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Sikerwar S, Yao L, Elfarra Y, Jesudian A. Optimal Management of the Inpatient With Decompensated Cirrhosis. J Clin Gastroenterol 2025; 59:420-432. [PMID: 39889207 DOI: 10.1097/mcg.0000000000002143] [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: 08/21/2024] [Accepted: 01/14/2025] [Indexed: 02/02/2025]
Abstract
Over the past several years, there has been a wealth of new data pertaining to the management of complications of cirrhosis, resulting in several important updates to best practices and consensus guidelines. Despite these advancements and numerous recent targeted quality initiatives, hospitalizations resulting from complications of cirrhosis remain frequent, costly and associated with poor patient outcomes. An emphasis on evidence-based management of hospitalized patients with decompensated cirrhosis has the potential to decrease readmission rates and length of stay while improving overall patient outcomes. Herein, we provide an updated, evidence-based overview of the optimal inpatient management of the most frequently encountered complications associated with cirrhosis.
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Affiliation(s)
- Sandeep Sikerwar
- NewYork-Presbyterian Hospital/Columbia University Medical Center
| | - Leah Yao
- NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY
| | - Yasmine Elfarra
- NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY
| | - Arun Jesudian
- NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY
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2
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Wang T, Zou D, Qi X. Editorial: Navigating the Beta-Blocker Dilemma in Advanced Liver Cirrhosis-When Is the Right Time to Discontinue? Authors' Reply. Aliment Pharmacol Ther 2025; 61:194-197. [PMID: 39497499 DOI: 10.1111/apt.18371] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Revised: 10/21/2024] [Accepted: 10/21/2024] [Indexed: 12/13/2024]
Affiliation(s)
- Ting Wang
- Department of Gastroenterology, General Hospital of Northern Theater Command (Teaching Hospital of Shenyang Pharmaceutical University), Shenyang, China
- Department of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, China
| | - Deli Zou
- Department of Gastroenterology, General Hospital of Northern Theater Command (Teaching Hospital of Shenyang Pharmaceutical University), Shenyang, China
| | - Xingshun Qi
- Department of Gastroenterology, General Hospital of Northern Theater Command (Teaching Hospital of Shenyang Pharmaceutical University), Shenyang, China
- Department of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, China
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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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4
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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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Xu X, Gao F, Wang T, Yang Z, Zhao Q, Qi X. Association of non-selective β blockers with the development of renal dysfunction in liver cirrhosis: a systematic review and meta-analysis. Ann Med 2024; 56:2305935. [PMID: 38271554 PMCID: PMC10812853 DOI: 10.1080/07853890.2024.2305935] [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: 04/03/2023] [Revised: 10/14/2023] [Accepted: 01/09/2024] [Indexed: 01/27/2024] Open
Abstract
BACKGROUND & AIMS Non-selective β blockers (NSBBs) may negatively influence renal function through decreasing heart rate and cardiac output. This study aimed to systematically investigate their association. METHODS PubMed, EMBASE, and Cochrane library databases were searched to identify all relevant studies evaluating the association of NSBBs with renal dysfunction in cirrhotic patients. Unadjusted and adjusted data were separately extracted. Odds ratios (ORs) and hazard ratios (HRs) were pooled. Subgroup meta-analyses were performed according to the proportions of ascites and Child-Pugh class B/C and the mean model for end-stage liver disease (MELD) score. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation framework. RESULTS Fourteen studies were finally included. Based on unadjusted data, NSBBs significantly increased the risk of developing renal dysfunction (OR = 1.49; p = 0.03), and this association remained significant in subgroup analyses of studies where the proportions of ascites was >70% and Child-Pugh class B/C was 100%. Based on adjusted data with propensity score matching (adjusted OR = 0.61; p = 0.08) and multivariable regression modelling (adjusted HR = 0.86; p = 0.713), NSBBs did not increase the risk of developing renal dysfunction, and this association remained not significant in subgroup analyses of studies where the proportions of ascites was >70% and <70%, the proportion of Child-Pugh class B/C was <100%, and the mean MELD score was <15. The quality of evidence was very low for all meta-analyses. CONCLUSIONS NSBBs may not be associated with the development of renal dysfunction in liver cirrhosis. However, more evidence is required to clarify their association in specific populations.
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Affiliation(s)
- Xiangbo Xu
- Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, China
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
- Department of Pharmacy, General Hospital of Northern Theater Command, Shenyang, China
| | - Fangbo Gao
- Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, China
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
| | - Ting Wang
- Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, China
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
| | - Zuyao Yang
- Division of Epidemiology, The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, China
| | - Qingchun Zhao
- Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, China
- Department of Pharmacy, General Hospital of Northern Theater Command, Shenyang, China
| | - Xingshun Qi
- Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, China
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
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Gao Y, Liu X, Gao Y, Duan M, Hou B, Chen Y. Pharmacological Interventions for Cirrhotic Ascites: From Challenges to Emerging Therapeutic Horizons. Gut Liver 2024; 18:934-948. [PMID: 39205495 PMCID: PMC11565010 DOI: 10.5009/gnl240038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 05/01/2024] [Accepted: 05/02/2024] [Indexed: 09/04/2024] Open
Abstract
Ascites is the most common complication in patients with decompensated cirrhosis. This condition results in a severely impaired quality of life, excessive healthcare use, recurrent hospitalizations and significant morbidity and mortality. While loop diuretics and mineralocorticoid receptor antagonists are commonly employed for symptom relief, our understanding of their impact on survival remains limited. A comprehensive understanding of the underlying pathophysiological mechanism of ascites is crucial for its optimal management. The renin-angiotensin-aldosterone system (RAAS) is increasingly believed to play a pivotal role in the formation of cirrhotic ascites, as RAAS overactivation leads to a reduction in urine sodium excretion then a decrease in the ability of the kidneys to excrete water. In this review, the authors provide an overview of the pathogenesis of cirrhotic ascites, the challenges associated with current pharmacologic treatments, and the previous attempts to modulate the RAAS, followed by a description of some emerging targeted RAAS agents with the potential to be used to treat ascites.
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Affiliation(s)
- Yuan Gao
- Fourth Department of Liver Disease, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Xin Liu
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University, Beijing, China
| | - Yunyi Gao
- School of Basic Medicine, Qingdao University, Qingdao, China
| | - Meili Duan
- Department of Critical Care Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Bing Hou
- Xenorm MedInfo Center, Beijing, China
| | - Yu Chen
- Fourth Department of Liver Disease, Beijing Youan Hospital, Capital Medical University, Beijing, China
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Wang T, Wang X, Jia S, Zhao H, Wang L, Zhang X, Fang X, He Y, Li H, Tacke F, Qi X. Impact of non-selective beta blockers on further decompensation and death in decompensated cirrhosis: Benefit and risk stratification by MELD score. Aliment Pharmacol Ther 2024; 60:1409-1420. [PMID: 39300691 DOI: 10.1111/apt.18261] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2024] [Revised: 07/24/2024] [Accepted: 08/29/2024] [Indexed: 09/22/2024]
Abstract
BACKGROUND Non-selective beta blockers (NSBBs) can reduce the risk of decompensation, but their impact on further decompensation has been rarely investigated. AIMS The aim is to evaluate the impact of NSBBs on further decompensation and death in decompensated cirrhosis stratified by the severity of liver disease. METHODS Overall, 332 decompensated cirrhotic patients were retrospectively included, of whom 149 used NSBBs. Kaplan-Meier and Nelson-Aalen cumulative risk curves as well as Cox regression and competing risk analyses were used to estimate the associations of NSBBs with further decompensation and death, if appropriate. Hazard ratio (HR) and sub-distribution HR (sHR) were calculated. Subgroup analyses were performed based on the model for end-stage liver disease (MELD) score at admission. RESULTS In the overall analysis, the use of NSBBs was not significantly associated with further decompensation in multivariate competing risk analysis (sHR = 1.09, p = 0.580). In the subgroup analysis of patients with a MELD score of ≤9, the use of NSBBs was significantly associated with decreased risk of further decompensation in multivariate competing risk analysis (sHR = 0.57, p = 0.021). In the subgroup analysis of patients with a MELD score of >9, the use of NSBBs was associated with increased risk of further decompensation in multivariate competing risk analysis (sHR = 1.45, p = 0.044). Regardless of overall and subgroup analyses, the use of NSBBs was not significantly associated with death in multivariate Cox regression analyses. CONCLUSION NSBBs may be beneficial for the prevention of further decompensation in cirrhotic patients with a MELD score of ≤9, but deleterious in those with a MELD score of >9.
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Affiliation(s)
- Ting Wang
- Department of Gastroenterology, General Hospital of Northern Theater Command (Teaching Hospital of Shenyang Pharmaceutical University), Shenyang, China
- Department of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, China
| | - Xueying Wang
- Department of Gastroenterology, General Hospital of Northern Theater Command (Teaching Hospital of Shenyang Pharmaceutical University), Shenyang, China
- Postgraduate College, Jinzhou Medical University, Jinzhou, China
| | - Siqi Jia
- Department of Gastroenterology, General Hospital of Northern Theater Command (Teaching Hospital of Shenyang Pharmaceutical University), Shenyang, China
- Department of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, China
| | - Haitao Zhao
- Medical Ethical Committee, General Hospital of Northern Theater Command, Shenyang, China
| | - Le Wang
- Department of Gastroenterology, General Hospital of Northern Theater Command (Teaching Hospital of Shenyang Pharmaceutical University), Shenyang, China
- Postgraduate College, China Medical University, Shenyang, China
| | - Xianxian Zhang
- Department of Gastroenterology, General Hospital of Northern Theater Command (Teaching Hospital of Shenyang Pharmaceutical University), Shenyang, China
- Department of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, China
| | - Xiaohui Fang
- Department of Gastroenterology, General Hospital of Northern Theater Command (Teaching Hospital of Shenyang Pharmaceutical University), Shenyang, China
- Department of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, China
| | - Yong He
- Department of Gastroenterology, General Hospital of Northern Theater Command (Teaching Hospital of Shenyang Pharmaceutical University), Shenyang, China
- Department of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, China
| | - Hongyu Li
- Department of Gastroenterology, General Hospital of Northern Theater Command (Teaching Hospital of Shenyang Pharmaceutical University), Shenyang, China
- Department of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, China
- Postgraduate College, China Medical University, Shenyang, China
| | - Frank Tacke
- Department of Hepatology and Gastroenterology, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum (CVK) and Campus Charité Mitte (CCM), Berlin, Germany
| | - Xingshun Qi
- Department of Gastroenterology, General Hospital of Northern Theater Command (Teaching Hospital of Shenyang Pharmaceutical University), Shenyang, China
- Department of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, China
- Postgraduate College, Jinzhou Medical University, Jinzhou, China
- Postgraduate College, China Medical University, Shenyang, China
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Ouyang H, Wang X, Deng D, Wang Q, Yu Y. Impact of beta-blocker usage on delirium in patients with sepsis in ICU: a cross-sectional study. Front Med (Lausanne) 2024; 11:1458417. [PMID: 39346947 PMCID: PMC11427366 DOI: 10.3389/fmed.2024.1458417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Accepted: 08/28/2024] [Indexed: 10/01/2024] Open
Abstract
Introduction Delirium in patients with sepsis can be life-threatening. This study aims to investigate the impact of the use of beta-blockers on the occurrence of delirium in patients with sepsis in the ICU by utilizing a comprehensive dataset. Methods This is a cross-sectional study conducted using the data obtained from a single ICU in the USA. Patients diagnosed with sepsis and receiving beta-blockers were compared with those not receiving beta-blockers. Propensity score matching (PSM) and multiple regression analysis were employed to adjust for potential confounders. Results Among the 19,660 patients hospitalized for sepsis, the beta-blocker and non-user groups comprised 13,119 (66.73%) and 6,541 (33.27%) patients, respectively. Multivariable logistic regression models revealed a significant reduction of 60% in 7-day delirium for beta-blocker users (OR = 0.40, 95% CI: 0.37-0.43, p < 0.001), for 30-day delirium (OR = 0.32, 95% CI: 0.29-0.35, p < 0.001), and for 90-day delirium (OR = 0.33, 95% CI: 0.30-0.35, p < 0.001). The PSM results further strengthen the validity of these findings. An analysis of safety issues demonstrated that beta-blockers may have an impact on the risk of acute kidney injury. However, following PSM, the results are not considered robust. Furthermore, there was no discernible change in the odds of renal replacement therapy and the length of ICU stays. Discussion Our findings suggest a potential protective effect of beta-blockers against delirium in patients with sepsis. Nevertheless, the observational design limits causal inference, necessitating future randomized controlled trials to validate these findings.
