Virulence factors in gut determine mortality in alcoholic hepatitis

The carriage of virulence factors in the commensal gut microbiota was associated with mortality in patients with alcoholic hepatitis, according to research presented at The Digital International Liver Congress.

In her presentation, Sonja Lang, MD, of the department of medicine at the University of California, San Diego, said that the gut microbiota might play an important role in the modulation of alcohol-associated liver disease, a leading cause of liver transplantation that comes with a mortality rate of up to 50%.

“Studies in mice have shown that colonizing mice with feces from an alcoholic hepatitis patient leads to increased liver damage in these mice compared with conventionally raised mice,” she said. “Whereas a lot of research has been done describing the prevalence or abundance of specific bacteria associated with disease, little is known about the bacterial expression of specific virulence factors of the commensal gut microbiota.”

Researchers analyzed intestinal bacterial metagenomes and genes that encode virulence factors in fecal samples from 81 patients with alcoholic hepatitis, 41 patients with alcohol use disorder and nine non-alcoholic controls. They compared virulence associated factors among the three groups and assessed the association of virulence factors with 180-day mortality.

The most common virulence factors came from Escherichia, Klebsiella, Shigella, Klebsiella, Yersinia, and Enterococcus.

Among fecal samples collected from patients with alcoholic hepatitis, 68% expressed at least one virulence factor gene, compared with 29% of patients with alcohol use disorder and 11% in the control group (P < .001).

At 180 days after enrollment, 82% of patients with alcoholic hepatitis who did not have a virulence factor were alive, compared with 18% among those who had positive virulence factor (adjusted HR = 5.32; 95% CI, 1.2-23.5).

“Mechanistic studies are needed to explore potential causal role of virulence factors in mediating alcohol-associated liver disease,” Lang said.