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The rapidly aging population in industrialized countries comes with an increased incidence of intrahepatic cholangiocarcinoma (iCC) which presents new challenges for oncological treatments especially in elderly patients. Thus, the question arises to what extent the benefit of surgical resections, as the only curative treatment option, outweighs possible perioperative risks in patients ≥ 80 years of age (octogenarians). We therefore retrospectively analyzed 311 patients who underwent resection for iCC at Hannover Medical School between January 1996 and December 2022. In total, there were 11 patients older than 80 years in our collective. Despite similar tumor size, octogenarians underwent comparatively less extensive surgery (54.5% major resections in octogenarians vs. 82.7% in all other patients; p = 0.033) with comparable rates of lymphadenectomy and tumor-free resection margins. Furthermore, we did not observe increased major postoperative morbidity (Clavien-Dindo ≥ IIIa complications: 27.3% vs. 34.3% in all other patients; p = 0.754) or mortality (estimated 1-year OS of 70.7% vs. 72.5% in all other patients, p = 0.099). The length of intensive care unit (ICU) or intermediate care unit (IMC) stay was significantly longer in octogenarians, however, with a comparable length in total hospital stay. The estimated overall survival (OS) did also not differ significantly, although a trend towards reduced long-term survival was observed (14.5 months vs. 28.03 months in all other patients; p = 0.099). In conclusion, primary resection is a justifiable and safe therapeutic option even in octogenarians but requires an even more thorough preoperative patient selection.
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INTRODUCTION: Hepatic artery complications (HACs), such as a thrombosis or stenosis, are serious causes of morbidity and mortality after paediatric liver transplantation (LT). This study will investigate the incidence, current management practices and outcomes in paediatric patients with HAC after LT, including early and late complications. METHODS AND ANALYSIS: The HEPatic Artery stenosis and Thrombosis after liver transplantation In Children (HEPATIC) Registry is an international, retrospective, multicentre, observational study. Any paediatric patient diagnosed with HAC and treated for HAC (at age <18 years) after paediatric LT within a 20-year time period will be included. The primary outcomes are graft and patient survivals. The secondary outcomes are technical success of the intervention, primary and secondary patency after HAC intervention, intraprocedural and postprocedural complications, description of current management practices, and incidence of HAC. ETHICS AND DISSEMINATION: All participating sites will obtain local ethical approval and (waiver of) informed consent following the regulations on the conduct of observational clinical studies. The results will be disseminated through scientific presentations at conferences and through publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: The HEPATIC registry is registered at the ClinicalTrials.gov website; Registry Identifier: NCT05818644.
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Arteria Hepática , Trasplante de Hígado , Complicaciones Posoperatorias , Sistema de Registros , Trombosis , Humanos , Trasplante de Hígado/efectos adversos , Estudios Retrospectivos , Niño , Incidencia , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Trombosis/etiología , Trombosis/epidemiología , Adolescente , Preescolar , Femenino , Masculino , Constricción Patológica/etiología , Lactante , Estudios Multicéntricos como AsuntoRESUMEN
BACKGROUND: Whenever the kidney standard allocation (SA) algorithms according to the Eurotransplant (ET) Kidney Allocation System or the Eurotransplant Senior Program fail, rescue allocation (RA) is initiated. There are 2 procedurally different modes of RA: recipient oriented extended allocation (REAL) and competitive rescue allocation (CRA). The objective of this study was to evaluate the association of patient survival and graft failure with RA mode and whether or not it varied across the different ET countries. METHODS: The ET database was retrospectively analyzed for donor and recipient clinical and demographic characteristics in association with graft outcomes of deceased donor renal transplantation (DDRT) across all ET countries and centers from 2014 to 2021 using Cox proportional hazards methods. RESULTS: Seventeen thousand six hundred seventy-nine renal transplantations were included (SA 15 658 [89%], REAL 860 [4.9%], and CRA 1161 [6.6%]). In CRA, donors were older, cold ischemia times were longer, and HLA matches were worse in comparison with REAL and especially SA. Multivariable analyses showed comparable graft and recipient survival between SA and REAL; however, CRA was associated with shorter graft survival. Germany performed 76% of all DDRTs after REAL and CRA and the latter mode reduced waiting times by up to 2.9 y. CONCLUSIONS: REAL and CRA are used differently in the ET countries according to national donor rates. Both RA schemes optimize graft utilization, lead to acceptable outcomes, and help to stabilize national DDRT programs, especially in Germany.
