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.

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.

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.

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.

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.

Alcoholic liver disease: A registry view on comorbidities and disease prediction.

Alcoholic-related liver disease (ALD) is the cause of more than half of all liver-related deaths. Sustained excess drinking causes fatty liver and alcohol-related steatohepatitis, which may progress to alcoholic liver fibrosis (ALF) and eventually to alcohol-related liver cirrhosis (ALC). Unfortunately, it is difficult to identify patients with early-stage ALD, as these are largely asymptomatic. Consequently, the majority of ALD patients are only diagnosed by the time ALD has reached decompensated cirrhosis, a symptomatic phase marked by the development of complications as bleeding and ascites. The main goal of this study is to discover relevant upstream diagnoses helping to understand the development of ALD, and to highlight meaningful downstream diagnoses that represent its progression to liver failure. Here, we use data from the Danish health registries covering the entire population of Denmark during nineteen years (1996-2014), to examine if it is possible to identify patients likely to develop ALF or ALC based on their past medical history. To this end, we explore a knowledge discovery approach by using high-dimensional statistical and machine learning techniques to extract and analyze data from the Danish National Patient Registry. Consistent with the late diagnoses of ALD, we find that ALC is the most common form of ALD in the registry data and that ALC patients have a strong over-representation of diagnoses associated with liver dysfunction. By contrast, we identify a small number of patients diagnosed with ALF who appear to be much less sick than those with ALC. We perform a matched case-control study using the group of patients with ALC as cases and their matched patients with non-ALD as controls. Machine learning models (SVM, RF, LightGBM and NaiveBayes) trained and tested on the set of ALC patients achieve a high performance for data classification (AUC = 0.89). When testing the same trained models on the small set of ALF patients, their performance unsurprisingly drops a lot (AUC = 0.67 for NaiveBayes). The statistical and machine learning results underscore small groups of upstream and downstream comorbidities that accurately detect ALC patients and show promise in prediction of ALF. Some of these groups are conditions either caused by alcohol or caused by malnutrition associated with alcohol-overuse. Others are comorbidities either related to trauma and life-style or to complications to cirrhosis, such as oesophageal varices. Our findings highlight the potential of this approach to uncover knowledge in registry data related to ALD.

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.

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.

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.

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.

Cirrhosis as new indication for statins.

In the recent years, there have been an increasing number of reports on favourable effects of statins in patients with advanced chronic liver disease. These include reduction in portal pressure, improved liver sinusoidal endothelial and hepatic microvascular dysfunction, decreased fibrogenesis, protection against ischaemia/reperfusion injury, safe prolongation of ex vivo liver graft preservation, reduced sensitivity to endotoxin-mediated liver damage, protection from acute-on-chronic liver failure, prevention of liver injury following hypovolaemic shock and preventing/delaying progression of cirrhosis of any aetiology. Moreover, statins have been shown to have potential beneficial effects in the progression of other liver diseases, such as chronic sclerosing cholangitis and in preventing hepatocellular carcinoma. Because of these many theoretically favourable effects, statins have evolved from being considered a risk to kind of wonder drugs for patients with chronic liver diseases. The present article reviews the current knowledge on the potential applications of statins in chronic liver diseases, from its mechanistic background to objective evidence from clinical studies.

ALPPS for Locally Advanced Intrahepatic Cholangiocarcinoma: Did Aggressive Surgery Lead to the Oncological Benefit? An International Multi-center Study.

