Proton pump inhibitors increase the severity of hepatic encephalopathy in cirrhotic patients

Abstract

BACKGROUND Liver cirrhosis is the late stage of hepatic fibrosis and is characterized by portal hypertension that can clinically lead to decompensation in the form of ascites, esophageal/gastric varices or encephalopathy. The most common sequelae associated with liver cirrhosis are neurologic and neuropsychiatric impairments labeled as hepatic encephalopathy (HE). Well established triggers for HE include infection, gastrointestinal bleeding, constipation, and medications. Alterations to the gut microbiome is one of the leading ammonia producers in the body, and therefore may make patients more susceptible to HE. AIM To investigate the relationship between the use of proton pump inhibitors (PPIs) and HE in patients with cirrhosis. METHODS This is a single center, retrospective analysis. Patients were included in the study with an admitting diagnosis of HE. The degree of HE was determined from subjective and objective portions of hospital admission notes using the West Haven Criteria. The primary outcome of the study was to evaluate the grade of HE in PPI users versus non-users at admission to the hospital and throughout their hospital course. Secondary outcomes included rate of infection, gastrointestinal bleeding within the last 12 mo, mean ammonia level, and model for end-stage liver disease scores at admission. RESULTS The HE grade at admission using the West Haven Criteria was 2.3 in the PPI group compared to 1.7 in the PPI nonuser group ( P = 0.001). The average length of hospital stay in PPI group was 8.3 d compared to 6.5 d in PPI nonusers ( P = 0.046). Twenty-seven (31.8%) patients in the PPI user group required an Intensive Care Unit admission during their hospital course compared to 6 in the PPI nonuser group (16.7%) ( P = 0.138). Finally, 10 (11.8%) patients in the PPI group expired during their hospital stay compared to 1 in the PPI nonuser group (2.8%) ( P = 0.220). CONCLUSION Chronic PPI use in cirrhotic patients is associated with significantly higher average West Haven Criteria for HE compared to patients that do not use PPIs.

Proton Pump Inhibitor Use Before ICU Admission Is Not Associated With Mortality of Critically Ill Patients

“…PPIs may affect renal function by damaging the glomerular interstitium and increasing the severity of hepatic encephalopathy or the risk of spontaneous bacterial peritonitis in liver cirrhosis patients 17‐19 . Therefore, to clarify the association between PPI and mortality, we also conducted subgroup analyses in patients with liver disease and renal disease.…”

Contribution of the Intestinal Microbiome and Gut Barrier to Hepatic Disorders

“…78 Furthermore, use of proton pump inhibitors (PPIs), which promotes small intestinal bacterial overgrowth, 87 is a risk factor for spontaneous bacterial peritonitis, more severe hepatic encephalopathy, and greater mortality. 88,89 Llorente et al 90 demonstrated that ethanol-fed mice treated with PPIs had overgrowth and increased gut translocation of Enterococcus spp, whereas human patients with ALD who used PPIs also had enrichment of Enterococcus spp in their feces.…”

“…150 HE is a serious complication of ESLD characterized by neurocognitive impairments, including confusion, lethargy, incoherent speech, sleep disturbances, and eventually coma. 88 The pathogenic mechanisms of HE are incompletely understood but appear to involve intestinal dysbiosis, increased production of ammonia by human cells and microbes, and systemic inflammation. 148,151,152 Kang et al 151 found that germ-free mice with liver fibrosis have lower serum levels of ammonia than conventionally housed mice with liver fibrosis, and unlike the conventional mice, the germ-free mice do not develop a neuroinflammatory response.…”

Use of proton pump inhibitors is associated with a higher risk of pneumonia in cirrhotic patients: a systematic review and meta-analysis

“…Therefore, 35 full-length articles were thoroughly reviewed, and 27 articles were further excluded as they did not report the outcome of interest. Finally, 3 cohort and 5 cross-sectional studies with a total of 40,295 participants met the eligibility criteria and were included in the metaanalysis [10][11][12][13][14][15][16][17]. Two of the 3 included cohort studies were published as conference abstracts [10,14].…”

“…The use of PPI may also lead to an increased risk of other types of organspecific bacterial infection. In fact, studies have suggested an increased risk of bacterial pneumonia among cirrhotic patients who use PPIs, although the results are inconsistent [10][11][12][13][14][15][16][17]. The current study aimed to further investigate this risk by identifying all available studies and summarizing their results together.…”