Combined heart and liver transplantation for homozygous familial hypercholesterolaemia: 35-year post-operative outcomes

Abstract

Combined heart–liver transplantation (CHLT) is an exceptionally rare multi-organ procedure undertaken in patients with concurrent end-stage cardiac and hepatic disease, or in those with inherited metabolic disorders—most notably homozygous familial hypercholesterolaemia (HoFH)—in which defective hepatic LDL receptor (LDL-R) function drives progressive and otherwise irreversible cardiovascular injury. We report a 35-year follow-up of a female patient who underwent simultaneous orthotopic cardiac and liver transplantation on 13 September 1990 for HoFH complicated by severe ischaemic cardiomyopathy and aortic valve stenosis. Pre-operative serum low-density lipoprotein cholesterol (LDL-C) was 13 mmol/L, refractory to all pharmacological interventions available at the time. Transplantation produced immediate normalisation of LDL-C to 2.1 mmol/L, reflecting instantaneous restoration of donor hepatic LDL-R function—consistent with the landmark observations reported by Bilheimer, Goldstein, Brown, and Starzl [1, 2]. This normalisation has been broadly maintained across three and a half decades of follow-up. Lipid-lowering therapy was commenced post-operatively to augment the normalised lipid profile, and dramatic regression of tendon xanthomata was documented within six months of transplantation [12].

Cardiac graft function has remained preserved, with ejection fraction (EF) of 64–68% on recent echocardiography and no inducible ischaemia on sequential myocardial perfusion scintigraphy (MPS) in May 2025. Progressive cardiac allograft vasculopathy (CAV) has been identified on coronary CT angiography (CTCA) in 2024 but without haemodynamic consequence. Rejection burden across 35 years has been remarkably low—comprising a mild episode at three weeks post-transplant and a single biopsy-confirmed Grade 1R episode in 2013—consistent with the hepatic immunological privilege hypothesis first elaborated by Calne and subsequently substantiated in combined organ transplantation literature [3, 4]. The dominant long-term complication has been end-stage renal failure secondary to calcineurin inhibitor (CNI) nephropathy—a well-recognised sequela of long-term CNI exposure [32]—necessitating haemodialysis via arteriovenous fistula.More recently, the patient sustained a low-impact femoral fracture reflecting steroid-associated osteoporosis, with subsequent prolonged hospitalisation, deconditioning, rotator cuff tear, and bilateral upper limb neuromuscular symptoms under active investigation. This case contributes exceptional 35-year outcome data in a field where long-term follow-up beyond ten to fifteen years remains sparse.