J. Tchervenkov

Efficacy of mycophenolate mofetil combined with very low-dose cyclosporine microemulsion in long-term liver-transplant patients with renal dysfunction.

Background. Cyclosporine (CsA)‐induced renal dysfunction is common after liver transplantation. We evaluated the efficacy of tapering CsA to a very low dose and introducing mycophenolate mofetil (MMF) in long‐term liver‐transplant recipients with renal dysfunction. In addition, we assessed the impact of this strategy on calcineurin inhibition and on transforming growth factor (TGF)‐&bgr; levels. Methods. We prospectively enrolled 19 adult, longterm (>1 year) liver‐transplant recipients with a decreased creatinine clearance greater than 25% compared with the first month posttransplant. MMF was introduced, and CsA was tapered to 25 mg twice daily. Calcineurin inhibition and TGF‐&bgr; were measured at baseline and 3 months thereafter. Results. The CsA dose was tapered over 13±3 weeks. At 1‐year follow‐up, serum creatinine decreased from 141±24 to 105±22 μmol/L (P=0.002), creatinine clearance increased from 53±9 to 71±19 ml/min (P=0.02), and glomerular filtration rate increased from 40±13 to 64±18 mL/min (P=0.002). The incidence of acute rejection was 29%. Antihypertensive medications were discontinued in 71% of the patients. Although CsA levels decreased significantly, serum TGF‐&bgr; did not differ from normal controls, and calcineurin inhibition remained stable. The incidence of gastrointestinal sideeffects and leukopenia was 18% and 24%, respectively. Conclusion. In long‐term liver‐transplant recipients with renal dysfunction, the introduction of MMF followed by tapering of CsA to a very low dose resulted in a significant improvement in renal function. However, this strategy maybe associated with a risk of acute rejection. The clinical pertinence of measuring serum TGF‐&bgr; levels and calcineurin inhibition remains to be determined.

Early renal function recovery and long‐term graft survival in kidney transplantation

Following kidney transplantation (KTx), renal function improves gradually until a baseline eGFR is achieved. Whether or not a recipient achieves the best‐predicted eGFR after KTx may have important implications for immediate patient management, as well as for long‐term graft survival. The aim of this cohort study was to calculate the renal function recovery (RFR) based on recipient and donor eGFR and to evaluate the association between RFR and long‐term death‐censored graft failure (DCGF). We studied 790 KTx recipients between January 1990 and August 2014. The last donor SCr prior to organ procurement was used to estimate donor GFR. Recipient eGFR was calculated using the average of the best three SCr values observed during the first 3 months post‐KTx. RFR was defined as the ratio of recipient eGFR to half the donor eGFR. 53% of recipients had an RFR ≥1. There were 127 death‐censored graft failures (16%). Recipients with an RFR ≥1 had less DCGF compared with those with an RFR <1 (HR 0.56; 95% CI 0.37–0.85; P = 0.006). Transplant era, acute rejection, ECD and DGF were also significant determinants of graft failure. Early recovery of predicted eGFR based on donor eGFR is associated with less DCGF after KTx.

Magnitude of change in alpha-fetoprotein in response to transarterial chemoembolization predicts survival in patients undergoing liver transplantation for hepatocellular carcinoma

BACKGROUNDnDownsizing strategies are often attempted for patients with hepatocellular carcinoma (hcc) before liver transplantation (lt). The objective of the present study was to determine clinical predictors of favourable survival outcomes after transarterial chemoembolization (tace) before lt for hcc outside the Milan criteria, so as to better select candidates for this strategy.nnnMETHODSnIn this retrospective study, patients with hcc tumours either beyond Milan criteria (single lesion > 5 cm, 3 lesions with 1 or more > 3 cm) or at the upper limit of Milan criteria (single lesions between 4.1 cm and 5.0 cm), with a predicted waiting time of more than 3 months, received carboplatin-based tace treatments. Exclusion criteria for tace included Child-Pugh C cirrhosis or the presence of portal vein invasion or extrahepatic disease on imaging. Only patients without tumour progression after tace underwent lt.nnnRESULTSnOf 160 hcc patients who received liver grafts between 1997 and 2010, 35 were treated with tace preoperatively. The median of the sum of tumour diameters was 6.7 cm (range: 4.8-8.5 cm), which decreased with tace to 5.0 cm (range: 3.3-7.0 cm) at transplantation (p < 0.0004). The percentage drop in alpha-fetoprotein (αfp) was a positive predictor (p = 0.0051) and the time from last tace treatment to transplantation was a negative predictor (p < 0.0001) for overall survival.nnnCONCLUSIONSnThe percentage drop in αfp and a shorter time from the final tace treatment to transplantation significantly predicted improved overall survival after lt for hcc downsized with tace. As a serum marker, αfp should be followed when tace is used as a strategy to stabilize or downsize hcc lesions before lt.

Activation of porcine hepatic microvascular sinusoidal endothelial cells in pig-to-human liver xenotransplantation.

THE ROLE of the endothelium in mediating rejection in discordant xenotransplantation is currently being defined. The literature has focused on cardiac and renal models of xenotransplantation, and the aortic endothelial cell (AEC) has become the prototypical cell for in vitro studies. The assumption that all EC behave similarly has never been validated. A recent study demonstrated that although cardiac microvascular endothelial cells (CMEC) and AEC behaved similarly, there were differences in comparison to human umbilical vein endothelial cells (HUVEC). The purpose of this study is to identify the early cytokine response of PHSEC to human serum in an in vitro model of pig-to-human discordant liver xenotransplantation.

Renal resistance thresholds during hypothermic machine perfusion and transplantation outcomes - a retrospective cohort study

Renal resistance (RR), of allografts undergoing hypothermic machine perfusion (HMP), is considered a measure of organ quality. We conducted a retrospective cohort study of adult deceased donor kidney transplant (KT) recipients whose grafts underwent HMP. Our aim was to evaluate whether RR is predictive of death‐censored graft failure (DCGF). Of 274 KT eligible for analysis, 59% were from expanded criteria donor. RR was modeled as a categorical variable, using a previously identified terminal threshold of 0.4, and 0.2 mmHg/ml/min (median in our cohort). Hazard ratios (HR) of DCGF were 3.23 [95% confidence interval (CI): 1.12–9.34, P = 0.03] and 2.67 [95% CI: 1.14–6.31, P = 0.02] in univariable models, and 2.67 [95% CI: 0.91–7.86, P = 0.07] and 2.42 [95% CI: 1.02–5.72, P = 0.04] in multivariable models, when RR threshold was 0.4 and 0.2, respectively. Increasing risk of DCGF was observed when RR over the course of HMP was modeled using mixed linear regression models: HR of 1.31 [95% CI: 1.07–1.59, P < 0.01] and 1.25 [95% CI: 1.00–1.55, P = 0.05], in univariable and multivariable models, respectively. This suggests that RR during HMP is a predictor of long‐term KT outcomes. Prospective studies are needed to assess the survival benefit of patients receiving KT with higher RR in comparison with staying wait‐listed.