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.

Preclinical validation of a customized circuit for ex situ uninterrupted cold-to-warm prolonged perfusion of the liver.

CONTEXT: Clinical adoption of ex situ liver perfusion is growing. While hypothermic perfusion protects against ischemia-reperfusion injury in marginal grafts, normothermic perfusion enables organ viability assessment and therefore selection of borderline grafts. The combination of hypothermic and normothermic perfusion, known as "cold-to-warm," may be the optimal sequence for organ preservation, but is difficult to achieve with most commercial perfusion systems. We developed an adaptable customized circuit allowing uninterrupted "cold-to-warm" perfusion and conducted preclinical studies on healthy porcine livers and discarded human livers to demonstrate the circuit's efficacy. METHODS: In collaboration with bioengineers, we developed a customized circuit that adapts to extracorporeal circulation consoles used in cardiovascular surgery and includes a proprietary reservoir enabling easy perfusate change without interrupting perfusion. This preclinical study was conducted on porcine and human livers. Perfusion parameters (pressures, flows, oxygenation) and organ viability were monitored. RESULTS: The customized circuit was adapted to a LivaNova S5® console, and the perfusions were flow-driven with real-time pressure monitoring. Ten porcine liver and 12 discarded human liver perfusions were performed during 14 to 18 h and 7 to 25 h, respectively. No hyperpressure was observed (porcine and human portal pressure 2-6 and 2-8 mm Hg; arterial pressure 10-65 and 20-65 mm Hg, respectively). No severe histological tissue injury was observed (Suzuki score ≤ 3 at the end of perfusion). Seven (70%) porcine livers and five (42%) human livers met the UK viability criteria. CONCLUSION: The customized circuit and system design enables smooth uninterrupted "cold-to-warm" perfusion not present in current commercial perfusion systems.

Evaluation of a delayed liver transplantation strategy for patients with HCC receiving bridging therapy: the DELTA-HCC study.

INTRODUCTION: To maximize utility and prevent premature liver transplantation (LT), a delayed LT strategy (DS) was adopted in France in 2015 in patients listed for any single HCC treated with resection or thermal-ablation during waiting phase, postponing LT until recurrence. The purpose of this study was to evaluate DS to make sure that it did not hamper pre and post-LT outcomes in DS patients. PATIENTS AND METHODS: Patients listed for HCC in France between 2015 and 2018 were studied. After data extraction from the national LT database, 2,025 patients were identified and classified according to 6 groups: single tumor entering DS, single tumor not entering DS, multiple tumors, no curative treatment, untreatable HCC or T1 tumors. 18-months Kaplan-Meier estimates of drop-out for death, too sick to be transplanted or tumor progression before LT, 5-year post-LT HCC recurrence and post LT-survival rates were compared. RESULTS: Median waiting-time in DS group was 910 days. Pre-LT drop-out probability was significantly lower in DS compare to other groups (13% vs 19%, p=0.0043) and significantly higher in the T1 group (25.4%, p=0.05). Post-LT HCC-recurrence rate in multiples nodules group was significantly higher (19.6%, p= 0.019) and post-LT 5-year survival did not differ among groups with 74% in DS group (p=0.22). CONCLUSION: The DELTA HCC study shows that DS does not negatively impact neither pre- nor post-LT patients 'outcomes, and has the potential to redistribute organs to patients in more urgent need of LT. It can reasonably be proposed and pursued. The unexpected high risk of drop out in T1 patients seems related to the MELD-based driving rules underserving this subgroup, calling for revision of allocation rules. IMPACTS AND IMPLICATIONS: To maximize utility and prevent premature liver transplantation (LT), a delayed LT strategy (DS) was adopted in France in 2015. It consists in postponing LT until recurrence in patients listed for any single HCC curatively treated by surgical resection or thermal ablation. The DELTA HCC study was conducted to evaluate this nationwide strategy. It shows in a non-US, European LT program that DS:- does not negatively impact pre- nor post-LT patients 'outcome,- concerns up to 20% of LT candidates-has therefore the potential to redistribute organs to patients in more urgent need of LT. Such a delayed strategy can reasonably be pursued and extended to other LT programs. Of note, an unexpected high risk of drop out in T1 patients, seemingly related to MELD-based offering rules which underserve these patients, calls for further scrutinization and revision of allocation rules in this subgroup.

