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El-Azab G, Zakareya T, Abdel Aleem M, Edrees A. Inappropriate use of proton pump inhibitors in patients with liver cirrhosis: a cross-sectional study. Eur J Gastroenterol Hepatol 2025:00042737-990000000-00522. [PMID: 40359285 DOI: 10.1097/meg.0000000000002985] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/15/2025]
Abstract
BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSION 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.
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Affiliation(s)
- Gasser El-Azab
- Hepatology and Gastroenterology Department, National Liver Institute, Menoufia University, Shebeen El-Kom
| | - Talaat Zakareya
- Hepatology and Gastroenterology Department, National Liver Institute, Menoufia University, Shebeen El-Kom
| | | | - Ahmed Edrees
- Hepatology and Gastroenterology Department, National Liver Institute, Menoufia University, Shebeen El-Kom
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El-Azab G. Proton Pump Inhibitors in Patients with Cirrhosis: Pharmacokinetics, Benefits and Drawbacks. Curr Gastroenterol Rep 2024; 26:323-334. [PMID: 39167119 DOI: 10.1007/s11894-024-00943-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/01/2024] [Indexed: 08/23/2024]
Abstract
PURPOSE OF REVIEW 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 FINDINGS 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.
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Affiliation(s)
- Gasser El-Azab
- Hepatology and Gastroenterology Department, National Liver Institute, Menoufia University, Shebin El-Kom, Menoufia, Egypt.
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Craciun A, Botto I, Lopes J, Moura M, Carvalhana S, Cortez-Pinto H, Marinho RT. Influence of COVID-19 on Patients with Esophageal Varices under Prophylactic Endoscopic Band Ligation Therapy. GE PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2024; 31:182-190. [PMID: 38757062 PMCID: PMC11095607 DOI: 10.1159/000531135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 04/25/2023] [Indexed: 05/18/2024]
Abstract
Background and Objectives Endoscopic band ligation (EBL) plays a critical role in patients with clinically significant portal hypertension, as variceal eradication (VE) is essential to prevent further variceal upper gastrointestinal bleeding (GI). The emergence of COVID-19 has led to a dramatic reduction in endoscopic activity. Our study aimed to evaluate the effect of COVID-19 on VE, GI, and 6-month mortality of patients treated with prophylactic EBL therapy. In addition, our goal was to identify the risk factors for our proposed outcomes. Methods A single-center retrospective cohort study included patients with esophageal varices treated with prophylactic EBL therapy between 2017 and 2021. To demonstrate the impact of COVID-19 on two independent groups on prophylactic EBL therapy with 1 year of follow-up, March 2019 was selected as the cut-off date. Clinical, laboratory, and endoscopic data were recovered from electronic reports. Results Ninety-seven patients underwent 398 prophylactic EBL sessions, 75 men (77.3%) with mean age 59 ± 12 years. Most achieved VE (60.8%), 14.4% had GI bleeding post-therapy, and 15.5% died at 6 months. The rate of variceal obliteration was significantly lower in the pandemic group (40.9% vs. 77.4% in the pre-pandemic group, p = 0.001). Mean number of EBL sessions and pandemic group were independently associated with incomplete VE, while MELD-Na, portal vein thrombosis and failed VE were identified as risk factors associated with mortality at 6 months. Conclusions Almost 60% of patients in the pandemic group failed to eradicate esophageal varices. Failure to achieve this result conferred a higher risk of GI bleeding and death at 6 months, the latter also significantly associated with the MELD-Na score and portal vein thrombosis. Our study is among the first to demonstrate the impact of COVID-19 in patients receiving prophylactic EBL therapy.
