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.

Refining Auxiliary Orthotopic Liver Transplantation (AOLT) Improves Outcomes in Adult Patients With Acute Liver Failure.

OBJECTIVE: To investigate whether and how experience accumulation and technical refinements simultaneously implemented in auxiliary orthotopic liver transplantation (AOLT) may impact on outcomes. BACKGROUND: AOLT for acute liver failure (ALF) provides the unique chance of complete immunosuppression withdrawal after adequate native liver remnant regeneration but is a technically demanding procedure. Our department is a reference center for ALF and an early adopter of AOLT. METHODS: This is a single-center retrospective before/after study of a prospectively maintained cohort of 48 patients with ALF who underwent AOLT between 1993 and 2019. In 2012, technical refinements were implemented to improve outcomes: (i) favoring the volume of the graft rather than that of the native liver, (ii) direct anastomosis of graft hepatic artery with recipient right hepatic artery instead of the use of large size vessels, (iii) end-to-side hepaticocholedocostomy instead of bilioenteric anastomosis. Early experience (1993-2011) group (n=26) and recent experience (2012-2019) group (n=22) were compared. Primary endpoint was 90-day severe morbidity rate (Clavien-Dindo≥IIIa) and secondary endpoints were overall patient survival and complete immunosuppression withdrawal rates. RESULTS: Compared with the earlier experience group, the recent experience group was associated with a lower severe complication rate (27% vs 65%, P <0.001), as well as less biliary (18% vs 54%, P =0.017) and arterial (0% vs 15%, P =0.115) complications. The 1-, 3-, and 5-year patient survival was significantly improved (91%, 91%, 91% vs 76%, 61%, 60%, P =0.045). The rate of complete immunosuppression withdrawal increased to 94% vs 70%, ( P =0.091) with no need of long-term graft explant. CONCLUSION: These technical refinements favoring the liver graft and reducing morbidity may promote AOLT implementation among LT centers.

Impact of COVID-19 on the management of hepatocellular carcinoma in a high-prevalence area: What's new 12 months later?

INTRODUCTION AND OBJECTIVES: The lockdown policy introduced in 2020 to minimize the spread of the COVID-19 pandemic, significantly affected the management and care of patients affected by hepatocellular carcinoma (HCC). The aim of this follow-up study was to determine the 12 months impact of the COVID-19 pandemic on the cohort of patients affected by HCC during the lockdown, within six French academic referral centers in the metropolitan area of Paris. MATERIALS AND METHODS: We performed a 12 months follow-up of the cross-sectional study cohort included in 2020 on the management of patients affected by HCC during the first six weeks of the COVID-19 pandemic (exposed), compared to the same period in 2019 (unexposed). Overall survival were compared between the groups. Predictors of mortality were analysed with Cox regression. RESULTS: From the initial cohort, 575 patients were included (n = 263 Exposed_COVID, n = 312 Unexposed_COVID). Overall and disease free survival at 12 months were 59.9 ± 3.2% vs 74.3 ± 2.5% (p<0.001) and 40.2 ± 3.5% vs 63.5 ± 3.1% (p<0.001) according to the period of exposure (Exposed_COVID vs Unexposed_COVID, respectively). Adjusted Cox regression revealed that the period of exposure (Exposed_COVID HR: 1.79, 95%CI (1.36, 2.35) p<0.001) and BCLC stage B, C and D (BCLC B HR: 1.82, 95%CI (1.07, 3.08) p = 0.027 - BCLC C HR: 1.96, 95%CI (1.14, 3.38) p = 0.015 - BCLC D HR: 3.21, 95%CI (1.76, 5.85) p<0.001) were predictors of death. CONCLUSIONS: Disruption of routine healthcare services because of the pandemic translated to reduced 1 year overall and disease-free survival among patients affected by HCC, in the metropolitan area of Paris, France.

Laparoscopic-assisted liver transplantation: A realistic perspective.

Laparoscopic approach was rarely described in recipients for liver transplantation (LT). We report the feasibility and safety of laparoscopic-assisted LT (LA-LT) in patients with unresectable liver metastases of neuroendocrine tumors. Total hepatectomy was performed laparoscopically with graft implantation through an upper midline incision. Liver grafts were retrieved from deceased donors. From July 2019 to July 2021, six patients (4 women, 2 men) underwent LA-LT. Median age and BMI were 46 (29-54) and 24 (19-35) kg/m2 , respectively. Implanted grafts were reduced (n = 3), full (n = 2), and a right split liver (n = 1). Median surgical time was 405 min (390-450) and median blood loss was 425 ml (250-600). Median cold and warm ischemia times were 438 min (360-575) and 35 min (30-40), respectively. Median anhepatic phase was 51 min (40-67) and midline incision was 14 cm (13-20) long. On postoperative day 5, median prothrombin index and serum bilirubin levels were 95% (70-117) and 11 (10-37) µmol/L, respectively. No Clavien-Dindo > III complications were encountered. Median hospital stay was 12 days (10-14). After a median follow-up of 8 (8-32) months, all patients were alive without tumor recurrence or adverse event. This preliminary series suggests that in selected patients, LA-LT is a safe and effective option.