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Affiliation(s)
- Honglian Ouyang
- Department of Critical Care Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Xiaoqi Wang
- Medical Intensive Care Unit, Sichuan Provincial Maternity and Child Health Care Hospital, Chengdu, Sichuan, China
- The Affiliated Women's and Children's Hospital of Chengdu Medical College, Chengdu, Sichuan, China
| | - Dingwei Deng
- Department of Critical Care Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Qianqian Wang
- Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yi Yu
- Department of Critical Care Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
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Ranjan A, Jindal A, Maiwall R, Vashishtha C, Vijayaraghavan R, Arora V, Sarin SK. Midodrine plus propranolol versus propranolol alone in preventing first bleed in patients with cirrhosis and severe ascites: a randomized controlled trial. Hepatol Int 2024; 18:1261-1270. [PMID: 38727780 DOI: 10.1007/s12072-024-10687-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Accepted: 04/21/2024] [Indexed: 08/04/2024]
Abstract
BACKGROUND Propranolol, a non-selective beta-blocker, commonly used to prevent variceal bleed, but might precipitate circulatory dysfunction in severe ascites. Midodrine, an alpha-1 adrenergic agonist improves renal perfusion and systemic hemodynamics. Addition of midodrine might facilitate higher maximum tolerated dose (MTD) of propranolol, thereby less risk of variceal bleed in cirrhosis patients with severe ascites. METHODS 140 patients with cirrhosis and severe/refractory ascites were randomized- propranolol and midodrine (Gr.A,n = 70) or propranolol alone (Gr.B,n = 70). Primary outcome was incidence of bleed at 1 year. Secondary outcomes included ascites control, achievement of target heart rate (THR), HVPG response and adverse effects. RESULTS Baseline characteristics were comparable between two groups. Cumulative incidence of bleed at 1 year was lower in Gr.A than B (8.5%vs.27.1%,p-0.043). The MTD of propranolol was higher in Gr.A (96.67 ± 36.6 mg vs. 76.52 ± 24.4 mg; p-0.01) and more patients achieved THR (84.2%vs.55.7%,p-0.034). Significantly higher proportion of patients in Gr.A had complete resolution of ascites [17.1%vs.11.4%,p-0.014), diuretic tolerance (80%vs.60%,p-0.047) at higher doses(p-0.02) and lesser need for paracentesis. Patients in Gr.A also had greater reduction in variceal grade (75.7%vs.55.7%;p-0.01), plasma renin activity (54.4% from baseline) (p = 0.02). Mean HVPG reduction was greater in Gr.A than B [4.38 ± 2.81 mmHg(23.5%) vs. 2.61 ± 2.87 mmHg(14.5%),p-0.045]. Complications like post-paracentesis circulatory dysfunction and spontaneous bacterial peritonitis on follow-up were higher in Gr.B than A (22.8%vs.51.4%,p = 0.013 and 10%vs.15.7%, p = 0.03, respectively). CONCLUSION Addition of midodrine facilitates effective use of propranolol in higher doses and greater HVPG reduction, thereby preventing first variceal bleed, reduced paracentesis requirements with fewer ascites- related complications in patients with cirrhosis with severe/refractory ascites.
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Affiliation(s)
- Abhijeet Ranjan
- Department of Hepatology, Institute of Liver and Biliary Sciences, D - 1, Vasant Kunj, New Delhi, 110070, India
| | - Ankur Jindal
- Department of Hepatology, Institute of Liver and Biliary Sciences, D - 1, Vasant Kunj, New Delhi, 110070, India
| | - Rakhi Maiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences, D - 1, Vasant Kunj, New Delhi, 110070, India
| | - Chitranshu Vashishtha
- Department of Hepatology, Institute of Liver and Biliary Sciences, D - 1, Vasant Kunj, New Delhi, 110070, India
| | - Rajan Vijayaraghavan
- Department of Hepatology, Institute of Liver and Biliary Sciences, D - 1, Vasant Kunj, New Delhi, 110070, India
| | - Vinod Arora
- Department of Hepatology, Institute of Liver and Biliary Sciences, D - 1, Vasant Kunj, New Delhi, 110070, India
| | - Shiv K Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, D - 1, Vasant Kunj, New Delhi, 110070, India.
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Jeong HW, Kim JH, Han SB, Kwon HM, Jun IG, Song JG, Hwang GS. Impact of preoperative nonselective beta-blocker use on acute kidney injury after living donor liver transplantation: Propensity score analysis. Ann Hepatol 2024; 29:101474. [PMID: 38331385 DOI: 10.1016/j.aohep.2024.101474] [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: 11/02/2023] [Revised: 01/11/2024] [Accepted: 01/18/2024] [Indexed: 02/10/2024]
Abstract
INTRODUCTION AND OBJECTIVES Acute kidney injury (AKI) is prevalent and has deleterious effects on postoperative outcomes following liver transplantation (LT). The impact of nonselective beta-blockers (NSBBs) in patients with liver cirrhosis remains controversial. This study investigated the association between preoperative NSBB use and AKI after living donor LT (LDLT). PATIENTS AND METHODS We evaluated 2,972 adult LDLT recipients between January 2012 and July 2022. The patients were divided into two groups based on the preoperative NSBB use. Propensity score matched (PSM) and inverse probability of treatment weighting (IPTW) analyses were performed to evaluate the association between preoperative NSBB use and postoperative AKI. Multiple logistic regression analyses were also used to identify the risk factors for AKI. RESULTS The overall incidence of AKI was 1,721 (57.9%) cases. The NSBB group showed a higher incidence of AKI than the non-NSBB group (62.4% vs. 56.7%; P = 0.011). After PSM and IPTW analyses, no significant difference in the incidence of AKI was found between the two groups (Odds ratio, OR 1.13, 95% confidence interval, CI 0.93-1.37, P = 0.230, PSM analysis; OR 1.20, 95% CI 0.99-1.44, P = 0.059, IPTW analysis). In addition, preoperative NSBB use was not associated with AKI after multivariate logistic regression analysis (OR 1.16, 95% CI 0.96-1.40, P = 0.118). CONCLUSIONS Preoperative NSBB use was not associated with AKI after LDLT. Further studies are needed to validate our results.
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Affiliation(s)
- Hye-Won Jeong
- Department of Anesthesiology and Pain Medicine, Chonnam National University Hospital, Gwangju, Korea
| | - Jae Hwan Kim
- Department of Anesthesiology and Pain Medicine, Laboratory for Cardiovascular Dynamics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sang-Bin Han
- Department of Anesthesiology and Pain Medicine, Laboratory for Cardiovascular Dynamics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hye-Mee Kwon
- Department of Anesthesiology and Pain Medicine, Laboratory for Cardiovascular Dynamics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - In-Gu Jun
- Department of Anesthesiology and Pain Medicine, Laboratory for Cardiovascular Dynamics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jun-Gol Song
- Department of Anesthesiology and Pain Medicine, Laboratory for Cardiovascular Dynamics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
| | - Gyu-Sam Hwang
- Department of Anesthesiology and Pain Medicine, Laboratory for Cardiovascular Dynamics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Cromer M, Wilcox CM, Shoreibah M. Beta-blockers and cirrhosis: Striking the right balance. Am J Med Sci 2024; 367:228-234. [PMID: 38262558 DOI: 10.1016/j.amjms.2024.01.009] [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] [Received: 06/30/2023] [Accepted: 01/16/2024] [Indexed: 01/25/2024]
Abstract
Decompensated cirrhosis is associated with a significantly increased risk of mortality. Variceal hemorrhage (VH) further increases the risk of mortality, and of future variceal bleed events. Non-selective beta-blockers (NSBBs) are effective therapy for primary and secondary prophylaxis of VH and have become the cornerstone of pharmacologic therapy in cirrhosis. Beta-blockers are associated with reduced overall mortality and GI-bleeding related mortality in patients with decompensated cirrhosis; they may also confer hemodynamically independent beneficial effects. Long-term treatment with beta-blockers may improve decompensation-free survival in compensated cirrhosis with clinically significant portal hypertension (CSPH). Carvedilol more effectively lowers the hepatic vein portal gradient than traditional NSBBs and has been shown to improve survival in compensated cirrhosis. Treatment goals in compensated cirrhosis with CSPH should focus on early utilization of beta-blockers to prevent decompensation and reduce mortality.