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Affiliation(s)
- Ana Craciun
- Gastroenterology and Hepatology Department, Hospital de Santa Maria, Lisbon, Portugal
- Clínica Universitária de Gastrenterologia, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal
| | - Inês Botto
- Gastroenterology and Hepatology Department, Hospital de Santa Maria, Lisbon, Portugal
| | - João Lopes
- Gastroenterology and Hepatology Department, Hospital de Santa Maria, Lisbon, Portugal
| | - Miguel Moura
- Gastroenterology and Hepatology Department, Hospital de Santa Maria, Lisbon, Portugal
| | - Sofia Carvalhana
- Gastroenterology and Hepatology Department, Hospital de Santa Maria, Lisbon, Portugal
| | - Helena Cortez-Pinto
- Gastroenterology and Hepatology Department, Hospital de Santa Maria, Lisbon, Portugal
- Clínica Universitária de Gastrenterologia, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal
| | - Rui Tato Marinho
- Gastroenterology and Hepatology Department, Hospital de Santa Maria, Lisbon, Portugal
- Clínica Universitária de Gastrenterologia, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal
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Zeng HT, Zhang ZL, Lin XM, Peng MS, Wang LS, Xu ZL. Aluminum phosphate gel reduces early rebleeding in cirrhotic patients with gastric variceal bleeding treated with histoacryl injection therapy. World J Gastrointest Endosc 2023; 15:153-162. [PMID: 37034972 PMCID: PMC10080557 DOI: 10.4253/wjge.v15.i3.153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Revised: 11/26/2022] [Accepted: 03/01/2023] [Indexed: 03/16/2023] Open
Abstract
BACKGROUND Esophageal-gastro varices bleeding (EGVB) is the most widely known cause of mortality in individuals with cirrhosis, with an occurrence rate of 5% to 15%. Among them, gastric varices bleeding (GVB) is less frequent than esophageal varices bleeding (EVB), but the former is a more critical illness and has a higher mortality rate. At present, endoscopic variceal histoacryl injection therapy (EVHT) is safe and effective, and it has been recommended by relevant guidelines as the primary method for the treatment of GVB. However, gastric varices after endoscopic treatment still have a high rate of early rebleeding, which is mainly related to complications of its treatment, such as bleeding from drained ulcers, rebleeding of varices etc. Therefore, preventing early postoperative rebleeding is very important to improve the quality of patient survival and outcomes. AIM To assess the efficacy of aluminium phosphate gel (APG) combined with proton pump inhibitor (PPI) in preventing early rebleeding after EVHT in individuals with GVB. METHODS Medical history of 196 individuals with GVB was obtained who were diagnosed using endoscopy and treated with EVHT in Shenzhen People's Hospital from January 2016 to December 2021. Based on the selection criteria, 101 patients were sorted into the PPI alone treatment group, and 95 patients were sorted into the PPI combined with the APG treatment group. The incidences of early rebleeding and corresponding complications within 6 wk after treatment were compared between both groups. Statistical methods were performed by two-sample t-test, Wilcoxon rank sum test and χ 2 test. RESULTS No major variations were noted between the individuals of the two groups in terms of age, gender, Model for End-Stage Liver Disease score, coagulation function, serum albumin, hemoglobin, type of gastric varices, the dose of tissue glue injection and EV that needed to be treated simultaneously. The early rebleeding rate in PPI + APG group was 3.16% (3/95), which was much lower than that in the PPI group (12.87%, 13/101) (P = 0.013). Causes of early rebleeding: the incidence of gastric ulcer bleeding in the PPI + APG group was 2.11% (2/95), which was reduced in comparison to that in the PPI group (11.88%, 12/101) (P = 0.008); the incidence of venous bleeding in PPI + APG group and PPI group was 1. 05% (1/95) and 0.99% (1/101), respectively, and there was no significant difference between them (0.999). The early mortality rate was 0 in both groups within 6 wk after the operation, and the low mortality rate was related to the timely hospitalization and active treatment of all patients with rebleeding. The overall incidence of complications in the PPI + APG group was 12.63% (12/95), which was not significantly different from 13.86% (14/101) in the PPI group (P = 0.800). of abdominal pain in the PPI + APG group was 3.16% (3/95), which was lower than that in the PPI group (11.88%, 12/101) (P = 0.022). However, due to aluminum phosphate gel usage, the incidence of constipation in the PPI + APG group was 9.47% (9/95), which was higher than that in the PPI group (1.98%, 2/101) (P = 0.023), but the health of the patients could be improved by increasing drinking water or oral lactulose. No patients in either group developed spontaneous peritonitis after taking PPI, and none developed hepatic encephalopathy and ectopic embolism within 6 wk of EVHT treatment. CONCLUSION PPI combined with APG can significantly reduce the incidence of early rebleeding and postoperative abdominal pain in cirrhotic patients with GVB after taking EVHT.
