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.

Impact of COVID-19 on the management of hepatocellular carcinoma in a high-prevalence area.

BACKGROUND & AIMS: Patients affected by hepatocellular carcinoma (HCC) represent a vulnerable population during the COVID-19 pandemic and may suffer from altered allocation of healthcare resources. The aim of this study was to determine the impact of the COVID-19 pandemic on the management of patients with HCC within 6 referral centres in the metropolitan area of Paris, France. METHODS: We performed a multicentre, retrospective, cross-sectional study on the management of patients with HCC during the first 6 weeks of the COVID-19 pandemic (exposed group), compared with the same period in 2019 (unexposed group). We included all patients discussed in multidisciplinary tumour board (MTB) meetings and/or patients undergoing a radiological or surgical programmed procedure during the study period, with curative or palliative intent. Endpoints were the number of patients with a modification in the treatment strategy, or a delay in decision-to-treat. RESULTS: After screening, n = 670 patients were included (n = 293 exposed to COVID, n = 377 unexposed to COVID). Fewer patients with HCC presented to the MTB in 2020 (p = 0.034) and fewer had a first diagnosis of HCC (n = 104 exposed to COVID, n = 143 unexposed to COVID, p = 0.083). Treatment strategy was modified in 13.1% of patients, with no differences between the 2 periods. Nevertheless, 21.5% vs. 9.5% of patients experienced a treatment delay longer than 1 month in 2020 compared with 2019 (p <0.001). In 2020, 7.1% (21/293) of patients had a diagnosis of an active COVID-19 infection: 11 (52.4%) patients were hospitalised and 4 (19.1%) patients died. CONCLUSIONS: In a metropolitan area highly impacted by the COVID-19 pandemic, we observed fewer patients with HCC, and similar rates of treatment modification, but with a significantly longer treatment delay in 2020 vs. 2019. LAY SUMMARY: During the coronavirus disease 2019 (COVID-19) pandemic era, fewer patients with hepatocellular carcinoma (HCC) presented to the multidisciplinary tumour board, especially with a first diagnosis of HCC. Patients with HCC had a treatment delay that was longer in the COVID-19 period than in 2019.

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.

Favorable Outcomes of Liver Transplantation from Controlled Circulatory Death Donors Using Normothermic Regional Perfusion Compared to Brain Death Donors.

BACKGROUND: Liver transplantation (LT) from controlled donation after circulatory death (cDCD) was initiated in France in 2015 under a protocol based on the use of normothermic regional perfusion (NRP) before organ procurement. The aim was to compare outcomes following cDCD LT with NRP and donation after brain death (DBD) LT. METHODS: This is a multicenter retrospective study comparing cDCD LT with NRP and DBD LT. A case-matched study (1:2) was performed using the variables such as recipient and donor age, indication of LT. RESULTS: A total of 50 patients from the cDCD group were matched to 100 patients from the DBD group. From postoperative days 1-4, serum transaminase release was significantly lower in the cDCD group compared to the DBD group (P < 0.05). Early allograft dysfunction (cDCD: 18% versus DBD: 32%; P = 0.11), acute kidney injury (26% versus 33%; P = 0.49), 90-d graft loss (2% versus 5%; P = 0.66), and arterial (4% versus 12%; P = 0.19) and biliary (16% versus 17%; P = 0.94) complications were similar between the 2 groups. The 2-y graft survival was 88% for cDCD group and 85% for DBD group (P = 0.91). The 2-y patient survival was 90% for cDCD group and 88% for DBD group (P = 0.68). CONCLUSIONS: This study provides evidence that cDCD LT following postmortem NRP can be safely and effectively performed in selected recipients with similar graft and patient survival outcomes, without increased rates of biliary complications and early graft dysfunction compared to DBD LT.

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.

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.

Liver Retransplantation Associated With Kidney Transplantation for End-stage Liver Graft Disease and Renal Insufficiency: A Morbid Procedure on a Unique Subgroup of Patients.

BACKGROUND: Chronic renal disease (CKD) jeopardizes the long-term outcomes of liver transplant recipients. In patients with end-stage liver graft disease and CKD, liver retransplantation associated with kidney transplantation (ReLT-KT) might be necessary. Yet, this specific subset of patients remains poorly described. METHODS: Indications, perioperative characteristics, and short- and long-term outcomes of patients undergoing ReLT-KT at 2 transplantation units from 1994 to 2012 were analyzed. Risk factors for postoperative mortality and long-term survivals were evaluated. RESULTS: Among 3060 patients undergoing liver transplantation (LT), 45 (1.5%) underwent ReLT-KT. The proportion of ReLT-KT among LT recipients continuously grew throughout the study period from 0.3% to 2.4% (P < 0.001). Median time from primary LT to ReLT-KT was 151.3 (7.5-282.9) months. The most frequent indications for liver retransplantation were recurrence of the primary liver disease and cholangitis in 15 (33.3%) cases each. CKD was related to calcineurin inhibitors toxicity in 38 (84.4%) cases. Twelve (26.7%) patients died postoperatively. D-MELD (donor age × recipients' MELD) was associated with postoperative mortality (HR: 8.027; 95% CI: 2.387-18.223; P = 0.026) and optimal cut-off value was 1039 (AUC: 0.801; P = 0.002). Overall 1, 3, and 5 years survivals were 68.8%, 65.9%, and 59.5%, respectively. D-MELD > 1039 was the only factor associated with poor survival (P = 0.021). CONCLUSIONS: ReLT-KT is a highly morbid increasingly performed procedure. Refinements in the selection of grafts and transplant candidates are required to limit the postoperative mortality of these patients.

