Right Ex-situ split grafts for adult liver transplantation - A Multicenter Benchmarking Analysis.

OBJECTIVE: To analyse outcomes after adult right ex-situ split graft liver transplantations (RSLT) and compare with available outcome benchmarks from whole liver transplantation (WLT). SUMMARY BACKGROUND DATA: Ex-situ SLT may be a valuable strategy to tackle the increasing graft shortage. Recently established outcome benchmarks in WLT offer a novel reference to perform a comprehensive analysis of results after ex-situ RSLT. METHODS: This retrospective multicenter cohort study analyzes all consecutive adult SLT performed using right ex-situ split grafts from 01.01.2014 to 01.06.2022. Study endpoints included 1 year graft and recipient survival, overall morbidity expressed by the comprehensive complication index (CCI©) and specific post-LT complications. Results were compared to the published benchmark outcomes in low-risk adult WLT scenarii. RESULTS: In 224 adult right ex-situ SLT, 1y recipient and graft survival rates were 96% and 91.5%, within the WLT benchmarks. The 1y overall morbidity was also within the WLT benchmark (41.8 CCI points vs. <42.1). Detailed analysis, revealed cut surface bile leaks (17%, 65.8% Grade IIIa) as a specific complication without a negative impact on graft survival. There was a higher rate of early hepatic artery thrombosis (HAT) after SLT, above the WLT benchmark (4.9% vs. ≤4.1%), with a significant impact on early graft but not patient survival. CONCLUSION: In this multicentric study of right ex-situ split graft LT, we report 1-year overall morbidity and mortality rates within the published benchmarks for low-risk WLT. Cut surface bile leaks and early HAT are specific complications of SLT and should be acknowledged when expanding the use of ex-situ SLT.

Harmonizing Definitions and Perspectives in Extreme Liver Surgery: A Delphi Experts Consensus.

OBJECTIVE: To propose to our community a common language about extreme liver surgery. BACKGROUND: The lack of a clear definition of extreme liver surgery prevents convincing comparisons of results among centers. METHODS: We used a two-round Delphi methodology to quantify consensus among liver surgery experts. For inclusion in the final recommendations, we established a consensus when the positive responses (agree and totally agree) exceeded 70%. The study steering group summarized and reported the recommendations. In general, a five-point Likert scale with a neutral central value was used, and in a few cases multiple choices. Results are displayed as numbers and percentages. RESULTS: A two-round Delphi study was completed by 38 expert surgeons in complex hepatobiliary surgery. The surgeon´s median age was 58 years old (52-63) and the median years of experience was 25 years (20-31). For the proposed definitions of total vascular occlusion, hepatic flow occlusion and inferior vein occlusion, the degree of agreement was 97%, 81% and 84%, respectively. In situ approach (64%) was the preferred, followed by ante situ (22%) and ex situ (14%). Autologous or cadaveric graft for hepatic artery or hepatic vein repair were the most recommended (89%). The use of veno-venous bypass or portocaval shunt revealed the divergence depending on the case. Overall, 75% of the experts agreed with the proposed definition for extreme liver surgery. CONCLUSION: Obtaining a consensus on the definition of extreme liver surgery is essential to guarantee the correct management of patients with highly complex hepatobiliary oncological disease. The management of candidates for extreme liver surgery involves comprehensive care ranging from adequate patient selection to the appropriate surgical strategy.

Intraoperative indocyanine green fluorescence imaging to predict early hepatic arterial complications after liver transplantation.

