781: patients with compensated cirrhosis and covid-19 have a higher short-term rate of decompensation and mortality but those who survive covid-19 have no difference in outcomes at 1 year: a multicenter research network study

Background: Alcohol use is a leading cause of chronic liver disease world-wide and changes in the gut microbiome increase the risk for liver disease progression in patients with alcohol use disorder (AUD).There are many studies on bacterial and fungal microbiomes, but less is known about the effects of AUD and abstinence on the intestinal virome and the interactions between bacteriophages and their target bacteria.Methods and Results: The viromes of 18 non-alcoholic controls and 62 well-characterized patients with AUD during active alcohol use and after two weeks of alcohol abstinence were evaluated by extracting virus-like particles from stool and performing metagenomic sequencing.The fecal virome was significantly different between controls and AUD patients during active alcohol use and after abstinence, as demonstrated by principal coordinate analysis (PCoA) (p-value = 0.027).Linear discriminant effect-size analysis (LEfSe) revealed the abundance of Lactobacillus, Leuconostoc, and Propionibacterium phages was decreased in AUD patients when compared with controls, but after abstinence for two weeks, AUD patients had significantly increased abundance of Lactobacillus, Leuconostoc, and Propionibacterium phages compared with during active alcohol use (p-value 0.007, 0.016, and 0.03 respectively).The intestinal virome signature was also significantly different by PCoA between AUD patients with non-progressive versus progressive liver disease using the liver cell necrosis and apoptosis marker caspase-cleaved and intact cytokeratin 18 (CK18-M65) as a serum biomarker (p-value = 0.002), with increased prevalence of phages targeting Enterobacteria, Escherichia, and Salmonella and decreased abundance of Lactococcus phages in AUD patients with progressive liver disease.With progression of liver disease, a positive correlation was demonstrated with relative abundance of Streptococcus phages (pvalue < 0.001) and a negative correlation with Lactococcus phages (p-value = 0.004).Moderation analyses using bacteria as the response, corresponding phages and progression of liver disease as the predictors, and a generalized estimating equation model for the interaction term between the phages and CK18-M65 showed that the interaction term was significant for the Enterobacteria, Escherichia, and Streptococcus bacteria-phage pairs (p-value < 0.001, = 0.018, and < 0.001, respectively), indicating that liver disease progression is significantly associated with changes in the dynamics between phages and their target bacteria.Conclusion: Active alcohol use and alcohol-associated progressive liver disease are associated with changes in the fecal virome, some of which are partially reversible after a short period of abstinence.Progression of alcohol-associated liver disease is associated with changes in phage-bacteria interactions.