Proton pump inhibitor use increases mortality and hepatic decompensation in liver cirrhosis

Roza, Marianne Anastasia De; Kai, Lim; Kam, Jia Wen; Chan, Yiong Huak; Kwek, Andrew; Ang, Tiing Leong; Hsiang, John

doi:10.3748/wjg.v25.i33.4933

Cited by 42 publications

(35 citation statements)

References 35 publications

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“…Among the 12 patients in the PH group, 11 were taking proton pump inhibitors (PPIs), so the relationship between the ongoing use of PPIs for the treatment of varices was also taken into consideration (12)(13)(14)(15). It has been reported that the partial changes in the gut microbiota caused by PPI usage are similar to the changes caused by the progression of liver cirrhosis, and increased inflow of oral flora to the intestines might create an intestinal environment that is a risk factor for the progression of liver cirrhosis, spontaneous bacterial peritonitis, and hepatic encephalopathy (9,(16)(17)(18)(19). The levels of genera (Lactobacillales, Streptococcus, Selenomonas, Veillonella, Campylobacter, and Haemophilus) have been reported to be high in PPI users (20).…”

Section: Discussionmentioning

confidence: 99%

Exploratory Research on the Relationship between Human Gut Microbiota and Portal Hypertension

et al. 2020

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Objective The relationship between gut microbiota and portal hypertension remains unclear. We investigated the characteristics of the gut microbiota in portal hypertension patients with esophago-gastric varices and liver cirrhosis. Methods Thirty-six patients (12 patients with portal hypertension, 12 healthy controls, and 12 non-cirrhosis patients) were enrolled in this university hospital study. Intestinal bacteria and statistical analyses were performed up to the genus level using the terminal restriction fragment length polymorphism method targeting 16S ribosomal RNA genes, with diversified regions characterizing each bacterium. Results Levels of Lactobacillales were significantly higher (p=0.045) and those of Clostridium cluster IV significantly lower (p=0.014) in patients with portal hypertension than in other patients. This Clostridium cluster contains many butanoic acid-producing strains, including Ruminococcace and Faecalibacterium prausnitzii. Clostridium cluster IX levels were also significantly lower (p=0.045) in portal hypertension patients than in other patients. There are many strains of Clostridium that produce propionic acid, and the effects on the host and the function of these bacterial species in the human intestine remain unknown. Regarding the Bifidobacterium genus, which is supposed to decrease as a result of cirrhosis, no significant decrease was observed in this study. Conclusion In the present study, we provided information on the characteristics of the gut microbiota of portal hypertension patients with esophago-gastric varices due to liver cirrhosis. In the future, we aim to develop probiotic treatments following further analyses that include the species level, such as the intestinal flora analysis method and next-generation sequencers.

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Section: Discussionmentioning

confidence: 99%

Exploratory Research on the Relationship between Human Gut Microbiota and Portal Hypertension

et al. 2020

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“…An early meta-analysis published in 2015 showed that PPI use was not associated with increased mortality in patients with cirrhosis [11]. However, only four cohort studies [14,16,17,19] were included in the present study, and many related cohort studies have been published since the previous meta-analysis [18,[20][21][22][23][24][25][26][27][28][29][30][31][32][33][34]. In addition, it remains unknown…”

Section: Introductionmentioning

confidence: 89%

“…Overall, 21 cohort studies with 20,899 patients and 7457 death events were included, of which 16 were retrospective cohort studies [16][17][18][19][22][23][24][25][26][27][28][29][30][31][32][33], while the other five were prospective cohort [14,15,20,21,34]. As for the ethnicity of the patients, 12 studies included Caucasian patients [15,16,18,[20][21][22]24,28,29,[32][33][34], 7 included Asians [17,19,23,25,26,30,31], and the remaining 2 included patients with mixed ethnicity [14,27]. Most of the studies included patients with hospitalized patients with cirrhosis without serious clinical complications [14][15][16][17][18]…”