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Importance: The potential association of low-volume paracentesis of less than 5 L with complications in patients with ascites remains unclear, and individuals with cirrhosis and refractory ascites (RA) treated with devices like Alfapump or tunneled-intraperitoneal catheters perform daily low-volume drainage without albumin substitution. Studies indicate marked differences regarding the daily drainage volume between patients; however, it is currently unknown if this alters the clinical course. Objective: To determine whether the incidence of complications, such as hyponatremia or acute kidney injury (AKI), is associated with the daily drainage volume in patients with devices. Design, Setting, and Participants: This retrospective cohort study of patients with liver cirrhosis, RA, and a contraindication for a transjugular intrahepatic portosystemic shunt who received either device implantation or standard of care (SOC; ie, repeated large-volume paracentesis with albumin infusion), and were hospitalized between 2012 and 2020 were included. Data were analyzed from April to October 2022. Interventions: Daily ascites volume removed. Main outcomes and Measures: The primary end points were 90-day incidence of hyponatremia and AKI. Propensity score matching was performed to match and compare patients with devices and higher or lower drainage volumes to those who received SOC. Results: Overall, 250 patients with RA receiving either device implantation (179 [72%] patients; 125 [70%] male; 54 [30%] female; mean [SD] age, 59 [11] years) or SOC (71 [28%] patients; 41 [67%] male; 20 [33%] female; mean [SD] age, 54 [8]) were included in this study. A cutoff of 1.5 L/d or more was identified to estimate hyponatremia and AKI in the included patients with devices. Drainage of 1.5 L/d or more was associated with hyponatremia and AKI, even after adjusting for various confounders (hazard ratio [HR], 2.17 [95% CI, 1.24-3.78]; P = .006; HR, 1.43 [95% CI, 1.01-2.16]; P = .04, respectively). Moreover, patients with taps of 1.5 L/d or more and less than 1.5 L/d were matched with patients receiving SOC. Those with taps of 1.5 L/d or more had a higher risk of hyponatremia and AKI compared with those receiving SOC (HR, 1.67 [95% CI, 1.06-2.68]; P = .02 and HR, 1.51 [95% CI, 1.04-2.18]; P = .03), while patients with drainage of less than 1.5 L/d did not show an increased rate of complications compared with those receiving SOC. Conclusions and Relevance: In this cohort study, clinical complications in patients with RA performing low-volume drainage without albumin infusion were associated with the daily volume drained. Based on this analysis, physicians should be cautious in patients performing drainage of 1.5 L/d or more without albumin infusion.
