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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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Eftimie Spitz R, Popa SL, Grad S, Dumitrascu DL, Ismaiel A, Surdea-Blaga T. The Use of Proton Pump Inhibitors in Patients with Liver Cirrhosis: Real Life Experience. J Clin Med 2024; 13:5155. [PMID: 39274368 PMCID: PMC11396469 DOI: 10.3390/jcm13175155] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Revised: 08/12/2024] [Accepted: 08/28/2024] [Indexed: 09/16/2024] Open
Abstract
(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.
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Affiliation(s)
- Raphaël Eftimie Spitz
- Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400000 Cluj-Napoca, Romania; (R.E.S.); (S.G.); (D.L.D.); (A.I.); (T.S.-B.)
| | - Stefan Lucian Popa
- Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400000 Cluj-Napoca, Romania; (R.E.S.); (S.G.); (D.L.D.); (A.I.); (T.S.-B.)
- 2nd Department of Internal Medicine, Emergency County Hospital, 400003 Cluj-Napoca, Romania
| | - Simona Grad
- Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400000 Cluj-Napoca, Romania; (R.E.S.); (S.G.); (D.L.D.); (A.I.); (T.S.-B.)
- 2nd Department of Internal Medicine, Emergency County Hospital, 400003 Cluj-Napoca, Romania
| | - Dan Lucian Dumitrascu
- Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400000 Cluj-Napoca, Romania; (R.E.S.); (S.G.); (D.L.D.); (A.I.); (T.S.-B.)
- 2nd Department of Internal Medicine, Emergency County Hospital, 400003 Cluj-Napoca, Romania
| | - Abdulrahman Ismaiel
- Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400000 Cluj-Napoca, Romania; (R.E.S.); (S.G.); (D.L.D.); (A.I.); (T.S.-B.)
- 2nd Department of Internal Medicine, Emergency County Hospital, 400003 Cluj-Napoca, Romania
| | - Teodora Surdea-Blaga
- Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400000 Cluj-Napoca, Romania; (R.E.S.); (S.G.); (D.L.D.); (A.I.); (T.S.-B.)
- 2nd Department of Internal Medicine, Emergency County Hospital, 400003 Cluj-Napoca, Romania
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Division of Gastroenterohepatology, Faculty of Medicine, Universitas Airlangga/Dr. Soetomo General Academic Teaching Hospital, Surabaya, Indonesia, Maimunah U, Kurniawan AA, Department of Internal Medicine, Faculty of Medicine Universitas Airlangga/Dr. Soetomo General Academic Teaching Hospital, Surabaya, Indonesia, Palayukan A, Department of Internal Medicine, Faculty of Medicine Universitas Airlangga/Dr. Soetomo General Academic Teaching Hospital, Surabaya, Indonesia. Adverse Effects of Long-term Proton Pump Inhibitors in Chronic Liver Disease Patients – A Preliminary Article Review. REVIEW OF CLINICAL PHARMACOLOGY AND PHARMACOKINETICS - INTERNATIONAL EDITION 2024; 38:87-97. [DOI: 10.61873/wway6273] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
Abstract
Background: Proton pump inhibitors (PPIs) are widely prescribed medications for the management of gastroesophageal reflux disease (GERD) and peptic ulcer disease. Despite their efficacy, concerns have emerged regarding their potential adverse effects, particularly in patients with chronic liver disease (CLD). CLD patients often experience gastrointestinal symptoms and may be prescribed PPIs, but the impact of PPI use on liver function and disease progression remains uncertain. Scope: This study aims to evaluate the adverse effects of PPIs on CLD patients through a review of available literature. The scope encompasses a review of studies examining the association between PPI use and liver-related outcomes, including hepatic encephalopathy, hepatic decompensation, liver cirrhosis progression, and mortality, among CLD patients. Method: A scoping review of relevant literature were conducted to identify studies investigating the adverse effects of PPIs in CLD patients. Databases including PubMed and Google Scholar were searched for articles published up to January, 1 2023. Eligible studies were selected based on predefined inclusion criteria. Results: The review identified 27 studies meeting the inclusion criteria, comprising observational studies and meta-analysis. The review revealed a significant association between PPI use and adverse liver outcomes in CLD patients. Specifically, PPI use was associated with increased risk of SBP based on studies reviewed, while other complications remained inconclusive. Conclusion: The findings suggest that PPI use may have detrimental effects on disease progression in CLD patients, Long-term use of PPIs can lead to higher risk of SBP in CLD patients. Clinicians should exercise caution when prescribing PPIs to this vulnerable population and consider alternative treatment options or minimize PPI use to mitigate potential adverse outcomes. Further research is warranted to elucidate the underlying mechanisms, confirm the effect of PPIs toward other complications of CLD and establish guidelines for PPI use in CLD patients.
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Lashen SA, Shamseya MM, Shamseya AM, Hablass FH. Efficacy of Vonoprazan vs. Pantoprazole or Non-acid Suppression in Prevention of Post-variceal Ligation Ulcer Bleeding in Portal Hypertension: A Multi-arm Randomized Controlled Trial. J Clin Exp Hepatol 2023; 13:962-971. [PMID: 37975046 PMCID: PMC10643493 DOI: 10.1016/j.jceh.2023.05.008] [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] [Received: 02/24/2023] [Accepted: 05/15/2023] [Indexed: 11/19/2023] Open
Abstract
BACKGROUND Up-to-date data about the role of acid suppression therapy e.g. proton-pump inhibitors; to reduce post-endoscopic variceal ligation (EVL) ulcer-bleeding are conflicting. Vonoprazan; a recently introduced potassium-competitor acid blocker, has not been studied to prevent post-EVL ulcer/bleeding. The aim was to evaluate the efficacy of vonoprazan vs. pantoprazole or non-acid suppression to prevent post-EVL ulcer/bleeding in portal hypertension patients. MATERIAL AND METHODS We enrolled 275 portal hypertension patients undergoing EVL in a three-arm randomized, single-blind, controlled study. A clinico-laboratory baseline evaluation was performed. Following EVL, patients were randomly and equally assigned to receive vonoprazan 20mg once daily, pantoprazole 40 mg once daily, or no acid suppression therapy. Post-EVL ulcer bleeding, ulcer dimensions, odynophagia as well as vonoprazan safety were evaluated after 2 weeks of EVL. RESULTS Post-EVL ulcer bleeding occurred among 2.15% of vonoprazan, 8.7% of pantoprazole, and 14.2% of the non-acid suppression groups (P < 0.001). Post-ligation ulcer frequency and dimensions were higher among non-acid suppression and pantoprazole groups vs. vonoprazan (P < 0.05). Chest pain and odynophagia were encountered among 73.6% and 54.9% of the non-acid suppression group vs. 39.6% and 45.1% in pantoprazole, and 17.2% and 21.5% in vonoprazan groups, respectively (P < 0.05). There were no vonoprazan-related adverse events. Non-use of vonoprazan was the strongest independent predictor for post-EVL bleeding. CONCLUSION Short course of vonoprazan 20 mg/day is safe and superior to pantoprazole 40 mg/day in the reduction of post-EVL ulcer dimensions at 2 weeks post-EVL, and prevention of ulcer-related bleeding. Acid suppression is superior to no acid suppression to prevent post-EVL complications.
