Arthur W. Yan

Enteric Dysbiosis Associated with a Mouse Model of Alcoholic Liver Disease

The translocation of bacteria and bacterial products into the circulation contributes to alcoholic liver disease. Intestinal bacterial overgrowth is common in patients with alcoholic liver disease. The aims of our study were to investigate bacterial translocation, changes in the enteric microbiome, and its regulation by mucosal antimicrobial proteins in alcoholic liver disease. We used a mouse model of continuous intragastric feeding of alcohol or an isocaloric diet. Bacterial translocation occurred prior to changes observed in the microbiome. Quantitative changes in the intestinal microflora of these animals were assessed first using conventional culture techniques in the small and large intestine. Although we found no difference after 1 day or 1 week, intestinal bacterial overgrowth was observed in the gastrointestinal tract of mice fed alcohol for 3 weeks compared with control mice fed an isocaloric liquid diet. Because <20% of all gastrointestinal bacteria can be cultured using conventional methodologies, we performed massively parallel pyrosequencing to further assess the qualitative changes in the intestinal microbiome following alcohol exposure. Sequencing of 16S ribosomal RNA genes revealed a relative abundance of Bacteroidetes and Verrucomicrobia bacteria in mice fed alcohol compared with a relative predominance of Firmicutes bacteria in control mice. With respect to the hosts transcriptome, alcohol feeding was associated with down‐regulation in gene and protein expression of bactericidal c‐type lectins Reg3b and Reg3g in the small intestine. Treatment with prebiotics partially restored Reg3g protein levels, reduced bacterial overgrowth, and lessened alcoholic steatohepatitis. Conclusion: Alcohol feeding is associated with intestinal bacterial overgrowth and enteric dysbiosis. Intestinal antimicrobial molecules are dysregulated following chronic alcohol feeding contributing to changes in the enteric microbiome and to alcoholic steatohepatitis. (HEPATOLOGY 2011)

Aggressive hydration with lactated Ringer's solution reduces pancreatitis after endoscopic retrograde cholangiopancreatography.

BACKGROUND & AIMS Pancreatitis is the most common serious complication of endoscopic retrograde cholangiopancreatography (ERCP). We performed a pilot study to determine whether aggressive periprocedural hydration with lactated Ringers solution reduces the incidence of pancreatitis after ERCP. METHODS Patients who underwent first-time ERCP were randomly assigned to groups (2:1) that received aggressive hydration with lactated Ringers solution (3 mL/kg/h during the procedure, a 20-mL/kg bolus after the procedure, and 3 mL/kg/h for 8 hours after the procedure, n = 39) or standard hydration with the same solution (1.5 mL/kg/h during and for 8 hours after procedure, n = 23). Serum levels of amylase, visual analogue pain scores (scale of 0-10), and volume overload were assessed at baseline and 2, 8, and 24 hours after ERCP. The primary end point, post-ERCP pancreatitis, was defined as hyperamylasemia (level of amylase >3 times the upper limit of normal) and increased epigastric pain (≥3 points on visual analogue scale) persisting for ≥24 hours after the procedure. Secondary end points included hyperamylasemia, increased pain, and volume overload. RESULTS None of the patients who received aggressive hydration developed post-ERCP pancreatitis, compared with 17% of patients who received standard hydration (P = .016). Hyperamylasemia developed in 23% of patients who received aggressive hydration vs 39% of those who received standard hydration (P = .116, nonsignificant); increased epigastric pain developed in 8% of patients who received aggressive hydration vs 22% of those who received standard hydration (P = .146, nonsignificant). No patients had evidence of volume overload. CONCLUSIONS On the basis of a pilot study, aggressive intravenous hydration with lactated Ringers solution appears to reduce the development of post-ERCP pancreatitis and is not associated with volume overload. ClinicalTrials.gov, Number: NCT 01758549.

