Publications by authors named "Christophe Duvoux"

125 Publications

Microsporidiosis after liver transplantation: a French nationwide retrospective study.

Transpl Infect Dis 2021 Jun 7:e13665. Epub 2021 Jun 7.

CHU Clermont-Ferrand, Service de Parasitologie-Mycologie, 3iHP, INSERM, Université Clermont Auvergne, Clermont-Ferrand, France.

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), dose reduction of corticosteroids (n=1). In addition, 15 patients received specific therapy against microsporidiosis: fumagilline (n=11) or albendazole (n=4). Median duration of treatment was 14 days (8-45 days). Finally, 7 patients had IS treatment tapering only. Microsporidiosis was complicated by renal failure in 15 patients, requiring dialysis in 1 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 deshydratation and renal failure. Therefore, it must be systematically sought in any case of persistent diarrhea after first line screening of frequent infectious causes.
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http://dx.doi.org/10.1111/tid.13665DOI Listing
June 2021

Limitations of current liver donor allocation systems and the impact of newer indications for liver transplantation.

J Hepatol 2021 Jul;75 Suppl 1:S178-S190

Liver Failure Group, Institute for Liver and Digestive Health, University College London, London and European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain.

Liver transplantation represents a life-saving treatment for patients with decompensated cirrhosis, a severe condition associated with a high risk of waiting list mortality. When decompensation occurs rapidly in the presence of extrahepatic organ failures, the condition is called acute-on-chronic liver failure, which is associated with an even higher risk of death, though liver transplantation can also markedly improve survival in affected patients. However, there are still gaps in our understanding of how to optimise prioritisation and organ allocation, as well as survival among patients with acute-on-chronic liver failure (both before and after transplant). Moreover, it is urgent to address inequalities in access to liver transplantation in patients with severe alcoholic hepatitis and non-alcoholic steatohepatitis. Several controversies still exist regarding gender and regional disparities, as well as the use of suboptimal donor grafts. In this review, we aim to provide a critical perspective on the role of liver transplantation in patients with decompensated cirrhosis and address areas of ongoing uncertainty.
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http://dx.doi.org/10.1016/j.jhep.2021.01.007DOI Listing
July 2021

Liver transplantation for patients with acute-on-chronic liver failure (ACLF) in Europe: results of the ELITA/EF-CLIF collaborative study (ECLIS).

J Hepatol 2021 Apr 24. Epub 2021 Apr 24.

Department of hepatogastroenterology, Hepatology and Liver Transplantation Unit, HCL Hopital de la Croix-Rousse, Lyon, France.

Background And Aims: Liver transplantation (LT) has been proposed to be an effective salvage therapy even for the sickest patients with acute-on-chronic liver failure (ACLF). This large collaborative study was designed to address the current clinical practice and outcomes of ACLF patients wait listed (WL) for LT in Europe.

Methods: Retrospective study including 308 consecutive ACLF patients, listed in 20 centres across 8 European countries, from January 2018 to June 2019.

Results: 2677 patients received a LT, 1216 (45.4%) for decompensated cirrhosis (DC). Of these, 234 (19.2%) had ACLF at LT: ACLF-1, 58 (4.8%); ACLF-2, 78 (6.4%); and ACLF-3, 98 (8.1%). Wide variations were observed amongst countries: France and Germany had high rates of ACLF-2/3 (27-41%); Italy, Switzerland, Poland and Netherlands had medium rates (9-15%); and United Kingdom and Spain had low rates (3-5%) (p <.0001). One-year probability of survival after LT for patients with ACLF was 81% (95% CI 74-87). Pre-LT arterial lactate levels >4 mmol/L (HR 3.14, 95% CI 1.37-7.19), recent infection from multi-drug resistant organisms (HR 3.67, 95% CI 1.63-8.28), and renal replacement therapy (HR 2.74, 95% CI 1.37-5.51) were independent predictors of post-LT mortality. During the same period, 74 patients with ACLF died on the WL. In an intention-to-treat analysis, one-year survival of ACLF patients on the LT WL was 73% for ACLF-1 or -2 and 50% for ACLF-3.

Conclusion: The results reveal wide variations in listing patients with ACLF in Europe despite favorable post-LT survival. Risk factors for mortality were identified, allowing a more precise prognostic assessment of ACLF patients for potential LT.

Lay Summary: Acute on chronic liver failure (ACLF) is a severe clinical condition for which liver transplantation is an effective therapeutic option. This study has demonstrated that in Europe, referral and access to liver transplantation (LT) for patients with ACLF needs to be harmonized to avoid inequities. Post-LT survival for patients with ACLF was >80% after 1 year and some factors have been identified for selecting patients with favorable outcomes.
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http://dx.doi.org/10.1016/j.jhep.2021.03.030DOI Listing
April 2021

Risk factors of de novo malignancies after liver transplantation: a French national study on 11004 adult patients.

Clin Res Hepatol Gastroenterol 2021 Mar 11;45(4):101514. Epub 2021 Mar 11.

Hôpital Jean Minjoz, Service d'Hépatologie et Soins Intensifs Digestifs, Besançon, France.

Background: After liver transplantation (LT),de novo malignancies are one of the leading causes of late mortality. The aim of the present retrospective study was to identify the risk factors of de novo malignancies in a large cohort of LT recipients in France, using Fine and Gray competing risks regression analysis.

Methods: The study population consisted in 11004 adults transplanted between 2000 and 2013, who had no history of pre-transplant malignancy, except primary liver tumor. A Cox model adapted to the identification of prognostic factors (competitive risks) was used.

