Recipient age influences survival after liver transplant: Results of the French national cohort 2007-2017.

BACKGROUND: In recent years, age at liver transplantation (LT) has markedly increased. In the context of organ shortage, we investigated the impact of recipient age on post-transplantation mortality. METHODS: All adult patients who received a first LT between 2007 and 2017 were included in this cross-sectional study. Recipients' characteristics at the time of listing, donor and surgery data, post-operative complications and follow-up of vital status were retrieved from the national transplantation database. The impact of age on 5-year overall mortality post-LT was estimated using a flexible multivariable parametric model which was also used to estimate the association between age and 10-year net survival, accounting for expected age- and sex-related mortality. RESULTS: Among the 7610 patients, 21.4% were aged 60-65 years, and 15.7% over 65. With increasing age, comorbidities increased but severity of liver disease decreased. Older recipient age was associated with decreased observed survival at 5 years after LT (p < .001), with a significant effect particularly during the first 2 years. The linear increase in the risk of death associated with age does not allow any definition of an age's threshold for LT (p = .832). Other covariates associated with an increased risk of 5-year death were dialysis and mechanical ventilation at transplant, transfusion during LT, hepatocellular carcinoma and donor age. Ten-year flexible net survival analysis confirmed these results. CONCLUSION: Although there was a selection process for older recipients, increasing age at LT was associated with an increased risk of death, particularly in the first years after LT.

Acute kidney injury in patients with cirrhosis: Acute Disease Quality Initiative (ADQI) and International Club of Ascites (ICA) joint multidisciplinary consensus meeting.

Patients with cirrhosis are prone to developing acute kidney injury (AKI), a complication associated with a markedly increased in-hospital morbidity and mortality, along with a risk of progression to chronic kidney disease. Whereas patients with cirrhosis are at increased risk of developing any phenotype of AKI, hepatorenal syndrome (HRS), a specific form of AKI (HRS-AKI) in patients with advanced cirrhosis and ascites, carries an especially high mortality risk. Early recognition of HRS-AKI is crucial since administration of splanchnic vasoconstrictors may reverse the AKI and serve as a bridge to liver transplantation, the only curative option. In 2023, a joint meeting of the International Club of Ascites (ICA) and the Acute Disease Quality Initiative (ADQI) was convened to develop new diagnostic criteria for HRS-AKI, to provide graded recommendations for the work-up, management and post-discharge follow-up of patients with cirrhosis and AKI, and to highlight priorities for further research.

Autoimmune hepatitis recurrence after liver transplantation: "Les jeux sont faits".

Autoimmune hepatitis (AIH) may recur after liver transplantation (LT). The aims of this study were to evaluate the incidence and risk factors for recurrent autoimmune hepatitis (rAIH). A multicenter retrospective French nationwide study, including all patients aged ≥16 transplanted for AIH, with at least 1 liver biopsy 1 year after LT, was conducted between 1985 and 2018. Risk factors for rAIH were identified using a multivariate Cox regression model. Three hundred and forty-four patients were included (78.8% women) with a median age at LT of 43.6 years. Seventy-six patients (22.1%) developed recurrence in a median time of 53.6 months (IQR, 14.1-93.2). Actuarial risk for developing rAIH was 41.3% 20 years after LT. In multivariate analysis, the strongest risk factor for rAIH was cytomegalovirus D+/R- mismatch status (HR=2.0; 95% CI: 1.1-3.6; p =0.03), followed by associated autoimmune condition. Twenty-one patients (27.6% of rAIH patients) developed liver graft cirrhosis after rAIH. Independent risk factors for these severe forms of rAIH were young age at LT, IgG levels >20.7 g/L, and LT in the context of (sub)fulminant hepatitis. Immunosuppression, especially long-term maintenance of corticosteroid therapy, was not significantly associated with rAIH. Recurrence of AIH after LT is frequent and may lead to graft loss. Recurrence is more frequent in young patients with active disease at the time of LT, yet systematic corticosteroid therapy does not prevent it.

