Conversion from twice-daily everolimus to once-daily sirolimus in long-term stable liver transplant recipients.

BACKGROUND: After organ transplantation, strategies for simplifying the therapeutic regimen may improve adherence and prevent acute organ rejection and/or late graft loss. The present study aimed to evaluate the safety and efficacy of conversion from everolimus (EVR) twice daily to sirolimus (SIR) once daily in a large cohort of liver transplantation (LT) patients. METHODS: We included 108 LT patients with at least 12 months of post-transplant follow-up and no rejection episodes in the last year. Conversion was based on a 1:1 ratio (but eventually adapted to available formulations of SIR). RESULTS: The median age at the time of conversion was 68.9 years (range: 26.1-83.6); 75.0% were men. The main indications for mTOR inhibitor use were renal failure (38.9%) and/or a history of malignancy (37.0%). Median conversion time after LT was 14.8 years (range: 2.3-31.5). The median dose of EVR and SIR (initially) was 1.50 mg/day (range: 0.5-4.5). The mean follow-up after conversion was 15.8±4.4 months. Median serum EVR/SIR trough levels before/after conversion were 3.85 ng/mL vs. 6.32 ng/mL (p < 0.05), i.e. a 1:1.64 ratio. At the end of follow-up after conversion, the median dose of SIR was 1.25 mg/day (range: 0.5-3.5), and the mean serum SIR trough level was 5.23 ng/mL; 9 patients (8.3%) had returned to EVR, because of side effects (mainly digestive), that resolved thereafter. No biopsy-proven acute rejection episode was observed. Finally, 87.1% of patients considered the conversion beneficial and the cost was reduced by 50.3%. CONCLUSION: The results of our study indicate that conversion from once-daily EVR to once-daily SIR in stable LT patients is safe, but needs dose adaptations and careful monitoring.

Dual alcohol and metabolic-related liver disease: Results from a population of liver transplant patients.

BACKGROUND & AIMS: If alcohol-related liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are now the two main indications for liver transplantation (LT), it has been recognized that both conditions can coexist in varying degrees and the concept of dual-aetiology fatty liver disease (DAFLD) has been proposed. This retrospective study aimed to evaluate, in a cohort of patients transplanted for ALD and NAFLD, the prevalence of DAFLD before LT and the impact on liver graft outcome. METHODS: From 1990 to 2010, all patients who underwent LT for the so-called ALD or NAFLD in our centre were included. Before LT, DAFLD was defined as patients with a history of excessive alcohol consumption and obesity associated with either diabetes or hypertension. Before LT, patients were separated into three groups: DAFLD, ALD, and NAFLD. Fatty liver graft disease was classified according to the FLIP algorithm. RESULTS: Out of 907, adult LT recipients were identified: 33 DAFLD patients, 333 ALD patients, and 24 NAFLD patients. After LT, ALD patients experienced significantly more alcohol relapse than DAFLD patients, who had twice more post-LT metabolic syndrome. Out of 926, post-LT biopsies, DAFLD patients had significantly more fatty liver graft disease due to metabolic syndrome features than ALD patients. CONCLUSION: Our results support that DAFLD recently emerged as an indication of LT. In the future, this particular population needs to be identified as a specific entity since post-LT outcome on the graft is different from ALD and more similar to NAFLD patients.

Determinants of early surgical complications after pediatric liver transplantation: A single center/single surgeon experience over 20 years.