Results: From the entire cohort, one (or more)de novo malignancy was reported in 1480 L T recipients (13.45%). The probability to develop a de novo malignancy after LT was 2.07% at 1 year, 13.30% at 5 years, and 28.01% at 10 years. Of the known reported malignancies, the most common malignancies were hematological malignancy (22.36%), non-melanoma skin cancer (19.53%) and lung cancer (12.36%). According to Fine and Gray competing risks regression multivariate analysis, were significant risk factors for post-LT de novo malignancy: recipient age (Subdistribution Hazard Ratio (SHR) = 1.03 95%CI 1.03-1.04), male gender (SHR = 1.45 95%CI 1.27-1.67), non-living donor (SHR = 1.67 95%CI 1.14-2.38), a first LT (SHR = 1.35 95%CI 1.09-1.69) and the type of initial liver disease (alcohol-related liver disease (SHR = 1.63 95%CI 1.22-2.17), primary sclerosing cholangitis (SHR = 1.98 95%CI 1.34-2.91), and primary liver tumor (SHR = 1.88 95%CI 1.41-2.54)). Initial immunosuppressive regimen had no significant impact.

Conclusion: The present study confirms that LT recipient characteristics are associated with the risk ofde novo malignancy and this underlines the need for personalized screening in order to improve survival.
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http://dx.doi.org/10.1016/j.clinre.2020.07.019DOI Listing
March 2021

Covid-19 in liver transplant recipients: the French SOT COVID registry.

Clin Res Hepatol Gastroenterol 2021 Jan 28;45(4):101639. Epub 2021 Jan 28.

AP-HP, Hôpital Paul Brousse, Centre Hépato-Biliaire, INSERM, Unité 1193, Villejuif, France.

Background: Notwithstanding the ongoing coronavirus disease-2019 (Covid-19) pandemic, information on its clinical presentation and prognosis in organ transplant recipients remains limited. The aim of this registry-based observational study was to report the characteristics and clinical outcomes of liver transplant (LT) recipients included in the French nationwide Registry of Solid Organ Transplant Recipients with Covid-19.

Methods: COVID-19 was diagnosed in patients who had a positive PCR assay for SARS-CoV-2 or in presence of typical lung lesions on imaging or specific SARS-CoV-2 antibodies. Clinical and laboratory characteristics, management of immunosuppression, treatment for Covid-19, and clinical outcomes (hospitalization, admission to intensive care unit, mechanical ventilation, or death) were recorded.

Results: Of the 104 patients, 67 were admitted to hospital and 37 were managed at home (including all 13 children). Hospitalized patients had a median age of 65.2 years (IQR: 58.1 - 73.2 years) and two thirds were men. Most common comorbidities included overweight (67.3%), hypertension (61.2%), diabetes (50.7%), cardiovascular disease (20.9%) and respiratory disease (16.4%). SARS-CoV-2 infection was identified after a median of 92.8 months (IQR: 40.1 - 194.7 months) from LT. During hospitalization, antimetabolites, mTOR inhibitor, and CNIs were withdrawn in 41.9%, 30.0% and 12.5% of patients, respectively. The composite endpoint of severe Covid-19 within 30 days after diagnosis was reached by 33.0% of the adult patients. The 30-day mortality rate was 20.0%, and 28.1% for hospitalized patients. Multivariate analysis identified that age was independently associated with mortality.

Conclusion: In our large nationwide study, Covid-19 in LT recipients was associated with a high mortality rate.
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http://dx.doi.org/10.1016/j.clinre.2021.101639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843027PMC
January 2021

Early liver transplantation for corticosteroid non-responders with acute severe autoimmune hepatitis: The SURFASA score.

J Hepatol 2021 Jun 24;74(6):1325-1334. Epub 2021 Jan 24.

CHRU Lille, Hôpital Claude Huriez, Service des Maladies de l'Appareil Digestif, Lille, France.

Background & Aims: In acute severe autoimmune hepatitis (AS-AIH), the optimal timing for liver transplantation (LT) remains controversial. The objectives of this study were to determine early predictive factors for a non-response to corticosteroids and to propose a score to identify patients in whom LT is urgently indicated.

Methods: This was a retrospective, multicenter study (2009-2016). A diagnosis of AS-AIH was based on: i) Definite or probable AIH based on the simplified IAIHG score; ii) international normalized ratio (INR) ≥1.5 and/or bilirubin >200 μmol/L; iii) No previous history of AIH; iv) Histologically proven AIH. A treatment response was defined as LT-free survival at 90 days. The evolution of variables from corticosteroid initiation (day-D0) to D3 was estimated from: Δ%3 = (D3-D0)/D0.

Results: A total of 128 patients were included, with a median age of 52 (39-62) years; 72% were female. Overall survival reached 88%. One hundred and fifteen (90%) patients received corticosteroids, with a LT-free survival rate of 66% at 90 days. Under multivariate analysis, D0-INR (odds ratio [OR] 6.85; 95% CI 2.23-21.06; p <0.001), Δ%3-INR ≥0.1% (OR 6.97; 95% CI 1.59-30.46; p <0.01) and Δ%3-bilirubin ≥-8% (OR 5.14; 95% CI 1.09-24.28; p <0.04) were predictive of a non-response. The SURFASA score: -6.80+1.92∗(D0-INR)+1.94∗(Δ%3-INR)+1.64∗(Δ%3-bilirubin), created by combining these variables, was highly predictive of LT or death (AUC = 0.93) (88% specificity; 84% sensitivity) with a cut-off point of <-0.9. Below this cut-off, the chance of responding was 75%. With a score higher than 1.75, the risk of dying or being transplanted was between 85% and 100%.

Conclusion: In patients with AS-AIH, INR at the introduction of corticosteroids and the evolution of INR and bilirubin are predictive of LT or death. Within 3 days of initiating corticosteroids, the SURFASA score can identify non-responders who require a referral for LT. This score needs to be validated in a prospective cohort.