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.

Tacrolimus Exposure Before and After a Switch From Twice-Daily Immediate-Release to Once-Daily Prolonged Release Tacrolimus: The ENVARSWITCH Study.

LCP-tacrolimus displays enhanced oral bioavailability compared to immediate-release (IR-) tacrolimus. The ENVARSWITCH study aimed to compare tacrolimus AUC0-24 h in stable kidney (KTR) and liver transplant recipients (LTR) on IR-tacrolimus converted to LCP-tacrolimus, in order to re-evaluate the 1:0.7 dose ratio recommended in the context of a switch and the efficiency of the subsequent dose adjustment. Tacrolimus AUC0-24 h was obtained by Bayesian estimation based on three concentrations measured in dried blood spots before (V2), after the switch (V3), and after LCP-tacrolimus dose adjustment intended to reach the pre-switch AUC0-24 h (V4). AUC0-24 h estimates and distributions were compared using the bioequivalence rule for narrow therapeutic range drugs (Westlake 90% CI within 0.90-1.11). Fifty-three KTR and 48 LTR completed the study with no major deviation. AUC0-24 h bioequivalence was met in the entire population and in KTR between V2 and V4 and between V2 and V3. In LTR, the Westlake 90% CI was close to the acceptance limits between V2 and V4 (90% CI = [0.96-1.14]) and between V2 and V3 (90% CI = [0.96-1.15]). The 1:0.7 dose ratio is convenient for KTR but may be adjusted individually for LTR. The combination of DBS and Bayesian estimation for tacrolimus dose adjustment may help with reaching appropriate exposure to tacrolimus rapidly after a switch.

An Efficient 5-Aminolevulinic Acid Photodynamic Therapy Treatment for Human Hepatocellular Carcinoma.

Photodynamic therapy (PDT) is a two-stage treatment relying on cytotoxicity induced by photoexcitation of a nontoxic dye, called photosensitizer (PS). Using 5-aminolevulinic acid (5-ALA), the pro-drug of PS protoporphyrin IX, we investigated the impact of PDT on hepatocellular carcinoma (HCC). Optimal 5-ALA PDT dose was determined on three HCC cell lines by analyzing cell death after treatment with varying doses. HCC-patient-derived tumor hepatocytes and healthy donor liver myofibroblasts were treated with optimal 5-ALA PDT doses. The proliferation of cancer cells and healthy donor immune cells cultured with 5-ALA-PDT-treated conditioned media was analyzed. Finally, therapy efficacy on humanized SCID mice model of HCC was investigated. 5-ALA PDT induced a dose-dependent decrease in viability, with an up-to-four-fold reduction in viability of patient tumor hepatocytes. The 5-ALA PDT treated conditioned media induced immune cell clonal expansion. 5-ALA PDT has no impact on myofibroblasts in terms of viability, while their activation decreased cancer cell proliferation and reduced the tumor growth rate of the in vivo model. For the first time, 5-ALA PDT has been validated on primary patient tumor hepatocytes and donor healthy liver myofibroblasts. 5-ALA PDT may be an effective anti-HCC therapy, which might induce an anti-tumor immune response.

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.

Impact of direct antiviral agents for hepatitis C virus -induced liver diseases on registration, waiting list and liver transplant activity in France.