Graft aberrant hepatic arteries in deceased donor liver transplantation: The "one liver, one artery" approach.

In liver transplantation (LT), graft aberrant hepatic arteries (aHAs) frequently require complex arterial reconstructions, potentially increasing the risk of post-operative complications. However, intrahepatic hilar arterial shunts are physiologically present and may allow selective aHA ligation. Thus, we performed a retrospective study from a single-center cohort of 618 deceased donor LTs where a selective reconstruction policy of aHAs was prospectively applied. In the presence of any aHA, the vessel with the largest caliber was first reconstructed. In case of adequate bilobar arterial perfusion assessed on intraparenchymal Doppler ultrasound, the remnant vessel was ligated; otherwise, it was reconstructed. Consequently, outcomes of three patient groups were compared: the "no aHAs" group (n = 499), the "reconstructed aHA" group (n = 25), and the "ligated aHA" group (n = 94). Primary endpoint was rate of biliary complications. Only 38.4% of right aHAs and 3.1% of left aHAs were reconstructed. Rates of biliary complications in the no aHA, reconstructed aHA, and ligated aHA groups were 23.4%, 28%, and 20.2% (p = 0.667), respectively. The prevalence rates of primary non-function (p = 0.534), early allograft dysfunction (p = 0.832), and arterial complications (p = 0.271), as well as patient survival (p = 0.266) were comparable among the three groups. Retransplantation rates were 3.8%, 4%, and 5.3% (p = 0.685), respectively. In conclusion, a selective reconstruction policy of aHAs based on Doppler assessment of bilobar intraparenchymal arterial flow did not increase post-operative morbidity and avoided unnecessary and complex arterial reconstructions.

Performance of non-invasive biomarkers compared with invasive methods for risk prediction of posthepatectomy liver failure in hepatocellular carcinoma.

BACKGROUND: Posthepatectomy liver failure (PHLF) is a rare but dreaded complication. The aim was to test whether a combination of non-invasive biomarkers (NIBs) and CT data could predict the risk of PHLF in patients who underwent resection of hepatocellular carcinoma (HCC). METHODS: Patients with HCC who had liver resection between 2012 and 2020 were included. A relevant combination of NIBs (NIB model) to model PHLF risk was identified using a doubly robust estimator (inverse probability weighting combined with logistic regression). The adjustment variables were body surface area, ASA fitness grade, male sex, future liver remnant (FLR) ratio, difficulty of liver resection, and blood loss. The reference invasive biomarker (IB) model comprised a combination of pathological analysis of the underlying liver and hepatic venous pressure gradient (HVPG) measurement. Various NIB and IB models for prediction of PHLF were fitted and compared. NIB model performances were validated externally. Areas under the curve (AUCs) were corrected using bootstrapping. RESULTS: Overall 323 patients were included. The doubly robust estimator showed that hepatitis C infection (odds ratio (OR) 4.33, 95 per cent c.i. 1.29 to 9.20; P = 0.001), MELD score (OR 1.26, 1.04 to 1.66; P = 0.001), fibrosis-4 score (OR 1.36, 1.06 to 1.85; P = 0.001), liver surface nodularity score (OR 1.55, 1.28 to 4.29; P = 0.031), and FLR volume ratio (OR 0.99, 0.97 to 1.00; P = 0.014) were associated with PHLF. Their combination (NIB model) was fitted externally (2-centre cohort, 165 patients) to model PHLF risk (AUC 0.867). Among 129 of 323 patients who underwent preoperative HVPG measurement, NIB and IB models had similar performances (AUC 0.753 versus 0.732; P = 0.940). A well calibrated nomogram was drawn based on the NIB model (AUC 0.740). The risk of grade B/C PHLF could be ruled out in patients with a cumulative score of less than 160 points. CONCLUSION: The NIB model provides reliable preoperative evaluation with performance at least similar to that of invasive methods for PHLF risk prediction.

