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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Summary: Background: Prophylaxis of HBV recurrence is critical after liver transplantation in HBV patients. Despite new prophylactic schemes, most European LT centres persist on a conservative approach combining hepatitis B immunoglobulin (HBIG) and nucleos(t)ides analogues (NA). Aim: This setting prompted the European Liver Intestine Transplantation Association (ELITA) to look for a consensus on the prevention of HBV recurrence. Methods: Based on a 4‐round Delphi process, ELITA investigated 16 research questions and established 50 recommendations. Results: Prophylaxis should be driven according to 3 simplified risk groups: Low and high virological risk patients, with undetectable and detectable HBV DNA pre‐LT, respectively, and special populations (HDV, HCC, poorly adherent patients). In low‐risk patients, short‐term (4 weeks) combination of third‐generation NA+ HBIG, or third generation NA monotherapy can be considered as prophylactic options. In high‐risk patients, HBIG can be discontinued once HBV DNA undetectable. Combined therapy for 1 year is advised. HBV‐HCC patients should be treated according to their virological risk. In HDV/HBV patients, indefinite dual prophylaxis remains the gold standard. Full withdrawal of HBV prophylaxis following or not HBV vaccination should only be attempted in the setting of clinical trials. Organs from HBsAg+ve donors may be considered after assessment of risks, benefits, and patient consent. They should not be used if HDV is present. In poorly adherent patients, dual long‐term prophylaxis is recommended. Budget impact analysis should be taken into account to drive prophylactic regimen. Conclusions: These ELITA recommendations should stimulate a more rational and homogeneous approach to HBV prophylaxis across LT programs. [ABSTRACT FROM AUTHOR]

Background: Microsporidiosis has been largely reported in patients with acquired immunodeficiency syndrome, but emerged as a cause of persistent diarrhea in solid organ transplant patients. Methods: Through the French Microsporidiosis Network and the Groupe français de recherche en greffe de foie, we collected all microsporidiosis cases identified in liver transplant patients between 1995 and 2020 in France. Results: We identified 24 liver transplant recipients with microsporidiosis. Sex ratio was balanced and median age was 58.8 (3.5‐83.5) years (there were 4 children). Microsporidiosis occurred at a median time of 3.9 (0.1‐18.9) years post‐transplant. Median duration of diarrhea before diagnosis was 22 days (12‐45). Therapeutic care included immunosuppressive therapy changes in 20 patients, as follows: stop cyclosporine or tacrolimus (n = 2), dose reduction of cyclosporine or tacrolimus (n = 12), stop MMF (n = 5), and dose reduction of corticosteroids (n = 1). In addition, 15 patients received specific therapy against microsporidiosis: fumagillin (n = 11) or albendazole (n = 4). Median duration of treatment was 14 days (8‐45 days). Finally, 7 patients had immunosuppressive treatment tapering only. Microsporidiosis was complicated by renal failure in 15 patients, requiring dialysis in one case. Two patients had infection relapse. No patient presented proven rejection within the 3 months after microsporidiosis. None of the patients died within the 3 months after microsporidiosis. Conclusions: Microsporidiosis is a very rare infection after liver transplantation but can induce severe dehydration and renal failure. Therefore, it must be systematically sought in any case of persistent diarrhea after first line screening of frequent infectious causes. [ABSTRACT FROM AUTHOR]

