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Ramsing MS, Jensen MD, Jepsen P. Use of Proton Pump Inhibitors Among Patients With Alcohol-Related Cirrhosis-A Danish Nationwide Cohort Study. Liver Int 2025; 45:e70061. [PMID: 40066903 PMCID: PMC11894920 DOI: 10.1111/liv.70061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2024] [Revised: 02/02/2025] [Accepted: 02/24/2025] [Indexed: 03/15/2025]
Abstract
BACKGROUND Use of proton pump inhibitors (PPIs) may have adverse effects in patients with alcohol-related cirrhosis (ALD cirrhosis), but PPIs continue to be used by many patients. AIMS We aimed to describe the prevalence and incidence of PPI use from filled prescriptions among patients with ALD cirrhosis and to identify predictors of PPI initiation after ALD cirrhosis diagnosis. METHODS We used Danish nationwide healthcare registries to investigate PPI use among patients diagnosed with ALD cirrhosis from 1997 to 2022. We used multivariable Cox regression to identify predictors of PPI initiation. RESULTS We identified 41 263 patients diagnosed with ALD cirrhosis in 1997-2022. In this cohort, the prevalence of PPI use rose to 40% in 2016 and plateaued at this level through 2022. Considering time since diagnosis, 26% were using PPI at the diagnosis of ALD cirrhosis, and the prevalence peaked at 38% 3 months later. Among PPI users, 79% used more than 30 defined daily doses per year on average during the follow-up. Patients older than 50 years were more likely than younger patients to initiate PPI treatment. CONCLUSION The use of PPIs continues to be prevalent among patients with ALD cirrhosis, with 40% of all patients using PPIs in 2022. Within the first 3 months after diagnosis, 38% of all patients were using PPIs. Our results provide essential background information for future RCTs on the risks and benefits of prescribing or deprescribing PPIs.
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Affiliation(s)
| | - Morten Daniel Jensen
- Department of Hepatology and GastroenterologyAarhus University HospitalAarhusDenmark
| | - Peter Jepsen
- Department of Hepatology and GastroenterologyAarhus University HospitalAarhusDenmark
- Department of Clinical EpidemiologyAarhus University HospitalAarhusDenmark
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Albillos A, Bañares R, Hernández-Gea V. Portal hypertension: recommendations for diagnosis and treatment. Consensus document sponsored by the Spanish Association for the Study of the Liver (AEEH) and the Biomedical Research Network Centre for Liver and Digestive Diseases (CIBERehd). GASTROENTEROLOGIA Y HEPATOLOGIA 2025; 48:502208. [PMID: 39756832 DOI: 10.1016/j.gastrohep.2024.502208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Revised: 04/07/2024] [Accepted: 04/09/2024] [Indexed: 01/07/2025]
Abstract
Portal hypertension is a hemodynamic abnormality that complicates the course of cirrhosis, as well as other diseases that affect the portal venous circulation. The development of portal hypertension compromises prognosis, especially when it rises above a certain threshold known as clinically significant portal hypertension (CSPH). In the consensus conference on Portal Hypertension promoted by the Spanish Association for the Study of the Liver and the Hepatic and Digestive diseases area of the Biomedical Research Networking Center (CIBERehd), different aspects of the diagnosis and treatment of portal hypertension caused by cirrhosis or other diseases were discussed. The outcome of this discussion was a set of recommendations that achieved varying degrees of consensus among panelists and are reflected in this consensus document. The six areas under discussion were: the relevance of CSPH and the non-invasive methods used for its diagnosis and that of cirrhosis, the prevention of the first episode of decompensation and its recurrence, the treatment of acute variceal bleeding and other complications of portal hypertension, the indications for the use of TIPS, and finally, the diagnosis and treatment of liver vascular diseases.
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Affiliation(s)
- Agustín Albillos
- Servicio de Gastroenterología y Hepatología, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Universidad de Alcalá, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España.
| | - Rafael Bañares
- Servicio de Medicina de Aparato Digestivo, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IISGM), Universidad Complutense, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España.
| | - Virginia Hernández-Gea
- Servicio de Hepatología, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universidad de Barcelona, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, España.
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Albillos A, Bañares R, Hernández-Gea V. Portal hypertension: recommendations for diagnosis and treatment. Consensus document sponsored by the Spanish Association for the Study of the Liver (AEEH) and the Biomedical Research Network Center for Liver and Digestive Diseases (CIBERehd). REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2025; 117:14-57. [PMID: 39350672 DOI: 10.17235/reed.2024.10805/2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/30/2025]
Abstract
Portal hypertension is a hemodynamic abnormality that complicates the course of cirrhosis, as well as other diseases that affect the portal venous circulation. The development of portal hypertension compromises prognosis, especially when it rises above a certain threshold known as clinically significant portal hypertension (CSPH). In the consensus conference on Portal Hypertension promoted by the Spanish Association for the Study of the Liver and the Hepatic and Digestive diseases area of the Biomedical Research Networking Center (CIBERehd), different aspects of the diagnosis and treatment of portal hypertension caused by cirrhosis or other diseases were discussed. The outcome of this discussion was a set of recommendations that achieved varying degrees of consensus among panelists and are reflected in this consensus document. The six areas under discussion were: the relevance of clinically significant portal hypertension and the non-invasive methods used for its diagnosis and that of cirrhosis, the prevention of the first episode of decompensation and its recurrence, the treatment of acute variceal bleeding and other complications of portal hypertension, the indications for the use of TIPS, and finally, the diagnosis and treatment of liver vascular diseases.
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Affiliation(s)
- Agustín Albillos
- Servicio de Gastroenterología y Hepatología, Hospital Universitario Ramón y Cajal, España
| | - Rafael Bañares
- Servicio de Medicina de Aparato Digestivo, Hospital General Universitario Gregorio Marañón
| | - Virginia Hernández-Gea
- Servicio de Hepatología, Hospital Clínic. Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
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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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Bettinger D, Thimme R, Sturm L. Editorial: Novel insights into the prognostic relevance of high-dose PPI treatment in patients with cirrhosis. Aliment Pharmacol Ther 2024; 59:1282-1283. [PMID: 38652787 DOI: 10.1111/apt.17928] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/25/2024]
Abstract
LINKED CONTENTThis article is linked to Yoon et al paper. To view this article, visit https://doi.org/10.1111/apt.17909
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Affiliation(s)
- Dominik Bettinger
- Department of Medicine II, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Robert Thimme
- Department of Medicine II, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Lukas Sturm
- Department of Medicine II, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- Berta-Ottenstein-Programme, Faculty of Medicine, University of Freiburg, Freiburg, Germany
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Yoon JS, Hong JH, Park SY, Kim SU, Kim HY, Kim JY, Hur MH, Park MK, Lee YB, Lee HA, Kim GA, Sinn DH, Park SJ, Lee YJ, Kim YJ, Yoon JH, Lee JH. High-dose proton pump inhibitor treatment is associated with a higher mortality in cirrhotic patients: A multicentre study. Aliment Pharmacol Ther 2024; 59:973-983. [PMID: 38389319 DOI: 10.1111/apt.17909] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2023] [Revised: 08/11/2023] [Accepted: 02/07/2024] [Indexed: 02/24/2024]
Abstract
BACKGROUND Proton pump inhibitors (PPI) are frequently used in patients with cirrhosis. AIMS This study aimed to determine whether PPI use is associated with the prognosis of cirrhotic patients. METHODS We conducted a multicentre retrospective cohort study involving 1485 patients who had experienced hepatic encephalopathy (HE) from 7 referral centres in Korea. The primary outcome was overall survival and secondary outcomes included the development of cirrhotic complications, including recurrent HE, spontaneous bacterial peritonitis (SBP), hepatorenal syndrome (HRS), and gastrointestinal bleeding. Patients treated with PPI with a mean defined daily dose (mDDD) ≥0.5 (high-dose PPI group) were compared to those treated with PPI of an mDDD < 0.5 (No or low-dose PPI group) for each outcome. RESULTS Among 1485 patients (median age, 61 years; male, 61%), 232 were assigned to the high-dose PPI group. High-dose PPI use was independently associated with a higher risk of death (adjusted HR [aHR] = 1.71, 95% confidence interval [CI] = 1.38-2.11, p < 0.001). This result was reproducible after propensity score-matching (PSM) (aHR = 1.90, 95% CI = 1.49-2.44, p < 0.001). High-dose PPI use was an independent risk factor of recurrent HE (before PSM: aHR = 2.04, 95% CI = 1.66-2.51, p < 0.001; after PSM: aHR = 2.16, 95% CI = 1.70-2.74, p < 0.001), SBP (before PSM: aHR = 1.87, 95% CI = 1.43-2.43, p < 0.001; after PSM: aHR = 1.76, 95% CI = 1.31-2.36, p = 0.002), HRS (before PSM: aHR = 1.48, 95% CI = 1.02-2.15, p = 0.04; after PSM: aHR = 1.47, 95% CI = 0.95-2.28, p = 0.09), and gastrointestinal bleeding (before PSM: aHR = 1.46, 95% CI = 1.12-1.90, p = 0.006; after PSM: aHR = 1.74, 95% CI = 1.28-2.37, p < 0.001). CONCLUSIONS The use of high-dose PPI was independently associated with increased risks of mortality and cirrhotic complications.
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Affiliation(s)
- Jun Sik Yoon
- Department of Internal Medicine, Busan Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea
| | - Ji Hoon Hong
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Soo Young Park
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Seung Up Kim
- Department of Internal Medicine and Yonsei Liver Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hwi Young Kim
- Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Republic of Korea
| | - Ju Yeon Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Moon Haeng Hur
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Min Kyung Park
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Yun Bin Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Han Ah Lee
- Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Republic of Korea
| | - Gi-Ae Kim
- Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Republic of Korea
| | - Dong Hyun Sinn
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Sung Jae Park
- Department of Internal Medicine, Busan Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea
| | - Youn Jae Lee
- Department of Internal Medicine, Busan Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea
| | - Yoon Jun Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jung-Hwan Yoon
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jeong-Hoon Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
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Low EXS, Wang YP, Lu CL. Risks of Proton Pump Inhibitors in Patients with Cirrhosis: Please Peruse the Indications. Dig Dis Sci 2024; 69:7-9. [PMID: 37968555 DOI: 10.1007/s10620-023-08153-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Accepted: 10/09/2023] [Indexed: 11/17/2023]
Abstract
The use of proton pump inhibitor (PPI) in cirrhotic patients can be associated with increased risks of long-term mortality, decompensation, hepatic encephalopathy, spontaneous bacterial peritonitis, and infection, but not with short-term mortality. Ensure clear indications at lowest effective dose of is mandatory for the use of PPI among cirrhotic patients.
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Affiliation(s)
- En Xian Sarah Low
- Endoscopy Center for Diagnosis and Treatment, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yen-Po Wang
- Endoscopy Center for Diagnosis and Treatment, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Ching-Liang Lu
- Endoscopy Center for Diagnosis and Treatment, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
- Institute of Brain Science, National Yang Ming Chiao Tung Univeristy, Taipei, Taiwan.
- Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
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Wong ZY, Koh JH, Muthiah M, Koh B, Ong EYH, Ong CEY, Ou KQ, Lim WH, Tan DJH, Chee D, Siah KTH, Wong Y, Kaewdech A, Wijarnpreecha K, Kulkarni AV, Nah B, Huang DQ, Noureddin M, Ng CH, Teng M. Proton Pump Inhibitors Increases Longitudinal Risk of Mortality, Decompensation, and Infection in Cirrhosis: A Meta-Analysis. Dig Dis Sci 2024; 69:289-297. [PMID: 37968557 DOI: 10.1007/s10620-023-08150-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2023] [Accepted: 10/09/2023] [Indexed: 11/17/2023]
Abstract
BACKGROUND/AIMS Proton pump inhibitors (PPIs) are frequently prescribed to cirrhotic patients, but there is limited longitudinal evidence regarding their effects. This study aimed to assess the impact of PPIs on adverse events in cirrhotic patients. METHODS A comprehensive search was conducted using the Medline and Embase databases to identify relevant articles. Pooled hazard ratios (HRs) using DerSimonian and Laird random-effects model were calculated to evaluate the risk of adverse events such as long-term mortality, hepatic decompensation, hepatic encephalopathy (HE), spontaneous bacterial peritonitis (SBP), and overall infection in cirrhotic patients with PPI use. RESULTS The analysis included 28 studies with 260,854 cirrhotic patients. The prevalence of PPI use among cirrhotic patients was 55.93%. The use of PPIs was not significantly associated with short-term mortality in cirrhotic patients. However, long-term mortality (HR 1.321, 95% CI 1.103-1.581, P = 0.002), decompensation (HR 1.646, 95% CI 1.477-1.835, P < 0.001), HE (HR 1.968, 95% CI 1.372-2.822, P < 0.001), SBP (HR 1.751, 95% CI 1.649-1.859, P < 0.001), and infection (HR 1.370, 95% CI 1.148-1.634, P < 0.001) were significantly associated with PPI use. Sensitivity analysis with prospective studies yielded similar results. CONCLUSION PPIs should be reserved for appropriate indications at lowest effective dose for cirrhotic patients due to the potential harm.
