# ALCOHOLIC HEPATITIS CLINICAL AND TRANSLATIONAL NETWORK: LATE PHASE CLINICAL TRIALS AND OBSERVATIONAL STUDIES 6/9

> **NIH NIH U01** · CLEVELAND CLINIC LERNER COM-CWRU · 2020 · $153,563

## Abstract

ABSTRACT
Despite the high clinical significance, there is limited knowledge of the management and treatment of COVID-
19. Patients with alcohol associated liver disease (ALD) and COVID-19 are at increased risk for severe disease,
morbidity and mortality. There are also data that alcohol consumption increases during isolation, like that caused
by social distancing measures enacted during the COVID-19 pandemic, therefore the incidence and severity of
ALD is likely to increase. Current treatment approaches for patients with severe COVID-19 include antiviral
agents and supportive care. In our preliminary and pilot studies we have observed sarcopenia or loss of skeletal
muscle mass and impaired muscle strength in patients with ALD. Sarcopenia and accompanying contractile
dysfunction contribute to longer hospital and intensive care stay, greater need for ventilatory support and poor
outcomes in acute respiratory distress syndrome (ARDS), a hallmark of severe COVID-19. The “cytokine storm”
that occurs in patients with COVID-19 is accompanied by elevated circulating IL-6, and emerging data suggests
that IL-6 inhibitors improve survival in patients with severe COVID-19. Despite the significant interest in IL-6
inhibitors with multiple ongoing clinical trials underway, these agents increase the risk for secondary infections
(a common occurrence in COVID-19) and are contraindicated in those with significant elevated plasma
transaminases. β-hydroxy β-methyl butyrate (HMB), a non-nitrogenous leucine metabolite with anabolic
properties, also inhibits plasma IL-6 while improving muscle mass and contractile function. We therefore
hypothesize that COVID-19 worsens clinical outcomes and muscle loss in ALD patients, and that reversal of
muscle loss by HMB through an IL-6 dependent manner will improve clinical outcomes in ALD patients. This
hypothesis will be tested through two interrelated, but independent specific aims: (1) establish the natural
course of COVID-19 infection in patients with ALD by determining whether COVID-19 is more severe in
ALD and whether COVID-19 worsens liver injury in ALD; (2) determine whether treatment with HMB
improves the acute and long-term consequences of COVID-19 in terms of skeletal muscle mass, skeletal
muscle function, and clinical outcomes in ALD patients. We will use clinical and biosamples to determine
outcomes and responses to intervention targeting the skeletal muscle in these patients. We anticipate HMB will
reduce inflammatory markers including circulating IL-6, improve clinical outcomes in-hospital, reverse
sarcopenia, and improve long-term clinical outcomes. These human studies have the potential for immediate
translation into clinical practice to rapidly improve immediate and long-term outcomes in ALD patients with
COVID-19. These studies will supplement the applicant’s ongoing alcoholic hepatitis network grant supported
by the NIAAA.

## Key facts

- **NIH application ID:** 10173034
- **Project number:** 3U01AA026976-03S1
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** Srinivasan Dasarathy
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $153,563
- **Award type:** 3
- **Project period:** 2018-08-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10173034

## Citation

> US National Institutes of Health, RePORTER application 10173034, ALCOHOLIC HEPATITIS CLINICAL AND TRANSLATIONAL NETWORK: LATE PHASE CLINICAL TRIALS AND OBSERVATIONAL STUDIES 6/9 (3U01AA026976-03S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10173034. Licensed CC0.

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