BACKGROUND: ALPPS is found to increase the resectability of primary and secondary liver malignancy at the advanced stage. The aim of the study was to verify the surgical and oncological outcome of ALPPS for intrahepatic cholangiocarcinoma (ICC). METHODS: The study cohort was based on the ALPPS registry with patients from 31 international centers between August 2009 and January 2018. Propensity score matched patients receiving chemotherapy only were selected from the SEER database as controls for the survival analysis. RESULTS: One hundred and two patients undergoing ALPPS were recruited, 99 completed the second stage with median inter-stage duration of 11 days. The median kinetic growth rate was 23 ml/day. R0 resection was achieved in 87 (85%). Initially high rates of morbidity and mortality decreased steadily to a 29% severe complication rate and 7% 90-day morbidity in the last 2 years. Post-hepatectomy liver failure remained the main cause of 90-day mortality. Multivariate analysis revealed insufficient future liver remnant at the stage-2 operation (FLR2) to be the only risk factor for severe complications (OR 2.91, p = 0.02). The propensity score matching analysis showed a superior overall survival in the ALPPS group compared to palliative chemotherapy (median overall survival: 26.4 months vs 14 months; 1-, 2-, and 3-year survival rates: 82.4%, 70.5% and 39.6% vs 51.2%, 21.4% and 11.3%, respectively, p < 0.01). The survival benefit, however, was not confirmed in the subgroup analysis for patients with insufficient FLR2 or multifocal ICC. CONCLUSION: ALPPS showed high efficacy in achieving R0 resections in locally advanced ICC. To get the most oncological benefit from this aggressive surgery, ALPPS would be restricted to patients with single lesions and sufficient FLR2.

Study protocol of the HYPER-LIV01 trial: a multicenter phase II, prospective and randomized study comparing simultaneous portal and hepatic vein embolization to portal vein embolization for hypertrophy of the future liver remnant before major hepatectomy for colo-rectal liver metastases.

BACKGROUND: In patients undergoing major liver resection, portal vein embolization (PVE) has been widely used to induce hypertrophy of the non-embolized liver in order to prevent post-hepatectomy liver failure. PVE is a safe and effective procedure, but does not always lead to sufficient hypertrophy of the future liver remnant (FLR). Hepatic vein(s) embolization has been proposed to improve FLR regeneration when insufficient after PVE. The sequential right hepatic vein embolization (HVE) after right PVE demonstrated an incremental effect on the FLR but it implies two different procedures with no time gain as compared to PVE alone. We have developed the so-called liver venous deprivation (LVD), a combination of PVE and HVE during the same intervention, to optimize the phase of liver preparation before surgery. The main objective of this randomized phase II trial is to compare the percentage of change in FLR volume at 3 weeks after LVD or PVE. METHODS: Patients eligible to this multicenter prospective randomized phase II study are subjects aged from 18 years old suffering from colo-rectal liver metastases considered as resectable and with non-cirrhotic liver parenchyma. The primary objective is the percentage of change in FLR volume at 3 weeks after LVD or PVE using MRI or CT-Scan. Secondary objectives are assessment of tolerance, post-operative morbidity and mortality, post-hepatectomy liver failure, rate of non-respectability due to insufficient FLR or tumor progression, per-operative difficulties, blood loss, R0 resection rate, post-operative liver volume and overall survival. Objectives of translational research studies are evaluation of pre- and post-operative liver function and determination of biomarkers predictive of liver hypertrophy. Sixty-four patients will be included (randomization ratio 1:1) to detect a difference of 12% at 21 days in FLR volumes between PVE and LVD. DISCUSSION: Adding HVE to PVE during the same procedure is an innovative and promising approach that may lead to a rapid and major increase in volume and function of the FLR, thereby increasing the rate of resectable patients and limiting the risk of patient's drop-out. TRIAL REGISTRATION: This study was registered on clinicaltrials.gov on 15th February 2019 (NCT03841305).

Factors associated with improvement in MELD score after antiviral treatment in patients with chronic hepatitis B.

BACKGROUND AND AIMS: Improvement in Model for End-Stage Liver Disease (MELD) score during antiviral treatment is associated with reduced hepatic decompensation and death in patients with chronic hepatitis B (CHB)-related cirrhosis. We aimed to identify factors associated with transplant-free survival and on-treatment MELD score improvement. METHODS: We identified patients with CHB-related cirrhosis and MELD score ≥ 15 at the start of entecavir and/or tenofovir disoproxil fumarate treatment between 2005 and 2017. The primary endpoint was transplant-free survival at month 6. The secondary endpoints at month 6 were transplant-free survival with > 5-point improvement in MELD score and transplant-free survival with MELD score < 15. RESULTS: Of 999 cirrhotic CHB patients, 605 (60.6%) achieved transplant-free survival at month 6. Proportion of transplant-free survival at month 6 stabilized at 10% in patients with high MELD. Patients who achieved transplant-free survival at month 6 were younger, had lower MELD score, lower alanine aminotransferase (ALT), and higher albumin at baseline. Of 605 patients with transplant-free survival, 276 (45.6%) achieved > 5-point improvement in MELD score; 183 (30.2%) had 1-point to 5-point improvement in MELD score; 146 (24.1%) had no improvement or a worsened MELD score. Also, 321 (53.1%) patients with transplant-free survival had a MELD score < 15 at month 6. CONCLUSION: On top of lower MELD score, patients with CHB-related cirrhosis who are younger, have higher albumin, and lower ALT are more likely to achieve transplant-free survival after 6 months of antiviral treatment.

