Liver transplantation in severe homozygous familial hypercholesterolaemia: a scoping review

BACKGROUND AND AIMS: Liver transplantation is the only known potentially curative treatment for homozygous familial hypercholesterolaemia (HoFH). While this procedure often normalises low-density lipoprotein cholesterol (LDL-C) levels and can reverse coronary atherosclerosis and regress xanthomata, its long-term risks and benefits remain elusive. The purpose of this review was to examine the extant literature on the safety and efficacy of liver transplantation in patients with HoFH. METHODS: A scoping review was conducted for relevant literature primarily focused on safety (e.g. surgical complications, rejection, immunosuppressive therapy, mortality) and effectiveness outcomes (e.g. serum LDL-C levels, xanthoma changes, atherosclerotic cardiovascular disease or events) of liver transplantation in severe HoFH. The PRISMA-ScR guideline was followed. We searched five databases (Medline, Embase, Global Health, Web of Science and CINAHL) from inception to September 2025. RESULTS: A total of 76 studies and 212 cases were included. The majority (53%) of studies were case reports. Liver transplantation was done mostly in children, genetically or phenotypically diagnosed with HoFH. The median follow-up time for individuals was 3.5 years. While the effectiveness of liver transplantation with reference to LDL-C reduction and xanthomata regression were well documented, long-term outcomes such as cardiovascular events and mortality were not consistently reported. CONCLUSIONS: While liver transplantation holds great potential for normalising circulatory LDL-C levels in patients with HoFH, due to the rare nature of HoFH, the current literature remains incomplete concerning its safety and efficacy. To fill this gap, future efforts should utilise liver transplantation registries, to increase sample size and standardise longer-term follow-up.