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. 2021 Dec;44(6 Suppl 2):S162-S170.
doi: 10.1016/j.bj.2020.08.010. Epub 2020 Sep 4.

Comparative analysis of the drug-drug interaction between immunosuppressants, safety and efficacy of rifabutin from rifampicin-based Anti-TB treatment in living donor liver transplant recipients with active tuberculosis

Yu-Chen Wang  1 , Noruel Gerard Salvador  1 , Chih-Che Lin  2 , Chao-Chien Wu  3 , Ting-Lung Lin  1 , Wei-Feng Lee  1 , Yi-Chia Chan  1 , Chao-Long Chen  1 , Jeffrey Samuel Co  1 , Domelle Dave Encarnacion  1
Affiliations

Comparative analysis of the drug-drug interaction between immunosuppressants, safety and efficacy of rifabutin from rifampicin-based Anti-TB treatment in living donor liver transplant recipients with active tuberculosis

Yu-Chen Wang et al. Biomed J. 2021 Dec.

Abstract

Background: The Interaction between anti-tuberculous and immunosuppressive drugs which may increase the risk of graft rejections is a major challenge in managing transplant recipients with tuberculosis (TB). Instead of rifampicin (RFM), most guidelines recommended the use of rifabutin (RFB) because of its reduced capacity to induce immunosuppressant metabolism while maintaining the same efficacy as RFM against TB. However, there has been no available data directly comparing the outcome of RFB from RFM-based anti-TB regimens in liver transplant patients with TB. This study aimed to compare the effects of RFB from RFM-based treatment in terms of the drug interaction with immunosuppressants, as well as the safety, efficacy and clinical outcomes of living donor liver transplant (LDLT) recipients with active TB.

Methods: A retrospective study was conducted on all adult LDLT recipients diagnosed with active TB from June 1994 to May 2016 that had concurrently and continuously received either RFB or RFM-based treatment and immunosuppressants.

Results: Twenty-two patients were included. Twelve (55%) patients were in the RFM group. Ten (45%) patients were in the RFB group. RFB group showed a lesser rate of immunosuppressant trough level reduction (20% vs 50%, p = 0.009) during TB treatment. There was no TB recurrence and no significant change in platelet or leukocyte count in either group. Acute cellular rejection (ACR), rate of TB-treatment completion and overall survival, rates were excellent and statistically similar in both groups.

Conclusion: The use of RFB in LDLT recipients with active TB, had a lesser drug interaction than when RFM was used. However, RFB did not significantly reduced the rate of ACR. RFB and RFM are both effective and safe to use in LDLT recipients with active TB.

Keywords: Liver transplant; Living donor liver transplant (LDLT); Rifabutin; Tuberculosis.

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Figures

Fig. 1
Fig. 1
Percentage change in immunosuppressant trough level during TB treatment.Bar graphs illustrating the median percentage change in immunosuppressant trough level during TB-treatment. (A) Difference in specific percent change of sirolimus and tacrolimus between rifampicin and rifabutin-based anti-TB drugs. (B) Difference in combined sirolimus and tacrolimus percent change between rifampicin and rifabutin-based anti-TB drugs. Abbreviations used: SRL: sirolimus; FK: tacrolimus; p value: calculated via Mann-Whitney U test.
Fig. 2
Fig. 2
(A) Clinical outcomes between RFB and RFM use in LDLT recipients with active TB. ACR rate; (B) TB-treatment completion rate; (C) Overall Survival, Abbreviations used: ACR: acute cellular rejection; RFB: rifabutin; RFM: rifampicin; LDLT: living donor liver transplant; TB: tuberculosis.
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