P54 β -hydroxy β-methylbutyrate (HMB) supplementation to improve functional status in people with advanced liver cirrhosis (BOOST): a multicentre double blind placebo-controlled randomised trial protocol

<h3></h3> Cirrhosis results in poor quality of life and high mortality. As cirrhosis progresses, complications of portal hypertension occur leading to greater morbidity and healthcare use. Irrespective of cirrhosis aetiology, a leaky gut due to poor gut barrier function drives progressive disease. There are currently no evidence-based treatments to prevent or delay progression of cirrhosis. Beta-hydroxy beta-methylbutyrate (HMB), a substance related to the amino acid leucine, increases muscle mass and function, and gut levels of short chain fatty acids, which are essential for maintaining gut barrier function. It is a candidate therapy to reduce gut barrier dysfunction and progression of liver disease. Pilot studies in people with cirrhosis show it improves muscle mass and function and is well-tolerated. We aim to conduct a definitive randomised double-blind placebo-controlled trial of 12-weeks supplementation with 3 g HMB per day in 124 people with advanced cirrhosis of any aetiology from 8 UK sites. Participants will be randomised 1:1 to receive 1.5 g HMB in capsules or matched placebo twice daily for 12 weeks. The primary outcome is the change in physical function as measured by the Liver Frailty Index (LFI) at week 12 post-baseline. Participants will be followed up by phone at Week 4 and in person at Weeks 12 and 24. We will collect data including liver disease severity (MELD and Child Pugh scores), Quality of Life (EQ-5D-5L; SF-36), mental wellbeing, infections, hospitalisations and adverse events. In a subgroup of participants, we will conduct semi-structured interviews to understand participant experience of the trial and intervention. Clinical effectiveness will be confirmed if there is an improvement of ≥0.4 in the LFI. The trial has been funded by the NIHR Research for Patient Benefit programme (NIHR260170). Recruitment is planned to commence in May 2025. If effective, HMB represents a cheap and readily available treatment for advanced cirrhosis. Given its likely safety, we anticipate early adoption into routine clinical care.