BACKGROUND: The risk of early surgical complications of liver transplantation (LT) is higher in children when compared with adults. The aims of the present retrospective study from a single center cohort/single surgeon were to identify the predictive factors for surgical complications after pediatric LT. METHODS: All children receiving a first LT from October 1990 to October 2010 in our center were included. RESULTS: Included 151 children (boys 55.0%), with a mean age of 4.8 ± 4.8 years, and a mean weight of 17.9 ± 14.4 kg. Thirty-seven patients were transplanted within the first year, and 59 patients had a body weight below 10 kg. The main initial liver disease was biliary atresia (49.0%). Living donor LT was performed in 39 cases (25.8%), cadaveric whole liver LT in 50 cases (33.1%), and cadaveric partial liver LT in 62 cases (41.1%). Early surgical complications included reoperation (37.8%), vascular complications (8.6%), i.e. arterial (3.3%) or portal thrombosis/stenosis (7.3%) within the first month, and biliary complications in the first 90 days occurred in 22.5% of the cases. The main indications for surgical revision were abdominal bleeding, treatment of a biliary complication, and bowel perforation. Multivariate analysis disclosed that only graft type (split and moreover from a living donor) was significantly and independently associated with the occurrence of biliary complication, and that indication for LT, period, graft type, and operative time were significantly and independently associated with the necessity of surgical revision. CONCLUSION: Our results emphasize that surgical complications are frequent and strongly depend on patient/graft characteristics.

Integrating an addiction team into the management of patients transplanted for alcohol-associated liver disease reduces the risk of severe relapse.

Background & Aims: Liver transplantation (LT) is a last resort treatment for patients at high risk of mortality from end-stage liver disease. Over the past years, alcohol-associated liver disease has become the most frequent indication for LT in the world. The outcomes of LT for alcohol-associated liver disease are good, but return to alcohol use is detrimental for medium-term survival because of cancer development, cardiovascular events, and recurrent alcohol-associated cirrhosis. Several strategies have been developed to prevent return to alcohol use during the pre- or post-LT period, but there are no specific recommendations. Therefore, the main objective of this study was to investigate if the integration of an addiction team in a LT unit affected the rate of severe alcohol relapse after LT. The secondary objectives were to assess the effects of addiction follow up on cardiovascular events, cancer, and overall survival. Methods: This study was a retrospective comparison between centres with or without addiction monitoring. Results: The study included 611 patients of which 79.4% were male with a mean age of 55.4 years at the time of LT, 190 were managed by an integrated addiction team. The overall alcohol relapse rate was 28.9% and the rate of severe relapse was 13.0%. Patients with addiction follow-up had significantly less frequent severe alcohol relapse than those in the control group (p = 0.0218). Addiction follow up (odds ratio = 0.19; p = 0.001) and age at LT (odds ratio = 1.23; p = 0.02) remained significantly associated with post-LT cardiovascular events. Conclusions: Our study confirms the benefits of integrating an addiction team to reduce return to alcohol use after LT. Clinical Trials registration: This study is registered at ClinicalTrials.gov (NCT04964687). Impact and implications: The main indication for liver transplantation is alcohol-associated cirrhosis. There are currently no specific recommendations on the addiction monitoring of transplant candidates, although severe return to alcohol use after liver transplantation has a negative impact on long-term survival of patients. In this study, we explored the impact of a systematic addiction intervention on the return to alcohol use rates. In our transplantation centre, we demonstrated the interest of an addiction follow up to limit the severe alcohol relapses rate. This information should be further investigated in prospective studies to validate these data.

Treatment of donor-specific anti-HLA antibodies-mediated rejection after liver transplantation: A French nationwide retrospective study.

The deleterious effect of donor-specific anti-HLA antibodies (DSA) after liver transplantation (LT) has been increasingly recognized during the past decade. Antibody-mediated rejection (AMR) represents a rare but severe complication in the presence of DSA. However, little is known concerning the treatment of AMR after LT. The nationwide French study aimed to describe LT recipients who received specific treatment of AMR. We performed a multicenter retrospective study on 44 patients who were treated with B-cell targeting agents from January 2008 to December 2020. Median patient age at the time of AMR treatment was 51.6 years (range: 17.9-68.0). AMR was classified as acute (n = 19) or chronic (n = 25). The diagnosis of AMR was made after a median time of 16.8 months (range: 0.4-274.2) after LT. The main therapeutic combination was plasma exchange/rituximab/IVIG (n = 25, 56.8%). The median follow-up after the treatment of AMR was 32 months (range: 1-115). After the treatment, 1-, 5- and 10-year patient and graft survivals were 77%, 55.9%, and 55.9%, and 69.5%, 47.0%, and 47.0%, respectively. Initial total bilirubin (Q1-Q3 vs. Q4) was significantly associated with patient survival (log-rank test, p = 0.005) and graft survival (log-rank test, p = 0.002). After a median follow-up of 21 months (range: 12-107), DSA became undetectable in 15/38 patients (39.5%) with available DSA monitoring. In conclusion, specific treatment of AMR in LT recipients has slowly emerged in France during the past decade and has probably been considered in the most severe patients; this explains the global poor outcome, even if the outcome was favorable in some cases.

