Cardiovascular risk after orthotopic liver transplantation, a review of the literature and preliminary results of a prospective study

Table 3 Post transplant metabolic syndrome manifestations and their possible therapy

Disease	Suggested therapy	Contraindicated therapy	Ref.
Diabetes mellitus	Insuline: in the early post-operative setting	Metformin: not usable with renal failure (lactic acidosis)	[130-133,151-157]
	Life-style modification (diet, physical activity)	Thiazolidinediones: may be associated to hepato and cardiotoxicity and are adipogenic
	Oral hypoglicemic agent (after steroids tapering):	Second generation sulfonylureas: determine weight gain, hypoglycaemia, may increase CNI level
	Metformin: less weight gain and hypoglicemia	Meglitinides: determine weight gain, hypoglycemia (only with renal insuff), CNI may increase repaglinide level, are expensive
	Thiazolidinediones: well tolerated, may improve post-LT NAFLD	Alpha-glucosidase inhibitors: determine gastrointestinal side effects,are less effective, are expensive
	Dypeptyl peptidase-4 (DPP4) inhibitors, well tolerate, no weight gain, no hypoglicemia, potential anti-inflammation, antihypertension, antiapoptosis effects and immunomodulation on the heart, vessels, and kidney, independent of their hypoglicemic effect	Selective renal sodium glucose co-transporter 2 (SGLT 2): dapagliflozin, canagliflozin, empagliflozin, well tolerated but reported hepato-toxicity, contraindicated in patients with renal impairment
Hyperlipidemia	Hypercholesterolemia responds to:	Statins (except pravastatin and flestatin) are metabolized by cytochrome P-450 3A4, the same that metabolize CNIs and sirolimus so they must be used with caution because of myotoxicity	[134-138]
	HMGCoA inibitors (statins): pravastatine is the most studied and used but also atorvastatin, simvastatin, lovastatin, cerivastatin and fluvastatin are used	If used with statins fibrates may increase calcineurin inibitors levels
	Diet rich in omega 3 fatty acids, fruits, vegetables and dietary fiber
	Hypertrigliceridemia responds to:
	Fish oil (omega 3)
	Fibric acid derivates (gemfibrosil, clofibrate, fenofibrate)
Arterial hypertension	First line agents: calcium channels blockers (amlodipine, isradipine, felodipine)	Nifedipine may increase CNI levels and may cause leg edema	[139-141]
	Second line agents: specific β-blockers, ACE inibitors, angiotensin receptors blockers and loop diuretics	ACE inibitors and angiotensin receptors blockers may exacerbate CNI-induced hyperkalemia, but may provide anti-fibrotic properties and possibly protect against calcineurin induced renal injury
		Thiazides and other diuretics must be used with close follow-up because of potentiation of electrolyte abnormalities, hyperuricemia and renal dysfunction
Obesity	Bariatric surgery: well tolerated and successful but require a complex reoperation	Orlistat (tetrahydrolipstatin), inhibitor of pancreatic lipase has limited efficacy and possibly interferes with immunosuppressive therapy	[141-144]
	Gastric banding at the time of liver transplant procedure seems successful and well tolerate	Gastric bypass surgery can affect intestinal drug absorption