Chronic opioid use is associated with altered gut microbiota and predicts readmissions in patients with cirrhosis.

Abstract

Opioid use is epidemic in cirrhosis, which could precipitate hepatic encephalopathy (HE) potentially through gut dysbiosis and inflammation. To define the effect of opioids on readmissions and on gut microbiota composition and functionality. Cohort 1 had 200 cirrhotic in-patients (with/without opioid use) followed prospectively through the index hospitalisation and 6months post discharge. Readmissions (HE-related/unrelated) were compared between patients discharged on opioids compared to the rest, including using a multi-variable analysis. Cohort 2 consisted of 72 cirrhotics on chronic opioids who were age/model for end-stage liver disease (MELD) and prior HE-balanced with 72 cirrhotics not on opioids. Stool microbiota composition (multi-tagged sequencing), predicted functionality (PiCRUST), endotoxemia and systemic inflammation (IL-6, IL-17) were compared. Cohort 1: Chronic opioid use was statistically similar between those admitted with/without HE, and was judged to be an HE precipitant in <5% of cases during the index hospitalisation. Of the 144 patients alive at 6months, 82 were readmitted. The opioid users had a significantly higher all cause (69% vs. 48%, P=0.008), but not HE-related readmissions (30% vs. 41%, P=0.30). On regression, opioid therapy and female gender were predictive of readmission independent of MELD score and previous HE. Cohort 2: Significant dysbiosis was noted in the opioid cohort, especially in HE+opioid patients with lower autochthonous taxa and Bacteroidaceae relative abundance. PiCRUST showed highest aromatic amino acid and endotoxin production in opioid users. Opioid users also had higher endotoxemia and IL-6 but not IL-17. Chronic opioid use in cirrhosis is associated with increased endotoxemia, dysbiosis and all-cause readmissions.