Lay Summary: The management of patients with acute severe autoimmune hepatitis is highly challenging, particularly regarding their early referral for liver transplantation. We found that international normalized ratio at the initiation of corticosteroid therapy and the evolution of international normalized ratio and bilirubin values after 3 days of therapy were highly predictive of liver transplantation or death. We are thus proposing a score that combines these variables and identifies patients in whom liver transplantation is urgently required.
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http://dx.doi.org/10.1016/j.jhep.2020.12.033DOI Listing
June 2021

Protective Role of Tacrolimus, Deleterious Role of Age and Comorbidities in Liver Transplant Recipients With Covid-19: Results From the ELITA/ELTR Multi-center European Study.

Gastroenterology 2021 03 9;160(4):1151-1163.e3. Epub 2020 Dec 9.

Liver and Multi-organ Transplantation, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.

Background And Aims: Despite concerns that liver transplant (LT) recipients may be at increased risk of unfavorable outcomes from COVID-19 due the high prevalence of co-morbidities, immunosuppression and ageing, a detailed analysis of their effects in large studies is lacking.

Methods: Data from adult LT recipients with laboratory confirmed SARS-CoV2 infection were collected across Europe. All consecutive patients with symptoms were included in the analysis.

Results: Between March 1 and June 27, 2020, data from 243 adult symptomatic cases from 36 centers and 9 countries were collected. Thirty-nine (16%) were managed as outpatients while 204 (84%) required hospitalization including admission to the ICU (39 of 204, 19.1%). Forty-nine (20.2%) patients died after a median of 13.5 (10-23) days, respiratory failure was the major cause. After multivariable Cox regression analysis, age >70 (HR, 4.16; 95% CI, 1.78-9.73) had a negative effect and tacrolimus (TAC) use (HR, 0.55; 95% CI, 0.31-0.99) had a positive independent effect on survival. The role of co-morbidities was strongly influenced by the dominant effect of age where comorbidities increased with the increasing age of the recipients. In a second model excluding age, both diabetes (HR, 1.95; 95% CI, 1.06-3.58) and chronic kidney disease (HR, 1.97; 95% CI, 1.05-3.67) emerged as associated with death CONCLUSIONS: Twenty-five percent of patients requiring hospitalization for COVID-19 died, the risk being higher in patients older than 70 and with medical co-morbidities, such as impaired renal function and diabetes. Conversely, the use of TAC was associated with a better survival thus encouraging clinicians to keep TAC at the usual dose.
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http://dx.doi.org/10.1053/j.gastro.2020.11.045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724463PMC
March 2021

Comment on "Shadows Behind Using Simple Risk Models in Selection of HCC Patients for LT".

Ann Surg 2020 Nov 17. Epub 2020 Nov 17.

Liver Transplant and Hepatology Unit, Hospital Universitario Austral, School of Biomedical Science, Austral University, Pilar, Argentina Institute for Clinical Effectiveness and Health Policy (IECS), Buenos Aires, Argentina Department of Liver Surgery, Henri-Mondor Hospital, APHP, Paris-Est University, Créteil, France Liver Transplant and Hepatology Unit, Hospital Universitario Austral, School of Biomedical Science, Austral University, Pilar, Argentina Hepato-Biliary Center, Paul Brousse Hospital, Paris, France Department of Hepatology, Medical Liver Transplant Unit, Henri-Mondor Hospital, APHP, Paris-Est University, Créteil, France.

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http://dx.doi.org/10.1097/SLA.0000000000004511DOI Listing
November 2020

Influence of everolimus-based treatment on circulating regulatory T cells after liver transplantation: Comparative study with tacrolimus-based therapy.

Clin Res Hepatol Gastroenterol 2020 Nov 13:101559. Epub 2020 Nov 13.

UMR_S 938, CDR Saint-Antoine, F-75012 Paris, France; Liver Transplantation Unit, AP-HP, Hôpital de la Pitié-Salpêtrière, 75012 Paris, France.

Liver transplantation remains the only treatment for terminal liver diseases. However, immunosuppressive drugs required for allograft acceptance are toxic and may be responsible for severe side effects. Modulating the immune system to induce tolerance is a promising approach to reduce immunosuppressive regimen. More particularly, promoting natural CD4 CD25 FoxP3 Tregs could be crucial in achieving tolerance. Contrary to calcineurin inhibitors, reports indicate that mTOR inhibitors may have a positive impact on Tregs. Here we present the first randomized prospective clinical study where Tregs levels from liver transplanted patients receiving either tacrolimus or everolimus were monitored for 6 months, starting from the day of transplantation. A total of 30 patients from four centers were monitored. Blood samples were obtained at day 0, day 14, one month, three months and six months post-transplantation. Flow-cytometry immunophenotyping of Tregs (CD4 CD25 CD127 FoxP3) and functional assays with Tregs were performed to assess their immunosuppressive capacity. Levels of Tregs were significantly reduced after one month of standard tacrolimus-based immunosuppressive regimen (p<0.05). Four months after conversion, levels of Tregs from patients treated with everolimus was significantly higher than patients under tacrolimus (p<0.02). Functional assays demonstrated that Tregs conserved their capacity to suppress the proliferation of activated PBMC.
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http://dx.doi.org/10.1016/j.clinre.2020.10.004DOI Listing
November 2020

Long term results of liver transplantation for alpha-1 antitrypsin deficiency.

Dig Liver Dis 2021 May 1;53(5):606-611. Epub 2020 Nov 1.

Hospices Civils de Lyon, Hôpital Edouard Herriot, Fédération des spécialités digestives, Lyon, France; Université de Lyon, Lyon, France. Electronic address:

Introduction: Liver transplantation (LT) is the therapeutic option for end-stage liver disease associated with alpha1 antitrypsin (A1AT) deficiency. The aim of the present retrospective study was to report on long-term outcomes following LT for A1AT deficiency.

Methods: The medical records of 90 pediatric and adult patients transplanted between 1982 and 2017 in France and Geneva (Switzerland) were reviewed.