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Affiliation(s)
- Mark Cromer
- Division of General Internal Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
| | - C Mel Wilcox
- Digestive Health Institute, Orlando Health, Orlando, FL, USA
| | - Mohamed Shoreibah
- Division of Gastroenterology & Hepatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
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12
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Sikerwar S, Zand S, Steel P, Jesudian A. Management of patients with cirrhosis in the emergency department: Implications for hospitalization outcomes. Liver Transpl 2024; 30:94-102. [PMID: 37851401 DOI: 10.1097/lvt.0000000000000285] [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: 06/29/2023] [Accepted: 10/11/2023] [Indexed: 10/19/2023]
Affiliation(s)
- Sandeep Sikerwar
- New York Presbyterian Weill Cornell Medical Center New York, New York, USA
- Columbia University Irving Medical Center, New York, New York, USA
| | - Sohrab Zand
- New York Presbyterian Weill Cornell Medical Center New York, New York, USA
| | - Peter Steel
- New York Presbyterian Weill Cornell Medical Center New York, New York, USA
| | - Arun Jesudian
- New York Presbyterian Weill Cornell Medical Center New York, New York, USA
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13
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Karagiannakis DS, Karakousis ND, Androutsakos T. B-Blockers in Liver Cirrhosis: A Wonder Drug for Every Stage of Portal Hypertension? A Narrative Review. Biomedicines 2023; 12:57. [PMID: 38255164 PMCID: PMC10813395 DOI: 10.3390/biomedicines12010057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2023] [Revised: 12/20/2023] [Accepted: 12/21/2023] [Indexed: 01/24/2024] Open
Abstract
In cirrhotic patients, non-selective b-blockers (NSBBs) constitute the reference treatment of choice as monotherapy or combined with band ligation for the prevention of first variceal bleeding and rebleeding, respectively. Furthermore, the last Baveno VII guidelines recommended carvedilol, a b-blocker with additional anti-a1 receptor activity, in all compensated cirrhotics with clinically significant portal hypertension, to prevent liver decompensation. Interestingly enough, NSBBs have been reported to have a potentially positive impact on the short-term mortality of patients with acute-on-chronic liver failure. However, concerns remain about the use of b-blockers in the presence of severe complications, such as refractory ascites, hepatorenal syndrome, spontaneous bacterial peritonitis, or established cirrhotic cardiomyopathy. In addition, it has not been verified yet whether carvedilol supersedes all the other NSBBs in every stage of liver disease, even when severe complications have developed. Therefore, this review aims to illustrate recent data regarding the potential role of b-blockers across all stages of liver disease, beyond the primary and secondary prophylaxis of variceal bleeding, and address the authors' proposals on the use of NSBBs concerning the severity of liver disease and the patient's performance status.
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Affiliation(s)
- Dimitrios S. Karagiannakis
- Academic Department of Gastroenterology, Laiko General Medicine, Medical School of National and Kapodistrian University of Athens, 11527 Athens, Greece
| | | | - Theodoros Androutsakos
- Department of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece;
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14
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Jung CY, Chang JW. Hepatorenal syndrome: Current concepts and future perspectives. Clin Mol Hepatol 2023; 29:891-908. [PMID: 37050843 PMCID: PMC10577351 DOI: 10.3350/cmh.2023.0024] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Revised: 04/10/2023] [Accepted: 04/10/2023] [Indexed: 04/14/2023] Open
Abstract
Hepatorenal syndrome (HRS), a progressive but potentially reversible deterioration of kidney function, remains a major complication in patients with advanced cirrhosis, often leading to death before liver transplantation (LT). Recent updates in the pathophysiology, definition, and classification of HRS have led to a complete revision of the nomenclature and diagnostic criteria for HRS type 1, which was renamed HRS-acute kidney injury (AKI). HRS is characterized by severe impairment of kidney function due to increased splanchnic blood flow, activation of several vasoconstriction factors, severe vasoconstriction of the renal arteries in the absence of kidney histologic abnormalities, nitric oxide dysfunction, and systemic inflammation. Diagnosis of HRS remains a challenge because of the lack of specific diagnostic biomarkers that accurately distinguishes structural from functional AKI, and mainly involves the differential diagnosis from other forms of AKI, particularly acute tubular necrosis. The optimal treatment of HRS is LT. While awaiting LT, treatment options include vasoconstrictor drugs to counteract splanchnic arterial vasodilation and plasma volume expansion by intravenous albumin infusion. In patients with HRS unresponsive to pharmacological treatment and with conventional indications for kidney replacement therapy (KRT), such as volume overload, uremia, or electrolyte imbalances, KRT may be applied as a bridging therapy to transplantation. Other interventions, such as transjugular intrahepatic portosystemic shunt, and artificial liver support systems have a very limited role in improving outcomes in HRS. Although recently developed novel therapies have potential to improve outcomes of patients with HRS, further studies are warranted to validate the efficacy of these novel agents.
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Affiliation(s)
- Chan-Young Jung
- Division of Nephrology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jai Won Chang
- Division of Nephrology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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15
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Danielsen KV, Nabilou P, Wiese SS, Hove JD, Bendtsen F, Møller S. Effect of beta-blockers on multiple haemodynamics in cirrhosis: A cross-over study by MR-imaging and hepatic vein catheterization. Liver Int 2023; 43:2245-2255. [PMID: 37387503 DOI: 10.1111/liv.15664] [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: 03/13/2023] [Revised: 05/25/2023] [Accepted: 06/19/2023] [Indexed: 07/01/2023]
Abstract
BACKGROUND Non-selective beta-blockers (NSBB) are widely used in the treatment of patients with cirrhosis. Only about 50% respond with a sufficient reduction in their hepatic venous pressure gradient (HVPG) and NSBB may induce detrimental cardiac and renal effects in the presence of severe decompensation. We aimed to assess the effects of NSBB on haemodynamics using magnetic resonance imaging (MRI) and to assess if these haemodynamic changes were related to the disease severity and HVPG response. METHOD A prospective cross-over study of 39 patients with cirrhosis. Patients underwent hepatic vein catheterization and MRI with assessments of HVPG, cardiac function, systemic and splanchnic haemodynamics before and after propranolol infusion. RESULTS Propranolol induced significant decreases in cardiac output (-12%) and blood flow of all vascular compartments, with the largest reductions seen in the azygos venous (-28%), portal venous (-21%), splenic (-19%) and superior mesenteric artery (-16%) blood flow. Renal artery blood flow fell by -5% in the total cohort, with a more pronounced reduction in patients without ascites than in those with ascites (-8% vs. -3%, p = .01). Twenty-four patients were NSBB responders. Their changes in HVPG after NSBB were not significantly associated with other haemodynamic changes. CONCLUSION The changes in cardiac, systemic and splanchnic haemodynamics did not differ between NSBB responders and non-responders. The effects of acute NSBB blockade on renal flow seem to depend on the severity of the hyperdynamic state, with the largest reduction in renal blood flow in compensated patients compared to decompensated patients with cirrhosis. However, future studies are needed to assess the effects of NSBB on haemodynamics and renal blood flow in patients with diuretic-resistant ascites.
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Affiliation(s)
- Karen Vagner Danielsen
- Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
- Department of Clinical Physiology and Nuclear Medicine, Centre of Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
| | - Puria Nabilou
- Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
| | - Signe Skovgaard Wiese
- Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
| | - Jens Dahlgaard Hove
- Department of Clinical Physiology and Nuclear Medicine, Centre of Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
- Department of Cardiology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
- Institute of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Flemming Bendtsen
- Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
- Institute of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Søren Møller
- Department of Clinical Physiology and Nuclear Medicine, Centre of Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
- Institute of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
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16
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Lai M, Fenton C, Ge J, Rubin J, Lai JC, Cullaro G. Nonselective beta-blockers may lead to stage 2 acute kidney injury and waitlist mortality in child class C cirrhosis. Hepatol Commun 2023; 7:e0255. [PMID: 37756037 PMCID: PMC10531476 DOI: 10.1097/hc9.0000000000000255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Accepted: 07/21/2023] [Indexed: 09/28/2023] Open
Abstract
BACKGROUND AND AIMS Nonselective beta-blockers (NSBB) protect patients with compensated cirrhosis; however, it is unclear if NSBB is associated with acute kidney injury (AKI) in patients with decompensated cirrhosis. We aimed to determine if the use of NSBB was associated with an increased risk of stage II AKI or greater and waitlist mortality (WLM) among patients with decompensated cirrhosis awaiting liver transplant stratified by cirrhosis severity. METHODS Included were 1816 outpatients listed for liver transplantation at UCSF from June 2012 to April 2022. Our primary outcome was stage 2 AKI (>200% increase in serum creatinine). Our secondary outcome was WLM (all-cause mortality). Our primary exposure was the use of any NSBB derived using natural language processing of clinical notes. Multivariable Cox proportional hazards models with time-dependent variables were used to determine the HR of NSBB use on stage 2 AKI and WLM, stratified by Child-Pugh Score. RESULTS The average age of the cohort was 58 years old, with 35% identifying as female. In multivariable time-dependent models, NSBB use was associated with 1.53 × (95 CI 1.19-1.97) the hazard of stage 2 AKI in the cohort overall and 1.80 × (95 CI 1.26-2.57) among those with Child C cirrhosis, respectively. Similarly, NSBB use was associated with 1.30 × (95 CI 1.07-1.59) and 1.45 × (95 CI 1.03-2.03) the hazard of WLM, overall and in Child C, respectively. NSBB use was not significantly associated with AKI nor WLM among those with Child A. CONCLUSION NSBB use is associated with Stage 2 AKI and WLM in patients awaiting liver transplantation and Child C cirrhosis. These data suggest cautious use of NSBBs in patients in this population.
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Mazumder NR, Junna S, Sharma P. The Diagnosis and Non-pharmacological Management of Acute Kidney Injury in Patients with Cirrhosis. Clin Gastroenterol Hepatol 2023; 21:S11-S19. [PMID: 37625862 DOI: 10.1016/j.cgh.2023.04.033] [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: 02/07/2023] [Revised: 03/01/2023] [Accepted: 04/06/2023] [Indexed: 08/27/2023]
Abstract
Acute kidney injury in patients with cirrhosis is quite common, and is seen in up to 50% of patients hospitalized for decompensated cirrhosis. Causes of acute kidney injury include prerenal, renal, or postrenal etiologies. The diagnosis and early institution of nonpharmacologic and pharmacologic management are key to the recovery of renal function. The objective of this review is to provide a practical approach to the use of diagnostic biomarkers and highlight the nonpharmacologic management and prevention of acute kidney injury.
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Affiliation(s)
- Nikhilesh R Mazumder
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan; Gastroenterology Section, VA Ann Arbor Healthcare System, Ann Arbor, Michigan
| | - Shilpa Junna
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan
| | - Pratima Sharma
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan; Gastroenterology Section, VA Ann Arbor Healthcare System, Ann Arbor, Michigan.
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18
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Wong F. Management of Portal Hypertension in Patients with Acute-on-Chronic Liver Disease. Clin Liver Dis 2023; 27:717-733. [PMID: 37380294 DOI: 10.1016/j.cld.2023.03.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/30/2023]
Abstract
Portal hypertension is central to the pathogenesis of complications of cirrhosis, including acute-on-chronic liver failure (ACLF). Both nonselective beta-blockers and preemptive transjugular portal-systemic stent shunt can lower portal pressure, reducing the risk of variceal bleeding, a known trigger for ACLF. However, in patients with advanced cirrhosis, both could potentially induce ACLF by causing hemodynamic instability and hepatic ischemia, respectively, and therefore must be used with caution. Lowering portal pressure with vasoconstrictor such as terlipressin can reverse the kidney failure but careful patient selection is key for success, with careful monitoring for complications.
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Affiliation(s)
- Florence Wong
- Department of Medicine, Division of Gastroenterology & Hepatology, University Health Network, University of Toronto, Toronto, Ontario, Canada.