Prognosis and oncologic treatment feasibility in solid organ transplant patients with de novo cancer remain poorly described. We investigated the impact of immunosuppressive therapy modifications after de novo cancer diagnosis on oncologic treatment feasibility, toxicities, and prognosis. Patients with de novo cancer (excluding nonmelanoma skin cancers) were selected from a monocentric cohort of 4,637 kidney and liver allograft recipients. We assessed oncologic treatment optimality according to guidelines and analyzed immunosuppressive drug modifications and oncologic treatment impacts on treatment feasibility, toxicities, and graft/patient survivals. A total of 180 patients with 205 cancers were included: mean age 60 years, median delay from transplantation to first de novo cancer 5 years. In 46% of cases, immunosuppressive therapy was modified after cancer diagnosis: 24% dose reduction and 22% mTOR inhibitor introduction. Optimal oncologic treatment was performed in 80% and 38% of patients with localized and advanced cancer respectively. Transplantation and immunosuppression hindered optimal oncologic treatment in 11% instances. Immunosuppressive therapy modifications did not affect oncologic treatment tolerance nor graft survival. In multivariate analysis, optimal oncologic treatment and mTOR inhibitor introduction improved survival of patients with de novo carcinoma. Optimal oncologic treatment is feasible in kidney and liver allograft recipients without safety concerns. Optimal oncologic treatment and mTOR inhibitor introduction seem to markedly improve survival of patients with de novo carcinoma. What's new? Risk of cancer after solid organ transplantation is increased, in part due to immunosuppressive treatments modifying the balance between immune tolerance and anti‐tumoral immunity. mTOR inhibitors, which today are used either as an immunosuppressive agent to prevent graft rejection or an anti‐tumor drug, have shown therapeutic promise for these patients, however. In this large well‐documented cohort, immunosuppression dose reduction does not translate into overall survival benefit. Rather, optimal oncological treatment and introduction of a mTOR inhibitor at immunosuppressive doses are feasible without safety concerns in solid organ transplant patients presenting with de novo carcinoma, and dramatically improve patient overall survival. [ABSTRACT FROM AUTHOR]

Summary: Background: The importance of primary biliary cholangitis as an indication for liver transplantation has probably been influenced by the introduction of therapies, and changes in selection criteria and disease epidemiology. Aims: To assess the time trends in liver transplantation for primary biliary cholangitis and to evaluate the characteristics of the patient population during the past three decades. Methods: Patients undergoing liver transplantation from 1986 to 2015 in centres reporting to the European Liver Transplantation Registry were included. We excluded combined organ transplantations and patients <18 years. Trends were assessed using linear regression models. Results: We included 112 874 patients, of whom 6029 (5.3%) had primary biliary cholangitis. After an initial increase in the first decade, the annual number of liver transplantation for primary biliary cholangitis remained stable at around 200. The proportion of liver transplantations for primary biliary cholangitis decreased from 20% in 1986 to 4% in 2015 (P < 0.001). Primary biliary cholangitis was the only indication showing a consistent proportional decrease throughout all decades. From the first to the third decade, the age at liver transplantation increased from 54 (IQR 47‐59) to 56 years (IQR 48‐62) and the proportion of males increased from 11% to 15% (both P < 0.001). Conclusions: We have found a proportional decrease in primary biliary cholangitis as indication for liver transplantation. However, despite treatment with ursodeoxycholic acid and improved disease awareness, the absolute annual number of liver transplantations has stabilised. [ABSTRACT FROM AUTHOR]

Background: In 2012, the Liver Transplant French Study Group built the alpha-fetoprotein-score (AFP-score), which improved significantly the prediction of tumor recurrence in case of liver transplantation for HCC when compared to Milan criteria. The aim of the study was to test the AFP score in case of liver resection (LR) for HCC.Methods: From 1990 to 2012, 347 patients underwent a liver resection for HCC developed on chronic liver disease (CLD). All patients with solitary HCC <60 mm were included. The primary end point was to investigate if the AFP-score at the first LR was predictive of recurrence and if recurrence occurred within the AFP-score. The secondary end points were overall survival (OS) and disease-free survival.Results: One hundred and eight patients fulfilled the inclusions criteria. After a median follow-up of 65.4IQR [13-114] months, recurrence occurred in 64.8% (70/108) patients. Among the study population, 96 were "in AFP-score" (i.e., ≤2) of whom 60.4% (58/96) developed a recurrence that was cured in curative intent. In contrast, all patients "out AFP-score" experienced recurrence, and 25% were eligible for curative treatment. At the end of the follow-up, 26 patients were listed for liver transplantation (LT). Among them, 21 were finally transplanted. The 5-year OS after salvage LT was 68.5%95%CI [50.2-93.0].Conclusion: AFP-score is a useful tool for patients selection after LR for solitary HCC developed on CLD. For patients "in AFP-score," up-front LR provides good survival and allows to avoid up-front LT in case of recurrence. [ABSTRACT FROM AUTHOR]