Section: Study Characteristics and Quality Evaluationmentioning

confidence: 99%

“…As for the ethnicity of the patients, 12 studies included Caucasian patients [15,16,18,[20][21][22]24,28,29,[32][33][34], 7 included Asians [17,19,23,25,26,30,31], and the remaining 2 included patients with mixed ethnicity [14,27]. Most of the studies included patients with hospitalized patients with cirrhosis without serious clinical complications [14][15][16][17][18][20][21][22][23][24][28][29][30]32,34], while six studies included cirrhotic patients with SBP [19,26], HE [25], Clostridium difficile infection [27], pneumonia [31], and after transjugular intrahepatic portosystemic shunt [33], respectively. The mean ages of the patients varied from 53 to 63 years, and the proportions of male patients varied from 53% to 77%.…”

Section: Study Characteristics and Quality Evaluationmentioning

confidence: 99%

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Proton pump inhibitor use and mortality in patients with cirrhosis: a meta-analysis of cohort studies

Wu¹,

Zhang

Yu³

et al. 2020

Bioscience Reports

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Background: Proton pump inhibitor (PPI) is commonly used in patients with cirrhosis. However, some studies demonstrated that PPI use was associated with adverse outcome in patients with cirrhosis. We aimed to perform a meta-analysis of cohort studies to evaluate the association between PPI use and mortality in cirrhotic patients. Methods: Relevant studies were obtained via search of PubMed and Embase databases. A randomized-effect model was used to pool the results. Subgroup analyses were performed to evaluate the source of heterogeneity. Results: Overall, 21 cohort studies with 20,899 patients and 7457 death events were included. The pooled results with a randomized-effect model showed that PPI use was associated with significantly increased risk of mortality in patients with cirrhosis (adjusted relative risk [RR] = RR: 1.39, P<0.001) with considerable heterogeneity (I2=73%). Subgroup analyses showed that characteristics such as patient ethnicity, sample size, definition of PPI use, and complications of patients did not affect the association. However, the association between PPI use and mortality was independent of study characteristics including patient ethnicity, sample size, complications, definition of PPI use, and follow-up duration. However, the association between PPI use and mortality in cirrhotic patients was significant in retrospective studies (RR: 1.40, P<0.001), but not in prospective studies (RR: 1.34, P=0.33). Conclusions: PPI use may be associated with moderately increased mortality in cirrhotic patients. Although prospective cohort studies are needed to validate our findings, PPI should only prescribed to cirrhotic patients with indications for the treatment.

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“…(73) Greater PPI exposure has also been reported to increase the risk of liver-related hospitalization and mortality. (74,75) In critically ill patients with decompensated cirrhosis admitted to a medical ICU, NSAIDs were associated with 46.1% of the instances of preventable medication-related harm, including melena or hematemesis and worsening renal function (reduced creatinine clearance). (14) Other studies demonstrated a decreased glomerular filtration rate by ~30% in patients with compensated cirrhosis, (42,43) explained by the inhibition of prostaglandin synthesis, which decreases vasodilation of the afferent renal arterioles.…”

Section: Medication Pkpd Change Clinical Impact Remarksmentioning

confidence: 99%

Improving Medication‐Related Outcomes in Chronic Liver Disease

Hayward

Weersink

2020

Hepatol. Commun.

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Patients with chronic liver disease (CLD) are becoming increasingly complex due to the rising prevalence of multimorbidity and polypharmacy. Medications are often essential to manage the underlying liver disease, complications of cirrhosis and portal hypertension, and comorbidities. However, medication‐related problems (MRPs) have been associated with adverse patient outcomes, including hospitalization and mortality. Factors that can contribute to MRPs in people with CLD are variable and often entwined. This narrative literature review discusses key barriers and opportunities to modify risk factors and improve medication‐related outcomes for people with CLD.

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Proton pump inhibitor use increases mortality and hepatic decompensation in liver cirrhosis

Cited by 42 publications

References 35 publications

Exploratory Research on the Relationship between Human Gut Microbiota and Portal Hypertension

Exploratory Research on the Relationship between Human Gut Microbiota and Portal Hypertension

Proton pump inhibitor use and mortality in patients with cirrhosis: a meta-analysis of cohort studies

Improving Medication‐Related Outcomes in Chronic Liver Disease

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