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Lesión Renal Aguda , Hiponatremia , Humanos , Masculino , Femenino , Persona de Mediana Edad , Paracentesis/efectos adversos , Ascitis/epidemiología , Ascitis/etiología , Ascitis/terapia , Estudios de Cohortes , Estudios Retrospectivos , Hiponatremia/epidemiología , Hiponatremia/etiología , Cirrosis Hepática/complicaciones , Albúminas , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/etiología , Lesión Renal Aguda/terapiaRESUMEN
The incidence of pediatric liver tumors in general has been rising over the last years and so is the number of children undergoing liver transplantation for this indication. To contribute to the ongoing improvement of pre- and post-transplant care, we aim to describe outcome and risk factors in our patient cohort. We have compared characteristics and outcome for patients transplanted for hepatoblastoma to other liver malignancies in our center between 1983 and 2022 and analysed influential factors on tumor recurrence and mortality using nominal logistic regression analysis. Of 39 children (16 f) who had transplants for liver malignancy, 31 were diagnosed with hepatoblastoma. The proportion of malignant tumors in the transplant cohort rose from 1.9% (1983-1992) to 9.1% in the current decade (p < 0.0001). Hepatoblastoma patients were transplanted at a younger age and were more likely to have tumor extent beyond the liver. Post-transplant bile flow impairment requiring intervention was significantly higher compared to our total cohort (48 vs. 24%, p > 0.0001). Hearing loss was a common side effect of ototoxic chemotherapy in hepatoblastoma patients (48%). The most common maintenance immunosuppression were mTor-inhibitors. Risk factors for tumor recurrence in patients with hepatoblastoma were higher AFP before transplant (AFPpre-LTX), a low ratio of AFPmax to AFPpre-LTX and salvage transplantation. Liver malignancies represent a rising number of indications for liver transplantation in childhood. Primary tumor resection can spare a liver transplant with all its long-term complications, but in case of tumor recurrence, transplantation might have inferior outcome. The rate of acute biopsy-proven rejections and biliary complications in comparison to our total transplant cohort needs further investigations.
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In pediatric liver transplantation (pLT), the risk for the manifestation and relevance of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) is high. This observational study aimed to evaluate the incidence, relevance and risk factors for IAH and ACS by monitoring the intra-abdominal pressure (IAP), macro- and microcirculation (near-infrared spectroscopy (NIRS)), clinical and laboratory status and outcomes of 27 patients (16 female) after pLT (median age at pLT 35 months). Of the patients, 85% developed an elevated IAP, most of them mild. However, 17% achieved IAH° 3, 13% achieved IAH° 4 and 63% developed ACS. A multiple linear regression analysis identified aortal hepatic artery anastomosis and cold ischemia time (CIT) as risk factors for increased IAP and longer CIT and staged abdominal wall closure for ACS. ACS patients had significantly longer mechanical ventilation (p = 0.004) and LOS-PICU (p = 0.003). No significant correlation between NIRS or biliary complications and IAH or ACS could be shown. IAH and ACS after pLT were frequent. NIRS or grade of IAH alone should not be used for monitoring. A longer CIT is an important risk factor for higher IAP and ACS. Therefore, approaches such as the ex vivo machine perfusion of donor organs, reducing CIT effects on them, have great potential. Our study provides important basics for studying such approaches.
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Background: Liver transplantation (LT) is considered a therapeutic option for unresectable perihilar cholangiocarcinoma (PHC) within defined criteria. It remains uncertain whether patients can safely receive adjuvant chemotherapy after LT. Methods: We performed a prospective, multi-center, randomized, non-blinded two-arm trial (pro-duct001). Patients after LT for unresectable PHC within defined criteria were randomized to adjuvant gemcitabine (LT-Gem group) and LT alone (LT alone group). The primary objective was to investigate if adjuvant chemotherapy is feasible in ≥ 85% of patients after LT. The primary endpoint was the percentage of patients completing the 24 weeks course of adjuvant chemotherapy. Secondary endpoints included overall survival (OS) and disease-free (DFS), and complication rates. Results: Twelve patients underwent LT for PHC, of which six (50%) were eligible for randomization (LT-Gem: three patients, LT alone: three patients). Two out of three patients discontinued adjuvant chemotherapy after LT due to intolerance. The study was prematurely terminated due to slow enrollment. One patient with PHC had underlying primary sclerosing cholangitis (PSC). Tumor-free margins could be achieved in all patients. In both the LT-Gem and the LT alone group, the cumulative 1-, 3-, and 5-year OS and DFS rates were 100%, 100%, 67%, and 100%, 67% and 67%, respectively. Conclusions: This prospective, multi-center study was prematurely terminated due to slow enrollment and a statement on the defined endpoints cannot be made. Nevertheless, long-term survival data are consistent with available retrospective data and confirm defined criteria for LT. Since more evidence of LT per se in unresectable PHC is urgently needed, a prospective, non-randomized follow-up study (pro-duct002) has since been launched.
