Changes in Serum Myostatin Levels in Alcoholic Hepatitis Correlate with Improvement in MELD

酒精性肝炎患者血清肌生长抑制素水平的变化与 MELD 改善相关

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作者:Hani Shamseddeen, Abhishek Madathanapalli, Vijay S Are, Vijay H Shah, Arun J Sanyal, Qing Tang, Tiebing Liang, Kayla Gelow, Teresa A Zimmers, Naga Chalasani, Archita P Desai

Aims

To investigate the association between myostatin, clinical variables, and outcomes in AH.

Background

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. Aims: To investigate the association between myostatin, clinical variables, and outcomes in AH.

Conclusions

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.

Methods

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.

Results

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). Conclusions: 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.

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