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Affiliation(s)
- Zhen Yu Wong
- Nottingham City Hospital, Nottingham University Hospitals NHS Trust, Nottingham, UK
| | - Jia Hong Koh
- Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Dr, Singapore, 117597, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
| | - Mark Muthiah
- Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Dr, Singapore, 117597, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
| | - Benjamin Koh
- Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Dr, Singapore, 117597, Singapore
| | - Elden Yen Hng Ong
- Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Dr, Singapore, 117597, Singapore
| | - Christen En Ya Ong
- Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Dr, Singapore, 117597, Singapore
| | - Kai Qi Ou
- Nottingham City Hospital, Nottingham University Hospitals NHS Trust, Nottingham, UK
| | - Wen Hui Lim
- Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Dr, Singapore, 117597, Singapore
| | - Darren Jun Hao Tan
- Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Dr, Singapore, 117597, Singapore
| | - Douglas Chee
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore
| | - Kewin Tien Ho Siah
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore
| | - Yujun Wong
- Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Dr, Singapore, 117597, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore
| | - Apichat Kaewdech
- Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand
| | - Karn Wijarnpreecha
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA
| | - Anand V Kulkarni
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, Telangana, India
| | - Benjamin Nah
- Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Dr, Singapore, 117597, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
| | - Daniel Q Huang
- Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Dr, Singapore, 117597, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore
- Division of Gastroenterology, NAFLD Research Center, University of California at San Diego, La Jolla, CA, USA
- National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
| | | | - Cheng Han Ng
- Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Dr, Singapore, 117597, Singapore.
| | - Margaret Teng
- Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Dr, Singapore, 117597, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore
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Sturm L, Hirose M, Stolz L, Schultheiss M, Zoldan K, Reincke M, Huber JP, Kaeser R, Boettler T, Thimme R, Albert E, Busch H, Künstner A, Bettinger D. Proton pump inhibitor treatment aggravates bacterial translocation in patients with advanced cirrhosis and portal hypertension. mBio 2023; 14:e0049223. [PMID: 37623323 PMCID: PMC10653923 DOI: 10.1128/mbio.00492-23] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Accepted: 05/02/2023] [Indexed: 08/26/2023] Open
Abstract
IMPORTANCE Long-term prescription of proton pump inhibitors (PPIs) in patients with cirrhosis is common practice. However, in recent years, several observational studies have reported increased complications and negative prognostic effects of PPI treatment in these patients. Judging the significance of these associations is complicated by the fact that a plausible underlying pathomechanism has not been identified so far. In the present study, we address this important issue by investigating the impact of PPI treatment on subclinical bacterial translocation from the gut into the blood stream in patients with advanced cirrhosis and portal hypertension. Indeed, we report significantly aggravated bacterial translocation in cirrhosis patients receiving PPI treatment. This finding is highly relevant, as bacterial translocation is known to promote the development of complications and impair prognosis in patients with cirrhosis. Hence, the present study could establish a plausible link between PPI treatment and adverse effects in cirrhosis.
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Affiliation(s)
- Lukas Sturm
- Department of Medicine II, Faculty of Medicine, Medical Center University of Freiburg, Freiburg, Germany
- Berta-Ottenstein-Programme, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Misa Hirose
- Luebeck Institute of Experimental Dermatology, University of Luebeck, Luebeck, Germany
| | - Laura Stolz
- Department of Medicine II, Faculty of Medicine, Medical Center University of Freiburg, Freiburg, Germany
| | - Michael Schultheiss
- Department of Medicine II, Faculty of Medicine, Medical Center University of Freiburg, Freiburg, Germany
- Berta-Ottenstein-Programme, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Katharina Zoldan
- Department of Medicine II, Faculty of Medicine, Medical Center University of Freiburg, Freiburg, Germany
| | - Marlene Reincke
- Department of Medicine II, Faculty of Medicine, Medical Center University of Freiburg, Freiburg, Germany
| | - Jan Patrick Huber
- Department of Medicine II, Faculty of Medicine, Medical Center University of Freiburg, Freiburg, Germany
| | - Rafael Kaeser
- Department of Medicine II, Faculty of Medicine, Medical Center University of Freiburg, Freiburg, Germany
- IMM-PACT-Programme, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Tobias Boettler
- Department of Medicine II, Faculty of Medicine, Medical Center University of Freiburg, Freiburg, Germany
| | - Robert Thimme
- Department of Medicine II, Faculty of Medicine, Medical Center University of Freiburg, Freiburg, Germany
| | - Elisabeth Albert
- Luebeck Institute of Experimental Dermatology, University of Luebeck, Luebeck, Germany
| | - Hauke Busch
- Luebeck Institute of Experimental Dermatology, University of Luebeck, Luebeck, Germany
- Institute for Cardiogenetics, University of Luebeck, Luebeck, Germany
| | - Axel Künstner
- Luebeck Institute of Experimental Dermatology, University of Luebeck, Luebeck, Germany
- Institute for Cardiogenetics, University of Luebeck, Luebeck, Germany
| | - Dominik Bettinger
- Department of Medicine II, Faculty of Medicine, Medical Center University of Freiburg, Freiburg, Germany
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10
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Balafar M, Ghojazadeh M, Shahsavarinia K, Parsian Z, Hamedani S, Soleimanpour H. Association Between Proton Pump Inhibitor Use and Spontaneous Bacterial Peritonitis or Hepatic Encephalopathy in Cirrhotic Patients: A Systematic Review and Meta-analysis. HEPATITIS MONTHLY 2023; 23. [DOI: 10.5812/hepatmon-132642] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Context: There is a link between proton pump inhibitors (PPIs) use and the occurrence of spontaneous bacterial peritonitis (SBP) in cirrhotic patients in some studies; however, in other studies, such a link does not exist. Objectives: The aim of the current systematic review and meta-analysis was to evaluate the association between PPI and the occurrence of SBP or hepatic encephalopathy (HE) in cirrhotic patients. Data Sources: A systematic search of sources was conducted in order to evaluate for any relationship between PPI and the risk of SBP in patients with liver diseases. Medline, Scopus, Ovid, ProQuest, Google Scholar, and Web of Science were searched to find any evidence in this regard from 1980 to November of 2021. Study Selection: The articles were evaluated by two independent reviewers according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses). After deleting the duplicates, first, the titles of the studies were evaluated, and then the full texts were evaluated. Any disagreement between the two researchers was solved by discussion or a third reviewer. Data Extraction: Appropriate Critical Appraisal Checklists of Joanna Briggs Institute (JBI) were used for the quality assessment of eligible studies. Statistical analysis was performed by CMA software (version 2.0), and a P-value of less than 0.05 was considered a significant level. Results: In the systematic search of sources, 3705 articles were identified. Finally, 33 studies were included in this meta-analysis study. A total of 6370 PPI users and 8037 patients in the control group experienced at least one of the complications of liver cirrhosis, including SBP or HE. According to meta-analysis, the risk of SBP or HE in the intervention group was 1.95 times higher than in the control group (RR = 1.95; 95% confidence interval [CI]: 1.53 - 2.48, P < 0.001). Conclusions: The use of PPIs is associated with a higher risk of SBP and HE in cirrhotic patients. However, the quality of included studies in the current systematic review and meta-analysis was moderate, and high-quality studies with a larger sample size are required.
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11
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Crocombe D, O’Brien A. Antimicrobial prophylaxis in decompensated cirrhosis: friend or foe? Hepatol Commun 2023; 7:e0228. [PMID: 37655979 PMCID: PMC10476838 DOI: 10.1097/hc9.0000000000000228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Accepted: 06/21/2023] [Indexed: 09/02/2023] Open
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Long B, Gottlieb M. Emergency medicine updates: Spontaneous bacterial peritonitis. Am J Emerg Med 2023; 70:84-89. [PMID: 37244043 DOI: 10.1016/j.ajem.2023.05.015] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Revised: 05/11/2023] [Accepted: 05/12/2023] [Indexed: 05/29/2023] Open
Abstract
INTRODUCTION Spontaneous bacterial peritonitis (SBP) is a common infection in patients with cirrhosis and ascites and is associated with significant risk of mortality. Therefore, it is important for emergency medicine clinicians to be aware of the current evidence regarding the diagnosis and management of this condition. OBJECTIVE This paper evaluates key evidence-based updates concerning SBP for the emergency clinician. DISCUSSION SBP is commonly due to Gram-negative bacteria, but infections due to Gram-positive bacteria and multidrug resistant bacteria are increasing. The typical presentation of SBP includes abdominal pain, worsening ascites, fever, or altered mental status in a patient with known liver disease; however, some patients may be asymptomatic or present with only mild symptoms. Paracentesis is the diagnostic modality of choice and should be performed in any patient with ascites and concern for SBP or upper gastrointestinal bleeding, or in those being admitted for a complication of cirrhosis. Ultrasound should be used to optimize the procedure. An ascites absolute neutrophil count (ANC) ≥ 250 cells/mm3 is diagnostic of SBP. Ascitic fluid should be placed in blood culture bottles to improve the culture yield. Leukocyte esterase reagent strips can be used for rapid diagnosis if available. While many patients will demonstrate coagulation panel abnormalities, routine transfusion is not recommended. Management traditionally includes a third-generation cephalosporin, but specific patient populations may require more broad-spectrum coverage with a carbapenem or piperacillin-tazobactam. Albumin infusion is associated with reduced risk of renal impairment and mortality. CONCLUSIONS An understanding of literature updates can improve the care of patients with suspected SBP.
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Affiliation(s)
- Brit Long
- SAUSHEC, Emergency Medicine, Brooke Army Medical Center, United States of America.
| | - Michael Gottlieb
- Department of Emergency Medicine, Rush University Medical Center, Chicago, IL, United States of America
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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: 0] [Impact Index Per Article: 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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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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15
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Crocombe D, Ahmed N, Balakrishnan I, Bordea E, Chau M, China L, Corless L, Danquah V, Dehbi HM, Dillon JF, Forrest EH, Freemantle N, Gear DP, Hollywood C, Hunter R, Jeyapalan T, Kallis Y, McPherson S, Munteanu I, Portal J, Richardson P, Ryder SD, Virk A, Wright G, O'Brien A. ASEPTIC: primary antibiotic prophylaxis using co-trimoxazole to prevent SpontanEous bacterial PeritoniTIs in Cirrhosis-study protocol for an interventional randomised controlled trial. Trials 2022; 23:812. [PMID: 36167573 PMCID: PMC9513307 DOI: 10.1186/s13063-022-06727-6] [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: 07/18/2022] [Accepted: 09/08/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Bacterial infection is a major cause of mortality in patients with cirrhosis. Spontaneous bacterial peritonitis (SBP) is a serious and common infection in patients with cirrhosis and ascites. Secondary prophylactic antibiotic therapy has been shown to improve outcomes after an episode of SBP but primary prophylaxis to prevent the first episode of SBP remains contentious. The aim of this trial is to assess whether primary antibiotic prophylaxis with co-trimoxazole improves overall survival compared to placebo in adults with cirrhosis and ascites. METHODS The ASEPTIC trial is a multicentre, placebo-controlled, double-blinded, randomised controlled trial (RCT) in England, Scotland, and Wales. Patients aged 18 years and older with cirrhosis and ascites requiring diuretic treatment or paracentesis, and no current or previous episodes of SBP, are eligible, subject to exclusion criteria. The trial aims to recruit 432 patients from at least 30 sites. Patients will be randomised in a 1:1 ratio to receive either oral co-trimoxazole 960 mg or an identical placebo once daily for 18 months, with 6 monthly follow-up visits thereafter (with a maximum possible follow-up period of 48 months, and a minimum of 18 months). The primary outcome is overall survival. Secondary outcomes include the time to the first incidence of SBP, hospital admission rates, incidence of other infections (including Clostridium difficile) and antimicrobial resistance, patients' health-related quality of life, health and social care resource use, incidence of cirrhosis-related decompensation events, liver transplantation, and treatment-related serious adverse events. DISCUSSION This trial will investigate the efficacy, safety, and cost-effectiveness of co-trimoxazole for patients with liver cirrhosis and ascites to determine whether this strategy improves clinical outcomes. Given there are no treatments that improve survival in decompensated cirrhosis outside of liver transplant, if the trial has a positive outcome, we anticipate widespread adoption of primary antibiotic prophylaxis. TRIAL REGISTRATION ClinicalTrials.gov NCT043955365 . Registered on 18 April 2020. Research ethical approval was granted by the Research Ethics Committee (South Central - Oxford B; REC 19/SC/0311) and the Medicines and Healthcare products Regulatory Agency (MHRA).
