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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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Maimunah U, Kurniawan AA, Palayukan A. Adverse Effects of Long-term Proton Pump Inhibitors in Chronic Liver Disease Patients – A Preliminary Article Review. REVIEW OF CLINICAL PHARMACOLOGY AND PHARMACOKINETICS - INTERNATIONAL EDITION 2024; 38:87-97. [DOI: 10.61873/wway6273] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
Abstract
Background: Proton pump inhibitors (PPIs) are widely prescribed medications for the management of gastroesophageal reflux disease (GERD) and peptic ulcer disease. Despite their efficacy, concerns have emerged regarding their potential adverse effects, particularly in patients with chronic liver disease (CLD). CLD patients often experience gastrointestinal symptoms and may be prescribed PPIs, but the impact of PPI use on liver function and disease progression remains uncertain. Scope: This study aims to evaluate the adverse effects of PPIs on CLD patients through a review of available literature. The scope encompasses a review of studies examining the association between PPI use and liver-related outcomes, including hepatic encephalopathy, hepatic decompensation, liver cirrhosis progression, and mortality, among CLD patients. Method: A scoping review of relevant literature were conducted to identify studies investigating the adverse effects of PPIs in CLD patients. Databases including PubMed and Google Scholar were searched for articles published up to January, 1 2023. Eligible studies were selected based on predefined inclusion criteria. Results: The review identified 27 studies meeting the inclusion criteria, comprising observational studies and meta-analysis. The review revealed a significant association between PPI use and adverse liver outcomes in CLD patients. Specifically, PPI use was associated with increased risk of SBP based on studies reviewed, while other complications remained inconclusive. Conclusion: The findings suggest that PPI use may have detrimental effects on disease progression in CLD patients, Long-term use of PPIs can lead to higher risk of SBP in CLD patients. Clinicians should exercise caution when prescribing PPIs to this vulnerable population and consider alternative treatment options or minimize PPI use to mitigate potential adverse outcomes. Further research is warranted to elucidate the underlying mechanisms, confirm the effect of PPIs toward other complications of CLD and establish guidelines for PPI use in CLD patients.
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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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Zhang P, Zhou L, Chen L, Zhang Z, Han R, Guo G, Zhou H. Electroencephalography Signatures for Hepatic Encephalopathy in Cirrhosis Patients Treated with Proton Pump Inhibitors: An Exploratory Pilot Study. Biomedicines 2022; 10:biomedicines10123040. [PMID: 36551796 PMCID: PMC9776374 DOI: 10.3390/biomedicines10123040] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Revised: 11/15/2022] [Accepted: 11/23/2022] [Indexed: 11/27/2022] Open
Abstract
(1) Background: Hepatic encephalopathy (HE) is a common complication in cirrhosis patients, and recently, clinical evidence indicates that a higher risk of HE is associated with the usage of proton pump inhibitors. However, the cortical mechanism underlying this neurological disorder of HE remains unknown. (2) Methods: We review the medical recordings of 260 patients diagnosed with liver cirrhosis between January 2021 and March 2022 in one tertiary hospital. Logistic regression analyses were performed to identify the risk factor of HE development. To examine the relationship between cortical dynamics and the administration of proton pump inhibitors, resting-state electroencephalograms (EEGs) were conducted in cirrhosis patients who were treated with proton pump inhibitors. (3) Results: About 28.5% (74 out of 260) of participants developed secondary HE in this study. The logistics regression model indicated that multiple risk factors were associated with the incidence of secondary HE, including proton pump inhibitors usage, white blood cell and neutrophil counts, hemoglobin, prothrombin time activity, and blood urea nitrogen. A total of twelve cirrhosis patients who were scheduled to use proton pump inhibitors consented to performing electroencephalogram recordings upon admission, and eight of twelve participants were diagnosed with HE. Spectral analysis revealed that the decrease in alpha oscillation activities was potentially associated with the development of HE. (4) Conclusions: Our data support the susceptibility of secondary HE in cirrhosis patients treated by proton pump inhibitors. One potential cortical mechanism underlying the neurological disease is the suppression of alpha oscillations in the brain.
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Affiliation(s)
- Pan Zhang
- Department of Infectious Diseases, Third Xiangya Hospital, Central South University, Changsha 410013, China
| | - Lizhi Zhou
- Department of Infectious Diseases, Third Xiangya Hospital, Central South University, Changsha 410013, China
- Department of Infectious Diseases, Xiangtan Central Hospital, Xiangtan 411100, China
| | - Li Chen
- Department of Pain, Third Xiangya Hospital and Institute of Pain Medicine, Central South University, Changsha 410013, China
| | - Zhen Zhang
- Department of Pain, Third Xiangya Hospital and Institute of Pain Medicine, Central South University, Changsha 410013, China
| | - Rui Han
- Department of Pain, Third Xiangya Hospital and Institute of Pain Medicine, Central South University, Changsha 410013, China
| | - Gangwen Guo
- Department of Pain, Third Xiangya Hospital and Institute of Pain Medicine, Central South University, Changsha 410013, China
- Correspondence: (G.G.); (H.Z.)
| | - Haocheng Zhou
- Department of Pain, Third Xiangya Hospital and Institute of Pain Medicine, Central South University, Changsha 410013, China
- Hunan Key Laboratory of Brain Homeostasis, Central South University, Changsha 410013, China
- Correspondence: (G.G.); (H.Z.)
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Sahra S, Abureesh M, Amarnath S, Alkhayyat M, Badran R, Jahangir A, Gumaste V. Clostridioides difficile infection in liver cirrhosis patients: A population-based study in United States. World J Hepatol 2021; 13:926-938. [PMID: 34552699 PMCID: PMC8422922 DOI: 10.4254/wjh.v13.i8.926] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Revised: 06/11/2021] [Accepted: 07/22/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Clostridioides (formerly Clostridium) difficile infection (CDI) is an increasingly frequent cause of morbidity and mortality in hospitalized patients. Multiple risk factors are documented in the literature that includes, but are not limited to, antibiotics use, advanced age, and gastric acid suppression. Several epidemiological studies have reported an increased incidence of CDI in advanced liver disease patients. Some have also demonstrated a higher prevalence of nosocomial infections in cirrhotic patients.
AIM To use a large nationwide database, we sought to determine CDI’s risk among liver cirrhosis patients in the United States.
METHODS We queried a commercial database (Explorys IncTM, Cleveland, OH, United States), and obtained an aggregate of electronic health record data from 26 major integrated United States healthcare systems comprising 360 hospitals in the United States from 2018 to 2021. Diagnoses were organized into the Systematized Nomenclature of Medicine Clinical Terms (SNOMED–CT) hierarchy. Statistical analysis for the multivariable model was performed using Statistical Package for Social Sciences (SPSS version 25, IBM CorpTM). For all analyses, a two-sided P value of < 0.05 was considered statistically significant.
RESULTS There were a total of 19387760 patients in the database who were above 20 years of age between the years 2018-2021. Of those, 133400 were diagnosed with liver cirrhosis. The prevalence of CDI amongst the liver cirrhosis population was 134.93 per 100.000 vs 19.06 per 100.000 in non-cirrhotic patients (P < 0.0001). The multivariate analysis model uncovered that cirrhotic patients were more likely to develop CDI (OR: 1.857; 95%CI: 1.665-2.113, P < 0.0001) compared to those without any prior history of liver cirrhosis.