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19
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Bani Hani A, Abu Abeeleh M, Al-Najjar S, Alzibdeh A, Mansour S, Bsisu I, Awamleh N, Farah R. Incidence, risk factors and outcomes of acute kidney injury in surgical intensive care unit octogenarians at the Jordan University Hospital. BMC Geriatr 2023; 23:266. [PMID: 37142956 PMCID: PMC10158325 DOI: 10.1186/s12877-023-03975-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Accepted: 04/15/2023] [Indexed: 05/06/2023] Open
Abstract
BACKGROUND Acute kidney damage (AKI) is among the most severe consequences observed in surgical intensive care units (SICUs). We aim to observe the incidence, risk factors, and outcomes of acute kidney injury in SICU octogenarians. METHODS A cross-sectional retrospective study was conducted at the SICU of Jordan University Hospital (JUH), a tertiary teaching hospital in a developing country, between January 2018 and December 2019. Patients who were 80 years or older at the time of data collection were included. The definition of AKI was based on Kidney Disease Improving Global Outcomes (KDIGO) criteria. Demographic, clinical, and laboratory data were reviewed. RESULTS A total number of 168 patients were included. The mean age was 84.0 ± 3.8 years, and 54.8% of the participants were women. Of those, 115 (68.5%) had surgery before or during ICU stay, and 28.7% of the patients' surgeries were an emergency surgery. Also, 47.8% of surgeries were considered by anesthesia to be high-risk surgeries. A total of 55 patients (32.7%) developed AKI during their SICU stay. The factors that were significantly associated with AKI in the ICU patients included use of beta blocker [AOR: 3.7; 95% CI: 1.2-11.8; p = 0.025], and inotropes [AOR:4.0; 95% CI: 1.2-13.3; p = 0.03]. The factors that were significantly associated with mortality in the ICU included using mechanical ventilation [AOR:18.7; 95% CI: 2.4-141.9; p = 0.005] and inotropes use [AOR: 12.3; 95% CI: 1.2-120.7; p = 0.031]. CONCLUSIONS The incidence of AKI during SICU stay in this study was 32.7% and it was significantly associated with the use of beta blockers, mechanical ventilation, and inotropes. The mortality rate among octogenarians who developed AKI during SICU stay was 36.4%. Further studies are needed globally to assess the incidence of AKI in octogenarian surgical patients and identify risk factors to provide preventative measurements and strategies.
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Affiliation(s)
- Amjad Bani Hani
- Department of General Surgery, School of Medicine, The University of Jordan, Amman, 11942, Jordan
| | - Mahmoud Abu Abeeleh
- Department of General Surgery, School of Medicine, The University of Jordan, Amman, 11942, Jordan
| | - Sondos Al-Najjar
- School of Medicine, The University of Jordan, Amman, 11942, Jordan
| | | | - Shahd Mansour
- School of Medicine, The University of Jordan, Amman, 11942, Jordan.
| | - Isam Bsisu
- Department of Anesthesia and Intensive Care, School of Medicine, The University of Jordan, Amman, 11942, Jordan
| | - Nour Awamleh
- School of Medicine, The University of Jordan, Amman, 11942, Jordan
| | - Randa Farah
- Department of Internal Medicine, School of Medicine, The University of Jordan, Amman, 11942, Jordan
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20
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Tittanegro T, China L, Forrest E, Kallis Y, Ryder SD, Wright G, Freemantle N, O'Brien A. Use of non-selective B-blockers is safe in hospitalised decompensated cirrhosis patients and exerts a potential anti-inflammatory effect: Data from the ATTIRE trial. EClinicalMedicine 2023; 55:101716. [PMID: 36407574 PMCID: PMC9672423 DOI: 10.1016/j.eclinm.2022.101716] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Revised: 10/06/2022] [Accepted: 10/10/2022] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Nonselective B-blockers (NSBBs) are believed to have pleiotropic effects beyond reducing portal pressure. However, studies also report potential harm in patients hospitalized with cirrhosis and ascites. We therefore investigated whether NSBB use at ATTIRE trial entry (Albumin to prevent infection in chronic liver failure, 2016-19) was associated with increased renal or cardiovascular dysfunction, compared the incidence of infection and plasma markers of systemic inflammation, and examined mortality at 28-days, 3 and 6-months. METHODS In ATTIRE patients grouped by NSBB use at trial entry, we studied infection at baseline, hospital acquired infection and organ dysfunction during trial treatment period and mortality, with propensity score matching to account for differences in disease severity. FINDINGS There were no differences in renal or cardiovascular dysfunction between patients treated with NSBBs or not, during days 3-15 of hospitalization, despite elevated serum creatinine in NSBB patients at hospitalisation. Use of NSBBs was associated with a significant reduction in infection at hospitalization (p = 0.006), lower white cell counts throughout hospital stay (p < 0.001) and reduced plasma procalcitonin (p = 0.009) and interlukin-8 levels (p = 0.04) at baseline, but markers of bacterial translocation and systemic inflammation were the same in treatment groups. There was no reduction in hospital acquired infections in patients taking NSBBs and no beneficial impact on mortality at 28-days, 3 and 6-months. INTERPRETATIONS Our real-world data from a completed randomised trial show that use of NSBBs in decompensated cirrhosis patients is safe during hospitalisation. We also show a potential anti-inflammatory role for NSBBs which may be mediated by a downregulation of IL-8 induced leucocytosis, that was associated with reduced infection at baseline but not a survival benefit. FUNDING Wellcome Trust and Department of Health and Social Care.
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Affiliation(s)
- Thais Tittanegro
- Institute of Liver and Digestive Health, University College London, United Kingdom
| | - Louise China
- 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, 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
- Corresponding author. UCL Institute for Liver and Digestive Health, Upper 3rd Floor, Division of Medicine, Royal Free Campus, Rowland Hill Street London NW3 2PF, United Kingdom. a.o'
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21
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Korobka VL, Pasetchnikov VD, Korobka RV, Pak ES, Shapovalov AM. Use of endoscopic band ligation alone and in combination with nonselective beta blockers for prevention of variceal bleeding in ascites patients on the liver transplant waiting list. RUSSIAN JOURNAL OF TRANSPLANTOLOGY AND ARTIFICIAL ORGANS 2022; 24:42-50. [DOI: 10.15825/1995-1191-2022-3-42-50] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Objective: to conduct a comparative analysis of the effectiveness of two methods – endoscopic band ligation (EBL) alone and in combination with nonselective beta blockers (NSBB) – used for prevention of variceal bleeding (VB); to evaluate their impact on patient survival in severe ascites during long-term stay on the liver transplant waiting list (LTWL). Materials and methods. A retrospective comparative study of two groups of patients with decompensated liver disease, ascites and varices included in the LTWL, who received EBL (n = 41, group 1) and EBL + NSBB (n = 45, group 2). Results. The groups being compared did not differ in demographics, clinical parameters, MELD and Child–Turcotte–Pugh scores. There were no significant differences in the incidence of severe ascites, particularly diuretic-resistant ascites. The study groups did not differ in the incidence of mediumand large-sized varices. Incidence of bleeding did not differ in both groups. Overall mortality was significantly higher in the EBL + NSBB group than in the EBL group. Patient survival was lower, while mortality was higher in the EBL + NSBB group. The combined therapy group had a significantly higher number of acute kidney injury (AKI) than the EBL group. Conclusion. The compared methods are equivalently effective in preventing VB in patients with decompensated cirrhosis with a prolonged stay on the waiting list. Survival rate is significantly lower, while mortality is significantly higher in the EBL + NSBB group than in the EBL group.
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Affiliation(s)
- V. L. Korobka
- Rostov Regional Clinical Hospital; Rostov State Medical University
| | | | - R. V. Korobka
- Rostov Regional Clinical Hospital; Rostov State Medical University
| | - E. S. Pak
- Rostov Regional Clinical Hospital; Rostov State Medical University
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22
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Fallahzadeh MA, Asrani SK, Tapper EB, Saracino G, Rahimi RS. Nonselective beta-blocker use is associated with increased hepatic encephalopathy-related readmissions in cirrhosis. World J Clin Cases 2022; 10:8097-8106. [PMID: 36159543 PMCID: PMC9403687 DOI: 10.12998/wjcc.v10.i23.8097] [Citation(s) in RCA: 4] [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: 03/07/2022] [Revised: 04/13/2022] [Accepted: 07/11/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatic encephalopathy (HE) is a neurocognitive condition in cirrhosis leading to frequent hospitalizations. Nonselective beta-blockers (NSBBs) are the mainstay of pharmacologic treatment in cirrhotic patients. We hypothesized that since NSBBs decrease cardiac output and portal flow, the decreased metabolic filtering process of liver parenchyma may lead to increased HE-related hospitalizations.
AIM To evaluate the impact of NSBB administration on HE-related readmissions in cirrhotic patients.
METHODS In this retrospective cohort study, we included 393 patients admitted to Baylor University Medical Center for liver-related portal hypertension indications between January 2013 and July 2018. Independent predictors of the first HE-related readmissions were identified using Cox proportional hazards analysis. The cumulative incidence of the first HE-related readmissions between patients receiving NSBBs and not receiving NSBBs was examined using Fine-Gray modeling to account for the competing risk of death or liver transplantation.
RESULTS The mean age was 58.1 ± 10.2 years and most patients fell into Child class C (49.1%) or B (43.8%). The median Model for End-Stage Liver Disease-Sodium score was 22 (IQR: 11). The cumulative incidence of the first HE-related readmissions was significantly higher in patients taking NSBBs compared to patients not receiving NSBBs (71.8% vs 41.8%, P < 0.0001). In multivariate analysis, after adjusting for demographics, markers of liver disease severity, selective beta-blocker, lactulose and rifaximin use, NSBB use [Hazard ratio: 1.74 (95%CI: 1.29-2.34)] was independently associated with the first HE-related readmissions over a median follow-up of 3.8 years.
CONCLUSION NSBB use is independently associated with increased HE-related readmissions in patients with cirrhosis, regardless of liver disease severity.
