This review articulates the significance of the gut-liver-brain axis in understanding hepatic encephalopathy (HE), emphasizing the role of gut microbiota in influencing liver and brain health. Key treatments like lactulose, rifaximin, probiotics, and fecal microbiota transplantation are examined for their ability to modulate the gut microbiome, thereby mitigating HE symptoms through reduced neurotoxin production and enhanced gut barrier integrity. The synopsis highlights both established and emerging microbial therapies, presenting them as crucial to the management and future strategies of HE. This comprehensive overview explores current therapeutic approaches alongside promising future interventions, suggesting that personalized microbiome-focused treatments may revolutionize HE management.

Proton pump inhibitors (PPIs) are widely prescribed for acid-related disorders; however, concerns have emerged regarding their misuse, particularly in patients with liver cirrhosis. This study aimed to assess the appropriateness of PPI prescriptions in patients with cirrhosis and to identify factors contributing to their overutilization in this patient population.

In this cross-sectional study, 1000 patients with cirrhosis receiving PPIs were enrolled. Data on demographics, clinical parameters, and endoscopic findings were collected, and indications for PPI therapy were assessed according to established guidelines.

Among patients with cirrhosis, 60.5% were prescribed PPIs, with pantoprazole being the most prescribed (55.7%). Inappropriate PPI use was observed in 53.6% of the patients, mainly because of lacking an approved indication (78.54%) or exceeding the recommended treatment duration (21.46%). Causes contributing to misuse included prolonged PPI use postendoscopic band ligation (29.1%), extended treatment for functional dyspepsia (21.46%), failure to discontinue PPIs upon hospital discharge (17.54%), using PPIs for preventing portal hypertensive gastropathy (PHG) or variceal bleeding (16.42%), and stress ulcer prophylaxis in non-ICU patients (15.86%). Multivariate analysis identified independent predictors of inappropriate PPI use, including Child classification C, Mayo End-Stage Liver Disease score greater than 18, hepatocellular carcinoma, and previous variceal bleeding, whereas hematemesis was identified as an independent predictor of appropriate use.

This study underscores the prevalent inappropriate prescription of PPIs in patients with liver cirrhosis, particularly in those with advanced liver disease or a history of variceal bleeding. Enhancing prescribing practices and adhering to evidence-based guidelines are essential to mitigate the risks associated with PPI misuse in patients with cirrhosis.

This review explores the pharmacokinetics, benefits, and risks of proton pump inhibitors (PPIs) in cirrhotic patients, focusing on the appropriateness of their use and potential adverse effects.

Recent studies highlight significant pharmacokinetic alterations in PPIs among cirrhotic patients, with marked increases in lansoprazole and pantoprazole exposure and relatively stable levels of esomeprazole. While effective for managing acid-related disorders and post-band ulcer rebleeding, evidence supporting PPI use for portal hypertension-related bleeding is lacking. Emerging research suggests potential adverse effects such as hepatic decompensation, spontaneous bacterial peritonitis, hepatic encephalopathy, and increased mortality, possibly linked to dysbiosis and bacterial translocation. PPI use in cirrhotic patients alters pharmacokinetics significantly, with esomeprazole potentially safer in advanced cirrhosis. The review advises caution in routine PPI use beyond acid-related conditions due to limited evidence and substantial risks. It underscores the need for careful risk-benefit assessments and exploration of alternative therapies. Future research should aim to identify safer management strategies for portal hypertension complications and to develop evidence-based guidelines for PPI use in patients with cirrhosis.