Results: The study population consisted of 32 adults and 58 children; median age at transplant was 13.0 years (range: 0.2-65.1), and 65 were male (72.2%). Eighty-two patients (94.8% of children and 84.4% of adults) had the PI*ZZ genotype/phenotype and eight patients (8.9%) had the Pi*SZ genotype/phenotype. Eighty-four patients (93.3%) were transplanted for end-stage liver disease and six (all Pi*ZZ adults) for HCC. Median follow-up after LT was 13.6 years (0.1-31.7). The overall cumulative patient survival rates post-transplant were 97.8% at 1 year, and 95.5%, 95.5%, 92.0%, 89.1% at 5, 10, 15, 20 years respectively. The overall cumulative graft survival rates were 92.2% at 1 year, and 89.9%, 89.9%, 84.4%, 81.5% at 5, 10, 15 and 20 years, respectively.

Conclusions: In a representative cohort of patients having presented with end-stage-liver disease or HCC secondary to A1AT, liver transplantation offered very good patient and graft survival rates.
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http://dx.doi.org/10.1016/j.dld.2020.10.016DOI Listing
May 2021

Reply to Rodriguez-Peralvarez et al.

Transpl Int 2020 12 9;33(12):1825-1826. Epub 2020 Nov 9.

Medical Liver Transplant Unit and Liver Department, Henri Mondor Hospital AP-HP, Paris Est University, Champs-sur-Marne, France.

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http://dx.doi.org/10.1111/tri.13765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675308PMC
December 2020

Mortality after Transplantation for Hepatocellular Carcinoma: A Study from the European Liver Transplant Registry.

Liver Cancer 2020 08 12;9(4):455-467. Epub 2020 May 12.

National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark.

Background And Aims: Prognosis after liver transplantation differs between hepatocellular carcinoma (HCC) arising in cirrhotic and non-cirrhotic livers and aetiology is poorly understood. The aim was to investigate differences in mortality after liver transplantation between these patients.

Methods: We included patients from the European Liver Transplant Registry transplanted due to HCC from 1990 to November 2016 and compared cirrhotic and non-cirrhotic patients using propensity score (PS) calibration of Cox regression estimates to adjust for unmeasured confounding.

Results: We included 22,787 patients, of whom 96.5% had cirrhosis. In the unadjusted analysis, non-cirrhotic patients had an increased risk of overall mortality with a hazard ratio (HR) of 1.37 (95% confidence interval [CI] 1.23-1.52). However, the HR approached unity with increasing adjustment and was 1.11 (95% CI 0.99-1.25) when adjusted for unmeasured confounding. Unadjusted, non-cirrhotic patients had an increased risk of HCC-specific mortality (HR 2.62, 95% CI 2.21-3.12). After adjustment for unmeasured confounding, the risk remained significantly increased (HR 1.62, 95% CI 1.31-2.00).

Conclusions: Using PS calibration, we showed that HCC in non-cirrhotic liver has similar overall mortality, but higher HCC-specific mortality. This may be a result of a more aggressive cancer form in the non-cirrhotic liver as higher mortality could not be explained by tumour characteristics or other prognostic variables.
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http://dx.doi.org/10.1159/000507397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506266PMC
August 2020

Temporal Trends and Outcomes in Liver Transplantation for Recipients With HIV Infection in Europe and United States.

Transplantation 2020 10;104(10):2078-2086

Keck School of Medicine, University of Southern California, Los Angeles, CA.

Background: We evaluated trends and outcomes of liver transplantation (LT) recipients with/without HIV infection.

Methods: LT recipients between 2008 and 2015 from the United Network for Organ Sharing and Organ Procurement and Transplantation Network and European Liver Transplant Registry were included. Trends and characteristics related to survival among LT recipients with HIV infection were determined.

Results: Among 73 206 LT patients, 658 (0.9%) were HIV-infected. The proportion of LT HIV-infected did not change over time (P-trend = 0.16). Hepatitis C virus (HCV) as indication for LT decreased significantly for HIV-infected and HIV-uninfected patients (P-trends = 0.008 and <0.001). Three-year cumulative graft survival in LT recipients with and without HIV infection was 64.4% and 77.3%, respectively (P < 0.001), with improvements over time for both, but with HIV-infected patients having greater improvements (P-trends = 0.02 and 0.03). Adjusted risk of graft loss was 41% higher in HIV-infected versus HIV-uninfected (adjusted hazard ratio [aHR], 1.41; P < 0.001). Among HIV-infected, model of end-stage liver disease (aHR, 1.04; P < 0.001), body mass index <21 kg/m (aHR, 1.61; P = 0.006), and HCV (aHR, 1.83; P < 0.001) were associated with graft loss, whereas more recent period of LT 2012-2015 (aHR, 0.58; P = 0.001) and donor with anoxic cause of death (aHR, 0.51; P = 0.007) were associated with lower risk of graft loss.

Conclusions: Patients with HIV infection account for only 1% of LTs in United States and Europe, with fewer LT for HCV disease over time. A static rate of LT among HIV-infected patients may reflect improvements in cirrhosis management and/or persistent barriers to LT. Graft and patient survival among HIV-infected LT recipients have shown improvement over time.
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http://dx.doi.org/10.1097/TP.0000000000003107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919403PMC
October 2020

Time to Conversion to an Everolimus-Based Regimen: Renal Outcomes in Liver Transplant Recipients From the EVEROLIVER Registry.

Liver Transpl 2020 11 12;26(11):1465-1476. Epub 2020 Oct 12.

Unité de Transplantation Hépatique, Hôpital Edouard Herriot, Lyon, France.

