(a)

	Participants	Study designa	Duration of study	Sirolimus dosing	Strength of study design based on defined criteriab
De novo dosing
Chinnakotla et al. Liver Transpl. 2009; 15: 1834–42 [55]	N = 227 recipients (i) n = 121 (SRL) (ii) n = 106 (TAC)	R/P	5 years	2 mg orally, once daily. Levels maintained at 5–8 ng/mL for the first 3 months and at 5 ng/mL thereafter	High
Asthana et al. Can J Gastroenterol. 2011; 25: 28–34 [56]	N = 141 recipients (i) n = 88 (de novo SRL) (ii) n = 53 (CNI)	R	12 months	Maintained at 8–12 ng/mL	Medium
McKenna et al. Am J Transpl. 2011; 11: 2379–87 [57]	N = 455 recipients (HCV-positive) (i) n = 173 (SRL) (ii) n = 282 (SRL-free)	R/P	2 years	2 mg daily without a loading dose beginning on the first postoperative day	Medium
Wagner et al. Int Immunopharmacol. 2010; 10: 990–3 [58]	N = 67 recipients (HCV-positive) (i) n = 39 (SRL) (ii) n = 28 (CNI)	P, C	12 months	Trough levels were maintained between 3 and 8 ng/mL	Medium
Zhou et al. Transplant Proc. 2008; 40: 3548–553 [59]	N = 73 recipients (HCC exceeding Milan criteria) (i) n = 27 (SRL) (ii) n = 46 (TAC)	R	2 years	Given 1 month after transplant: initial dose of 3 mg/m2 adjusted over time to achieve steady-state trough levels of ≈5–8 ng/mL	Medium
Asthana et al. Presented at AASLD 2011 (Abstract 184) [60]	N = 100 recipients (recurrent HCV) (i) n = 40 (SRL) (ii) n = 35 (TAC) (iii) n = 24 (cyclosporine) (iv) n = 36 lost to followup	P, C	Median of 77.6 months	Not stated	Low
Campsen et al. J Transplant. 2011; 2011: 913094 [54]	N = 672 recipients (i) n = 328 (CNI + MPS at time of discharge) (ii) n = 135 (CNI + MPS at time of discharge; SRL added within the first 6 months and continued through the first year) (iii) n = 15 (CNI + MPS at time of discharge; SRL was added within the first 6 months and discontinued before the first year) (iv) n = 156 (SRL as primary immunosuppression)  (v) n = 38 (SRL as primary immunosuppression and discontinued before the first year)	R	1 year	Not stated	Low
Dunkelberg et al. Liver Transpl. 2003; 9: 463–8 [61]	N = 350 recipients (i) n = 170 (SRL) (ii) n = 180 (historic controls)	R	12 months	6 mg on day 0, and 2 mg/day thereafter no target level was specified	Low
Jiménez-Romero et al. Hepatogastroenterology. 2011; 58: 115–21 [62]	N = 16 recipients who developed de novo tumors  All switched from CNI/MMF to SRL monotherapy	P, S	Mean of 15.7 months	Loading dose: 4 mg, followed by 2 mg/day until 8–12 days, thereafter dose adjusted to achieve target blood level of 5–10 ng/mL	Low
Kneteman et al. Liver Transpl. 2004; 10: 1301–11 [63]	N = 40 recipients (HCC)  All given SRL	P, S	4 years	Adjusted to achieve target levels of 12–20 ng/mL	Low
Maramattom and WijdicksNeurology. 2004; 63: 1958–9 [64]	N = 202 recipients  All received SRL	R	18 months	Loading dose: 6 mg, thereafter: 1–10 mg/day with target blood level of 8–15 ng/mL	Low
Molinari et al. Transpl Intl. 2010; 23: 155–68 [53]	N = 543 recipients (i) n = 252 (SRL) (ii) n = 291 (CNI)	R	5 years	Oral dose adjusted to keep the blood levels in the range of 10–15 ng/mL during the first 3–6 months and then in the range of 5–10 ng/mL afterwards	Low
Toso et al. Hepatology. 2010; 51: 1237–43 [65]	N = 2491 recipients (HCC) (i) n = 109 (SRL) (ii) n = 2382 (SRL-free)	R	5 years	Not stated	Low
Wiesner et al. Am J Transplant. 2002; 2 (s3): 464 (Abstract 1294) [44]	N = 163 recipients (i) n = 111 (SRL + CsA) (ii) n = 52 (concentration-controlled TAC (trough levels 5–15 ng/mL) + corticosteroids)	P, Ra	6 months	Fixed-dose of 5 mg/day	Low
Zimmerman et al. Liver Transpl. 2008; 14: 633–8 [15]	N = 97 recipients (cirrhosis + concomitant HCC) (i) n = 45 (SRL) (ii) n = 52 (standard regimen including CNIs, MMF, and corticosteroids)	R	5 years	Bolus dose of 6 mg on day 0 and given on 2 mg/day thereafter	Low
Combination of de novo and maintenance dosing
Kazimi et al. Transplantation. 2010; 90 (2S): 697 (Abstract 1950) [66]	N = 114 recipients (i) n = 65 (SRL) (ii) n = 49 (CNI)	R	1111 ± 800 days	Not stated	Low