Proton Pump Inhibitor Initiation and Withdrawal affects Gut Microbiota and Readmission Risk in Cirrhosis.

OBJECTIVES: Cirrhosis is associated with gut microbial dysbiosis, high readmissions and proton pump inhibitor (PPI) overuse, which could be inter-linked. Our aim was to determine the effect of PPI use, initiation and withdrawl on gut microbiota and readmissions in cirrhosis. METHODS: Four cohorts were enrolled. Readmissions study: Cirrhotic inpatients were followed throughout the hospitalization and 30/90-days post-discharge. PPI initiation, withdrawal/continuation patterns were analyzed between those with/without readmissions. Cross-sectional microbiota study: Cirrhotic outpatients and controls underwent stool microbiota analysis. Beneficial autochthonous and oral-origin taxa analysis vis-à-vis PPI use was performed. Longitudinal studies: Two cohorts of decompensated cirrhotic outpatients were enrolled. Patients on chronic unindicated PPI use were withdrawn for 14 days. Patients not on PPI were started on omeprazole for 14 days. Microbial analysis for oral-origin taxa was performed pre/post-intervention. RESULTS: Readmissions study: 343 inpatients (151 on admission PPI) were enrolled. 21 were withdrawn and 45 were initiated on PPI resulting in a PPI use increase of 21%. PPIs were associated with higher 30 (p = 0.002) and 90-day readmissions (p = 0.008) independent of comorbidities, medications, MELD and age. Cross-sectional microbiota: 137 cirrhotics (59 on PPI) and 45 controls (17 on PPI) were included. PPI users regardless of cirrhosis had higher oral-origin microbiota while cirrhotics on PPI had lower autochthonous taxa compared to the rest. Longitudinal studies: Fifteen decompensated cirrhotics tolerated omeprazole initiation with an increase in oral-origin microbial taxa compared to baseline. PPIs were withdrawn from an additional 15 outpatients, which resulted in a significant reduction of oral-origin taxa compared to baseline. CONCLUSIONS: PPIs modulate readmission risk and microbiota composition in cirrhosis, which responds to withdrawal. The systematic withdrawal and judicious use of PPIs is needed from a clinical and microbiological perspective in decompensated cirrhosis.

Mild alcohol consumption is not associated with increased fibrosis in patients with chronic hepatitis C.

BACKGROUND: Excessive alcohol consumption is associated with an increased risk for fibrosis progression and cirrhosis in patients with chronic hepatitis C virus (HCV) infection. However, the impact of mild-moderate alcohol use on the severity of liver fibrosis is unclear. GOALS: The objective of this retrospective study was to assess the impact of mild alcohol consumption on liver fibrosis in patients with chronic HCV. STUDY: 857 patients with well-characterized chronic HCV were enrolled. All underwent liver biopsy to assess hepatic fibrosis. The duration of HCV infection was determined by detailed questionnaires and personal interviews. Alcohol use history was estimated by the Skinner Alcohol Examination Questionnaire. Mild alcohol use was defined as 1 to 3 alcoholic beverages/day (<30 grams/d). Participants were divided into 4 groups based on their average lifetime daily alcohol consumption (essentially none, <1, 1 to 3 or >3 drinks/d) and into quartiles based on their presumed duration of HCV infection (<23, 23 to 31, 31 to 38, or >38 y). RESULTS: Mean alcohol consumption was 2.7 drinks/d; mean duration of HCV infection was 29 years. Daily alcohol consumption was not significantly higher among participants with advanced fibrosis (bridging fibrosis or cirrhosis) when compared with those with none or portal fibrosis (3.2 vs. 2.2 drinks/d, respectively, P=NS). The degree of fibrosis increased significantly with the duration of HCV infection (P<0.0001) and was independent of mild-moderate alcohol consumption. CONCLUSIONS: Mild alcohol use does not seem to adversely affect the severity of fibrosis in patients with chronic HCV.

Complications and use of intracranial pressure monitoring in patients with acute liver failure and severe encephalopathy.

Monitoring of intracranial pressure (ICP) in acute liver failure (ALF) is controversial as a result of the reported complication risk (approximately 20%) and limited therapeutic options for intracranial hypertension. Using prospectively collected information from 332 patients with ALF and severe encephalopathy, we evaluated a recent experience with ICP monitoring in the 24 centers constituting the U.S. ALF Study Group. Special attention was given to the rate of complications, changes in management, and outcome after liver transplantation (LT). ICP monitoring was used in 92 patients (28% of the cohort), but the frequency of monitoring differed between centers (P < 0.001). ICP monitoring was strongly associated with the indication of LT (P < 0.001). A survey performed in a subset of 58 patients with ICP monitoring revealed intracranial hemorrhage in 10.3% of the cohort, half of the complications being incidental radiological findings. However, intracranial bleeding could have contributed to the demise of 2 patients. In subjects listed for LT, ICP monitoring was associated with a higher proportion of subjects receiving vasopressors and ICP-related medications. The 30-day survival post-LT was similar in both monitored and nonmonitored groups (85% vs. 85%). In conclusion, the risk of intracranial hemorrhage following ICP monitoring may have decreased in the last decade, but major complications are still present. In the absence of ICP monitoring, however, patients listed for LT appear to be treated less aggressively for intracranial hypertension. In view of the high 30-day survival rate after LT, future studies of the impact of intracranial hypertension should also focus on long-term neurological recovery from ALF.