CONCLUSION In this large database study, we uncovered that cirrhotic patients have a significantly higher CDI prevalence than those without cirrhosis. Liver cirrhosis may be an independent risk factor for CDI. Further prospective studies are needed to clarify this possible risk association that may lead to the implementation of screening methods in this high-risk population.
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Affiliation(s)
- Syeda Sahra
- Department of Internal Medicine, Staten Island University Hospital, Staten Island, NY 10305, United States
| | - Mohammad Abureesh
- Department of Internal Medicine, Staten Island University Hospital, Staten Island, NY 10305, United States
| | - Shivantha Amarnath
- Department of Internal Medicine, Staten Island University Hospital, Staten Island, NY 10305, United States
| | - Motasem Alkhayyat
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, OH 44195, United States
| | - Rawan Badran
- Department of Internal Medicine, Staten Island University Hospital, Staten Island, NY 10305, United States
| | - Abdullah Jahangir
- Department of Internal Medicine, Staten Island University Hospital, Staten Island, NY 10305, United States
| | - Vivek Gumaste
- Department of Gastroenterology, Staten Island University Hospital, Staten Island, NY 10305, United States
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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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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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Fecal Microbiota Transplantation for Clostridioides Difficile Infection in Patients with Chronic Liver Disease. Int J Hepatol 2020; 2020:1874570. [PMID: 32047670 PMCID: PMC7007953 DOI: 10.1155/2020/1874570] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2019] [Revised: 12/22/2019] [Accepted: 01/17/2020] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Fecal microbiota transplantation (FMT) is a well-established therapeutic option for patients with antibiotic resistant Clostridioides difficile infection (CDI). However, the efficacy of FMT in patients with chronic liver disease remains elusive. AIMS We studied the effect of FMT on chronic liver disease (CLD) patients with CDI at our tertiary medical center. METHODS A cohort of all patients who received FMT from December 2012 to May 2014 for refractory or recurrent CDI was identified. Patients were monitored for a year after FMT. Descriptive analysis was conducted to compare the effect of FMT in patients with and without CLD. RESULTS A total of 201 patients with CDI received FMT, 14 of which had a history of CLD. Nine of these patients exhibited cirrhosis of the liver with a mean Child-Turcotte-Pugh score of 8. CDI development in these patients was associated with recent exposure to antibiotics and was observed to be significantly different between both groups (17% of CLD patients vs. 58% in the general cohort, p = 0.01). Four patients with CLD received >1 FMT, of which 2 did not respond to treatment. There was no significant difference between patients with liver disease and the rest of the cohort with regard to FMT response (12/14 (87%) vs. 164/187 (88%), p = 0.01). Four patients with CLD received >1 FMT, of which 2 did not respond to treatment. There was no significant difference between patients with liver disease and the rest of the cohort with regard to FMT response (12/14 (87%) vs. 164/187 (88%). CONCLUSION FMT is a safe and effective therapy against CDI for patients with CLD and cirrhosis.
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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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Nardelli S, Gioia S, Ridola L, Farcomeni A, Merli M, Riggio O. Proton Pump Inhibitors Are Associated With Minimal and Overt Hepatic Encephalopathy and Increased Mortality in Patients With Cirrhosis. Hepatology 2019; 70:640-649. [PMID: 30289992 DOI: 10.1002/hep.30304] [Citation(s) in RCA: 64] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2018] [Accepted: 10/02/2018] [Indexed: 12/12/2022]
Abstract
Minimal hepatic encephalopathy (MHE) is a subclinical cognitive impairment frequently observable in patients with cirrhosis. Proton pump inhibitors (PPIs) can contribute to small-bowel bacterial overgrowth, but no study has investigated the link between PPIs and MHE. We investigated the relationship between MHE and PPI use as well as the role of PPI use in the development of overt HE and survival. Consecutive patients with cirrhosis (n = 310) were included in the study and followed up for 14.1 ± 12.3 months. At entry, MHE was diagnosed when the Psychometric Hepatic Encephalopathy Score was ≤-4. Data were analyzed by logistic regression for the factors associated with MHE and by time-related models for overt HE development and survival. At inclusion, 131 out of 310 patients with cirrhosis (42%) were affected by MHE. One hundred and twenty-five patients (40%) were using PPIs. The variables independently associated with the presence of MHE were PPI use, previous overt HE, low albumin, low sodium, and age. During follow-up, the development of overt HE was higher (64% versus 25%, P < 0.001) and overall survival lower (41% versus 81%, P < 0.001) in PPI users than in nonusers. Variables independently associated with the development of overt HE were PPIs, history of overt HE, low albumin, MHE, and age, while variables independently associated with mortality were PPIs, development of overt HE, Model for End-Stage Liver Disease score, low sodium, and age. Conclusion: The study identifies a potentially removable factor associated with the presence of MHE and related to the development of overt HE and survival in patients with liver cirrhosis.
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Affiliation(s)
- Silvia Nardelli
- Department of Clinical Medicine, "Sapienza" University of Rome, Rome, Italy
| | - Stefania Gioia
- Department of Clinical Medicine, "Sapienza" University of Rome, Rome, Italy
| | - Lorenzo Ridola
- Department of Clinical Medicine, "Sapienza" University of Rome, Rome, Italy
| | - Alessio Farcomeni
- Department of Public Health and Infectious Diseases, "Sapienza" University of Rome, Rome, Italy
| | - Manuela Merli
- Department of Clinical Medicine, "Sapienza" University of Rome, Rome, Italy
| | - Oliviero Riggio
- Department of Clinical Medicine, "Sapienza" University of Rome, Rome, Italy
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Tantai XX, Yang LB, Wei ZC, Xiao CL, Chen LR, Wang JH, Liu N. Association of proton pump inhibitors with risk of hepatic encephalopathy in advanced liver disease: A meta-analysis. World J Gastroenterol 2019; 25:2683-2698. [PMID: 31210719 PMCID: PMC6558434 DOI: 10.3748/wjg.v25.i21.2683] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2019] [Revised: 04/21/2019] [Accepted: 05/03/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Several studies have explored the association between the use of proton pump inhibitors (PPIs) and the risk of developing hepatic encephalopathy (HE) in patients with advanced liver disease. However, the evidence-based conclusions are controversial. We hypothesized that using PPIs may increase the risk of HE in patients with advanced liver disease. If confirmed, clinicians must strictly adhere to the indications for PPI treatment in this population. AIM To evaluate the pooled risk of HE in patients with advanced liver disease who use PPIs. METHODS Three electronic databases (PubMed, EMBASE, and the Cochrane Library) were searched from the date of database inception through January 8, 2019 to identify comparative studies evaluating the association between PPI use and the risk of HE. Data from the included studies were extracted. The random-effects model was used for pooling risk estimates and the corresponding 95% confidence intervals (CIs). Subgroup and sensitivity analyses were also performed. RESULTS In total, 4342 patients from five case-control studies and 188053 patients from four cohort studies were included in this analysis. In patients with advanced liver disease, PPI use was associated with an elevated risk of developing HE, with significant heterogeneity. The pooled odds ratio for case-control studies was 2.58 (95%CI: 1.68-3.94, I 2 = 72%). The pooled RR for cohort studies was 1.67 (95%CI: 1.30-2.14, I 2 = 67%). The results of the subgroup analyses suggested that the heterogeneity may be the result of differences in the study designs and the definitions of PPI use. The sensitivity and subgroup analyses did not alter our findings. CONCLUSION In patients with advanced liver disease, PPI use is associated with an elevated risk of HE. Future large prospective studies are needed to confirm this association.
