Perioperative glucose management and outcomes in liver transplant recipients: A qualitative systematic review

Table 1 Characteristics of retrospective studies

Ref.	Country	Year	n	Group 1	Group 2	Study outcome(s)	Comments
Ammori et al[5]	United States	2007	184	Strict glucose control (BG < 150 mg/dL)	Poor Glucose control (BG ≥ 150 mg/dL)	Mortality Infection rate
Chung et al[25]	South Korea	2014	211	BG decline during the Neohepatic Phase (Yes)	BG decline during the Neohepatic Phase (No)	Mortality, length of ICU stay, early allograft dysfunction, MELD Score recovery	Outcomes were assessed relative to the drop in hyperglycemia after the neohepatic phase
Gelley et al[21]	Hungary	2011	310	De novo diabetes	Control	HepC recurrence and association with NODAT
Hartog et al[23]	United Kingdom	2014	430	DBD	DCD	NODAT
Keegan et al[17]	United States	2010	161 (158 were available for analysis)	Pre-protocol	Protocol	Mortality Morbidity Graft function
Linder et al[18]	United States	2016	114	PTDM	Non-PTDM	PTDM	BPAR, allograft failure, death, CMV infection are additional endpoints
Park et al[4]	United States/Taiwan	2009	680	SSI (Yes)	SSI (No)	SSI
Trail et al[20]	United States	1996	497	PTDM	Case-control	PTDM morbidity	PTDM leading to infections and graft rejection
Wallia et al[1]	United States	2010	144	BG > 200 mg/dL	BG < 200 mg/dL	Graft rejection, infection, and re-hospitalization	Graft survival and prolonged ventilation
Wallia et al[19]	United States	2011	73	Glucose management service	Non-Glucose Management Service	Graft rejection, infection, and re-hospitalization	Graft survival and prolonged ventilation
Yoo et al[6]	South Korea	2016	304	Normoglycemia (BG: 80-200 mg/dL)	Mild hyperglycemia (BG: 200-250 mg/dL)	AKI	Group 3: Moderate hyperglycemia (250-300 mg/dL) Group 4: Severe hyperglycemia (> 300 mg/dL)

DBD: Donated after brain death; PTDM: Post-transplant diabetes mellitus; Non-PTDM: Transplant diabetes mellitus free; DCD: Donated after circulatory death; NODAT: New onset diabetes after transplantation; AKI: Acute kidney injury.

Table 2 Characteristics of prospective studies and the cross-sectional study

Ref.	Country	Year	n	Group 1	Group 2	Outcome	Comment
Alvarez-Sotomayor et al[24]	Spain	2016	344	Diabetes before transplantation	No diabetes before transplantation	PTDM	Cross-sectional study
Villanueva et al[22]	United States	2005	107	Rosiglitazone	-	PTDM
Welsh et al[28]	United States	2016	164	Intensive glycemic control	Moderate glycemic control	Hypoglycemia	Insulin requirements

PTDM: Transplant diabetes mellitus.

Table 3 Summary of important findings of perioperative glucose control on liver transplant outcomes

Outcome of interest	Important findings	Data sources
Mortality	Mean BG ≥ 150 mg/dL increases mortality Nurse initiated insulin protocol did not impact mortality PTDM influenced glucose levels but did not change mortality	Ammori et al[5] (retrospective study) Keegan et al[17] (retrospective study Linder et al[18] (retrospective study)
Graft rejection	Mean BG > 200 mg/dL increases risk of rejection Although, mean BG were lower with the use of GMS, it did not lead to lower rate of rejection Conflicting evidence exists relating to the development of PTDM and its relation to rejection	Wallia et al[1] (retrospective study) Wallia et al[19] (retrospective study) Linder et al[18] and Trail et al[20] (retrospective studies)
Infection rate	BG ≥ 150 mg/dL is associated with higher infection rate BG ≥ 200 mg/dL increases risk of SSIs Use of GMS led to lower rate of infection Higher BG levels post-LT also led to increased incidence of HCV recurrence No association between BG levels and post-LT CMV infection Development of PTDM did not lead to higher infection rate	Ammori et al[5] (retrospective study) Park et al[27] (retrospective study) Wallia et al[1] (retrospective study) Gelley et al[21] (retrospective study) Linder et al[18] (retrospective study) Trail et al[20] (retrospective study)
Post-transplant diabetes mellitus/new onset diabetes mellitus	Rosiglitazone ± sulfonylurea is a potential option for the management of PTDM Post-LT hyperglycemia is associated with the development of PTDM Insulin use was significantly higher in PTDM patients with inadequate BG	Villanueva et al[22] (prospective study) Linder et al[18] (retrospective study) Alvarez-Sotomayor et al[24] (retrospective study)
Acute kidney injury and graft survival	High glucose variability is associated with post-LT acute kidney injury No association between post-LT BG levels and graft survival	Yoo et al[6] (retrospective study) Wallia et al[1] and Trail et al[20] (retrospective studies)

BG: Blood glucose; PTDM: Post-transplant diabetes mellitus; GMS: Glucose management service; HCV: Hepatitis C virus; LT: Liver transplantation.