RER in predicting PHLF was test by receiver operating characteristic curve. Results: PHLF occurred in 42 patients according to ISGLS standard. Among them, 31 cases had level A liver failure, 9 cases had level B liver failure and 2 had level C failure. There was a significant correlation between RER and overall level of PHLF and RER was also significantly associated with severe B to C level of PHLF (P<0.05) .The further receiver operating characteristics curve analysis showed that the diagnostic accuracy of RER on overall PHLF was 0.818 (sensitivity 72.9%, specificity 83.3%, cut-off value 73.5%, 95%CI: 0.75 to 0.887) and on severe PHLF was 0.924 (sensitivity 97.0%, specificity 90.9%, cut-off value: 61.5%, 95%CI: 0.79 to 0.90) . Conclusion: For patients who planned to undergo major resection of liver cancer, preoperative Gd-EOB-DTPA-enhanced MRI can help with the assessment of liver function and predicting the risk for post-hepatectomy liver failure.