Genetic Risk Factors for Steatotic Liver Disease After Liver Transplantation.

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Tác giả: Fredrik Åberg, Johanna Arola, Martti Färkkilä, Kati Hyvärinen, Jouni Lauronen, Ville Liukkonen, Arno Nordin, Jukka Partanen, Maria Semenova

Ngôn ngữ: eng

Ký hiệu phân loại: 324.22 Leadership

Thông tin xuất bản: United States : Liver international : official journal of the International Association for the Study of the Liver , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 712993

BACKGROUND: The role of genetic risk factors for steatotic liver disease (SLD) is intriguing in liver transplantation (LT), as both donor and recipient genetic factors may play a role. There are only a few small-scale studies published so far. METHODS: We analysed the incidence and risk factors for post-LT SLD and the impact of 56 SLD-associated genetic variants in 595 donor-recipient pairs with liver biopsy available ≥ 6 months after LT. We evaluated whether the polygenic risk score (PRS-5) improves the ability to predict post-LT SLD in addition to non-genetic risk factors. RESULTS: SLD after LT was diagnosed in 34.5% of patients during a median 7.6-year follow-up. In multivariate analysis including non-genetic risk factors, donor PNPLA3 rs738409-G (HR for SLD: C/G 1.34, p = 0.051, G/G 2.25, p = 0.004), donor HSD17B13 rs72613567-TA (HR for SLD: TA/T 0.68, p = 0.02 TA/TA HR 0.50, p = 0.10) and recipient UCP2 rs695366-G (HR for SLD: A/G 0.63, p = 0.002, G/G HR 0.50, p = 0.04) appeared as the most important genetic risk factors for post-LT SLD. The addition of PRS-5 to a multivariate regression model (including non-genetic risk factors) improved the predictive ability for SLD only modestly (AUC 0.78 to 0.80). CONCLUSIONS: Various genetic variants contribute to post-LT SLD with separate variants among recipients and donors, with donor PNPLA3 rs738409-G as the most significant risk allele. Still, donor and recipient genotyping provide only modest additional value for individual risk stratification over phenotype data, highlighting the role of modifiable risk factors.
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