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

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

doi:10.1007/s10620-020-06632-5

Cited by 3 publications

(2 citation statements)

References 33 publications

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“…Of the participants enrolled, 258 AH cases and 181 HD completed the Medical Short Form‐36 (SF‐36) questionnaire at time of initial enrolment and were included in this analysis. Participants in these analyses have been included in several other publications from the TREAT consortium (Liangpunsakul et al, 2016, 2018; Samala et al, 2018; Shamseddeen et al, 2021). After enrolment and baseline assessment, subjects were prospectively followed through in‐person study visits at 6 and 12 months, at which time all initial study assessments including the SF‐36 were readministered (Figure ).…”

Section: Methodsmentioning

confidence: 99%

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Health‐related quality of life is dynamic in alcoholic hepatitis and responds to improvement in liver disease and reduced alcohol consumption

Madathanapalli

Tang

Lammert

et al. 2021

Alcoholism Clin & Exp Res

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Background The impact of alcoholic hepatitis (AH) on health‐related quality of life (HRQOL) remains inadequately described. We aimed to characterize HRQOL in AH and heavy drinkers (HD), and its associations with clinical variables and outcomes. Methods This is a post hoc analysis of participants in the Translational Research and Evolving Alcoholic Hepatitis Treatment 001 study (NCT02172898). HRQOL was measured using Short Form Health Survey (SF‐36). Mean SF‐36 scores were compared in AH and HD with two‐sample t‐tests. Associations among clinical characteristics, 30‐day mortality, and SF‐36 mental and physical component scores (MC, PC) were investigated with generalized linear and logistic multivariate regression models. Trends of MC and PC scores were analyzed using one‐way ANOVA. Results Participants with AH (n = 258) and HD (n = 181) were similar demographically. AH cases had a mean Model for End‐stage Liver Disease (MELD) score of 23 (7). AH cases had lower PC scores [37 (10) vs. 48 (11), p < 0.001] but higher MC scores [37 (13) vs. 32 (13), p < 0.001]. MC scores were independently associated with age, male gender, and daily alcohol consumption; PC scores were independently associated with age, BMI, alanine aminotransferase concentration, alkaline phosphatase concentration, white blood cell counts, and the presence of ascites. With each 5‐point decrease in the baseline PC score, the adjusted odds of dying within 30 days increased by 26.7% (95% CI 1% to 46%). Over time, HRQOL in AH improved (day 0 to day 180 delta PC score: 4.5 ± 1.7, p = 0.008; delta MC score: 9.8 ± 2.0, p < 0.001). Participants with a MELD score <15 by day 180 had greater increases in PC scores than those with MELD score ≥15 (delta PC score 7.1 ± 1.8 vs. −0.7 ± 2.3, p = 0.009), while those abstinent by day 180 had greater increases in MC scores than those who were not abstinent (delta MC score 9.1 ± 1.8 vs. 2.8 ± 2.4, p = 0.044). Conclusions HRQOL is poor in AH and HD in a domain‐specific pattern. Independent of MELD score, lower baseline HRQOL is associated with higher 30‐day mortality. Over time, HRQOL improves with greater gains seen in individuals with improved MELD scores and those who were abstinent.

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Section: Methodsmentioning

confidence: 99%

“…This is a post hoc analysis of individuals who were recruited as part of the TREAT001 study (NCT02172898), which has been previously described (Shamseddeen et al, 2021). Participants were enrolled from May 2013 to May 2016 and followed for 1 year.…”

Section: Methodsmentioning

confidence: 99%

Health‐related quality of life is dynamic in alcoholic hepatitis and responds to improvement in liver disease and reduced alcohol consumption

Madathanapalli

Tang

Lammert

et al. 2021

Alcoholism Clin & Exp Res

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A low baseline serum myostatin concentration is associated with poor clinical outcome in patients with primary biliary cholangitis