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Affiliation(s)
- Dominic Crocombe
- UCL Institute of Liver and Digestive Health, Sheila Sherlock Liver Centre, Royal Free London NHS Foundation Trust, London, UK
| | - Norin Ahmed
- University College London Comprehensive Clinical Trials Unit, London, UK
| | - Indran Balakrishnan
- Royal Free London NHS Foundation Trust, University College London, London, UK
| | - Ekaterina Bordea
- University College London Comprehensive Clinical Trials Unit, London, UK
| | - Marisa Chau
- University College London Comprehensive Clinical Trials Unit, London, UK
| | - Louise China
- UCL Institute of Liver and Digestive Health, Sheila Sherlock Liver Centre, Royal Free London NHS Foundation Trust, London, UK
| | | | - Victoria Danquah
- University College London Comprehensive Clinical Trials Unit, London, UK
| | - Hakim-Moulay Dehbi
- University College London Comprehensive Clinical Trials Unit, London, UK
| | - John F Dillon
- Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee, Dundee, UK
| | - Ewan H Forrest
- Gastroenterology Unit, Glasgow Royal Infirmary, University of Glasgow, Glasgow, UK
| | - Nick Freemantle
- University College London Comprehensive Clinical Trials Unit, London, UK
| | | | - Coral Hollywood
- Gloucestershire Hospitals NHS Foundation Trust, Gloucester, UK
| | - Rachael Hunter
- University College London Comprehensive Clinical Trials Unit, London, UK
| | - Tasheeka Jeyapalan
- University College London Comprehensive Clinical Trials Unit, London, UK
| | - Yiannis Kallis
- The Blizard Institute, Queen Mary University of London, London, UK
| | - Stuart McPherson
- Liver Unit, The Newcastle Upon Tyne Hospitals NHS Foundation Trust, The Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Iulia Munteanu
- University College London Comprehensive Clinical Trials Unit, London, UK
| | - Jim Portal
- University Hospitals Bristol NHS Foundation Trust, Bristol, UK
| | - Paul Richardson
- Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - Stephen D Ryder
- NIHR Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust, University of Nottingham, Nottingham, UK
| | - Amandeep Virk
- University College London Comprehensive Clinical Trials Unit, London, UK
| | - Gavin Wright
- Mid & South Essex NHS Foundation Trust, Basildon, UK
| | - Alastair O'Brien
- UCL Institute of Liver and Digestive Health, Sheila Sherlock Liver Centre, Royal Free London NHS Foundation Trust, London, UK. a.o'.,University College London Comprehensive Clinical Trials Unit, London, UK. a.o'.,University College London Hospitals NHS Foundation Trust, London, UK. a.o'
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16
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Association Between Proton Pump Inhibitor Therapy and Spontaneous Bacterial Peritonitis Occurrence in Cirrhotic Patients: A Clinical Review. Curr Med Sci 2022; 42:673-680. [PMID: 35870102 DOI: 10.1007/s11596-022-2607-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2021] [Accepted: 01/20/2022] [Indexed: 11/26/2022]
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Mahmud N, Serper M, Taddei TH, Kaplan DE. The Association Between Proton Pump Inhibitor Exposure and Key Liver-Related Outcomes in Patients With Cirrhosis: A Veterans Affairs Cohort Study. Gastroenterology 2022; 163:257-269.e6. [PMID: 35398042 PMCID: PMC10020994 DOI: 10.1053/j.gastro.2022.03.052] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Revised: 03/24/2022] [Accepted: 03/29/2022] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS The impact of proton pump inhibitory (PPI) medications on adverse outcomes in cirrhosis remains controversial. We aimed to evaluate the association between PPI exposure and all-cause mortality, infection, and decompensation in a large national cohort. METHODS This was a retrospective study of patients with cirrhosis in the Veterans Health Administration. PPI exposure was classified as a time-updating variable from the index time of the cirrhosis diagnosis. Inverse probability treatment weighting-adjusted Cox regression was performed with additional adjustment for key time-varying covariates, including cardiovascular comorbidities, gastrointestinal bleeding (GIB), and statin exposure. RESULTS The study included 76,251 patients, 23,628 of whom were on a PPI at baseline. In adjusted models, binary (yes/no) PPI exposure was associated with reduced hazard of all-cause mortality in patients with hospitalization for GIB (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.84-0.91; P < .001) but had no significant association in all others (HR, 0.99; 95% CI, 0.97-1.02; P = .58). However, cumulative PPI exposure was associated with increased mortality in patients without hospitalization for GIB (HR, 1.07 per 320 mg-months [omeprazole equivalents]; 95% CI, 1.06-1.08; P < .001). PPI exposure was significantly associated with severe infection (HR, 1.21; 95% CI, 1.18-1.24; P < .001) and decompensation (HR, 1.64; 95% CI, 1.61-1.68; P < .001). In a cause-specific mortality analysis, PPI exposure was associated with increased liver-related mortality (HR, 1.23; 95% CI, 1.19-1.28) but with decreased nonliver-related mortality (HR, 0.88; 95% CI, 0.85-0.91). CONCLUSIONS PPI exposure is associated with increased risk of infection and decompensation in cirrhosis, which may mediate liver-related mortality. However, PPI use was associated with reduced all-cause mortality in those with prior GIB, suggesting benefit in the presence of an appropriate indication.
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Affiliation(s)
- Nadim Mahmud
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; Department of Medicine, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania; Leonard David Institute of Health Economics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics, Epidemiology & Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
| | - Marina Serper
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; Department of Medicine, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania; Leonard David Institute of Health Economics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
| | - Tamar H Taddei
- Division of Digestive Diseases, Yale University School of Medicine, New Haven, Connecticut; Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut
| | - David E Kaplan
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; Department of Medicine, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania
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18
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Macken L, Corrigan M, Prentice W, Finlay F, McDonagh J, Rajoriya N, Salmon C, Donnelly M, Evans C, Ganai B, Bedlington J, Steer S, Wright M, Hudson B, Verma S. Palliative long-term abdominal drains for the management of refractory ascites due to cirrhosis: a consensus document. Frontline Gastroenterol 2022; 13:e116-e125. [PMID: 35812034 PMCID: PMC9234735 DOI: 10.1136/flgastro-2022-102128] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Accepted: 05/15/2022] [Indexed: 02/06/2023] Open
Abstract
Palliative care remains suboptimal in advanced cirrhosis, in part relating to a lack of evidence-based interventions. Ascites remains the most common cirrhosis complication resulting in hospitalisation. Many patients with refractory ascites are not candidates for liver transplantation or transjugular intrahepatic portosystemic shunt, and therefore, require recurrent palliative large volume paracentesis in hospital. We review the available evidence on use of palliative long-term abdominal drains in cirrhosis. Pending results of a national trial (REDUCe 2) and consistent with recently published national and American guidance, long-term abdominal drains cannot be regarded as standard of care in advanced cirrhosis. They should instead be considered only on a case-by-case basis, pending definitive evidence. This manuscript provides consensus to help standardise use of long-term abdominal drains in cirrhosis including patient selection and community management. Our ultimate aim remains to improve palliative care for this under researched and vulnerable cohort.
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Affiliation(s)
- Lucia Macken
- Gastroenterology and Hepatology, University Hospitals Sussex NHS Foundation Trust, Brighton, UK
| | - Margaret Corrigan
- Hepatology, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - Wendy Prentice
- Department of Palliative Care Medicine, King's College Hospital NHS Foundation Trust, London, UK
| | - Fiona Finlay
- Palliative Medicine, Queen Elizabeth University Hospital Campus, Glasgow, UK
| | | | - Neil Rajoriya
- Liver Unit, Queen Elizabeth Hospital, Birmingham, UK
| | - Claire Salmon
- Hepatology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | | | | | - Bhaskar Ganai
- Gastroenterology and Hepatology, University Hospitals Sussex NHS Foundation Trust, Brighton, UK
| | | | - Shani Steer
- Patient and Public involvement, Brighton, UK
| | - Mark Wright
- Hepatology, University Hospital Southampton, Southampton, UK
| | - Ben Hudson
- Hepatology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
| | - Sumita Verma
- Gastroenterology and Hepatology, University Hospitals Sussex NHS Foundation Trust, Brighton, UK,Clinical and Experimental Medicine, Brighton and Sussex Medical School, Brighton, UK
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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: 2] [Impact Index Per Article: 0.7] [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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20
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Chinzon D, Domingues G, Tosetto N, Perrotti M. SAFETY OF LONG-TERM PROTON PUMP INHIBITORS: FACTS AND MYTHS. ARQUIVOS DE GASTROENTEROLOGIA 2022; 59:219-225. [PMID: 35830032 DOI: 10.1590/s0004-2803.202202000-40] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Accepted: 01/06/2022] [Indexed: 06/15/2023]
Abstract
BACKGROUND Proton pump inhibitors (PPIs) are one of the most prescribed drugs in the world. Frequent use and long-term maintenance of these drugs drew the attention of researchers for sporadic adverse effects reports. OBJECTIVE The purpose of this narrative review is to discuss appropriate data and causality related to these adverse events and PPIs. METHODS A narrative review was conducted by systematizing information about safety and adverse events on PPIs from 2015 to 2020. A structured search on Pubmed was performed to identify systematic reviews and meta-analysis investigating the following situations: a) gastric cancer; b) micronutrients deficiency; c) acid rebound; d) infections; e) fractures; f) dementia; g) kidney disease; and h) sudden death and cardiovascular changes. RESULTS Recent studies have potentially associated PPIs with some adverse events as osteoporosis-related fractures. There are also reports of intestinal infections, including Clostridium difficile, besides poor vitamins absorption and minerals such as vitamin B12, magnesium, and iron. Furthermore, there are some dementia, pneumonia, kidney disease, myocardial infarction, and stroke reports. For kidney diseases, studies consistently suggest that the use of PPI may be associated with an increased risk of adverse kidney events, especially in the elderly, with long-term PPI use and pre-existing kidney disease. Another additional question is whether chronic PPI use would also lead to the onset of gastric cancer. The abrupt discontinuation of PPIs is also related to increased gastric acid production above pre-PPI treatment levels; this phenomenon is called acid rebound. CONCLUSION The key to mitigate adverse effects is the rational use of PPIs at the lowest effective dose and in the shortest possible duration. Although these adverse effects have a potential clinical impact, their causal association is still subject to validation.
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Affiliation(s)
- Decio Chinzon
- Faculdade de Medicina da Universidade de São Paulo, Departamento de Gastroenterologia, São Paulo, SP, Brasil
| | - Gerson Domingues
- Faculdade de Medicina da Universidade do Estado do Rio Janeiro, Departamento de Gastroenterologia, Rio de Janeiro, RJ, Brasil
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21
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Liu YB, Chen MK. The impact of proton pump inhibitors in liver diseases and the effects on the liver. J Dig Dis 2022; 23:196-208. [PMID: 35357775 DOI: 10.1111/1751-2980.13093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Revised: 03/09/2022] [Accepted: 03/29/2022] [Indexed: 12/11/2022]
Abstract
In this systematic and comprehensive overview, we aimed to evaluate the impact of proton pump inhibitors (PPIs) on chronic liver diseases, especially on cirrhosis. A manual and comprehensive search of the PubMed database was conducted to obtain relevant literatures. PPIs altered the composition and function of the intestinal microflora and might lead to small intestinal bacterial overgrowth and bacterial translocation, which were associated with adverse effects in liver diseases. They might increase the risk of hepatic encephalopathy, spontaneous bacterial peritonitis, infections, and are related to an increased mortality in cirrhosis. PPIs might lead to an increased risk of hepatocellular carcinoma, although the mechanism is unknown, and the results are controversial. PPIs also had an impact on the direct-acting antiviral regimen in patients with chronic hepatitis C. They were associated with an increased risk of liver abscess and increased mortality. Additionally, PPIs might lead to metabolic risk events, such as liver steatosis and weight gain. PPIs are associated with several adverse outcomes in liver diseases. Cautious use of PPIs is recommended and clinicians should be aware of the indications for their use in patients with liver diseases.
