Letter: proton pump inhibitors and prognosis of cirrhosis – searching for the balance point

Schiavon, Leonardo Lucca; Silva, T. E.; Fischer, Josiane; Narciso-Schiavon, Janaína Luz

doi:10.1111/apt.13873

Cited by 5 publications

(9 citation statements)

References 7 publications

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“…The elevated risk of HE for PPI users was consistent regardless of the study design, definition of PPI use, study location, type of advanced liver disease, and outcomes analyzed. Previous studies revealed that HE was a predictor of PPI therapy[26,27], which suggests that the elevated risk of HE for PPI users may be affected by confounding by indication. However, the sensitivity analysis focusing on patients without past HE episodes showed a similar result.…”

Section: Discussionmentioning

confidence: 99%

Association of proton pump inhibitors with risk of hepatic encephalopathy in advanced liver disease: A meta-analysis

Tantai

Yang

Wei

et al. 2019

WJG

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BACKGROUND Several studies have explored the association between the use of proton pump inhibitors (PPIs) and the risk of developing hepatic encephalopathy (HE) in patients with advanced liver disease. However, the evidence-based conclusions are controversial. We hypothesized that using PPIs may increase the risk of HE in patients with advanced liver disease. If confirmed, clinicians must strictly adhere to the indications for PPI treatment in this population. AIM To evaluate the pooled risk of HE in patients with advanced liver disease who use PPIs. METHODS Three electronic databases (PubMed, EMBASE, and the Cochrane Library) were searched from the date of database inception through January 8, 2019 to identify comparative studies evaluating the association between PPI use and the risk of HE. Data from the included studies were extracted. The random-effects model was used for pooling risk estimates and the corresponding 95% confidence intervals (CIs). Subgroup and sensitivity analyses were also performed. RESULTS In total, 4342 patients from five case-control studies and 188053 patients from four cohort studies were included in this analysis. In patients with advanced liver disease, PPI use was associated with an elevated risk of developing HE, with significant heterogeneity. The pooled odds ratio for case-control studies was 2.58 (95%CI: 1.68-3.94, I 2 = 72%). The pooled RR for cohort studies was 1.67 (95%CI: 1.30-2.14, I 2 = 67%). The results of the subgroup analyses suggested that the heterogeneity may be the result of differences in the study designs and the definitions of PPI use. The sensitivity and subgroup analyses did not alter our findings. CONCLUSION In patients with advanced liver disease, PPI use is associated with an elevated risk of HE. Future large prospective studies are needed to confirm this association.

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Section: Discussionmentioning

confidence: 99%

Association of proton pump inhibitors with risk of hepatic encephalopathy in advanced liver disease: A meta-analysis

Tantai

Yang

Wei

et al. 2019

WJG

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“…The developed practical guidance is based on information from the product information (Table ) and data extracted from 69 articles included in the literature review (Figure ) . Twelve of the included studies focused on pharmacokinetics (Table ), 51 on safety, and six studied both safety and pharmacokinetics of PPIs.…”

Section: Resultsmentioning

confidence: 99%

“…Thirty‐seven articles studied the safety of PPIs as a group in patients with cirrhosis (Table S1) . These studies mostly focused on the risk of spontaneous bacterial peritonitis or infections in general.…”

Section: Resultsmentioning

confidence: 99%

“…Twenty‐four observational studies (level 3 and 4) and seven systematic reviews (level 2) explored the risk of spontaneous bacterial peritonitis with PPI use in cirrhotics. All meta‐analyses detected a significant association between PPI use and the development of spontaneous bacterial peritonitis .…”

Section: Resultsmentioning

confidence: 99%

“…Six observational studies (level 3, 4) looked at the risk of HE with the use of PPIs [6,8,[69][70][71][72]. Four found an increased risk of HE with PPI use in cirrhotics [6,8,69,70], while two did not [71,72]. The case-control study of Tsai and colleagues [8] provided sub-analyses per PPI and per dose and duration of treatment.…”

