Phage therapy hope for alcoholic liver disease

Phage therapy – which involves using viruses to destroy bacteria – could help treat liver disease caused by alcohol, scientists say.

Experiments on mice have shown that targeting “a precise cocktail of phages” at a specific type of gut bacteria known as Enterococcus faecalis (E. faecalis) can get rid of alcoholic hepatitis, an inflammation of the liver caused by drinking excessive amounts of alcohol.

Based on the findings, published in the journal Nature, researchers are calling for the treatment to be expanded so it can be tested in human clinical trials.

A team of scientists, from King’s College London and the University of California San Diego School of Medicine, found that E. faecalis releases a toxin called cytolysin, which can damage liver cells.

While this bacteria is generally present in low numbers in a healthy human gut, the researchers found that people with alcoholic hepatitis have more cytolysin-producing E. faecalis in their guts than healthy people.

To investigate if phage therapy would work, the researchers isolated four different phages that specifically target cytolysin-producing E. faecalis.

According to the researchers, their “precise cocktail of phages” was able to get rid of the bacteria in mice and eradicate alcohol-induced liver disease.

Bernd Schnabl, a professor of medicine and gastroenterology at University of California San Diego School of Medicine and senior author on the study, said: “We not only linked a specific bacterial toxin to worse clinical outcomes in patients with alcoholic liver disease, we found a way to break that link by precisely editing gut microbiota with phages.”

Alcohol stock
Alcoholic liver disease accounted for 80% of the 5,843 alcohol-specific deaths in the UK in 2017 (Dominic Lipinski/PA)

The research also found that around 90% of cytolysin-positive patients with alcoholic hepatitis died within six months of hospital admission, compared to approximately 4% of cytolysin-negative patients.

Prof Schnabl added: “Based on this finding, we believe detection of the cytolysin-gene in faeces from patients with alcoholic hepatitis could be a very good biomarker for liver disease severity and risk of death.”

Alcoholic hepatitis is generally treated with corticosteroids, and in critical cases, liver transplantation may be recommended.

In 2017, alcoholic liver disease accounted for 80% of the 5,843 alcohol-specific deaths in the UK, according to figures from the Office for National Statistics.

With antibiotic-resistant infections on the rise, scientists have renewed their interest in phage therapy.

Professor Debbie Shawcross, professor of hepatology and chronic liver failure at King’s College London and one of the study authors, said: “This novel avenue of research now needs to be expanded to test the safety and effectiveness of phage therapy in human clinical trials in patients with alcohol-related disease.

“It is also likely that other forms of chronic liver disease associated with changes in the gut microbiome will also benefit from this novel approach, such as fatty liver disease.”

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