Osteoporosis and Fragility Fractures in Patients With Cirrhosis Evaluated for Liver Transplantation: Identification of High-Risk Patients Based on Computed Tomography at Evaluation.

INTRODUCTION: Osteoporosis in candidates for liver transplantation (LT) is often underdiagnosed despite the important consequences of morbidity. METHODS: We included 376 patients with cirrhosis evaluated for LT with available computed tomography (CT) scans. Prevalent vertebral fractures (VFs) were identified on CT reconstructions, and bone density was assessed by measuring CT attenuation of the L1 vertebra (L1-CT). RESULTS: We identified 139 VFs in 55 patients (14.6%). Logistic regression models showed that low L1-CT was the only independent determinant of VF. DISCUSSION: In patients with cirrhosis evaluated for LT, CT scans identified persons with severe osteoporosis without additional costs.

Identification of liver transplant biopsy phenotypes associated with distinct liver biological markers and allograft survival.

The intricate association between histologic lesions and circulating antihuman leucocyte antigen donor-specific antibodies (DSA) in liver transplantation (LT) requires further clarification. We conducted a probabilistic, unsupervised approach in a comprehensively well-annotated LT cohort to identify clinically relevant archetypes. We evaluated 490 pairs of LT biopsies with DSA testing from 325 recipients transplanted between 2010 and 2020 across 3 French centers and an external cohort of 202 biopsies from 128 recipients. Unsupervised archetypal analysis integrated all clinico-immuno-histologic parameters of each biopsy to identify biopsy archetypes. The median time after LT was 1.17 (interquartile range, 0.38-2.38) years. We identified 7 archetypes distinguished by clinico-immuno-histologic parameters: archetype #1: severe T cell-mediated rejection (15.9%); #2: chronic rejection with ductopenia (1.8%); #3: architectural and microvascular damages (3.5%); #4: (sub)normal (55.9%); #5: mild T cell-mediated rejection (4.9%); #6: acute antibody-mediated rejection (6.5%); and #7: chronic rejection with DSA (11.4%). Cell infiltrates vary in the archetype. These archetypes were associated with distinct liver biological markers and allograft outcomes. These findings remained consistent when stratified using the patient's age or indications for LT, with good performance in the external cohort (mean highest probability assignment = 0.58, standard deviation ± 0.17). In conclusion, we have identified clinically meaningful archetypes, providing valuable insights into the intricate DSA-histology association, which may help standardize liver allograft pathology classification.

Liver disease in germline mutations of telomere-related genes: Prevalence, clinical, radiological, pathological features, outcome, and risk factors.

BACKGROUND AND AIM: Germline mutations of telomere-related genes (TRG) induce multiorgan dysfunction, and liver-specific manifestations have not been clearly outlined. We aimed to describe TRG mutations-associated liver diseases. APPROACH AND RESULTS: Retrospective multicenter analysis of liver disease (transaminases > 30 IU/L and/or abnormal liver imaging) in patients with TRG mutations. Main measurements were characteristics, outcomes, and risk factors of liver disease in a TRG mutations cohort. The prevalence of liver disease was compared to a community-based control group (n = 1190) stratified for age and matched 1:3 for known risk factors of liver disease. Among 132 patients with TRG mutations, 95 (72%) had liver disease, with associated lung, blood, skin, rheumatological, and ophthalmological TRG diseases in 82%, 77%, 55%, 39%, and 30% of cases, respectively. Liver biopsy was performed in 52/95 patients, identifying porto-sinusoidal vascular disease in 48% and advanced fibrosis/cirrhosis in 15%. After a follow-up of 21 months (12-54), ascites, hepato-pulmonary syndrome, variceal bleeding, and HCC occurred in 14%, 13%, 13%, and 2% of cases, respectively. Five-year liver transplantation-free survival was 69%. A FIB-4 score ≥ 3·25 and ≥1 risk factor for cirrhosis were associated with poor liver transplantation-free survival. Liver disease was more frequent in patients with TRG mutations than in the paired control group [80/396, (20%)], OR 12.9 (CI 95%: 7.8-21.3, p < 0.001). CONCLUSIONS: TRG mutations significantly increase the risk of developing liver disease. Although symptoms may be mild, they may be associated with severe disease. Porto-sinusoidal vascular disease and cirrhosis were the most frequent lesions, suggesting that the mechanism of action is multifactorial.