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Affiliation(s)
- Yuan Bin Liu
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
| | - Ming Kai Chen
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
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22
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Samonakis DN, Gatselis N, Bellou A, Sifaki-Pistolla D, Mela M, Demetriou G, Thalassinos E, Rigopoulou EI, Kevrekidou P, Tziortziotis I, Azariadi K, Kavousanaki M, Digenakis E, Vassiliadis T, Kouroumalis EA, Dalekos GN. Spontaneous bacterial peritonitis: a prospective Greek multicenter study of its epidemiology, microbiology, and outcomes. Ann Gastroenterol 2022; 35:80-87. [PMID: 34987293 PMCID: PMC8713337 DOI: 10.20524/aog.2021.0674] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2020] [Accepted: 07/20/2021] [Indexed: 11/11/2022] Open
Abstract
Background Spontaneous bacterial peritonitis (SBP) is an ominous complication of decompensated cirrhosis. This study aimed to assess several epidemiological, clinical, microbiological and outcome characteristics in Greek patients with SBP, as no solid representative nationwide data of this type was available. Methods During a 3-year period, 77 consecutive patients with SBP (61 male; median age: 67 years; model for end-stage liver disease [MELD] score: 20), diagnosed and followed in 5 tertiary liver units, were prospectively recruited and studied. Various prognostic factors for disease outcome were studied. Results Thirty-eight patients had alcohol-related cirrhosis, 17 viral hepatitis, 6 non-alcoholic steatohepatitis, 6 autoimmune liver diseases, and 10 cryptogenic cirrhosis. Hepatocellular carcinoma (HCC) was present in 23 (29.9%), whereas 10 (13%) had portal vein thrombosis. The first SBP episode at baseline was community-acquired in 53 (68.8%), while in 24 (31.1%) was hospital-acquired, with predominant symptoms abdominal pain and encephalopathy. A positive ascitic culture was documented in 36% of patients in the initial episode, with almost equal gram (+) and gram (-) pathogens, including 3 multidrug-resistant pathogens. Significant factors for 6-month survival were: higher MELD score, previous b-blocker use, lower serum albumin, higher lactate on admission and need for vasopressors, while factors for 12-month survival were MELD score and lactate. For overall survival, higher MELD score and lactate along with HCC presence were negative predictive factors. Conclusions MELD score, lactate, albumin, HCC and treatment with vasopressors were predictive of survival in SBP patients. In hospital-acquired SBP the prevalence of difficult-to-treat pathogens was higher.
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Affiliation(s)
- Dimitrios N Samonakis
- Department of Gastroenterology and Hepatology, University Hospital of Heraklion Crete, Greece (Dimitrios N. Samonakis, George Demetriou, Emmanuel Digenakis, Elias A. Kouroumalis)
| | - Nikolaos Gatselis
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Greece (Nikolaos Gatselis, Aristea Bellou, Eirini I. Rigopoulou, Kalliopi Azariadi, George N. Dalekos)
| | - Aristea Bellou
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Greece (Nikolaos Gatselis, Aristea Bellou, Eirini I. Rigopoulou, Kalliopi Azariadi, George N. Dalekos).,3 Department of Internal Medicine, Papageorgiou General Hospital, Aristotle University of Thessaloniki, Greece (Aristea Bellou, Polyxeni Kevrekidou, Themistoklis Vassiliadis)
| | - Dimitra Sifaki-Pistolla
- Clinic of Social and Family Medicine, School of Medicine, University of Crete, Heraklion, Crete, Greece (Dimitra Sifaki-Pistolla, Ioannis Tziortziotis)
| | - Maria Mela
- Department of Gastroenterology, Evangelismos Hospital, Athens, Greece (Maria Mela)
| | - George Demetriou
- Department of Gastroenterology and Hepatology, University Hospital of Heraklion Crete, Greece (Dimitrios N. Samonakis, George Demetriou, Emmanuel Digenakis, Elias A. Kouroumalis)
| | - Evangelos Thalassinos
- Department of Internal Medicine, Venizeleion Hospital, Heraklion, Crete, Greece (Evangelos Thalassinos, Melina Kavousanaki)
| | - Eirini I Rigopoulou
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Greece (Nikolaos Gatselis, Aristea Bellou, Eirini I. Rigopoulou, Kalliopi Azariadi, George N. Dalekos)
| | - Polyxeni Kevrekidou
- 3 Department of Internal Medicine, Papageorgiou General Hospital, Aristotle University of Thessaloniki, Greece (Aristea Bellou, Polyxeni Kevrekidou, Themistoklis Vassiliadis)
| | - Ioannis Tziortziotis
- Clinic of Social and Family Medicine, School of Medicine, University of Crete, Heraklion, Crete, Greece (Dimitra Sifaki-Pistolla, Ioannis Tziortziotis)
| | - Kalliopi Azariadi
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Greece (Nikolaos Gatselis, Aristea Bellou, Eirini I. Rigopoulou, Kalliopi Azariadi, George N. Dalekos)
| | - Melina Kavousanaki
- Department of Internal Medicine, Venizeleion Hospital, Heraklion, Crete, Greece (Evangelos Thalassinos, Melina Kavousanaki)
| | - Emmanuel Digenakis
- Department of Gastroenterology and Hepatology, University Hospital of Heraklion Crete, Greece (Dimitrios N. Samonakis, George Demetriou, Emmanuel Digenakis, Elias A. Kouroumalis)
| | - Themistoklis Vassiliadis
- 3 Department of Internal Medicine, Papageorgiou General Hospital, Aristotle University of Thessaloniki, Greece (Aristea Bellou, Polyxeni Kevrekidou, Themistoklis Vassiliadis)
| | - Elias A Kouroumalis
- Department of Gastroenterology and Hepatology, University Hospital of Heraklion Crete, Greece (Dimitrios N. Samonakis, George Demetriou, Emmanuel Digenakis, Elias A. Kouroumalis)
| | - George N Dalekos
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Greece (Nikolaos Gatselis, Aristea Bellou, Eirini I. Rigopoulou, Kalliopi Azariadi, George N. Dalekos)
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Sun S, Ye W, Zhao R, Hu J, Zhang X, Yang M, Zhao H, Sheng J. Proton Pump Inhibitor Therapy Does Not Affect Prognosis of Cirrhosis Patients With Acute Decompensation and Acute-on-Chronic Liver Failure: A Single-Center Prospective Study. Front Med (Lausanne) 2021; 8:763370. [PMID: 34859015 PMCID: PMC8631392 DOI: 10.3389/fmed.2021.763370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Accepted: 10/07/2021] [Indexed: 11/18/2022] Open
Abstract
Background: The aim of this study was to investigate the impact of proton pump inhibitor (PPI) therapy on complications and prognosis in cirrhosis patients with and without acute-on-chronic liver failure (ACLF). Materials and Methods: Cirrhosis patients with acute decompensation (AD) (n = 489) admitted in our center were enrolled in this prospective observational cohort study. According to treatment received, patients were identified as users or nonusers of PPI. Clinical and laboratory data, complications during hospitalization, and overall survival were recorded in all the patients. Results: Of the 489 patients, 299 (61.1%) patients received PPI therapy. The logistic regression analysis showed that age, albumin, history of previous hepatic encephalopathy (HE), and the chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score were independent risk factors for HE in patients with decompensated cirrhosis [odds ratio (OR) = 1.07, 95% CI: 1.03–1.12, p = 0.001; OR = 1.13, 95% CI: 1.04–1.24, p = 0.006; OR = 242.52, 95% CI: 40.17–1464.11, p < 0.001; and OR = 2.89, 95% CI: 2.11–3.96, p < 0.001, respectively]. Previous severe liver injury and previous bacterial infections were independent risk factors for spontaneous bacterial peritonitis (SBP) in patients with decompensated cirrhosis (OR = 3.43, 95% CI: 1.16–10.17, p = 0.026 and OR = 6.47, 95% CI: 2.29–18.29, p < 0.001, respectively). The multivariate Cox proportional hazards regression model showed that the type and dose of the PPI used were not related to 28-day and 90-day mortality in cirrhosis patients with AD or ACLF. Conclusion: PPI use does not appear to increase mortality or the risk of HE and SBP in the hospitalized cirrhosis patients with and without ACLF.
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Affiliation(s)
- Shanshan Sun
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Wenyi Ye
- Department of Traditional Chinese Internal Medicine, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
| | - Ruihong Zhao
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jianhua Hu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xuan Zhang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Meifang Yang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Hong Zhao
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jifang Sheng
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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24
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Zhang M, Xu X, Liu W, Zhang Z, Cheng Q, Yang Z, Liu T, Liu Y, Ning Q, Chen T, Qi J. Proton Pump Inhibitor Therapy Increases the Risk of Spontaneous Bacterial Peritonitis in Patients with HBV-Related Acute-on-Chronic Liver Failure. Adv Ther 2021; 38:4675-4694. [PMID: 34308513 DOI: 10.1007/s12325-021-01844-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Accepted: 06/24/2021] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Spontaneous bacterial peritonitis (SBP) is a common infection in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF). SBP significantly increases the mortality rate and medical costs. The association between proton pump inhibitor (PPI) use and SBP remains unclear. We conducted a retrospective study to investigate the association between PPI use and SBP in patients with HBV-related ACLF and to explore the risk factors for SBP. METHODS We compared the SBP incidence between the PPI and non-PPI groups before and after propensity score matching and explored the association between the duration and type of PPI and SBP occurrence. Risk factors for SBP occurrence were determined by univariate and multivariate logistic regression analysis. RESULTS The SBP incidence was higher in the PPI group than in the non-PPI group before and after propensity score matching. The SBP incidence increased for elevated MELD scores in PPI users. There was a similar SBP incidence in both different types and durations of PPI users. MELD score, old age, male sex, and high WBC count were significant independent risk factors for SBP in PPI users with HBV-related ACLF in the hospital. CONCLUSIONS PPI therapy increases the risk of SBP development in patients with HBV-related ACLF. MELD score, old age, male sex, and high WBC count could serve as predictors of SBP in PPI users. Caution should be taken regarding PPI use, especially for patients with MELD scores > 30.
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Affiliation(s)
- Meng Zhang
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095, Jiefang Avenue, Wuhan, 430030, People's Republic of China
| | - Xin Xu
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095, Jiefang Avenue, Wuhan, 430030, People's Republic of China
| | - Wei Liu
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095, Jiefang Avenue, Wuhan, 430030, People's Republic of China
| | - Zhongwei Zhang
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095, Jiefang Avenue, Wuhan, 430030, People's Republic of China
| | - Qiuyu Cheng
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095, Jiefang Avenue, Wuhan, 430030, People's Republic of China
| | - Zhongyuan Yang
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095, Jiefang Avenue, Wuhan, 430030, People's Republic of China
| | - Tingting Liu
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095, Jiefang Avenue, Wuhan, 430030, People's Republic of China
| | - Yunhui Liu
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095, Jiefang Avenue, Wuhan, 430030, People's Republic of China
| | - Qin Ning
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095, Jiefang Avenue, Wuhan, 430030, People's Republic of China
| | - Tao Chen
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095, Jiefang Avenue, Wuhan, 430030, People's Republic of China.
| | - Junying Qi
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095, Jiefang Avenue, Wuhan, 430030, People's Republic of China.
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25
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Sakamaki A, Kamimura K, Yokoo T, Osaki A, Yoshikawa S, Arao Y, Setsu T, Kamimura H, Waguri N, Takeuchi M, Funakoshi K, Terai S. The prognosis and incidence of hepatic encephalopathy of patients with liver cirrhosis treated with proton pump inhibitors: A multicenter retrospective study in Japan. Medicine (Baltimore) 2021; 100:e26902. [PMID: 34397919 PMCID: PMC8360404 DOI: 10.1097/md.0000000000026902] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Revised: 10/12/2020] [Accepted: 11/22/2020] [Indexed: 01/04/2023] Open
Abstract
Gastrointestinal bleeding, hepatic encephalopathy (HE), and hepatocarcinogenesis are associated with the prognosis of patients with liver cirrhosis (LC). Proton pump inhibitors (PPIs) have been used to prevent bleeding, however the effects of PPIs on overall survival have not yet been elucidated. Therefore, this multicenter retrospective study aimed to assess the effect of PPI on the prognosis and HE occurrence of the patients with liver cirrhosis in Japan.A total of 456 patients diagnosed with LC at the 4 institutes during the study period (2010-2014) were assessed. PPI-treated and non-treated patients were compared using propensity score matching analysis. Primary and secondary endpoints of the study were set as the occurrence of HE and overall survival, respectively.A comparison of all cases showed a significantly poorer hepatic reserve function in the PPI-treated patients. The propensity-score matching analysis was performed and 120 PPI-treated patients were 1:1 matched with non-treated patients. The analysis revealed a higher incidence of HE in the PPI-treated than in the non-treated patients (P = .032; hazard ratio [HR], 2.162; 95% confidence interval [CI], 1.066-4.176), but the prognosis of PPI-treated patients was no worse than that of non-treated patients (P = .676; HR, 1.101; 95% CI, 0.702-1.726).This retrospective study showed that PPI administration for the patients with liver cirrhosis may partly be related to the increased incidence of HE but not worsen the patient prognosis.
