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Novel mechanism based treatment to improve tissue injury in alcoholic hepatitis

Description: Project Narrative Despite the high clinical significance of alcoholic hepatitis (AH), targeting hepatic injury alone has been of limited therapeutic benefit. Loss of muscle mass or sarcopenia is frequent and adversely affects clinical outcomes in AH. We propose to use a specific molecular weight hyaluronan, HA35, to restore skeletal muscle protein homeostasis and improve outcomes in AH. We will ascertain whether HA35 protects against ethanol-induced tissue injury in healthy subjects and patients with moderate AH.
Funding type: research
Funder scheme: R01
Start date: 2020-09-25
End date: 2025-07-31
Institutions: Cleveland Clinic Lerner College of Medicine, CLEVELAND CLINIC LERNER COM-CWRU
Field: Medicine
Funded outputs count: 27
Funder award ID: R01AA028190
OpenAlex ID: G2018494330
MyD88 ‐Family Adaptors: Compartmentalised Signalling and Non‐Immune Functions
2026 · Seshu Vardhan Pothabathula, Saurabh Mishra, et al. · Immunology
Hyaluronan 35 prevents endotoxin-mediated dysregulated skeletal muscle proteostasis during ethanol exposure
2026 · Nicole Welch, Pugazhendhi Kannan, et al. · American Journal of Physiology-Endocrinology and Metabolism
Natural history and development of a novel composite endpoint in patients with alcohol-associated hepatitis: Data from a prospective multicenter study
2025 · Srinivasan Dasarathy, Wanzhu Tu, et al. · Hepatology · 12
The pyruvate dehydrogenase kinase inhibitor dichloroacetate mitigates alcohol-induced hepatic inflammation and metabolic disturbances in mice
2024 · Jianguo Wu, Emily Huang, et al. · Hepatology Communications · 5
Differential impact of sex on regulation of skeletal muscle mitochondrial function and protein homeostasis by hypoxia‐inducible factor‐1α in normoxia
2024 · Nicole Welch, Saurabh Mishra, et al. · The Journal of Physiology · 8
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Development and evaluation of objective trial performance metrics for multisite clinical studies: Experience from the AlcHep Network
2024 · Srinivasan Dasarathy, Wanzhu Tu, et al. · Contemporary Clinical Trials · 17
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Emergency services utilization by patients with alcohol‐associated hepatitis: An analysis of national trends
2024 · Shreya Sengupta, Akhil Anand, et al. · Alcoholism Clinical and Experimental Research · 4
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L-Isoleucine reverses hyperammonemia-induced myotube mitochondrial dysfunction and post-mitotic senescence
2023 · Avinash Kumar, Annette Bellar, et al. · The Journal of Nutritional Biochemistry · 11
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Fuel to the fire: The impact of COVID‐19 on alcohol‐associated hepatitis
2023 · Shreya Sengupta, Srinivasan Dasarathy · Alcoholism Clinical and Experimental Research
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Liver transplantation in the patient with physical frailty
2023 · Puneeta Tandon, Alberto Zanetto, et al. · Journal of Hepatology · 70
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Alcohol-induced extracellular ASC specks perpetuate liver inflammation and damage in alcohol-associated hepatitis even after alcohol cessation
2023 · Marcelle de Carvalho Ribeiro, Arvin Iracheta-Vellve, et al. · Hepatology · 21
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Adaptive exhaustion during prolonged intermittent hypoxia causes dysregulated skeletal muscle protein homeostasis
2022 · Amy H. Attaway, Annette Bellar, et al. · The Journal of Physiology · 47
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Reply
2022 · Gyongyi Szabo, Mack Mitchell, et al. · Hepatology · 4
IL‐1 receptor antagonist plus pentoxifylline and zinc for severe alcohol‐associated hepatitis
2022 · Gyongyi Szabo, Mack Mitchell, et al. · Hepatology · 111
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Gut microbial trimethylamine is elevated in alcohol-associated hepatitis and contributes to ethanol-induced liver injury in mice
2022 · Robert N. Helsley, Tatsunori Miyata, et al. · eLife · 58
Metabolic reprogramming during hyperammonemia targets mitochondrial function and postmitotic senescence
2021 · Avinash Kumar, Nicole Welch, et al. · JCI Insight · 41
Integrated multiomics analysis identifies molecular landscape perturbations during hyperammonemia in skeletal muscle and myotubes
2021 · Nicole Welch, Shashi Shekhar Singh, et al. · Journal of Biological Chemistry · 19
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Malnutrition, Frailty, and Sarcopenia in Patients With Cirrhosis: 2021 Practice Guidance by the American Association for the Study of Liver Diseases
2021 · Jennifer C. Lai, Puneeta Tandon, et al. · Hepatology · 794
Sarcopenia and frailty in decompensated cirrhosis
2021 · Puneeta Tandon, Aldo J. Montano-Loza, et al. · Journal of Hepatology · 450
Hepatocellular Carcinoma in Patients Without Cirrhosis: The Fibrosis Stage Distribution, Characteristics and Survival
2021 · Kanokwan Pinyopornpanish, Wael Al-Yaman, et al. · Digestive Diseases and Sciences · 30
Alcohol Consumption Is Associated with Poor Prognosis in Obese Patients with COVID-19: A Mendelian Randomization Study Using UK Biobank
2021 · Xiude Fan, Zhengwen Liu, et al. · Nutrients · 29
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Clinical impact of compound sarcopenia in hospitalized older adult patients with heart failure
2021 · Amy Attaway, Annette Bellar, et al. · Journal of the American Geriatrics Society · 39
Quantitative Computed Tomography Assessment of Pectoralis and Erector Spinae Muscle Area and Disease Severity in Chronic Obstructive Pulmonary Disease Referred for Lung Volume Reduction
2021 · Amy H. Attaway, Nicole Welch, et al. · COPD Journal of Chronic Obstructive Pulmonary Disease · 25
Multiomics-Identified Intervention to Restore Ethanol-Induced Dysregulated Proteostasis and Secondary Sarcopenia in Alcoholic Liver Disease
2021 · Shashi Shekhar Singh, Avinash Kumar, et al. · Cellular Physiology and Biochemistry · 40
Activated Protein Phosphatase 2A Disrupts Nutrient Sensing Balance Between Mechanistic Target of Rapamycin Complex 1 and Adenosine Monophosphate–Activated Protein Kinase, Causing Sarcopenia in Alcohol‐Associated Liver Disease
2020 · Gangarao Davuluri, Nicole Welch, et al. · Hepatology · 28