Division of Gastroenterology and Hepatology, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA.
University of Connecticut School of Medicine, Farmington, CT, USA.
Dig Dis Sci. 2021 Sep;66(9):3062-3073. doi: 10.1007/s10620-020-06632-5. Epub 2020 Oct 19.
Alcoholic hepatitis (AH) is a serious clinical syndrome often associated with muscle wasting. Myostatin, a member of the transforming growth factor-β superfamily, has been studied in diseases with muscle wasting; however, the role of myostatin in AH is unknown.
To investigate the association between myostatin, clinical variables, and outcomes in AH.
We analyzed data for cases of AH and controls of heavy drinkers (HD) in TREAT001 (NCT02172898) with serum myostatin levels (AH: n = 131, HD: n = 124). We compared characteristics between the two groups at baseline, 30, and 90 days and explored correlations between myostatin and clinical variables. We then modeled the relationship of myostatin to other variables, including mortality.
Baseline median myostatin was lower in AH compared to HD (males: 1.58 vs 3.06 ng/ml, p < 0.001; females: 0.84 vs 2.01 ng/ml, p < 0.001). In multivariable linear regression, bilirubin, WBC, and platelet count remained negatively correlated with myostatin in AH. AH females who died at 90 days had significantly lower myostatin, but in a multivariable logistic model with MELD and myostatin, only MELD remained significantly associated with 90-day mortality. During 1-year follow-up, AH cases (n = 30) demonstrated an increase in myostatin (mean, 1.73 ng/ml) which correlated with decreasing MELD scores (ρ = - 0.42, p = 0.01).
Myostatin levels are significantly lower in AH compared to HD and are negatively correlated with total bilirubin, WBC, and platelet count. Myostatin increased as patients experienced decreases in MELD. Overall, myostatin demonstrated a dynamic relationship with AH outcomes and future studies are needed to understand the prognostic role of myostatin in AH.
酒精性肝炎(AH)是一种严重的临床综合征,常伴有肌肉减少症。肌肉生长抑制素(Myostatin)是转化生长因子-β超家族的成员,已在伴有肌肉减少症的疾病中进行了研究;然而,其在 AH 中的作用尚不清楚。
研究 Myostatin 与 AH 中的临床变量和结局的关系。
我们分析了 TREAT001 研究(NCT02172898)中 AH 病例和重度饮酒者(HD)对照者的血清 Myostatin 水平数据(AH:n=131,HD:n=124)。我们比较了两组在基线、30 天和 90 天时的特征,并探讨了 Myostatin 与临床变量之间的相关性。然后,我们构建了 Myostatin 与其他变量(包括死亡率)的关系模型。
与 HD 相比,AH 患者的基线中位 Myostatin 水平较低(男性:1.58 vs 3.06 ng/ml,p<0.001;女性:0.84 vs 2.01 ng/ml,p<0.001)。在多变量线性回归中,胆红素、白细胞和血小板计数与 AH 中的 Myostatin 呈负相关。90 天死亡的 AH 女性的 Myostatin 水平显著较低,但在包含 MELD 和 Myostatin 的多变量逻辑模型中,只有 MELD 与 90 天死亡率显著相关。在 1 年的随访期间,30 例 AH 患者的 Myostatin 水平升高(平均升高 1.73 ng/ml),与 MELD 评分降低相关(ρ=-0.42,p=0.01)。
与 HD 相比,AH 患者的 Myostatin 水平显著降低,与总胆红素、白细胞和血小板计数呈负相关。随着患者 MELD 降低,Myostatin 增加。总的来说,Myostatin 与 AH 结局之间存在动态关系,需要进一步研究以了解其在 AH 中的预后作用。