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Affiliation(s)
- Sameh A. Lashen
- Department of Internal Medicine (Hepatology & Gastroenterology Division), Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Mohammed M. Shamseya
- Department of Clinical and Experimental Internal Medicine, Medical Research Institute, Alexandria University, Alexandria, Egypt
| | - Ayman M. Shamseya
- Department of Internal Medicine (Hepatology & Gastroenterology Division), Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Fahmy H. Hablass
- Department of Internal Medicine (Hepatology & Gastroenterology Division), Faculty of Medicine, Alexandria University, Alexandria, Egypt
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Dutta AK, Jain A, Jearth V, Mahajan R, Panigrahi MK, Sharma V, Goenka MK, Kochhar R, Makharia G, Reddy DN, Kirubakaran R, Ahuja V, Berry N, Bhat N, Dutta U, Ghoshal UC, Jain A, Jalihal U, Jayanthi V, Kumar A, Nijhawan S, Poddar U, Ramesh GN, Singh SP, Zargar S, Bhatia S. Guidelines on optimizing the use of proton pump inhibitors: PPI stewardship. Indian J Gastroenterol 2023; 42:601-628. [PMID: 37698821 DOI: 10.1007/s12664-023-01428-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2023] [Accepted: 07/10/2023] [Indexed: 09/13/2023]
Abstract
Proton pump inhibitors (PPIs) have been available for over three decades and are among the most commonly prescribed medications. They are effective in treating a variety of gastric acid-related disorders. They are freely available and based on current evidence, use of PPIs for inappropriate indications and duration appears to be common. Over the years, concerns have been raised on the safety of PPIs as they have been associated with several adverse effects. Hence, there is a need for PPI stewardship to promote the use of PPIs for appropriate indication and duration. With this objective, the Indian Society of Gastroenterology has formulated guidelines on the rational use of PPIs. The guidelines were developed using a modified Delphi process. This paper presents these guidelines in detail, including the statements, review of literature, level of evidence and recommendations. This would help the clinicians in optimizing the use of PPIs in their practice and promote PPI stewardship.
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Affiliation(s)
- Amit Kumar Dutta
- Department of Gastroenterology, Christian Medical College and Hospital, Vellore, 632 004, India.
| | | | - Vaneet Jearth
- Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Ramit Mahajan
- Dayanand Medical College and Hospital, Ludhiana, 141 001, India
| | | | - Vishal Sharma
- Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | | | | | - Govind Makharia
- All India Institute of Medical Sciences, New Delhi, 110 029, India
| | | | - Richard Kirubakaran
- Center of Biostatistics and Evidence Based Medicine, Vellore, 632 004, India
| | - Vineet Ahuja
- All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Neha Berry
- BLK Institute of Digestive and Liver Disease, New Delhi, 201 012, India
| | - Naresh Bhat
- Aster CMI Hospital, Bengaluru, 560 092, India
| | - Usha Dutta
- Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Uday Chand Ghoshal
- Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, 226 014, India
| | - Ajay Jain
- Choithram Hospital and Research Center, Indore, 452 014, India
| | | | - V Jayanthi
- Sri Ramachandra Medical College, Chennai, 600 116, India
| | - Ajay Kumar
- Institute of Digestive and Liver Diseases, BLK - Max Superspeciality Hospital, New Delhi, 201 012, India
| | | | - Ujjal Poddar
- Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, 226 014, India
| | | | - Shivram P Singh
- Kalinga Gastroenterology Foundation, Cuttack, 753 001, India
| | - Showkat Zargar
- Department of Gastroenterology, Sher-i-Kashmir Institute of Medical Sciences, Kashmir, 190 011, India
| | - Shobna Bhatia
- Sir H N Reliance Foundation Hospital, Mumbai, 400 004, India
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China L, Tittanegro T, Crocombe D, Forrest E, Kallis Y, Ryder SD, Wright G, Freemantle N, O'Brien A. Investigating potential confounding by indication when considering the association between proton pump inhibitor use, infection, hepatic encephalopathy and mortality in hospitalised decompensated cirrhosis: a post-hoc analysis of the ATTIRE trial. EClinicalMedicine 2023; 58:101924. [PMID: 37090442 PMCID: PMC10119493 DOI: 10.1016/j.eclinm.2023.101924] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Revised: 02/25/2023] [Accepted: 03/08/2023] [Indexed: 04/25/2023] Open
Abstract
Background Proton pump inhibitors (PPIs) are commonly prescribed to prevent and treat upper gastrointestinal ulceration and bleeding. Studies have identified increased incidence of spontaneous bacterial peritonitis and hepatic encephalopathy (HE) in cirrhosis patients taking PPIs. However, results are conflicting, and as PPIs are prescribed for variceal bleeding, a major risk factor for infection and HE, it is challenging to discern whether these associations are causal. Methods In this post-hoc analysis of the ATTIRE trial, we pooled all patient data to investigate the effects of PPI use on clinical outcomes. ATTIRE was a multicentre, open-label, randomised trial of targeted 20% human albumin solution (HAS) daily infusions versus standard care involving 777 adults with decompensated cirrhosis hospitalised with acute complications and albumin <30 g/L. Study recruitment was between Jan 25, 2016, and June 28, 2019, at 35 hospitals across England, Scotland, and Wales. Key exclusion criteria were advanced hepatocellular carcinoma with life expectancy <8 weeks and patients receiving palliative care. In ATTIRE, patients were grouped by PPI use at trial entry. We studied infection and HE at baseline and incidence of hospital acquired infection, new onset HE, renal dysfunction and mortality. We attempted with propensity score matching to account for differences in disease severity. Findings Overall PPI use at baseline was not associated with increased incidence of infection, renal dysfunction or mortality, but was associated with significantly increased incidence of grade III/IV HE during hospital stay (P = 0.011). This was only significant for those taking intravenous PPIs and these patients had >10 times the incidence of variceal bleeding and near double the 28-day mortality compared to non-PPI patients. However, propensity score matching was not possible as there was such a strong selection of patients for PPI use, that we could not find sufficient non-PPI patients to match to. We found no impact of PPI use on plasma markers of bacterial translocation, infection or systemic inflammation. Interpretations Our real-world data from a completed randomised trial show that PPIs are widely prescribed in the UK and judicious use appears safe in patients hospitalised with decompensated cirrhosis. However, patients prescribed PPIs had fundamentally different phenotypes to those not prescribed PPIs, a form of confounding by indication, which should be strongly considered when interpreting studies and making recommendations about their use. Funding Wellcome Trust and Department of Health and Social Care.
