Expert consensus on management of metabolic disease in Chinese liver transplant recipients

Table 1 Adverse effects of immunosuppressive agents on post-liver transplant metabolic disease

Metabolic disease	Glucocorticoids	CNIs (TAC)	CNIs (CsA)	mTORi	MPA	Antibody drugs (ATG/basiliximab)
Diabetes mellitus	+++	++	+	+	-	-
Hypertension	++	++	++	-	-	-
Dyslipidemia	++	+	++	+++	-	-
Obesity	+	+	+	-	-	-
Hyperuricemia	-	++	++	-	-	-

CNI: Calcineurin inhibitor; TAC: Tacrolimus; CsA: Cyclosporine A; mTORi: Mammalian target of rapamycin; MPA: Mycophenolic acids.

Table 2 2019 diagnostic criteria for diabetes and prediabetes by American Diabetes Association[24,25]

Diagnosis	ADA criteria
Diabetes	FPG ≥ 126 mg/dL (7.0 mmol/L). Fasting is defined as no caloric intake for at least 8 h.1 OR
	2-h PG ≥ 200 mg/dL (11.1 mmol/L) during OGTT. The test should be performed as described by the WHO, using a glucose load containing the equivalent of 75-g anhydrous glucose dissolved in water.1 OR
	A1C ≥ 6.5% (48 mmol/mol). The test should be performed in a laboratory using a method that is NGSP certified and standardized to the DCCT assay.1 OR
	in a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, an RPG ≥ 200 mg/dL (11.1 mmol/L).
Prediabetes	FPG 5.6-6.9 mmol/L (100-125mg/dL) (IFG) OR
	2HPG 7.8-11.0 mmol/L(IGT) OR
	A1c 5.7%-6.4%

¹In the absence of unequivocal hyperglycemia, diagnosis requires two abnormal test results from the same sample or in two separate test samples. ADA: American Diabetes Association; RPG: Random plasma glucose: refers to the blood glucose level at any time regardless of the time of the last meal in 1 d; FPG: Fasting plasma glucose; OGTT: Oral glucose tolerance test; 2HPG is the blood glucose level 2 h after OGTT; HbA1c is glycosylated hemoglobin; the symptoms of diabetes mellitus include polyuria, polydipsia and unexplained weight loss. Intravenous blood glucose levels must be measured on the next day once the blood glucose level is detected abnormal to confirm the diagnosis. Hyperglycemia caused by specific acute metabolic abnormalities must be excluded; DCCT assay: Diabetes Control and Complications Trial assay.

Table 3 Relevant mechanisms of hypertension after liver transplantation induced by common immunosuppressive agents[42]

Category	Drug	Mechanism
CNI	TAC, CsA		Increasing vascular tension: reducing nitric oxide (NO) and increasing endothelin level
			Increasing sympathetic excitability
			Activating the angiotensin-aldosterone system: elevated blood pressure, water, and sodium retention
			Activating sodium-chloride synergistic transport receptors in distal tubules: increased sodium reabsorption and excessive capacity
			Nephrotoxicity: AKI induced by vasoconstriction Chronic ischemia, glomerulosclerosis, interstitial fibrosis, and tubular atrophy
Glucocorticoid	Methylprednisolone		Increasing sympathetic excitability
			Increasing vascular tension
			Increasing activity of mineralocorticoids

CNI: Calcineurin inhibitor; TAC: Tacrolimus; AKI: Acute kidney injury; CsA: Cyclosporine A.

Table 4 Monitoring of metabolic disease after liver transplantation

Metabolic disease	Monitoring indicator	Target	Other related examination items
Diabetes mellitus	FPG, HbA1c, and OGTT	FPG < 6.7 mmol/L, peak value < 8.88 mmol/L or HbA1c < 7%	Urinary protein, ophthalmoscopy, B-mode ultrasonography of the carotid artery, and coronary CT angiography
Hypertension	Arterial pressure	Arterial pressure < 130/80 mmHg	24-h ambulatory blood pressure, ECG, coronary CT angiography, urinary protein, ophthalmoscopy
Dyslipidemia	LDL-C, TC, TG	LDL-C < 100 mg/dL; patients with cardiovascular risk factors, LDL-C < 70 mg/dL	ECG, B-mode ultrasonography of the carotid artery and coronary CT angiography
Hyperuricemia	SUA	SUA < 360 μmol/L; patients with gout attack, SUA < 300 μmol/L	Urinary protein, serum creatinine, glomerular filtration rate, bilateral renal ultrasound, joint ultrasound, joint X-ray or CT
Obesity	BMI	BMI < 25 kg/m2	Coronary CT angiography and B-mode ultrasonography of the carotid artery

CT: Computed tomography; ECG: Electrocardiogram; SUA: Serum uric acid; BMI: Body mass index; LDL-C: Low density lipoprotein cholesterol; TC: Cholesterol; TG: Triglycerides; FPG: Fasting plasma glucose; HbA1c: Glycated hemoglobin; OGTT: Oral glucose tolerance test.