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

Abstract

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.

Establishment and validation of a prognosis nomogram for MIMIC-III patients with liver cirrhosis complicated with hepatic encephalopathy

“…According to reports, PPI could increase the mortality of patients with liver cirrhosis and HE without active gastrointestinal bleeding [ 47 ]. However, a multicenter retrospective study found that for patients with cirrhosis, frequent treatment with PPI administration may increase the risk of HE incidence without worsening the prognosis of the patients [ 48 ]. In another single-center prospective study of 489 cirrhosis patients with or without acute-on-chronic liver failure, studied in subgroups with or without PPI therapy, it was found that PPI use did not increase mortality or the risk of HE in patients with cirrhosis [ 49 ].…”

The impact of proton pump inhibitors in liver diseases and the effects on the liver

“…Previous studies have shown that PPIs are associated with the development of HE (Table 2). 2,10,54,59–62 Several meta‐analyses have also confirmed a positive association between PPIs and the development of HE 66–70 . A recent meta‐analysis showed a pooled odds ratio (OR) and 95% confidence interval (CI) of 1.97 (1.51–2.58), suggesting an association between PPIs and HE 71 .…”

Effects of Proton Pump Inhibitors in Cirrhotic Patients: What Do We Really Know?

“…11,12 Furthermore, because it remains difficult to find a consensus regarding the real side effects attributable to this class of drugs in the general population, the correct definition of these effects in patients with liver cirrhosis is even more complicated and the real effect of PPIs on cirrhotic patients remains controversial. [13][14][15][16][17] Considering that liver cirrhosis is per se a condition in which it is common to find alterations in the intestinal microbiome, anemia, encephalopathy, and a greater susceptibility to infections, it is necessary to clarify what is the impact of the use of PPIs in this group of patients. Relevantly, it would be important to clarify whether there is a concentration of PPIs intake that can be considered safe and if there is a correlation between the duration of PPIs intake and the onset of side effects or even if the different classes of PPIs have any effects on the outcomes.…”