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Leukocyte telomere length (LTL) is a marker for biological age. Pediatric liver transplant recipients show a high rate of subclinical atherosclerosis, indicated by elevated intima-media thickness (IMT). We hypothesized that atherosclerosis is associated with biological age in these patients and investigated the course of LTL over time. We measured LTL from peripheral blood leukocytes by quantitative polymerase chain reaction and IMT from 97 pediatric patients after liver transplantation in a prospective cohort study. Of the patients, 71% (n = 69) had two or more assessments (total, 228 observations; median follow-up, 1.1 years). Lower LTL was associated with higher IMT (ß = -0.701, p = 0.01) and higher aspartate aminotransferase (ß = -0.001, p = 0.02), adjusted for age, sex, and age at transplantation. Of the patients, 45% showed decreasing LTL over time, whereas 55% exhibited stable LTL. Patients with stable LTL showed a decrease in IMT (median, -0.02 mm/year) and a decrease of tacrolimus trough levels (median, -0.08 µg/L/year). LTL is associated with IMT independent of age in pediatric liver transplant patients, suggesting that early aging contributes to the high burden of subclinical cardiovascular damage and may furthermore negatively affect the graft.
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Aterosclerosis , Trasplante de Hígado , Aspartato Aminotransferasas , Aterosclerosis/epidemiología , Aterosclerosis/etiología , Grosor Intima-Media Carotídeo , Niño , Humanos , Leucocitos , Trasplante de Hígado/efectos adversos , Estudios Prospectivos , Tacrolimus , TelómeroRESUMEN
This study aims to evaluate the long-term efficacy and reintervention rate after primary percutaneous portal vein stent angioplasty for portal vein stenosis (PVS) in pediatric liver transplantation (LT) recipients. From 2004 to 2020, a total of 470 pediatric LTs were performed in our center. All cases were screened for interventional PVS treatment and analyzed retrospectively. We identified 44 patients with 46 percutaneous angioplasties for posttransplantation PVS. The median interval from LT to percutaneous catheter intervention was 5 months (16 days-104 months) with a median follow-up (f/u) period after catheter intervention of 5.7 years (2-156 months). In 40 patients, an endovascular stent was placed as primary (n = 38) or secondary (n = 2) intervention. The median age at stent placement was 23 (6-179) months with a median weight of 10 kg (6-46 kg). Technical success and relief of PVS were achieved in all patients irrespective of age or weight. Adverse events occurred peri-interventionally in two patients and were resolved with standard care. All primary portal vein (PV) stents remained patent until the end of f/u. Reinterventions have been successfully performed in 10 patients for suspected or proven restenosis, resulting in a primary patency rate of 75% and an assisted patency rate of 25%. The median time to reintervention was 6.2 years (range 1-10 years). The need for reintervention was independent of age or weight at both transplantation and initial angioplasty as well as of additional risk factors due to portal hypertension. Percutaneous transhepatic PV stent angioplasty in children is safe and effective in all age groups, with excellent long-term patency. Primary stent angioplasty should be considered as first-line treatment for PVS after pediatric LT.
