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26. Jahrestagung der Deutschen Transplantationsgesellschaft

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27.10.2017 - Rheinlobby | 11:45 - 12:15 
iCal 
Postervorträge VII

Vorsitz: W. Arns (Köln, DE), P. Fornara (Halle, DE)

PV51 Everolimus with reduced tacrolimus maintains efficacy following living-donor liver transplantation (LDLT): 12-month results from an international randomized trial (NCT01888432)
*Felix Braun1, Utz Settmacher2, Patricia M Lopez3, Jossy Kochuparampil3, Sebastian Lieb4
1 Universitätsklinikum Schleswig-Holstein, , Kiel, Deutschland
2 Universitätsklinikum Jena, Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Jena, Deutschland
3 Novartis Pharma AG, , Basel, Schweiz
4 Novartis Pharma GmbH, TA Transplantation & Rheumatology, Nürnberg, Deutschland
Abstract-Text :

Background


Everolimus (EVR) with reduced-exposure tacrolimus (rTAC) after deceased-donor liver transplantation has been shown to be effective but trials in LDLT are lacking.


Methods


In an international, open-label, phase III trial (H2307), adult primary LDLT patients were randomized at day 30 post-Tx to continue standard tacrolimus (TAC-Control) or to EVR rTAC, both±corticosteroids. Here, we present efficacy data from the study.


Results


284 patients were randomized (mean 54 years, 72% male, 79% Asian, mean [SD] MELD score 14 [5.5]; 42% hepatocellular carcinoma [HCC], 30% positive for hepatitis B virus). Mean TAC trough concentration at month 12 was 36% lower with EVR rTAC than TAC-Control. The primary endpoint, a composite of graft loss (GL), death or treated biopsy-proven acute rejection (tBPAR) at month 12 post-Tx, was similar with EVR rTAC or TAC-Control (n [Kaplan-Meier%]): primary endpoint 7 (5.1%) versus 8 (5.8%). No GL occurred and patient survival was comparable in both groups. Although tBPAR rates were similar in EVR rTAC [3 (2.2%)] and TAC-Control [5 (3.6%)], moderate or severe episodes occurred only with TAC-Control. Mean estimated GFR (eGFR, MDRD-4) was numerically higher with EVR rTAC up to Month 12. HCC recurrence was seen only in 5 patients in TAC-Control group. Study drug withdrawal due to adverse events (AEs) was similar in both groups. Withdrawal was similar with EVR rTAC or TAC-Control: 18 (12.7%) versus 15 (10.6%)


Conclusion


Early initiation of EVR rTAC after LDLT demonstrated comparable efficacy and numerically better renal function at M12 compared to TAC-Control. HCC recurrence was not observed in the EVR rTAC cohort but affected only TAC-Control patients, a finding that merits further investigation.



PV52 Effect of everolimus with reduced tacrolimus on renal function (RF) after living-donor liver transplantation (LDLT): 12-month results from an international randomized trial (NCT01888432)
*Felix Braun1, Utz Settmacher2, Patricia M Lopez3, Carole Sips3, Sebastian Lieb4
1 Universitätsklinikum Schleswig-Holstein, , Kiel, Deutschland
2 Universitätsklinikum Jena, Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Jena, Deutschland
3 Novartis Pharma AG, , Basel, Schweiz
4 Novartis Pharma GmbH, TA Transplantation & Rheumatology, Nürnberg, Deutschland
Abstract-Text :

Background


Everolimus with reduced tacrolimus (EVR rTAC) has been shown to offer a renal advantage versus standard TAC (TAC-Control) in deceased-donor LTx but data are lacking after LDLT.


Methods


In a multicenter, 24M, open-label phase III study (H2307), patients were randomized at day 30 post-LDLT to start EVR rTAC or continue standard TAC, both ± steroids. Here, we present the RF results from the study.