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Affiliation(s)
- Xin-Xing Tantai
- Division of Gastroenterology, The Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
| | - Long-Bao Yang
- Division of Gastroenterology, The Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
| | - Zhong-Cao Wei
- Division of Gastroenterology, The Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
| | - Cai-Lan Xiao
- Division of Gastroenterology, The Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
| | - Li-Rong Chen
- Division of Gastroenterology, The Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
| | - Jin-Hai Wang
- Division of Gastroenterology, The Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
| | - Na Liu
- Division of Gastroenterology, The Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
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Fernandes SR, Tato Marinho R. The Dark Side of the Long-Term Use of Proton Pump Inhibitors in Chronic Liver Disease. GE PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2019; 26:79-80. [PMID: 30976610 PMCID: PMC6454383 DOI: 10.1159/000489640] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/19/2018] [Accepted: 04/26/2018] [Indexed: 06/09/2023]
Affiliation(s)
| | - Rui Tato Marinho
- Serviço de Gastrenterologia e Hepatologia, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal
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13
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Bremer SCB, Reinhardt L, Sobotta M, Hasselluhn MC, Lorf T, Ellenrieder V, Schwörer H. Pantoprazole Does not Affect Serum Trough Levels of Tacrolimus and Everolimus in Liver Transplant Recipients. Front Med (Lausanne) 2018; 5:320. [PMID: 30510930 PMCID: PMC6253821 DOI: 10.3389/fmed.2018.00320] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2018] [Accepted: 10/30/2018] [Indexed: 12/27/2022] Open
Abstract
Background: Liver transplant recipients are frequently treated with proton pump inhibitors. Drug interactions have been described especially with respect to omeprazole. Due to the lower binding capacity of pantoprazole to CYP2C19 this drug became preferred and became the most used proton pump inhibitor in Germany. The data on the influence of pantoprazole on immunosuppressive drugs in liver transplant recipients a very scarce. Methods: The authors performed a single center analysis in liver transplant recipients on the effect of pantoprazole on the serum trough levels of different immunosuppressants. The trough levels were compared over a period of 1 year before and after start or stop of a continuous oral co-administration of 40 mg pantoprazole once daily. Results: The serum trough levels of tacrolimus (n = 30), everolimus (n = 7), or sirolimus (n = 3) remain constant during an observation period of at least 1 year before and after co-administration of pantoprazole. None of the included patients needed a change of dosage of the observed immunosuppressants during the observation period. Conclusions: The oral co-administration of pantoprazole is safe in immunosuppressed liver transplant recipients according to the serum trough levels of tacrolimus, everolimus, and sirolimus. This analysis provides first data on the influence of pantoprazole on immunosuppressive drugs in liver transplant recipients.
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Affiliation(s)
- Sebastian C B Bremer
- Clinic for Gastroenterology and Gastrointestinal Oncology, University Medical Center Goettingen, Georg-August-University, Goettingen, Germany.,Liver Center Goettingen, University Medical Center Goettingen, Georg-August-University, Goettingen, Germany
| | - Lars Reinhardt
- Clinic for Gastroenterology and Gastrointestinal Oncology, University Medical Center Goettingen, Georg-August-University, Goettingen, Germany.,Liver Center Goettingen, University Medical Center Goettingen, Georg-August-University, Goettingen, Germany
| | - Michael Sobotta
- Clinic for Gastroenterology and Gastrointestinal Oncology, University Medical Center Goettingen, Georg-August-University, Goettingen, Germany.,Clinic for Anesthesiology, University Medical Center Goettingen, Georg-August-University, Goettingen, Germany
| | - Marie C Hasselluhn
- Clinic for Gastroenterology and Gastrointestinal Oncology, University Medical Center Goettingen, Georg-August-University, Goettingen, Germany
| | - Thomas Lorf
- Liver Center Goettingen, University Medical Center Goettingen, Georg-August-University, Goettingen, Germany.,Clinic for General, Visceral and Pediatric Surgery, University Medical Center Goettingen, Georg-August-University, Goettingen, Germany
| | - Volker Ellenrieder
- Clinic for Gastroenterology and Gastrointestinal Oncology, University Medical Center Goettingen, Georg-August-University, Goettingen, Germany.,Liver Center Goettingen, University Medical Center Goettingen, Georg-August-University, Goettingen, Germany
| | - Harald Schwörer
- Clinic for Gastroenterology and Gastrointestinal Oncology, University Medical Center Goettingen, Georg-August-University, Goettingen, Germany.,Liver Center Goettingen, University Medical Center Goettingen, Georg-August-University, Goettingen, Germany
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Thomson MJ, Lok AS, Tapper EB. Optimizing medication management for patients with cirrhosis: Evidence-based strategies and their outcomes. Liver Int 2018; 38:1882-1890. [PMID: 29845749 PMCID: PMC6202194 DOI: 10.1111/liv.13892] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2018] [Accepted: 05/22/2018] [Indexed: 12/13/2022]
Abstract
Cirrhosis is a morbid condition associated with frequent hospitalizations and high mortality. Management of cirrhosis requires complex medication regimens to treat underlying liver disease, complications of cirrhosis and comorbid conditions. This review examines the complexities of medication management in cirrhosis, barriers to optimal medication use, and potential interventions to streamline medication regimens and avoid medication errors. A literature review was performed by searching PUBMED through December 2017 and article reference lists to identify articles relevant to medication management, complications, adherence, and interventions to improve medication use in cirrhosis. The structural barriers in cirrhosis include sheer medication complexity related to the number of medications and potential for cognitive impairment in this population, faulty medication reconciliation and limited adherence. Tested interventions have included patient self-education, provider driven patient education, intensive case management including medication blister packs and smartphone applications. Initiatives are needed to improve patient, caregiver and provider education on appropriate use of medications in patients with cirrhosis. A multidisciplinary team should be established to coordinate care with close monitoring, address patient and caregiver concerns, and to provide timely access to outpatient evaluation of urgent/complex issues. Future studies evaluating the clinical outcomes and cost effectiveness of interventions are needed.