Novel prognostic biomarkers in decompensated cirrhosis: a systematic review and meta-analysis.

BACKGROUND: Patients with decompensated cirrhosis experience high mortality rates. Current prognostic scores, including the model for end-stage liver disease (MELD), may underperform in settings other than in those they were initially developed. Novel biomarkers have been proposed to improve prognostication accuracy and even to predict development of complications. METHODS: We performed a systematic review and meta-analysis on novel urine and blood biomarkers and their ability to predict 90-day mortality in patients with decompensated cirrhosis. Secondary outcomes included 28-day and 1-year mortality, and development of acute-on-chronic liver failure, acute kidney injury and other complications. To overcome differences in units, temporal changes in assays and reporting heterogeneity, we used the ratio of means (RoM) as measure of association for assessing strength in predicting outcomes. An RoM>1 implies that the mean biomarker level is higher in those that develop the outcome than in those that do not. RESULTS: Of 6629 unique references, 103 were included, reporting on 29 different biomarkers, with a total of 31 362 biomarker patients. Most studies were prospective cohorts of hospitalised patients (median Child-Pugh-Turcotte score of 9 and MELD score of 18). The pooled 90-day mortality rate was 0.27 (95% CI 0.24 to 0.29). The RoM for predicting 90-day mortality was highest for interleukin 6 (IL-6) (2.56, 95% CI 2.39 to 2.74), followed by urinary neutrophil gelatinase-associated lipocalin (uNGAL) (2.42, 95% CI 2.20 to 2.66) and copeptin (2.33, 95% CI 2.17 to 2.50). These RoMs were all higher than for MELD (1.44, 95% CI 1.42 to 1.46). CONCLUSION: Novel biomarkers, including IL-6, uNGAL and copeptin, can probably improve prognostication of patients with decompensated cirrhosis compared with MELD alone.

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.

Bariatric surgery and liver transplantation, here we are now: A French nationwide retrospective study.

At the time of the growing obesity epidemic worldwide, liver transplantation (LT) and metabolic syndrome are closely linked: non-alcohol-related fatty liver disease (NAFLD) is one of the leading indications for liver transplantation, and metabolic syndrome can also appear after liver transplantation, in relation to immunosuppressive medications and weight gain, whatever was the initial liver disease leading to the indication of LT. Therefore, the role of bariatric surgery (BS) is important due to its longer-lasting effect and efficacy. We performed a retrospective review of all 50 adult French liver transplant recipients who had a history of bariatric surgery, including 37 procedures before transplantation, and 14 after. There were three significantly different characteristics when comparing pre-and post-LT BS: patients were older (at the time of BS), presented more frequently arterial hypertension (at the time of LT), and the proportion of NAFLD as initial liver disease leading to LT was lower, in the post-LT group. Regarding pre-LT BS, in one case BS was complicated by liver failure leading to the rapid indication of LT; it was the single patient for whom the delay between BS and LT was less than 1 year; there was no patient who specifically underwent BS for the purpose of LT listing.

CT Volumetry Can Be Used for Monitoring Liver Function Recovery in Auxiliary Partial Orthotopic Liver Transplantation.

