The curative treatment of familial hypercholesterolemia: Liver transplantation

Kirnap, Nazlı Gülsoy; Kırnap, Mahir; Tütüncü, Neslihan Başçıl; Moray, Gökhan; Haberal, Mehmet

doi:10.1111/ctr.13730

Cited by 11 publications

(6 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although substantially lowering the LDL-C level may be achieved with LT, the reduction in LDL-C levels may fluctuate and rebound, and the progression of ASCVDs can be problematic. In line with our results, previous studies have reported fluctuating LDL-C levels in HoFH patients after LT [ 30 , 31 , 32 , 33 , 34 , 37 ], perhaps because of residual extrahepatic LDL receptors and immunosuppressive drug-induced hyperlipidemia [ 37 ]. Consequently, postoperative lipid-lowering therapy may be crucial for achieving acceptable LDL-C levels and halting progression of ASCVDs.…”

Section: Discussionsupporting

confidence: 92%

“…Other attractive approaches, such as gene therapy [ 26 , 27 ] or hepatocyte transplantation [ 28 ], are largely underexplored. Finally, LT has been a last resort for pediatric patients with HoFH since the 1980s [ 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ]. In our case series, none of these six children with HoFH received aggressive lipid-lowering therapy with mipomersen, evolocumab, evinacumab, or LDL apheresis before LT, which may reflect a real problem with undertreatment in settings where availability of lipid-lowering therapy is limited.…”

Section: Discussionmentioning

confidence: 99%

“…Other promising approaches, such as gene therapy [ 26 , 27 ] and hepatocyte transplantation [ 28 ], are currently being explored. Finally, liver transplantation (LT) has been considered a therapeutic alternative for HoFH patients, especially when all other traditional options have been exhausted [ 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Perioperative Management and Clinical Outcomes of Liver Transplantation for Children with Homozygous Familial Hypercholesterolemia

2022

View full text Add to dashboard Cite

Background and Objectives: Liver transplantation (LT) has been accepted as a life-saving option as a last resort for children with homozygous familial hypercholesterolemia (HoFH). Perioperative management of LT for HoFH poses extra challenges for clinicians largely due to premature atherosclerotic cardiovascular diseases (ASCVDs). We aimed to analyze our data of pediatric LT recipients with HoFH, with special attention paid to perioperative management and clinical outcomes. Materials and Methods: After obtaining approval from the local ethics committee, the clinical data of pediatric patients with HoFH who underwent LT at our institution between January 2014 and February 2021 were retrospectively studied. Results: Six pediatric LT recipients with HoFH were included in the analysis. Although ASCVDs were common before LT, all children with HoFH survived the perioperative period without in-hospital mortality. However, one patient experienced acute myocardial infarction two months following LT and was successfully treated with medical interventions. Post-LT metabolic improvement was shown by declines in serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels in the early post-LT period (for TC: 14.7 ± 3.2 mmol/L vs. 5.5 ± 1.8 mmol/L, p < 0.001; for LDL-C: 10.6 ± 2.2 mmol/L vs. 3.6 ± 1.2 mmol/L, p < 0.001, respectively) and at the last follow-up (for TC: 14.7 ± 3.2 mmol/L vs. 4.5 ± 0.9 mmol/L, p = 0.001; for LDL-C: 10.6 ± 2.2 mmol/L vs. 2.8 ± 0.6 mmol/L, p = 0.001, respectively). Dietary restrictions could be lifted after LT. However, three patients required restarting lipid-lowering therapy after LT due to suboptimal LDL-C levels and progression of ASCVDs. Conclusions: Our data suggest that LT can be a safe and feasible therapeutic option for well-selected patients with HoFH, offering relaxed dietary restrictions and remarkable reductions in LDL-C levels. However, concerns remain regarding progression of ASCVDs after LT.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Perioperative Management and Clinical Outcomes of Liver Transplantation for Children with Homozygous Familial Hypercholesterolemia

2022

View full text Add to dashboard Cite

show abstract

“…Limited studies are available on long-term survival after treatment of HoFH with LT. Results from an Iranian study [21,22] indicated that survival rates in HoFH patients after LT at 0.5, 1 and 5 years were 92%, 94% and 91%, respectively. In another case on the long-term survival in a HoFH patient who underwent OLT from a cadaveric donor liver at 12 years after a diagnosis of HoFH, the patient's skin xanoma and atherosclerotic plaques were completely resolved at 9 years after the transplantation and endothelial function was normal [14].…”

