Cannabinoid Use Among Liver Transplant Recipients.

The effect of cannabinoids on liver transplant outcomes is an area of active research. We aimed to investigate marijuana (MJ) and cannabidiol (CBD) use among liver transplant recipients at the University of Colorado Hospital (UCH), specifically prevalence, habits, and predictors of use. Liver transplant recipients followed at UCH with valid email addresses were sent an informed consent postcard and survey invitation. This exploratory survey was conducted using REDCap. IBM SPSS Statistics software was used for statistical analysis. Of 1227 recipients who were sent surveys, 538 people responded. On average, respondents were 59 years old, with 63.7% male and 81.7% White. Hepatitis C virus (HCV; 30.4%) and alcohol use (17.7%) were the most common etiologies of liver disease. Among respondents, 23.8% reported current MJ use. Methods of use included smoking (72.4%), ingestion (55.3%), and vaporization (31.7%). Top reasons for MJ use were recreation (56.5%), anxiety (54.8%), and pain (53.2%). Among respondents, 21.0% currently used CBD, usually in the form of creams or lotions (58.9%) and to relieve pain (84.9%) and anxiety (31.1%). In multivariable analysis, age (odds ratio [OR], 0.941; 95% confidence interval [CI], 0.923-0.959; P < 0.001), diabetes mellitus (OR, 0.357; 95% CI, 0.171-0.746; P = 0.01), HCV cirrhosis (OR, 3.949; 95% CI, 2.281-6.835; P < 0.001), alcohol-related cirrhosis (OR, 2.101; 95% CI, 1.202-3.671; P = 0.01), and current tobacco use (OR, 2.918; 95% CI, 1.065-7.990; P = 0.04) were significant predictors of MJ use. Our study shows that cannabinoid use after liver transplant is common. MJ use is associated with decreasing age, alcohol-related and HCV cirrhosis, and tobacco use. Anxiety, pain, and recreation were top reasons for its use. Transplant teams should address reasons why their patients use MJ and CBD and develop programs to mitigate anxiety and pain after transplant. Further studies are needed to examine effects of cannabinoids on liver transplant outcomes.

Factors impacting physicians' decisions to prevent variceal hemorrhage.

BACKGROUND: Reasons underlying the variability of physicians' preferences for non-selective beta-blockers (BBs) and endoscopic variceal ligation (EVL) to prevent a first variceal bleed have not been empirically studied. Our aims were to examine whether 1) gastroenterologists can be classified into distinct subgroups based on how they prioritize specific treatment attributes and 2) physician characteristics are associated with treatment preference. METHODS: We surveyed physicians to determine their preferred treatment for a standardized patient with large varices and examined the influence of treatment characteristics on physicians' decision making using best-worst scaling. Latent class analysis was used to examine whether physicians could be classified into groups with similar decision-making styles. RESULTS: 110 physicians were interviewed (participation rate 39%). The majority spent two or more days a week performing endoscopies and had practices comprising less than 25% of patients with liver disease. Latent class analysis demonstrated that physicians could be classified into at least two distinct groups. Most (n = 80, Group 1) were influenced solely by the ability to visually confirm eradication of varices. In contrast, members of Group 2 (n = 30) were influenced by the side effects and mechanism of action of BBs. Group 1 members were more likely to have practices that included fewer patients with liver disease and more likely to choose options including EVL (p = 0.01 for both). CONCLUSIONS: Among physicians, where the majority performs endoscopy on two or more days per week, most prefer prevention strategies which include EVL. This may be due to the strong appeal of being able to visualize eradication of varices.

Obeticholic Acid Decreases Intestinal Content of Enterococcus in Rats With Cirrhosis and Ascites.

The intestinal microbiome and bacterial translocation (BT), the passage of microorganisms from the gut lumen to mesenteric lymph nodes and other extra-intestinal sites, are main mechanisms implicated in liver injury and further decompensation in patients with cirrhosis. We hypothesized that obeticholic acid (OCA), a semisynthetic bile acid, would change the microbiome composition and reduce bacterial translocation in experimental cirrhosis. Rats with cirrhosis induced by carbon tetrachloride inhalation (a nonseptic model) with ascites present for at least 7 days were randomized to receive a 14-day course of OCA at a dose of 5 mg/kg/day (n = 34) or placebo (n = 34). Stool was collected at days 1 (randomization), 8, and 14 (sacrifice) for analysis of intestinal microbiome using the V4 hypervariable region of the bacterial 16S gene amplified by polymerase chain reaction. Bacteriological cultures of mesenteric lymph nodes, blood, and ascites were performed at end of study. Twenty-four animals in each group reached the end of study. Compared with placebo, rats treated with OCA had decreased relative abundance of Enterococcus in both ileum content (P = 0.02) and in stool (P < 0.001). BT from pathogenic bacteria was not different between groups. At end of treatment, rats on OCA had a significantly lower aspartate aminotransferase (AST) (266 vs. 369 IU/L; P < 0.01) and higher serum albumin (0.9 vs. 0.7 g/dL; P < 0.01) than rats on placebo. Conclusion: Although OCA did not appear to reduce BT by pathogenic bacteria, the reduction in intestinal content of Enterococcus, which has been associated with hepatocyte death, in OCA-treated animals is consistent with our observed improvements in AST and in liver function, as evidenced by higher serum albumin.

Novel prevention strategies for bacterial infections in cirrhosis.

INTRODUCTION: Bacterial infections are a serious complication of cirrhosis, as they can lead to decompensation, multiple organ failure, and/or death. Preventing infections is therefore very relevant. Because gut bacterial translocation is their main pathogenic mechanism, prevention of infections is mostly based on the use of orally administered poorly absorbed antibiotics such as norfloxacin (selective intestinal decontamination). However, antibiotic prophylaxis leads to antibiotic resistance, limiting therapy and increasing morbidity and mortality. Prevention of bacterial infections in cirrhosis should therefore move away from antibiotics. AREAS COVERED: This review focuses on various potentially novel methods to prevent infections in cirrhosis focusing on non-antibiotic strategies. The use of probiotics, nonselective intestinal decontamination with rifaximin, prokinetics and beta-blockers or fecal microbiota transplant as means of targeting altered gut microbiota, bile acids and FXR agonists are all potential alternatives to selective intestinal decontamination. Prokinetics and beta-blockers can improve intestinal motility, while bile acids and FXR agonists help by improving the intestinal barrier. Finally, granulocyte colony stimulating factor (G-CSF) and statins are emerging therapeutic strategies that may improve immune dysfunction in cirrhosis. EXPERT OPINION: Evidence for these strategies has been restricted to animal studies and proof-of concept studies but we expect this to change in coming years.