BACKGROUND: Scintigraphy with a 99m TC-trimethyl-Br-IDA tracer (TBIDA) is used to monitor liver function regeneration after auxiliary partial orthotopic liver transplantation (APOLT) for acute liver failure (ALF). As computed tomography (CT) is also regularly performed during patient follow-up, CT volumetry could be used as an alternative to monitor native liver recovery after APOLT for ALF. METHODS: This was a retrospective cohort study of all patients who underwent APOLT (October 2006-July 2019). Collected data included liver graft and native liver CT volumetry measurements (expressed as fractions), TBIDA scintigraphy results, and biological and clinical data including immunosuppression therapy after APOLT. Four follow-up time points were defined (baseline, discontinuation of mycophenolate mofetil, beginning of tacrolimus reduction, and tacrolimus discontinuation) for analysis. RESULTS: Twenty-four patients (7 men; median age 28.5 y old) were included. The main etiologies of ALF were acetaminophen intoxication (n = 12), hepatitis B virus (n = 5), and amanita phalloides intoxication (n = 3). The median native liver function fractions on scintigraphy at baseline, at discontinuation of mycophenolate mofetil, at tacrolimus reduction, and at tacrolimus discontinuation were 22.0% (interquartile range 14.0-30.8), 30.5% (21.5-49.0), 32.0% (28.0-62.0), and 93.0% (77.0-100.0), respectively. The corresponding median native liver volume fractions on CT were 12.8% (10.4-17.3), 20.5% (14.2-27.3), 24.7% (21.3-48.4), and 77.9% (62.5-96.9), respectively. Volume and function were strongly correlated (r = 0.918; 95% confidence interval, 0.878-0.945; P < 0.01). Median time-to-immunosuppression discontinuation was 25.0 (17.0-35.0) mo. Estimated time-to-immunosuppression discontinuation was shorter in patients with acetaminophen-induced ALF (22 versus 35 mo; P = 0.035). CONCLUSIONS: In patients who receive APOLT for ALF, CT-based liver volumetry closely parallels native liver function recovery evaluated on TBIDA scintigraphy.

Liver Transplantation 2023: Status Report, Current and Future Challenges.

Liver transplantation offers live-saving therapy for patients with complications of cirrhosis and stage T2 hepatocellular carcinoma. The demand for organs far outstrips the supply, and innovations aimed at increasing the number of usable deceased donors as well as alternative donor sources are a major focus. The etiologies of cirrhosis are shifting over time, with more need for transplantation among patients with alcohol-associated liver disease and nonalcoholic/metabolic fatty liver disease and less for viral hepatitis, although hepatitis B remains an important indication for transplant in countries with high endemicity. The rise in transplantation for alcohol-associated liver disease and nonalcoholic/metabolic fatty liver disease has brought attention to how patients are selected for transplantation and the strategies needed to prevent recurrent disease. In this review, we present a status report on the most pressing topics in liver transplantation and future challenges.

Evaluation of transcranial Doppler use in patients with acute liver failure listed for emergency liver transplantation.

PURPOSE: Acute liver failure (ALF) is characterized by hepatic encephalopathy (HE) often due to intracranial hypertension (ICH). The risk/benefit-balance of intraparenchymal pressure catheter monitoring is controversial during ALF. AIMS: Perform an evaluation of transcranial Doppler (TCD) use in patients with ALF listed for emergency liver transplantation. MATERIAL AND METHODS: Single center retrospective cohort study including all patients registered on high emergency LT list between 2012 and 2018. All TCD measurements performed during ICU stay after listing and after LT (when performed) were recorded. TCD was considered abnormal when pulsatility index (PI) was >1.2. RESULTS: Among 106 patients with ALF, forty-seven (44%) had a TCD while on list. They had more severe liver and extrahepatic organ failure. When performed, TCD was abnormal in 51% of patients. These patients more frequently developed ICH events (45% vs. 13%, p = .02) and more frequently required increase in sedative drugs and vasopressors. While 22% of patients with normal TCD spontaneously survived, all of those with abnormal TCD died or were transplanted (p = .02). All transplanted patients who had abnormal exams normalized their TCD within 2 (1-2) days after LT. CONCLUSION: TCD may be a useful non-invasive tool for ICH detection and management, then guide sedation withdrawal.

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.

Long-term outcome of liver transplantation for autoimmune hepatitis: A French nationwide study over 30 years.