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Affiliation(s)
- Louise China
- Institute of Liver and Digestive Health, University College London, United Kingdom
| | - Thais Tittanegro
- Institute of Liver and Digestive Health, University College London, United Kingdom
| | - Dominic Crocombe
- Institute of Liver and Digestive Health, University College London, United Kingdom
| | - Ewan Forrest
- Glasgow Royal Infirmary, Glasgow, United Kingdom
| | - Yiannis Kallis
- Barts and the London School of Medicine and Dentistry Queen Mary University of London, United Kingdom
| | - Stephen D. Ryder
- National Institute for Health Research Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust and the University of Nottingham, Queens Medical Centre, Nottingham, United Kingdom
| | - Gavin Wright
- Mid and South Essex NHS Foundation Trust, Basildon & Thurrock University Hospitals NHS Foundation Trust, Gastroenterology, Hepatology and Hepatobiliary Medicine, The Royal Free Hospital, University College London, Kings College London, United Kingdom
| | - Nick Freemantle
- Comprehensive Clinical Trials Unit, University College London, United Kingdom
| | - Alastair O'Brien
- Institute of Liver and Digestive Health, University College London, United Kingdom
- Comprehensive Clinical Trials Unit, University College London, United Kingdom
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Chen X, Zhou T, Zhou T, Li Y, Sun X, Cheng B, Zhong N, Lu X, Gao Y. Effects of proton pump inhibitor on gastroesophageal varices in patients with cirrhosis: A randomized controlled trial from China. PORTAL HYPERTENSION & CIRRHOSIS 2023; 2:1-8. [DOI: 10.1002/poh2.37] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Accepted: 11/24/2022] [Indexed: 01/04/2025]
Abstract
AbstractAimsProton pump inhibitors (PPI) are widely used for gastroesophageal varices in patients with cirrhosis after endoscopic therapy, although the effect of PPI on these patients remains controversial. This study aimed to evaluate the effect of PPI on gastroesophageal varices in patients with cirrhosis after endoscopic therapy, including variceal bleeding and adverse events.MethodsCirrhotic patients with endoscopically confirmed gastroesophageal varices were enrolled in this study between May 2017 and June 2019. Eligible patients were randomized into two groups: one group received PPI for 14 days and the other group did not receive PPI treatment (n = 53 in each group). All patients were followed for 8 weeks.ResultsDuring the follow‐up period, three patients (5.66%) in the PPI group experienced variceal bleeding on days 9, 16, and 25 after endoscopic therapy, including two patients with acute bleeding and one with primary prophylaxis. In the non‐PPI group, three patients (5.66%) experienced variceal bleeding on days 7, 42, and 56 after endoscopic therapy, including one patient with acute bleeding and two with secondary prophylaxis (p = 0.990). The incidence of adverse events was similar between the two groups (37.74% vs. 28.30%, p = 0.30).ConclusionsPPI did not appear to reduce variceal bleeding and adverse events in patients with cirrhosis after endoscopic therapy.
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Affiliation(s)
- Xiaoning Chen
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine Shandong University Jinan Shandong China
| | - Tao Zhou
- Department of Geriatric Medicine, Qilu Hospital, Cheeloo College of Medicine Shandong University Jinan Shandong China
| | - Ting Zhou
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine Shandong University Jinan Shandong China
| | - Yueyue Li
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine Shandong University Jinan Shandong China
| | - Xin Sun
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine Shandong University Jinan Shandong China
| | - Baoquan Cheng
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine Shandong University Jinan Shandong China
| | - Ning Zhong
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine Shandong University Jinan Shandong China
| | - Xuefeng Lu
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine Shandong University Jinan Shandong China
| | - Yanjing Gao
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine Shandong University Jinan Shandong China
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Muacevic A, Adler JR, Awan SA, Shaikh AJ, Abbasi AA. Effectiveness of Proton Pump Inhibitor Therapy in the Prevention of Bleeding After Prophylactic Endoscopic Variceal Band Ligation. Cureus 2023; 15:e33932. [PMID: 36819375 PMCID: PMC9937675 DOI: 10.7759/cureus.33932] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/18/2023] [Indexed: 01/19/2023] Open
Abstract
Background Endoscopic variceal ligation (EVL) is a surgical intervention that can work well to curb variceal bleeding in people with liver cirrhosis. However, it could make ulcer bleeding worse and be fatal in some cases. The widespread use of proton pump inhibitors (PPI) in cirrhotic individuals with variceal bleeding is empirical rather than based on scientific data. According to many studies, PPIs reduce the size of post-EVL ulcers. This study aimed to see if PPI use could reduce rebleeding after endoscopy therapy in cirrhotic patients with variceal bleeding. Methodology A retrospective cross-sectional study was conducted at a tertiary care hospital from August 2019 to September 2021. Cirrhotic patients with bleeding gastroesophageal varices (GEVs) who had undergone EVL at the same hospital were enrolled in the study. Medical records were organized, and the sample was divided into two groups based on whether or not PPI was given. Both PPI and non-PPI patients had their endoscopic findings, initial hemostasis outcomes, rebleeding rates, bleeding-related mortality rates, and treatment-related comorbidities compared. Results A total of 46 patients were selected for the study and divided into two groups (PPI group n=28 and non-PPI group n=18). The majority of the patients were males. The PPI group had a mean age of 58.6 ±7.8 years, whereas the non-PPI group had a mean age of 53.6 ±4.4 years. Hepatitis B virus (HBV) infection was the most prevalent cause of cirrhosis in both groups. After endoscopic treatment, three patients (16%) in the non-PPI group suffered a variceal hemorrhage. Bleeding-related fatalities and the time it took for the bleeding to stop varied significantly between the two groups. History of variceal bleeding (relative risk (RR)=1.45; 95% confidence interval (CI), 1.60-7.67; p=0.02), presence of gastric varices (RR=2.23; 95% CI, 2.56-9.832; p=0.035), and not administering PPIs (RR =7.542; 95% CI, 3.98-29.13; p=0.008) were linked with rebleeding. The presence of red concurrent esophageal varices (RR=6.37; 95% CI, 0.562-15.342; p=0.002) and failure to provide PPIs (RR=2.3; 95% CI, 1.621-25.64; p=0.04) were linked with post-EVL bleeding in a multivariate analysis. Conclusions Proton pump inhibitors reduce the occurrence of early bleeding and adverse events after EVL in cirrhotic patients. Not prescribing PPIs and the presence of GEVs were substantially related to a higher risk of bleeding during preventative EVL. Not initiating PPI medication immediately was the sole predictor of bleeding complications in patients who had undergone EVL without gastric varix treatment. To lower the risk of post-EVL ulcer bleeding, we recommend PPI use in patients undergoing EVL.
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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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11
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Garcia-Saenz-de-Sicilia M, Al-Obaid L, Hughes DL, Duarte-Rojo A. Mastering Core Recommendations during HEPAtology ROUNDS in Patients with Advanced Chronic Liver Disease. Semin Liver Dis 2022; 42:341-361. [PMID: 35764316 DOI: 10.1055/a-1886-5909] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Efficient and thorough care of hospitalized patients with advanced chronic liver disease is of utter importance to improve outcomes and optimize quality of life. This requires understanding current evidence and best practices. To facilitate focus on up-to-date knowledge and a practical approach, we have created the HEPA-ROUNDS mnemonic while outlining a practical review of the literature with critical appraisal for the busy clinician. The HEPA-ROUNDS mnemonic provides a structured approach that incorporates critical concepts in terms of prevention, management, and prognostication of the most common complications frequently encountered in patients with advanced chronic liver disease. In addition, implementing the HEPA-ROUNDS mnemonic can facilitate education for trainees and staff caring for patients with advanced chronic liver disease.