Section: Discussionmentioning

confidence: 99%

Liver transplantation for Homozygous Familial hypercholesterolemia: A retrospective analyses from Chinese experience

Zhan

Lin

et al. 2023

Preprint

View full text Add to dashboard Cite

Background Homozygous familial hypercholesterolaemia (HoFH) increase risk of premature cardiovascular events and cardiac death. In severe cases of HoFH, clinical signs and symptoms cannot be controlled well by non-surgical treatments, liver transplantation (LT) currently represents the viable option.Method To assess the clinical efficacy, prognosis and optimal timing of LT for HoFH, a retrospective analysis was conducted on the preoperative, surgical conditions and postoperative follow-up of children who received a LT for HoFH at the Beijing Friendship Hospital over the period from December 2014 to August 2022.Results Xanthoma and decreased activity tolerance were the primary clinical manifestations in the 7 HoFH children initially assessed (one child died suddenly prior to surgery due to cardiac arrest). Accompanying these symptoms were increased blood total cholesterol(TC) and low density lipoprotein (LDL) levels, along with severe cardiovascular diseases. HoFH was confirmed in all cases by genetic and biochemical assays. Initial treatments administered to these patients consisted of low-fat diets and lipid-lowering drugs with poor outcomes. Accordingly, all 6 patients received orthotopic liver transplantations(OLT), with the result that significant postoperative reductions were observed in levels of TC and LDL. The median follow-up of these six cases was 37.41 months (range: 19.40 to 94.10 months). Regular postoperative follow-ups revealed that all children survived, were in good health and showed significant improvements in their clinical symptoms.Conclusion LT can serve as an effective means for treatment of HoFH in children. This LT should be performed prior to the onset of cardiovascular diseases to achieve maximal effects in improving the quality of life for these children.

show abstract

“…In the post-LT period, the cholesterol levels fall to normal within a week’s time. LT by improving the dyslipidemia is known to prevent the progression to coronary artery disease[ 69 , 70 ]. Pathological findings in liver include accumulation of lipid in hepatocytes and Kupffer cells.…”

Section: Group Bmentioning

confidence: 99%

Pediatric metabolic liver diseases: Evolving role of liver transplantation

Menon¹,

Vij²,

Sachan³

et al. 2021

WJT

View full text Add to dashboard Cite

Metabolic liver diseases (MLD) are the second most common indication for liver transplantation (LT) in children. This is based on the fact that the majority of enzymes involved in various metabolic pathways are present within the liver and LT can cure or at least control the disease manifestation. LT is also performed in metabolic disorders for end-stage liver disease, its sequelae including hepatocellular cancer. It is also performed for preventing metabolic crisis’, arresting progression of neurological dysfunction with a potential to reverse symptoms in some cases and for preventing damage to end organs like kidneys as in the case of primary hyperoxalosis and methyl malonic acidemia. Pathological findings in explant liver with patients with metabolic disease include unremarkable liver to steatosis, cholestasis, inflammation, variable amount of fibrosis, and cirrhosis. The outcome of LT in metabolic disorders is excellent except for patients with mitochondrial disorders where significant extrahepatic involvement leads to poor outcomes and hence considered a contraindication for LT. A major advantage of LT is that in the post-operative period most patients can discontinue the special formula which they were having prior to the transplant and this increases their well-being and improves growth parameters. Auxiliary partial orthotopic LT has been described for patients with noncirrhotic MLD where a segmental graft is implanted in an orthotopic position after partial resection of the native liver. The retained native liver can be the potential target for future gene therapy when it becomes a clinical reality.

show abstract

The curative treatment of familial hypercholesterolemia: Liver transplantation

Cited by 11 publications

References 31 publications

Perioperative Management and Clinical Outcomes of Liver Transplantation for Children with Homozygous Familial Hypercholesterolemia

Perioperative Management and Clinical Outcomes of Liver Transplantation for Children with Homozygous Familial Hypercholesterolemia

Liver transplantation for Homozygous Familial hypercholesterolemia: A retrospective analyses from Chinese experience

Pediatric metabolic liver diseases: Evolving role of liver transplantation

Contact Info

Product

Resources

About