Corticosteroid-free immunosuppression in liver transplantation: An evidence-based review

Table 4 Summary of the strength and quality of the evidence

Intervention	Level of evidence	Degree of recommendation
Studies including adult patients undergoing first OLT for any indication
Steroid replacement results in fewer cases of overall acute rejection in the corticosteroid-free immunosuppression arm	1a-	D
Steroid replacement by daclizumab + MMF results in fewer cases of BPAR at 24 wk in the corticosteroid-free immunosuppression arm	1b	A
Initial steroid administration for two weeks and early tacrolimus monotherapy is a feasible immunosuppression regimen without steroid replacement, although in view of chronic rejections, further investigations are needed	1b	A
Ab initio tacrolimus monotherapy is a viable immunosuppressive approach in liver transplantation and is associated with lower rejection rates compared to microemulsified cyclosporine	2b	B
Renal insufficiency, de novo hypertension, neurological disorders and infectious complications do not differ significantly among steroid and steroid-free groups	1a	B
Diabetes mellitus, cholesterol levels and CMV infection had a higher incidence in the steroid group. The differences in cases of diabetes mellitus and hypercholesterolemia are independent of steroid replacement	1a-	D
Hypertension, thrombocytopenia, renal impairment and overall incidence of infections do not differ significantly among steroid and steroid-free groups (steroids replaced by daclizumab + MMF)	1b	A
Early tapering down of steroids to tacrolimus monotherapy is possible with significantly fewer cases of diabetes and hypercholesterolemia	1b	A
Side-effects related to monotherapy with microemulsified cyclosporine or tacrolimus are comparable	2b	B
Complete corticosteroid avoidance in adult OLT using basiliximab induction with CNI and EC-MPS maintenance is as safe and as effective as standard corticosteroid containing immunosuppression	2b	B
No significant differences were noted between treatment groups in terms of patient and graft survival regardless of steroid replacement	1b	A
Actuarial 5-yr patient and graft survival related to monotherapy with microemulsified cyclosporine or tacrolimus are comparable	2b	B
Steroid withdrawal should be attempted in OLT recipients with underlying autoimmune hepatitis	2b-	D
Which immunosuppression regimen? Both, tacrolimus-based regimens with daclizumab induction or the addition of MMF, allow for avoidance of steroid treatment	1b	A
Studies addressing exclusively transplanted HCV patients
A significant reduction in HCV recurrence independent of steroid replacement may be expected in steroid-free groups	1a-	D
MMF does not appear to have a significant antiviral effect despite early reports	1b	A
Male gender of donors and recipients, living donors, cold ischemia times, acute rejection, and early histological recurrence are related to the development of advanced hepatitis	1b	A
Donor age, grade 2 inflammation at day 90 or one-year liver biopsy and diagnosis of acute hepatitis may be associated with the development of bridging fibrosis or cirrhosis	2b	B

CMV: Cytomegalovirus; MMF: Mycophenolate Mofetil; OLT: Orthotopic liver transplantation; EC-MPS: Enteric-coated mycophenolate sodium; BPAR: Biopsy-proven acute rejection; CNI: Calcineurin inhibitor; HCV: Hepatitis C virus.