Intestinal Virome in Patients With Alcoholic Hepatitis

Abstract

BaCKgRoUND aND aIMS: Alcoholic hepatitis (AH) is a severe manifestation of alcohol-associated liver disease (ALD) with high mortality. Although gut bacteria and fungi modulate disease severity, little is known about the effects of the viral microbiome (virome) in patients with ALD. appRoaCH aND ReSUltS: We extracted virus-like particles from 89 patients with AH who were enrolled in a multicenter observational study, 36 with alcohol use disorder (AUD), and 17 persons without AUD (controls). Virus-like particles from fecal samples were fractionated using differential filtration techniques, and metagenomic sequencing was performed to characterize intestinal viromes. We observed an increased viral diversity in fecal samples from patients with ALD, with the most significant changes in samples from patients with AH. Escherichia-, Enterobacteria-, and Enterococcus phages were over-represented in fecal samples from patients with AH, along with significant increases in mammalian viruses such as Parvoviridae and Herpesviridae. Antibiotic treatment was associated with higher viral diversity. Specific viral taxa, such as Staphylococcus phages and Herpesviridae, were associated with increased disease severity, indicated by a higher median Model for End-Stage Liver Disease score, and associated with increased 90-day mortality. CoNClUSIoNS: In conclusion, intestinal viral taxa are altered in fecal samples from patients with AH and associated with disease severity and mortality. Our study describes an intestinal virome signature associated with AH.

Gut dysbiosis as a driver in alcohol-induced liver injury

“…Herpesviridae, as well as Staphylococcus phages, were associated with higher MELD scores and increased mortality [29]. Other bacteriophages were more abundant in the AH group, including…”

“…Escherichia-, Enterobacteria-, and Enterococcus phages [29]. In contrast to bacterial and fungal J o u r n a l P r e -p r o o f diversity, viral diversity was increased in patients in alcohol consuming groups, and is most pronounced in patients with AH [29]. This may be attributed to phage-bacteria dynamics and incorporation of phage genetic material into their bacterial hosts.…”

“…It is predominantly made up of bacteriophages (lytic phages which can infect and lyse bacterial hosts), but also includes eukaryotic viruses, many of which are known to cause human disease [26]. Alterations in the enteric virome has been seen in certain gastrointestinal conditions such as inflammatory bowel disease and colorectal malignancy, however, there is a paucity of data in patients with liver disease [27,28] Herpesviridae family was exclusively found in patients with AH, and was predominantly comprised of Epstein-Barr Virus, which is a well described hepatic pathogen [29].…”

“…Patients with AH had a marked increase in mammalian viruses, particularly Parvoviridae and Herpesviridae . 29 The Herpesviridae family was exclusively found in patients with AH, and was predominantly comprised of Epstein-Barr virus, which is a well described hepatic pathogen. 29 Herpesviridae , as well as Staphylococcus phages, were associated with higher MELD scores and increased mortality.…”

The gut mycobiome: a novel player in chronic liver diseases

“…Recent studies showed that alcohol consumption is associated with decreased bacterial diversity and altered gut microbiome in animal models and human patients [83,84]. Furthermore, intestinal virome characterization showed an increased viral diversity in fecal samples from patients with ALD compared with nonalcoholic controls, and altered viral taxa are associated with disease severity and mortality in alcoholic hepatitis patients [85]. Research in the field of mycobiome showed changes in the composition of fecal mycobiome in patients with ALD compared with non-alcoholic controls.…”