BACKGROUND & AIMS: Autoimmune hepatitis (AIH) is a rare indication for liver transplantation (LT). The aims of this study were to evaluate long-term survival after LT for AIH and prognostic factors, especially the impact of recurrent AIH (rAIH). METHODS: A multicentre retrospective nationwide study including all patients aged ≥16 transplanted for AIH in France was conducted. Early deaths and retransplantations (≤6 months) were excluded. RESULTS: The study population consisted of 301 patients transplanted from 1987 to 2018. Median age at LT was 43 years (IQR, 29.4-53.8). Median follow-up was 87.0 months (IQR, 43.5-168.0). Seventy-four patients (24.6%) developed rAIH. Graft survival was 91%, 79%, 65% at 1, 10 and 20 years respectively. Patient survival was 94%, 84% and 74% at 1, 10 and 20 years respectively. From multivariate Cox regression, factors significantly associated with poorer patient survival were patient age ≥58 years (HR = 2.9; 95% CI, 1.4-6.2; p = 0.005) and occurrence of an infectious episode within the first year after LT (HR = 2.5; 95% CI, 1.2-5.1; p = 0.018). Risk factors for impaired graft survival were: occurrence of rAIH (HR = 2.7; 95% CI, 1.5-5.0; p = 0.001), chronic rejection (HR = 2.9; 95% CI, 1.4-6.1; p = 0.005), biliary (HR = 2.0; 95% CI, 1.2-3.4; p = 0.009), vascular (HR = 1.8; 95% CI, 1.0-3.1; p = 0.044) and early septic (HR = 2.1; 95% CI, 1.2-3.5; p = 0.006) complications. CONCLUSION: Our results confirm that survival after LT for AIH is excellent. Disease recurrence and chronic rejection reduce graft survival. The occurrence of an infectious complication during the first year post-LT identifies at-risk patients for graft loss and death.

Diagnosis and management of hepatic encephalopathy: The French recommendations.

Hepatic encephalopathy (HE) is a frequent and severe complication of liver disease with poor patient outcomes. However, it is a poorly understood complication, with no consensus for diagnosis. Therefore, HE is often underdiagnosed. Differential diagnosis may be cumbersome because of non-specific symptoms, such as confusion, cognitive disorders, the aetiological factors of cirrhosis and comorbidities, which are often observed in cirrhotic patients. Therefore, an overt or covert form of HE should be systematically investigated. Advice is provided to drive patient work-up. Effective treatments are available to prevent or treat HE bouts, but the issue of single or combination therapy has not been resolved. Transjugular intrahepatic portosystemic shunt (TIPS) placement largely improved the prognosis of cirrhotic patients, but HE occurrence of HE is often a fear, even when post-TIPS HE can be avoided by a careful selection of patients and preventive treatment. HE is an indication of liver transplantation. However, its reversibility post-transplantation and the consequences of transplantation in patients with other causes of neurological disorders remain controversial, which supports the performance of an extensive work-up in expert centres for this subset of patients. The present guidelines assist clinicians in the diagnosis of the overt or covert form of HE to implement curative and preventive treatments and clarify which patients require referral to expert centres for consideration for liver transplantation. These guidelines are very clinically oriented and address different frequent clinical issues to help physicians make bedside decisions.

Liver transplantation for autoimmune hepatitis: Pre-transplant does not predict the early post-transplant outcome.

BACKGROUND AND AIMS: Autoimmune hepatitis (AIH) is a rare indication (<5%) for liver transplantation (LT). The aim of this study was to describe the early outcome after LT for AIH. METHODS: A multicenter retrospective nationwide study including all patients aged ≥16 transplanted for AIH in France was conducted. Occurrences of biliary and vascular complications, rejection, sepsis, retransplantation and death were collected during the first year after LT. RESULTS: A total of 344 patients (78.8% of women, 17.0% of (sub)fulminant hepatitis and 19.2% of chronic liver diseases transplanted in the context of acute-on-chronic liver failure [ACLF]) were included, with a median age at LT of 43.6 years. Acute rejection, sepsis, biliary and vascular complications occurred in respectively 23.5%, 44.2%, 25.3% and 17.4% of patients during the first year after LT. One-year graft and patient survivals were 84.3% and 88.0% respectively. The main cause of early death was sepsis. Pre-LT immunosuppression was not associated with an increased risk for early infections or surgical complications. Significant risk factors for septic events were LT in the context of (sub)fulminant hepatitis or ACLF, acute kidney injury at the time of LT (AKI) and occurrence of biliary complications after LT. AKI was the only independent factor associated with graft (HR = 2.5; 95% CI: 1.1-5.4; p = .02) and patient survivals (HR = 2.6; 95% CI: 1.0-6.5; p = .04). CONCLUSION: Early prognosis is good after LT for AIH and is not impacted by pre-LT immunosuppression but by the presence of AKI at the time of LT.