The Soluble Adenylyl Cyclase Inhibitor LRE1 Prevents Hepatic Ischemia/Reperfusion Damage Through Improvement of Mitochondrial Function.

Hepatic ischemia/reperfusion (I/R) injury is a leading cause of organ dysfunction and failure in numerous pathological and surgical settings. At the core of this issue lies mitochondrial dysfunction. Hence, strategies that prime mitochondria towards damage resilience might prove applicable in a clinical setting. A promising approach has been to induce a mitohormetic response, removing less capable organelles, and replacing them with more competent ones, in preparation for an insult. Recently, a soluble form of adenylyl cyclase (sAC) has been shown to exist within mitochondria, the activation of which improved mitochondrial function. Here, we sought to understand if inhibiting mitochondrial sAC would elicit mitohormesis and protect the liver from I/R injury. Wistar male rats were pretreated with LRE1, a specific sAC inhibitor, prior to the induction of hepatic I/R injury, after which mitochondria were collected and their metabolic function was assessed. We find LRE1 to be an effective inducer of a mitohormetic response based on all parameters tested, a phenomenon that appears to require the activity of the NAD+-dependent sirtuin deacylase (SirT3) and the subsequent deacetylation of mitochondrial proteins. We conclude that LRE1 pretreatment leads to a mitohormetic response that protects mitochondrial function during I/R injury.

[Prevention and treatment of infection after artificial liver treatment].

Artificial liver support system is an important method of treating liver failure, but after artificial liver treatment, secondary infections are usually amalgamated. Additionally, infection is a risk factor that aggravates liver failure, leading to an increased mortality and poor prognosis. Therefore, how to prevent and treat occurrence of infection in patients with liver failure is a key factor to improve the efficacy of artificial liver treatment.

[Advances in early warning and treatment of pre-hepatic failure].

Liver function of patients with pre-hepatic failure deteriorates rapidly, and with this there exists a risk of liver failure and high rates of mortality. This paper summarizes the concept of pre-hepatic failure, particularly the advances in early warning and treatment of pre-hepatic failure developing into hepatic failure, with a view to enhance clinicians' concerns to pre-hepatic failure for promoting the advancement of liver failure prevention and treatment, and improving the success rate of liver failure treatment.

[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.

[Specific complications of liver resection and their prevention]. / Rezektsiia pecheni. Spetsificheskie oslozhneniia i ikh profilaktika.

AIM: To improve the results of treatment of patients with focal liver formations by preventing the development of postoperative complications after liver resections. METHODS: The study included 304 patients with benign and malignant liver lesions. In 196 (64.4%) patients, resections were performed for malignant liver damage, in 108 (35.6%) - for a benign process. To assess the impact of ongoing measures to prevent the development of postoperative complications, patients were divided into two time periods: from 2007 to 2012 and from 2013 to 2018. RESULTS: The introduction of a protocol of preoperative examination of patients for whom resection of 3 or more liver segments is planned, with the inclusion of SPECT/CT, which allows determining the volume of the remaining functioning liver parenchyma, allowed to reduce the percentage of development of acute post-resection liver failure from 11.6% to 3.6% during the second time period (p=0.0064). The use of modern suture material, surgical binocular loops, as well as the use of the concept of predominantly performing parenchyma-saving resections, reduced the number of biliary complications from 8.1% to 5.7% (p=0.1). The use of a proprietary dissection algorithm for the liver parenchyma significantly reduced hemorrhagic complications from 5.3% to 1.04% (p=0.0074). CONCLUSION: The use of modern pre- and intraoperative technologies has reduced the number of postoperative complications after liver resections from 38.3% to 20.9% (p=0.018) and mortality from 2.6% to 0.5% (p=0.004), thereby improving the results of liver resections.