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Affiliation(s)
| | - Lolwa Al-Obaid
- Division of Gastroenterology, Washington University School of Medicine in St. Louis, St. Louis, Missouri
| | - Dempsey L Hughes
- Division of Gastroenterology, Hepatology and Nutrition, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Andrés Duarte-Rojo
- Division of Gastroenterology, Hepatology and Nutrition, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
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12
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Wehmeyer MH, Horvatits T, Buchholz A, Krause L, Walter S, Zapf A, Lohse AW, Kluwe J. Stop of proton-pump inhibitor treatment in patients with liver cirrhosis (STOPPIT): study protocol for a prospective, multicentre, controlled, randomized, double-blind trial. Trials 2022; 23:302. [PMID: 35414106 PMCID: PMC9003168 DOI: 10.1186/s13063-022-06232-w] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Accepted: 03/27/2022] [Indexed: 11/21/2022] Open
Abstract
Background Proton-pump inhibitors (PPI) are liberally prescribed in patients with liver cirrhosis. Observational studies link PPI therapy in cirrhotic patients with an increased risk for infectious complications, hepatic encephalopathy and an increased risk for hospitalization and mortality. However, patients with liver cirrhosis are also considered to be at risk for peptic ulcer bleeding. The STOPPIT trial evaluates if discontinuation of a pre-existing PPI treatment delays a composite endpoint of re-hospitalization and/or death in patients (recently) hospitalized with liver cirrhosis compared to patients on continued PPI medication. Methods The STOPPIT-trial is a prospective, multicentre, randomized, double-blinded, placebo-controlled, parallel-group trial. In total, 476 patients with complicated liver cirrhosis who already receive long-term PPI therapy without evidence-based indication are 1:1 randomized to receive either esomeprazole 20 mg (control group) or placebo (intervention group) for 360 days. Patients with an indication for PPI therapy (such as a recent diagnosis of peptic ulcers, severe reflux esophagitis, severe hemorrhagic gastritis, recent endoscopic therapy for oesophageal varices) are excluded. The primary composite endpoint is the time-to re-hospitalization and/or death. Secondary endpoints include rates of re-hospitalization, mortality, occurrence of infections, hepatic decompensation and acute-on-chronic liver failure. The safety endpoint is defined as manifestation of an evidence-based indication for PPI re-therapy. The impact of PPI continuation or discontinuation on the intestinal microbiota will be studied. The recruitment will take place at 18 study sites throughout Germany. Recruitment has started in April 2021. Discussion The STOPPIT trial is the first clinical trial to study the effects of PPI withdrawal on relevant outcome variables in patients with complicated liver cirrhosis. If the hypothesis that PPI withdrawal improves clinical outcomes of cirrhosis patients is confirmed, this would argue for a strong restriction of the currently liberal prescription practice of PPIs in this population. If, on the other hand, the trial demonstrates an increased risk of gastrointestinal bleeding events in patients after PPI withdrawal, this could create a rationale for a more liberal, prophylactic PPI treatment in patients with liver cirrhosis. Trial registration EU clinical trials register EudraCT 2019-005008-16 (registered December 27, 2019). ClinicalTrials.gov NCT04448028 (registered June 25, 2020). German Clinical Trials Register DRKS00021290 (registered March 10, 2021).
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Affiliation(s)
- Malte H Wehmeyer
- I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
| | - Thomas Horvatits
- I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Anika Buchholz
- Institute of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Linda Krause
- Institute of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Sarah Walter
- Coordinating Center for Clinical Trials Heidelberg, University Hospital Heidelberg, Heidelberg, Germany
| | - Antonia Zapf
- Institute of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Ansgar W Lohse
- I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Johannes Kluwe
- I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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Rajabnia M, Hatami B, Ketabi Moghadam P, Mohammadi M, Rafizadeh M, Mangeli F, Fathi M, Jahanian A. Comparison of portal hypertensive gastropathy and gastric antral vascular ectasia: an update. GASTROENTEROLOGY AND HEPATOLOGY FROM BED TO BENCH 2022; 15:204-218. [PMID: 36311963 PMCID: PMC9589138 DOI: 10.22037/ghfbb.v15i3.2561] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Accepted: 07/01/2022] [Indexed: 11/18/2022]
Abstract
Portal hypertensive gastropathy (PHG) and gastric antral vascular ectasia (GAVE) are two distinct entities that are frequently mistaken with each other, because they present with similar manifestations. This issue may cause catastrophic outcomes, as each one of them has a unique pathophysiology, thereby making their management approaches completely different. There are clinical clues that help physicians distinguish these two. Direct vision via upper endoscopy is often mandatory to establish the diagnosis, and sometimes biopsy is required. In this review, we sought to discuss different aspects of both conditions and highlight clinical evidence that may help in identifying and managing the disease appropriately.
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Affiliation(s)
- Mohsen Rajabnia
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Behzad Hatami
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Pardis Ketabi Moghadam
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahsa Mohammadi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mitra Rafizadeh
- Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Forogh Mangeli
- Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mobin Fathi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ali Jahanian
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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14
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Koya Y, Shibata M, Watanabe T, Kumei S, Miyagawa K, Oe S, Honma Y, Kume K, Yoshikawa I, Harada M. Influence of gastroesophageal flap valve on esophageal variceal bleeding in patients with liver cirrhosis. Dig Endosc 2021; 33:100-109. [PMID: 32274835 DOI: 10.1111/den.13685] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2020] [Accepted: 04/01/2020] [Indexed: 02/06/2023]
Abstract
OBJECTIVES Esophageal variceal bleeding can be fatal in patients with liver cirrhosis. The aim of this study was to investigate the relationship between gastroesophageal flap valve (GEFV) and esophageal variceal bleeding. METHODS Subjects were cirrhotic patients with endoscopically diagnosed esophageal varices treated at our hospital between 2005 and 2019, excluding those with F3 form and red color (RC) signs at first endoscopy. Sixty-five patients with normal GEFV (Hill grade I or II) and 42 with abnormal GEFV (Hill grade III or IV) were enrolled. Propensity score matching eliminated the baseline differences, resulting in a sample size of 30 patients per cohort. The primary endpoint was esophageal variceal bleeding, and the secondary endpoint was variceal bleeding or appearance of RC sign. We analyzed the cumulative incidences and predictors of each endpoint. RESULTS The 3-, 5-, and 10-year cumulative incidences of the primary endpoints were all 3.4% in the normal GEFV group, and 19.0%, 24.6% and 34.0% in the abnormal GEFV group, respectively (log-rank P = 0.011). Cumulative incidence of the secondary endpoint was 13.8%, 33.1% and 39.2% in the normal GEFV group, and 42.2%, 54.6% and 84.9% in the abnormal GEFV group, respectively (log-rank P = 0.001). In multivariate Cox regression analyses, hazard ratios of abnormal GEFV of the primary and secondary endpoints were 12.79 (95% confidence interval 1.331-122.8) and 3.600 (1.653-7.840), respectively. CONCLUSIONS Abnormal GEFV was an independent risk factor for esophageal variceal bleeding and appearance of RC sign.