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Affiliation(s)
- Hao-Tian Zeng
- Department of Gastroenterology, The Second Clinical Medical College, Jinan University, Shenzhen 518000, Guangdong Province, China
| | - Zhu-Liang Zhang
- Department of Gastroenterology, The Second Clinical Medical College, Jinan University, Shenzhen 518000, Guangdong Province, China
| | - Xi-Min Lin
- Department of Gastroenterology, The Second Clinical Medical College, Jinan University, Shenzhen 518000, Guangdong Province, China
| | - Min-Si Peng
- Department of Gastroenterology, The Second Clinical Medical College, Jinan University, Shenzhen 518000, Guangdong Province, China
| | - Li-Sheng Wang
- Department of Gastroenterology, Shenzhen People’s Hospital, The Second Clinical Medical College, Jinan University, Shenzhen 518000, Guangdong Province, China
| | - Zheng-Lei Xu
- Department of Gastroenterology, Shenzhen People’s Hospital, The Second Clinical Medical College, Jinan University, Shenzhen 518000, Guangdong Province, China
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Elseidy SA, Sayed A, Awad AK, Mandal D, Mostafa M, Adigun A, Vorla M, Zamani Z, Iqbal A. PPI efficacy in the reduction of variceal bleeding incidence and mortality, a meta-analysis. THE EGYPTIAN JOURNAL OF INTERNAL MEDICINE 2022. [DOI: 10.1186/s43162-022-00156-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Objective
To review the efficacy and safety of proton pump inhibitors (PPIs) in gastroesophageal varices (GEVs).
Methods
We searched PubMed MEDLINE, Scopus, and Web of Science for studies that measured the effect of PPI for prophylaxis and treatment of post-band ligation ulcers up to July 20, 2021. We included studies that measured the effect of PPI as treatment or prophylaxis for post-band ligation ulcers; articles that were published in peer-reviewed international journals and had enough data for qualitative and quantitative analysis were included with no language restriction. Heterogeneity was evaluated using the inconsistency (I2) and chi-squared (χ2) test. I2 > 50% was considered substantial heterogeneity in the studies, and a P value less than 0.05 was considered statistically significant. The data was continuous, and we used the standardized mean difference (MD) and risk ratio (RR) with a 95% confidence interval to assess the estimated effect measure.
Results
A total of 7 studies with 2030 patients were included in our study of which 1480 participants were males (72%) and 550 females (18%). Mean age was 59.7 years old. Rebleeding post-band ligation was compared between PPI and placebo with significant favor for PPI (p = 0.00001). The pooled risk ratio was 0.53 (95% CI of 0.41, 0.68); furthermore, bleeding-related death at a 1-month period was compared between PPI and placebo with significant favor for PPI (p = 0.00001). The pooled risk ratio was significant at 0.33 (95% CI of 0.20, 0.53). The length of hospital stay postoperative was compared between PPI and placebo with cumulative mean difference of 0.13 (95% CI of −1.13, 1.39), yet without significance.
Conclusions
The study suggests a twofold reduction in the risk of bleeding and a threefold reduction in the risk of bleeding-related death with the use of PPI following EVL.
