Tacrolimus therapy causes hepatotoxicity in patients with a history of liver disease.
OBJECTIVE
Tacrolimus is known to have little hepatotoxicity. Nevertheless, a few case studies have shown liver toxicities of tacrolimus, particularly in patients on multiple medications. This study is a retrospective data analysis on the potential of tacrolimus hepatotoxicity.


METHODS
A data analysis was conducted on the electronic medical records (EMRs) of 2,462 Korean patients taking tacrolimus or cyclosporine from 2002 through to 2008. Alanine aminotransferase (ALT) and total bilirubin level (TBL) were also monitored. The maximum ALT, time to reach ALTmax (TALTmax), and TBL(ALTmax) were compared between the tacrolimus and cyclosporine groups. Other possible factors that may aggravate liver function were also investigated.


RESULTS
ALTmax and TBL(ALTmax) were higher in the tacrolimus group compared to the cyclosporine group (i.e., 50 IU/L vs. 41 IU/L and 1 mg/dL vs. 0.9 mg/dL, respectively), and TALTmax was shorter (i.e., 101 days vs. 142 days) in the tacrolimus group. In addition, the frequency of ALTmax > 3x upper limit of normal (ULN) (i.e., ALTmax > 120) was significantly increased in the tacrolimus group compared to the cyclosporine group (30% vs. 21%). The severity of tacrolimusinduced liver damage was greater in patients with history of liver disease, as indicated by > two-fold greater ALTmax than that of cyclosporine (i.e., 153 IU/L vs. 65 IU/L). Moreover, the ALTmax was significantly lowered by switching from tacrolimus to cyclosporine in patients with a history of liver disease. In patients with preexisting renal disease, neither tacrolimus nor cyclosporine showed any effect on ALTmax.


CONCLUSIONS
Results indicate that tacrolimus may have a higher risk of inducing liver injury in Korean patients with a history of liver disease and may require close monitoring.
Myong Suk
MS
Ko
Young Hee
YH
Choi
Sun Hoi
SH
Jung
Jenny Sue
JS
Lee
Hyang Sook
HS
Kim
Chang Ho
CH
Lee
Sang Geon
SG
Kim
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000097:blood; D001663:Bilirubin / Q000097:blood; D015415:Biomarkers / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000175:diagnosis / Q000209:etiology*; D016572:Cyclosporine / Q000009:adverse effects; D016903:Drug Monitoring; D057286:Electronic Health Records; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D008107:Liver Diseases / Q000150:complications*; D008297:Male; D008875:Middle Aged; D056910:Republic of Korea; D012189:Retrospective Studies; D012307:Risk Factors; D016559:Tacrolimus / Q000009:adverse effects*; D013997:Time Factors; D055815:Young Adult
D015415:Biomarkers; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000410:Alanine Transaminase; D001663:Bilirubin; D016559:Tacrolimus