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Affiliation(s)
- Yudai Koya
- Departments of, Department of, Third Department of Internal Medicine, University of Occupational and Environmental Health, Fukuoka, Japan
| | - Michihiko Shibata
- Departments of, Department of, Third Department of Internal Medicine, University of Occupational and Environmental Health, Fukuoka, Japan
| | - Tatsuyuki Watanabe
- Departments of, Department of, Third Department of Internal Medicine, University of Occupational and Environmental Health, Fukuoka, Japan
| | - Shinsuke Kumei
- Departments of, Department of, Third Department of Internal Medicine, University of Occupational and Environmental Health, Fukuoka, Japan
| | - Koichiro Miyagawa
- Departments of, Department of, Third Department of Internal Medicine, University of Occupational and Environmental Health, Fukuoka, Japan
| | - Shinji Oe
- Departments of, Department of, Third Department of Internal Medicine, University of Occupational and Environmental Health, Fukuoka, Japan
| | - Yuichi Honma
- Departments of, Department of, Third Department of Internal Medicine, University of Occupational and Environmental Health, Fukuoka, Japan
| | - Keiichiro Kume
- Departments of, Department of, Third Department of Internal Medicine, University of Occupational and Environmental Health, Fukuoka, Japan
| | - Ichiro Yoshikawa
- Department of, Endoscopy, University of Occupational and Environmental Health, Fukuoka, Japan
| | - Masaru Harada
- Departments of, Department of, Third Department of Internal Medicine, University of Occupational and Environmental Health, Fukuoka, Japan
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15
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Proton-pump-inhibitor use associated with lower short-term rebleeding and mortality in patients receiving esophageal variceal band ligation: a retrospective cohort study. Eur J Gastroenterol Hepatol 2020; 32:1571-1578. [PMID: 32868651 DOI: 10.1097/meg.0000000000001905] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
BACKGROUND The impact of proton-pump inhibitor (PPI) therapy on subsequent hemorrhage and mortality after variceal hemorrhage is unclear. AIM Evaluate the associations of PPI use with upper gastrointestinal bleeding (UGIB) and death within 30 days of undergoing esophageal variceal band ligation (EBL) separately in inpatient and outpatient settings. METHODS Retrospective review of cirrhotic patients with variceal hemorrhage who underwent EBL between 2005 and 2018. Endoscopic findings, PPI use at admission (inpatients only), PPI use at discharge (inpatients and outpatients), and adverse outcomes data (liver transplant, UGIB, transjugular intrahepatic portosystemic shunt, and death within 30 days of discharge or death during hospitalization) were reviewed. RESULTS A total of 446 patients (164 inpatients, 282 outpatients) were included. The most commonly observed outcomes were death within 30 days of discharge in inpatients (12.8%), UGIB within 30 days of discharge in inpatients (21.3%), and UGIB within 30 days of discharge in outpatients (8.5%). For inpatients, prescription of PPI at discharge was associated with a lower risk of bleeding within 30 days (odds ratio: 0.30, P = 0.025) and death within 30 days (odds ratio = 0.16, P = 0.002). No other significant associations of PPI with death or UGIB were reported. CONCLUSION Post-EBL PPI therapy is associated with reduced risk of bleeding and death within 30 days after variceal hemorrhage in hospitalized patients.
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16
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Proton pump inhibitors in chronic liver disease: accomplice or bystander? Hepatol Int 2020; 14:299-301. [PMID: 32304088 DOI: 10.1007/s12072-020-10033-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Accepted: 03/13/2020] [Indexed: 10/24/2022]
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Abstract
OBJECTIVES Proton pump inhibitors(PPIs) are widely prescribed to patients with liver cirrhosis. We hypothesized that long-standing PPI use is associated with spontaneous bacterial peritonitis(SBP) and accelerated development of disease-specific complications and liver-related death. METHODS A 5-year follow-up observational cohort study assessed the impact of long-standing PPI use on the clinical course of cirrhosis in a large referral patient cohort. Three hundred fifty patients with cirrhosis (alcohol:69.1%, Child-Pugh stage A/B/C:206/108/36) were assigned to two groups: regular PPI users (n=196) and nonusers (n=154). Occurrence of SBP, decompensation events (ascites, hepatic encephalopathy and variceal bleeding), and liver-related death were assessed. RESULTS Regular PPI use was associated with an increased cumulative probability of SBP compared to nonusers [55% vs. 24.8%, hazard ratio(HR):4.25; P=0.05], in patients without previous SBP episode (n=84). A similar association was found between regular PPI use and decompensation events. The risk of the development of a first decompensation was higher in regular PPI users compared with nonusers, in patients with compensated clinical stage at enrollment (HR: 2.81, P= 0.008, n=146). The risk of liver-related death was also significantly increased among regular PPI users (P<0.001). In multivariate Cox-regression analysis, regular PPI use (HR:2.81, P=0.003) and MELD score (HR:1.21, P<0.001) was an independent predictor of mortality. CONCLUSION In the present follow-up cohort study, long-term PPI use was associated with the development of SBP and a progressive disease course in patients with cirrhosis that may have been caused by enhanced pathologic bacterial translocation, accelerated development of bacterial translocation-dependent disease-specific complications, and liver-related death.
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18
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Hung TH, Lee HF, Tseng CW, Tsai CC, Tsai CC. Effect of proton pump inhibitors in hospitalization on mortality of patients with hepatic encephalopathy and cirrhosis but no active gastrointestinal bleeding. Clin Res Hepatol Gastroenterol 2018; 42:353-359. [PMID: 29551615 DOI: 10.1016/j.clinre.2017.11.011] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2017] [Revised: 10/29/2017] [Accepted: 11/27/2017] [Indexed: 02/04/2023]
Abstract
BACKGROUND Hepatic encephalopathy (HE) is a neuropsychiatric complication of decompensated cirrhosis. Proton pump inhibitors (PPIs), used as potent acid suppressants, are associated with HE occurrence in cirrhotic patients. However, it is still unknown if PPIs contribute to mortality in cirrhotic patients with HE and no active gastrointestinal bleeding. METHODS We used the Taiwan National Health Insurance Database to identify 1004 cirrhotic patients with HE and no active gastric bleeding, who received oral PPIs between January 1, 2010 and December 31, 2013. On the basis of comorbid disorder data, we used propensity score matching at a 1:4 ratio to select 4016 cirrhotic patients with HE and no active gastric bleeding who did not receive PPIs as a comparison group. All patients were followed up for one year from the index time. RESULTS The overall 30-day, 90-day, and 1-year mortalities were 36.1%, 52.6%, and 70.1% in PPI group, and 27.5%, 41.7%, and 62.4% in non-PPI group. Using Cox regression model analysis with adjustment for age, gender, and other comorbid disorders, we obtained hazard ratios of 1.360 (95% CI: 1.208-1.532, P<0.001), 1.563 (95% CI: 1.314-1.859; P<0.001), and 1.187 (95% CI: 1.008-1.398; P=0.040) for, respectively, 30-day, 30-day to 90-day, and 90-day to 1-year mortality in patients taking PPIs. CONCLUSION PPIs increase short-term and long-term mortality of cirrhotic patients with HE and no active gastrointestinal bleeding.