The purpose of this study was to propose an innovative intraoperative criterion in a liver transplantation setting that would judge arterial flow abnormality that may lead to early hepatic arterial occlusion, that is, thrombosis or stenosis, when left untreated and to carry out reanastomosis. After liver graft implantation, and after ensuring that there is no abnormality on the Doppler ultrasound (qualitative and quantitative assessment), we intraoperatively injected indocyanine green dye (0.01 mg/Kg), and we quantified the fluorescence signal at the graft pedicle using ImageJ software. From the obtained images of 89 adult patients transplanted in our center between September 2017 and April 2019, we constructed fluorescence intensity curves of the hepatic arterial signal and examined their relationship with the occurrence of early hepatic arterial occlusion (thrombosis or stenosis). Early hepatic arterial occlusion occurred in 7 patients (7.8%), including 3 thrombosis and 4 stenosis. Among various parameters of the flow intensity curve analyzed, the ratio of peak to plateau fluorescence intensity and the jagged wave pattern at the plateau phase were closely associated with this dreaded event. By combining the ratio of peak to plateau at 0.275 and a jagged wave, we best predicted the occurrence of early hepatic arterial occlusion and thrombosis, with sensitivity/specificity of 0.86/0.98 and 1.00/0.94, respectively. Through a simple composite parameter, the indocyanine green fluorescence imaging system is an additional and promising intraoperative modality for identifying recipients of transplant at high risk of developing early hepatic arterial occlusion. This tool could assist the surgeon in the decision to redo the anastomosis despite normal Doppler ultrasonography.

Complex Hepatectomy Under Total Vascular Exclusion of the Liver Preserving the Caval Flow with Portal Hypothermic Perfusion and Temporary Portacaval Shunt: A Proof of Concept.

BACKGROUND: Hypothermic liver perfusion decreases ischemia/reperfusion injury during hepatectomy under standard total vascular exclusion (TVE) of the liver. This surgery needs venovenous bypass and is hampered by high morbi-mortality. TVE preserving the inferior vena cava (IVC) flow is hemodynamically well tolerated but remains limited in duration when performed under liver normothermia. The objective of this study was to report the results of TVE preserving the caval flow, modified to allow hypothermic liver perfusion and obviate splanchnic congestion. PATIENTS AND METHODS: The technique, indicated for tumors abutting large tributaries of the hepatic veins but sparing their roots in IVC and the latter, was applied when TVE was anticipated to last for ≥ 60 min. It combines continuous TVE preserving the IVC flow with hypothermic liver perfusion and temporary portacaval shunt (PCS). Results are given as median (range). RESULTS: Vascular control was achieved in 13 patients with excellent hemodynamical tolerance. PCS was direct or via an interposed synthetic graft (five and eight cases, respectively). Liver temperature dropped to 16.5 (6-24) °C under perfusion of 2 (2-4) L of cold perfusate. TVE lasted 67 (54-125) min and 4.5 (0-8) blood units were transfused. Resection was major in nine cases and was complete in all cases. Five complications occurred in four patients, and the 90-day mortality rate was zero. CONCLUSIONS: This technique maintains stable hemodynamics and combines the advantages of in situ or ex situ standard TVE with hypothermic liver perfusion, without their inherent prolongation of ischemia time and need for venovenous bypass.

Comprehensive review of hepatocellular carcinoma with portal vein tumor thrombus: State of art and future perspectives.

BACKGROUND: Despite advances in the diagnosis of patients with hepatocellular carcinoma (HCC), 70%-80% of patients are diagnosed with advanced stage disease. Portal vein tumor thrombus (PVTT) is among the most ominous signs of advanced stage disease and has been associated with poor survival if untreated. DATA SOURCES: A systematic search of MEDLINE (PubMed), Embase, Cochrane Library and Database for Systematic Reviews (CDSR), Google Scholar, and National Institute for Health and Clinical Excellence (NICE) databases until December 2022 was conducted using free text and MeSH terms: hepatocellular carcinoma, portal vein tumor thrombus, portal vein thrombosis, vascular invasion, liver and/or hepatic resection, liver transplantation, and systematic review. RESULTS: Centers of surgical excellence have reported promising results related to the individualized surgical management of portal thrombus versus arterial chemoembolization or systemic chemotherapy. Critical elements to the individualized surgical management of HCC and portal thrombus include precise classification of the portal vein tumor thrombus, accurate identification of the subgroups of patients who may benefit from resection, as well as meticulous surgical technique. This review addressed five specific areas: (a) formation of PVTT; (b) classifications of PVTT; (c) controversies related to clinical guidelines; (d) surgical treatments versus non-surgical approaches; and (e) characterization of surgical techniques correlated with classifications of PVTT. CONCLUSIONS: Current evidence from Chinese and Japanese high-volume centers demonstrated that patients with HCC and associated PVTT can be managed with surgical resection with acceptable results.