Section: Risk Of Hementioning

confidence: 99%

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Safe use of proton pump inhibitors in patients with cirrhosis

Weersink

Bouma

Burger

et al. 2018

Brit J Clinical Pharma

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AimsProton pump inhibitors (PPIs) belong to the most frequently used drugs, also in patients with cirrhosis. PPIs are extensively metabolized by the liver, but practice guidance on prescribing in cirrhosis is lacking. We aim to develop practical guidance on the safe use of PPIs in patients with cirrhosis.MethodsA systematic literature search identified studies on the safety (i.e. adverse events) and pharmacokinetics of PPIs in cirrhotic patients. This evidence and data from the product information was reviewed by an expert panel who classified drugs as safe; no additional risks known; additional risks known; unsafe; or unknown. Guidance was aimed at the oral use of PPIs and categorized by the severity of cirrhosis, using the Child–Turcotte–Pugh (CTP) classification.ResultsA total of 69 studies were included. Esomeprazole, omeprazole and rabeprazole were classified as having ‘no additional risks known’. A reduction in maximum dose of omeprazole and rabeprazole is recommended for CTP A and B patients. For patients with CTP C cirrhosis, the only PPI advised is esomeprazole at a maximum dosage of 20 mg per day. Pantoprazole and lansoprazole were classified as unsafe because of 4‐ to 8‐fold increased exposure. The use of PPIs in cirrhotic patients has been associated with the development of infections and hepatic encephalopathy and should be carefully considered.ConclusionsWe suggest using esomeprazole, omeprazole or rabeprazole in patients with CTP A or B cirrhosis and only esomeprazole in patients with CTP C. Pharmacokinetic changes are also important to consider when prescribing PPIs to vulnerable, cirrhotic patients.

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The prognosis and incidence of hepatic encephalopathy of patients with liver cirrhosis treated with proton pump inhibitors

et al. 2021

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Gastrointestinal bleeding, hepatic encephalopathy (HE), and hepatocarcinogenesis are associated with the prognosis of patients with liver cirrhosis (LC). Proton pump inhibitors (PPIs) have been used to prevent bleeding, however the effects of PPIs on overall survival have not yet been elucidated. Therefore, this multicenter retrospective study aimed to assess the effect of PPI on the prognosis and HE occurrence of the patients with liver cirrhosis in Japan.A total of 456 patients diagnosed with LC at the 4 institutes during the study period (2010–2014) were assessed. PPI-treated and non-treated patients were compared using propensity score matching analysis. Primary and secondary endpoints of the study were set as the occurrence of HE and overall survival, respectively.A comparison of all cases showed a significantly poorer hepatic reserve function in the PPI-treated patients. The propensity-score matching analysis was performed and 120 PPI-treated patients were 1:1 matched with non-treated patients. The analysis revealed a higher incidence of HE in the PPI-treated than in the non-treated patients (P = .032; hazard ratio [HR], 2.162; 95% confidence interval [CI], 1.066–4.176), but the prognosis of PPI-treated patients was no worse than that of non-treated patients (P = .676; HR, 1.101; 95% CI, 0.702–1.726).This retrospective study showed that PPI administration for the patients with liver cirrhosis may partly be related to the increased incidence of HE but not worsen the patient prognosis.

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Letter: proton pump inhibitors and prognosis of cirrhosis – searching for the balance point

Abstract: Linked Content This article is linked to Dultz et al paper. To view this article visit https://doi.org/10.1111/apt.13061.

Cited by 5 publications

References 7 publications

Association of proton pump inhibitors with risk of hepatic encephalopathy in advanced liver disease: A meta-analysis

Association of proton pump inhibitors with risk of hepatic encephalopathy in advanced liver disease: A meta-analysis

Safe use of proton pump inhibitors in patients with cirrhosis

The prognosis and incidence of hepatic encephalopathy of patients with liver cirrhosis treated with proton pump inhibitors

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