Direct-acting antivirals (DAA) has dramatically improved the prognosis of liver transplantation (LT) candidates for HCV end-stage liver disease (ESLD). We aimed to evaluate the impact of DAA on waiting list (WL) registration and LT activity in France. We evaluated all patients registered to the French WL for HCV ESLD between 2000 and 2018. Timespan was divided into two periods according to DAA availability: 2010-2013 versus 2014-2018. Changes in the indications of LT, outcome on WL were evaluated. Then, we evaluated the activity of LT and outcome for HCV recipients in France. Among 3,173 HCV candidates, registration on WL decreased by 33% between 2013 and 2018. The 1-year waitlist survival increased from 76.9% (95%CI: 74.2%-79.4%) in 2010-2013 to 79.8% (95%CI: 77.2%-82.1%) in 2014-2018 (p < 0.01). Regarding LT activity, the part of HCV ESLD decreased from 26% in 2010 to 16% in 2018. The 1-year graft survival rate in HCV recipients increased from 76.9% (95%CI: 73.7%-79.7%) in 2010-2012 to 84.9% (95%CI: 82.9%-86.7%) in 2013-2018 (p < 0.01). The availability of DAA to treat HCV infection is associated with a significant decrease of registration for LT, death and drop out for worsening condition on the LT. In addition, it has decreased the number of HCV+ LT and improved the 1-year graft survival in France.

Current challenges and future perspectives in treating patients with NAFLD-related cirrhosis.

Despite the slow, progressive nature of NAFLD, the number of patients with NAFLD-related cirrhosis has significantly increased. Although the management of patients with cirrhosis is constantly evolving, improving the prognosis of patients with NAFLD-related cirrhosis is a challenge because it is situated at the crossroads between the liver, the metabolic, and the cardiovascular diseases. Therefore, the therapeutic interventions should not only target the liver but also the associated cardiometabolic conditions and should be adapted accordingly. The objective of the current review is to critically discuss the particularities in the management of patients with NAFLD-related cirrhosis. We relied on the recommendations of scientific societies and discussed them in the specific context of NAFLD cirrhosis and the surrounding cardiometabolic milieu. Herein, we covered the following aspects: (1) the weight loss strategies through lifestyle interventions to avoid sarcopenia and improve portal hypertension; (2) the optimal control of metabolic comorbidities in particular type 2 diabetes aimed not only to improve cardiovascular morbidity/mortality but also to lower the incidence of cirrhosis-related complications (we discussed various aspects related to the safety of oral antidiabetic drugs in cirrhosis); (3) the challenges in performing bariatric surgery in patients with cirrhosis related to the portal hypertension and the risk of cirrhosis decompensation; (4) the particularities in the diagnosis and management of the portal hypertension and the difficulties in managing patients awaiting for liver transplantation; and (5) the difficulties in developing drugs and conducting clinical trials in patients with NAFLD-related cirrhosis. Moreover, we discussed the emerging options to overcome these obstacles.

Therapeutic potentials of mesenchymal stromal cells-derived extracellular vesicles in liver failure and marginal liver graft rehabilitation: a scoping review.

Liver failure includes distinct subgroups of diseases: Acute liver failure (ALF) without preexisting cirrhosis, acute-on-chronic liver failure (ACLF) (severe form of cirrhosis associated with organ failures and excess mortality), and liver fibrosis (LF). Inflammation plays a key role in ALF, LF, and more specifically in ACLF for which we have currently no treatment other than liver transplantation (LT). The increasing incidence of marginal liver grafts and the shortage of liver grafts require us to consider strategies to increase the quantity and quality of available liver grafts. Mesenchymal stromal cells (MSCs) have shown beneficial pleiotropic properties with limited translational potential due to the pitfalls associated with their cellular nature. MSC-derived extracellular vesicles (MSC-EVs) are innovative cell-free therapeutics for immunomodulation and regenerative purposes. MSC-EVs encompass further advantages: pleiotropic effects, low immunogenicity, storage stability, good safety profile, and possibility of bioengineering. Currently, no human studies explored the impact of MSC-EVs on liver disease, but several preclinical studies highlighted their beneficial effects. In ALF and ACLF, data showed that MSC-EVs attenuate hepatic stellate cells activation, exert antioxidant, anti-inflammatory, anti-apoptosis, anti-ferroptosis properties, and promote regeneration of the liver, autophagy, and improve metabolism through mitochondrial function recovery. In LF, MSC-EVs demonstrated anti-fibrotic properties associated with liver tissue regeneration. Normothermic-machine perfusion (NMP) combined with MSC-EVs represents an attractive therapy to improve liver regeneration before LT. Our review suggests a growing interest in MSC-EVs in liver failure and gives an appealing insight into their development to rehabilitate marginal liver grafts through NMP.