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Angioplastia de Balón , Trasplante de Hígado , Angioplastia/efectos adversos , Angioplastia de Balón/métodos , Niño , Constricción Patológica/etiología , Constricción Patológica/cirugía , Humanos , Trasplante de Hígado/efectos adversos , Vena Porta/diagnóstico por imagen , Vena Porta/cirugía , Estudios Retrospectivos , Stents , Resultado del TratamientoRESUMEN
The reported prevalence of autoantibodies (AAB) (ANA, SMA, LKM, SLA) after pediatric liver transplantation (pLTX) varies considerably from 26-75%, but their clinical impact on outcome is uncertain. We aimed to study the prevalence of AAB after pLTX, their association with donor-, transplant-, and recipient-characteristics, and their relation to outcome. In our multicenter retrospective study, we aimed to clarify conflicting results from earlier studies. Six ERN TransplantChild centers reported data on 242 patients, of whom 61% were AAB positive. Prevalence varied across these centers. Independent of the interval between pLTX and AAB analysis, a one-hour increase in CIT resulted in an odds ratio (OR) of 1.37 (95% CI 1.11-1.69) for SMA positivity and an OR of 1.42 (95%CI 1.18-1.72) for ANA positivity. Steroid-free immunosuppression (IS) versus steroid-including IS (OR 5.28; 95% CI 1.45-19.28) was a risk factor for SMA positivity. Liver enzymes were not associated with ANA or SMA positivity. We did not observe an association of rejection activity index with ANA or SMA. However, the liver fibrosis score in follow-up biopsies was associated with ANA titer and donor age. In conclusion, this first multicenter study on AAB after pLTX showed high AAB prevalence and varied widely between centers. Longer CIT and prednisolone-free-IS were associated with AAB positivity, whereas AAB were not indicative of rejection, but instead were associated with graft fibrosis. The detection of AAB may be a marker of liver fibrosis and may be taken into consideration when indications for liver biopsy and immunosuppressive regimes, or reduction of immunosuppression in long-term follow-up, are being discussed. Prospective immunological profiling of pLTX patients, including AAB, is important to further improve our understanding of transplant immunology and silent graft fibrosis.
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BACKGROUND: Potential indications for surgery frequently arise in patients awaiting liver transplantation. There is a risk of hepatic decompensation and death triggered by surgical trauma, but this has not been studied in detail in this unique population. We aimed to quantify the impact of surgical interventions in patients awaiting liver transplantation on hepatic function and identify risk factors for decompensation. METHODS: All surgeries between 2000 and 2018 in patients awaiting liver transplantation in a highvolume German liver transplant center were analyzed retrospectively. Change in liver function measured as indicated by MELD score was assessed and complication rates recorded. The primary endpoint was a composite of an increase in MELD score by > 5 points or death. A logistic regression model was used for multivariate analysis to identify risk factors. RESULTS: In total, 177 surgical procedures in 148 patients were analyzed. The primary endpoint was reached in 42 cases (23.7%). The overall in-hospital complication rate (including death) was 44.1%. Multivariate analysis identified elevated leukocyte count, perioperative blood transfusion, preoperative presence of ascites, and preoperative circulatory support as independent risk factors for a decline in liver function or death. CONCLUSION: Surgery in patients awaiting liver transplantation carries a relevant risk of hepatic decompensation and death that needs to be considered when deciding whether to perform elective surgery prior to or defer until after liver transplantation.
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Graft survival beyond year 1 has not changed after orthotopic liver transplantation (OLT) over the last decades. Likewise, OLT causes comorbidities such as infection, renal impairment and cancer. We evaluated our single-center real-world individualized immunosuppression program after OLT, based on 211 baseline surveillance biopsies (svLbx) without any procedural complications. Patients were classified as low, intermediate and high rejection risk based on graft injury in svLbx and anti-HLA donor-specific antibodies. While 32% of patients had minimal histological inflammation, 57% showed histological inflammation and 23% advanced fibrosis (>F2), which was not predicted by lab parameters. IS was modified in 79% of patients after svLbx. After immunosuppression reduction in 69 patients, only 5 patients showed ALT elevations and three of these patients had a biopsy-proven acute rejection, two of them related to lethal comorbidities. The rate of liver enzyme elevation including rejection was not significantly increased compared to a svLbx control cohort prior to the initiation of our structured program. Immunosuppression reduction led to significantly better kidney function compared to this control cohort. In conclusion, a biopsy guided personalized immunosuppression protocol after OLT can identify patients requiring lower immunosuppression or patients with graft injury in which IS should not be further reduced.