Repeat laparoscopic liver resection after an initial open hepatectomy.

BACKGROUND: Repeat open hepatectomy (ROH) for recurrent liver tumors is the preferred approach especially after initial open hepatectomy (OH). The aim of this study is to assess feasibility and safety of repeat laparoscopic hepatectomy (RLH) after initial OH in 2 high volume hepato-biliary hospitals. METHODS: Patients were retrieved from prospective data bases from 2012 to 2020. The patients were divided into two groups according to the approach used for repeat hepatectomy, ROH and RLH groups. RESULTS: Sixty-seven patients matched the criteria, 20 in RLH and 47 in ROH. Diagnoses were hepatocellular carcinoma in 52.3%, intrahepatic cholangiocarcinoma in 7.7% and colorectal liver metastases in 40%. Median operative time and blood loss were lower in RLH (199 vs 260 min, and 100 vs 400 ml respectively), as well as overall postoperative complications (20% vs 49%). There were 2 conversions (10%) due to adhesions and one died of postoperative pancreatitis in RLH. Median hospital stay was lower in RLH (5 vs 9 days). CONCLUSION: RLH is a feasible, safe technique and a realistic option to be considered in selected patients after previous OH. Early conversion should be considered when adhesions are more severe than expected.

European validation of the classification for the anticipated difficulty of liver transplantation.

BACKGROUND: Appropriate risk stratification for the difficulty of liver transplantation (LT) is essential to guide the selection and acceptance of grafts and avoid morbidity and mortality. METHODS: Based on 987 LTs collected from 5 centers, perioperative outcomes were analyzed across the 3 difficulty levels. Each LT was retrospectively scored from 0 to 10. Scores of 0-2, 3-5 and 6-10 were then translated into respective difficulty levels: low, moderate and high. Complications were reported according to the comprehensive complication index (CCI). RESULTS: The difficulty level of LT in 524 (53%), 323 (32%), and 140 (14%) patients was classified as low, moderate and high, respectively. The values of major intraoperative outcomes, such as cold ischemia time (p = 0.04) and operative time (p < 0.0001) increased gradually with statistically significant values among difficulty levels. There was a corresponding increase in CCI (p = 0.04), severe complication rates (p = 0.05) and length of ICU (p = 0.01) and hospital (p = 0.004) stays across the different difficulty levels. CONCLUSION: The LT difficulty classification has been validated.

Comparing indications, complexity and outcomes of laparoscopic liver resection between centers with and without a liver transplant program: a French nationwide study.

BACKGROUND: There are no data to evaluate the difference in populations and impact of centers with liver transplant programs in performing laparoscopic liver resection (LLR). METHODS: This was a multicenter study including patients undergoing LLR for benign and malignant tumors at 27 French centers from 1996 to 2018. The main outcomes were postoperative severe morbidity and mortality. RESULTS: A total of 3154 patients were included, and 14 centers were classified as transplant centers (N = 2167 patients, 68.7 %). The transplant centers performed more difficult LLRs and more resections for hepatocellular carcinoma (HCC) in patients who more frequently had cirrhosis. A higher rate of performing the Pringle maneuver, a lower rate of blood loss and a higher rate of open conversion (all p < 0.05) were observed in the transplant centers. There was no association between the presence of a liver transplant program and either postoperative severe morbidity (<10 % in each group; p = 0.228) or mortality (1 % in each group; p = 0.915). CONCLUSIONS: Most HCCs, difficult LLRs, and cirrhotic patients are treated in transplant centers. We show that all centers can achieve comparable safety and quality of care in LLR independent of the presence of a liver transplant program.