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Affiliation(s)
- Akira Sakamaki
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan
| | - Kenya Kamimura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan
| | - Takeshi Yokoo
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan
| | - Akihiko Osaki
- Division of Gastroenterology and Hepatology, Niigata City General Hospital, Niigata, Niigata, Japan
| | - Seiichi Yoshikawa
- Division of Gastroenterology and Hepatology, Nagaoka Red Cross Hospital, Nagaoka, Niigata, Japan
| | - Yoshihisa Arao
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan
| | - Toru Setsu
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan
| | - Hiroteru Kamimura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan
| | - Nobuo Waguri
- Division of Gastroenterology and Hepatology, Niigata City General Hospital, Niigata, Niigata, Japan
| | - Manabu Takeuchi
- Division of Gastroenterology and Hepatology, Nagaoka Red Cross Hospital, Nagaoka, Niigata, Japan
| | - Kazuhiro Funakoshi
- Division of Gastroenterology and Hepatology, Niigata Central Prefectural Hospital, Joetsu, Niigata, Japan
| | - Shuji Terai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan
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26
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Yoshiji H, Nagoshi S, Akahane T, Asaoka Y, Ueno Y, Ogawa K, Kawaguchi T, Kurosaki M, Sakaida I, Shimizu M, Taniai M, Terai S, Nishikawa H, Hiasa Y, Hidaka H, Miwa H, Chayama K, Enomoto N, Shimosegawa T, Takehara T, Koike K. Evidence-based clinical practice guidelines for Liver Cirrhosis 2020. J Gastroenterol 2021; 56:593-619. [PMID: 34231046 PMCID: PMC8280040 DOI: 10.1007/s00535-021-01788-x] [Citation(s) in RCA: 206] [Impact Index Per Article: 51.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Accepted: 02/25/2021] [Indexed: 02/07/2023]
Abstract
The first edition of the clinical practice guidelines for liver cirrhosis was published in 2010, and the second edition was published in 2015 by the Japanese Society of Gastroenterology (JSGE). The revised third edition was recently published in 2020. This version has become a joint guideline by the JSGE and the Japan Society of Hepatology (JSH). In addition to the clinical questions (CQs), background questions (BQs) are new items for basic clinical knowledge, and future research questions (FRQs) are newly added clinically important items. Concerning the clinical treatment of liver cirrhosis, new findings have been reported over the past 5 years since the second edition. In this revision, we decided to match the international standards as much as possible by referring to the latest international guidelines. Newly developed agents for various complications have also made great progress. In comparison with the latest global guidelines, such as the European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases (AASLD), we are introducing data based on the evidence for clinical practice in Japan. The flowchart for nutrition therapy was reviewed to be useful for daily medical care by referring to overseas guidelines. We also explain several clinically important items that have recently received focus and were not mentioned in the last editions. This digest version describes the issues related to the management of liver cirrhosis and several complications in clinical practice. The content begins with a diagnostic algorithm, the revised flowchart for nutritional therapy, and refracted ascites, which are of great importance to patients with cirrhosis. In addition to the updated antiviral therapy for hepatitis B and C liver cirrhosis, the latest treatments for non-viral cirrhosis, such as alcoholic steatohepatitis/non-alcoholic steatohepatitis (ASH/NASH) and autoimmune-related cirrhosis, are also described. It also covers the latest evidence regarding the diagnosis and treatment of liver cirrhosis complications, namely gastrointestinal bleeding, ascites, hepatorenal syndrome and acute kidney injury, hepatic encephalopathy, portal thrombus, sarcopenia, muscle cramp, thrombocytopenia, pruritus, hepatopulmonary syndrome, portopulmonary hypertension, and vitamin D deficiency, including BQ, CQ and FRQ. Finally, this guideline covers prognosis prediction and liver transplantation, especially focusing on several new findings since the last version. Since this revision is a joint guideline by both societies, the same content is published simultaneously in the official English journal of JSGE and JSH.
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Affiliation(s)
- Hitoshi Yoshiji
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan.
- Department of Gastroenterology, Nara Medical University, Shijo-cho 840, Kashihara, Nara, 634-8522, Japan.
| | - Sumiko Nagoshi
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Takemi Akahane
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Yoshinari Asaoka
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Yoshiyuki Ueno
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Koji Ogawa
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Takumi Kawaguchi
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Masayuki Kurosaki
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Isao Sakaida
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Masahito Shimizu
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Makiko Taniai
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Shuji Terai
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Hiroki Nishikawa
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Yoichi Hiasa
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Hisashi Hidaka
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Hiroto Miwa
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Kazuaki Chayama
- The Japan Society of Hepatology, Kashiwaya 2 Building 5F, 3-28-10 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan
| | - Nobuyuki Enomoto
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Tooru Shimosegawa
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Tetsuo Takehara
- The Japan Society of Hepatology, Kashiwaya 2 Building 5F, 3-28-10 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan
| | - Kazuhiko Koike
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
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27
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Yoshiji H, Nagoshi S, Akahane T, Asaoka Y, Ueno Y, Ogawa K, Kawaguchi T, Kurosaki M, Sakaida I, Shimizu M, Taniai M, Terai S, Nishikawa H, Hiasa Y, Hidaka H, Miwa H, Chayama K, Enomoto N, Shimosegawa T, Takehara T, Koike K. Evidence-based clinical practice guidelines for liver cirrhosis 2020. Hepatol Res 2021; 51:725-749. [PMID: 34231046 DOI: 10.1111/hepr.13678] [Citation(s) in RCA: 100] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Accepted: 05/26/2021] [Indexed: 12/14/2022]
Abstract
The first edition of the clinical practice guidelines for liver cirrhosis was published in 2010, and the second edition was published in 2015 by the Japanese Society of Gastroenterology (JSGE). The revised third edition was recently published in 2020. This version has become a joint guideline by the JSGE and the Japanese Society of Hepatology (JSH). In addition to the clinical questions (CQs), background questions (BQs) are new items for basic clinical knowledge, and future research questions (FRQs) are newly added clinically important items. Concerning the clinical treatment of liver cirrhosis, new findings have been reported over the past 5 years since the second edition. In this revision, we decided to match the international standards as much as possible by referring to the latest international guidelines. Newly developed agents for various complications have also made great progress. In comparison with the latest global guidelines, such as the European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases (AASLD), we are introducing data based on the evidence for clinical practice in Japan. The flowchart for nutrition therapy was reviewed to be useful for daily medical care by referring to overseas guidelines. We also explain several clinically important items that have recently received focus and were not mentioned in the last editions. This digest version describes the issues related to the management of liver cirrhosis and several complications in clinical practice. The content begins with a diagnostic algorithm, the revised flowchart for nutritional therapy, and refracted ascites, which are of great importance to patients with cirrhosis. In addition to the updated antiviral therapy for hepatitis B and C liver cirrhosis, the latest treatments for non-viral cirrhosis, such as alcoholic steatohepatitis/non-alcoholic steatohepatitis (ASH/NASH) and autoimmune-related cirrhosis, are also described. It also covers the latest evidence regarding the diagnosis and treatment of liver cirrhosis complications, namely gastrointestinal bleeding, ascites, hepatorenal syndrome and acute kidney injury, hepatic encephalopathy, portal thrombus, sarcopenia, muscle cramp, thrombocytopenia, pruritus, hepatopulmonary syndrome, portopulmonary hypertension, and vitamin D deficiency, including BQ, CQ and FRQ. Finally, this guideline covers prognosis prediction and liver transplantation, especially focusing on several new findings since the last version. Since this revision is a joint guideline by both societies, the same content is published simultaneously in the official English journal of JSGE and JSH.
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Affiliation(s)
- Hitoshi Yoshiji
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan.,Department of Gastroenterology, Nara Medical University, Nara, Japan
| | - Sumiko Nagoshi
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Takemi Akahane
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Yoshinari Asaoka
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Yoshiyuki Ueno
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Koji Ogawa
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Takumi Kawaguchi
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Masayuki Kurosaki
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Isao Sakaida
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Masahito Shimizu
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Makiko Taniai
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Shuji Terai
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Hiroki Nishikawa
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Yoichi Hiasa
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Hisashi Hidaka
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Hiroto Miwa
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | | | - Nobuyuki Enomoto
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Tooru Shimosegawa
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | | | - Kazuhiko Koike
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
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Campbell KA, Trivedi HD, Chopra S. Infections in Cirrhosis: A Guide for the Clinician. Am J Med 2021; 134:727-734. [PMID: 33607090 DOI: 10.1016/j.amjmed.2021.01.015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2020] [Revised: 12/31/2020] [Accepted: 01/25/2021] [Indexed: 12/13/2022]
Abstract
Cirrhosis contributes significantly to morbidity and mortality worldwide. Infections in patients with cirrhosis are common and significantly impact health-related quality of life. As our understanding of immune dysfunction associated with cirrhosis grows and as rates of drug-resistant organisms increase, the management of infections in cirrhosis has become increasingly nuanced. In this review, we discuss the current understanding of cirrhosis-associated immune deficiency, review the most common infections in patients with cirrhosis, and highlight techniques for the general clinician in the prevention and treatment of infections in this high-risk population.
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Affiliation(s)
- Kirsti A Campbell
- Beth Israel Deaconess Medical Center, Boston, Mass; Harvard Medical School, Boston, Mass.
| | - Hirsh D Trivedi
- Beth Israel Deaconess Medical Center, Boston, Mass; Harvard Medical School, Boston, Mass
| | - Sanjiv Chopra
- Beth Israel Deaconess Medical Center, Boston, Mass; Harvard Medical School, Boston, Mass
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Shaikh BA, Shaikh ZA, Shah AH, Kumar A. Determining the Risk of Spontaneous Bacterial Peritonitis due to increase use of Proton Pump Inhibitors among cirrhotic patients with ascites. Pak J Med Sci 2021; 37:1075-1079. [PMID: 34290786 PMCID: PMC8281193 DOI: 10.12669/pjms.37.4.3476] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Revised: 10/12/2020] [Accepted: 03/25/2021] [Indexed: 12/19/2022] Open
Abstract
Objectives The current study aimed to determine the Spontaneous Bacterial Peritonitis (SBP) risk due to increased use of Proton Pump Inhibitors (PPIs) among cirrhotic patients with ascites. Methods This retrospective case-control study was conducted at Chandka Medical College & Hospital, Larkana from March 2013 to February 2014, involving 215 cirrhotic patients with ascites. Paracentesis was performed to distinguish cirrhotic patients with SBP and Polymorphonuclear Neutrophil (PMN) count ≥ 250 neutrophils/mm3 (cases) and non-SBP with PMN count < 250 neutrophils/mm3 (controls). The demographic details, history of PPIs use before admission and duration of Chronic Liver Disease (CLD) were inquired and statistical analysis was carried through SPSS Version 23.0. Results Increased pre-hospital PPI intake was observed among cirrhotic patients with SBP (69.8%) as compared to those without SBP (48.8%; p = 0.014). The mean duration of PPI use was 19.16 ± 4.772 days, and it was more significant among older cirrhotic patients (p < 0.05). Increased duration of CLD was observed among PPI users, i.e. 20.47 ± 6.305 months vs. 18.95 ± 5.527 months among non-PPI users (p < 0.05). Conclusions Our results show that cirrhotic patients with ascites consuming PPIs are more likely to develop SBP as compared to non-PPI users.
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Affiliation(s)
- Bashir Ahmed Shaikh
- Bashir Ahmed Shaikh, FCPS, FRCP. Chandka Medical College Hospital, Shaheed Mohtarma Benazir Bhutto Medical University (SMBBMU), Larkana, Sindh, Pakistan
| | - Zahid Ali Shaikh
- Zahid Ali Shaikh, FCPS. Chandka Medical College Hospital, Shaheed Mohtarma Benazir Bhutto Medical University (SMBBMU), Larkana, Sindh, Pakistan
| | - Aftab Hussain Shah
- Aftab Hussain Shah, FCPS, FRCP. Chandka Medical College Hospital, Shaheed Mohtarma Benazir Bhutto Medical University (SMBBMU), Larkana, Sindh, Pakistan
| | - Aneel Kumar
- Aneel Kumar, FCPS. Chandka Medical College Hospital, Shaheed Mohtarma Benazir Bhutto Medical University (SMBBMU), Larkana, Sindh, Pakistan
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Alhumaid S, Al Mutair A, Al Alawi Z, Zaidi ARZ, Rabaan AA, Elhazmi A, Al-Omari A. Proton pump inhibitors use and risk of developing spontaneous bacterial peritonitis in cirrhotic patients: A systematic review and meta-analysis. Gut Pathog 2021; 13:17. [PMID: 33741033 PMCID: PMC7977161 DOI: 10.1186/s13099-021-00414-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Accepted: 03/11/2021] [Indexed: 02/06/2023] Open
Abstract
Background Spontaneous bacterial peritonitis (SBP) is one of the most common infectious diseases in patients with cirrhosis and is associated with serious prognosis. A prevailing dogma posits that SBP is exacerbated by the frequent use of proton pump inhibitors (PPIs). Aims To re-assess the association between PPIs use and SBP incidence with larger and better-quality data. Method The studies were identified by searching Proquest, Medline, and Embase for English language articles published between January 2008 and March 2020 using the following keywords alone or in combination: anti-ulcer agent, antacid, proton pump inhibitor, proton pumps, PPI, omeprazole, rabeprazole, lansoprazole, pantoprazole, esomeprazole, peritonitis, spontaneous bacterial peritonitis, SBP, ascites, cirrhosis, ascitic and cirrhotic. Three authors critically reviewed all of the studies retrieved and selected those judged to be the most relevant. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was followed. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Sub-group analyses were done to decrease the heterogeneity. Results A total of twenty-three studies: seven case–control, and sixteen cohorts, involving 10,386 patients were analyzed. The overall results showed a statistically significant association between SBP and PPIs use (pooled odds ratio (OR): 1.80, 95% CI of 1.41 to 2.31). Substantial heterogeneity was observed. On subgroup analysis involving cohort studies, the association was weaker (OR: 1.55 with 95% CI of 1.16 to 2.06 p < 0.00001) but still statistically significant and with high heterogeneity (Chi2p = 57.68; I2 = 74%). For case–control studies, the OR was 2.62 with a 95% CI of 1.94 to 3.54. The funnel plot was asymmetric and Egger’s test confirmed asymmetry suggesting publication bias (intercept = − 0.05, SE = 0.27, P = 0.850 two-tailed). Conclusion This meta-analysis sheds light on the conflicting results raised by previous studies regarding the association of SBP with PPIs use. Our meta-analysis showed that there is a weak association, although statistically significant, between SBP and PPIs use. However, the magnitude of the possible association diminished when analysis focused on higher quality data that were more robust. Thus, this updated meta-analysis suggests judicious use of PPIs among cirrhotic patients with ascites.