Laparoscopic Liver Transplantation: Dream or Reality? The First Step With Laparoscopic Explant Hepatectomy.

OBJECTIVE: To introduce the laparoscopic approach in liver transplant recipients. SUMMARY OF BACKGROUND DATA: Despite the increasingly frequent use of laparoscopy in living donor hepatectomy, the laparoscopic approach has never been reported in liver transplant recipients. METHODS: A 52-year-old woman (body mass index: 18.5 kg/m) with neuroendocrine liver metastases of a digestive origin underwent hybrid liver transplantation by pure laparoscopic total hepatectomy and liver graft implantation using a preexisting midline incision. The hepatic pedicle vessels were dissected after division of the bile duct without a porto-caval shunt. Left lateral sectionectomy and early division of the common trunk allowed near completion of caval dissection with no prolonged inflow occlusion. The liver graft was reduced and latero-lateral caval anastomosis was performed. RESULTS: Surgery lasted 400 minutes with 400 mL of blood loss. The anhepatic phase lasted 43 minutes. Warm ischemia time and cold ischemia times were 38 and 466 minutes, respectively. The postoperative course was uneventful. CONCLUSIONS: This case study suggests that the hybrid approach may be feasible and safe in selected recipients. The decision to use this surgical approach should be made in transplant centers with significant expertise in both laparoscopic liver and pancreatic surgery. Further reducing the size of the abdominal incision is the next step, which may be achieved with the development of vascular anastomoses devices.

Hypothermic Oxygenated Perfusion Versus Normothermic Regional Perfusion in Liver Transplantation From Controlled Donation After Circulatory Death: First International Comparative Study.

OBJECTIVE: To compare HOPE and NRP in liver transplantation from cDCD. SUMMARY OF BACKGROUND DATA: Liver transplantation after cDCD is associated with higher rates of graft loss. Dynamic preservation strategies such as NRP and HOPE may offer safer use of cDCD grafts. METHODS: Retrospective comparative cohort study assessing outcomes after cDCD liver transplantation in 1 Swiss (HOPE) and 6 French (NRP) centers. The primary endpoint was 1-year tumor-death censored graft and patient survival. RESULTS: A total of 132 and 93 liver grafts were transplanted after NRP and HOPE, respectively. NRP grafts were procured from younger donors (50 vs 61 years, P < 0.001), with shorter functional donor warm ischemia (22 vs 31 minutes, P < 0.001) and a lower overall predicted risk for graft loss (UK-DCD-risk score 6 vs 9 points, P < 0.001). One-year tumor-death censored graft and patient survival was 93% versus 86% (P = 0.125) and 95% versus 93% (P = 0.482) after NRP and HOPE, respectively. No differences in non-anastomotic biliary strictures, primary nonfunction and hepatic artery thrombosis were observed in the total cohort and in 32 vs. 32 propensity score-matched recipients CONCLUSION:: NRP and HOPE in cDCD achieved similar post-transplant recipient and graft survival rates exceeding 85% and comparable to the benchmark values observed in standard DBD liver transplantation. Grafts in the HOPE cohort were procured from older donors and had longer warm ischemia times, and consequently achieved higher utilization rates. Therefore, randomized controlled trials with intention-to-treat analysis are needed to further compare both preservation strategies, especially for high-risk donor-recipient combinations.

Laparoscopic right hepatectomy using the caudal approach is superior to open right hepatectomy with anterior approach and liver hanging maneuver: a comparison of short-term outcomes.

BACKGROUND: A standardized laparoscopic right hepatectomy (LRH) approach named the "caudal approach" was recently reported. Yet, the value of this approach compared with state-of-the-art open right hepatectomy (ORH) remains unknown. The purpose of this study was therefore to compare the short-term outcomes of LRH using the caudal approach and ORH with anterior approach and liver hanging maneuver. METHODS: One-hundred eleven consecutive patients who underwent LRH with caudal approach were prospectively collected; 346 patients who underwent ORH with anterior approach and liver hanging maneuver were enrolled as a control group. Propensity score matching (PSM) of patients in a ratio of 1: 1 was conducted and the perioperative outcomes were compared. RESULTS: After PSM, two well-balanced groups of 72 patients each were analyzed and compared. The conversion rate in the LRH group was 18.1%. Perioperative blood loss and transfusion rates were significantly lower in the LRH group as compared to the ORH group (median, 200 ml vs. 500 ml, p < 0.001 and 9.9% vs. 26.8%, p = 0.009, respectively), while operation time was significantly longer (median, 348 min vs. 290 min, p < 0.001). Overall (26.4% vs. 48.6%, p = 0.006) and symptomatic pulmonary (6.9% vs. 19.4%, p = 0.027) complication rates were significantly lower in the LRH group. Hospital stay was significantly shorter in the LRH group (median, 8 days vs. 9 days, p = 0.013). CONCLUSIONS: LRH using the caudal approach is associated with improved short-term outcomes compared to state-of-the-art ORH in patients qualifying for both approaches, and can be proposed as standard practice.