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Affiliation(s)
| | - Sumeet K Asrani
- Division of Hepatology, Baylor University Medical Center, Dallas, TX 75246, United States
| | - Elliot B Tapper
- Division of Hepatology, University of Michigan, Ann Arbor, MI 48109, United States
| | - Giovanna Saracino
- Division of Hepatology, Baylor University Medical Center, Dallas, TX 75246, United States
| | - Robert S Rahimi
- Division of Hepatology, Baylor University Medical Center, Dallas, TX 75246, United States
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23
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Propranolol vs. band ligation for primary prophylaxis of variceal hemorrhage in cirrhotic patients with ascites: a randomized controlled trial. Hepatol Int 2022; 16:944-953. [DOI: 10.1007/s12072-022-10361-4] [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: 03/02/2022] [Accepted: 05/07/2022] [Indexed: 11/04/2022]
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24
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Téllez L, Albillos A. Non-selective beta-blockers in patients with ascites: The complex interplay among the liver, kidney and heart. Liver Int 2022; 42:749-761. [PMID: 35051310 DOI: 10.1111/liv.15166] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 12/31/2021] [Accepted: 01/09/2022] [Indexed: 12/12/2022]
Abstract
Non-selective beta-blockers (NSBBs) are the cornerstone of the primary and secondary prophylaxis of variceal bleeding in cirrhotic patients. They additionally prevent ascites development and death in compensated patients with clinically significant portal hypertension. After ascites onset, NSBBs remain beneficial for preventing further decompensations. However, as the cirrhosis progresses, the inflammation increases, systemic vasodilatation worsens, ascites turns refractory and cardiodynamic equilibrium becomes extremely fragile. In this scenario, NSBBs can critically impair the cardiac reserve and facilitate a haemodynamic breakdown, imperilling renal perfusion. Consequently, NSBB treatment should be carefully monitored or even avoided in such patients, and other options for portal hypertension management should be considered. In the present review, we explore the effects of NSBBs in patients with ascites and discuss the complex interplay among their hepatic, systemic and renal haemodynamic effects in this scenario.
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Affiliation(s)
- Luis Téllez
- Department of Gastroenterology and Hepatology, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Madrid, Spain
| | - Agustín Albillos
- Department of Gastroenterology and Hepatology, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Madrid, Spain
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Guo D, Wang H, Lai X, Li J, Xie D, Zhen L, Jiang C, Li M, Liu X. Development and validation of a nomogram for predicting acute kidney injury after orthotopic liver transplantation. Ren Fail 2021; 43:1588-1600. [PMID: 34865599 PMCID: PMC8648040 DOI: 10.1080/0886022x.2021.2009863] [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] [Indexed: 10/26/2022] Open
Abstract
BACKGROUND We aim to develop and validate a nomogram model for predicting severe acute kidney injury (AKI) after orthotopic liver transplantation (OLT). METHODS A total of 576 patients who received OLT in our center were enrolled. They were assigned to the development and validation cohort according to the time of inclusion. Univariable and multivariable logistic regression using the forward variable selection routine were applied to find risk factors for post-OLT severe AKI. Based on the results of multivariable analysis, a nomogram was developed and validated. Patients were followed up to assess the long-term mortality and development of chronic kidney disease (CKD). RESULTS Overall, 35.9% of patients were diagnosed with severe AKI. Multivariable logistic regression analysis revealed that recipients' BMI (OR 1.10, 95% CI 1.04-1.17, p = 0.012), hypertension (OR 2.32, 95% CI 1.22-4.45, p = 0.010), preoperative serum creatine (sCr) (OR 0.96, 95% CI 0.95-0.97, p < 0.001), and intraoperative fresh frozen plasm (FFP) transfusion (OR for each 1000 ml increase 1.34, 95% CI 1.03-1.75, p = 0.031) were independent risk factors for post-OLT severe AKI. They were all incorporated into the nomogram. The area under the ROC curve (AUC) was 0.73 (p < 0.05) and 0.81 (p < 0.05) in the development and validation cohort. The calibration curve demonstrated the predicted probabilities of severe AKI agreed with the observed probabilities (p > 0.05). Kaplan-Meier survival analysis showed that patients in the high-risk group stratified by the nomogram suffered significantly poorer long-term survival than the low-risk group (HR 1.92, p < 0.01). The cumulative risk of CKD was higher in the severe AKI group than no severe AKI group after competitive risk analysis (HR 1.48, p < 0.05). CONCLUSIONS With excellent predictive abilities, the nomogram may be a simple and reliable tool to identify patients at high risk for severe AKI and poor long-term prognosis after OLT.
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Affiliation(s)
- Dandan Guo
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Huifang Wang
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Xiaoying Lai
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Junying Li
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Demin Xie
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Li Zhen
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Chunhui Jiang
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Min Li
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Xuemei Liu
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China
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Conversion of Propranolol to Carvedilol Improves Renal Perfusion and Outcome in Patients With Cirrhosis and Ascites. J Clin Gastroenterol 2021; 55:721-729. [PMID: 32991355 DOI: 10.1097/mcg.0000000000001431] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Accepted: 08/18/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND In recent years, concerns have been raised on the potential adverse effects of nonselective beta-blockers, and particularly carvedilol, on renal perfusion and survival in decompensated cirrhosis with ascites. We investigated the long-term impact of converting propranolol to carvedilol on systemic hemodynamics and renal function, and on the outcome of patients with stable cirrhosis and grade II/III nonrefractory ascites. PATIENTS AND METHODS Ninety-six patients treated with propranolol for esophageal varices' bleeding prophylaxis were prospectively evaluated. These patients were randomized in a 2:1 ratio to switch to carvedilol at 12.5 mg/d (CARVE group; n=64) or continue propranolol (PROPRA group; n=32). Systemic vascular resistance, vasoactive factors, glomerular filtration rate, and renal blood flow were evaluated at baseline before switching to carvedilol and after 6 and 12 months. Further decompensation and survival were evaluated at 2 years. RESULTS During a 12-month follow-up, carvedilol induced an ongoing improvement of systemic vascular resistance (1372±34 vs. 1254±33 dynes/c/cm5; P=0.02) along with significant decreases in plasma renin activity (4.05±0.66 vs. 6.57±0.98 ng/mL/h; P=0.01) and serum noradrenaline (76.7±8.2 vs. 101.9±10.5 pg/mL; P=0.03) and significant improvement of glomerular filtration rate (87.3±2.7 vs. 78.7±2.3 mL/min; P=0.03) and renal blood flow (703±17 vs. 631±12 mL/min; P=0.03); no significant effects were noted in the PROPRA group. The 2-year occurrence of further decompensation was significantly lower in the CARVE group than in the PROPRA group (10.5% vs. 35.9%; P=0.003); survival at 2 years was significantly higher in the CARVE group (86% vs. 64.1%; P=0.01, respectively). CONCLUSION Carvedilol at the dose of 12.5 mg/d should be the nonselective beta-blocker treatment of choice in patients with cirrhosis and nonrefractory ascites, as it improves renal perfusion and outcome.
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Yoon KT, Liu H, Lee SS. β-blockers in advanced cirrhosis: More friend than enemy. Clin Mol Hepatol 2021; 27:425-436. [PMID: 33317244 PMCID: PMC8273637 DOI: 10.3350/cmh.2020.0234] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Revised: 11/10/2020] [Accepted: 11/18/2020] [Indexed: 12/16/2022] Open
Abstract
Nonselective beta-adrenergic blocker (NSBB) therapy for the prevention of initial and recurrent gastrointestinal bleeding in cirrhotic patients with gastroesophageal varices has been used for the past four decades. NSBB therapy is considered the cornerstone of treatment for varices, and has become the standard of care. However, a 2010 study from the group that pioneered β-blocker therapy suggested a detrimental effect of NSBBs in decompensated cirrhosis, especially in patients with refractory ascites. Since then, numerous additional studies have incompletely resolved whether NSBBs are deleterious, although more recent evidence weighs against a harmful effect. The possibility of a "therapeutic window" has also been raised. We aimed to review the literature to analyze the pros and cons of using NSBBs in patients with cirrhosis, not only with respect to bleeding or mortality but also to other potential benefits and risks. β-blockers are highly effective in preventing first bleeding and recurrent bleeding. Furthermore, NSBBs improve congestion/ischemia of the gut mucosa, decrease intestinal permeability, and therefore indirectly alleviate systemic inflammation. β-blockers shorten the electrocardiographic prolonged QTc interval and may also decrease the incidence of hepatocellular carcinoma. On the other hand, the possibility of deleterious effects in cirrhosis has not been completely eliminated. NSBBs may be associated with an increased risk of portal vein thrombosis, although this could be correlational artifact. Overall, we conclude that β-blockers in cirrhosis are much more of a friend than enemy.
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Affiliation(s)
- Ki Tae Yoon
- Liver Unit, University of Calgary Cumming School of Medicine, Calgary, Canada
| | - Hongqun Liu
- Liver Unit, University of Calgary Cumming School of Medicine, Calgary, Canada
| | - Samuel S. Lee
- Liver Unit, University of Calgary Cumming School of Medicine, Calgary, Canada
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Maiwall R, Pasupuleti SSR, Jain P, Sarin SK. Degree of Portal and Systemic Hemodynamic Alterations Predict Recurrent AKI and Chronic Kidney Disease in Patients With Cirrhosis. Hepatol Commun 2021; 5:293-308. [PMID: 33553976 PMCID: PMC7850308 DOI: 10.1002/hep4.1607] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Accepted: 08/23/2020] [Indexed: 02/04/2023] Open
Abstract
The relevance of hemodynamic derangements on the incidence of recurrent acute kidney injury (AKI) and chronic kidney disease (CKD) in patients with cirrhosis is largely unknown. Consecutive patients with cirrhosis with a complete record of baseline hemodynamics were followed for identifying risk factors for the development of recurrent AKI and CKD by using negative binomial regression and competing risk analysis, respectively. Consecutive patients with cirrhosis (n = 2013, age 50.1 ± 11.8 years, 80% male, Child A:B:C percentage 13.7:52.9:33.4, and mean Child-Turcotte-Pugh score 8.6 ± 1.8) were enrolled, 893 (44.3%) of whom received beta-blockers, with 44.2% responders. Prior AKI was noted in 12.4% at enrollment. At a median follow-up of 379 (interquartile range: 68-869) days, AKI developed at a rate of 0.37 episodes per person-year, and 26% patients developed CKD. A lower mean number of AKI episodes (0.05 ± 0.25 vs. 0.42 ± 0.868; P < 0.001), CKD (subdistribution hazard ratio 0.74 [0.54-1.02]), and mortality (hazard ratio 0.21 [0.06-0.73]) were observed in beta-blocker responders. Albuminuria was an independent risk factor for recurrent AKI, CKD, and mortality (P < 0.05). Lower systemic vascular resistance index predicted hemodynamic response (odds ratio 2.04 [1.29-3.22]), cumulative AKI episodes (ratio of means 0.10 [0.08-0.14]), and development of CKD (subdistribution hazard ratio 0.70 [0.58-0.83]). Higher hepatic venous pressure gradient (≥17 mm Hg) predicted AKI episodes (ratio of means 1.76 [1.32-2.35]) but not CKD. Conclusion: High portal pressure and severe vasodilatation predispose patients with cirrhosis to repeated AKI episodes and development of CKD. Response to beta-blockers and therapies targeting the vasodilatory state could prevent frequent AKI and the risk of CKD development. Albuminuria could serve as an early marker of renal dysfunction in patients with cirrhosis.