Defining Surgical Difficulty of Liver Transplantation.

OBJECTIVE: To define technically Diff-LT. SUMMARY OF BACKGROUND DATA: Currently, there is no acknowledged definition of Diff-LT. METHODS: This retrospective study included all first consecutive liver-only transplantations performed in 2 centers from 2011 to 2015. Diff-LT was defined as the combination of the number of blood units transfused, cold ischemia time, and duration of operation, all at or above the median value of the entire population. The correlation of Diff-LT with short- (including the comprehensive complication index) and long-term outcomes was assessed. Outcomes were also compared to the 90-day benchmark cutoffs of LT. Predictors of Diff-LT were identified by multivariable analysis, first using only recipient data and then using all recipient, donor, graft, and surgical data. RESULTS: The study population included 467 patients. The incidence of Diff- LT was 18.8%. Diff-LT was associated with short-term outcomes, including the comprehensive complication index and mortality, but not with patient or graft long-term survival. Previous abdominal surgery, intensive care unitbound at the time of LT, split graft use, nonstandard arterial reconstruction, and porto-systemic shunt ligation were independent predictors of Diff-LT. The proportion of variables below the corresponding LT 90-day benchmark cutoffs was 8/13 (61.5%) for non-Diff-LT, and 4/13 (30.8%) for Diff-LT. CONCLUSIONS: Diff-LT, as defined, occurred frequently. Adjusting modifiable variables might decrease the risk of Diff-LT and improve the postoperative course. This definition of Diff-LT might be useful for patient information, comparison between centers and surgeons, and as a metric in future trials.

Towards refining the utility of dual (18F-FDG / 18F-Choline) PET/CT for the management of hepatocellular carcinoma: a tertiary center study.

BACKGROUND: The role of positron emission tomography/computed tomography (PET/CT) in hepatocellular carcinoma (HCC) management is not clearly defined. Our objective was to analyze the utility of dual-PET/CT (18F-FDG + 18F-Choline) imaging findings on the BCLC staging and treatment decision for HCC patients. METHODS: Between January 2011 and April 2019, 168 consecutive HCC patients with available baseline dual-PET/CT imaging data were retrospectively analyzed. To identify potential refinement criteria for surgically-treated patients, survival Kaplan-Meier curves of various standard-of-care and dual-PET/CT baseline parameters were estimated. Finally, multivariate cox proportional hazard ratios of the most relevant clinico-biological and/or PET parameters were estimated. RESULTS: Dual-PET/CT findings increased the score of BCLC staging in 21 (12.5%) cases. In 24.4% (N.=41) of patients, the treatment strategy was modified by the PET findings. Combining AFP levels at a threshold of 10 ng/mL with 18F-FDG or 18F-Choline N status significantly impacted DFS (P<0.05). In particular, the combined criteria of the N+ status assessed by 18F-Choline with AFP threshold of 10 ng/mL provided a highly predictive composite parameter for estimation of DFS according to multivariate analysis (HR=10.6, P<0.05). CONCLUSIONS: The 18F-Choline / AFP composite parameter appears promising, and further prospective studies are mandatory to validate its oncological impact.

Evidence for Alloimmune Sinusoidal Injury in De Novo Nodular Regenerative Hyperplasia After Liver Transplantation.