Results


284 patients were randomized (142 EVR rTAC, 142 TAC-Control; mean[SD] MELD score 14[5.5]). Mean TAC trough concentration in the EVR rTAC group exceeded target range until month 6 and remained close to the upper threshold thereafter. Efficacy at month 12 was similar with EVR rTAC or TAC-Control. Mean estimated GFR (eGFR, MDRD-4) at randomization was 90mL/min/1.73m2 in both groups. Observed mean eGFR was numerically higher with EVR rTAC to month 12. The EVR rTAC group was non-inferior to TAC-Control for the key endpoint of change in eGFR from randomization to month 12 post-Tx: mean (SE) –8.0 (1.8) versus –12.1 (1.8) mL/min/1.73m2; mean difference 4.2 mL/min/1.73m2; p<0.001 for non-inferiority. Among patients who remained on study drug (120 EVR rTAC, 116 TAC-Control), change in eGFR was in favor of EVR rTAC: mean (SE) –8.0 (1.9) versus –13.3 (1.9) mL/min/1.73m2 with TAC-Control, a mean difference of 5.3mL/min/1.73m2 (p=0.046). At month 12, urine protein:creatinine ratio was ≥3000mg/g in 1.6% and 0% of EVR rTAC and TAC-Control patients, respectively; no patient required renal replacement therapy.


Conclusion


Mean eGFR was numerically higher to month 12 after starting EVR rTAC versus TAC-Control. These data show that in LDLT, even in the setting of excellent renal function, EVR with low-exposure tacrolimus offers a renal advantage.



PV53 Urinary proteins in long-term follow up after living donation
*Kersten Fischer1, Gerit Theil1, Paolo Fornara1
1 Universitätsklinikum Halle, Urologische Universitätsklinik, Halle, Deutschland
Abstract-Text :

In a previous study, it was found that about 2/3 of the living donors showed abnormal urinary protein findings one year after donor nephrectomy. We wanted to know if and how they change in a long-term follow up.


Within the ambulant follow-up the glomerular (immunoglobulin G, albumin and transferrin) and the tubular (a1-microglobulin, retinol-binding protein, ß2-microglobulin) urinary proteins, the urinary enzyme N-acetyl-β-glucosaminidase and the total protein of 63 living donors were determined. A comparison with the results one year after living donation was made to check to what extent the number and patterns of urinary proteins changed in the long-term follow-up. Therefor, the urine results of the patients were divided into 4 groups depending on the time after donor nephrectomy: <1 year (group 1), 1 to 5 years (group 2), 5 to 10 years (group 3) and >10 years (group 4) after living donation.


While one year after donor nephrectomy 2/3 (n = 27/40) of the patients still show an abnormal protein pattern, there are only 50% (n = 15/30) in group 2, 45% (n = 10/22) in group 3 and 40% (4/10) in group 4. One year after living donation, the tubular urinary protein patterns (38%, n = 15/40) have been dominated. In the following years, the glomerular urinary proteins were more often detected, about 20% in groups 2 to 4. After more than 10 years, we found no pure tubular urinary protein pattern anymore.


On the one hand, our results show that there is an improvement of the condition of the donor's solitary kidney in the long-term course, which speaks for living donation as a type of treatment of renal insufficiency. On the other hand, the determination of urinary proteins could provide an early indication of a possible kidney damage, thus enabling an early therapeutic intervention. A claim to the universal validity of these results can not be obtained because of the low number of cases.



PV54 Retroperitoneoscopic donor nephrectomy reduces operation time, hospital stay, and surgical complications compared to a mini open procedure
*Martina Koch1, Sylvia Kröncke2, Jun Li1, Lutz Fischer1, Björn Nashan1
1 UKE, Hepatobiliäre Chirurgie, Hamburg, Deutschland
2 UKE, Transplantationspsychologie, Hamburg, Deutschland
Abstract-Text :

A major goal in living kidney transplantation is to reduce the burden of the living donor (LD). It has been shown that laparoscopic and retroperitoneoscopic techniques are safe for the LD and the recipient, but comprehensive data regarding the latter procedure are still rare.