Endoscopic treatment of anastomotic biliary stricture after adult deceased donor liver transplantation with multiple plastic stents versus self-expandable metal stents: a systematic review and meta-analysis.

Anastomotic biliary strictures (ABSs) occur in up to 15% of patients after liver transplantation (LT). The aim of this study was to compare the efficacy and safety of self-expandable metal stents (SEMS) versus multiple plastic stents (MPS). Databases were searched through April 2017. The outcome measures were technical success, stricture resolution, recurrence and complications. We synthesized the findings descriptively and performed a meta-analysis. Three randomized controlled trials and one retrospective cohort study were identified, including 179 MPS and 119 SEMS patients. Outcome data were pooled in a meta-analysis that showed an advantage of SEMS in terms of the number of ERCP procedures (mean difference: 1.69 ERCP; 95% CI, 1-2.39; P < 0.00001) and treatment days (mean difference: 40.2 days; 95% CI, 3.9-76.4; P = 0.03), with no differences in terms of ABS resolution or recurrence. Fourteen case series reported MPS outcomes and fifteen reported SEMS outcomes, including 647 and 419 patients, respectively. Based on low-quality evidence, we cannot draw any reliable conclusions on the superiority of MPS or SEMS strategies. Even though shorter treatment times and fewer ERCP procedures support the use of SEMS, whether one technique has well-defined advantages over the other remains unclear.

Clinical impact of laparoscopic hepatectomy: technical and oncological viewpoints.

The objective of this study was to assess the clinical impact of laparoscopic hepatectomy from technical and oncological viewpoints through the consecutive 5-year experience of an expert team. The subjects consisted of 491 consecutive hepatectomies performed over the course of 5 years. A total of 190 hepatectomies (38.6 %) were performed laparoscopically, and the remaining 301 (61.4 %) were open hepatectomies. Chronological trends of operative procedures and their indications were evaluated, and patients with hepatocellular carcinoma (HCC) were analyzed from an oncological viewpoint. The proportion of laparoscopic hepatectomies performed increased significantly during the study period (from 17.6 to 49.5 %). According to chronological trends, right hepatectomy was standardized using consecutive steps after minor hepatectomy, left lateral sectionectomy, and left hepatectomy were standardized. The proportion of laparoscopic hepatectomies performed for HCC increased from 21.4 to 71.0 %. No significant difference was observed in the proportion of major hepatectomies performed for HCC between the open and laparoscopy groups (50.6 vs. 48.6 %, p = 0.8053), whereas that of anatomical segmentectomy for HCC was significantly lower in the laparoscopy group (28.7 vs. 11.1 %, p = 0.0064). All laparoscopic anatomical segmentectomies were of segments 5 and 6, and there was no segmentectomy of posterosuperior lesions. The present study shows the consecutive technical developmental processes for minor hepatectomy, left lateral sectionectomy, left hepatectomy, and right hepatectomy without compromising oncological principles. Laparoscopic anatomical segmentectomy for posterosuperior lesions may be the most technically demanding procedure, requiring individualized standardization.

Improving graft survival by understanding the mechanism of segment 4 complications after split liver transplantation.

BACKGROUND: This study was designed to assess the actual mechanism of segment 4 (S4)-related complications after split liver transplantation (SLT) and their impact on graft and overall survival with reference to those of left lateral sectionectomy for pediatric living donor liver transplantation (LLSLD). METHODS: Clinical data from 53 SLT recipients and 62 LLSLD patients were assessed to determine the mechanism of S4-related complications. The postoperative parameters of SLT and their impact on graft and overall survival were also evaluated. RESULTS: Although two biliary leakages were noted (3.2%), no necrosis of S4 developed after LLSLD. S4-related complications were seen in 15 (28.3%) patients after SLT. Radiological volumetry of S4 and the ischemic area after SLT showed no significant difference between those with and without S4-related complications. There were no significant differences between the patients with and without S4-related complications regarding both overall and graft survival rates. Significant better overall and graft survival rates were observed in patients treated during the later period. CONCLUSIONS: S4-related complications after SLT are totally independent of the S4 volume, and biliary leakage is inherently an actual mechanism. Adequate intervention with early identification leads to better graft and overall survival, which validates SLT as a treatment option.