Hayashi,

Abe,

Sugaya

et al. 2024

J of Gastro and Hepatol

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Background and AimPrimary biliary cholangitis (PBC) is an autoimmune‐mediated cholestatic liver disease that can progress to biliary cirrhosis and liver‐related death. The associations between baseline myostatin levels and clinical outcomes in PBC patients are unknown. We aimed to clarify the influence of myostatin levels on the clinical outcomes of PBC patients.MethodsA total of 119 PBC patients were analyzed in this study. Myostatin levels were measured in stored sera before ursodeoxycholic acid treatment, and their associations with the clinical features and prognosis of PBC patients were analyzed. We analyzed the correlation between serum myostatin and chemokines/cytokines.ResultsSerum myostatin was significantly lower in PBC patients (2343 pg/mL) than in healthy controls (4059 pg/mL, P < 0.001). The prevalence of patients with low myostatin levels increased according to the severity of histological fibrosis. The serum myostatin concentration was negatively correlated with the IL‐6 and leucine‐rich α2 glycoprotein levels, but the chemokine concentration was not correlated with the myostatin concentration. Low myostatin in PBC patients was associated with shorter survival without liver‐related complications (hazard ratio [HR], 3.598; 95% confidence interval [CI], 1.27–10.1; P = 0.015) and shorter transplant‐free survival (HR, 3.129; 95% CI, 1.02–9.56; P = 0.045) independent of pretreatment GLOBE score. Patients with both high pretreatment GLOBE scores and low myostatin levels had poor prognoses (log–rank test: P < 0.001).ConclusionsA low serum myostatin concentration at diagnosis was associated with poor clinical outcomes. Assessment of circulating myostatin levels may improve the prediction of outcomes in patients with PBC.

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The Effects of Dietary Supplements, Nutraceutical Agents, and Physical Exercise on Myostatin Levels: Hope or Hype?

2022

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Myostatin, a secreted growth factor belonging to the transforming growth factor β (TGF-β) family, performs a role in hindering muscle growth by inhibiting protein kinase B (Akt) phosphorylation and the associated activation of hypertrophy pathways (e.g., IGF-1/PI3K/Akt/mTOR pathway). In addition to pharmacological agents, some supplements and nutraceutical agents have demonstrated modulatory effects on myostatin levels; however, the clinical magnitude must be appraised with skepticism before translating the mechanistic effects into muscle hypertrophy outcomes. Here, we review the effects of dietary supplements, nutraceutical agents, and physical exercise on myostatin levels, addressing the promise and pitfalls of relevant randomized clinical trials (RCTs) to draw clinical conclusions. RCTs involving both clinical and sports populations were considered, along with wasting muscle disorders (e.g., sarcopenia) and resistance training-induced muscle hypertrophy, irrespective of disease status. Animal models were considered only to expand the mechanisms of action, and observational data were consulted to elucidate potential cutoff values. Collectively, the effects of dietary supplements, nutraceutical agents, and physical exercise on myostatin mRNA expression in skeletal muscle and serum myostatin levels are not uniform, and there may be reductions, increases, or neutral effects. Large amounts of research using resistance protocols shows that supplements or functional foods do not clearly outperform placebo for modulating myostatin levels. Thus, despite some biological hope in using supplements or certain functional foods to decrease myostatin levels, caution must be exercised not to propagate the hope of the food supplement market, select health professionals, and laypeople.

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

Cited by 3 publications

References 33 publications

Health‐related quality of life is dynamic in alcoholic hepatitis and responds to improvement in liver disease and reduced alcohol consumption

Health‐related quality of life is dynamic in alcoholic hepatitis and responds to improvement in liver disease and reduced alcohol consumption

A low baseline serum myostatin concentration is associated with poor clinical outcome in patients with primary biliary cholangitis

The Effects of Dietary Supplements, Nutraceutical Agents, and Physical Exercise on Myostatin Levels: Hope or Hype?

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