Backgrounds & Aims: Treating patients with decompensated cirrhosis with direct‐acting antiviral (DAA) therapy while on the waiting list for liver transplantation results in substantial improvement of liver function allowing 1 in 4 patients to be removed from the waiting list or delisted, as reported in a previous study promoted by the European Liver and Intestine Transplant Association (ELITA). The aim of this study was to report on clinical outcomes of delisted patients, including mortality risk, hepatocellular carcinoma development and clinical decompensation requiring relisting. Methods: One hundred and forty‐two HCV‐positive patients on the liver transplant waiting list for decompensated cirrhosis, negative for hepatocellular carcinoma, between February 2014 and June 2015 were treated with DAA therapy and were prospectively followed up. Results: Forty‐four patients (30.9%) were delisted following clinical improvement. This percentage was higher than in the original study because of a number of patients being delisted long after starting DAAs. The median Child‐Pugh and MELD score of delisted patients was 5.5 and 9 respectively. Four patients were relisted, because of HCC diagnosis in 1 case and 3 patients developed ascites. One further patient died (2.4%) because of rapidly progressing hepatocellular carcinoma twenty‐two months after delisting. Of the 70 patients who received a liver graft, 9 died (13%). Conclusions: Antiviral therapy allows for a long‐term improvement of liver function and the delisting of one‐third of treated patients with risk of liver‐related complications after delisting being very low. [ABSTRACT FROM AUTHOR]

Background & Aim Sorafenib is the standard of care for patients with hepatocellular carcinoma ( HCC) and macrovascular invasion ( MVI), with limited survival. Retrospective surgical studies have reported prolonged survival in this situation. This study aimed to compare the overall survival of patients with HCC and MVI treated with surgical resection or sorafenib. Methods A total of 143 patients with HCC and MVI but no extra-hepatic spread, treated with surgical resection ( SR-patients; n=75) or sorafenib ( SOR-patients; n=68) in four French centres between 1990 and 2013 were reviewed retrospectively. A propensity score analysis was performed to reduce bias. Results SR-patients were significantly younger and had a lower tumour burden than SOR-patients. Median overall survival ( OS) rates were 10.1 months [95% CI: 4.1-16.1] in SR-patients and 12.9 months [95% CI: 7.9-17.9] in SOR-patients ( P=.959). The 90-day mortality rate was 16% (n=12) in SR-patients and 7.5% (n=5) in SOR-patients ( P=.196). SR-patients had a median disease-free survival of 4.60 months [95% CI: 3.3-5.9]. Under the propensity analysis, median OS was 12.0 months [95% CI: 5.5-18.5] in SR-patients vs 9.7 months [95% CI: 6.1-13.3] in SOR-patients ( P=.682). Under multivariate analysis, extensive MVI ( HR=1.956, P=.024) and bilirubin >17 μmol/L ( HR=1.738, P=.011) were the two factors significantly associated with mortality. Conclusion Under a propensity score analysis, the overall survival of patients with HCC and MVI undergoing surgical resection was similar to that achieved with sorafenib. We were not able to identify a patient subgroup experiencing a surgery-related improvement in survival, and quality of life was not evaluable. [ABSTRACT FROM AUTHOR]

