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

Abstract

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.

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.

Keywords: Alcoholism; Biomarker; Muscle wasting; TREAT001.

Conflict of interest statement

Conflicts of Interest: None for all authors.

© 2020. Springer Science+Business Media, LLC, part of Springer Nature.

Figures

Figure 1.. Inclusions and Exclusion Flow Diagram.

Flow diagram showing participants in TREAT001 who were included in the study analyses

Figure 2.. Myostatin Levels in Alcoholic Hepatitis (AH) and Heavy Drinking (HD) Controls at Baseline in Males and Females.

Males had higher myostatin levels than females and HD had higher myostatin levels than AH. *HDC: heavy drinking controls

Figure 3.. Trends in Myostatin over a One Year Follow up in Alcoholic Hepatitis (AH) and Heavy Drinkers (HD).

Trends in myostatin levels over the one year follow up period showing that AH displayed a trend of increasing myostatin levels while HD did not display a trend.

Figure 4.. Trends in Myostatin over a One Year Follow up in Females and Males with Alcoholic Hepatitis, Stratified by Abstinence (panel A) or Corticosteroid use (panel B) and Change in MELD.

Trends in myostatin in males and females with AH showing that both genders had a trend to increase myostatin levels while achieving abstinence and decreasing their MELD scores. Trends were not different by corticosteroid use.

Figure 5.. Delta Myostatin as a function of Delta MELD score in Abstinent and Non-abstinent AH Cases.

Scatter plot with a fitted linear approximation showing delta myostatin correlating negatively with delta MELD score in both abstinent and non-abstinent AH cases.