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.

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.

Five-year outcomes in liver transplant patients receiving everolimus with or without a calcineurin inhibitor: Results from the CERTITUDE study.

BACKGROUND AND AIMS: To report 5-year outcomes of the CERTITUDE study. METHODS: An observational study in patients with liver transplantation (LTx) compared the long-term impact of immunosuppression (with/without a calcineurin inhibitor) on renal function, cancers, major cardiovascular events (MACEs) and other safety parameters. All patients completing the 6-month SIMCER study were recruited and analysed according to treatment received at randomization and actual treatment received during the follow-up. RESULTS: Of the 143 enrolled patients, 119 completed the 5-year follow-up (everolimus [EVR], n = 55; tacrolimus [TAC], n = 64). The mean absolute change in estimated glomerular filtration rate was not statistically different between both groups (TAC, -15.53 ml/min/1.73 m2 and EVR, -14.56 ml/min/1.73 m2 ). In the treatment subgroups based on actual treatment received, renal function was preserved better in the EVR subgroup compared with other subgroups (p = .051). Treated biopsy-proven acute rejection was higher in the EVR group (15.4% vs. 6.4%); however, the majority of events were mild in severity. MACE occurred in 9.2% vs. 14.1% of patients in the EVR and TAC groups respectively (p = .370). De novo cancer was reported in 14 and 5 patients in EVR and TAC groups respectively. Hepatocellular carcinoma (HCC) recurrence was observed in the TAC group alone (n = 4). Adverse events and treatment discontinuation owing to an adverse event were higher in the EVR group. CONCLUSIONS: The CERTITUDE study demonstrated that EVR- and TAC-based regimens have comparable efficacy, safety and tolerability up to 5 years post-LTx.

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.

Posttransplant immune-mediated cholangiopathies.

PURPOSE OF REVIEW: Liver transplantation (LT) is the treatment of end-stage chronic liver diseases, mainly decompensated cirrhosis and hepatocellular carcinoma. Biliary complications can be schematically classified into macroscopic versus microscopic lesions. Immune-related cholangiopathies include rejection, graft-versus-host disease (GVHD) and recurrence of pre-LT auto-immune biliary diseases, i.e. primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Here, we review the various types of posttransplant immune-related cholangiopathies, and discuss their clinical implications, especially diagnostic issues. RECENT FINDINGS: Recurrence of PBC and PSC after LT is increasingly well described in large cohorts and long-term follow-up. In this setting, the preventive effect of ursodeoxycholic acid on PBC recurrence, as well as the deleterious role of tacrolimus are now well documented. In addition, the significant negative impact of recurrent PBC on survival after LT has recently been demonstrated. With respect to rejection-associated biliary injury, a growing body of evidence is emerging on the role of anti-HLA antibody-mediated rejection. SUMMARY: Immune-mediated cholangiopathies occurring after LT can be divided in two main nosologic groups: biliary lesions due to recurrence of PBC or PSC, or in the context of rejection, either acute or chronic, T-cell- or antibody-mediated. GVHD is very rare. Final diagnosis is strongly based on clinical context (indication for LT, delay since transplantation, biological abnormalities, imaging) but also and to an even greater extent on biopsy of liver graft. Clinico-pathological discussions are recommended, hearing in mind that diseases can be intertwined.