(d)

	Participants	Study designa	Study duration	Everolimus dosing	Strength of study design based on criteriab
Early conversion (≤3 months after transplantation)
De Simone et al. Am J Transplant. 2012; 12: 3008–20 [87]	N = 719 recipients (i) n = 245 (EVR + TAC-RD) (ii) n = 231 (EVR + TAC-WD)  (iii) n = 243 (TAC-SD)	P, Ra	12 months	For EVR + TAC-WD, EVR initiated at a dose of 1.0 mg b.i.d. within 24 h of randomization with the dose adjusted from day 5 onward, to maintain C0 3–8 ng/mL until month 4 after transplantation, after which the target range increased to 6–10 ng/mL. In the EVR + TAC-RD arm, EVR initiated and monitored as for EVR + TAC-WD, but the initial target range of 3–8 ng/mL maintained throughout the study	High
Fischer et al.  Am J Transplant. 2012; 12: 1855–65 [50]	N = 203 recipients on CNI with/out corticosteroids (i) n = 101 (EVR) (ii) n = 102 (CNI continuation)	P, Ra	12 months	EVR started at 1.5 mg b.i.d. and adjusted to achieve a target trough level of 5–12 ng/mL (8–12 ng/mL in patients on treatment with CsA), when CNI was tapered by 70% of the initial CNI dose	High
Masetti et al. Am J Transplant. 2010; 10: 2252–62 [89]	N = 78 recipients (i) n = 52 (EVR) (ii) n = 26 (CsA)	P, Ra	12 months	Initial dose: 2.0 mg/day, trough level of 6–10 ng/mL. When CsA discontinued, trough level: 8–12 ng/mL until end of month 6 and 6–10 ng/mL thereafter	High
Saliba et al. AASLD 2012 [90]	N = 719 recipients from De Simone et al. Am J Transplant. 2012 [40] (i) n = 245 (EVR + TAC-RD) (ii) n = 231 (EVR + TAC-WD) (iii) n = 243 (TAC-SD)	P, Ra	24 months	Same as De Simone et al. Am J Transplant. 2012 [40]	High
Schlitt et al. AASLD 2012 [91]	N = 81 recipients from Fischer et al. Am J Transplant. 2012 (i) n = 41 (EVR with/out corticosteroids) (ii) n = 40 (CNI with/out corticosteroids)	P, Ra	35 months	Same as Fischer et al. Am J Transplant. 2012 [43]	High
Late conversion (>3 months after transplantation)
Bilbao et al.  Transplant Proc. 2009; 41: 2172–6 [92]	N = 25 recipients  All converted to EVR	R	Mean of 10 ± 9 months	In refractory rejection: initial dose 0.5 mg/12 h. Trough levels 5 ng/mL. For CNI-related adverse events, EVR started at 0.5 mg once or twice a day. For malignancy, EVR introduced at 0.5 mg/day, adjusting trough levels to <3 ng/mL	Medium
Casanovas et al. Transplant Proc. 2011; 43: 2216–9 [93]	N = 35 recipients  All converted to EVR	P, S	Mean of 134 months	Initial dose 0.25 mg/12 h for the first 4 days. Target trough 3–5 ng/mL	Medium
Castroagudín et al. Liver Transpl. 2009; 15: 1792–7 [94]	N = 21 recipients (chronic renal dysfunction)  All converted to EVR	P, S	Median of 19.8 months	0.75 mg b.i.d., with target trough levels of 3–8 ng/mL	Medium
De Simone et al.  Transpl Int. 2009; 22: 279–86 [95]	N = 40 recipients	P, S	12 months	EVR 1.5 mg/day. Trough level of 3–8 ng/mL	Medium
De Simone et al.  Liver Transpl. 2009; 15: 1262–9 [96]	N = 145 recipients (i) n = 72 (EVR therapy with CNI reduction or discontinuation) (ii) n = 73 (CNI continuation)	P, Ra	12 months	Initial: 3 mg/day ×2 on day 1. After week 2: EVR trough level maintained at 3–8 ng/mL during concomitant CNI administration and 6–12 ng/mL if CNI eliminated	Medium
Bilbao et al. Presented at ILTS; 2011 (Abstract P-68) [97]	N = 62 recipients  All received EVR	R	Median of 12 months	EVR trough level at ~3 ng/mL	Low
Saliba et al. Liver Transpl. 2011; 17: 905–13 [98]	N = 240 maintenance recipients  All received EVR	R	12 months	Introduced at mean 2.4 mg/day. The mean trough level = 7.3 ng/mL at month 1 and 8.1 ng/mL at month 12 across total population, with higher values in monotherapy cohort (8.8 ng/mL at month 12)	Low
Vallin et al. Clin Transplant. 2011; 25: 660–9 [99]	N = 94 recipients  All received EVR	R	Mean of 12 ± 7 months	Initial dose 0.75–1.5 mg b.i.d. Trough adjusted to 3–8 ng/mL	Low

P values are included where available.

Search terms were ‘‘everolimus liver transplantation” OR ‘‘everolimus liver transplant.”

AASLD: Annual Meetings of the American Association for the Study of Liver Diseases; b.i.d.: twice daily; CNI: calcineurin inhibitor; CsA: cyclosporin A; EVR: everolimus; ILTS: 2011 Joint International Congress of the International Liver Transplantation Society; TAC: tacrolimus; TAC-RD: reduced-dose tacrolimus; TAC-SD: standard-dose tacrolimus; TAC-WD: tacrolimus withdrawn.

^aStudy design: P: prospective; R: retrospective; Ra: randomized; S: single-arm.

^bSee Section 2 for description of how criteria are defined.