The Role of mTOR Inhibitors in Liver Transplantation: Reviewing the Evidence

Table 7

Effects of mTOR inhibitors on hepatitis C virus and fibrosis progression in hepatitis C virus liver transplant recipients.

	Patient survival	Graft survival	Fibrosis	HCV recurrence rate	Other
Sirolimus
Maintenance dosing
Wagner et al. Int Immunopharmacol. 2010; 10: 990–3 [58]	95% survival in whole group; lower survival in SRL versus CNI according to log rank test (𝑃<0.03)			Viral load (×10^6): 6.9 versus 21.3 (SRL versus CNI, 𝑃<0.001)
De novo dosing
McKenna et al. Am J Transplant. 2011; 11: 2379–87 [57]	1 year after transplant: patient survival: 92.5% versus 87.9% (SRL versus control, 𝑃=0.15); 5 years after transplant: similar patient and graft survival (Kaplan–Meier analysis)		Fibrosis state ≥2,; 1 year after transplant: 15.3% versus 36.2% (SRL versus control, 𝑃<0.0001); 2 years after transplant: 30.1% versus 50.5% (SRL versus control, 𝑃=0.001)	Mean HCV RNA, 1 year after transplant: 9.16×10^6 versus 6.90×10^6 (SRL versus control, 𝑃=NS); 2 years: 6.12×10^6 versus 4.83×10^6 (𝑃=NS)
Asthana et al. Can J Gastroenterol. 2011; 25: 28–34 [56]			Change in mean fibrosis score: +1.1 versus −0.52 (CNI versus SRL, 𝑃=0.002); Change in mean activity: +0.24 versus −0.25 (CNI versus SRL, 𝑃=0.056)	HCV recurrence: 75% versus 69.8% (SRL versus controls, 𝑃=NS)
Asthana et al. Presented at AASLD 2011 (Abstract 184) [60]					SVR: 60%, 43%, 29% (SRL versus TAC versus CsA); SRL-based immunosuppression impacted SVR (OR 2.41, 95% CI 1.1, 5.5)
Late conversion (>3 months after transplantation)
Stein et al. Presented at the American Transplant Congress 2011 (Abstract 817) [79]		1-, 3- and 5-year allograft survival probability (%): 100, 92, 78 (SRL) and 100, 95, 90 (TAC), log rank −0.6, respectively	1- and 3-year fibrosis and activity scores: 𝑃=NS (SRL versus TAC)
Everolimus
De novo dosing
Dopazo et al. Presented at ILTS; 2011 (Abstract P-460) [102]			Fibrosis stages I and II–IV, respectively: 8% and 30% (EVR), and 5% and 36% (control group) (𝑃=NS)
Maintenance dosing
Grazi et al. Presented at ILTS; 2011 (Abstract P-256) [88]				HCV recurrence rate: 54% versus 33% (EVR versus TAC, 𝑃=NS)
Early conversion (≤3 months after transplantation)
Masetti et al. Am J Transplant. 2010; 10: 2252–62 [89]				HCV recurrence rate: 65% versus 75% (EVR versus CsA, 𝑃=1)

𝑃 values are included where available.
AASLD: The Liver Meeting 62nd Annual Meeting of the American Association for the Study of Liver Diseases; EVR: everolimus; HCV: hepatitis C virus; ILTS: 2011 Joint International Congress of the International Liver Transplantation Society; NS: nonsignificant; SRL: sirolimus; SVR: sustained virologic response; TAC: tacrolimus.