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Immunosuppression impact on long-term cardiovascular complications after liver transplantation
John M Rabkin1, Christopher L Corless, Hugo R Rosen
1Department of Surgery, Division of Abdominal Organ Transplantation, Oregon Health Sciences University, 3181 SW Sam Jackson Park Rd. L590, Portland, Oregon 97201-3098, USA. rabkinj@ohsu.edu
Insights
Tacrolimus (FK-506) immunosuppression after liver transplant (OLTx) showed significantly lower rates of rejection, hypertension, and cardiovascular disease compared to cyclosporine (CSA). This suggests FK-506 may improve long-term outcomes for OLTx patients.
Area of Science:
- Transplantation Medicine
- Immunosuppression Therapy
- Cardiovascular Risk in Transplant Patients
Background:
- Long-term complications, particularly cardiovascular disease, are critical in liver transplant (OLTx) patient outcomes.
- Immunosuppressive pharmacologic regimens are implicated as risk factors for these complications.
Purpose of the Study:
- To compare the incidence of hypertension, hyperlipidemia, diabetes mellitus, nephrotoxicity, and cardiovascular disease at 3 years post-OLTx.
- To evaluate rejection rates and analyze the impact of these complications on mortality.
- To compare outcomes between tacrolimus (FK-506) and cyclosporine (CSA) immunosuppression.
Main Methods:
- Analysis of 87 OLTx recipients with at least 3 years follow-up, divided into CSA (n=50) and FK-506 (n=37) cohorts.
- Pre-transplant cardiac evaluations were performed for high-risk patients (age >50, alcoholic cirrhosis, cardiac history).
Main Results:
- FK-506 recipients had significantly lower rates of acute rejection (19% vs. 40%), hypertension (38% vs. 62%), and cardiovascular disease (0% vs. 18%) at 3 years compared to CSA recipients.
- No cardiovascular-related deaths occurred in the FK-506 group, versus 20% in the CSA group.
Conclusions:
- Tacrolimus (FK-506) is associated with significantly reduced rejection rates post-OLTx compared to cyclosporine (CSA).
- FK-506 demonstrates a lower incidence of hypertension and cardiovascular disease, suggesting improved long-term safety profiles.
Background:
With current early transplant patient and allograft survivals nearly optimized, long-term medical complications have become a significant focus for potential improvement in patient outcomes. Cardiovascular disease and associated risk factors have been shown in renal transplant patients to be related to the pharmacologic immunosuppression employed.
Objective:
The objective of this study is to investigate at 3 years postliver transplant (OLTx) the incidence of hypertension (HTN), hyperlipidemia (HLIP), diabetes mellitus (DM), nephrotoxicity (NTX), and cardiovascular disease (MI, angioplasty, CHF, CVA, and seborth) as well as rejection in two cohorts of liver transplant recipients who received either tacrolimus (FK-506) or cyclosporine (CSA) and to analyze the consequences of these complications on mortality following transplantation.
Methods:
Eighty-seven sequential patients (CSA: n = 50, mean age 48 years, M/F 32/18; and FK-506: n = 37, mean age 45 years, M/F 22/15) who underwent OLTx between 1994 and 1998, were >/=18 years, and had a minimum of 3 years of complete follow-up were included in the analysis. All OLTx candidates over age 50, who had a history of alcoholic cirrhosis, or had a history of cardiac conditions/events underwent complete cardiac consultation including an echocardiogram with additional cardiac investigation as indicated prior to OLTx.
Results:
At 3 years following OLTx, the incidence of acute rejection (40% versus 19%, P < 0.05), HTN (62% versus 38%, P < 0.05), HLIP (14% versus 5%, P = 0.08), and cardiovascular disease (18% versus 0%, P < 0.001), were significantly greater for the CSA patients compared with the FK-506 patients. Eight (20%) of the CSA patients who died before 3 years had their death attributed to cardiovascular events versus none in the FK-506 group.
Conclusion:
Compared with CSA, FK-506 was associated with significantly less rejection and a reduced incidence of HTN and cardiovascular disease.