We analysed the impact of the switch from a mini open nephrectomy (MON) to a retroperitoneoscopic donor nephrectomy (RPDN) in our centre. We compared the last 50 MON to the first 100 RPDN regarding operation time, complications, length of hospital stay, and patients" own rating of the surgical burden. All LD between 2009 and 2015 were included. The patients" rating of the surgical strain was assessed 3 months after nephrectomy in both groups.


LD demographics were not different between the groups (mean age 52 y in MON and 54 y in RPDN; mean BMI 25 in MON and 26 in RPDN). The mean operation time was shorter in RPDN (118 min vs. 175 min, p<0.001). Patients were discharged from hospital earlier (5.0 d  vs. 6.3 d,  p<0.001). 17 surgical complications occurred in the MON group (34%). Most complications were mild (Clavien grade I or II, e.g. postoperative pain, UTI). In two donors, severe complications occurred: lung embolism and bowel injury (grade IV) and a granuloma on the vocal cord needing operative resection (grade IIIb). In the RPDN group, 15 complications occurred (15%). They were mild in 14 patients. In one patient, open conversion was needed due to bleeding (no transfusion, grade IIIb). There were significantly less complications in the RPDN group (p=0.01). Three months after nephrectomy, RPDN patients reported less physical strain (p=0.008), less post-operative pain (p<0.001), and felt less bothered by the surgical scar (p=0.02).


In summary, RPDN can be performed safely with short operation time. Patients profit from earlier discharge and less complications, and they report less surgical strain. We recommend to switch to RPDN to reduce the physical burden of the LD.



PV55 Efficacy and safety of everolimus with reduced tacrolimus in living-donor liver transplant recipients with hepatocellular carcinoma: Subgroup analysis from the H2307-Study (NCT01888432)
*Utz Settmacher1, Felix Braun2, Patricia M Lopez3, Jossy Kochuparampil3, Sebastian Lieb4
1 Universitätsklinikum Jena, Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Jena, Deutschland
2 Universitätsklinikum Schleswig-Holstein, , Kiel, Deutschland
3 Novartis Pharma AG, , Basel, Schweiz
4 Novartis Pharma GmbH, TA Transplantation & Rheumatology, Nürnberg, Deutschland
Abstract-Text :

Background: The use of the mammalian target of rapamycin inhibitor (mTORi) has been reported to reduce hepatocellular carcinoma (HCC) recurrence post-LTx. We report 12M results of everolimus plus reduced tacrolimus (EVR rTAC) versus standard tacrolimus (sTAC) in living-donor liver transplant (LDLT) recipients with HCC.


Methods: H2307 is a 24M, multicenter, open-label, controlled study in which LDLT recipients were randomized to EVR rTAC (N=142) or sTAC (N=142) after a run-in period of 30±5 days post-LTx. 119 had HCC of which 56 patients were randomized to EVR rTAC arm and 63 to sTAC. Outcome measurements included assessment of renal function (estimated glomerular filtration rate [eGFR] as assessed by modification of diet in renal disease [MDRD4]); the incidence of composite efficacy failure (CEF: treated biopsy proven acute rejection [tBPAR], graft loss [GL] or death); and HCC recurrence in patients transplanted for HCC disease. 


Results: Baseline HCC-related parameters were comparable between EVR rTAC and sTAC arms. At M12, mean eGFR was significantly higher for EVR rTAC versus sTAC in the HCC subpopulation (88.3±30.8 vs 74.0±21.1 mL/min/1.73m2, P = 0.01). CEF and its components at M12 were comparable for EVR rTAC versus sTAC (CEF in %: 7.1 vs 4.8; tBPAR: 3.6 vs 1.6; GL/death: 3.6 vs 3.2; P>0.05). At M12, no recurrence of HCC (0%) was reported in EVR rTAC arm whereas 5 patients (8.1%) in the sTAC arm had developed recurrent HCC (P = 0.059), 3 of them outside Milan criteria.


Conclusion: In HCC subpopulation of the H2307 trial, patients who received EVR rTAC versus sTAC regimen had better renal function with comparable efficacy and a reduced incidence of recurrent HCC. The use of EVR rTAC in preventing recurrence needs to be confirmed with longer follow-up.