Posttransplant nodular regenerative hyperplasia (NRH) mostly remains unexplained. Microvascular injury due to antibody-mediated rejection (AMR) is suspected, but lack of donor specific antibody (DSA) testing makes it difficult to prove. Centered around a 1-year period of routine DSA testing, concomitant protocol, and indicated posttransplant liver biopsies (LB), recipients with NRH (n = 18) were compared with a matched control group (n = 36). All index, previous, and subsequent LB were reviewed. Both groups were similar in terms of demographics, timing of index LB, and DSA. In the index LB, the NRH group had higher sinusoidal C4d positivity (p = 0.029) and perisinusoidal fibrosis (p = 0.034), both independently associated with NRH (p = 0.038 and 0.050, respectively). Features of "possible" chronic AMR were detected in 28.5% of the NRH group without a known cause and 0% of the control group (p = 0.009). The NRH group had more preceding indicated LB with increased incidence of rejection and biliary obstruction pattern. In the follow-up histology, overall, sinusoidal and portal C4d positivity, sinusoidal microvasculitis, and perisinusoidal fibrosis were also higher (all p < 0.050). In conclusion, we provide evidence towards the hypothesis that some cases of posttransplant NRH are related to preceding active and persistent AMR. Large multicenter studies with protocol DSA testing are required to confirm.

Simultaneous portal and hepatic vein embolization is better than portal embolization or ALPPS for hypertrophy of future liver remnant before major hepatectomy: A systematic review and network meta-analysis.

BACKGROUND: Post-hepatectomy liver failure (PHLF) is the Achilles' heel of hepatic resection for colorectal liver metastases. The most commonly used procedure to generate hypertrophy of the functional liver remnant (FLR) is portal vein embolization (PVE), which does not always lead to successful hypertrophy. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been proposed to overcome the limitations of PVE. Liver venous deprivation (LVD), a technique that includes simultaneous portal and hepatic vein embolization, has also been proposed as an alternative to ALPPS. The present study aimed to conduct a systematic review as the first network meta-analysis to compare the efficacy, effectiveness, and safety of the three regenerative techniques. DATA SOURCES: A systematic search for literature was conducted using the electronic databases Embase, PubMed (MEDLINE), Google Scholar and Cochrane. RESULTS: The time to operation was significantly shorter in the ALPPS cohort than in the PVE and LVD cohorts by 27 and 22 days, respectively. Intraoperative parameters of blood loss and the Pringle maneuver demonstrated non-significant differences between the PVE and LVD cohorts. There was evidence of a significantly higher FLR hypertrophy rate in the ALPPS cohort when compared to the PVE cohort, but non-significant differences were observed when compared to the LVD cohort. Notably, the LVD cohort demonstrated a significantly better FLR/body weight (BW) ratio compared to both the ALPPS and PVE cohorts. Both the PVE and LVD cohorts demonstrated significantly lower major morbidity rates compared to the ALPPS cohort. The LVD cohort also demonstrated a significantly lower 90-day mortality rate compared to both the PVE and ALPPS cohorts. CONCLUSIONS: LVD in adequately selected patients may induce adequate and profound FLR hypertrophy before major hepatectomy. Present evidence demonstrated significantly lower major morbidity and mortality rates in the LVD cohort than in the ALPPS and PVE cohorts.

Renoportal Anastomosis During Liver Transplantation in Patients With Portal Vein Thrombosis: First Long-term Results From a Multicenter Study.

OBJECTIVE: To evaluate the short- and long-term outcomes of RPA in a large multicentric series. SUMMARY BACKGROUND: The current knowledge on RPA for portal reconstruction during LT in patients with diffuse PVT and a large splenorenal shunt is poor and limited to case reports and small case series. METHODS: All consecutive LTs with RPA performed in 5 centers between 1998 and 2020 were included. RPA was physiological provided it drained the splanchnic venous return through a large splenorenal shunt (≥ 1 cm diameter). Complications of PHT, long-term RPA patency, and patient and graft survival were assessed. RPA success was achieved provided the 3 following criteria were all fulfilled: patients were alive with patent RPA and without clinical PHT. RESULTS: RPA was attempted and feasible in 57 consecutive patients and was physiological in 51 patients (89.5%). Ninety-day mortality occurred in 5 (8.5%) patients, and PHT-related complications occurred in 42.9% of patients. With a median follow-up of 63 months, the 1-, 3- and 5-year patient and graft survival rates were 87%, 83%, and 76% and 82%, 80%, and 73%, respectively. The primary and primary-assisted patency rates at 5 years were 84.5% and 94.3%, respectively. Success was achieved in 90% (27/30) of patients with a follow-up ≥5 years. CONCLUSIONS: Despite a high rate of PHT-related complications, excellent long-term patient and graft survival could be achieved. RPA could be considered successful in the vast majority of patients. The expanded use of RPA is warranted.