Background & Aims A major limitation to liver transplantation is organ shortage leading to the use of non-optimal liver grafts. The Donor Risk Index has been validated and recommended to select donors/organs. The Eurotransplant Donor Risk Index was derived from the Donor Risk Index. The objective of our study was to perform an external validation of both Donor Risk Index and Eurotransplant-Donor Risk Index against the French liver transplantation Cristal registry according to recommendations of the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis. Methods Liver transplantations performed in France between 2009 and 2013 were used to perform the validation study for the Donor Risk Index and the Eurotransplant-Donor Risk Index respectively. We applied on the French data the models used to construct the Donor Risk Index and the Eurotransplant-Donor Risk Index respectively. Results Neither the Donor Risk Index nor the Eurotransplant-Donor Risk Index were validated against this dataset. Discrimination and calibration of these scores were not preserved according to our data. Important donor and candidates differences between our dataset and the Organ Procurement and Transplantation Network or the Eurotransplant datasets may explain why the Donor Risk Index and the Eurotransplant-Donor Risk Index appeared unadapted to the French transplant registry. Conclusion Neither of these risk indexes were suitable to optimize the French liver allocation system. Thus, our next step will be to propose a general adaptive model for a Donor Risk Index. [ABSTRACT FROM AUTHOR]

Aim Discordance between pre- LT imaging and explanted liver findings have been reported after liver transplantation ( LT) for hepatocellular carcinoma ( HCC), suggesting the need of reassessing the risk of HCC recurrence post- LT. Our aims were to compare pre- LT imaging and explants features and to test the performances of four explant-based predictive models of recurrence in an external cohort. Methods Staging according to pre- LT imaging and explant features were compared. Four explants-based models were retrospectively tested in a cohort of 372 patients transplanted for HCC in 19 French centres between 2003 and 2005. Accuracies of the scores were compared. Results Pre- LT imaging underestimated tumour burden in 83 (22.7%) patients according to Milan criteria. The highest AUCs for prediction of 5-years recurrence were observed in the 'Up to seven' (0.7915 [95% CI: 0.7339-0.849]) and Decaens models (0.747 [95% CI: 0.6877-0.806]), with two levels of risk: low (10%) and high (>50%). Chan and Iwatsuki models identified 3 and 4 levels of risk, but had lower AUCs (0.68 and 0.70) respectively. Accuracy of the 'Up to seven' model was superior to the Decaens model ( P=.034), which was superior to the Chan model ( P=.0041) but not to the Iwatsuki model ( P=.17). Conclusion Pre- LT imaging underestimates tumour burden, and prediction of recurrence should be reassessed after LT. The explant-based 'Up to seven' and Decaens models provided the best accuracy for prediction of 5-year recurrence, identifying only two levels of risk. New models are needed to further refine the prediction of recurrence after LT. [ABSTRACT FROM AUTHOR]

Background & Aims The French alpha-fetoprotein ( AFP) model has recently shown superior results compared to Milan criteria ( MC) for prediction of hepatocellular carcinoma ( HCC) recurrence after liver transplantation ( LT) in European populations. The aim of this study was to explore the predictive capacity of the AFP model for HCC recurrence in a Latin-American cohort. Methods Three hundred twenty-seven patients with HCC were included from a total of 2018 patients transplanted at 15 centres. Serum AFP and imaging data were both recorded at listing. Predictability was assessed by the Net Reclassification Improvement ( NRI) method. Results Overall, 82 and 79% of the patients were within MC and the AFP model respectively. NRI showed a superior predictability of the AFP model against MC. Patients with an AFP score >2 points had higher risk of recurrence at 5 years Hazard Ratio ( HR) of 3.15 ( P = 0.0001) and lower patient survival ( HR = 1.51; P = 0.03). Among patients exceeding MC, a score ≤2 points identified a subgroup of patients with lower recurrence (5% vs 42%; P = 0.013) and higher survival rates (84% vs 45%; P = 0.038). In cases treated with bridging procedures, following restaging, a score >2 points identified a higher recurrence ( HR 2.2, P = 0.12) and lower survival rate ( HR 2.25, P = 0.03). A comparative analysis between HBV and non- HBV patients showed that the AFP model performed better in non- HBV patients. Conclusions The AFP model could be useful in Latin-American countries to better select patients for LT in subgroups presenting with extended criteria. However, particular attention should be focused on patients with HBV. [ABSTRACT FROM AUTHOR]

