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
{"title":"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","authors":"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","doi":"10.1111/liv.70300","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background & Aims</h3>\n \n <p>Steatotic liver disease (SLD) is characterised by liver fat accumulation exceeding 5%. Lean body weight (BMI ≤ 25 kg/m<sup>2</sup>) 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.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>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 <i>PNPLA3</i>. 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 <i>GCKR</i>. The Fib-4 score, a tool for screening advanced liver disease in SLD, accurately predicted advanced fibrosis among lean individuals with non-alcoholic SLD.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>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 <i>GCKR</i> risk allele is associated with MASLD in lean individuals, and the risk factors for cryptogenic SLD remain unclear.</p>\n </section>\n </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 10","pages":""},"PeriodicalIF":5.2000,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Clinical and Genetic Predictors of Non-Alcoholic Steatotic Liver Disease and Fibrosis in Lean Individuals\",\"authors\":\"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\",\"doi\":\"10.1111/liv.70300\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background & Aims</h3>\\n \\n <p>Steatotic liver disease (SLD) is characterised by liver fat accumulation exceeding 5%. Lean body weight (BMI ≤ 25 kg/m<sup>2</sup>) 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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>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 <i>PNPLA3</i>. 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 <i>GCKR</i>. The Fib-4 score, a tool for screening advanced liver disease in SLD, accurately predicted advanced fibrosis among lean individuals with non-alcoholic SLD.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>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 <i>GCKR</i> risk allele is associated with MASLD in lean individuals, and the risk factors for cryptogenic SLD remain unclear.</p>\\n </section>\\n </div>\",\"PeriodicalId\":18101,\"journal\":{\"name\":\"Liver International\",\"volume\":\"45 10\",\"pages\":\"\"},\"PeriodicalIF\":5.2000,\"publicationDate\":\"2025-09-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Liver International\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/liv.70300\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Liver International","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/liv.70300","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
Clinical and Genetic Predictors of Non-Alcoholic Steatotic Liver Disease and Fibrosis in Lean Individuals
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.
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.
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