Novel Composite Endpoint for Assessing Outcomes in Liver Transplantation: Arterial and Biliary Complication-Free Survival.

Transplant and patient survival are the validated endpoints to assess the success of liver transplantation (LT). This study evaluates arterial and biliary complication-free survival (ABCFS) as a new metric. ABC, considered as an event, was an arterial or biliary complication of Dindo-Clavien grade ≥III complication dated at the interventional, endoscopic, or surgical treatment required to correct it. ABCFS was defined as the time from the date of LT to the dates of first ABC, death, relisting, or last follow-up (transplant survival is time from LT to repeat LT or death). Following primary whole LT (n = 532), 106 ABCs occurred and 99 (93%) occurred during the first year after LT. An ABC occurring during the first year after LT (overall rate 19%) was an independent factor associated with transplant survival (hazard ratio [HR], 3.17; P < 0.001) and patient survival (HR, 2.7; P = 0.002) in univariate and multivariate analyses. This result was confirmed after extension of the cohort to split-liver graft, donation after circulatory death, or re-LT (n = 658). Data from 2 external cohorts of primary whole LTs (n = 249 and 229, respectively) confirmed that the first-year ABC was an independent prognostic factor for transplant survival but not for patient survival. ABCFS was correlated with transplant and patient survival (ρ = 0.85 [95% CI, 0.78-0.90] and 0.81 [95% CI, 0.71-0.88], respectively). Preoperative factors known to influence 5-year transplant survival influenced ABCFS after 1 year of follow-up. The 1-year ABCFS was indicative of 5-year transplant survival. ABCFS is a reproducible metric to evaluate the results of LT after 1 year of follow-up and could serve as a new endpoint in clinical trials.

Subjective Difficulty Scale in Liver Transplantation: A Prospective Observational Study.

The predictive value of a subjective difficulty scale (DS) after surgical procedures is unknown. The objective of this study was to evaluate the prognostic value of a DS after liver transplantation (LT) and to identify predictors of difficulty. Surgeons prospectively evaluated the difficulty of 441 consecutive liver transplantations from donation after brain death at the end of the surgery by using a DS from 0 to 10 ("the easiest to the hardest you can imagine"). DS was associated with severe morbidity. The risk of graft loss at 1 year remained unchanged from 0 to 6 but increased beyond 6. Graft survival and patient survival of group with DS 7-10 was significantly impaired compared to groups with DS: 0-3 or DS: 4-6 but were significantly impaired for the group with DS: 7-10. Independent predictors of difficult LT (DS ≥ 7) were annular segment 1, transjugular intrahepatic portosystemic shunt, retransplantation beyond 30 days, portal vein thrombosis, and ascites. Of them, ascites was a borderline non-significant covariate (p = .04). Vascular complications occurred more often after difficult LT (20.5% vs. 5.9%), whereas there was no difference in the other types of complications. DS can be used to tailor monitoring and anticipate early complications. External validation is needed.

The rex shunt for left portal vein reconstruction during hepatectomy for malignancy using of rex-shunt in adults for oncoliver surgery.