Preliminary report of major surgery in liver transplant recipients receiving m-TOR inhibitors without therapeutic discontinuation.

INTRODUCTION: Mammalian target rapamycin inhibitors (m-TORi) are increasingly used in patients undergoing liver transplantation (LT). Yet, there is rising concern that they also could impair wound healing and favor the development of several surgical complications. This report was designed to evaluate both feasibility and safety of major surgery in liver transplant recipients receiving m-TORi-based immunosuppression without therapeutic discontinuation. METHODS: From 2007 to 2012, six liver transplant recipients underwent nine major abdominal or thoracic surgical procedures without m-TORi discontinuation or specific dosage adjustment. Their characteristics and postoperative outcomes were retrospectively analyzed. RESULTS: Indications for m-TORi were de novo or recurrent malignant disease in five patients and calcineurin inhibitors related neurologic toxicity in one patient. Abdominal procedures, thoracic procedures, and combined thoracic and abdominal procedures were performed in six, two, and one cases respectively. Emergency surgery was performed in one case and elective procedures were performed in eight cases, including five for malignant disease and three for late surgical complications following LT. No patient died postoperatively. One major complication was observed, but no patient required reoperation. No evisceration, incisional surgical site infection, or lymphocele occurred. CONCLUSIONS: Major surgery in liver transplant recipients receiving m-TOR inhibitors appears both feasible and safe without therapeutic discontinuation or specific dosage adjustment.

Split liver transplantation using extended right grafts: the natural history of segment 4 and its impact on early postoperative outcomes.

Split liver transplantation (SLT) using extended right grafts is associated with complications related to ischemia of hepatic segment 4 (S4), and these complications are associated with poor outcomes. We retrospectively analyzed 36 SLT recipients so that we could assess the association of radiological, biological, and clinical features with S4 ischemia. The overall survival rates were 84.2%, 84.2%, and 77.7% at 1, 3, and 5 years, respectively. The recipients were mostly male (24/36 or 67%) and had a median age of 52 years (range = 13-63 years), a median body mass index of 22.9 kg/m(2) (range = 17.3-29.8 kg/m(2) ), and a median graft-to-recipient weight ratio of 1.3% (range = 0.9%-1.9%). S4-related complications were diagnosed in 22% of the patients (8/36) with a median delay of 22 days (range = 10-30 days). Secondary arterial complications were seen in 3 of these patients and led to significantly decreased graft survival in comparison with the graft survival of patients without complications (50.0% versus 85.6%, P = 0.017). Patients developing S4-related complications had significantly elevated aspartate aminotransferase (AST) levels (>1000 IU/L) on postoperative day (POD) 1 and elevated gamma-glutamyl transpeptidase (GGT) levels (>300 IU/L) on PODs 7 and 10 (P < 0.05). These AST and GGT elevations conferred a significantly high risk of developing these complications (odds ratio = 42, 95% confidence interval = 4-475, P < 0.05). The ischemic volume of S4 was extremely variable (0%-95%) and did not correlate with S4-related complications. In conclusion, our results suggest that S4-related complications are risk factors for worse graft survival, and the development of these complications can be anticipated by the early identification of a specific biological profile and a routine radiological examination.

Removable intraductal stenting in duct-to-duct biliary reconstruction in liver transplantation.

Biliary reconstruction during liver transplantation (LT) is most oftenly performed by duct-to-duct biliary anastomosis. We hypothesized that the internal stenting might diminish the incidence and severity of biliary complications in patients receiving small duct size donor grafts. The purpose of this study was to report a technique of biliary reconstruction, including intraductal stent tube (IST) placement followed by postoperative endoscopic removal. A custom-made segment of a T-tube was placed into the bile in 20 patients in whom the diameter of the graft bile duct was smaller than 5 mm. The tube was removed endoscopically 4-8 months after LT, or in case of IST-related adverse events. After a median follow-up of 15.2 (range 2.5-27.5) months, endoscopic removal of the IST was performed in 17 patients. No technical failure and no procedure-related complications were recorded during drain removal. Biliary complications occurred in four patients, including one cholangitis, one hemobilia, one asymptomatic biliary leakage, and one anastomotic stricture. No biliary complication occurred in the group of patients who underwent deceased donor whole graft LT. IST is technically feasible and safe, and may help to prevent severe biliary complication when duct-to-duct biliary anastomosis is performed on small size bile ducts.