Abstract
Background: Mammalian target of rapamycin (mTOR) inhibitors, such as everolimus and sirolimus, may be efficacious in preserving renal function in liver transplantation (LT) recipients while preventing hepatocellular carcinoma (HCC) recurrence. Materials and Methods: In this study, we retrospectively evaluated the safety, efficacy, and renoprotective effects of mTOR inhibitors in LT recipients. Among the 84 patients enrolled, mTOR inhibitor was commenced during the first year after LT. Renal function was measured by estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease equation. Results: Regarding the type of mTOR inhibitor, everolimus was used in 71 patients and sirolimus in 13 patients. Concomitant tacrolimus was used in 63 patients (75.0%). For total enrolled patients, kidney function did not significantly change during 12 months after initiation of mTOR inhibitors, although tacrolimus-withdrawn patients (n = 21) showed better kidney function compared to tacrolimus-minimized patients (n = 63) after conversion. However, a significant improvement in kidney function was observed in the eGFR <60 ml/min/1.73 m2 group (n = 19) 12 months after initiation of mTOR inhibitors, for both patient groups with early + mid starters (n = 7, stating within 1 year after LT) and late starters (n = 12, starting over 1 year after LT). mTOR inhibitors were safely administered without serious adverse events that led to drug discontinuation. Conclusion: We demonstrated that patients with renal impairment showed significant improvement in renal function regardless of the timing of mTOR inhibitor start, suggesting that switch to mTOR inhibitors may be beneficial when renal function declines.
Highlights
The liver is considered an immune-tolerant organ
hepatocellular carcinoma (HCC) resulting from chronic hepatitis B (n 54, 64.3%) was the most common reason for liver transplantation (LT)
TAC, prednisolone, and mycophenolate mofetil (MMF) are usually administered to LT recipients. 6 months after LT, most patients (n 78, 92.9%) still received TAC. mammalian target of rapamycin (mTOR) inhibitor was commenced following median of 269 days after LT
Summary
The liver is considered an immune-tolerant organ. It has been reported that the liver contains tolerance mechanisms to prevent immune hyper-activation in response to foreign antigens (Sung and Jang, 2018). After CKD develops, frequently prescribed alternatives to TAC include anti-metabolites, such as mycophenolic acid derivatives, and mammalian target of rapamycin (mTOR) inhibitors (Saliba et al, 2011) Among these drugs, mTOR inhibitors have been shown to have a favorable adverse event profile and to be effective in preventing acute cellular rejection while protecting kidney function in LT patients to whom immunosuppressants are usually administered in the outpatient clinic (De Simone et al, 2009; Saliba et al, 2011; De Simone et al, 2012; Bilbao et al, 2015; Saliba et al, 2017; Saliba et al, 2019; Nogueras Lopez et al, 2020; Saliba et al, 2020). Mammalian target of rapamycin (mTOR) inhibitors, such as everolimus and sirolimus, may be efficacious in preserving renal function in liver transplantation (LT) recipients while preventing hepatocellular carcinoma (HCC) recurrence
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