Longterm use of a calcineurin inhibitor (CNI)-based regimen is one of the major reasons for chronic renal failure in liver transplantation recipients (LTRs). The Everolimus Liver registry (EVEROLIVER) evaluated renal function in LTRs who were converted to everolimus (EVR). This observational registry included all LTRs receiving EVR across 9 centers from France. Data are being collected in an electronic database over 10 years (12 visits/patient) to evaluate efficacy, renal function (estimated glomerular filtration rate [eGFR]), and safety of EVR use in clinical practice, and the current analysis is reporting up to 60 months of findings. Until September 2017, 1045 patients received EVR after a mean time of 3.6 ± 5.1 years. CNI withdrawal was feasible in 57.7% of patients as of month 60. Mean eGFR improved in patients with baseline eGFR <60 mL/minute/1.73 m and was maintained in those with baseline eGFR ≥60 mL/minute/1.73 m . Among patients with chronic kidney disease (CKD; baseline eGFR <60 mL/minute/1.73 m ), 55% converted to EVR within 3 months (early conversion) and 39.4% converted between 4 and 12 months after transplantation (mid-conversion) experienced improvement in eGFR (≥60 mL/minute/1.73 m ) at month 36. Only 20.9% and 17.4% among those converted beyond 12 months (late conversion) experienced improvement respectively at month 36 and 60. A logistic regression analysis in patients with CKD stage ≥3 demonstrated that late conversion, age, and female sex were associated with nonimprovement of eGFR (≥60 mL/minute/1.73 m ). Data from this real-life use of EVR indicate that renal function was maintained from the preconversion period until month 36 even in patients with advanced CKD. However, early rather than late conversion appears to be a safe approach to preserve longterm renal function in LTRs.
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http://dx.doi.org/10.1002/lt.25879DOI Listing
November 2020

Impact of COVID-19 on liver transplantation in Europe: alert from an early survey of European Liver and Intestine Transplantation Association and European Liver Transplant Registry.

Transpl Int 2020 10 13;33(10):1244-1252. Epub 2020 Aug 13.

Medical Liver Transplant Unit and Liver Department, Henri Mondor Hospital AP-HP, Paris Est University, Créteil, France.

There are scarce data on the impact of COVID-19 pandemic on liver transplantation (LT) in Europe. The aim of this study was to obtain a preliminary data on incidence, management, and outcome of COVID-19 in liver transplant recipients and candidates in Europe. An Internet-based survey was sent to the centers affiliated with European Liver Transplant Registry (ELTR). One hundred nine out of 149 (73%) of ELTR centers located in 28 European countries (93%) responded. Ninety-four (86%) of the centers tested all donors, and 75 (69%) centers tested all LT recipients for SARS-CoV-2. Seventy-three (67%) centers selected recipients for LT in the COVID-19 pandemic, whereas 33% did not. Eighty-eight centers reported COVID-19 infection in 57 LT candidates and in 272 LT recipients. Overall crude incidence of COVID-19 among LT candidates and recipients was estimated 1.05% (range 0.5-20%) and 0.34% (range 0.1-4.8%), respectively, and it was significantly higher among candidates (P < 0.001). Crude rate of death was 18% (10/57) among candidates and 15% (36/244) among recipients. This first large-scale European snapshot study clearly shows that both LT candidates and recipients are at a high risk for COVID-19. These results plead for an early and pro-active screening of COVID-19 symptoms in these populations.
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http://dx.doi.org/10.1111/tri.13680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361228PMC
October 2020

Socioeconomic Deprivation Does Not Impact Liver Transplantation Outcome for HCC: A Survival Analysis From a National Database.

Transplantation 2021 May;105(5):1061-1068

Anticipe, INSERM U1086, Pôle de Recherche du CHU de Caen, Centre François Baclesse, Caen cedex, France.

Background: To investigate the value of European deprivation index (EDI) and hepatocellular carcinoma (HCC) characteristics and their relationships with outcome after liver transplantation (LT).

Methods: Patients undergoing LT for HCC were included from a national database (from "Agence de la Biomédecine" between 2006 and 2016. Characteristics of the patients were blindly extracted from the database. Thus, EDI was calculated in 5 quintiles and prognosis factors of survival were determined according to a Cox model.

Results: Among the 3865 included patients, 33.9% were in the fifth quintile (quintile 1, N = 562 [14.5%]; quintile 2, N = 647 [16.7%]; quintile 3, N = 654 [16.9%]; quintile 4, N = 688 [17.8%]). Patients in each quintile were comparable regarding HCC history, especially median size of HCC, number of nodules of HCC and alpha-fetoprotein score. In the univariate analysis of the crude survival, having >2 nodules of HCC before LT and time on waiting list were associated with a higher risk of death (P < 0.0001 and P = 0.03, respectively). EDI, size of HCC, model for end-stage liver disease score, Child-Pugh score were not statistically significant in the crude and net survival. In both survival, time on waiting list and number of HCC ≥2 were independent factor of mortality after LT for HCC (P = 0.009 and 0.001, respectively, and P = 0.03 and 0.02, respectively).

Conclusions: EDI does not impact overall survival after LT for HCC. Number of HCC and time on waiting list are independent prognostic factors of survival after LT for HCC.
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http://dx.doi.org/10.1097/TP.0000000000003340DOI Listing
May 2021

Liver transplantation in patients with sickle cell disease: possible but challenging-a cohort study.

Transpl Int 2020 10 6;33(10):1220-1229. Epub 2020 Jul 6.

Centre Hepato-Biliaire, AP-HP Paul Brousse Hospital, Villejuif, France.

The liver is frequently affected in patients with sickle cell disease (SCD), but few reports have described liver transplantation (LT) in patients with SCD. We present a thorough analysis of the largest single-center series of LT in patients with SCD and the first systematic review. There were 21 patients with a median age of 37.6 years. LT was performed for acute liver failure related to the sickling process (57%) or electively for end-stage liver disease (43%). Prior to LT, 13 patients (62%) were in the intensive care unit and required mechanical ventilation (33%), vasopressor therapy (24%), renal replacement therapy (10%), or molecular adsorbent recirculating system therapy (19%). Post-LT morbidity and mortality were 95% and 33%, respectively. Patient survival at 1 and 5 years were 58.3% and 41.7%, respectively, in the urgent group and 88.9% and 77.8%, respectively, in the elective group. A total of 22 transplant patients with SCD are described in 20 articles in the literature. The 1- and 5-year patient survival rates for the 18 evaluable patients were 75% and 65%, respectively. LT improves survival in patients with SCD and acute liver failure or end-stage liver disease but is associated with high morbidity during the early postoperative course.
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http://dx.doi.org/10.1111/tri.13669DOI Listing
October 2020

Longterm Survival After Liver Transplantation for Autoimmune Hepatitis: Results From the European Liver Transplant Registry.