Iterative antibody-induced bile salt export pump deficiency after successive liver transplantations successfully treated with plasmapheresis and rituximab.

Post-transplantation evolution of progressive familial intrahepatic cholestasis type 2 patients can be complicated by antibody-induced bile salt export pump deficiency (AIBD). There is no consensus on its management. We describe a patient who presented two episodes, 9 years apart. The first episode was refractory to plasmapheresis and intravenous immunoglobulin (IVIG) started 2 months after AIBD onset, leading to graft loss. The second episode responded to plasmapheresis, IVIG and rituximab initiated less than 2 weeks after the beginning of symptoms, allowing for long-term recovery. This case suggests that intensive treatment with minimum delay after symptoms onset could sponsor a better evolution.

Inevitability of disease recurrence after liver transplantation for NAFLD cirrhosis.

Background & Aims: Liver transplantation (LT) is the only available treatment for end-stage non-alcoholic fatty liver disease (NAFLD) (related decompensated cirrhosis and/or hepatocellular carcinoma). The aim of our study was to evaluate the risk of disease recurrence after LT and the factors influencing it. Method: This retrospective multicenter study included adults transplanted for NAFLD cirrhosis between 2000 and 2019 in 20 participating French-speaking centers. Disease recurrence (steatosis, steatohepatitis and fibrosis) was diagnosed from liver graft biopsies. Results: We analyzed 150 patients with at least one graft liver biopsy available ≥6 months after transplantation, among 361 patients transplanted for NAFLD. The median (IQR) age at LT was 61.3 (54.4-64.6) years. The median follow-up after LT was 4.7 (2.8-8.1) years. The cumulative recurrence rates of steatosis and steatohepatitis at 5 years were 80.0% and 60.3%, respectively. Significant risk factors for steatohepatitis recurrence in multivariate analysis were recipient age at LT <65 years (odds ratio [OR] 4.214; p = 0.044), high-density lipoprotein-cholesterol <1.15 mmol/L after LT (OR 3.463; p = 0.013) and grade ≥2 steatosis on the graft at 1 year after LT (OR 10.196; p = 0.001). The cumulative incidence of advanced fibrosis (F3-F4) was 20.0% at 5 years after LT and significant risk factors from multivariate analysis were metabolic syndrome before LT (OR 8.550; p = 0.038), long-term use of cyclosporine (OR 11.388; p = 0.031) and grade ≥2 steatosis at 1 year after LT (OR 10.720; p = 0.049). No re-LT was performed for NAFLD cirrhosis recurrence. Conclusion: Our results strongly suggest that recurrence of initial disease after LT for NAFLD is inevitable and progressive in a large proportion of patients; the means to prevent it remain to be further evaluated. Impact and implications: Non-alcoholic fatty liver disease (NAFLD) is a growing indication for liver transplantation, but the analysis of disease recurrence, based on graft liver biopsies, has been poorly studied. Cumulative incidences of steatosis, steatohepatitis and NAFLD-related significant fibrosis recurrence at 5 years were 85.0%, 60.3% and 48.0%, respectively. Grade ≥2 steatosis on graft biopsy at 1 year (present in 25% of patients) is highly predictive of recurrence of steatohepatitis and advanced fibrosis: bariatric surgery should be discussed in these patients specifically.

