YKL-40: Revolutionizing cardiac risk prediction and therapy in liver transplantation

Table 2 Non-graft-related causes of mortality in liver transplantation

Cause of mortality	Condition	Pathophysiology and clinical impact
CVD and related complications	CAD	Accelerated atherosclerosis, endothelial dysfunction, and pre-existing metabolic risk factors contribute to higher rates of MI, IHD, and HF post-LT
	HF and cirrhotic cardiomyopathy	Many LT candidates have underlying myocardial dysfunction due to cirrhosis-related hyperdynamic circulation, leading to increased HF risk after LT
	Arrhythmias and sudden cardiac death	Post-LT arrhythmias, particularly AF, increase the likelihood of stroke, thromboembolic events, and sudden cardiac death, contributing to long-term mortality
Renal dysfunction and CKD	CNI-induced nephrotoxicity	Prolonged exposure to CNIs (tacrolimus, cyclosporine) can lead to progressive renal dysfunction, increasing the risk of ESKD and cardiovascular mortality
	Cardiorenal syndrome	Many LT recipients develop concurrent renal and cardiac dysfunction, further complicating post-LT management
Metabolic disorders and graft function decline	DM and metabolic syndrome	PTDM, dyslipidemia, and obesity contribute to long-term cardiovascular risk, exacerbating non-graft-related mortality
	Late graft dysfunction and chronic rejection	While primary graft failure is a well-recognized early risk, chronic rejection and immune-mediated injury can lead to progressive hepatic dysfunction, affecting long-term survival
Infections and sepsis	Opportunistic infections	CMV, fungal infections, and multidrug-resistant bacterial infections are frequent causes of morbidity and mortality in immunosuppressed LT recipients
	Sepsis and multi-organ failure	Infection-related complications, particularly in the first year post-LT, remain a significant cause of non-graft-related mortality
Malignancies: De novo and recurrent cancers	HCC recurrence	While LT is a curative treatment for selected patients with HCC, recurrence occurs in 10% to 20% of cases, significantly affecting survival
	PTLD	Linked to chronic immunosuppression, PTLD and other malignancies increase the risk of non-graft-related mortality
	De novo cancers	Immunosuppressive therapy contributes to higher rates of skin cancers, gastrointestinal malignancies, and hematologic malignancies, impacting long-term outcomes

AF: Atrial fibrillation; CAD: Coronary artery disease; CKD: Chronic kidney disease; CMV: Cytomegalovirus; CNI: Calcineurin inhibitor; CVD: Cardiovascular disease; DM: Diabetes mellitus; ESKD: End-stage kidney disease; HCC: Hepatocellular carcinoma; HF: Heart failure; IHD: Ischemic heart disease; LT: Liver transplantation; MI: Myocardial infarction; post-LT: Post liver transplantation; PTDM: Post-transplant diabetes mellitus; PTLD: Post-transplant lymphoproliferative disorder.