Liver Transpl 2020 07 1;26(7):866-877. Epub 2020 May 1.

I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

The aim of this study was to analyze longterm patient and graft survival after liver transplantation for autoimmune hepatitis (AIH-LT) from the prospective multicenter European Liver Transplant Registry. Patient and liver graft survival between 1998 and 2017 were analyzed. Patients after AIH-LT (n = 2515) were compared with patients receiving LT for primary biliary cholangitis (PBC-LT; n = 3733), primary sclerosing cholangitis (PSC-LT; n = 5155), and alcohol-related cirrhosis (AC-LT; n = 19,567). After AIH-LT, patient survival was 79.4%, 70.8%, and 60.3% and graft survival was 73.2%, 63.4%, and 50.9% after 5, 10, and 15 years of follow-up. Overall patient survival was similar to patients after AC-LT (P = 0.44), but worse than after PBC-LT (hazard ratio [HR], 1.48; P < 0.001) and PSC-LT (HR, 1.19; P = 0.002). AIH-LT patients were at increased risk for death (HR, 1.37-1.84; P < 0.001) and graft loss (HR, 1.35-1.80; P < 0.001) from infections compared with all other groups and had a particularly increased risk for lethal fungal infections (HR, 3.38-4.20; P ≤ 0.004). Excluding patients who died within 90 days after LT, risk of death after AIH-LT was superior compared with AC-LT (HR, 0.84; P = 0.004), worse compared with PBC-LT (HR, 1.38; P < 0.001) and similar compared with PSC-LT (P = 0.93). Autoimmune hepatitis (AIH) patients with living donor liver transplantation (LDLT) showed reduced survival compared with patients receiving donation after brain death (HR, 1.96; P < 0.001). In AIH-LT patients, overall survival is inferior to PBC-LT and PSC-LT. The high risk of death after AIH-LT is caused mainly by early fatal infections, including fungal infections. Patients with LDLT for AIH show reduced survival.
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http://dx.doi.org/10.1002/lt.25739DOI Listing
July 2020

Early Switch From Tacrolimus to Everolimus After Liver Transplantation: Outcomes at 2 Years.

Liver Transpl 2019 12;25(12):1822-1832

Hôpital Pitié Salpêtrière, AP-HP, Paris, France.

The observational CERTITUDE study follows liver transplant patients who completed the SIMCER trial. SIMCER randomized patients at month 1 after transplant to everolimus (EVR) with stepwise tacrolimus (TAC) withdrawal or to standard TAC, both with basiliximab induction and mycophenolic acid ± steroids. After completing SIMCER at 6 months after transplant, 65 EVR-treated patients and 78 TAC-treated patients entered CERTITUDE. At month 24 after transplant, 34/65 (52.3%) EVR-treated patients remained calcineurin inhibitor (CNI) free. Mean estimated glomerular filtration rate (eGFR) was significantly higher with EVR versus TAC during months 3-12. At month 24, eGFR values were 83.6 versus 75.3 mL/minute/1.73 m , respectively (P = 0.90) and adjusted mean change in eGFR from randomization was -8.0 versus -13.5 mL/minute/1.73 m (P = 0.15). At month 24, 45.9%, 31.1%, and 23.0% of EVR-treated patients had chronic kidney disease stages 1, 2, and 3, respectively, versus 25.7%, 45.7%, and 28.6% of TAC-treated patients (P = 0.05). Treated biopsy-proven acute rejection affected 4 EVR-treated patients and 2 TAC patients during months 6-24. Adverse events led to study discontinuation in 15.4% and 7.7% of EVR-treated and TAC-treated patients, respectively. Grade 3 or 4 hematological events were rare in both groups. A CNI-free EVR-based maintenance regimen appears feasible in approximately half of liver transplant patients. It preserves renal function effectively with good efficacy without compromising safety or hematological tolerance.
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http://dx.doi.org/10.1002/lt.25664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383505PMC
December 2019

Anonymous living donation in liver transplantation: Squaring the circle or condemned to vanish?

J Hepatol 2019 11 24;71(5):864-866. Epub 2019 Sep 24.

Medical Liver Transplant Unit and Liver Department, Henri Mondor Hospital-APH, Paris Est University, France. Electronic address:

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http://dx.doi.org/10.1016/j.jhep.2019.08.028DOI Listing
November 2019

A Multicenter, Prospective, Observational Study of Conversion from Twice-Daily Immediate-Release to Once-Daily Prolonged-Release Tacrolimus in Liver Transplant Recipients in France: The COBALT Study.

Ann Transplant 2019 Aug 27;24:506-516. Epub 2019 Aug 27.

Departement of Hepatology, Pontchaillou Hospital, Rennes, France.