Are protocol graft biopsies after pediatric liver transplantation useful? Experience in a single center over 20 years.

BACKGROUND: The role of protocol liver biopsies (PLB) in the follow-up of pediatric liver transplant recipients remains questionable. This single-center retrospective study aimed to evaluate their clinical impact on the long-term management of pediatric liver transplant recipients. METHODS: We described histopathological lesions and clinical consequences for patient management of PLB performed 1, 5, 10, 15, 20, and 25 years after pediatric liver transplantation (LT). RESULTS: A total of 351 PLB performed on 133 patients between 1992 and 2021 were reviewed. PLB found signs of rejection in 21.7% of cases (76/351), and moderate to severe fibrosis in 26.5% of cases (93/351). Overall, 264 PLB (75.2%) did not cause any changes to patient care. Immunosuppression was enhanced after 63 PLB, including 23 cases of occult rejection. The 1-year PLB triggered significantly more changes, while biopsies at 15, 20, and 25 years produced the lowest rates of subsequent modifications. PLB had a significantly higher probability of inducing therapeutic changes if the patient had abnormal biological or imaging results (odds ratio [OR] 2.82 and 2.06), or a recent history of rejection or bacterial infection (OR 2.22 and 2.03). CONCLUSION: Our results suggest that, although it often does not prompt any treatment changes, PLB could be performed because of its ability to detect silent rejection requiring an increase in immunosuppression. PLB could be carried out 1, 5, and 10 years after LT and then every 10 years in patients with normal biological and imaging results and no recent complications, while other patients could be kept on a 5-year protocol.

Antineoplastic chemotherapy and immunosuppression in liver transplant recipients: Squaring the circle?

BACKGROUND: Malignancies are a major cause of late death after liver transplantation (LT). In LT recipients presenting a malignancy, antineoplastic chemotherapy is central part of the therapeutic arsenal, but management of both immunosuppressive and antineoplastic chemotherapy can be very challenging. The aim of the present retrospective study was to describe a recent single center cohort of LT recipients treated with antineoplastic cytotoxic chemotherapy. METHODS: All LT recipients who received antineoplastic chemotherapy in our center between 2005 and 2021 were included. RESULTS: The study population included 72 antineoplastic chemotherapy courses in 69 patients. There was a majority of men (81.9%); median age at LT was 54.9 (range 1-68) and was 63.0 (18-79) at the diagnosis of malignancy. Lung carcinomas (23.6%), head and neck carcinomas (20.8%), lymphomas (16.7%), and recurrent hepatocellular carcinoma (HCC) (8.3%) were the most frequent malignancies. Neoadjuvant (30.6%), adjuvant (12.5%) or palliative (54.2%) chemotherapy was performed. Immunosuppressive regimen was modified from a calcineurin inhibitor (CNI)-based to an everolimus-based regimen (63.5% of CNI discontinuation). Median survival after diagnosis of malignancy was 22.5 months and 5-year survival was 30.1%. Chemotherapy regimen was considered optimal in 81.9% of the cases. Multivariate analysis disclosed that non-PTLD N+ stage malignancy (HR = 5.52 95%CI [1.40;21.69], p = .014), non-PTLD M+ stage malignancy (HR = 10.55 95%CI [3.20;34.73], p = .0001), and suboptimal chemotherapy (HR = 2.73 95%CI [1.34;5.56], p = .005) were significantly associated with poorer prognosis. No rejection episode occurred during chemotherapy. CONCLUSIONS: The present study is the first one focused on antineoplastic chemotherapy in LT recipients. Our results suggest that immunosuppressive drugs and antineoplastic chemotherapy can be managed satisfactorily in most cases but this needs confirmation from larger cohorts.

Liver transplantation for NAFLD cirrhosis: Age and recent coronary angioplasty are major determinants of survival.

