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

Cirrhosis is liver scarring, caused mainly by alcohol or fatty liver in the UK. People with cirrhosis have poorer quality of life than healthy people. As cirrhosis worsens, they develop more symptoms and require hospital admissions. Cirrhosis causes over 75,000 admissions and costs the NHS £17 billion annually.

A leaky gut, due to breakdown of the gut lining, drives liver damage in cirrhosis. Changes in gut bacteria mean there are fewer bacteria that can break down fibre into short chain fatty acids (SCFAs). SCFAs are important for the proper function of cells lining the gut. Without them the gut becomes leaky, letting parts of bacteria into the bloodstream leading directly to the liver. This triggers liver inflammation and scar formation.

There are no treatments for liver scarring or the leaky gut. Increasing gut SCFAs may be effective to treat cirrhosis by restoring the gut lining. HMB, a naturally occurring substance that is already available as a dietary supplement to increase muscle strength, also increases SCFA levels in the gut. In small test trials, HMB was safe and had only minor side-effects in people with cirrhosis.

Design and methods
We will conduct a trial of HMB compared to dummy treatment (placebo) in 124 patients with cirrhosis from eight hospital outpatient clinics in England. Patients will be randomly allocated to HMB or placebo twice daily for 12 weeks and followed up for another 12 weeks. At the start and during the trial we will measure the Liver Frailty Index, a combination of strength and function tests, and measures of liver disease, quality of life and mental wellbeing. We will consider the treatment effective if there is meaningful improvement in the Liver Frailty Index after 12 weeks of HMB compared to placebo.

Patient and public involvement
We held four meetings with 10 patients with lived experience of cirrhosis. They assisted in developing this project and decided on the type of HMB (powder) to test and which measures were important for patients (function and quality of life). A patient representative is part of the project team and others will assist with the running of the trial.

Dissemination
Our patient group will produce a summary which will be sent to liver patient groups. We will publish results in the scientific literature and present them at conferences. If the trial shows HMB is effective, we will work with national
societies and healthcare professionals to ensure it is regularly used in routine patient care without delay as it is cheap and widely available.

This project aims to address the lack of treatment options for people with liver cirrhosis by testing whether the dietary supplement beta-hydroxy beta-methylbutyrate (HMB) improves their physical function and quality of life.