BACKGROUND In adult liver transplant patients, the use of prolonged-release tacrolimus may have treatment adherence benefits over the immediate-release formulation. The aim of this study was to characterise real-world practice data on conversion of liver transplant recipients from immediate- to prolonged-release tacrolimus in France. MATERIAL AND METHODS A prospective, observational study (NCT02143479) was conducted in 18 transplant centers in France between June 2014 and March 2016. Liver transplant recipients (n=398) included patients who changed from immediate-release to prolonged-release tacrolimus within the first three months (early conversion group) (n=205) or between three and 12 months after transplantation (late conversion group) (n=184). Clinical data were collected at an initial baseline outpatient visit and six-month and 12-month follow-up visits. Endpoints included the dose conversion ratio from immediate-release to prolonged-release tacrolimus, number of and reasons for additional visits due to conversion, safety, and tolerability. RESULTS Baseline clinical and demographic characteristics were similar between the two cohorts. The mean ±SD ratio of conversion of tacrolimus dose was 1.04±0.28; 1.01±0.28 (early) and 1.08±0.28 (late) (p=0.0247). The mean ±SD time from conversion to the first tacrolimus trough blood concentration was 30.8±42.8 days; 24.8±45.4 days (early) and 37.5±38.7 days (late). Only one patient required an additional visit due to conversion. Reasons for conversion included the physician's preference (56.3%), center practice (38.6%), and the dosing frequency (36.0%). Conversion was associated with a low rate of graft rejection, and no new safety issues were reported. CONCLUSIONS Conversion of liver transplant recipients from immediate-release to prolonged-release tacrolimus within three to 12 months of transplantation was easy to manage and associated with favorable clinical outcomes and safety profiles.
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http://dx.doi.org/10.12659/AOT.916041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6728630PMC
August 2019

Comparison of the effect of direct-acting antiviral with and without ribavirin on cyclosporine and tacrolimus clearance values: results from the ANRS CO23 CUPILT cohort.

Eur J Clin Pharmacol 2019 Nov 5;75(11):1555-1563. Epub 2019 Aug 5.

AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, France.

Purpose: Direct-acting antiviral agents have demonstrated their efficacy in treating HCV recurrence after liver transplantation and particularly the sofosbuvir/daclatasvir combination. Pharmacokinetic data on both calcineurin inhibitors and direct-acting antiviral exposure in liver transplant recipients remain sparse.

Methods: Patients were enrolled from the ANRS CO23 CUPILT cohort. All patients treated with sofosbuvir/daclatasvir with or without ribavirin were included in this study when blood samples were available to estimate the clearance of immunosuppressive therapy before direct-acting antiviral initiation and during follow-up. Apparent tacrolimus and cyclosporine clearances were estimated from trough concentrations measured using validated quality control assays.

Results: Sixty-seven mainly male patients (79%) were included, with a mean age of 57 years and mean MELD score of 8.2; 50 were on tacrolimus, 17 on cyclosporine. Ribavirin was combined with sofosbuvir/daclatasvir in 52% of patients. Cyclosporine clearance remained unchanged as well as tacrolimus clearance under the ribavirin-free regimen. Tacrolimus clearance increased 4 weeks after direct-acting antivirals and ribavirin initiation versus baseline (geometric mean ratio 1.81; 90% CI 1.30-2.52). Patients under ribavirin had a significantly higher fibrosis stage (> 2) (p = 0.02) and lower haemoglobin during direct-acting antiviral treatment (p = 0.02) which impacted tacrolimus measurements. Direct-acting antiviral exposure was within the expected range.

Conclusion: Our study demonstrated that liver transplant patients with a recurrence of hepatitis C who are initiating ribavirin combined with a sofosbuvir-daclatasvir direct-acting antiviral regimen may be at risk of lower tacrolimus concentrations because of probable ribavirin-induced anaemia and higher fibrosis score, although there are no effects on cyclosporine levels.

Trial Registration: NCT01944527.
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http://dx.doi.org/10.1007/s00228-019-02725-xDOI Listing
November 2019

Improved Survival in Liver Transplant Patients Receiving Prolonged-release Tacrolimus-based Immunosuppression in the European Liver Transplant Registry (ELTR): An Extension Study.

Transplantation 2019 09;103(9):1844-1862

Department of Surgery and Liver Transplantation, Fundeni Clinical Institute, University of Medicine "Carol Davila", Bucharest, Romania.

Background: We compared, through the European Liver Transplant Registry, long-term liver transplantation outcomes with prolonged-release tacrolimus (PR-T) versus immediate-release tacrolimus (IR-T)-based immunosuppression. This retrospective analysis comprises up to 8-year data collected between 2008 and 2016, in an extension of our previously published study.

Methods: Patients with <1 month follow-up were excluded; patients were propensity score matched for baseline characteristics. Efficacy measures included: univariate/multivariate analyses of risk factors influencing graft/patient survival up to 8 years posttransplantation, and graft/patient survival up to 4 years with PR-T versus IR-T. Overall, 13 088 patients were included from 44 European centers; propensity score-matched analyses comprised 3006 patients (PR-T: n = 1002; IR-T: n = 2004).

Results: In multivariate analyses, IR-T-based immunosuppression was associated with reduced graft survival (risk ratio, 1.49; P = 0.0038) and patient survival (risk ratio, 1.40; P = 0.0215). There was improvement with PR-T versus IR-T in graft survival (83% versus 77% at 4 y, respectively; P = 0.005) and patient survival (85% versus 80%; P = 0.017). Patients converted from IR-T to PR-T after 1 month had a higher graft survival rate than patients receiving IR-T at last follow-up (P < 0.001), or started and maintained on PR-T (P = 0.019). One graft loss in 4 years was avoided for every 14.3 patients treated with PR-T versus IR-T.

Conclusions: PR-T-based immunosuppression might improve long-term outcomes in liver transplant recipients than IR-T-based immunosuppression.
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http://dx.doi.org/10.1097/TP.0000000000002700DOI Listing
September 2019

Clinical Impact of Genomic Diversity From Early to Advanced Hepatocellular Carcinoma.

Hepatology 2020 01 12;71(1):164-182. Epub 2019 Aug 12.

Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, USPC, Université Paris Descartes, Université Paris Diderot, Université Paris 13, Functional Genomics of Solid Tumors Laboratory, Paris, France.

