Reduced calcineurin inhibitor exposure with antibody induction and recurrent hepatocellular carcinoma after liver transplantation

Abstract

Background

Hepatocellular carcinoma (HCC) is a common indication for liver transplantation (LT), but post-LT tumor recurrence remains a concern. Early post-LT immunosuppression is suggested to affect recurrence risk. We evaluated the impact on HCC recurrence of an immunosuppression protocol introduced in 2010 with interleukin-2 receptor antibody (IL-2RA) induction and delayed-introduction of reduced-dose tacrolimus with mycophenolate.

Methods

We included consecutive HCC patients transplanted 2000–2017 in Gothenburg. The impact on HCC recurrence of IL-2RA induction and mean tacrolimus trough concentration during the first 20 post-LT days was analyzed by multivariable Cox regression and propensity score-adjusted analyses.

Results

The study comprised 235 patients (mean age 57 yrs, men 80%, mean MELD 13, within Milan criteria 57%). The cumulative 5-yr HCC recurrence rate among patients transplanted before and after 2010 were 28.6% and 19.7%, respectively. IL-2RA induction had no independent effect on HCC recurrence. High tacrolimus exposure (mean 20-day tacrolimus concentration ≥8ng/mL) was associated with increased HCC recurrence risk on univariable analysis (HR 2.22, 95% CI 1.23–4.01, p = .008), but was non-significant on multivariable analysis (p = .17). Outside Milan criteria, high tacrolimus exposure was significant for HCC recurrence (HR 3.68, 95% CI 1.34–10.11, p = .012) independently of tumor characteristics and AFP level. This was confirmed on multivariable propensity score-adjusted analysis.

Conclusions

Reduced early tacrolimus exposure, facilitated by IL-2RA induction, was associated with reduced risk for HCC recurrence among patients outside Milan criteria. Prospective studies are needed to confirm if early tacrolimus-minimization strategies can help reduce HCC recurrence rates and help extend transplant criteria.

Keywords:

• Tacrolimus
• HCC
• interleukin-2 receptor antibody
• basiliximab
• recurrence

Author contributions

JA, MSE, MR, FÅ: Participated in research design; JA, MSE, MR, WB, FÅ: Participated in the writing of the paper; JA, MSE, FÅ: Participated in the performance of the research; JA, MSE, MR, WB, FÅ: Participated in data analysis.

Acknowledgments

Scholarship: Fredrik Åberg received a research grant from Stiftelsen för Transplantations- och Cancerforskning.

Disclosure statement

The authors declare no conflicts of interest.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.