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Affiliation(s)
- Mary J Thomson
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA
- Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor, MI, USA
| | - Anna S Lok
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA
- Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor, MI, USA
| | - Elliot B Tapper
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA
- Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor, MI, USA
- Veterans Affairs Hospital, Ann Arbor, MI, USA
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15
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Miozzo SAS, John JA, Appel-da-Silva MC, Dossin IA, Tovo CV, Mattos AA. Influence of proton pump inhibitors in the development of spontaneous bacterial peritonitis. World J Hepatol 2017; 9:1278-1285. [PMID: 29290909 PMCID: PMC5740091 DOI: 10.4254/wjh.v9.i35.1278] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2017] [Revised: 08/25/2017] [Accepted: 11/03/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate whether the use of proton pump inhibitors (PPIs) increases the incidence of spontaneous bacterial peritonitis (SBP) in patients with cirrhosis and ascites. METHODS An historical cohort study was carried out in cirrhotic outpatients with ascites followed in a specialized clinic at a tertiary hospital in Southern Brazil. Patient charts were reviewed to collect information on the variables of interest as the use of PPIs. Primary outcome was defined as development of SBP during the study period. SBP was diagnosed based on ascitic fluid polymorphonuclear cell count ≥ 250 cells/mm³ without evidence of an intra-abdominal, surgically treatable source of infection. RESULTS Of 738 cirrhotic patients, 582 (58.2% male) were enrolled, with mean age of 53.6 ± 12 years. Hepatitis C virus infection (36.2%) and alcohol abuse (25.6%) were the main etiologies of cirrhosis. The presence of ascites was detected in 299 (51.4%) patients during the development of the study. Nineteen patients with previous diagnosis of SBP undergoing secondary prophylaxis and 22 patients with insufficient PPI data were further excluded. Of 258 patients with ascites, 151 used PPIs, and 34 developed SBP (22.5%). Among 107 non-users of PPIs, 23 developed SBP (21.5%) (HR = 1.44, 95%CI: 0.85-2.47, P = 0.176). The median follow-up time of patients using PPI was 27 mo vs 32 mo for non-users. Univariate analysis of the risk factors associated with the development of SBP revealed a significant association of SPB with the severity of liver disease according to the Child-Turcotte-Pugh (CTP) score. Multivariate analysis confirmed that CTP score was the only independent variable influencing the occurrence of SBP. Survival at 60 mo (Kaplan-Meier analysis) was similar in users and non-users of PPI, independently of the presence of SBP (58.4% vs 62.7% respectively, P = 0.66). For patients with SBP, survival at 60 mo was 55.1%, vs 61.7% in patients without SBP (P = 0.34). CONCLUSION In conclusion, the rate of SBP was not significantly different in users or non-users of PPIs in this cohort of cirrhotic with ascites.
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Affiliation(s)
- Suelen A S Miozzo
- Graduate Program in Medicine, Hepatology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre CEP 90430-080, Brazil
| | - Jorge A John
- Graduate Program in Medicine, Hepatology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre CEP 90430-080, Brazil
| | - Marcelo C Appel-da-Silva
- Graduate Program in Medicine, Hepatology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre CEP 90430-080, Brazil
| | - Isabella A Dossin
- Graduate Program in Medicine, Hepatology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre CEP 90430-080, Brazil
| | - Cristiane V Tovo
- Graduate Program in Medicine, Hepatology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre CEP 90430-080, Brazil.
| | - Angelo A Mattos
- Graduate Program in Medicine, Hepatology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre CEP 90430-080, Brazil
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Triantos C, Kalafateli M, Spantidea PI, Goukos D, Koutroumpakis E, Konstantakis C, Assimakopoulos SF, Gogos C, Mouzaki A, Daikos G, Thomopoulos K. Bacterial load and cytokine profile in patients with cirrhosis following therapy with proton pump inhibitors: a prospective cohort study. Ann Gastroenterol 2017; 30:450-456. [PMID: 28655984 PMCID: PMC5480000 DOI: 10.20524/aog.2017.0142] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2017] [Accepted: 03/08/2017] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND The aim of this study was to explore the presence of bacterial products and the cytokine profile in outpatients with cirrhosis before and after short-term (4-8 weeks) administration of proton pump inhibitors (PPIs). METHODS Seventeen patients with cirrhosis-male/female: 12/5; age: median 59.2 years (49-65); etiology: HBV±HDV 23.5%, HCV 17.7%, alcohol 41.2%, other 17.6%; Child-Pugh score: median 7.5 (5-12); Model for End-stage Liver Disease: 10.5 (7-21); ascites (%): 3 (17.7)-attending the outpatient clinics were included. None had hepatocellular carcinoma. Indications for PPIs were: esophagitis (n=6, 35.3%), peptic ulcer (n=10, 58.6%) and other (n=1, 5.9%). Bacterial DNA in serum and the levels of endotoxin, lipopolysaccharide binding protein, transforming growth factor-β, interleukin -1β, -6, -8, -12, -10, tumor necrosis factor-α and nitric oxide were assessed at baseline (time 1) and at the end of treatment (time 2). The Wilcoxon signed rank test was used to evaluate significant differences in the parameters assayed before and after PPI administration. RESULTS No patients developed infection during the study period. Bacterial DNA was not detected before or after treatment. No significant differences were observed between the concentrations of any indices between times 1 and 2 (P>0.05). Subgroup analysis according to Child-Pugh stage yielded similar results. CONCLUSION Short-term administration of PPIs had no effect on bacterial DNA, bacterial products or cytokine concentrations in patients with liver cirrhosis.
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Affiliation(s)
- Christos Triantos
- Department of Gastroenterology, University Hospital of Patras (Christos Triantos, Maria Kalafateli, Efstratios Koutroumpakis, Christos Konstantakis, Konstantinos Thomopoulos)
| | - Maria Kalafateli
- Department of Gastroenterology, University Hospital of Patras (Christos Triantos, Maria Kalafateli, Efstratios Koutroumpakis, Christos Konstantakis, Konstantinos Thomopoulos)
| | - Panagiota I. Spantidea
- Division of Hematology, Department of Internal Medicine, Medical School, University of Patras (Panagiota Spadidea, Athanasia Mouzaki)
| | - Dimitrios Goukos
- Department of Propedeutic Medicine, Laiko General Hospital, Athens (Dimitrios Goukos, Georgios Daikos)
| | - Efstratios Koutroumpakis
- Department of Gastroenterology, University Hospital of Patras (Christos Triantos, Maria Kalafateli, Efstratios Koutroumpakis, Christos Konstantakis, Konstantinos Thomopoulos)
| | - Christos Konstantakis
- Department of Gastroenterology, University Hospital of Patras (Christos Triantos, Maria Kalafateli, Efstratios Koutroumpakis, Christos Konstantakis, Konstantinos Thomopoulos)
| | - Stelios F. Assimakopoulos
- Department of Internal Medicine, University Hospital of Patras (Stelios Assimakopoulos, Charalambos Gogos), Greece
| | - Charalambos Gogos
- Department of Internal Medicine, University Hospital of Patras (Stelios Assimakopoulos, Charalambos Gogos), Greece
| | - Athanasia Mouzaki
- Division of Hematology, Department of Internal Medicine, Medical School, University of Patras (Panagiota Spadidea, Athanasia Mouzaki)
| | - Georgios Daikos
- Department of Propedeutic Medicine, Laiko General Hospital, Athens (Dimitrios Goukos, Georgios Daikos)
| | - Konstantinos Thomopoulos
- Department of Gastroenterology, University Hospital of Patras (Christos Triantos, Maria Kalafateli, Efstratios Koutroumpakis, Christos Konstantakis, Konstantinos Thomopoulos)
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17
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Tsai CF, Chen MH, Wang YP, Chu CJ, Huang YH, Lin HC, Hou MC, Lee FY, Su TP, Lu CL. Proton Pump Inhibitors Increase Risk for Hepatic Encephalopathy in Patients With Cirrhosis in A Population Study. Gastroenterology 2017; 152:134-141. [PMID: 27639806 DOI: 10.1053/j.gastro.2016.09.007] [Citation(s) in RCA: 130] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2016] [Revised: 08/23/2016] [Accepted: 09/05/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Hepatic encephalopathy (HE) is a serious complication of cirrhosis and is associated with gut dysbiosis. Proton pump inhibitors (PPIs), frequently prescribed to patients with cirrhosis, can contribute to small-bowel bacterial overgrowth. We investigated whether PPI predisposes patients with cirrhosis to HE using a large database of patients. METHODS We performed a case-control study nested within a sample of Taiwan National Health Insurance beneficiaries (n = 1,000,000), followed up longitudinally from 1998 through 2011. Patients with cirrhosis and an occurrence of HE (n = 1166) were selected as the case cohort and matched to patients without HE (1:1, controls) for sex, enrollment time, end point time, follow-up period, and advanced cirrhosis. Information on prescribed drugs, drug dosage, supply days, and numbers of dispensed pills was extracted from the Taiwan National Health Insurance database. PPI use was defined as more than 30 cumulative defined daily doses (cDDDs); PPI nonuse was defined as 30 cDDDs or fewer. We performed logistic regression analyses to estimate the association between PPI use and the occurrence of HE. RESULTS Among patients with cirrhosis and an occurrence of HE, 38% (n = 445) had a history of PPI use before HE occurrence. We observed a relationship between dose of PPI taken and HE risk. The confounder-adjusted odd ratios were 1.41 (95% confidence interval [CI], 1.09-1.84), 1.51 (95% CI, 1.11-2.06), and 3.01 (95% CI, 1.78-5.10) for patients with 30-120 cDDDs, 120-365 cDDDs, and more than 365 cDDDs, respectively, compared with PPI nonusers. All categories of PPIs, except rabeprazole, were associated with an increased risk of HE. CONCLUSIONS Based on an analysis of data from Taiwan National Health Insurance beneficiaries, we found that use of PPIs in patients with cirrhosis increases the risk for HE; risk increases with dose. It therefore is important for health care providers to carefully consider prolonged PPI use by patients with cirrhosis.
