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Liver-function studies in heart-transplant recipients treated with cyclosporin A
1Department of Clinical Chemistry, Hôpital Erasme, ULB, Brussels, Belgium.
Insights
Cyclosporine (CsA) therapy in heart transplant patients showed minimal liver function changes. Only patients with pre-existing liver issues had altered bile acids and GGT, with improved aminopyrine breath test results.
Area of Science:
- Hepatology
- Transplantation Medicine
- Clinical Pharmacology
Background:
- Cyclosporine (CsA) is a key immunosuppressant post-heart transplantation (HTx).
- While CsA hepatotoxicity is known, systematic studies are limited.
- Understanding CsA's impact on liver function is crucial for patient management.
Purpose of the Study:
- To systematically evaluate the effects of CsA on liver function in heart transplant recipients.
- To identify specific biomarkers indicative of CsA-induced liver alterations.
- To investigate the mechanism of CsA's hepatic impact.
Main Methods:
- Prospective study of 17 heart transplant patients on CsA, azathioprine, and corticosteroids.
- Assessment of liver function using five tests: total bile acids (BA), alkaline phosphatase (AP), gamma-glutamyltransferase (GGT), total bilirubin, and aminopyrine breath test (ABT).
- Patients were categorized into three groups based on pre-HTx liver function (normal, mild, severe).
Main Results:
- No significant changes in liver function tests were observed in patients with normal or mildly altered pre-transplant liver function.
- Patients with severely altered pre-transplant liver function (Group III) showed increases in BA and GGT during CsA therapy.
- The aminopyrine breath test (ABT) significantly improved in Group III patients during CsA treatment.
Conclusions:
- CsA therapy appears to have a limited impact on liver function in heart transplant patients, particularly those with normal baseline liver health.
- CsA directly interferes with the bile acid secretion mechanism.
- The mechanism behind CsA-induced GGT increase requires further investigation.
Abstract:
Cyclosporine (CsA) hepatotoxicity has been reported but has not been studied systematically. This study includes 17 patients undergoing heart transplantation (HTx) and being treated with CsA, azathioprine, and corticosteroids. We assessed liver function in these patients before HTx and during the following month by five biological tests: total bile acids (BA), alkaline phosphatase (AP), gamma-glutamyltransferase (GGT), and total bilirubin in serum, and the aminopyrine breath test (ABT). With these tests we could classify the patients into three groups before HTx: normal (group I), mildly altered (group II), and severely altered (group III) liver function. During CsA therapy we did not observe any changes in any test results except for BA and GGT, and these only in group III. The ABT improved significantly in this group. During kinetic studies in patients without liver dysfunction, we confirmed a direct interference of CsA on BA secretion mechanism, but not the GGT increase, which remains to be explained.