BACKGROUND AND AIMS: Liver transplantation (LT) is the treatment of end-stage non-alcoholic liver disease (NAFLD), that is decompensated cirrhosis and/or complicated by hepatocellular carcinoma (HCC). Few data on long-term outcome are available. The aim of this study was to evaluate overall patient and graft survivals and associated predictive factors. METHOD: This retrospective multicentre study included adult transplant patients for NAFLD cirrhosis between 2000 and 2019 in participating French-speaking centres. RESULTS: A total of 361 patients (69.8% of male) were included in 20 centres. The median age at LT was 62.3 years [57.4-65.9] and the median MELD score was 13.9 [9.1-21.3]; 51.8% of patients had HCC on liver explant. Between 2004 and 2018, the number of LT for NAFLD cirrhosis increased by 720%. A quarter of the patients had cardiovascular history before LT. Median follow-up after LT was 39.1 months [15.8-72.3]. Patient survival at 1, 5 and 10 years after LT was 89.3%, 79.8% and 68.1% respectively. The main causes of death were sepsis (37.5%), malignancies (29.2%) and cardiovascular events (22.2%). In multivariate analysis, three risk factors for overall mortality after LT were recipient pre-LT BMI < 32 kg/m2 at LT time (OR: 2.272; p = .012), pre-LT angioplasty during CV check-up (OR: 2.916; p = .016), a combined donor and recipient age over 135 years (OR: 2.020; 95%CI: p = .035). CONCLUSION: Survival after LT for NAFLD cirrhosis is good at 5 years. Donor and recipient age, and cardiovascular history, are major prognostic factors to consider.

Prophylactic sequential antibiotic therapy for recurrent liver/biliary sepsis.

BACKGROUND AND AIMS: Recurrent liver/biliary sepsis are rare and can occur in different situations. Curative treatment of acute septic episodes is based on antibiotics. Nevertheless, recurrent sepsis can be life-threatening, and the treatment of the underlying disease could be complex, and eventually not possible. The aim of the present study was to report our experience on prophylactic sequential antibiotic therapy for recurrent liver/biliary sepsis in a large cohort of patients with long follow-up. METHODS: All patients who received a prophylactic sequential antibiotic therapy for recurrent liver/biliary sepsis in our institution from 2005 to 2020 were included. Prophylactic sequential antibiotic therapy was based on per os antibiotics with expected antibacterial activity on digestive bacteria, mainly Gram-negative bacilli. The primary end-point was the reduction of the number of septic episodes to 1 or less episode per year, and not severe (not requiring hospitalization). RESULTS: Were included 33 adult patients and the main initial disease/condition leading to prophylaxis was history of hepaticojejunostomy (78.8%). The majority of septic episodes required hospitalization (57.6%). First line prophylactic sequential antibiotic therapy was weekly ciprofloxacin in all cases. First line therapy was successful in the long-term in 19 patients (57.6%), with a median follow-up of 92 months (range: 25-206). Global efficacy (first-second-third lines) was 28/33 (84.8%). CONCLUSIONS: The results of the present study with very long follow-up suggest that prophylactic sequential antibiotic therapy can successfully prevent recurrent liver/biliary sepsis with good tolerance.

Partial splenectomy in children undergoing liver transplantation or venous shunt for severe hypersplenism: A case control comparative study.