Bacterial translocation and changes in the intestinal microbiome associated with alcoholic liver disease

Alcoholic liver disease progresses through several stages of tissue damage, from simple steatosis to alcoholic hepatitis, fibrosis, or cirrhosis. Alcohol also affects the intestine, increases intestinal permeability and changes the bacterial microflora. Liver disease severity correlates with levels of systemic bacterial products in patients, and experimental alcoholic liver disease is dependent on gut derived bacterial products in mice. Supporting evidence for the importance of bacterial translocation comes from animal studies demonstrating that intestinal decontamination is associated with decreased liver fibrogenesis. In addition, mice with a gene mutation or deletion encoding receptors for either bacterial products or signaling molecules downstream from these receptors, are resistant to alcohol-induced liver disease. Despite this strong association, the exact molecular mechanism of bacterial translocation and of how changes in the intestinal microbiome contribute to liver disease progression remains largely unknown. In this review we will summarize evidence for bacterial translocation and enteric microbial changes in response to alcoholic liver injury and chronic alcoholic liver disease. We will further describe consequences of intestinal dysbiosis on host biology. We finally discuss how therapeutic interventions may modify the gastrointestinal microflora and prevent or reduce alcoholic liver disease progression.

Randomized trial of 1-week versus 2-week intervals for endoscopic ligation in the treatment of patients with esophageal variceal bleeding.

The appropriate interval between ligation sessions for treatment of esophageal variceal bleeding is uncertain. The optimal interval would provide variceal eradication as rapidly as possible to lessen early rebleeding while minimizing ligation‐induced adverse events. We randomly assigned patients hospitalized with acute esophageal variceal bleeding who had successful ligation at presentation to repeat ligation at 1‐week or 2‐week intervals. Beta‐blocker therapy was also prescribed. Ligation was performed at the assigned interval until varices were eradicated and then at 3 and 9 months after eradication. The primary endpoint was the proportion of patients with variceal eradication at 4 weeks. Four‐week variceal eradication occurred more often in the 1‐week than in the 2‐week group: 37/45 (82%) versus 23/45 (51%); difference = 31%, 95% confidence interval 12%‐48%. Eradication occurred more rapidly in the 1‐week group (18.1 versus 30.8 days, difference = −12.7 days, 95% confidence interval −20.0 to −5.4 days). The mean number of endoscopies to achieve eradication or to the last endoscopy in those not achieving eradication was comparable in the 1‐week and 2‐week groups (2.3 versus 2.1), with the mean number of postponed ligation sessions 0.3 versus 0.1 (difference = 0.2, 95% confidence interval −0.02 to 0.4). Rebleeding at 4 weeks (4% versus 4%) and 8 weeks (11% versus 9%), dysphagia/odynophagia/chest pain (9% versus 2%), strictures (0% versus 0%), and mortality (7% versus 7%) were similar with 1‐week and 2‐week intervals. Conclusion: One‐week ligation intervals led to more rapid eradication than 2‐week intervals without an increase in complications or number of endoscopies and without a reduction in rebleeding or other clinical outcomes; the decision regarding ligation intervals may be individualized based on patient and physician preferences and local logistics and resources. (Hepatology 2016;64:549‐555)

Gastroenterologists' practice patterns for positive fecal occult blood test.

Goals: To evaluate gastroenterologists’ use of esophagogastroduodenoscopy (EGD) for positive fecal occult blood test (FOBT). Background: Colonoscopy is recommended when an FOBT performed for colorectal cancer screening is positive. Guidelines suggest no further evaluation if anemia and gastrointestinal (GI) symptoms are absent. Methods: Online surveys included 4 vignettes: positive FOBT in average-risk adults 50 years of age or older with/without iron-deficiency anemia and with/without upper GI symptoms. For each scenario, respondents were asked if they would perform colonoscopy only, EGD only, colonoscopy+EGD on same day, or colonoscopy followed by EGD on different day if colonoscopy was negative. Results: Surveys were returned by 778 (11%) of 7094 potential responders. In patients without anemia or upper GI symptoms, 65% performed colonoscopy only; 35% added EGD (9% same day, 25% different day). EGD was added in 91% with anemia, 96% with symptoms, and 100% with anemia+symptoms. In patients with positive FOBT alone (no symptoms or anemia), multivariate analysis revealed fear of litigation as the primary factor associated with adding EGD to colonoscopy (odds ratio=4.1; 95% confidence interval, 2.3-7.3). When EGD+colonoscopy were planned for positive FOBT, private practice was associated with performing EGD on a different day (odds ratio=6.3; 95% confidence interval, 2.9-13.5 for private versus academic setting). Conclusions: One third of gastroenterologists perform EGD in addition to colonoscopy for a positive FOBT alone. Fear of litigation is the most important factor in deciding whether to add EGD to colonoscopy. When both procedures are planned, they are more likely to be performed on different days in a private practice setting than in an academic setting.