Modified Technique of Total Hepatectomy in Polycystic Liver Disease With Caval Flow Preservation: The Exposure Left Lateral Sectionectomy.

BACKGROUND: Liver transplantation (LT) for polycystic liver disease (PLD) is rare, extremely challenging and hemorrhagic, without standard approach. Moreover, LT for PLD presents the highest mortality rate (12% to 18%) among all causes of LT. In this setting, the combination of difficult mobilization of a heavy polycystic native liver with narrow access to inferior vena cava and fragile venous wall may lead to venous tearing and cataclysmic bleeding during dissection. The aim of this study was to evaluate a modified technique of total hepatectomy to limit hazardous liver manipulation and improve exposure of inferior vena cava in patients with massive hepatomegaly related to PLD: the exposure left lateral sectionectomy (ELLS). METHODS: From 2011 to 2018, ELLS was performed during LT for PLD. Key technical points for safe and fast ELLS include avoidance of left triangular ligament section and placement of a tape behind the left lateral section allowing its ascension and prior dissection of the hepatic pedicle to limit bleeding. The transection plane is mainly composed of cysts, with limited parenchyma, which allows for rapid and bloodless transection using electric scalpel. RESULTS: Fifteen patients had ELLS with no postoperative death or intraoperative complication. Median ELLS duration was 16 minutes, and no massive bleeding occurred during this step. During total hepatectomy, median blood loss was 500 mL, and no patient required total caval clamping. All patients were alive at the end of the follow-up. CONCLUSIONS: ELLS during LT for PLD facilitates total hepatectomy with vena cava and caval flow preservation.

Endovascular Treatment of Arterial Complications After Liver Transplantation: Long-Term Follow-Up Evaluated on Doppler Ultrasound and Magnetic Resonance Cholangiopancreatography.

PURPOSE: To evaluate long-term arterial patency and abnormalities of bile ducts in patients that had endovascular treatment for arterial complications after liver transplantation (LT). MATERIALS AND METHODS: Between 2004 and 2014, 1048 LTs were consecutively performed in our institution and 53 patients (42 men; age range 19-69) were diagnosed and treated by endovascular techniques for arterial complications such as stenosis, thrombosis, dissection or kinking of the hepatic artery (HA). Radiological and surgical data were retrospectively analyzed, and survivors were contacted to undergo follow-up Doppler ultrasound (DUS) of the HA and magnetic resonance cholangiopancreatography. RESULTS: The primary technical success of endovascular treatment was 94% (n = 50). The patency rate of HA at 5-year was 81%. After a median follow-up of 58 months, 17 patients (32%) developed radiological features of ischemic cholangiopathy (IC), including 7 patients with abnormal DUS and 10 with normal DUS. Patients who presented with complications of the HA in the first 3 months after LT developed IC more frequently (42%) than others (12%) (p = 0.028). No other factor was associated with the development of IC. CONCLUSION: IC was more often observed when HA complication occurred within the first 3 months after LT. The presence of IC was not excluded by a normal DUS during follow-up.

Computer-assisted liver graft steatosis assessment via learning-based texture analysis.

PURPOSE: Fast and accurate graft hepatic steatosis (HS) assessment is of primary importance for lowering liver dysfunction risks after transplantation. Histopathological analysis of biopsied liver is the gold standard for assessing HS, despite being invasive and time consuming. Due to the short time availability between liver procurement and transplantation, surgeons perform HS assessment through clinical evaluation (medical history, blood tests) and liver texture visual analysis. Despite visual analysis being recognized as challenging in the clinical literature, few efforts have been invested to develop computer-assisted solutions for HS assessment. The objective of this paper is to investigate the automatic analysis of liver texture with machine learning algorithms to automate the HS assessment process and offer support for the surgeon decision process. METHODS: Forty RGB images of forty different donors were analyzed. The images were captured with an RGB smartphone camera in the operating room (OR). Twenty images refer to livers that were accepted and 20 to discarded livers. Fifteen randomly selected liver patches were extracted from each image. Patch size was [Formula: see text]. This way, a balanced dataset of 600 patches was obtained. Intensity-based features (INT), histogram of local binary pattern ([Formula: see text]), and gray-level co-occurrence matrix ([Formula: see text]) were investigated. Blood-sample features (Blo) were included in the analysis, too. Supervised and semisupervised learning approaches were investigated for feature classification. The leave-one-patient-out cross-validation was performed to estimate the classification performance. RESULTS: With the best-performing feature set ([Formula: see text]) and semisupervised learning, the achieved classification sensitivity, specificity, and accuracy were 95, 81, and 88%, respectively. CONCLUSIONS: This research represents the first attempt to use machine learning and automatic texture analysis of RGB images from ubiquitous smartphone cameras for the task of graft HS assessment. The results suggest that is a promising strategy to develop a fully automatic solution to assist surgeons in HS assessment inside the OR.