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Affiliation(s)
- Chia-Fen Tsai
- Institute of Brain Science, National Yang-Ming University School of Medicine, Taipei, Taiwan; Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan; Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Mu-Hong Chen
- Institute of Brain Science, National Yang-Ming University School of Medicine, Taipei, Taiwan; Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan; Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yen-Po Wang
- Institute of Brain Science, National Yang-Ming University School of Medicine, Taipei, Taiwan; Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan; Division of Gastroenterology, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Chi-Jen Chu
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan; Division of Gastroenterology, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yi-Hsiang Huang
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan; Division of Gastroenterology, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Han-Chieh Lin
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan; Division of Gastroenterology, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Ming-Chih Hou
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan; Division of Gastroenterology, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Fa-Yauh Lee
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan; Division of Gastroenterology, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Tung-Ping Su
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan; Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Ching-Liang Lu
- Institute of Brain Science, National Yang-Ming University School of Medicine, Taipei, Taiwan; Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan; Division of Gastroenterology, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
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18
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Cole HL, Pennycook S, Hayes PC. The impact of proton pump inhibitor therapy on patients with liver disease. Aliment Pharmacol Ther 2016; 44:1213-1223. [PMID: 27774677 DOI: 10.1111/apt.13827] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2016] [Revised: 08/21/2016] [Accepted: 09/21/2016] [Indexed: 12/13/2022]
Abstract
BACKGROUND Proton pump inhibitor (PPI) therapy has been reported to be an independent mortality risk factor in patients with cirrhosis. AIM To identify the prevalence of PPI prescription, the appropriateness of this therapy and to investigate the relationship between PPI therapy and overall survival in patients with liver disease. METHODS This retrospective cohort study used patient data for 2012 to 2014 collected from the Scottish Liver Transplant Unit and the Hepatology Ward at the New Royal Infirmary of Edinburgh. RESULTS A total of 64% of the 198 patients discharged from the Hepatology ward were prescribed a PPI. Of the 206 patients assessed and listed for orthotopic liver transplant (OLT), 55% were prescribed a PPI. These percentages are significant, particularly as the majority had no recorded appropriate indication for this therapy. For patients listed for OLT, a logistic regression model revealed significant associations between PPI treatment and male sex, higher model of end-stage liver disease (MELD) scores and patient encephalopathy. A multivariate Cox regression model showed that MELD and UK model for end-stage liver disease scores were independent predictors of patient mortality, while alcoholic liver disease aetiology was a protective factor. There was no statistically significant difference in survival between patients who were prescribed a PPI at assessment and those who were not. CONCLUSION Associations between PPI use, encephalopathy and higher MELD scores imply caution should be exercised in prescribing gastric acid suppressants to patients with cirrhosis, particularly in the absence of clear indications.
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Affiliation(s)
- H L Cole
- University of Edinburgh, Edinburgh, UK
| | | | - P C Hayes
- University of Edinburgh, Edinburgh, UK
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Trifan A, Stoica O, Stanciu C, Cojocariu C, Singeap AM, Girleanu I, Miftode E. Clostridium difficile infection in patients with liver disease: a review. Eur J Clin Microbiol Infect Dis 2015; 34:2313-2324. [PMID: 26440041 DOI: 10.1007/s10096-015-2501-z] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2015] [Accepted: 09/28/2015] [Indexed: 02/05/2023]
Abstract
Over the past two decades, there has been a dramatic worldwide increase in both the incidence and severity of Clostridium difficile infection (CDI). Paralleling the increased incidence of CDI in the general population, there has been increased interest in CDI among patients with liver disease, particularly in those with liver cirrhosis and post liver transplantation. MEDLINE and several other electronic databases from January 1995 to December 2014 were searched in order to identify potentially relevant literature. Patients with cirrhosis and liver transplant recipients are at high risk for the development CDI because of antibiotics and proton pump inhibitors use, frequent and prolonged hospitalization, immunosuppressant therapy, and multiple comorbidities. Enzyme immunoassay to detect C. difficile toxins A and B in stool remains the most widely used test for CDI diagnosis, although, more recently, polymerase chain reaction (PCR)-based assays have become the preferred diagnostic test in many laboratories. Metronidazole and vancomycin, given orally, have proved to be effective in the treatment of CDI. Both cirrhotic patients and liver transplant recipients with CDI have longer length of hospital stay, increased mortality, and higher healthcare costs than those without CDI. A rapid diagnosis and adequate therapy of CDI are of paramount importance to improve liver disease patients' outcome. The aim of this review is to provide up-to-date information on the epidemiology, risk factors, pathogenesis, treatment, and outcomes in liver disease patients with CDI.