(1) Background: Proton pump inhibitors (PPIs) are commonly prescribed for gastric disorders. In patients with liver cirrhosis, PPI use is associated with an increased risk of spontaneous bacterial peritonitis and increased mortality rates; therefore, they should be used with caution. This study aims to evaluate the appropriateness of PPI prescriptions in hospitalized cirrhotic patients against current clinical guidelines to identify patterns of misuse and guide better prescribing practices. (2) Methods: A retrospective study was conducted on liver cirrhosis inpatients in an internal medicine department from January 2022 to May 2023. The primary measure was the proportion of PPI prescriptions aligned with clinical guidelines. Medical files were entirely reviewed by researchers to assess the appropriateness of PPI prescriptions using the current guidelines. Outcomes included the identification of common reasons for PPI prescription and the rate of inappropriate PPI use among the study population. (3) Results: The study included 189 cirrhotic patients, with PPIs prescribed to 95 (50.2%) patients during hospitalization and 75 (39.7%) patients at discharge. Among those, 47.4% of the inpatients and 34.7% at discharge had no valid indication for PPI administration. The most common reason for PPI prescription during hospital stays was gastritis, followed by antiplatelet use in high-risk patients, ulcers, and upper gastrointestinal bleeding. The most common inappropriate indication was portal hypertensive gastropathy (PHG), followed by treatment with corticosteroids and anticoagulants alone. We did not find an association between PPI administration during hospital stays and infections. Only in 4% of cases patients should have received PPIs and did not. (4) Conclusions: There is a concerning overprescription of PPIs in cirrhotic patients, often deviating from established guidelines. It subjects patients to unnecessary risks. There is an urgent need for increased awareness and adherence to clinical guidelines regarding PPI prescriptions in cirrhotic patients.

Proton pump inhibitors (PPI) are frequently used in patients with cirrhosis.

This study aimed to determine whether PPI use is associated with the prognosis of cirrhotic patients.

We conducted a multicentre retrospective cohort study involving 1485 patients who had experienced hepatic encephalopathy (HE) from 7 referral centres in Korea. The primary outcome was overall survival and secondary outcomes included the development of cirrhotic complications, including recurrent HE, spontaneous bacterial peritonitis (SBP), hepatorenal syndrome (HRS), and gastrointestinal bleeding. Patients treated with PPI with a mean defined daily dose (mDDD) ≥0.5 (high-dose PPI group) were compared to those treated with PPI of an mDDD < 0.5 (No or low-dose PPI group) for each outcome.

Among 1485 patients (median age, 61 years; male, 61%), 232 were assigned to the high-dose PPI group. High-dose PPI use was independently associated with a higher risk of death (adjusted HR [aHR] = 1.71, 95% confidence interval [CI] = 1.38-2.11, p < 0.001). This result was reproducible after propensity score-matching (PSM) (aHR = 1.90, 95% CI = 1.49-2.44, p < 0.001). High-dose PPI use was an independent risk factor of recurrent HE (before PSM: aHR = 2.04, 95% CI = 1.66-2.51, p < 0.001; after PSM: aHR = 2.16, 95% CI = 1.70-2.74, p < 0.001), SBP (before PSM: aHR = 1.87, 95% CI = 1.43-2.43, p < 0.001; after PSM: aHR = 1.76, 95% CI = 1.31-2.36, p = 0.002), HRS (before PSM: aHR = 1.48, 95% CI = 1.02-2.15, p = 0.04; after PSM: aHR = 1.47, 95% CI = 0.95-2.28, p = 0.09), and gastrointestinal bleeding (before PSM: aHR = 1.46, 95% CI = 1.12-1.90, p = 0.006; after PSM: aHR = 1.74, 95% CI = 1.28-2.37, p < 0.001).

The use of high-dose PPI was independently associated with increased risks of mortality and cirrhotic complications.

This editorial describes the contemporary concepts of prevention and management of gastroesophageal variceal bleeding in liver cirrhosis (LC) patients according to the current guidelines. Gastroesophageal variceal bleeding is the most dangerous complication of portal hypertension in LC patients. Risk stratification and determination of an individual approach to the choice of therapeutic measures aimed at their prevention and management has emerged as one of the top concerns in modern hepatology. According to the current guidelines, in the absence of clinically significant portal hypertension, etiological and non-etiological therapies of LC is advisable for the primary preventing gastroesophageal variceal bleeding, whereas its presence serves as an indication for the administration of non-selective β-blockers, among which carvedilol is the drug of choice. Non-selective β-blockers, as well as endoscopic variceal ligation and transjugular intrahepatic portosystemic shunt can be used to prevent recurrence of gastroesophageal variceal bleeding. Pharmacotherapy with vasoactive drugs (terlipressin, somatostatin, octreotide), endoscopic variceal ligation, endovascular techniques and transjugular intrahepatic portosystemic shunt are recommended for the treatment of acute gastroesophageal variceal bleeding. Objective and accurate risk stratification of gastroesophageal variceal bleeding will allow developing individual strategies for their prevention and management, avoiding the first and further decompensation in LC, which will improve the prognosis and survival of patients suffering from it.