Background: Tacrolimus and cyclosporin inhibits the activity of calcineurin, a serine/threonine phosphatase that is involved in many physiological and pathological pathways. However, the baseline calcineurin phosphatase activity (CPA) measured before the transplant is unknown. In this study, we determine baseline CPA in liver transplant (LT) candidates and explore some factors that might modify it. Patients and methods: Thirty-two consecutive LT candidates (25 men, seven women, average age 53.4 years) were included. Seven millilitres of whole blood was collected from each patient. CPA was determined in lymphocytes quantifying a dephosphorylated peptide phosphorylated previously (D-L-D-V-P-I-P-G-R-F-D-R-R-V-S-V-A-A-E) by high-performance liquid chromatography. The relationship between CPA and the quantitative variables was tested according to Pearson's correlation. A two-way analysis of variance was performed to test the independent role of categorical parameters in CPA. Results: The median CPA was significantly lower in LT candidates than in healthy volunteers [179.2 (146.9–226.3) vs 247.8 (220.9–292.5) pmol/min/106 peripheral blood mononuclear cell (PBMC), respectively, P=0.0002]. CPA was also significantly lower in alcoholic cirrhosis (152.2 vs 211.1 pmol/min/106 PBMC, P=0.04) and in the presence of hepatocellular carcinoma (HCC) (152.0 vs 213.5 pmol/min/106 PBMC, P=0.0074) compared with other liver diseases. A two-way analysis of variance showed that these parameters were independently associated with lower CPA ( P=0.05 for alcohol and P=0.0056 for HCC respectively). Conclusion: This pilot study showed a lower CPA in patients with AC and HCC. This phenomenon may contribute towards lowering the risk of acute rejection in these patients after LT and, on the other hand, may increase the risk of de novo cancers. [ABSTRACT FROM AUTHOR]

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., (© 2024 The Authors. Liver International published by John Wiley & Sons Ltd.)

Aim: To generate a new score with improved accuracy compared with Milan criteria to select patients., Patients: The training cohort comprised 373 patients transplanted for hepatocellular carcinoma (HCC) between 1988 and 1998 (cohort 1). An algorithm was derived from the analysis of patient data by the proportional hazard Cox regression model. The area under the receiver operating characteristic (AUROC) was used to determine a cut-off value. The validation cohort comprised 140 patients transplanted between 1999 and 2001 (cohort 2)., Results: Multivariate analysis identified three predictors of 5-year tumour-free survival: tumour differentiation (P=0.02), diameter (P<0.0001) and number of nodules (P=0.04). A cut-off value of 4 was derived from the AUROC of the final score. Five-year tumour-free survival was 60.2 ± 3.1% in patients with as score <4 and 36.4 ± 4.7% in individuals with a score ≥4, P<0.0001. In the validation cohort, 5-year tumour-free survival was 82.8 ± 3.6% (score <4) and 50.0 ± 10.7% (score ≥4), P=0.0003. In patients with a score <4, there was no significant difference in 5-year tumour-free survival between Milan+ and Milan- patients, either in cohort 1 or 2. Five-year tumour-free survival of Milan- patients was significantly better in individuals with a score <4 compared with those with a score ≥4, both in cohort 1 (61.5 ± 9.1 vs 31.4 ± 4.6%, P=0.009) and in cohort 2 (P=0.02)., Conclusion: A novel score taking into account tumour differentiation shows higher accuracy than Milan criteria in predicting 5-year tumour-free survival following liver transplantation for HCC. Prospective studies should validate these findings., (© 2011 John Wiley & Sons A/S.)