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Affiliation(s)
- A Trifan
- "Gr. T. Popa" University of Medicine and Pharmacy, 700111, Iasi, Romania
- Institute of Gastroenterology and Hepatology, "St. Spiridon" Emergency University Hospital, Independentei Street no. 1, 700111, Iasi, Romania
| | - O Stoica
- "Gr. T. Popa" University of Medicine and Pharmacy, 700111, Iasi, Romania
| | - C Stanciu
- Institute of Gastroenterology and Hepatology, "St. Spiridon" Emergency University Hospital, Independentei Street no. 1, 700111, Iasi, Romania.
| | - C Cojocariu
- "Gr. T. Popa" University of Medicine and Pharmacy, 700111, Iasi, Romania
- Institute of Gastroenterology and Hepatology, "St. Spiridon" Emergency University Hospital, Independentei Street no. 1, 700111, Iasi, Romania
| | - A-M Singeap
- "Gr. T. Popa" University of Medicine and Pharmacy, 700111, Iasi, Romania
- Institute of Gastroenterology and Hepatology, "St. Spiridon" Emergency University Hospital, Independentei Street no. 1, 700111, Iasi, Romania
| | - I Girleanu
- "Gr. T. Popa" University of Medicine and Pharmacy, 700111, Iasi, Romania
| | - E Miftode
- Hospital of Infectious Diseases, "Gr. T. Popa" University of Medicine and Pharmacy, 700111, Iasi, Romania
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Subsequent Bacterial Infections in Patients With Cirrhosis and the Role of Proton-Pump Inhibitors. Clin Gastroenterol Hepatol 2015; 13:2026-7. [PMID: 25541194 DOI: 10.1016/j.cgh.2014.12.015] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2014] [Accepted: 12/15/2014] [Indexed: 02/07/2023]
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21
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Dultz G, Piiper A, Zeuzem S, Kronenberger B, Waidmann O. Proton pump inhibitor treatment is associated with the severity of liver disease and increased mortality in patients with cirrhosis. Aliment Pharmacol Ther 2015; 41:459-66. [PMID: 25523381 DOI: 10.1111/apt.13061] [Citation(s) in RCA: 77] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2014] [Revised: 10/06/2014] [Accepted: 12/02/2014] [Indexed: 12/16/2022]
Abstract
BACKGROUND Proton pump inhibitors (PPI) are widely used in patients with liver diseases. Within the last years, there have been concerns about the PPI use as they may promote infections in patients with cirrhosis. AIM As there are sparse data of the prognostic relevance of PPI treatment, to perform a prospective study investigating the relation of PPI treatment and overall survival (OS) in cirrhotic individuals. METHODS Patients with cirrhosis were enrolled and followed prospectively. The primary end point was OS. PPI treatment and additional clinical and laboratory data were assessed at the day of the study inclusion. The time until the end point death was assessed and the individual risks were calculated with Cox regression analyses. RESULTS A total of 272 patients were included and 213 individuals (78.3%) were on PPI treatment. In multivariate logistic regression analysis, PPI treatment was associated with higher MELD scores (P = 0.027) and ascites (P = 0.039). In a multivariate Cox regression model, PPI use was an independent predictor of mortality (hazard ratio 2.330, 95% confidence interval 1.264-4.296, P = 0.007) in addition to the model of end-stage liver disease (MELD) score, hepatocellular carcinoma and hepatic decompensation. CONCLUSIONS PPI use is an independent risk factor for mortality in patients with cirrhosis. Although a causative role for increased mortality in patients taking PPI is still missing, the prescription of PPI in cirrhotics should be considered carefully taking into account its potential adverse effects.
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Affiliation(s)
- G Dultz
- Medizinische Klinik 1, Schwerpunkt Gastroenterologie und Hepatologie, Universitätsklinikum Frankfurt, Goethe-Universität, Frankfurt/Main, Germany
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Sargenti K, Prytz H, Strand A, Nilsson E, Kalaitzakis E. Healthcare-associated and nosocomial bacterial infections in cirrhosis: predictors and impact on outcome. Liver Int 2015; 35:391-400. [PMID: 25039438 DOI: 10.1111/liv.12625] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2014] [Accepted: 06/19/2014] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Population-based data on the occurrence of healthcare-associated (HCA) and hospital-acquired (HA) bacterial infections in cirrhosis, their predictors, and their impact on outcome are limited. METHODS All patients with incident cirrhosis in 2001-2010 residing in an area of 600,000 inhabitants were retrospectively identified. All serious bacterial infections (resulting in or occurring during an inpatient hospital episode) during this period were registered. Acquisition type, site of infection, occurrence of infection-related acute-on-chronic liver failure (ACLF), acute kidney injury (AKI) and bacterial resistance were analysed. Patients were followed longitudinally until death, transplant or end of 2011. RESULTS A total of 398 serious infections occurred in 241/633 (38%) patients. Forty-seven per cent were HCA and 21% HA. Proton pump inhibitor (PPI) use was more common in HA (80%) vs. HCA (64%) vs. community-acquired (44%) infections (P < 0.001). In regression analysis, decompensated status, use of antibiotics and PPIs at infection diagnosis were independent predictors of HCA/HA infections (P < 0.05). After adjustment for confounders, HCA/HA infections were significantly related to infection-related ACLF (P < 0.05), but not severe sepsis, AKI or infection-related mortality (P > 0.05). Antibiotic-resistant infections were more frequent among HA (17%) than HCA (6%) or community-acquired (8%) infections (P < 0.05). Antibiotic-resistant HCA/HA infections were independently related to severe sepsis (P < 0.05). CONCLUSIONS In a population-based cirrhotic cohort, two-thirds of serious bacterial infections were HCA or HA. Decompensated liver disease, antibiotics and PPIs were predictors of serious HCA/HA infections, which were associated with the development of ACLF. Antibiotic resistance was frequent, especially in HA infections, and contributed to risk of severe sepsis.
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Affiliation(s)
- Konstantina Sargenti
- Department of Gastroenterology, Skåne University Hospital, University of Lund, Lund, Sweden
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23
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Association between proton pump inhibitor use and spontaneous bacterial peritonitis in cirrhotic patients with ascites. Can J Gastroenterol Hepatol 2014; 28:330-4. [PMID: 24945188 PMCID: PMC4072237 DOI: 10.1155/2014/751921] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND There are data suggesting a link between proton pump inhibitor (PPI) use and the development of spontaneous bacterial peritonitis (SBP) in cirrhotic patients with ascites; however, these data are controversial. OBJECTIVE To assess whether the use of PPIs in cirrhotic patients with ascites is associated with an increased risk for SBP. METHODS A retrospective case-control study (June 2004 to June 2010) was conducted at the Centre Hospitalier de l'Université de Montréal in Montreal, Quebec. Fifty-one cirrhotic patients admitted with paracentesis-proven SBP (≥250 neutrophils/mm3), occurring within seven days of hospital admission, met the inclusion criteria. These patients were matched 1:2 (for age, Child-Pugh class and year of admission) with 102 comparable cirrhotic patients with ascites who were admitted for conditions other than SBP. RESULTS Patients with SBP had a significantly higher rate of pre-hospital PPI use (60.8%) compared with cirrhotic patients without SBP (42.2%; P=0.03). On multivariate analysis, PPI use was the only factor independently associated with SBP (OR 2.09 [95% CI 1.04 to 4.23]; P=0.04). Thirty-five (35%) patients in both groups had no documented indication for PPI use in their charts. Forty-five percent of the remaining cirrhotic patients with SBP had an inappropriate indication, as defined in the protocol, for PPI use compared with 25% of controls. CONCLUSIONS Cirrhotic patients with SBP were twice as likely to have taken PPIs than patients without SBP. These findings reinforce the association between PPI use and SBP observed in other studies. A high percentage of cirrhotic patients were taking a PPI without any documented indication.