BACKGROUND: Immediate portal reperfusion is mandatory following hepatectomy combined with portal vein (PV) resection. This retrospective study analyzes the feasibility and the outcomes of the Rex shunt (RS) for reconstruction of the left portal vein (LPV) and reperfusion of the remnant left liver or lobe following hepatectomy for cancer combined with resection of the PV in adult patients. METHODS: From 2018 to 2021, an RS was used in the above setting to achieve R0 resection or when the standard LPV reconstruction failed or was deemed technically impossible. RESULTS: There were 6 male and 5 female patients (median age, 58 years) with perihilar cancer (5 cases) or miscellaneous cancers invading the PV (6 cases). A major hepatectomy was performed in 10/11 patients. The RS was indicated to achieve R0 resection or for technical reasons in 8 and 3 cases, respectively, and was feasible in all consecutive attempts with (10 cases) or without an interposed synthetic graft (1 case). Two fatal complications (PV thrombosis and pulmonary embolism) and three non-severe complications occurred in four patients within 90 days of surgery. Two patients died of tumor recurrence with a patent RS at 13 and 29 months, and 7 were recurrence free with a patent shunt with a follow-up of 1 to 37 months (median, 15 months). CONCLUSION: In case of remnant left liver or lobe following hepatectomy combined with resection of the PV, the RS may help to achieve R0 resection and is a valuable option to perform technically satisfying portal reperfusion of the remnant left liver or lobe.

Incidental finding of elevated pulmonary arterial pressures during liver transplantation and postoperative pulmonary complications.

BACKGROUND: In patients with end stage liver disease (ESLD) scheduled for liver transplantation (LT), an intraoperative incidental finding of elevated mean pulmonary arterial pressure (mPAP) may be observed. Its association with patient outcome has not been evaluated. We aimed to estimate the effects of an incidental finding of a mPAP > 20 mmHg during LT on the incidence of pulmonary complications. METHODS: We examined all patients who underwent a LT at Paul-Brousse hospital between January 1,2015 and December 31,2020. Those who received: a LT due to acute liver failure, a combined transplantation, or a retransplantation were excluded, as well as patients for whom known porto-pulmonary hypertension was treated before the LT or patients who underwent a LT for other etiologies than ESLD. Using right sided pulmonary artery catheterization measurements made following anesthesia induction, the study cohort was divided into two groups using a mPAP cutoff of 20 mmHg. The primary outcome was a composite of pulmonary complications. Univariate and multivariable logistic regression analyses were performed to identify variables associated with the primary outcome. Sensitivity analyses of multivariable models were also conducted with other mPAP cutoffs (mPAP ≥ 25 mmHg and ≥ 35 mmHg) and even with mPAP as a continuous variable. RESULTS: Of 942 patients who underwent a LT, 659 met our inclusion criteria. Among them, 446 patients (67.7%) presented with an elevated mPAP (mPAP of 26.4 ± 5.9 mmHg). When adjusted for confounding factors, an elevated mPAP was not associated with a higher risk of pulmonary complications (adjusted OR: 1.16; 95%CI 0.8-1.7), nor with 90 days-mortality or any other complications. In our sensitivity analyses, we observed a lower prevalence of elevated mPAP when increasing thresholds (235 patients (35.7%) had an elevated mPAP when defined as ≥ 25 mmHg and 41 patients (6.2%) had an elevated mPAP when defined as ≥ 35 mmHg). We did not observe consistent association between a mPAP ≥ 25 mmHg or a mPAP ≥ 35 mmHg and our outcomes. CONCLUSION: Incidental finding of elevated mPAP was highly prevalent during LT, but it was not associated with a higher risk of postoperative complications.

Donor HLA Class 1 Evolutionary Divergence Is a Major Predictor of Liver Allograft Rejection : A Retrospective Cohort Study.