BACKGROUND AND AIM: Hypersplenism is a consequence of portal hypertension and splenomegaly secondary to cirrhosis or portal cavernoma in children. In order to avoid persistent hypersplenism and splenomegaly after liver transplantation (LT) or venous shunt (VS), partial splenectomy (PS) may represent a relevant therapeutic option. The aim of this retrospective study was to evaluate the results of PS performed in children presenting hypersplenism. METHODS: The following end-points were evaluated: (1) reversion of hypersplenism and its durability over time, (2) postoperative outcome, (3) courses of spleen size and volume and (4) comparison to a control group in which PS was not performed. RESULTS: Between 1996 and 2020, 16 children underwent PS associated with LT (8 cases) for cirrhosis or VS (8 cases) for portal cavernoma. From Day 0 to 1 month, mean platelet and white blood cell counts (WBC) dramatically improved from 48 ±â€¯19 at day 0 to 176 ±â€¯70 × 109/L (P < 0.0001) and from 2469 ±â€¯853 to 7198 ±â€¯3982/L (P = 0.001) respectively. PS allowed significant reduction of splenic length and volume from 176 ±â€¯33 to 112 ±â€¯24 cm (P < 0.0001) and from 1228 ±â€¯464 to 450 ±â€¯297 cm3 (P = 0.0003) respectively. After a mean follow-up of 92.6 ±â€¯84.7 months (range: 4.1-210.7), 14 patients are alive with normal platelet and WBC counts and persistent spleen size reduction. Compared to control group, PS was associated with a significant platelet count rise from baseline to one year. CONCLUSIONS: PS appears to be effective for treatment of hypersplenism and splenomegaly in combination with LT or VS without compromising outcome.

Mycophenolate mofetil decreases humoral responses to three doses of SARS-CoV-2 vaccine in liver transplant recipients.

BACKGROUND AND AIMS: After 2 doses, the efficacy of anti-SARS-CoV-2 vaccination seems to be lower in solid organ transplant recipients than in the immunocompetent population. The objective of this study was to determine the humoral response rate after vaccination, including with a booster dose, and to identify risk factors for non-responsiveness in liver transplant recipients. METHODS: We included all patients seen in consultation in two French liver transplant centres between January 1, 2021, and March 15, 2021. RESULTS: 598 liver transplant recipients were enrolled and 327 were included for analysis. Sixteen patients received one dose, 63 patients two doses and 248 patients three doses. Anti-SARS-Cov-2 antibodies were detected in 242 out of 327 (74.0%) liver transplant patients after vaccination. Considering an optimal serologic response defined as an antibody titre >260 BAU/ml, 172 patients (52.6%) were responders. Mycophenolate mofetil (MMF) treatment was an independent risk factor for a failure to develop anti-SARS-CoV-2 antibodies after vaccination (OR 0.458; 95%CI 0.258-0.813; p = .008). Conversely, male gender (OR 2.247, 95%CI 1.194-4.227; p = .012) and receiving an mRNA vaccine (vs a non-mRNA vaccine) (OR 4.107, 95%CI 1.145-14.731; p = .030) were independent predictive factors for developing an optimal humoral response after vaccination. None of the patients who received the vaccine experienced any serious adverse events. CONCLUSIONS: Even after a third booster dose, response rate to vaccination is decreased in liver transplant recipients. MMF appears to be a major determinant of seroconversion and optimal response to vaccination in these patients.

Impact of calcineurin inhibitor-free immunosuppression on de novo donor-specific antibody formation in liver transplant recipients.

BACKGROUND & AIMS: Low calcineurin inhibitor (CNI) levels expose liver transplant recipients to rejection episodes and potentially to antibody-mediated rejection. There are little data on the impact of CNI-free immunosuppression on de novo donor-specific HLA antibody (dnDSA) development. Here we evaluated the prevalence of dnDSA in liver transplant recipients on CNI-free maintenance regimens and their associations with histopathological abnormalities of allografts. METHODS: Seven hundred and twenty-seven liver transplant recipients underwent a first liver transplant between 2000 and 2018 in three French transplant centres and had protocolized follow-up with dnDSA screening and allograft biopsy 1, 5 and 10 years after transplantation. RESULTS: CNIs were withdrawn in 166 (22.8%) patients with or without conversion to mammalian target of rapamycin inhibitors and/or maintenance with mycophenolic acid. DSA were present after withdrawal in 30.1% (50/166) patients on CNI-free immunosuppression compared with 16% (90/561) on CNI maintenance therapy (p < 0.001). The cumulative incidence of dnDSA 10 years after transplant was 20% in the CNI group versus 28% in the CNI-free group (p < 0.01). dnDSAs were associated with histological graft abnormalities (significant allograft fibrosis or rejection) (HR 2.24, 95% CI 1.2-4.1; p = 0.01). In univariate Cox regression analysis, being on a CNI-free regimen did not impact graft histology. CONCLUSIONS: Patients on a CNI-free IS regimen have a higher prevalence of dnDSA than patients on a standard IS regimen. dnDSAs but not CNI-free immunosuppression were associated with abnormal allograft histology.

