Genetic Risk Factors for Steatotic Liver Disease After Liver Transplantation

IF 6 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Liver International Pub Date : 2025-03-15 DOI:10.1111/liv.70067

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

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Abstract

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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背景脂肪性肝病（SLD）的遗传风险因素在肝脏移植（LT）中的作用令人好奇，因为供体和受体的遗传因素都可能起作用。迄今为止，仅有少数几项小规模研究发表。方法我们分析了肝移植后 SLD 的发病率和风险因素，以及 56 个与 SLD 相关的基因变异对 595 对肝移植后≥ 6 个月可进行肝活检的供体和受体的影响。我们评估了除非遗传性风险因素外，多基因风险评分（PRS-5）是否能提高预测LT后SLD的能力。结果在中位 7.6 年的随访中，34.5% 的患者在 LT 后被诊断出 SLD。在包括非遗传风险因素的多变量分析中，供体 PNPLA3 rs738409-G（SLD 的 HR：C/G 1.34，p = 0.051，G/G 2.25，p = 0.004）、供体 HSD17B13 rs72613567-TA（SLD 的 HR：TA/T 0.68，p = 0.02 TA/TA HR 0.50，p = 0.10）和受体 UCP2 rs695366-G（SLD 的 HR：A/G 0.63，p = 0.002，G/G HR 0.50，p = 0.04）似乎是 LT 后 SLD 最重要的遗传风险因素。将 PRS-5 加入多变量回归模型（包括非遗传风险因素）后，SLD 的预测能力仅略有提高（AUC 0.78 至 0.80）。结论各种遗传变异会导致 LT 后 SLD，受体和供体中存在不同的变异，供体 PNPLA3 rs738409-G 是最重要的风险等位基因。尽管如此，与表型数据相比，供体和受体基因分型在个体风险分层方面仅提供了适度的额外价值，突出了可改变的风险因素的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Liver International 医学-胃肠肝病学

CiteScore

13.90

自引率

4.50%

发文量

348

审稿时长

2 months

期刊介绍： Liver International promotes all aspects of the science of hepatology from basic research to applied clinical studies. Providing an international forum for the publication of high-quality original research in hepatology, it is an essential resource for everyone working on normal and abnormal structure and function in the liver and its constituent cells, including clinicians and basic scientists involved in the multi-disciplinary field of hepatology. The journal welcomes articles from all fields of hepatology, which may be published as original articles, brief definitive reports, reviews, mini-reviews, images in hepatology and letters to the Editor.