BACKGROUND: The HLA evolutionary divergence (HED), a continuous metric quantifying the peptidic differences between 2 homologous HLA alleles, reflects the breadth of the immunopeptidome presented to T lymphocytes. OBJECTIVE: To assess the potential effect of donor or recipient HED on liver transplant rejection. DESIGN: Retrospective cohort study. SETTING: Liver transplant units. PATIENTS: 1154 adults and 113 children who had a liver transplant between 2004 and 2018. MEASUREMENTS: Liver biopsies were done 1, 2, 5, and 10 years after the transplant and in case of liver dysfunction. Donor-specific anti-HLA antibodies (DSAs) were measured in children at the time of biopsy. The HED was calculated using the physicochemical Grantham distance for class I (HLA-A or HLA-B) and class II (HLA-DRB1 or HLA-DQB1) alleles. The influence of HED on the incidence of liver lesions was analyzed through the inverse probability weighting approach based on covariate balancing, generalized propensity scores. RESULTS: In adults, class I HED of the donor was associated with acute rejection (hazard ratio [HR], 1.09 [95% CI, 1.03 to 1.16]), chronic rejection (HR, 1.20 [CI, 1.10 to 1.31]), and ductopenia of 50% or more (HR, 1.33 [CI, 1.09 to 1.62]) but not with other histologic lesions. In children, class I HED of the donor was also associated with acute rejection (HR, 1.16 [CI, 1.03 to 1.30]) independent of the presence of DSAs. There was no effect of either donor class II HED or recipient class I or class II HED on the incidence of liver lesions in adults and children. LIMITATION: The DSAs were measured only in children. CONCLUSION: Class I HED of the donor predicts acute or chronic rejection of liver transplant. This novel and accessible prognostic marker could orientate donor selection and guide immunosuppression. PRIMARY FUNDING SOURCE: Institut National de la Santé et de la Recherche Médicale.

Tumors located in the central column of the liver are associated with increased surgical difficulty and postoperative complications following open liver resection for colorectal metastases.

BACKGROUND: To assess the impact of difficult location (based on preoperative computed tomography) of liver metastases from colorectal cancer (LMCRC) on surgical difficulty, and occurrence of severe postoperative complications (POCs). METHODS: A retrospective single-centre study of 911 consecutive patients with LMCRC who underwent hepatectomy by the open approach between 1998 and 2011, before implementation of laparoscopic surgery to obviate approach selection bias. LMCRC with at least one of the following four features on preoperative imaging: tumor invading the hepatocaval confluence or retro-hepatic inferior vena cava, centrally located (Segments 4,5,8) and >10 cm in diameter, abutting the supra-hilar area, or involving the paracaval portion or caudate process of Segment 1; were considered as topographically difficult (top-diff). Independent predictors of surgical difficulty assessed by number of blood units transfused, duration of ischemia, and number of sessions of pedicle clamping during surgery and of severe POCs were identified by multivariate analysis before, and after propensity score matching. RESULTS: Top-diff tumor location independently predicted surgical difficulty. Severe POCs were associated with the tumor location [top-diff vs. topographically non difficult (non top-diff)], preoperative portal vein embolization, and variables related to surgical difficulty. CONCLUSION: LMCRC in difficult location independently predicts surgical difficulty and severe POCs.

The impact of advanced patient age in liver transplantation: a European Liver Transplant Registry propensity-score matching study.

BACKGROUND: The futility of liver transplantation in elderly recipients remains under debate in the HCV eradication era. METHODS: The aim was to assess the effect of older age on outcome after liver transplantation. We used the ELTR to study the relationship between recipient age and post-transplant outcome. Young and elderly recipients were compared using a PSM method. RESULTS: A total of 10,172 cases were analysed. Recipient age >65 years was identified as an independent risk factor associated with reduced patient survival (HR:1.42 95%CI:1.23-1.65,p < 0.001). After PSM, 2124 patients were matched, and the same association was found between elderly recipients and patient survival and graft survival (p < 0.001). As hepatocellular carcinoma and alcoholic cirrhosis were independent prognostic factors for patient and graft survival a propensity score-matching was performed for each. Patient and graft survival were significantly worse (p < 0.05) in the alcoholic cirrhosis elderly group. However, patient and graft survival in the hepatocellular carcinoma cohort were similar (p > 0.05) between groups. CONCLUSION: Liver transplantation is an acceptable and safe curative option for elderly transplant candidates, with worse long-term outcomes compare to young candidates. The underlying liver disease for liver transplantation has a significant impact on the selection of elderly patients.