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Lin ZN, Zuo YQ, Hu P. Association of Proton Pump Inhibitor Therapy with Hepatic Encephalopathy in Hepatitis B Virus-related Acute-on-Chronic Liver Failure. HEPATITIS MONTHLY 2014; 14:e16258. [PMID: 24748895 PMCID: PMC3989600 DOI: 10.5812/hepatmon.16258] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/18/2013] [Revised: 01/20/2014] [Accepted: 02/14/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND Hepatic encephalopathy (HE) is an important neuropsychiatry complication of acute-on-chronic liver failure (ACLF). PPI therapy may increase the intestinal bacterial overgrowth and infections. OBJECTIVES The aim of this study was to assess whether PPI use in ACLF is associated with HE. PATIENTS AND METHODS A retrospective case-control study was performed. Fifty five admitted patients with hepatitis B virus (HBV)-related ACLF complicated by Stage II-IV HE developed after admission between January 2008 and December 2012 were matched (by sex, age, and MELD score) with comparable HBV-related ACLF patients (n = 110) who did not develop this complication during hospitalization. We excluded combined HE upon admission and other neurological disorders in patients with ACLF. Univariate and multivariate analyses of 30 variables (laboratory examination, predisposition, treatment, etc.) before the occurrence of HE were carried out to identify the factors predictive of HE. RESULTS In univariate analysis, patients with HE in ACLF had a significantly higher rate of PPI use (89.1%) compared with non-HE (63.6%, P = 0.001). In addition, clinical and standard laboratory variables were significantly different between the two groups regarding the infection rate, hyponatremia, alpha-fetoprotein (AFP), Arginine Hydrochloride use and Lactulose use. Logistic regression analysis was used to examine the combined effects of the variables with HE as the outcome. HE in ACLF was associated with hyponatremia (odds ratio (OR) = 6. 318, 95% confidence interval (CI) = 2. 803-14.241; P = 0. 000), PPI use was independently associated with HE (OR = 4. 392, CI = 1. 604-12.031; P = 0. 004), and lactulose use was protective (OR = 0. 294, CI = 0. 136-0.675; P = 0. 003). CONCLUSIONS The occurrence of HE is associated with hyponatremia and PPI use in patients with ACLF.
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Affiliation(s)
- Zhao-Ni Lin
- Department of Infectious Diseases, Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yong-Qing Zuo
- Department of Infectious Diseases, Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Peng Hu
- Department of Infectious Diseases, Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Corresponding Author: Peng Hu, Department of Infectious Diseases, Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China. Tel: +86-2363693289, Fax: +86-2363703790, E-mail:
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25
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Kwon JH, Koh SJ, Kim W, Jung YJ, Kim JW, Kim BG, Lee KL, Im JP, Kim YJ, Kim JS, Yoon JH, Lee HS, Jung HC. Mortality associated with proton pump inhibitors in cirrhotic patients with spontaneous bacterial peritonitis. J Gastroenterol Hepatol 2014; 29:775-81. [PMID: 24219827 DOI: 10.1111/jgh.12426] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/01/2013] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM The aims of this study were to investigate whether acid suppressive therapy increases the risk of spontaneous bacterial peritonitis (SBP) and to define factors associated with mortality in cirrhotic patients with SBP. METHODS Cirrhotic patients who had undergone paracentesis after hospitalization were included. Those patients were divided into two groups according to the presence or absence of SBP. Factors associated with the development of SBP were analyzed. Mortality rates during hospitalization or within 30 days after SBP and the factors associated with mortality were also analyzed. RESULTS A total of 1140 patients (median age, 62; men, 75%; model for end-stage liver disease [MELD] score, 17) were included. Five hundred thirty-three patients were identified as having SBP. In the logistic regression, the use of histamine-2 receptor antagonists, the use of proton pump inhibitors (PPIs), a high admission MELD score, and old age were associated with the development of SBP. The use of PPIs within 30 days (adjusted odds ratio [aOR] 1.960; 95% confidence interval [CI] 1.190-3.227; P = 0.008), a higher admission MELD score (aOR 1.054; 95% CI 1.032-1.076; P < 0.001), and hepatocellular carcinoma (aOR 1.852; 95% CI 1.256-2.730; P = 0.002) were associated with mortality after SBP. CONCLUSIONS Acid suppressive therapy is associated with the development of SBP in cirrhotic patients with ascites. The use of PPIs is associated with mortality after SBP independent of the severity of the underlying liver disease in our retrospective cohort study.
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Affiliation(s)
- Jee Hye Kwon
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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26
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Kalaitzakis E, Josefsson A, Castedal M, Henfridsson P, Bengtsson M, Andersson B, Björnsson E. Gastrointestinal symptoms in patients with cirrhosis: a longitudinal study before and after liver transplantation. Scand J Gastroenterol 2013; 48:1308-16. [PMID: 24063547 DOI: 10.3109/00365521.2013.836755] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Gastrointestinal (GI) symptoms are common in cirrhosis and have an impact on quality of life. Their pathophysiology and their relation to energy intake have not been fully elucidated and the effect of liver transplantation on GI symptoms has not been studied. We aimed to prospectively evaluate GI symptoms and their determinants before and after transplantation and their potential relation with energy intake in cirrhosis. METHODS A total of 108 cirrhotic liver transplant candidates completed the Gastrointestinal Symptom Rating Scale (GSRS) and the hospital anxiety and depression scale. Fasting serum glucose and insulin were measured in all patients. Serum thyrotropin, free T3/T4, cortisol, free testosterone, estradiol, dehydroepiandrosterone sulfate, interleukin-6 and tumor necrosis factor-α were measured in a subgroup of 80 patients. Transplant recipients were followed for 1 year. A separate cohort of 40 cirrhotic patients underwent a high-caloric satiation drinking test (SDT). RESULTS GI symptoms were more severe in cirrhotics compared to controls from the general population. In regression analysis, the total GSRS score was independently related to lactulose, anxiety and low free testosterone (p < 0.05 for all). Four out of six GSRS domain scores improved significantly 1 year post-transplant (p < 0.05) but the total GSRS score remained higher compared to controls. GI symptoms predicted ingestion of fewer calories at SDT compared to other patients and controls (p < 0.05). CONCLUSIONS Psychological distress, lactulose treatment and low testosterone are predictors of GI symptoms which are common among cirrhotic transplant candidates. They are also associated with decreased energy intake as measured by a SDT. GI symptoms remain of concern post-transplant.