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Affiliation(s)
- Saad Alhumaid
- Administration of Pharmaceutical Care, Al-Ahsa Health Cluster, Ministry of Health, Al-Ahsa, Saudi Arabia.
| | - Abbas Al Mutair
- Research Center, Almoosa Specialist Hospital, Al-Ahsa, Saudi Arabia.,College of Nursing, Princess Nourah Bint Abdul Rahman University, Riyadh, Saudi Arabia.,School of Nursing, University of Wollongong, Wollongong, Australia
| | - Zainab Al Alawi
- Department of Paediatrics, College of Medicine, King Faisal University, Al-Ahsa, Saudi Arabia
| | - Abdul Rehman Zia Zaidi
- Research Center, Dr. Sulaiman Al Habib Medical Group, Riyadh, Saudi Arabia.,College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
| | - Ali A Rabaan
- Molecular Diagnostic Laboratory, Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia
| | - Alyaa Elhazmi
- Research Center, Dr. Sulaiman Al Habib Medical Group, Riyadh, Saudi Arabia
| | - Awad Al-Omari
- Research Center, Dr. Sulaiman Al Habib Medical Group, Riyadh, Saudi Arabia.,College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
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Aithal GP, Palaniyappan N, China L, Härmälä S, Macken L, Ryan JM, Wilkes EA, Moore K, Leithead JA, Hayes PC, O'Brien AJ, Verma S. Guidelines on the management of ascites in cirrhosis. Gut 2021; 70:9-29. [PMID: 33067334 PMCID: PMC7788190 DOI: 10.1136/gutjnl-2020-321790] [Citation(s) in RCA: 221] [Impact Index Per Article: 55.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Revised: 08/27/2020] [Accepted: 09/04/2020] [Indexed: 12/15/2022]
Abstract
The British Society of Gastroenterology in collaboration with British Association for the Study of the Liver has prepared this document. The aim of this guideline is to review and summarise the evidence that guides clinical diagnosis and management of ascites in patients with cirrhosis. Substantial advances have been made in this area since the publication of the last guideline in 2007. These guidelines are based on a comprehensive literature search and comprise systematic reviews in the key areas, including the diagnostic tests, diuretic use, therapeutic paracentesis, use of albumin, transjugular intrahepatic portosystemic stent shunt, spontaneous bacterial peritonitis and beta-blockers in patients with ascites. Where recent systematic reviews and meta-analysis are available, these have been updated with additional studies. In addition, the results of prospective and retrospective studies, evidence obtained from expert committee reports and, in some instances, reports from case series have been included. Where possible, judgement has been made on the quality of information used to generate the guidelines and the specific recommendations have been made according to the 'Grading of Recommendations Assessment, Development and Evaluation (GRADE)' system. These guidelines are intended to inform practising clinicians, and it is expected that these guidelines will be revised in 3 years' time.
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Affiliation(s)
- Guruprasad P Aithal
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
- Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK
| | - Naaventhan Palaniyappan
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
- Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK
| | - Louise China
- Institute of Liver Disease and Digestive Health, University College London, London, UK
| | - Suvi Härmälä
- Institute of Health Informatics, University College London, London, UK
| | - Lucia Macken
- Department of Clinical and Experimental Medicine, Brighton and Sussex Medical School, Brighton, UK
- Department of Gastroenterology and Hepatology, Brighton and Sussex University Hospitals NHS Trust, Brighton, UK
| | - Jennifer M Ryan
- Institute of Liver Disease and Digestive Health, University College London, London, UK
- Royal Free London NHS Foundation Trust, London, UK
| | - Emilie A Wilkes
- Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK
- Nottingham University Hospitals NHS Trust, Nottingham, UK
| | - Kevin Moore
- Institute of Liver Disease and Digestive Health, University College London, London, UK
| | - Joanna A Leithead
- Liver Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Peter C Hayes
- Hepatology Department, Royal Infirmary of Edinburgh, Edinburgh, UK
| | - Alastair J O'Brien
- Institute of Liver Disease and Digestive Health, University College London, London, UK
| | - Sumita Verma
- Department of Clinical and Experimental Medicine, Brighton and Sussex Medical School, Brighton, UK
- Department of Gastroenterology and Hepatology, Brighton and Sussex University Hospitals NHS Trust, Brighton, UK
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Lu Z, Sun X, Han J, Jin B, Zhang W, Han J, Ma X, Liu B, Yu X, Wu Q, Wang Y, Li H. Characteristics of peptic ulcer bleeding in cirrhotic patients with esophageal and gastric varices. Sci Rep 2020; 10:20068. [PMID: 33208832 PMCID: PMC7674460 DOI: 10.1038/s41598-020-76530-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Accepted: 10/14/2020] [Indexed: 02/07/2023] Open
Abstract
Upper gastrointestinal bleeding (UGIB) is common in liver cirrhosis. Although esophageal and gastric varices (EGV) is the main bleeding source, there were still a proportion of patients with peptic ulcer bleeding. Thus, this study aimed to analyze the characteristic of variceal bleeding and peptic ulcer bleeding in liver cirrhosis. Cirrhotic patients with confirmed UGIB by urgent endoscopy from July 2012 to June 2018 were enrolled, and classified into peptic ulcer bleeding group (n = 248) and variceal bleeding group (n = 402). Clinical and endoscopic characteristics, therapeutic efficacy and prognosis were evaluated, and independent risk factors for 42-day morality were determined. The mean age and gender ratio of peptic ulcer bleeding group were higher than those in variceal bleeding group (55.58 ± 11.37 vs. 52.87 ± 11.57, P < 0.01; 4.51:1 vs. 2.87:1, P = 0.023). Variceal bleeding group most commonly presented as red blood emesis and coffee grounds (67.16%), while peptic ulcer group primarily manifested as melena (62.10%). Hepatocellular carcinoma was more prevalent in peptic ulcer group (141 vs. 119, P < 0.01). Albumin level in variceal bleeding group was lower higher (P < 0.01), but serum bilirubin, creatinine and prothrombin time were significantly higher (all P < 0.01). Success rate of endoscopic hemostasis for variceal bleeding and peptic ulcer bleeding was 89.05% and 94.35% (P = 0.021). Univariate and multivariate analysis identified prothrombin time (P = 0.041, OR [95% CI] 0.884 [0.786–0.995]), MELD score (P = 0.000, OR [95% CI] 1.153 [1.073–1.240]), emergency intervention (P = 0.002, OR [95% CI] 8.656 [2.219–33.764]), hepatic encephalopathy before bleeding (P = 0.003, OR [95% CI] 8.119 [2.084–31.637]) and hepatic renal syndrome before bleeding (P = 0.029, OR [95% CI] 3.877 [1.152–13.045]) as the independent predictors for 42-day mortality. Peptic ulcer bleeding should be distinguished from variceal bleeding by clinical and endoscopic characteristics.
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Affiliation(s)
- Zheng Lu
- Liver Cirrhosis Diagnosis and Treatment Center, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China
| | - Xiaotian Sun
- Departement of Internal Medicine, Beijing South Medical District of Chinese PLA General Hospital, No. 1 North Liuli Bridge, Beijing, 100161, China
| | - Jingjing Han
- Liver Cirrhosis Diagnosis and Treatment Center, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China
| | - Bo Jin
- Liver Cirrhosis Diagnosis and Treatment Center, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China
| | - Wenhui Zhang
- Liver Cirrhosis Diagnosis and Treatment Center, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China
| | - Jun Han
- Liver Cirrhosis Diagnosis and Treatment Center, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China
| | - Xuemei Ma
- Liver Cirrhosis Diagnosis and Treatment Center, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China
| | - Bo Liu
- Liver Cirrhosis Diagnosis and Treatment Center, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China
| | - Xiaoli Yu
- Liver Cirrhosis Diagnosis and Treatment Center, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China
| | - Qin Wu
- Liver Cirrhosis Diagnosis and Treatment Center, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China
| | - Yanling Wang
- Liver Cirrhosis Diagnosis and Treatment Center, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China
| | - Hanwei Li
- Liver Cirrhosis Diagnosis and Treatment Center, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China.
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Su T. The concerns of proton pump inhibitors usage in cirrhotic patients with ascites. ADVANCES IN DIGESTIVE MEDICINE 2020. [DOI: 10.1002/aid2.13241] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Affiliation(s)
- Tung‐Hung Su
- Division of Gastroenterology and Hepatology, Department of Internal Medicine National Taiwan University Hospital Taipei Taiwan
- Hepatitis Research Center National Taiwan University Hospital Taipei Taiwan
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34
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Latest insights into the hot question of proton pump inhibitor safety - a narrative review. Dig Liver Dis 2020; 52:842-852. [PMID: 32513631 DOI: 10.1016/j.dld.2020.04.020] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Revised: 04/14/2020] [Accepted: 04/17/2020] [Indexed: 02/06/2023]
Abstract
Proton pump inhibitors (PPIs) are among the most widely prescribed medications worldwide and their use is continuously increasing. Although they have been shown to combine high therapeutic efficacy and good safety profile in many studies, in last years we have witnessed the publication of many articles reporting the possible association of long-term PPI therapy with important unexpected adverse events and these observations have created alarmism in both patients and physicians. However, the majority of these studies are observational, retrospective and prone to residual confounding. Also, the odds ratio values are generally comprised between 1 and 2 and therefore devoid of strong clinical relevance. As it is unlikely that prospective randomized trials will be ever done to reinforce these associations, we can only attempt to distinguish clear- from unclear-defined adverse events from the available literature. Nowadays we can reasonably exclude cardiovascular diseases, community-acquired pneumonia, all-cause mortality, dementia and bone fractures from PPI-related adverse events. However, physicians should be aware of the existence of possible risks when treating their patients, especially the elderly and frail ones, with long-term PPIs, which should be prescribed only to persons with defined indications and at lowest dose and duration.
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Macken L, Bremner S, Sheridan D, Verma S. Editorial: palliative long-term abdominal drains in refractory ascites-a step in the right direction, but not the complete solution. Authors' reply. Aliment Pharmacol Ther 2020; 52:723-724. [PMID: 32886369 DOI: 10.1111/apt.15928] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Affiliation(s)
- Lucia Macken
- Department of Clinical and Experimental Medicine, Brighton and Sussex Medical School, Brighton, UK.,Department of Gastroenterology and Hepatology, Brighton and Sussex University Hospitals NHS Trust, Brighton, UK
| | | | - David Sheridan
- Institute of Translational & Stratified Medicine, University of Plymouth and South West Liver Unit, University Hospital Plymouth NHS Trust, Plymouth, UK
| | - Sumita Verma
- Department of Clinical and Experimental Medicine, Brighton and Sussex Medical School, Brighton, UK.,Department of Gastroenterology and Hepatology, Brighton and Sussex University Hospitals NHS Trust, Brighton, UK
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Macken L, Bremner S, Gage H, Touray M, Williams P, Crook D, Mason L, Lambert D, Evans CJ, Cooper M, Timeyin J, Steer S, Austin M, Parnell N, Thomson SJ, Sheridan D, Wright M, Isaacs P, Hashim A, Verma S. Randomised clinical trial: palliative long-term abdominal drains vs large-volume paracentesis in refractory ascites due to cirrhosis. Aliment Pharmacol Ther 2020; 52:107-122. [PMID: 32478917 DOI: 10.1111/apt.15802] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Revised: 02/12/2020] [Accepted: 04/28/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND Palliative care remains suboptimal in end-stage liver disease. AIM To inform a definitive study, we assessed palliative long-term abdominal drains in end-stage liver disease to determine recruitment, attrition, safety/potential effectiveness, questionnaires/interview uptake/completion and make a preliminary cost comparison. METHODS A 12-week feasibility nonblinded randomised controlled trial comparing large-volume paracentesis vs long-term abdominal drains in refractory ascites due to end-stage liver disease with fortnightly home visits for clinical/questionnaire-based assessments. Study success criteria were attrition not >50%, <10% long-term abdominal drain removal due to complications, the long-term abdominal drain group to spend <50% ascites-related study time in hospital vs large-volume paracentesis group and 80% questionnaire/interview uptake/completion. RESULTS Of 59 eligible patients, 36 (61%) were randomised, 17 to long-term abdominal drain and 19 to large-volume paracentesis. Following randomisation, median number (IQR) of hospital ascitic drains (long-term abdominal drain group vs large-volume paracentesis group) were 0 (0-1) vs 4 (3-7); week 12 serum albumin (g/L) and serum creatinine (μmol/L) were 29 (26.5-32.5) vs 30 (25-35) and 104.5 (81-115.5) vs 127 (63-158) respectively. Total attrition was 42% (long-term abdominal drain group 47%, large-volume paracentesis group 37%). Median (IQR) fortnightly community/hospital/social care ascites-related costs and percentage study time in hospital were lower in the long-term abdominal drain group, £329 (253-580) vs £843 (603-1060) and 0% (0-0.74) vs 2.75% (2.35-3.84) respectively. Self-limiting cellulitis/leakage occurred in 41% (7/17) in the long-term abdominal drain group vs 11% (2/19) in the large-volume paracentesis group; peritonitis incidence was 6% (1/17) vs 11% (2/19) respectively. Questionnaires/interview uptake/completion were ≥80%; interviews indicated that long-term abdominal drains could transform the care pathway. CONCLUSIONS The REDUCe study demonstrates feasibility with preliminary evidence of long-term abdominal drain acceptability/effectiveness/safety and reduction in health resource utilisation. TRIAL REGISTRATION ISRCTN30697116, date assigned: 07/10/2015.