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Affiliation(s)
- Rakhi Maiwall
- Department of HepatologyInstitute of Liver and Biliary sciencesNew DelhiIndia
| | | | - Priyanka Jain
- Department of BiostatisticsInstitute of Liver and Biliary SciencesNew DelhiIndia
| | - Shiv Kumar Sarin
- Department of HepatologyInstitute of Liver and Biliary sciencesNew DelhiIndia
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Piccolo Serafim L, Simonetto DA. Primary Prophylaxis of Variceal Bleeding in Liver Cirrhosis. VARICEAL BLEEDING IN LIVER CIRRHOSIS 2021:67-75. [DOI: 10.1007/978-981-15-7249-4_6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Sharma S, Agarwal S, Gunjan D, Kaushal K, Anand A, Gopi S, Mohta S, Saraya A. Outcomes of Portal Pressure-Guided Therapy in Decompensated Cirrhosis With Index Variceal Bleed in Asian Cohort. J Clin Exp Hepatol 2021; 11:443-452. [PMID: 34276151 PMCID: PMC8267357 DOI: 10.1016/j.jceh.2020.11.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Accepted: 11/06/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND AND AIMS Hemodynamic response to pharmacotherapy improves survival in patients with cirrhosis post variceal bleeding, but long-term outcomes remain unexplored especially in this part of the world. We aimed to study the long-term impact of portal pressure reduction on liver-related outcomes after index variceal bleed. METHODS Patients with hepatic venous pressure gradient (HVPG) more than 12 mm Hg after index variceal bleed were given non-selective beta-blockers in combination with variceal band ligation. HVPG response was assessed after 4 weeks. Patients were followed up for rebleed events, survival, additional decompensation events and safety outcomes. Rebleed and other decompensations were compared using competing risks analysis, taking death as competing event, and survival was compared using Kaplan-Meier analysis. RESULTS Forty-eight patients (29 responders and 19 non-responders) were followed up for a median duration of 45 (24-56) months. Rebleeding rates at 1, 3 and 5 years were 10.3%, 20.7% and 20.7% in responders and 15.8%, 44.7% and 51.1% in non-responders, respectively (Gray's test, P = 0.044). Survival rates at 1, 3 and 5 years were 89.7%, 72.1% and 51.9% in responders and 89.5%, 44% and 37.7% in non-responders, respectively (log-rank test, P = 0.1). Both severity of liver disease (MELD score, multivariate sub-distributional hazards ratio: 1.166 [1.014-1.341], P = 0.030) and HVPG non-response (multivariate sub-distributional hazards ratio: 2.476 [1.87-7.030], P = 0.045) predicted rebleeding risk while survival was dependent only on severity of liver disease (MELD > 12, multivariate hazards ratio: 2.36 [1.04-5.38], P = 0.041). CONCLUSION Baseline severity of liver disease predicted survival and rebleed in these patients. Hemodynamic response, although associated with lower rebleeding rate, had limited impact on survival.
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Key Words
- ACLF, acute on chronic liver failure
- AFP, alpha-fetoprotein
- AVB, acute variceal bleed
- CT, computed tomography
- CTP, Child–Turcotte–Pugh
- EASL-CLIF, European Association of Study of Liver Disease – Chronic Liver Failure Consortium
- EBL, endoscopic band ligation
- EGD, esophagogastroduodenoscopy
- HE, hepatic encephalopathy
- HRS, hepatorenal syndrome
- HVPG, hepatic venous pressure gradient
- MELD, model for end-stage liver disease
- NSBB, non-selective beta-blockers
- SBP, spontaneous bacterial peritonitis
- acute variceal bleed
- hemodynamic response and carvedilol
- hepatic venous pressure gradient
- non-selective beta-blockers
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Affiliation(s)
| | | | | | | | | | | | | | - Anoop Saraya
- Address for correspondence: Anoop Saraya, Professor and Head of Department, Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110029, India.
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Carvedilol Combined With Ivabradine Improves Left Ventricular Diastolic Dysfunction, Clinical Progression, and Survival in Cirrhosis. J Clin Gastroenterol 2020; 54:561-568. [PMID: 31305281 DOI: 10.1097/mcg.0000000000001219] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Left ventricular diastolic dysfunction (LVDD) refers to impaired cardiac diastolic relaxation and may be improved by targeted heart rate reduction (THR). The authors evaluated whether a combination of carvedilol and ivabradine, an If channel blocker that reduces heart rate without affecting blood pressure, could improve LVDD and outcomes in cirrhosis. PATIENTS AND METHODS THR was defined as heart rate reduction to 55 to 65 beats per minute. Of 260 patients with cirrhosis, 189 (72%) with LVDD were randomized to THR [group (Gr.)A; n=94; carvedilol±ivabradine)] or standard care (Gr.B; n=95; no β-blockers) and followed for 12 months. RESULTS In Gr.A, THR was achieved at 4 weeks in 88 (93%) patients (responders, R): 48 (61.5%) with carvedilol alone and 40 (86.9%) of 46 patients with additional ivabradine. In Gr.A, LVDD reversed in 16 (20.5%) and improved from grade 2 to 1 in 34 (35.4%)], whereas in Gr.B, it progressed from grade 1 to 2 in 10 (10.5%) patients. At 12 months, 21 (11.1%) patients died, 6 (14%) in Gr.A and 15 (18%) in Gr.B (P=0.240), but no mortality was seen in those who had persistent THR at 1 year (n=78; P=0.000). In multivariate analysis, model for end-stage liver disease [hazard ratio (HR), 1.52; 95% confidence interval (CI), 1.22-2.75; P=0.034] and E-wave transmitral/early diastolic mitral annular velocity (HR, 1.28; 95% CI, 1.23-2.42; P=0.048) predicted 1-year mortality. Nonresponders had an increased mortality risk (HR, 1.3; 95% CI, 1.2-1.8; P=0.046) independent of age, gender, and baseline model for end-stage liver disease. Levels of norepinephrine, N terminal brain natriuretic peptide, plasma renin activity, and aldosterone were reduced (P<0.01) in responders. More patients in Gr.B developed acute kidney injury (odds ratio, 4.2; 95% CI, 2.8-10.5; P=0.027) and encephalopathy (odds ratio, 6.6; 95% CI, 1.9-9.7; P=0.040). CONCLUSIONS Ivabradine combined with carvedilol improves LVDD, achieves THR more often and reduces risk of encephalopathy, acute kidney injury with improved survival in patients with cirrhosis.
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Impact of cardiac function, refractory ascites and beta blockers on the outcome of patients with cirrhosis listed for liver transplantation. J Hepatol 2020; 72:463-471. [PMID: 31622697 DOI: 10.1016/j.jhep.2019.10.002] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2019] [Revised: 09/27/2019] [Accepted: 10/07/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Whether non-selective beta blockers (NSBBs) are deleterious in patients with end-stage cirrhosis and refractory ascites has been widely debated. We hypothesized that only the subset of patients on the liver transplant waiting list who had impaired cardiac performance would be at increased risk of mortality if receiving NSBBs. METHODS This study included 584 consecutive patients with cirrhosis evaluated for transplantation between 1999 and 2014. All patients had right heart catheterization with hemodynamic measurements at evaluation. Fifty percent received NSBBs. Refractory ascites was present in 33%. Cardiac performance was assessed by left ventricular stroke work index (LVSWI). Waiting list mortality without liver transplantation was explored using competing risk analysis. RESULTS LVSWI was significantly lower in patients with refractory ascites. In multivariate analysis using competing risk, refractory ascites, NSBBs and LVSWI were associated with waiting list mortality in the whole population, with a statistically significant interaction between NSBBs and LVSWI. The most discriminant value of LVSWI was 64.1 g-m/m2. In the final model, refractory ascites (subdistribution hazard ratio 1.52; 95% CI1.01-2.28; p = 0.0083) and treatment by NSBBs with LVSWI <64.1 g-m/m2 (subdistribution hazard ratio 1.96; 95% CI 1.32-2.90; p = 0.0009) were significantly associated with waiting list mortality, taking into account serum sodium and the model for end-stage liver disease score. CONCLUSIONS This study suggests that compromised cardiac performance is more common in patients with refractory ascites and that NSBBs are deleterious in cirrhotic patients with compromised cardiac performance. These results highlight the prognostic value of cardiac function in patients with end-stage cirrhosis. LAY SUMMARY There are still controversies concerning the impact of non-selective beta blockers on outcomes in patients with decompensated cirrhosis, especially in those with refractory ascites. In this study of 584 cirrhotic patients evaluated for liver transplantation, who underwent right heart catheterization, we have shown that global cardiac performance measured by left ventricular stroke work index is lower in patients with refractory ascites. Administration of non-selective beta blockers in patients with compromised cardiac performance may increase waiting list mortality. These results highlight the prognostic value of global cardiac performance in patients with end-stage cirrhosis.
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Rodrigues SG, Mendoza YP, Bosch J. Beta-blockers in cirrhosis: Evidence-based indications and limitations. JHEP Rep 2020; 2:100063. [PMID: 32039404 PMCID: PMC7005550 DOI: 10.1016/j.jhepr.2019.12.001] [Citation(s) in RCA: 94] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2019] [Revised: 11/29/2019] [Accepted: 12/03/2019] [Indexed: 02/07/2023] Open
Abstract
Non-selective beta-blockers (NSBBs) are the mainstay of treatment for portal hypertension in the setting of liver cirrhosis. Randomised controlled trials demonstrated their efficacy in preventing initial variceal bleeding and subsequent rebleeding. Recent evidence indicates that NSBBs could prevent liver decompensation in patients with compensated cirrhosis. Despite solid data favouring NSBB use in cirrhosis, some studies have highlighted relevant safety issues in patients with end-stage liver disease, particularly with refractory ascites and infection. This review summarises the evidence supporting current recommendations and restrictions of NSBB use in patients with cirrhosis.
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Key Words
- ACLF
- ACLF, acute-on-chronic liver failure
- AKI, acute kidney injury
- ALD, alcohol-related liver disease
- ARD, absolute risk difference
- AV, atrioventricular
- EBL, endoscopic band ligation
- GOV, gastroesophageal varices
- HRS, hepatorenal syndrome
- HVPG, hepatic venous pressure gradient
- IGV, isolated gastric varices
- IRR, incidence rate ratio
- ISMN, isosorbide mononitrate
- MAP, mean arterial pressure
- NASH, non-alcoholic steatohepatitis
- NNH, number needed to harm
- NNT, number needed to treat
- NR, not reported
- NSBBs
- NSBBs, non-selective beta-blockers
- OR, odds ratio
- PH, portal hypertension
- PHG, portal hypertensive gastropathy
- RCT, randomised controlled trials
- RR, risk ratio
- SBP, spontaneous bacterial peritonitis
- SCL, sclerotherapy
- TIPS, transjugular intrahepatic portosystemic shunt
- ascites
- cirrhosis
- portal hypertension
- spontaneous bacterial peritonitis
- varices
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Affiliation(s)
- Susana G. Rodrigues
- Swiss Liver Center, UVCM, Inselspital, Bern University Hospital, Department of Biomedical Research, University of Bern, Bern, Switzerland
| | - Yuly P. Mendoza
- Swiss Liver Center, UVCM, Inselspital, Bern University Hospital, Department of Biomedical Research, University of Bern, Bern, Switzerland
| | - Jaime Bosch
- Swiss Liver Center, UVCM, Inselspital, Bern University Hospital, Department of Biomedical Research, University of Bern, Bern, Switzerland
- Corresponding author. Address: Swiss Liver Center, UVCM, Inselspital, Bern University Hospital, Department of Biomedical Research, University of Bern, Bern, Switzerland.