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Trasplante de Hígado , Biopsia , Rechazo de Injerto/patología , Supervivencia de Injerto , Humanos , Terapia de Inmunosupresión , Inmunosupresores/uso terapéutico , Trasplante de Hígado/efectos adversosRESUMEN
(1) Background and Aim: Despite excellent long-term results in pediatric liver transplantation (pLTx), mortality and graft loss still are to be diminished. We aim to describe time-dependent changes and long-term outcome of a large single-center pLTx cohort and to identify independent recipient-related risk factors impairing patient and graft survival. (2) Methods: This is a retrospective single-center study analyzing all pediatric liver transplants from 1983-2020. Risk factors for mortality and graft loss were identified by univariable and multi-linear regression analysis. (3) Results: We analyzed 858 liver transplantations in 705 pediatric patients. Five-year patient/graft survival increased from 60.9%/48.0% (1983-1992) to 97.5%/86.5% (OR = 12.5; p < 0.0001/OR = 6.5; p < 0.0001) (2014-2020). Indications changed significantly over time, with a higher proportion of patients being transplanted for malignancies and metabolic disease and indications of PFIC and α1AT-deficiency declining. The era of transplantation (log7.378/9.657; p < 0.0001) and indication of acute liver failure (log = 1.944/2.667; HR = 2.015/1.772; p = 0.0114/0.002) impairs patient/graft survival significantly in the multivariate analysis. Furthermore, patient survival is worsened by re-transplantation (log = 1.755; HR = 1.744; p = 0.0176) and prolonged waiting times in high-urgency status (log = 2.588; HR = 1.073; p = 0.0026), whereas the indication of biliary atresia improved outcome (log = 1.502; HR = 0.575; p = 0.0315). Graft survival was additionally impaired by pre-existing portal vein thrombosis (log = 1.482; HR = 2.016; p = 0.0330). (4) Conclusions: Despite more complex indications, patient and graft survival after pLTx continue to improve.. Acute liver failure remains the indication with poorest outcome, and listing for high urgency liver transplantation should be considered carefully and early to keep waiting time on HU list short. Furthermore, pre-transplant portal vein thrombosis should be prevented whenever possible to improve graft survival.
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BACKGROUND Our kidney transplant waitlist includes 20% re-transplantations (TX2). Knowing what to expect is a clinical obligation. MATERIAL AND METHODS We compared graft and patient survival of all 162 TX2 patients, transplanted 2000 to 2009, with 162 patients after first transplantation (TX1) matched for age, sex, living/non-living donation, and transplantation date. Patient follow-up was 10 years. RESULTS TX2 graft and patient survivals were inferior to TX1 (p<0.001 and p=0.047). TX2 patients had a longer cumulative dialysis vintage, more human leucocyte antigen (HLA) mismatches, more panel-reactive HLA antibodies, more often received induction therapy with rabbit-antithymocyte globulin (rATG), and had a lower body mass index (all p<0.05). Death from infection and graft failure by rejection was more frequent after TX2 (both p<0.05) but not after TX1. Multivariable Cox regression analysis revealed that both cohorts had graft failure and death risk associated with infection and cardiovascular disease, and graft failure by humoral rejection. However, only TX2 patients had an additional risk of graft failure with early inferior graft function and of patient death with ≥2 comorbidities. Moreover, Kaplan-Meier analysis showed that TX2 and not TX1 patients had a lower graft and patient survival associated with infection and with ≥2 comorbidities (all p<0.05). CONCLUSIONS Re-transplantation is associated with worse graft outcomes mainly because of immunologic and graft-quality reasons, although the high number of comorbidities and infection severities aside from cardiovascular disease drive mortality. The more frequent rATG induction of TX2 patients could promote infection by enhancing immunosuppression. By addressing comorbidities, outcomes could possibly be improved.