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Affiliation(s)
- Evangelos Kalaitzakis
- Institute of Internal Medicine, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden
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27
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de Vos M, De Vroey B, Garcia BG, Roy C, Kidd F, Henrion J, Deltenre P. Role of proton pump inhibitors in the occurrence and the prognosis of spontaneous bacterial peritonitis in cirrhotic patients with ascites. Liver Int 2013; 33:1316-23. [PMID: 23730823 DOI: 10.1111/liv.12210] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2012] [Accepted: 05/05/2013] [Indexed: 12/11/2022]
Abstract
BACKGROUND Proton pump inhibitors (PPIs) facilitate intestinal bacterial translocation. No robust data exist demonstrating that PPIs increase the risk of spontaneous bacterial peritonitis (SBP) and that PPIs worsen the prognosis of SBP patients. PPI use might be unsuitable for cirrhotic patients. AIMS To analyse: (i) the role of PPIs in the occurrence of SBP in cirrhotic patients; (ii) their impact on the prognosis of SBP patients; and (iii) the suitability of their use. METHODS In this retrospective case-control study, PPI use was first assessed in cirrhotic patients consecutively admitted with SBP (group I) and in a control group that included the same number of uninfected cirrhotic patients with ascites (group II). Afterwards, the impact of PPIs on SBP was assessed in group I by comparing survival of patients with and without PPIs. RESULTS A total of 102 patients were included, 51 in each group. (i) SBP patients were more frequently treated by PPIs than controls (49 vs. 25%, P = 0.014). (ii) In group I, patients with (n = 25) and without (n = 26) PPIs had similar survival rates at 1 month (64.0 ± 9.6% vs. 59.4 ± 10.0%), 3 months (41.2 ± 10.2% vs. 44.6 ± 10.6%), and 1 year (26.6 ± 9.6% vs. 28.9 ± 10.1%), and similar median age at death (53 vs. 57 years). (iii) The reason for PPI use was inappropriate or undocumented in 34% of group I and II. CONCLUSIONS Proton pump inhibitors were more frequently used in SBP patients than in controls, but did not influence the prognosis in SBP. Overuse of PPIs was encountered in one-third of cirrhotic patients and should be avoided.
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Affiliation(s)
- Marie de Vos
- Service d'Hépato-Gastroentérologie, Hôpital de Jolimont, Haine-Saint-Paul, Belgium
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28
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Trikudanathan G, Israel J, Cappa J, O'Sullivan DM. Association between proton pump inhibitors and spontaneous bacterial peritonitis in cirrhotic patients - a systematic review and meta-analysis. Int J Clin Pract 2011; 65:674-8. [PMID: 21564440 DOI: 10.1111/j.1742-1241.2011.02650.x] [Citation(s) in RCA: 85] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Acid suppressive therapy, in the form of proton pump inhibitor (PPI), is widely used in cirrhotic patients, often in indications which are not clearly justified. PPI facilitates enteric bacterial colonisation, overgrowth and translocation, which might predispose to spontaneous bacterial peritonitis. However, observational studies evaluating the association of PPI and SBP in cirrhotic patients have yielded inconsistent results. We therefore conducted a meta-analysis of relevant clinical studies to determine the nature of this association. Observational studies assessing the association between SBP and PPI in cirrhosis, conducted in adult population and published in all languages, were identified through systematic search in the MEDLINE, EMBASE and manual reviews of all major gastroenterology meeting proceedings up to May 2010. The relevant studies were pooled using traditional meta-analytic techniques with a random-effects model. Four studies were identified and included in the meta-analysis. The pooled analysis, involving a total of 772 patients, found a significant association between the use of PPI and the development of SBP (OR 2.77, 95% CI 1.82-4.23). There was very little degree of heterogeneity as reflected by an I(2) value of 22% and the visual inspection of the funnel plot. There is a potential association between use of PPI and development of SBP. Therefore, PPIs should be used judiciously and only when clearly indicated in cirrhotics. Further studies are essential to clarify this relationship and elucidate the underlying mechanisms.
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Affiliation(s)
- G Trikudanathan
- Department of Internal Medicine, University of Connecticut Medical Center, Farmington, CT, USA.
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29
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Choi EJ, Lee HJ, Kim KO, Lee SH, Eun JR, Jang BI, Kim TN. Association between acid suppressive therapy and spontaneous bacterial peritonitis in cirrhotic patients with ascites. Scand J Gastroenterol 2011; 46:616-20. [PMID: 21275825 DOI: 10.3109/00365521.2011.551891] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Proton pump inhibitor (PPI) or histamine-2 receptor antagonist (H2RA) therapy may cause intestinal bacterial overgrowth and translocation. Therefore, acid suppressive therapy may increase the risk of spontaneous bacterial peritonitis (SBP) in cirrhotic patients with ascites. MATERIAL AND METHODS A total of 176 cirrhotic patients with ascites who underwent diagnostic paracentesis between September 2004 and April 2009 were included in the analysis. Patients with gastrointestinal hemorrhage and/or antibiotic therapy within 2 weeks prior to hospital admission were excluded. SBP was defined as ≥250/mm(3) polymorphonuclear white blood cells with or without a positive culture from the ascitic fluid. Eighty-three patients (mean age 56.1 years, 63 males) had SBP and 93 (mean age 54.7 years, 75 males) did not. RESULTS On the multivariate analysis, a Child-Pugh class C (OR = 2.890, 95% CI 1.443-5.786; p = 0.003), high MELD scores (≥ 20, OR = 3.540, 95% CI 1.155-10.849; p = 0.027), and PPI use (OR = 3.443, 95% CI 1.164-10.188; p = 0.025) were risk factors for SBP. H2RA was not associated with SBP. CONCLUSIONS PPI use, as well as Child-Pugh class C and high MELD scores, was an independent risk factor for the development of SBP in cirrhotic patients with ascites. Further prospective studies are warranted to clarify this issue.
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Affiliation(s)
- Eun Jung Choi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Republic of Korea
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Garcia-Saenz-de-Sicilia M, Sanchez-Avila F, Chavez-Tapia NC, Lopez-Arce G, Garcia-Osogobio S, Ruiz-Cordero R, Tellez-Avila FI. PPIs are not associated with a lower incidence of portal-hypertension-related bleeding in cirrhosis. World J Gastroenterol 2010; 16:5869-73. [PMID: 21155009 PMCID: PMC3001979 DOI: 10.3748/wjg.v16.i46.5869] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine if proton pump inhibitor use in cirrhotic patients with endoscopic findings of portal hypertension is associated with a lower frequency of gastrointestinal bleeding.
METHODS: Patients with cirrhosis and endoscopic findings related to portal hypertension, receiving or not receiving proton pump inhibitor (PPI) therapy, were included retrospectively. We assigned patients to two groups: group 1 patients underwent PPI therapy and group 2 patients did not undergo PPI therapy.
RESULTS: One hundred and five patients with a median age of 58 (26-87) years were included, 57 (54.3%) of which were women. Esophageal varices were found in 82 (78%) patients, portal hypertensive gastropathy in 72 (68.6%) patients, and gastric varices in 15 (14.3%) patients. PPI therapy was used in 45.5% of patients (n = 48). Seventeen (16.1%) patients presented with upper gastrointestinal bleeding; in 14/17 (82.3%) patients, bleeding was secondary to esophageal varices, and in 3/17 patients bleeding was attributed to portal hypertensive gastropathy. Bleeding related to portal hypertension according to PPI therapy occurred in 18.7% (n = 9) of group 1 and in 14% (n = 8) of group 2 (odds ratio: 0.83, 95% confidence interval: 0.5-1.3, P = 0.51).
CONCLUSION: Portal hypertension bleeding is not associated with PPI use. These findings do not support the prescription of PPIs in patients with chronic liver disease with no currently accepted indication.
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Editorial: Clostridium difficile infection: Yet another predictor of poor outcome in cirrhosis. Am J Gastroenterol 2010; 105:114-6. [PMID: 20054307 DOI: 10.1038/ajg.2009.604] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The development of Clostridium difficile infection in cirrhosis is predictive of death, independent of severity of liver disease. The main risk factors are the use of antibiotics and proton-pump inhibitors (PPIs). This is further evidence that supports the wise and cautious use of antibiotics in cirrhosis and suggests avoiding the use of PPIs in these patients except for indications of proven benefit.
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