血清胆汁酸升高与代谢功能障碍相关脂肪性肝病高危患者的瘙痒独立相关。
Serum Bile Acid Elevation is an Independently Associated With Pruritus in Patients With At-risk Metabolic Dysfunction-associated Steatotic Liver Disease.
作者信息
Younossi Zobair M, Estep Michael J, Felix Sean, Lam Brian, Mukherjee Sumanta, Swift Brandon, Casillas Linda, de Souza Andrea R, Hunnicutt Jake, McLaughlin Megan M, Racila Andrei, Nader Fatema, Stepanova Maria
机构信息
The Global NASH Council, Washington DC, USA.
Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, VA, USA.
出版信息
J Clin Exp Hepatol. 2025 Jul-Aug;15(4):102549. doi: 10.1016/j.jceh.2025.102549. Epub 2025 Mar 20.
BACKGROUND AND AIMS
Elevated serum bile acids are associated with pruritus in cholestatic liver diseases. We assessed the association of serum bile acids and other putative biomarkers of cholestatic pruritus (autotaxin and interleukin-31 (IL-31) with pruritus in patients with metabolic dysfunction-associated steatotic liver disease (MASLD).
METHODS
We used serum from patients with MASLD and metabolic dysfunction-associated steatohepatitis (MASH), viral hepatitis B, viral hepatitis C, and healthy blood donors to measure the levels of bile acids, autotaxin, and IL-31. Clinically significant pruritus was defined from the Chronic Liver Disease Questionnaire.
RESULTS
Six hundred fifty-one subjects were included [MASLD (N = 497, 88 MASH), viral hepatitis B and C (VH, N = 98), healthy controls (N = 56)]. Post hoc definitions of high biomarker levels associated with the presence of clinically significant pruritus were as follows: high bile acids ≥5.9 μmol/L, high autotaxin ≥220 ng/mL, and high IL-31 ≥ 25 pg/mL. The VH patients had the highest bile acids levels and lowest levels were in healthy controls ( < 0.0001). The highest autotaxin levels were seen in hepatitis C, while the highest IL-31 levels in MASH. MASH patients had higher levels of all three biomarkers than non-MASH-MASLD. Also, at-risk MASLD or MASLD with advanced fibrosis (AF) had higher bile acids and autotaxin (all < 0.01) but not IL-31 ( > 0.05). MASLD patients with high bile acids had more pruritus (all MASLD: 25% vs. 17%; MASH 30% vs. 13%; at-risk MASLD: 33% vs. 12%; AF: 41% vs. 8%). In multivariable logistic regressions, having high bile acids was an independent predictor of pruritus in at-risk MASLD [odds ratio (OR) (95% CI) = 4.4 (1.6-12.1)] and MASLD with advanced fibrosis [OR = 7.5 (2.0-29.0)]; but not autotaxin or IL-31 (all > 0.05).
CONCLUSIONS
High serum bile acid level is independently associated with pruritus in at-risk MASLD.
背景与目的
血清胆汁酸升高与胆汁淤积性肝病的瘙痒相关。我们评估了血清胆汁酸以及胆汁淤积性瘙痒的其他假定生物标志物（自分泌运动因子和白细胞介素-31（IL-31））与代谢功能障碍相关脂肪性肝病（MASLD）患者瘙痒的相关性。
方法
我们使用了MASLD和代谢功能障碍相关脂肪性肝炎（MASH）患者、乙型病毒性肝炎、丙型病毒性肝炎患者以及健康献血者的血清来测量胆汁酸、自分泌运动因子和IL-31的水平。临床显著瘙痒根据慢性肝病问卷来定义。
结果
纳入了651名受试者[MASLD（N = 497，88例MASH）、乙型和丙型病毒性肝炎（VH，N = 98）、健康对照（N = 56）]。与临床显著瘙痒存在相关的生物标志物高水平的事后定义如下：高胆汁酸≥5.9 μmol/L、高自分泌运动因子≥220 ng/mL以及高IL-31≥25 pg/mL。VH患者的胆汁酸水平最高，健康对照的水平最低（<0.0001）。丙型肝炎患者的自分泌运动因子水平最高，而MASH患者的IL-31水平最高。MASH患者的所有三种生物标志物水平均高于非MASH-MASLD患者。此外，有风险的MASLD或伴有晚期纤维化（AF）的MASLD患者的胆汁酸和自分泌运动因子水平更高（均<0.01），但IL-31水平无差异（>0.05）。胆汁酸水平高的MASLD患者瘙痒更多（所有MASLD：25%对17%；MASH 30%对13%；有风险的MASLD：33%对12%；AF：41%对8%）。在多变量逻辑回归中，胆汁酸水平高是有风险的MASLD[比值比（OR）（95%置信区间）=4.4（1.6 - 12.1）]和伴有晚期纤维化的MASLD患者瘙痒的独立预测因素[OR = 7.5（2.0 - 29.0）]；但自分泌运动因子或IL-31并非如此（均>0.05）。
结论
血清胆汁酸水平高与有风险的MASLD患者的瘙痒独立相关。
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