Polycystic liver: automatic segmentation using deep learning on CT is faster and as accurate compared to manual segmentation.

OBJECTIVE: This study aimed to develop and investigate the performance of a deep learning model based on a convolutional neural network (CNN) for the automatic segmentation of polycystic livers at CT imaging. METHOD: This retrospective study used CT images of polycystic livers. To develop the CNN, supervised training and validation phases were performed using 190 CT series. To assess performance, the test phase was performed using 41 CT series. Manual segmentation by an expert radiologist (Rad1a) served as reference for all comparisons. Intra-observer variability was determined by the same reader after 12 weeks (Rad1b), and inter-observer variability by a second reader (Rad2). The Dice similarity coefficient (DSC) evaluated overlap between segmentations. CNN performance was assessed using the concordance correlation coefficient (CCC) and the two-by-two difference between the CCCs; their confidence interval was estimated with bootstrap and Bland-Altman analyses. Liver segmentation time was automatically recorded for each method. RESULTS: A total of 231 series from 129 CT examinations on 88 consecutive patients were collected. For the CNN, the DSC was 0.95 ± 0.03 and volume analyses yielded a CCC of 0.995 compared with reference. No statistical difference was observed in the CCC between CNN automatic segmentation and manual segmentations performed to evaluate inter-observer and intra-observer variability. While manual segmentation required 22.4 ± 10.4 min, central and graphics processing units took an average of 5.0 ± 2.1 s and 2.0 ± 1.4 s, respectively. CONCLUSION: Compared with manual segmentation, automated segmentation of polycystic livers using a deep learning method achieved much faster segmentation with similar performance. KEY POINTS: • Automatic volumetry of polycystic livers using artificial intelligence method allows much faster segmentation than expert manual segmentation with similar performance. • No statistical difference was observed between automatic segmentation, inter-observer variability, or intra-observer variability.

European Liver Transplant Registry: Donor and transplant surgery aspects of 16,641 liver transplantations in children.

BACKGROUND AND AIMS: The European Liver Transplant Registry (ELTR) has collected data on liver transplant procedures performed in Europe since 1968. APPROACH AND RESULTS: Over a 50-year period (1968-2017), clinical and laboratory data were collected from 133 transplant centers and analyzed retrospectively (16,641 liver transplants in 14,515 children). Data were analyzed according to three successive periods (A, before 2000; B, 2000-2009; and C, since 2010), studying donor and graft characteristics and graft outcome. The use of living donors steadily increased from A to C (A, n = 296 [7%]; B, n = 1131 [23%]; and C, n = 1985 [39%]; p = 0.0001). Overall, the 5-year graft survival rate has improved from 65% in group A to 75% in group B (p < 0.0001) and to 79% in group C (B versus C, p < 0.0001). Graft half-life was 31 years, overall; it was 41 years for children who survived the first year after transplant. The late annual graft loss rate in teenagers is higher than that in children aged <12 years and similar to that of young adults. No evidence for accelerated graft loss after age 18 years was found. CONCLUSIONS: Pediatric liver transplantation has reached a high efficacy as a cure or treatment for severe liver disease in infants and children. Grafts that survived the first year had a half-life similar to standard human half-life. Transplantation before or after puberty may be the pivot-point for lower long-term outcome in children. Further studies are necessary to revisit some old concepts regarding transplant benefit (survival time) for small children, the role of recipient pathophysiology versus graft aging, and risk at transition to adult age.