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Trasplante de Riñón , Reoperación , Enfermedad Aguda , Femenino , Rechazo de Injerto/etiología , Humanos , Riñón , Masculino , Persona de Mediana Edad , Pancreatitis , Factores de RiesgoRESUMEN
BACKGROUND: In spite of renal graft shortage and increasing waiting times for transplant candidates, simultaneous heart and kidney transplantation (HKTx) is an increasingly performed procedure established for patients with combined end-stage cardiac and renal failure. Although data on renal graft outcome in this setting is limited, reports on reduced graft survival in comparison to solitary kidney transplantation (KTx) have led to an ongoing discussion of adequate organ utilization. METHODS: This retrospective study was conducted to evaluate prognostic factors and outcomes of 27 patients undergoing HKTx in comparison to a matched cohort of 27 patients undergoing solitary KTx between September 1987 and October 2019 in one of Europe's largest transplant centers. RESULTS: Median follow-up was 100.33 (0.46-362.09) months. Despite lower five-year kidney graft survival (62.6% versus 92.1%; 111.73 versus 183.08 months; p = 0.189), graft function and patient survival (138.90 versus 192.71 months; p = 0.128) were not significantly inferior after HKTx in general. However, in case of prior cardiac surgery requiring sternotomy we observed significantly reduced early graft and patient survival (57.00 and 94.09 months, respectively) when compared to patients undergoing solitary KTx (183.08 and 192.71 months; p < 0.001, respectively) or HKTx without prior cardiac surgery (203.22 and 203.22 months; p = 0.016 and p = 0.019, respectively), most probably explained by the significantly increased rate of primary nonfunction (33.3%) and in-hospital mortality (25.0%). CONCLUSIONS: Our data demonstrates the increased rate of early kidney graft loss and thus significantly inferior graft survival in high-risk patients undergoing HKTx. Thus, we advocate for a "kidney-after-heart" program in such patients to ensure responsible and reasonable utilization of scarce resources in times of ongoing organ shortage crisis.
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Supervivencia de Injerto , Trasplante de Corazón , Trasplante de Riñón , Adulto , Anciano , Femenino , Alemania , Trasplante de Corazón/efectos adversos , Trasplante de Corazón/mortalidad , Mortalidad Hospitalaria , Humanos , Inmunosupresores/uso terapéutico , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/mortalidad , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Estudios Retrospectivos , Factores de Riesgo , Facultades de Medicina , Resultado del TratamientoRESUMEN
OBJECTIVES: Cystic fibrosis-related liver disease (CFLD) with consecutive cirrhosis is the third most common cause of death in CF patients. The aim of this study was to identify the potential long-term benefits of liver transplantation (LTx) in a match-control comparison. METHODS: Retrospective single-center data analysis of all pediatric LTx for CFLD between 1998 and 2014. A control group was selected from the local CF patient registry. Data were collected from case report forms and included clinical and laboratory data, lung function tests, the indication for LTx, and details of surgical procedures. RESULTS: At our institution, 23 patients with severe CFLD median age 13.8âyears (range 8.7-17.4; 16 boys) underwent LTx between 1998 and 2014. In all patients, normalization of hepatic CF manifestations were achieved after LTx. But obviously there was no significant positive influence on nutritional status. Signs of posttransplant liver steatosis were documented by ultrasound in 17 patients. Liver biopsies after LTx were performed in 19 patients, in 42% (nâ=â8) of these biopsies a fatty degeneration was observed. Five patients died after LTx, none because of primary hepatic dysfunction (1 because of posttransplant proliferative disorder, 4 because of infection). Analysis of matched control pairs revealed that liver function, anthropometry, pulmonary function, and life expectancy of CFLD patients with LTx are comparable with matched CF peers without CFLD. CONCLUSIONS: Isolated LTx normalizes the hepatic manifestation of CF disease. LTx enables children and adolescents with severe CFLD to have a comparable prognosis in terms of growth, life expectancy, and lung function as CF patients without advanced liver involvement. Our data clarifies the long-term perspectives of affected patients.