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Affiliation(s)
- Tsung-Hsing Hung
- Division of Gastroenterology, Department of Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan; School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Hsing-Feng Lee
- Division of Gastroenterology, Department of Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan; School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Chih-Wei Tseng
- Division of Gastroenterology, Department of Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan; School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Chih-Chun Tsai
- Department of Mathematics, Tamkang University, Tamsui, Taiwan
| | - Chen-Chi Tsai
- School of Medicine, Tzu Chi University, Hualien, Taiwan; Division of Infectious Diseases, Department of Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan.
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19
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Li DK, Chung RT. Use of proton pump inhibitors in chronic liver diseases. Clin Liver Dis (Hoboken) 2018; 10:148-151. [PMID: 30992776 PMCID: PMC6467129 DOI: 10.1002/cld.678] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2017] [Revised: 10/14/2017] [Accepted: 10/28/2017] [Indexed: 02/06/2023] Open
Affiliation(s)
- Darrick K. Li
- Department of GastroenterologyMassachusetts General HospitalBostonMA
| | - Raymond T. Chung
- Department of GastroenterologyMassachusetts General HospitalBostonMA
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20
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Li DK, Yan P, Abou-Samra AB, Chung RT, Butt AA. Proton pump inhibitors are associated with accelerated development of cirrhosis, hepatic decompensation and hepatocellular carcinoma in noncirrhotic patients with chronic hepatitis C infection: results from ERCHIVES. Aliment Pharmacol Ther 2018; 47:246-258. [PMID: 29105111 DOI: 10.1111/apt.14391] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2017] [Revised: 03/12/2017] [Accepted: 09/30/2017] [Indexed: 12/19/2022]
Abstract
BACKGROUND Proton pump inhibitors are among the most commonly prescribed medications in the United States. Their safety in cirrhosis has recently been questioned, but their overall effect on disease progression in noncirrhotic patients with chronic liver disease remains unclear. AIM To determine the impact of proton pump inhibitors on the progression of liver disease in noncirrhotic patients with hepatitis C virus (HCV) infection. METHODS Using the electronically retrieved cohort of HCV-infected veterans (ERCHIVES) database, we identified all subjects who received HCV treatment and all incident cases of cirrhosis, hepatic decompensation and hepatocellular carcinoma. Proton pump inhibitor use was measured using cumulative defined daily dose. Multivariate Cox regression analysis was performed after adjusting univariate predictors of cirrhosis and various indications for proton pump inhibitor use. RESULTS Among 11 526 eligible individuals, we found that exposure to proton pump inhibitors was independently associated with an increased risk of developing cirrhosis (hazard ratio [HR]: 1.32; 95% confidence interval: [1.17, 1.49]). This association remained robust to sensitivity analysis in which only patients who achieved sustained virologic response were analysed as well as analysis excluding those with alcohol abuse/dependence. Proton pump inhibitor exposure was also independently associated with an increased risk of hepatic decompensation (HR: 3.79 [2.58, 5.57]) and hepatocellular carcinoma (HR: 2.01 [1.50, 2.70]). CONCLUSIONS In patients with chronic HCV infection, increasing proton pump inhibitor use is associated with a dose-dependent risk of progression of chronic liver disease to cirrhosis, as well as an increased risk of hepatic decompensation and hepatocellular carcinoma.
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Affiliation(s)
- D K Li
- Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - P Yan
- VA Pittsburgh Healthcare System, Pittsburgh, PA, USA
| | - A-B Abou-Samra
- Hamad Healthcare Quality Institute, Hamad Medical Corporation, Doha, Qatar
| | - R T Chung
- Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.,Division of Gastroenterology, Department of Medicine, Liver Center, Massachusetts General Hospital, Boston, MA, USA
| | - A A Butt
- VA Pittsburgh Healthcare System, Pittsburgh, PA, USA.,Hamad Healthcare Quality Institute, Hamad Medical Corporation, Doha, Qatar.,Weill Cornell Medical College, Doha, Qatar.,Weill Cornell Medical College, New York, NY, USA
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Abstract
This narrative review summarises the benefits, risks and appropriate use of acid-suppressing drugs (ASDs), proton pump inhibitors and histamine-2 receptor antagonists, advocating a rationale balanced and individualised approach aimed to minimise any serious adverse consequences. It focuses on current controversies on the potential of ASDs to contribute to infections-bacterial, parasitic, fungal, protozoan and viral, particularly in the elderly, comprehensively and critically discusses the growing body of observational literature linking ASD use to a variety of enteric, respiratory, skin and systemic infectious diseases and complications (Clostridium difficile diarrhoea, pneumonia, spontaneous bacterial peritonitis, septicaemia and other). The proposed pathogenic mechanisms of ASD-associated infections (related and unrelated to the inhibition of gastric acid secretion, alterations of the gut microbiome and immunity), and drug-drug interactions are also described. Both probiotics use and correcting vitamin D status may have a significant protective effect decreasing the incidence of ASD-associated infections, especially in the elderly. Despite the limitations of the existing data, the importance of individualised therapy and caution in long-term ASD use considering the balance of benefits and potential harms, factors that may predispose to and actions that may prevent/attenuate adverse effects is evident. A six-step practical algorithm for ASD therapy based on the best available evidence is presented.
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Affiliation(s)
- Leon Fisher
- Frankston Hospital, Peninsula Health, Melbourne, Australia.
| | - Alexander Fisher
- The Canberra Hospital, ACT Health, Canberra, Australia
- Australian National University Medical School, Canberra, Australia
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22
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Cole HL, Pennycook S, Hayes PC. The impact of proton pump inhibitor therapy on patients with liver disease. Aliment Pharmacol Ther 2016; 44:1213-1223. [PMID: 27774677 DOI: 10.1111/apt.13827] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2016] [Revised: 08/21/2016] [Accepted: 09/21/2016] [Indexed: 12/13/2022]
Abstract
BACKGROUND Proton pump inhibitor (PPI) therapy has been reported to be an independent mortality risk factor in patients with cirrhosis. AIM To identify the prevalence of PPI prescription, the appropriateness of this therapy and to investigate the relationship between PPI therapy and overall survival in patients with liver disease. METHODS This retrospective cohort study used patient data for 2012 to 2014 collected from the Scottish Liver Transplant Unit and the Hepatology Ward at the New Royal Infirmary of Edinburgh. RESULTS A total of 64% of the 198 patients discharged from the Hepatology ward were prescribed a PPI. Of the 206 patients assessed and listed for orthotopic liver transplant (OLT), 55% were prescribed a PPI. These percentages are significant, particularly as the majority had no recorded appropriate indication for this therapy. For patients listed for OLT, a logistic regression model revealed significant associations between PPI treatment and male sex, higher model of end-stage liver disease (MELD) scores and patient encephalopathy. A multivariate Cox regression model showed that MELD and UK model for end-stage liver disease scores were independent predictors of patient mortality, while alcoholic liver disease aetiology was a protective factor. There was no statistically significant difference in survival between patients who were prescribed a PPI at assessment and those who were not. CONCLUSION Associations between PPI use, encephalopathy and higher MELD scores imply caution should be exercised in prescribing gastric acid suppressants to patients with cirrhosis, particularly in the absence of clear indications.
