Immunosuppressive drug withdrawal late after liver transplantation leads to an improvement of lipid metabolism and liver function

A.A. Duizendstra, R.J. de Knegt, M.G.H. Betjes, S. Coenen, S. Darwish Murad, R.A. de Man, H.J. Metselaar, N.H.R. Litjens, J. Kwekkeboom

Thursday 15 march 2018

11:40 - 11:50h at Van Rijck/Ruys Zaal

Categories: Clinical, Session (parallel)

Parallel session: Parallel session 5: Clinical

Background

Lifelong treatment with immunosuppressive drugs (IS) to prevent graft rejection in transplant recipients is accompanied by adverse effects, such as nephrotoxicity, recurrent infections, cardiovascular complications, and malignancies. Occasionally, liver transplant (LTx) recipients discontinue IS for medical reasons, without developing a rejection. These rejection and IS free LTx recipients have developed tolerance to their graft.

Objective

To assess the clinical effects of IS withdrawal late after LTx.

Methods

The study cohort consisted of tolerant LTx recipients (n=11), who had been withdrawn from IS for medical reasons on average 12 (range: 6-20) years after transplantation. The control group were LTx patients on IS (n=20; CNI n=17, IMPDH inhibitor n=3) matched with the study cohort for time after LTx, age, gender and primary disease. Liver and kidney function and lipid metabolism parameters at 1 year before, just before and 2 and 4 years after complete IS withdrawal for the tolerant group or matching time points after LTx for the control group were retrieved from electronic patient records.

Results

Liver function parameters bilirubin, aspartate transaminase (AST) and alanine transaminase (ALT) levels significantly improved (p=0.028, p=0.046, p=0.049, respectively) in the tolerant group 4 years after IS withdrawal compared to 1 year before withdrawal (averages 13.5 vs 11.3 μmol/L, 34.9 vs 27.9 U/L, 36.6 vs 33.5 U/L respectively). In the control group only ALT levels improved. Kidney function parameters (glomerular filtration rate (GFR), urea, and creatinine), did not improve after IS withdrawal in the tolerant group. Low-density lipoproteins (LDL) levels significantly decreased (p=0.027) in the tolerant group 4 years after IS withdrawal (average 3.0 vs 2.6 mmol/L), and high-density lipoproteins (HDL) levels remained stable. While HDL levels and HDL/LDL ratios were lower in the tolerant group before IS withdrawal compared to the control group, these differences disappeared after IS withdrawal in the tolerant group.

Conclusion

In tolerant LTx patients, lipid metabolism and liver functions improve after late IS withdrawal, but kidney function does not. It is likely that kidney damage is irreversible after long-term IS therapy. These results demonstrate the need for an accurate tolerance identification profile enabling identification of LTx patients eligible for safe IS weaning early after transplantation.