Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2026
Polygenic Risk Score Predicts Prognosis in Nonobese Metabolic Dysfunction-Associated Steatotic Liver Disease but not in Obese Metabolic Dysfunction-Associated Steatotic Liver Disease in Japan: A Multicenter Cohort Study.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Shirono Takao, Iwaki Michihiro, Seko Yuya, Jun Dae Won, Shima Toshihide, Takahashi Hirokazu, Kawanaka Miwa, Tanaka Saiyu, Yamaguchi Kanji, Yoneda Masato, Nakajima Atsushi, Itoh Yoshito, Okanoue Takeshi
Аннотация
BACKGROUND & AIMS: Prognosis in nonobese vs obese metabolic dysfunction-associated steatotic liver disease remains uncertain, and genetic effects may differ by obesity. We examined whether a 2-variant polygenic risk score (PNPLA3 rs738409 and TM6SF2 rs58542926) predicts liver-related events and overall survival across obesity strata.
METHODS: This multicenter Japan Genetic Study of Nonalcoholic Fatty Liver Disease Research (JAGUAR) cohort included 1304 Japanese patients with biopsy-proven metabolic dysfunction-associated steatotic liver disease. We examined the relationship between the 2-variant polygenic risk score and liver-related events or overall survival according to obesity status. External validation used an independent Korean, nonbiopsied cohort; validation focused on overall survival, including a clinically enriched subset with fatty liver and Fibrosis-4 index >1.3.
RESULTS: Median follow-up was 8.1 years (range, 1.0-24.0). Overall, 103 liver-related events (7.9%) and 65 deaths (5.0%) occurred; 10-year liver-related event incidence was 10.1% and 10-year overall survival was 95.0%. Liver-related event risk did not differ by obesity (10.0% vs10.4%). Two-variant polygenic risk score independently predicted liver-related events in both strata (per 0.1-unit: obese hazard ratio, 1.207; nonobese hazard ratio, 1.454). For overall survival, the 2-variant polygenic risk score was significant only in nonobese patients (hazard ratio, 1.365), not in obese patients. Adding the 2-variant polygenic risk score improved discrimination in nonobese patients for both liver-related events and overall survival but not for overall survival in obese patients. In external validation, the 2-variant polygenic risk score was not significantly associated with overall survival, including in the enriched subset.
CONCLUSIONS: In biopsy-proven metabolic dysfunction-associated steatotic liver disease, the 2-variant polygenic risk score improves liver-related event prediction regardless of obesity and shows the strongest association with overall survival among nonobese patients; these overall survival associations were not reproduced in a predominantly mild-spectrum, nonbiopsied cohort.
METHODS: This multicenter Japan Genetic Study of Nonalcoholic Fatty Liver Disease Research (JAGUAR) cohort included 1304 Japanese patients with biopsy-proven metabolic dysfunction-associated steatotic liver disease. We examined the relationship between the 2-variant polygenic risk score and liver-related events or overall survival according to obesity status. External validation used an independent Korean, nonbiopsied cohort; validation focused on overall survival, including a clinically enriched subset with fatty liver and Fibrosis-4 index >1.3.
RESULTS: Median follow-up was 8.1 years (range, 1.0-24.0). Overall, 103 liver-related events (7.9%) and 65 deaths (5.0%) occurred; 10-year liver-related event incidence was 10.1% and 10-year overall survival was 95.0%. Liver-related event risk did not differ by obesity (10.0% vs10.4%). Two-variant polygenic risk score independently predicted liver-related events in both strata (per 0.1-unit: obese hazard ratio, 1.207; nonobese hazard ratio, 1.454). For overall survival, the 2-variant polygenic risk score was significant only in nonobese patients (hazard ratio, 1.365), not in obese patients. Adding the 2-variant polygenic risk score improved discrimination in nonobese patients for both liver-related events and overall survival but not for overall survival in obese patients. In external validation, the 2-variant polygenic risk score was not significantly associated with overall survival, including in the enriched subset.
CONCLUSIONS: In biopsy-proven metabolic dysfunction-associated steatotic liver disease, the 2-variant polygenic risk score improves liver-related event prediction regardless of obesity and shows the strongest association with overall survival among nonobese patients; these overall survival associations were not reproduced in a predominantly mild-spectrum, nonbiopsied cohort.