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Affiliation(s)
- H L Cole
- University of Edinburgh, Edinburgh, UK
| | | | - P C Hayes
- University of Edinburgh, Edinburgh, UK
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23
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Gjeorgjievski M, Cappell MS. Portal hypertensive gastropathy: A systematic review of the pathophysiology, clinical presentation, natural history and therapy. World J Hepatol 2016; 8:231-262. [PMID: 26855694 PMCID: PMC4733466 DOI: 10.4254/wjh.v8.i4.231] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2015] [Revised: 11/30/2015] [Accepted: 01/16/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To describe the pathophysiology, clinical presentation, natural history, and therapy of portal hypertensive gastropathy (PHG) based on a systematic literature review. METHODS Computerized search of the literature was performed via PubMed using the following medical subject headings or keywords: "portal" and "gastropathy"; or "portal" and "hypertensive"; or "congestive" and "gastropathy"; or "congestive" and "gastroenteropathy". The following criteria were applied for study inclusion: Publication in peer-reviewed journals, and publication since 1980. Articles were independently evaluated by each author and selected for inclusion by consensus after discussion based on the following criteria: Well-designed, prospective trials; recent studies; large study populations; and study emphasis on PHG. RESULTS PHG is diagnosed by characteristic endoscopic findings of small polygonal areas of variable erythema surrounded by a pale, reticular border in a mosaic pattern in the gastric fundus/body in a patient with cirrhotic or non-cirrhotic portal hypertension. Histologic findings include capillary and venule dilatation, congestion, and tortuosity, without vascular fibrin thrombi or inflammatory cells in gastric submucosa. PHG is differentiated from gastric antral vascular ectasia by a different endoscopic appearance. The etiology of PHG is inadequately understood. Portal hypertension is necessary but insufficient to develop PHG because many patients have portal hypertension without PHG. PHG increases in frequency with more severe portal hypertension, advanced liver disease, longer liver disease duration, presence of esophageal varices, and endoscopic variceal obliteration. PHG pathogenesis is related to a hyperdynamic circulation, induced by portal hypertension, characterized by increased intrahepatic resistance to flow, increased splanchnic flow, increased total gastric flow, and most likely decreased gastric mucosal flow. Gastric mucosa in PHG shows increased susceptibility to gastrotoxic chemicals and poor wound healing. Nitrous oxide, free radicals, tumor necrosis factor-alpha, and glucagon may contribute to PHG development. Acute and chronic gastrointestinal bleeding are the only clinical complications. Bleeding is typically mild-to-moderate. Endoscopic therapy is rarely useful because the bleeding is typically diffuse. Acute bleeding is primarily treated with octreotide, often with concomitant proton pump inhibitor therapy, or secondarily treated with vasopressin or terlipressin. Nonselective β-adrenergic receptor antagonists, particularly propranolol, are used to prevent bleeding after an acute episode or for chronic bleeding. Iron deficiency anemia from chronic bleeding may require iron replacement therapy. Transjugular-intrahepatic-portosystemic-shunt and liver transplantation are highly successful ultimate therapies because they reduce the underlying portal hypertension. CONCLUSION PHG is important to recognize in patients with cirrhotic or non-cirrhotic portal hypertension because it can cause acute or chronic GI bleeding that often requires pharmacologic therapy.
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Affiliation(s)
- Mihajlo Gjeorgjievski
- Mihajlo Gjeorgjievski, Mitchell S Cappell, Division of Gastroenterology and Hepatology, William Beaumont Hospital, Royal Oak, MI 48073, United States
| | - Mitchell S Cappell
- Mihajlo Gjeorgjievski, Mitchell S Cappell, Division of Gastroenterology and Hepatology, William Beaumont Hospital, Royal Oak, MI 48073, United States
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Picardi A, Vespasiani-Gentilucci U. Proton pump inhibitor prescription abuse and sepsis in cirrhosis. World J Gastrointest Pharmacol Ther 2016; 7:1-4. [PMID: 26855807 PMCID: PMC4734942 DOI: 10.4292/wjgpt.v7.i1.1] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2015] [Revised: 09/08/2015] [Accepted: 11/03/2015] [Indexed: 02/06/2023] Open
Abstract
Proton pump inhibitors (PPIs) represent one of the most extensively prescribed classes of drugs in general and in patients with liver cirrhosis. Many prescriptions are made without a clear adherence to standard indications. As a class of ordinarily well tolerated drug, PPIs are not free of side-effects and concerns have been raised about a possible role for PPIs in predisposing patients to an increased risk of bacterial infections and sepsis. As evidences of different power are accumulating on this topic, prospective studies are needed to reach a more universal agreement, but definitely more attention is needed by prescribers in being more adherent to the few recognized indications for the use of PPIs, particularly in patients with liver cirrhosis. Otherwise, doctors could run the risk of being accused of "abused" prescription.
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Lo EAG, Wilby KJ, Ensom MHH. Use of proton pump inhibitors in the management of gastroesophageal varices: a systematic review. Ann Pharmacother 2015; 49:207-19. [PMID: 25583938 DOI: 10.1177/1060028014559244] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
OBJECTIVE To review the efficacy and safety of proton pump inhibitors (PPIs) in gastroesophageal varices (GEVs). DATA SOURCES MEDLINE (1946 to September 2014), EMBASE (1974 to September 2014), International Pharmaceutical Abstracts (1970 to September 2014), Cochrane Central Register of Controlled Trials (1991 to September 2014), Google, and Google Scholar were searched using the following terms: esophageal varices, gastroesophageal varices, variceal hemorrhage, variceal bleeding, banding ligation, endoscopic variceal ligation, sclerotherapy, proton pump inhibitor, PPI, omeprazole, pantoprazole, lansoprazole, dexlansoprazole, rabeprazole, and esomeprazole. STUDY SELECTION AND DATA EXTRACTION Published and unpublished studies evaluating the clinical outcomes of PPI use for GEVs were included regardless of study design. Non-English and nonhuman studies were excluded. DATA SYNTHESIS Of 1156 studies, 20 were included after assessment. There was wide methodological heterogeneity and moderately high risk of bias among studies. Level I evidence suggests that PPIs reduce esophageal ulcer size post-elective esophageal ligation; the clinical importance of such findings is not known given the self-limiting nature of esophageal ulcer. Available evidence does not support a role of PPIs for long-term prophylaxis of portal hypertension-related bleeding and high-dose infusion for acute management of GEV hemorrhage. Retrospective data demonstrate a potential increase in the incidence of spontaneous bacterial peritonitis in patients with cirrhosis receiving PPIs. CONCLUSIONS The best available evidence supports the use of short-course (10 days) PPI post-endoscopic variceal ligation to reduce ulcer size if ulcer healing is a concern. Practices such as high-dose infusion and prolonged use should be discouraged until evidence of benefit becomes available.
