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. 2021 Apr 7;10(8):1558.
doi: 10.3390/jcm10081558.

Effect of Mycophenolate Mofetil Therapy on Recurrence of Hepatocellular Carcinoma after Liver Transplantation: A Population-Based Cohort Study

Yung-Fong Tsai  1   2 , Fu-Chao Liu  1   2 , Chun-Yu Chen  1   2 , Jr-Rung Lin  3   4 , Huang-Ping Yu  1   2
Affiliations

Effect of Mycophenolate Mofetil Therapy on Recurrence of Hepatocellular Carcinoma after Liver Transplantation: A Population-Based Cohort Study

Yung-Fong Tsai et al. J Clin Med. .

Abstract

Hepatocellular carcinoma (HCC) recurrence after liver transplantation is associated with immunosuppressants. However, the appropriate immunosuppressant for HCC recipients is still debated. Data for this nationwide population-based cohort study were extracted from the National Health Insurance Research Database of Taiwan. A total of 1250 liver transplant recipients (LTRs) with HCC were included. We analyzed the risk factors for post-transplant HCC recurrences. Cumulative defined daily dose (cDDD) represented the exposure duration and was calculated as the amount of dispensed defined daily dose (DDD) of mycophenolate mofetil (MMF). The dosage effects of MMF on HCC recurrence and liver graft complication rates were investigated. A total of 155 LTRs, having experienced post-transplant HCC recurrence, exhibited low survival probability at 1-, 3-, 5-, and 10-year observations. Our results demonstrated increased HCC recurrence rate after liver transplantation (p = 0.0316) following MMF administration; however, no significant increase was demonstrated following cyclosporine, tacrolimus, or sirolimus administration. Notably, our data demonstrated significantly increased HCC recurrence rate following MMF administration with cDDD > 0.4893 compared with cDDD ≤ 0.4893 or no administration of MMF (p < 0.0001). MMF administration significantly increases the risk of HCC recurrence. Moreover, a MMF-minimizing strategy (cDDD ≤ 0.4893) is recommended for recurrence-free survival.

Keywords: hepatocellular carcinoma; immunosuppressant; liver transplantation; mycophenolate mofetil; population-based study; recommended defined daily dose; recurrence.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Flowchart of study selection. LTRs, liver transplant recipients; HCC, hepatocellular carcinoma; MMF, mycophenolate mofetil.
Figure 2
Figure 2
Annual incidence of de novo liver malignancy in general Taiwanese populations from 1998 through 2012.
Figure 3
Figure 3
Cumulative probability of hepatocellular carcinoma recurrence in the liver transplant recipients.
Figure 4
Figure 4
Effects of hepatocellular carcinoma recurrence on mortality of liver transplant recipients. HR, hazard ratio; CI, confidence interval.
See this image and copyright information in PMC

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