Gender and Racial Disparity Among Liver Transplantation Professionals: Report of a Global Survey.

Equality, diversity, and inclusion (EDI) are fundamental principles. Little is known about the pattern of practice and perceptions of EDI among liver transplant (LT) providers. International Liver Transplant Society (ILTS) EDI Committee survey around topics related to discrimination, mentorship, and gender. Answers were collected and analyzed anonymously. Worldwide female leadership was also queried via publicly available data. The survey was e-mailed to 1312 ILTS members, 199 responses (40.7% female) were collected from 38 countries (15.2% response rate). Almost half were surgeons (45.7%), 27.6% hepatologists and 26.6% anesthetists. Among 856 LT programs worldwide, 8.2% of leadership positions were held by females, and 22% of division chiefs were female across all specialties. Sixty-eight of respondents (34.7%) reported some form of discrimination during training or at their current position, presumably related to gender/sexual orientation (20.6%), race/country of origin (25.2%) and others (7.1%). Less than half (43.7%) received mentorship when discrimination occurred. An association between female responses and discrimination, differences in compensation, and job promotion was observed. This survey reveals alarmingly high rate of experience with racial and gender disparity, lack of mentorship, and very low rates of female leadership in the LT field and calls to action to equity and inclusion.

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.

Women Leadership in Liver Transplantation-Results of an International Survey.

BACKGROUND: The International Liver Transplantation Society (ILTS) has placed a strong focus on achieving gender equality and equity in liver transplant (LT). We aimed to understand gender distribution in leadership positions among LT physicians around the world and within ILTS. METHODS: In 2019, the ILTS Equality, Diversity, and Inclusion Committee distributed a survey to obtain granular data on gender and characteristics of transplant physicians as well as those in leadership positions in each center. Additionally, data were collected on the gender composition of the ILTS membership, council, chairpersons, and committees and from the United Network for Organ Sharing. RESULTS: Data were collected from 243 transplant centers. Thirty-two (13.2%) had at least 1 woman as the director of LT, chief of transplant surgery, or chief of transplant hepatology. Of the 243 centers, 133 reported the age and gender of the leadership personnel. Women physicians comprised 152 of the 833 transplant surgeons (18.2%) and 298 of the 935 hepatologists (31.9%). Among the 1331 ILTS physician members, 588 (44.2%) provided gender information in their member profiles, and 155 (26.3%) identified themselves as women. Of the 26 ILTS leadership positions, 7 (26.9%) were held by women. CONCLUSIONS: This analysis of worldwide gender distribution in the LT physician workforce showed notable gender disparity in LT leadership around the globe and within the ILTS. These data provide a launching point for promoting and achieving gender equality and equity in LT.

Respiratory events with terlipressin and albumin in hepatorenal syndrome: A review and clinical guidance.

Hepatorenal syndrome-acute kidney injury (HRS-AKI) is a serious complication of severe liver disease with a clinically poor prognosis. Supportive care using vasoconstrictors and intravenous albumin are the current mainstays of therapy. Terlipressin is an efficacious vasoconstrictor that has been used for 2 decades as the first-line treatment for HRS-AKI in Europe and has demonstrated greater efficacy in improving renal function compared to placebo and other vasoconstrictors. One of the challenges associated with terlipressin use is monitoring and mitigating serious adverse events, specifically adverse respiratory events, which were noted in a subset of patients in the recently published CONFIRM trial, the largest randomized trial examining terlipressin use for HRS-AKI. In this article, we review terlipressin's pharmacology, hypothesize how its mechanism contributes to the risk of respiratory compromise and propose strategies that will decrease the frequency of these events by rationally selecting patients at lower risk for these events.