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Affiliation(s)
- Elaine A G Lo
- University of British Columbia, Vancouver, British Columbia, Canada
| | | | - Mary H H Ensom
- University of British Columbia, Vancouver, British Columbia, Canada Children's and Women's Health Centre of British Columbia, Vancouver, British Columbia, Canada
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Lin ZN, Zuo YQ, Hu P. Association of Proton Pump Inhibitor Therapy with Hepatic Encephalopathy in Hepatitis B Virus-related Acute-on-Chronic Liver Failure. HEPATITIS MONTHLY 2014; 14:e16258. [PMID: 24748895 PMCID: PMC3989600 DOI: 10.5812/hepatmon.16258] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/18/2013] [Revised: 01/20/2014] [Accepted: 02/14/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND Hepatic encephalopathy (HE) is an important neuropsychiatry complication of acute-on-chronic liver failure (ACLF). PPI therapy may increase the intestinal bacterial overgrowth and infections. OBJECTIVES The aim of this study was to assess whether PPI use in ACLF is associated with HE. PATIENTS AND METHODS A retrospective case-control study was performed. Fifty five admitted patients with hepatitis B virus (HBV)-related ACLF complicated by Stage II-IV HE developed after admission between January 2008 and December 2012 were matched (by sex, age, and MELD score) with comparable HBV-related ACLF patients (n = 110) who did not develop this complication during hospitalization. We excluded combined HE upon admission and other neurological disorders in patients with ACLF. Univariate and multivariate analyses of 30 variables (laboratory examination, predisposition, treatment, etc.) before the occurrence of HE were carried out to identify the factors predictive of HE. RESULTS In univariate analysis, patients with HE in ACLF had a significantly higher rate of PPI use (89.1%) compared with non-HE (63.6%, P = 0.001). In addition, clinical and standard laboratory variables were significantly different between the two groups regarding the infection rate, hyponatremia, alpha-fetoprotein (AFP), Arginine Hydrochloride use and Lactulose use. Logistic regression analysis was used to examine the combined effects of the variables with HE as the outcome. HE in ACLF was associated with hyponatremia (odds ratio (OR) = 6. 318, 95% confidence interval (CI) = 2. 803-14.241; P = 0. 000), PPI use was independently associated with HE (OR = 4. 392, CI = 1. 604-12.031; P = 0. 004), and lactulose use was protective (OR = 0. 294, CI = 0. 136-0.675; P = 0. 003). CONCLUSIONS The occurrence of HE is associated with hyponatremia and PPI use in patients with ACLF.
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Affiliation(s)
- Zhao-Ni Lin
- Department of Infectious Diseases, Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yong-Qing Zuo
- Department of Infectious Diseases, Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Peng Hu
- Department of Infectious Diseases, Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Corresponding Author: Peng Hu, Department of Infectious Diseases, Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China. Tel: +86-2363693289, Fax: +86-2363703790, E-mail:
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Yoshida H, Mamada Y, Taniai N, Yoshioka M, Hirakata A, Kawano Y, Mizuguchi Y, Shimizu T, Ueda J, Uchida E. Risk factors for bleeding esophagogastric varices. J NIPPON MED SCH 2014; 80:252-9. [PMID: 23995567 DOI: 10.1272/jnms.80.252] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Bleeding from gastric varices (GVs) is generally considered more severe than that from esophageal varices (EVs) but occurs less frequently. We review the risk factors for bleeding EVs and GVs. GVs were divided into 2 groups: cardiac varices (CVs, Lg-c) and fundal varices (FVs), i.e., varices involving the fundus alone (Lg-f) or varices involving both the cardia and fundus (Lg-cf). Elevated pressure in the portal vein is a risk factor for bleeding EVs. The portal pressure in patients with GVs and a gastrorenal shunt is lower than that in patients with EVs. The large size of varices is a risk factor for bleeding EVs. Red color signs are elevated red areas that are important for predicting the risk of variceal bleeding, and red wale markings, dilated venules oriented longitudinally on the mucosal surface, have been considered to be the sign with the highest risk. Red color signs are rare in FVs, possibly because of the pronounced thickness of the mucosal layer. Bleeding EVs are not associated with use of antiulcer drugs or nonsteroidal anti-inflammatory drugs (NSAIDs). Although, in patients with bleeding GVs, "occasional" use of an oral NSAID is an important step leading to variceal hemorrhage, especially from FVs, even if the mucosa is protected by antiulcer drugs. Constipation, vomiting, severe coughing, and excessive consumption of alcohol may precipitate rupture of EVs.
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Affiliation(s)
- Hiroshi Yoshida
- Department of Surgery, Nippon Medical School Tama Nagayama Hospital, Tokyo, Japan.
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Siple JF, Morey JM, Gutman TE, Weinberg KL, Collins PD. Proton pump inhibitor use and association with spontaneous bacterial peritonitis in patients with cirrhosis and ascites. Ann Pharmacother 2012; 46:1413-8. [PMID: 23032651 DOI: 10.1345/aph.1r174] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVE To evaluate the literature regarding the efficacy and safety of proton pump inhibitors (PPIs) when they are used in patients with cirrhosis and ascites. DATA SOURCES A literature search was conducted using MEDLINE (1966-May 2012) and Web of Science (1990-May 2012) with the terms proton pump inhibitor, antisecretory therapy, cirrhosis, ascites, spontaneous bacterial peritonitis, and Clostridium difficile. The search was restricted to articles published in English on the use of PPIs in humans. Reference citations from identified published articles were reviewed for relevant information. STUDY SELECTION AND DATA EXTRACTION All articles in English identified from the data sources were evaluated for inclusion. One case series, 8 retrospective case-control trials, and 1 meta-analysis were identified. DATA SYNTHESIS Cirrhosis may cause complications such as portal hypertension, esophageal varices, and ascites. Patients may be prescribed PPIs without clear indications or because of their propensity to develop upper gastrointestinal symptoms and bleeding. However, gastric acidity is a major nonspecific defense mechanism and there is insufficient evidence on the need for chronic acid suppression in patients with cirrhosis. It is postulated that the portal hypertensive environment in cirrhosis and the acid suppression from PPIs can increase the risk of spontaneous bacterial peritonitis and C. difficile infection in patients with cirrhosis with ascites. Several retrospective studies and 1 meta-analysis have confirmed this association. CONCLUSIONS Patients with cirrhosis and ascites should be monitored carefully while on PPIs for a possible increased risk of infection from spontaneous bacterial peritonitis and C. difficile. Prospective randomized trials are needed to confirm this association. Clinicians should be aware of this lesser known adverse effect of PPIs.
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Affiliation(s)
- Jolene F Siple
- Vancouver Primary Care, Portland Veterans Affairs Medical Center, WA, USA.
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