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

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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.

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Abbreviations

AH:

Alcoholic hepatitis

HD:

Heavy drinking

TREAT001:

Translational Research and Evolving Alcoholic Hepatitis Treatment 001 Study

INR:

International normalized ratio

WBC:

White blood cells

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

ALP:

Alkaline phosphatase

MELD:

Model for End-Stage Liver Disease

DF:

Discriminate factor

TGF-®:

Transforming growth factor-®

GDF-8:

Growth differentiation factor-8

ELISA:

Enzyme-linked immunosorbent assay

AIC:

Akaike information criterion

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Funding

APD is funded by the American Association for the Study of Liver Disease Foundation’s 2017 Career Development Award. Collection of serum samples and serum myostatin analysis was funded by the NIH 3U01AA021840-07S1.

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Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA

    Hani Shamseddeen, Vijay S. Are, Tiebing Liang, Kayla Gelow, Naga Chalasani & Archita P. Desai

  2. University of Connecticut School of Medicine, Farmington, CT, USA

    Abhishek Madathanapalli

  3. Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA

    Vijay H. Shah

  4. Division of Gastroenterology and Hepatology, VCU School of Medicine, Richmond, VA, USA

    Arun J. Sanyal

  5. Department of Biostatistics, Indiana University School of Medicine, Indianapolis, IN, USA

    Qing Tang

  6. Surgical Oncology, Surgery-Chairman’s Office, Indiana University School of Medicine, Indianapolis, IN, USA

    Teresa A. Zimmers

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  1. Hani Shamseddeen
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Correspondence to Archita P. Desai.

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For full disclosure, Dr. Naga Chalasani has ongoing paid consulting activities (or had in preceding 12 months) with NuSirt, Abbvie, Afimmune (DS Biopharma), Allergan (Tobira), Madrigal, Siemens, Foresite, Galectin, Zydus, and La Jolla. These consulting activities are generally in the areas of nonalcoholic fatty liver disease and drug hepatotoxicity. Dr. Chalasani receives research grant support from Exact Sciences, Intercept, and Galectin Therapeutics where his institution receives the funding. Over the last decade, Dr. Chalasani has served as a paid consultant to more than 35 pharmaceutical companies and these outside activities have regularly been disclosed to his institutional authorities.

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Shamseddeen, H., Madathanapalli, A., Are, V.S. et al. Changes in Serum Myostatin Levels in Alcoholic Hepatitis Correlate with Improvement in MELD. Dig Dis Sci 66, 3062–3073 (2021). https://doi.org/10.1007/s10620-020-06632-5

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