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Turco L, Villanueva C, La Mura V, García-Pagán JC, Reiberger T, Genescà J, Groszmann RJ, Sharma BC, Merkel C, Bureau C, Alvarado E, Abraldes JG, Albillos A, Bañares R, Peck-Radosavljevic M, Augustin S, Sarin SK, Bosch J, García-Tsao G. Lowering Portal Pressure Improves Outcomes of Patients With Cirrhosis, With or Without Ascites: A Meta-Analysis. Clin Gastroenterol Hepatol 2020; 18:313-327.e6. [PMID: 31176013 DOI: 10.1016/j.cgh.2019.05.050] [Citation(s) in RCA: 87] [Impact Index Per Article: 17.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2019] [Accepted: 05/24/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS In unselected patients with cirrhosis, those with reductions in hepatic venous pressure gradient (HVPG) to below a defined threshold (responders) have a reduced risk of variceal hemorrhage (VH) and death. We performed a meta-analysis to compare this effect in patients with vs without ascites. METHODS We collected data from 15 studies of primary or secondary prophylaxis of VH that reported data on VH and death in responders vs nonresponders. We included studies in which data on ascites at baseline and on other relevant outcomes during follow-up evaluation were available. We performed separate meta-analyses for patients with vs without ascites. RESULTS Of the 1113 patients included in the studies, 968 patients (87%) had been treated with nonselective β-blockers. In 993 patients (89%), HVPG response was defined as a decrease of more than 20% from baseline (>10% in 11% of patients) or to less than 12 mm Hg. In the 661 patients without ascites, responders (n = 329; 50%) had significantly lower odds of events (ascites, VH, or encephalopathy) than nonresponders (odds ratio [OR], 0.35; 95% CI, 0.22-0.56). Odds of death or liver transplantation were also significantly lower among responders than nonresponders (OR, 0.50, 95% CI, 0.32-0.78). In the 452 patients with ascites, responders (n = 188; 42%) had significantly lower odds of events (VH, refractory ascites, spontaneous bacterial peritonitis, or hepatorenal syndrome) than nonresponders (OR, 0.27; 95% CI, 0.16-0.43). Overall, odds of death or liver transplantation were lower among responders (OR, 0.47; 95% CI, 0.29-0.75). No heterogeneity was observed among studies. CONCLUSIONS In a meta-analysis of clinical trials, we found that patients with cirrhosis with and without ascites who respond to treatment with nonselective β-blockers (based on reductions in HVPG) have a reduced risk of events, death, or liver transplantation.
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Affiliation(s)
- Laura Turco
- Division of Gastroenterology, Azienda Ospedaliero, Universitaria di Modena, University of Modena and Reggio Emilia, Modena, Italy; PhD Program in Clinical and Experimental Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Candid Villanueva
- Department of Gastroenterology, Hospital Santa Creu i Sant Pau, Barcelona, Spain; Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid, Spain
| | - Vincenzo La Mura
- Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca' Granda, Ospedale Maggiore Policlinico, Medicina Generale - Emostasi e Trombosi, Milano, Italy; Centro Ricerca e Cura "Angela Maria ed Antonio Migliavacca" per lo Studio e la Cura delle Malattie del Fegato and Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milano, Italy
| | - Juan Carlos García-Pagán
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid, Spain; Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Universitat de Barcelona, Barcelona, Spain
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Joan Genescà
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid, Spain; Liver Unit, Department of Medicine, Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Roberto J Groszmann
- Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut; Section of Digestive Diseases, VA Connecticut Healthcare System, West Haven, Connecticut
| | - Barjesh C Sharma
- Department of Gastroenterology, Govind Ballabh Pant Institute of Postgraduate Medical Education & Research, New Delhi, India
| | - Carlo Merkel
- Department of Medicine Dipartimento di Medicina and Centro Interdipartimentale di Ricerca sulla Modellistica delle Alterazioni Neuropsichiche in Medicina Clinica, University of Padua, Padua, Italy
| | - Christophe Bureau
- Service d'Hépato-Gastroentérologie, Hôpital Purpan Centre Hospitalier Universitaire Toulouse, Université Paul Sabatier, Toulouse, France
| | - Edilmar Alvarado
- Department of Gastroenterology, Hospital Santa Creu i Sant Pau, Barcelona, Spain; Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid, Spain
| | - Juan Gonzalez Abraldes
- Cirrhosis Care Clinic, Division of Gastroenterology (Liver Unit), University of Alberta, Centre of Excellence for Gastrointestinal Inflammation and Immunity Research, Edmonton, Canada
| | - Agustin Albillos
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid, Spain; Department of Gastroenterology and Hepatology, Hospital Universitario Ramón y Cajal, University of Alcalá, Instituto Ramón y Cajal de Investigación Sanitaria, Madrid, Spain
| | - Rafael Bañares
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid, Spain; Hospital General Universitario Gregorio Marañón, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain
| | - Markus Peck-Radosavljevic
- Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria; Klinikum Klagenfurth am Wörthersee, Klagenfurth, Austria
| | - Salvador Augustin
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid, Spain; Liver Unit, Department of Medicine, Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Shiv K Sarin
- Department of Gastroenterology, Govind Ballabh Pant Institute of Postgraduate Medical Education & Research, New Delhi, India
| | - Jaime Bosch
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid, Spain; Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Universitat de Barcelona, Barcelona, Spain; Swiss Liver Center, Hepatology, University Clinic for Visceral Surgery and Medicine, Inselspital, University of Bern, Bern, Switzerland
| | - Guadalupe García-Tsao
- Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut; Section of Digestive Diseases, VA Connecticut Healthcare System, West Haven, Connecticut.
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Ngwa T, Orman E, Gomez EV, Vuppalanchi R, Kubal C, Chalasani N, Ghabril M. Non-selective beta blocker use is associated with improved short-term survival in patients with cirrhosis referred for liver transplantation. BMC Gastroenterol 2020; 20:4. [PMID: 31906860 PMCID: PMC6945622 DOI: 10.1186/s12876-019-1155-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Accepted: 12/23/2019] [Indexed: 02/06/2023] Open
Abstract
Background Recent evidence cautions against the use of non-selective beta-blockers (NSBB) in patients with refractory ascites or spontaneous bacterial peritonitis while other data suggests a survival benefit in patients with advanced liver disease. The aim of this study was to describe the use and impact of NSBB in patients with cirrhosis referred for liver transplantation. Methods A single-center cohort of patients with cirrhosis, who were referred and evaluated for liver transplantation between January and June 2012 were studied for baseline characteristics and clinical outcomes. Patients were grouped according to the use of NSBB at initial evaluation, with the endpoint of 90-day mortality. Results Sixty-five (38%) of 170 consecutive patients evaluated for liver transplantation were taking NSBB. Patients taking NSBB had higher MELD and Child Pugh score. NSBB use was associated with lower 90-day mortality (6% vs. 15%) with a risk adjusted hazard ratio of 0.27 (95%CI .09–0.88, p = .03). Patients taking NSBB developed acute kidney injury (AKI) within 90 days more frequently than patients not taking NSBB (22% vs 11%), p = 0.048). However, this was related to increased stage 1 AKI episodes, all of which resolved. Twelve (27%) of 45 patients with > 90 day follow up discontinued NSBB, most commonly for hypotension and AKI, had increased subsequent MELD and mortality. Conclusions NSBB use in patients with cirrhosis undergoing liver transplant evaluation is associated with better short-term survival. Nevertheless, ongoing tolerance of NSBB in this population is dynamic and may select a subset of patients with better hemodynamic reserve.
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Affiliation(s)
- Taiwo Ngwa
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA
| | - Eric Orman
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA
| | - Eduardo Vilar Gomez
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA
| | - Raj Vuppalanchi
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA
| | - Chandrashekhar Kubal
- Transplant Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Naga Chalasani
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA
| | - Marwan Ghabril
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA.
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36
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Yoo JJ, Kim SG, Kim YS, Lee B, Jeong SW, Jang JY, Lee SH, Kim HS, Jun BG, Kim YD, Cheon GJ. Propranolol plus endoscopic ligation for variceal bleeding in patients with significant ascites: Propensity score matching analysis. Medicine (Baltimore) 2020; 99:e18913. [PMID: 32000397 PMCID: PMC7004788 DOI: 10.1097/md.0000000000018913] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
The use of beta-blockers in decompensated cirrhosis accompanying ascites is still under debate. The aim of this study was to compare overall survival (OS) and incidence of cirrhotic complications between endoscopic variceal ligation (EVL) only and EVL + non-selective beta-blocker (NSBB) combination therapy in cirrhotic patients with significant ascites (≥grade 2).This retrospective study included 271 consecutive cirrhotic patients with ascites who were treated with EVL only or EVL + NSBB combination therapy as a primary prophylaxis of esophageal varices. The primary outcome was all-cause mortality. Propensity score matching was performed between the 2 groups to minimize baseline difference.Median observation period was 42.1 months (interquartile range, 18.4-75.1 months). All patients had deteriorated liver function: 81.1% Child-Pugh class B and 18.9% Child-Pugh class C. All-cause mortality was significantly higher in the EVL + NSBB group than in the EVL only group not only in non-matched cohort, but also in matched cohort (48.9% vs 31.2%; P = .039). More people died from hepatic failure in the EVL + NSBB group than that in the EVL only group (40.5% vs 20.0%; P = .020). However, the incidence of variceal bleeding, hepatorenal syndrome (HRS), or spontaneous bacterial peritonitis (SBP) was not significantly different between the 2 groups.The use of NSBB might worsen the prognosis of cirrhotic patients with significant ascites. These results suggest that EVL alone is a more appropriate treatment option for prophylaxis of esophageal varices than propranolol combination therapy when patients have significant ascites.
