Clinical and Genetic Predictors of Non-Alcoholic Steatotic Liver Disease and Fibrosis in Lean Individuals

IF 5.2 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Liver International Pub Date : 2025-09-13 DOI:10.1111/liv.70300

Karina Sato-Espinoza, Robert A. Vierkant, Perapa Chotiprasidhi, Filippo Pinto e Vairo, Shulan Tian, Jun Ma, Daniel O'Brien, Konstantinos N. Lazaridis, Carola Dlugosch, Carolin Scheider, Alina M. Allen, Kirk J. Wangensteen

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引用次数: 0

Abstract

Background & Aims

Steatotic liver disease (SLD) is characterised by liver fat accumulation exceeding 5%. Lean body weight (BMI ≤ 25 kg/m²) with non-alcoholic SLD is a rare phenotype, and the balance of risks related to metabolic conditions or genetic predisposition, or the risk of progressive liver disease, is not known. This study evaluates clinical and genetic predictors of non-alcoholic SLD and advanced liver disease in lean individuals.

Methods

We used International Classification of Disease codes, radiology and pathology review to identify 177 lean non-alcoholic SLD cases (47 cryptogenic, 130 MASLD), 677 matched lean controls, and 3090 overweight/obese SLD cases in the Mayo Clinic Biobank and Tapestry databases. We performed case–control and cross-sectional comparisons of clinical and genetic factors between these groups, using univariable and multivariable analyses.

Results

Lean individuals with non-alcoholic SLD exhibited metabolic and genetic profiles that were intermediate between those of lean controls without SLD and overweight/obese SLD individuals, including intermediate rates of diabetes, hypertension, hyperlipidaemia and of homozygosity for the risk allele of PNPLA3. Multivariable analysis indicated that diabetes was an independent predictor of SLD among lean individuals. Among lean individuals with non-alcoholic SLD, those with metabolic-associated SLD (MASLD), as compared to those with cryptogenic SLD (without metabolic risk factor), were more likely to be homozygous for risk alleles in GCKR. The Fib-4 score, a tool for screening advanced liver disease in SLD, accurately predicted advanced fibrosis among lean individuals with non-alcoholic SLD.

Conclusion

Diabetes serves as a primary predictor of non-alcoholic SLD in lean individuals. These results support the recommendation to screen for SLD in patients with diabetes, regardless of BMI. The GCKR risk allele is associated with MASLD in lean individuals, and the risk factors for cryptogenic SLD remain unclear.

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瘦人非酒精性脂肪变性肝病和纤维化的临床和遗传预测因素

背景和目的脂肪肝（SLD）以肝脏脂肪堆积超过5%为特征。瘦体重（BMI≤25kg /m2）非酒精性SLD是一种罕见的表型，与代谢状况或遗传易感性相关的风险平衡，或进展性肝病的风险尚不清楚。本研究评估了瘦人非酒精性SLD和晚期肝病的临床和遗传预测因素。方法采用国际疾病分类编码、放射学和病理学检查，在Mayo Clinic Biobank和Tapestry数据库中确定177例瘦肉非酒精性SLD（47例隐源性SLD， 130例MASLD）、677例匹配的瘦肉对照组和3090例超重/肥胖SLD。我们使用单变量和多变量分析对这些组之间的临床和遗传因素进行了病例对照和横断面比较。结果：非酒精性SLD的瘦人的代谢和遗传特征介于没有SLD的瘦人对照组和超重/肥胖SLD个体之间，包括糖尿病、高血压、高脂血症和PNPLA3风险等位基因的纯合子率中等。多变量分析表明，糖尿病是瘦个体发生SLD的独立预测因子。在患有非酒精性SLD的瘦人中，与那些患有隐性SLD（没有代谢危险因素）的人相比，那些患有代谢相关SLD （MASLD）的人更有可能是GCKR中风险等位基因的纯合子。Fib-4评分是筛选SLD患者晚期肝病的工具，可准确预测非酒精性SLD患者的晚期纤维化。结论糖尿病是瘦人非酒精性SLD的主要预测因素。这些结果支持对糖尿病患者进行SLD筛查的建议，无论BMI如何。在瘦人中，GCKR风险等位基因与MASLD相关，而隐源性SLD的风险因素尚不清楚。

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.