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Abstract
BACKGROUND AND AIMS Recurrence of spontaneous bacterial peritonitis (SBP) is still a matter of debate. We conducted this study to evaluate the probable factors that predict the recurrence of SBP in patients who recovered from the first episode of SBP and the long-term outcomes of SBP recurrence. METHODS One hundred twenty-four patients diagnosed with liver cirrhosis, SBP and did not receive secondary prophylaxis either with norfloxacin or other antibiotics were included in this prospective cohort pilot study. Clinical, biochemical and ascitic fluid analysis parameters were evaluated. Ascitic fluid interferon-γ-induced protein (IP-10), calprotectin, interleukin-6 and tumor necrosis factor-α were measured by ELISA. RESULTS Of these, 76 patients survived with an in-hospital mortality rate of 38.7%. The survivors were classified into two groups according to recurrence and nonrecurrence of SBP and survival time, clinical parameters and cause of death were investigated. Thirty-one participants had one or more attacks of SBP, with a recurrence rate of 40.8% within one-year follow-up. Before discharge, multivariate analysis showed that ascitic IP-10 (≥1220 pg/ml), ascitic calprotectin (≥550 ng/ml), serum albumin (≤2.5 g/dl), nonuse of prophylactic β-blockers and use of proton-pump inhibitors (PPIs) were the independent variables in predicting recurrent SBP. Sepsis-related organ failure was the most common etiology of mortality in the recurrent SBP group within 3 and 6 months. CONCLUSION Increased ascitic calprotectin and IP-10, hypoalbuminemia, nonuse of prophylactic β-blockers and use of PPI were independently associated with increased SBP recurrence rate. Sepsis-related organ failure was the most common etiology of mortality.
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Wongtrakul W, Charoenngnam N, Ungprasert P. Use of proton pump inhibitors is associated with a higher risk of pneumonia in cirrhotic patients: a systematic review and meta-analysis. Ann Gastroenterol 2020; 33:277-284. [PMID: 32382231 PMCID: PMC7196626 DOI: 10.20524/aog.2020.0483] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2020] [Accepted: 03/04/2020] [Indexed: 12/15/2022] Open
Abstract
Background Proton pump inhibitors (PPIs) are commonly prescribed for cirrhotic patients. However, the use of PPIs in these patients may increase the risk of bacterial infection. The current study aimed to investigate the risk of developing pneumonia among cirrhotic patients exposed to PPIs. Methods A literature search was independently conducted by 2 investigators using the MEDLINE and EMBASE databases up to September 2019. To be eligible, a study had to be an observational (cohort, case-control or cross-sectional) study that included one group of cirrhotic patients with PPI use and another group of cirrhotic patients without PPI use. Effect estimates of the association between PPI use and pneumonia had to be reported. Point estimates and standard errors from each eligible study were combined together using the generic inverse variance method of DerSimonian and Laird. Results Of 1947 articles identified from the 2 databases, 3 cohort and 5 cross-sectional studies with 40,295 participants met the eligibility criteria and were included in the meta-analysis. The pooled analysis found that cirrhotic patients with a history of PPI use had a significantly higher risk of developing pneumonia than those without PPI use, with a pooled risk ratio of 1.36 (95% confidence interval 1.00-1.85; I2 47%). Conclusion A significantly increased risk of pneumonia among cirrhotic patients exposed to PPIs was demonstrated in this study.
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Affiliation(s)
| | | | - Patompong Ungprasert
- Clinical Epidemiology Unit, Department of Research and Development, Faculty of Medicine (Patompong Ungprasert), Siriraj Hospital, Mahidol University, Bangkok, Thailand
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Chang TS, Tsai YH, Lin YH, Chen CH, Lu CK, Huang WS, Yang YH, Chen WM, Hsieh YY, Wu YC, Tung SY, Huang YH. Limited effects of antibiotic prophylaxis in patients with Child-Pugh class A/B cirrhosis and upper gastrointestinal bleeding. PLoS One 2020; 15:e0229101. [PMID: 32084186 PMCID: PMC7034903 DOI: 10.1371/journal.pone.0229101] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2019] [Accepted: 01/29/2020] [Indexed: 01/09/2023] Open
Abstract
Current guidelines recommend antibiotic prophylaxis for all patients with various degrees of cirrhosis and upper gastrointestinal (UGI) bleeding. This study assessed the need for antibiotic prophylaxis in patients with low Child–Pugh scores. We retrospectively screened all patients with cirrhosis who underwent upper endoscopies for UGI bleeding in a referral hospital in Taiwan between 2003 and 2014, from which 913 patients were enrolled after excluding patients with active bacterial infections, recent antibiotic use, early death, and Child–Pugh class C cirrhosis. Among them, 73 (8%) received prophylactic antibiotics, and 45 (4.9%) exhibited 14-day bacterial infection. Neither Child–Pugh score nor model for end stage liver disease score were optimal for predicting bacterial infection because their areas under the curves were 0.610 (95% confidence interval [CI]: 0.529–0.691) and 0.666 (95% CI: 0.591–0.742), respectively. Antibiotic prophylaxis did not reduce the risks of 14-day bacterial infection (relative risk [RR]: 0.932, 95% CI: 0.300–2.891, P = 0.902), 14-day rebleeding (RR: 0.791, 95% CI: 0.287–2.181, P = 0.650), or 42-day mortality (RR: 2.710, 95% CI: 0.769–9.524, P = 0.121). The results remained similar after propensity score adjustment. On-demand antibiotic treatment might suffice for patients with Child–Pugh class A/B cirrhosis and UGI bleeding.
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Affiliation(s)
- Te-Sheng Chang
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Chiayi, Taiwan.,College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Department of Biochemistry and Molecular Cell Biology, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Ying-Huang Tsai
- College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Yi-Heng Lin
- Department of Biochemistry and Molecular Cell Biology, College of Medicine, Taipei Medical University, Taipei, Taiwan.,Research Center for Cell Therapy and Regeneration Medicine, Taipei Medical University, Taipei, Taiwan
| | - Chun-Hsien Chen
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Chung-Kuang Lu
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Wen-Shih Huang
- College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Yao-Hsu Yang
- College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan.,Health Information and Epidemiology Laboratory of Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Wei-Ming Chen
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Chiayi, Taiwan.,College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Yung-Yu Hsieh
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Chiayi, Taiwan.,College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Yu-Chih Wu
- Research Center for Cell Therapy and Regeneration Medicine, Taipei Medical University, Taipei, Taiwan
| | - Shui-Yi Tung
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Chiayi, Taiwan.,College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Yen-Hua Huang
- Department of Biochemistry and Molecular Cell Biology, College of Medicine, Taipei Medical University, Taipei, Taiwan.,Research Center for Cell Therapy and Regeneration Medicine, Taipei Medical University, Taipei, Taiwan.,Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.,Center for Reproductive Medicine, Taipei Medical University Hospital, Taipei, Taiwan.,Comprehensive Cancer Center of Taipei Medical University, Taipei, Taiwan.,International PhD Program for Cell Therapy and Regeneration Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
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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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41
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Lin L, Hou L, Deng Y, Zhao T, Wang B, Sun C. Acid suppression therapy and its association with spontaneous bacterial peritonitis incidence: A systemic review and meta-analysis. Hepatol Res 2020; 50:233-245. [PMID: 31667938 DOI: 10.1111/hepr.13447] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2019] [Revised: 10/02/2019] [Accepted: 10/04/2019] [Indexed: 12/16/2022]
Abstract
AIM It is well known that the use of proton pump inhibitor (PPI) is widespread in patients with liver cirrhosis. PPI counteracts H2 receptor inhibitor (H2 RA) with its strong acid suppression effect. However, there is always a concern that PPI use may increase spontaneous bacteria peritonitis (SBP) development in cirrhotic patients. We aimed to investigate the association between acid suppression therapy (i.e. PPI or H2 RA) and SBP through meta-analysis. METHODS We searched PubMed, Medline, Web of Science, Cochrane library, and Embase for relevant studies published up to April 2019. Pooled OR and 95% CI were calculated by a random-effects model. Funnel plots and Egger's tests were performed for the evaluation of publication bias. Non-parametric "trim-and-fill" tests were conducted for sensitivity analysis. RESULTS A total of 20 original articles including 9566 cirrhotic patients were analyzed. The overall meta-analysis highlighted that PPI use was associated with the risk of SBP (pooled OR 1.77, 95% CI 1.49-2.11). The conclusion was irrespective of study methods, whereas the result was inconsistent only in South America. However, the conclusion might not be stable enough and should be extrapolated with caution. Unlike PPI, we found H2 RA was not associated with SBP (pooled OR 1.06, 95% CI 0.75-1.48). CONCLUSIONS In conclusion, PPI use, but not H2 RA, will increase the incidence of SBP in cirrhotic patients. In addition, H2 RA might be beneficial for patients who require long-term acid suppression therapy.
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Affiliation(s)
- Lin Lin
- Department of Gastroenterology, Tianjin Medical University General Hospital Airport Hospital, Tianjin, China
| | - Lijun Hou
- Department of Gastroenterology, Tianjin Medical University General Hospital Airport Hospital, Tianjin, China
| | - You Deng
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
| | - Tianming Zhao
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
| | - Bangmao Wang
- Department of Gastroenterology, Tianjin Medical University General Hospital Airport Hospital, Tianjin, China
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
| | - Chao Sun
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
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42
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Abstract
A substantial volume of literature exists linking proton pump inhibitor (PPI) use with a multitude of serious adverse events. There is uncertainty, however, over whether these associations are clinically important. Excessive concern about PPI-related adverse events may leave patients at risk of harm by leaving acid-related upper gastrointestinal disease untreated. Conversely, the risk of treatments may outweigh the benefits if any of the purported adverse events are directly caused by PPI use; this is of particular concern where indications for PPI use are not present. In this paper, we review the studies which have reported associations between adverse events and PPI use, discuss the proposed mechanisms of action, grade the confidence in whether these associations are truly causal, and provide advice regarding balancing the benefits of PPI use against their possible harms.
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Affiliation(s)
- Evan Elias
- Section of Gastroenterology, Department of Internal Medicine, Rady School of Medicine, University of Manitoba, 805G-715 McDermot Avenue, Winnipeg, MB, R3E 3P4, Canada
| | - Laura E Targownik
- Section of Gastroenterology, Department of Internal Medicine, Rady School of Medicine, University of Manitoba, 805G-715 McDermot Avenue, Winnipeg, MB, R3E 3P4, Canada.