To date, genomic analyses of hepatocellular carcinoma (HCC) have been limited to early stages obtained from liver resection. We aim to describe the genomic profiling of HCC from early to advanced stages. We analyzed 801 HCC from 720 patients (410 resections, 137 transplantations, 122 percutaneous ablations, and 52 noncurative) for 190 gene expressions and for 31 gene mutations. Forty-one advanced HCC and 156 whole exome of Barcelona Clinic Liver Cancer (BCLC) 0/A were analyzed by whole-exome sequencing. Genomic profiling was correlated with tumor stages, clinical features, and survival. Our cohort included patients classified in BCLC stage 0 (9.4%), A (59.5%), B (16.2%), and C (14.9%). Among the overall 801 HCC, the most frequently mutated genes were telomerase reverse transcriptase (TERT) (58.1%), catenin beta 1 (CTNNB1) (30.7%), tumor protein 53 (TP53; 18.7%), AT-rich interaction domain 1A (ARID1A) (13%), albumin (11.4%), apolipoprotein B (APOB) (9.4%), and AXIN1 (9.2%). Advanced-stage HCC (BCLC B/C) showed higher frequencies of splicing factor 3b subunit 1 (SF3B1) (P = 0.0003), TP53 (P = 0.0006), and RB Transcriptional Corepressor 1 mutations (P = 0.03). G1-G6 transcriptomic classification and the molecular prognostic 5-gene score showed different distributions according to the stage of the disease and the type of treatment with an enrichment of G3 (P < 0.0001), poor prognostic score (P < 0.0001), and increased proliferation and dedifferentiation at the transcriptomic level in advanced HCC. The 5-gene score predicted survival in patients treated by resection (P < 0.0001) and ablation (P = 0.01) and in advanced HCC (P = 0.04). Twenty-two percent of advanced HCC harbored potentially druggable genetic alterations, and MET amplification was associated with complete tumor response in patients with advanced HCC treated by a specific MET inhibitor. Conclusion: Genomic analysis across the different stages of HCC revealed the mechanisms of tumor progression and helped to identify biomarkers of response to targeted therapies.
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http://dx.doi.org/10.1002/hep.30811DOI Listing
January 2020

Outcomes of liver transplantation for non-alcoholic steatohepatitis: A European Liver Transplant Registry study.

J Hepatol 2019 08 7;71(2):313-322. Epub 2019 May 7.

Department of Visceral, Transplant and Thoracic Surgery, Innsbruck Medical University, Innsbruck, Austria.

Background & Aims: Little is known about outcomes of liver transplantation for patients with non-alcoholic steatohepatitis (NASH). We aimed to determine the frequency and outcomes of liver transplantation for patients with NASH in Europe and identify prognostic factors.

Methods: We analysed data from patients transplanted for end-stage liver disease between January 2002 and December 2016 using the European Liver Transplant Registry database. We compared data between patients with NASH versus other aetiologies. The principle endpoints were patient and overall allograft survival.

Results: Among 68,950 adults undergoing first liver transplantation, 4.0% were transplanted for NASH - an increase from 1.2% in 2002 to 8.4% in 2016. A greater proportion of patients transplanted for NASH (39.1%) had hepatocellular carcinoma (HCC) than non-NASH patients (28.9%, p <0.001). NASH was not significantly associated with survival of patients (hazard ratio [HR] 1.02, p = 0.713) or grafts (HR 0.99; p = 0.815) after accounting for available recipient and donor variables. Infection (24.0%) and cardio/cerebrovascular complications (5.3%) were the commonest causes of death in patients with NASH without HCC. Increasing recipient age (61-65 years: HR 2.07, p <0.001; >65: HR 1.72, p = 0.017), elevated model for end-stage liver disease score (>23: HR 1.48, p = 0.048) and low (<18.5 kg/m: HR 4.29, p = 0.048) or high (>40 kg/m: HR 1.96, p = 0.012) recipient body mass index independently predicted death in patients transplanted for NASH without HCC. Data must be interpreted in the context of absent recognised confounders, such as pre-morbid metabolic risk factors.

Conclusions: The number and proportion of liver transplants performed for NASH in Europe has increased from 2002 through 2016. HCC was more common in patients transplanted with NASH. Survival of patients and grafts in patients with NASH is comparable to that of other disease indications.

Lay Summary: The prevalence of non-alcoholic fatty liver disease has increased dramatically in parallel with the worldwide increase in obesity and diabetes. Its progressive form, non-alcoholic steatohepatitis, is a growing indication for liver transplantation in Europe, with good overall outcomes reported. However, careful risk factor assessment is required to maintain favourable post-transplant outcomes in patients with non-alcoholic steatohepatitis.
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http://dx.doi.org/10.1016/j.jhep.2019.04.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6656693PMC
August 2019

Trends in liver transplantation for primary biliary cholangitis in Europe over the past three decades.

Aliment Pharmacol Ther 2019 02 18;49(3):285-295. Epub 2018 Dec 18.

Rotterdam, The Netherlands.

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.
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http://dx.doi.org/10.1111/apt.15060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590354PMC
February 2019

2018 Annual Report of the European Liver Transplant Registry (ELTR) - 50-year evolution of liver transplantation.

Transpl Int 2018 12;31(12):1293-1317

University of Edinburgh Royal Infirmary, Edinburgh, UK.

The purpose of this registry study was to provide an overview of trends and results of liver transplantation (LT) in Europe from 1968 to 2016. These data on LT were collected prospectively from 169 centers from 32 countries, in the European Liver Transplant Registry (ELTR) beginning in 1968. This overview provides epidemiological data, as well as information on evolution of techniques, and outcomes in LT in Europe over more than five decades; something that cannot be obtained from only a single center experience.
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http://dx.doi.org/10.1111/tri.13358DOI Listing
December 2018

Optimal oncologic management and mTOR inhibitor introduction are safe and improve survival in kidney and liver allograft recipients with de novo carcinoma.

Int J Cancer 2019 02 20;144(4):886-896. Epub 2018 Nov 20.

Medical Oncology, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris, 94100, Créteil, France.

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.
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http://dx.doi.org/10.1002/ijc.31769DOI Listing
February 2019