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Fibrosis Quística , Trasplante de Hígado , Adolescente , Niño , Fibrosis Quística/complicaciones , Fibrosis Quística/cirugía , Humanos , Cirrosis Hepática , Masculino , Análisis por Apareamiento , Estudios RetrospectivosRESUMEN
OBJECTIVES: A combined lung and liver transplant in patients with cystic fibrosis (CF) is an uncommon procedure. The goal of this study was to compare long-term outcomes between patients with CF who underwent either a combined lung-liver or a lung-only transplant. METHODS: This is a retrospective single-centre study of patients with CF who underwent a lung transplant between January 2005 and May 2020. Since 2006, our preference for a combined lung-liver transplant was to transplant the liver first and then the lung. Outcomes were compared using the Kaplan-Meier analysis and the log-rank test. Median follow-up was 53 (23-97) months. RESULTS: During the study period, among 357 patients with CF who underwent a lung transplant, 14 (4%) required a lung-liver transplant whereas 343 (96%) had a lung-only transplant. Lung cold ischaemic time was longer in the lung-liver transplant group, but no patient in this group showed primary graft dysfunction at 72 h after the transplant. Prevalence of anti-human leucocyte antigen donor-specific antibodies was 7.1% vs 13.7% in the lung-liver versus the lung-only transplant group (P = 0.42). At 5 years, lung graft survival (78% vs 69%) and freedom from chronic lung allograft dysfunction (79% vs 62%) did not differ between the lung-liver versus the lung-only groups (P = 0.45 and P = 0.55, respectively). Freedom from lung biopsy-confirmed rejection was significantly higher in patients undergoing a lung-liver transplant (91% vs 50%; P = 0.027). CONCLUSIONS: A lung-liver transplant did not impair lung graft function. The lower prevalence of donor-specific antibodies and the better freedom from lung biopsy-confirmed rejection suggest tolerogenic effects of the liver graft.
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Fibrosis Quística , Trasplante de Hígado , Trasplante de Pulmón , Fibrosis Quística/cirugía , Humanos , Hígado , Pulmón , Estudios RetrospectivosRESUMEN
Growth failure persists after pediatric liver transplantation and impairs pediatric development and quality of life. Steroid dose minimization attempts to prevent growth impairment, yet long-term assessment in pediatric liver recipients is lacking. We identified risk factors for impaired linear growth after pediatric liver transplantation, with a special focus on low-dose steroid therapy. This is a single-center retrospective analysis of height development in pediatric liver recipients up to 5 years after transplantation. Risk factors for impaired linear growth (height Z-scores≤-2) at transplantation, after two (n = 347) and five years (n = 210) were identified by univariate and multivariate logistic regression. At transplantation, growth retardation was found in 52.2%, predominantly younger children. Height Z-scores improved from -2.23 to -1.40 (SE 0.11; 95%CI 0.74-1.16; p < .001) two years and -1.19 (SE 0.07;0.08-0.34; p = .017) five years post-transplant. Multivariate analysis showed previous growth impairment (OR=1.484; 95%-CI=1.107-1.988; p = .004), graft loss (49.006;2.232-1076; p = .006), and prolonged cold ischemic time (1.034;1.007-1.061; p = .011) as main long-term risk factors; steroid use was a significant predictor of 2-year but not 5-year growth impairment. In univariate analysis, impaired growth after 2 and 5 years was associated with continuous low-dose (2.5 mg/m2 BSA) steroid therapy (OR=3.323;1.578-6.996; p < .001/OR=8.352;1.089-64.07; p = .006)and graft loss (OR=2.513;1.395-4.525; p = .003/OR=3.378;1.815-7.576; p < .001). Furthermore, indication and era of transplantation affected growth. Our results show significant catch-up growth after pediatric liver transplantation, yet growth failure strongly affects particularly young liver recipients. The main influenceable long-term risk factor is pre-existing growth failure, emphasizing the importance of early aggressive nutritional therapy. Moreover, low-dose steroid therapy might impair growth and should therefore be critically questioned in long-term immunosuppression.