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43
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Properly prescribed, proton pump inhibitors are largely safe, but precautions are needed to prevent potential problems, overuse and misuse. DRUGS & THERAPY PERSPECTIVES 2019. [DOI: 10.1007/s40267-019-00671-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
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44
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Lanas-Gimeno A, Hijos G, Lanas Á. Proton pump inhibitors, adverse events and increased risk of mortality. Expert Opin Drug Saf 2019; 18:1043-1053. [DOI: 10.1080/14740338.2019.1664470] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
| | - Gonzalo Hijos
- Servicio de Aparato Digestivo, Hospital Clínico Universitario, Zaragoza, Spain
- Instituto de Investigación Sanitaria Aragón, Zaragoza, Spain
| | - Ángel Lanas
- Servicio de Aparato Digestivo, Hospital Clínico Universitario, Zaragoza, Spain
- Instituto de Investigación Sanitaria Aragón, Zaragoza, Spain
- CIBERehd, Madrid, Spain
- Department of Medicine, Universidad de Zaragoza, Zaragoza, Spain
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45
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Khan R, Ravi S, Chirapongsathorn S, Jennings W, Salameh H, Russ K, Skinner M, Mudumbi S, Simonetto D, Kuo YF, Kamath PS, Singal AK. Model for End-Stage Liver Disease Score Predicts Development of First Episode of Spontaneous Bacterial Peritonitis in Patients With Cirrhosis. Mayo Clin Proc 2019; 94:1799-1806. [PMID: 31400909 PMCID: PMC9709904 DOI: 10.1016/j.mayocp.2019.02.027] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2018] [Revised: 02/13/2019] [Accepted: 02/19/2019] [Indexed: 12/13/2022]
Abstract
OBJECTIVE To examine whether baseline model for end-stage liver disease (MELD) score in patients with cirrhosis and ascites predicts the future development of first spontaneous bacterial peritonitis (SBP) episode. METHODS A retrospective case-control study was performed at three academic centers to select patients admitted with first SBP episode (cases) and those with ascites admitted for decompensation without SBP (controls). Medical records from these centers were reviewed between January 1, 2008, and December 31, 2013. Cases and controls were matched (1:2) for age, sex, and race. Conditional logistic recession models were built to determine whether baseline MELD score (within a month before hospitalization) predicts first SBP episode. RESULTS Of 697 patients (308, 230, and 159 from centers A, B, and C, respectively), cases and controls were matched in 94%, 89%, and 100% at three respective centers. In the pooled sample, probability of SBP was 11%, 31%, 71%, and 93% at baseline MELD scores less than or equal to 10, from 11 to 20, from 21 to 30, and greater than 30, respectively. Compared with MELD score less than or equal to 10, patients with MELD scores from 11 to 20, 21 to 30, and greater than 30 had six- (3- to 11-), 29- (12- to 69-), and 115- (22- to 598-) folds (95% CI) risk of SBP, respectively. Based on different MELD score cutoff points, MELD score greater than 17 was most accurate in predicting SBP occurrence. Analyzing 315 patients (152 cases) with available data on ascitic fluid protein level controlling for age, sex, and center, MELD score but not ascitic fluid protein associated with first SBP episode with respective odds ratios of 1.20 (1.14 to 1.26) and 0.88 (0.70 to 1.11). CONCLUSION Baseline MELD score predicts first SBP episode in patients with cirrhosis and ascites.
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Affiliation(s)
- Rashid Khan
- Division of Gastroenterology and Hepatology, UTMB, Galveston, TX
| | - Sujan Ravi
- Department of Internal Medicine, UAB, Birmingham, AL
| | | | - Whitney Jennings
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, AL
| | - Habeeb Salameh
- Division of Gastroenterology and Hepatology, UTMB, Galveston, TX
| | - Kirk Russ
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, AL
| | - Matt Skinner
- Department of Internal Medicine, UAB, Birmingham, AL
| | | | - Douglas Simonetto
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Yong-Fang Kuo
- Department of Preventive Medicine and Biostatistics, UTMB, Galveston, TX
| | - Patrick S Kamath
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Ashwani K Singal
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, AL.
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Facciorusso A, Antonino M, Orsitto E, Sacco R. Primary and secondary prophylaxis of spontaneous bacterial peritonitis: current state of the art. Expert Rev Gastroenterol Hepatol 2019; 13:751-759. [PMID: 31304804 DOI: 10.1080/17474124.2019.1644167] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2019] [Accepted: 07/12/2019] [Indexed: 02/07/2023]
Abstract
Introduction: Spontaneous bacterial peritonitis represents a frequent and severe complication in cirrhotic patients with ascites. In daily practice, the diagnosis of spontaneous bacterial peritonitis might be challenging in the absence of the typical signs and symptoms of infection such as fever or leukocytosis. Areas covered: Aim of this review is to revise the current state of the art on primary and secondary spontaneous bacterial peritonitis. Literature search in Medline/Pubmed was performed. Expert opinion: Historically, gram-negative bacteria were the most frequent etiologic agents of spontaneous bacterial peritonitis, with Escherichia coli and Klebsiella spp. being the most frequently isolated bacteria. However, major changes in this regard occurred over the last few decades with an increasing prevalence of gram-positive, quinolone-resistant, and multidrug-resistant bacteria. In particular, the increasing prevalence of quinolone-resistant bacteria challenged the prominent role of norfloxacin in spontaneous bacterial peritonitis prevention. Given the high mortality rate and the risk of developing the hepatorenal syndrome, prophylaxis of spontaneous bacterial peritonitis is indicated in three high-risk populations: patients with acute gastrointestinal hemorrhage, patients with low total protein content in ascitic fluid and advanced cirrhosis, and patients with a previous history of spontaneous bacterial peritonitis (secondary prophylaxis).
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Affiliation(s)
- Antonio Facciorusso
- a Department of Medical Sciences, Ospedali Riuniti di Foggia , Foggia , Italy
| | - Matteo Antonino
- a Department of Medical Sciences, Ospedali Riuniti di Foggia , Foggia , Italy
| | - Eugenio Orsitto
- b Department of Radiology, Azienda Ospedaliero-Universitaria Pisana , Pisa , Italy
| | - Rodolfo Sacco
- a Department of Medical Sciences, Ospedali Riuniti di Foggia , Foggia , Italy
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47
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Fiore M, Di Franco S, Alfieri A, Passavanti MB, Pace MC, Kelly ME, Damiani G, Leone S. Spontaneous bacterial peritonitis caused by Gram-negative bacteria: an update of epidemiology and antimicrobial treatments. Expert Rev Gastroenterol Hepatol 2019; 13:683-692. [PMID: 31107612 DOI: 10.1080/17474124.2019.1621167] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2019] [Accepted: 05/16/2019] [Indexed: 12/15/2022]
Abstract
Introduction: Spontaneous bacterial peritonitis (SBP) is a main infectious complication in end-stage liver disease (ESLD) patients. The increasing trend of bacterial resistance in ESLD patients with SBP has been associated with low treatment efficacy of traditional therapy. Cephalosporin use has been restricted to community-acquired infections and in areas/health care settings with low rates of multidrug-resistant (MDR) bacteria. To date, several changes are necessary with regard to empiric therapy recommendations in areas/health care settings with high rates of MDR bacteria. Areas covered: An overview of the epidemiology and antimicrobial treatments of SBP caused by Gram-negative bacteria. Expert opinion: Broad-spectrum antibiotics have been recommended as empiric therapy for suspected SBP in areas/health care settings with high rates of MDR bacteria and secondary treatment, with newer antibiotics, for SBP caused by MDR-Gram-negative bacteria (i.e. new beta-lactam/beta-lactamase inhibitor combinations, cefiderocol, plazomicin, and eravacycline) either alone or in combination.
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Affiliation(s)
- Marco Fiore
- a Department of Women , Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli" , Naples , Italy
| | - Sveva Di Franco
- a Department of Women , Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli" , Naples , Italy
| | - Aniello Alfieri
- a Department of Women , Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli" , Naples , Italy
| | - Maria Beatrice Passavanti
- a Department of Women , Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli" , Naples , Italy
| | - Maria Caterina Pace
- a Department of Women , Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli" , Naples , Italy
| | - Molly E Kelly
- b Case Western Reserve University School of Medicine , Cleveland , OH , USA
| | - Giovanni Damiani
- c Department of Pathophysiology and Transplantation , University of Milan , Italy
| | - Sebastiano Leone
- d Division of Infectious Diseases , "San Giuseppe Moscati" Hospital , Avellino , Italy
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Ribiere S, Guillaumot MA, Barré A, Abou Ali E, Barret M, Chaussade S, Coriat R. Quel est le VRAI risque au long cours des inhibiteurs de la pompe à protons ? Presse Med 2019; 48:503-510. [PMID: 30926204 DOI: 10.1016/j.lpm.2019.02.011] [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: 01/29/2019] [Accepted: 02/11/2019] [Indexed: 11/30/2022] Open
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49
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Kao WY, Su CW, Chia-Hui Tan E, Lee PC, Chen PH, Tang JH, Huang YH, Huo TI, Chang CC, Hou MC, Lin HC, Wu JC. Proton Pump Inhibitors and Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B or C. Hepatology 2019; 69:1151-1164. [PMID: 30175498 DOI: 10.1002/hep.30247] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2018] [Accepted: 08/21/2018] [Indexed: 12/16/2022]
Abstract
Researchers have hypothesized that the long-term use of proton pump inhibitors (PPIs) can increase the risk of developing cancer. However, the association between PPI use and hepatocellular carcinoma (HCC) risk is unclear. Using data from the Taiwan National Health Insurance Research Database for the period between 2003 and 2013, we identified 35,356 patients with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections. One-to-one propensity score matching by gender, age, cohort entry year, comorbidity, and medication resulted in the inclusion of 7,492 pairs of patients (PPI users and non-PPI users) for analyses. We performed multivariate and stratified analysis using the Kaplan-Meier method and Cox proportional hazards models in order to estimate the association between PPI use and the risk of developing HCC. In the HBV cohort, 237 patients developed HCC during a median follow-up of 53 months. However, PPI use was not associated with an increased risk of developing HCC (adjusted hazard ratio [aHR], 1.25; 95% confidence interval [CI], 0.90-1.73; P = 0.18). In the HCV cohort, 211 patients developed HCC; but again, PPI use was not associated with an increase in the risk of developing HCC (aHR, 1.19; 95% CI, 0.88-1.61; P = 0.25). We observed no relationship between a dose-dependent effect of PPI use and HCC risk. Subgroup analysis also confirmed that PPI use was not correlated to an increased HCC risk. Conclusion: Based on a retrospective population-based cohort study throughout Taiwan, where the prescription of PPI is tightly regulated, PPI use is not associated with the risk of developing HCC among patients with chronic HBV or HCV infections.
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Affiliation(s)
- Wei-Yu Kao
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Chien-Wei Su
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Elise Chia-Hui Tan
- National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan
| | - Pei-Chang Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Institute of Pharmacology, Taipei, Taiwan
| | - Ping-Hsien Chen
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Jui-Hsiang Tang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Teh-Ia Huo
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Institute of Pharmacology, Taipei, Taiwan
| | - Chun-Chao Chang
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan
| | - Ming-Chih Hou
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Jaw-Ching Wu
- National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan.,Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan
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Elzouki AN, Neffati N, Rasoul FA, Abdallah A, Othman M, Waness A. Increased Risk of Spontaneous Bacterial Peritonitis in Cirrhotic Patients Using Proton Pump Inhibitors. GE PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2019; 26:83-89. [PMID: 30976612 PMCID: PMC6454390 DOI: 10.1159/000487963] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/28/2017] [Accepted: 02/23/2018] [Indexed: 12/21/2022]
Abstract
BACKGROUND The association between bacterial infections and proton pump inhibitors (PPIs) has recently been studied with debatable results. AIM The aim of this study was to investigate the relationship between PPIs and the development of spontaneous bacterial peritonitis (SBP) or other bacterial infections in cirrhotic patients. MATERIALS AND METHODS Consecutive cirrhotic patients hospitalized from 2007 through 2012 to Hamad General Hospital-, Doha, Qatar, were enrolled and classified as PPI users or non-users according to PPI consumption in the 90 days prior to hospitalization. Cirrhosis was clinically diagnosed by a combination of physical, biochemical, radiological, and endoscopic findings, or by liver biopsy. RESULTS A total of 333 patients were included in this study, of whom 171 (51.4%) used PPIs and 162 (48.6%) did not use PPIs. PPI users were significantly older in age (p = 0.001). There was no statistical difference between the 2 groups in sex distribution and etiology of cirrhosis (p > 0.05 for both parameters). PPI users had a significantly higher incidence of overall bacterial infection (38%) than non-PPI users (13.6%), p = 0.0001. Statistical significance is observed specifically for SBP and chest infection (p = 0.0006 and p = 0.01, respectively). In multivariate analysis, older age (> 60 years; OR = 1.246, 95% CI 1.021-08.486; p = 0.02), and PPI use (OR = 2.149, 95% CI 1.124-06.188; p = 0.01) were independent predicting factors for SBP and overall bacterial infection. CONCLUSION The present study shows that PPI use, as well as older age (> 60 years), was an independent predicting factor for the development of overall infection and SBP in hospitalized cirrhotic patients. Unless it is indicated, PPI therapy should be avoided in this group of patients, particularly in those older than 60 years of age.
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Affiliation(s)
- Abdel-Naser Elzouki
- aDepartment of Medicine, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar
- bWeill Cornell Medical College, Doha, Qatar
| | - Nadia Neffati
- aDepartment of Medicine, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar
| | - Fatma A. Rasoul
- aDepartment of Medicine, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar
| | - Ali Abdallah
- aDepartment of Medicine, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar
| | - Muftah Othman
- aDepartment of Medicine, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar
| | - Abdelkarim Waness
- aDepartment of Medicine, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar
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