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Zhang ZL, Peng MS, Chen ZM, Long T, Wang LS, Xu ZL. Effect of aluminum phosphate gel on prevention of early rebleeding after ligation of esophageal variceal hemorrhage. World J Gastrointest Surg 2021; 13:1651-1659. [PMID: 35070070 PMCID: PMC8727181 DOI: 10.4240/wjgs.v13.i12.1651] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Revised: 07/14/2021] [Accepted: 11/14/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Liver cirrhosis is the main cause of portal hypertension. The leading cause of death in patients with liver cirrhosis is its most common complication, esophageal variceal bleeding (EVB). Endoscopic variceal ligation (EVL) is recommended by many guidelines to treat EVB and prevent rebleeding; however, esophageal ulcers occur after treatment. Delayed healing of ulcers and unhealed ulcers lead to high rebleeding and mortality rates. Thus, the prevention of early postoperative rebleeding is of great significance in improving the quality of life and prognosis of patients. AIM To evaluate the efficacy of aluminum phosphate gel (APG) plus a proton pump inhibitor (PPI) in the prevention of early rebleeding after EVL in patients with EVB. METHODS The medical records of 792 patients who were diagnosed with EVB and in whom bleeding was successfully stopped by EVL at Shenzhen People's Hospital, Guangdong Province, China from January 2015 to December 2020 were collected. According to the study inclusion and exclusion criteria, 401 cases were included in a PPI-monotherapy group (PPI group), and 377 cases were included in a PPI and APG combination therapy (PPI + APG) group. We compared the incidence rates of early rebleeding and other complications within 6 wk after treatment between the two groups. The two-sample t-test, Wilcoxon rank-sum test, and chi-squared test were adopted for statistical analyses. RESULTS No significant differences in age, sex, model for end-stage liver disease score, coagulation function, serum albumin level, or hemoglobin level were found between the two groups. The incidence of early rebleeding in the PPI + APG group (9/337; 2.39%) was significantly lower than that in the PPI group (30/401; 7.48%) (P = 0.001). Causes of early rebleeding in the PPI group were esophageal ulcer (3.99%, 16/401) and esophageal varices (3.49%, 14/401), while those in the PPI + APG group were also esophageal ulcers (5/377; 1.33%) and esophageal varices (4/377; 1.06%); such causes were significantly less frequent in the PPI + APG group than in the PPI group (P = 0.022 and 0.024, respectively). The early mortality rate within 6 wk in both groups was 0%, which was correlated with the timely rehospitalization of all patients with rebleeding and the conduct of emergency endoscopic therapy. The incidence of adverse events other than early bleeding in the PPI + APG group (28/377; 7.43%) was significantly lower than that in the PPI group (63/401; 15.71%) (P < 0.001). The incidence of chest pain in the PPI + APG group (9/377; 2.39%) was significantly lower than that in the PPI group (56/401; 13.97%) (P < 0.001). The incidence of constipation in the PPI + APG group (16/377; 4.24%) was significantly higher than that in the PPI group (3/401; 0.75%) (P = 0.002) but constipation was relieved after patients drank more water or took lactulose. In the PPI and PPI + APG groups, the incidence rates of spontaneous peritonitis within 6 wk after discharge were 0.50% (2/401) and 0.53% (2/377), respectively, and those of hepatic encephalopathy were 0.50% (2/401) and 0.27% (1/377), respectively, presenting no significant difference (P > 0.999). CONCLUSION PPI + APG combination therapy significantly reduces the incidence of early rebleeding and chest pain in patients with EVB after EVL.
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Affiliation(s)
- Zhu-Liang Zhang
- The Second Clinical Medical College of Jinan University, Shenzhen 518000, Guangdong Province, China
- Department of Gastroenterology, Shenzhen People's Hospital, Shenzhen 518020, Guangdong Province, China
| | - Min-Si Peng
- The Second Clinical Medical College of Jinan University, Shenzhen 518000, Guangdong Province, China
- Department of Gastroenterology, Shenzhen People's Hospital, Shenzhen 518020, Guangdong Province, China
| | - Ze-Ming Chen
- The Second Clinical Medical College of Jinan University, Shenzhen 518000, Guangdong Province, China
- Department of Gastroenterology, Shenzhen People's Hospital, Shenzhen 518020, Guangdong Province, China
| | - Ting Long
- The Second Clinical Medical College of Jinan University, Shenzhen 518000, Guangdong Province, China
- Department of Pathology, Shenzhen People’s Hospital, Shenzhen 518020, Guangdong Province, China
| | - Li-Sheng Wang
- The Second Clinical Medical College of Jinan University, Shenzhen 518000, Guangdong Province, China
- Department of Gastroenterology, Shenzhen People's Hospital, Shenzhen 518020, Guangdong Province, China
| | - Zheng-Lei Xu
- The Second Clinical Medical College of Jinan University, Shenzhen 518000, Guangdong Province, China
- Department of Gastroenterology, Shenzhen People's Hospital, Shenzhen 518020, Guangdong Province, China
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