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Affiliation(s)
- Jeong-Ju Yoo
- Department of Gastroenterology and Hepatology, Soon Chun Hyang University School of Medicine
| | - Sang Gyune Kim
- Department of Gastroenterology and Hepatology, Soon Chun Hyang University School of Medicine
| | - Young Seok Kim
- Department of Gastroenterology and Hepatology, Soon Chun Hyang University School of Medicine
| | - Bora Lee
- Department of Statistics, Graduate School, Chung-Ang University, Seoul
| | - Soung Won Jeong
- Department of Gastroenterology and Hepatology, Soon Chun Hyang University School of Medicine
| | - Jae Young Jang
- Department of Gastroenterology and Hepatology, Soon Chun Hyang University School of Medicine
| | - Sae Hwan Lee
- Department of Gastroenterology and Hepatology, Soon Chun Hyang University School of Medicine
| | - Hong Soo Kim
- Department of Gastroenterology and Hepatology, Soon Chun Hyang University School of Medicine
| | - Baek-Gyu Jun
- Department of Internal Medicine, Gangneug Asan Hospital, Republic of Korea
| | - Young Don Kim
- Department of Internal Medicine, Gangneug Asan Hospital, Republic of Korea
| | - Gab Jin Cheon
- Department of Internal Medicine, Gangneug Asan Hospital, Republic of Korea
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Zanetto A, Garcia-Tsao G. Gastroesophageal Variceal Bleeding Management. THE CRITICALLY ILL CIRRHOTIC PATIENT 2020:39-66. [DOI: 10.1007/978-3-030-24490-3_4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Bultas AC, Teshome B, Richter SK, Schafers S, Cooke E, Call WB. Use of Nonselective β-Blockers in Patients With End-Stage Liver Disease and Select Complications. Ann Pharmacother 2019; 54:583-593. [PMID: 31810371 DOI: 10.1177/1060028019893092] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Objective: To review the literature and recommendations for nonselective β-blockers (NSBBs) in the setting of variceal bleeding prophylaxis and decompensated liver disease. Data Sources: Literature search of MEDLINE was performed (1988 to October 2019) using the following search terms: cirrhosis, advanced cirrhosis, β-blocker, decompensation, prophylaxis. Abstracts, peer-reviewed publications, clinical practice guidelines, and product monographs were reviewed. Study Selection and Data Extraction: Relevant English language studies and those conducted in humans were considered for analysis and inclusion. Data Synthesis: Evidence that suggests that NSBBs are harmful in advanced cirrhosis is overshadowed by confounding variables and small patient populations. The majority of the available evidence suggests neutral or beneficial effects on mortality with continuation of NSBBs despite liver disease progression. Based on the available literature, guidelines, and expert consensuses, NSBBs can be considered within this patient population and may have a positive impact on the majority of these patients. Relevance to Patient Care and Clinical Practice: This review summarizes current place in therapy for NSBBs in the setting of cirrhosis and variceal bleeding prophylaxis. It also includes a discussion of the literature for use of NSBBs within the setting of different acute decompensations in which the data and recommendations for use are less clear. Conclusions: Recent evidence shows neutral or positive results for NSBB use in particular decompensation subgroups, which suggests that NSBBs can be used cautiously with close monitoring in patients with advanced cirrhosis. Questions still remain regarding optimal agent and dose and whether agents can be safely restarted after an acute decompensation episode.
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Affiliation(s)
| | | | | | | | - Emily Cooke
- Barnes-Jewish Hospital, Saint Louis, MO, USA
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39
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Wong RJ, Robinson A, Ginzberg D, Gomes C, Liu B, Bhuket T. Assessing the safety of beta-blocker therapy in cirrhosis patients with ascites: A meta-analysis. Liver Int 2019; 39:1080-1088. [PMID: 30614656 DOI: 10.1111/liv.14040] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2018] [Revised: 12/26/2018] [Accepted: 01/01/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND & AIMS Beta-blocker therapy is effective at reducing risks of variceal bleeding. However, beta-blockers may detrimentally exacerbate the underlying haemodynamic changes in cirrhosis. A systematic review and meta-analysis was performed to evaluate impact of beta-blockers on all-cause mortality among cirrhosis patients with ascites. METHODS A literature search identified studies that evaluated beta-blocker vs no beta-blocker therapy in cirrhosis patients with ascites. The primary outcome was all-cause mortality with subcohort analysis of patients with refractory or severe ascites. Quality of observational studies was assessed with Newcastle-Ottawa Scale and overall certainty of the evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. RESULTS Eight observational studies, representing 3627 cirrhosis patients with ascites (1630 treated with beta-blockers and 1997 not treated), were included. Pooled all-cause mortality was 38.6% in beta-blocker group vs 42.2% in no beta-blocker group (RR 0.93, 95% CI 0.77-1.13, χ2 = 54.03, I2 = 87%). Subcohort analysis of cirrhosis patients with refractory or severe ascites demonstrated 33.3% mortality in beta-blocker group vs 32.1% in no beta-blocker group (RR 0.99, 95% CI 0.70-1.40, χ2 = 32.99, and I2 = 82%). Three studies were good quality and five studies were fair quality. GRADE rating was 'very low' certainty of evidence, given concern for bias and inconsistency stemming from significant heterogeneity. CONCLUSION No significant increase in all-cause mortality was observed in cirrhosis patients with ascites treated with beta-blockers. However, given the low certainty of the evidence, high quality prospective studies are needed.
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Affiliation(s)
- Robert J Wong
- Department of Medicine, Division of Gastroenterology and Hepatology, Alameda Health System - Highland Hospital, Oakland, CA
| | - Ann Robinson
- Department of Medicine, Division of Gastroenterology and Hepatology, Alameda Health System - Highland Hospital, Oakland, CA
| | - Dina Ginzberg
- Department of Medicine, Division of Gastroenterology and Hepatology, Alameda Health System - Highland Hospital, Oakland, CA
| | - Chantal Gomes
- Department of Medicine, Division of Gastroenterology and Hepatology, Alameda Health System - Highland Hospital, Oakland, CA
| | - Benny Liu
- Department of Medicine, Division of Gastroenterology and Hepatology, Alameda Health System - Highland Hospital, Oakland, CA
| | - Taft Bhuket
- Department of Medicine, Division of Gastroenterology and Hepatology, Alameda Health System - Highland Hospital, Oakland, CA
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40
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Kockerling D, Nathwani R, Forlano R, Manousou P, Mullish BH, Dhar A. Current and future pharmacological therapies for managing cirrhosis and its complications. World J Gastroenterol 2019; 25:888-908. [PMID: 30833797 PMCID: PMC6397723 DOI: 10.3748/wjg.v25.i8.888] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2018] [Revised: 01/17/2019] [Accepted: 01/26/2019] [Indexed: 02/06/2023] Open
Abstract
Due to the restrictions of liver transplantation, complication-guided pharmacological therapy has become the mainstay of long-term management of cirrhosis. This article aims to provide a complete overview of pharmacotherapy options that may be commenced in the outpatient setting which are available for managing cirrhosis and its complications, together with discussion of current controversies and potential future directions. PubMed/Medline/Cochrane Library were electronically searched up to December 2018 to identify studies evaluating safety, efficacy and therapeutic mechanisms of pharmacological agents in cirrhotic adults and animal models of cirrhosis. Non-selective beta-blockers effectively reduce variceal re-bleeding risk in cirrhotic patients with moderate/large varices, but appear ineffective for primary prevention of variceal development and may compromise renal function and haemodynamic stability in advanced decompensation. Recent observational studies suggest protective, haemodynamically-independent effects of beta-blockers relating to reduced bacterial translocation. The gut-selective antibiotic rifaximin is effective for secondary prophylaxis of hepatic encephalopathy; recent small trials also indicate its potential superiority to norfloxacin for secondary prevention of spontaneous bacterial peritonitis. Diuretics remain the mainstay of uncomplicated ascites treatment, and early trials suggest alpha-adrenergic receptor agonists may improve diuretic response in refractory ascites. Vaptans have not demonstrated clinical effectiveness in treating refractory ascites and may cause detrimental complications. Despite initial hepatotoxicity concerns, safety of statin administration has been demonstrated in compensated cirrhosis. Furthermore, statins are suggested to have protective effects upon fibrosis progression, decompensation and mortality. Evidence as to whether proton pump inhibitors cause gut-liver-brain axis dysfunction is conflicting. Emerging evidence indicates that anticoagulation therapy reduces incidence and increases recanalisation rates of non-malignant portal vein thrombosis, and may impede hepatic fibrogenesis and decompensation. Pharmacotherapy for cirrhosis should be implemented in accordance with up-to-date guidelines and in conjunction with aetiology management, nutritional optimisation and patient education.
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Affiliation(s)
- David Kockerling
- Liver Unit/Division of Integrative Systems Medicine and Digestive Disease, Imperial College London, London W2 1NY, United Kingdom
| | - Rooshi Nathwani
- Liver Unit/Division of Integrative Systems Medicine and Digestive Disease, Imperial College London, London W2 1NY, United Kingdom
| | - Roberta Forlano
- Liver Unit/Division of Integrative Systems Medicine and Digestive Disease, Imperial College London, London W2 1NY, United Kingdom
| | - Pinelopi Manousou
- Liver Unit/Division of Integrative Systems Medicine and Digestive Disease, Imperial College London, London W2 1NY, United Kingdom
| | - Benjamin H Mullish
- Liver Unit/Division of Integrative Systems Medicine and Digestive Disease, Imperial College London, London W2 1NY, United Kingdom
| | - Ameet Dhar
- Liver Unit/Division of Integrative Systems Medicine and Digestive Disease, Imperial College London, London W2 1NY, United Kingdom
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Fu H, Sun K, Li J, Gong W, Agopian V, Yan M, Busuttil RW, Steadman RH, Xia VW. Preoperative beta blockade and severe intraoperative bradycardia in liver transplantation. Clin Transplant 2018; 32:e13422. [PMID: 30312516 DOI: 10.1111/ctr.13422] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2018] [Revised: 09/07/2018] [Accepted: 10/07/2018] [Indexed: 01/19/2023]
Affiliation(s)
- Hong Fu
- Department of Anesthesiology; Chongqing Traditional Chinese Medicine Hospital; Chongqing China
- Department of Anesthesiology and Perioperative Medicine; David Geffen School of Medicine at UCLA; Los Angeles California
| | - Kai Sun
- Department of Anesthesiology; Second Affiliated Hospital of Zhejiang University of School of Medicine; Hangzhou Zhejiang China
| | - Jun Li
- Department of Anesthesiology; Mianyang Central Hospital; Mianyang City Sichuan Province China
| | - Weiyi Gong
- Department of Anesthesiology; Baoan District People’s Hospital; Shenzhen China
| | - Vatche Agopian
- Department of Surgery; David Geffen School of Medicine at UCLA; Los Angeles California
| | - Min Yan
- Department of Anesthesiology; Second Affiliated Hospital of Zhejiang University of School of Medicine; Hangzhou Zhejiang China
| | - Ronald W. Busuttil
- Department of Surgery; David Geffen School of Medicine at UCLA; Los Angeles California
| | - Randolph H. Steadman
- Department of Anesthesiology and Perioperative Medicine; David Geffen School of Medicine at UCLA; Los Angeles California
| | - Victor W. Xia
- Department of Anesthesiology and Perioperative Medicine; David Geffen School of Medicine at UCLA; Los Angeles California
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Aday AW, Rich NE, Mufti AR, Tujios SR. CON ("The window is closed"): In patients with cirrhosis with ascites, the clinical risks of nonselective beta-blocker outweigh the benefits and should NOT be prescribed. Clin Liver Dis (Hoboken) 2018; 11:123-127. [PMID: 30992802 PMCID: PMC6385953 DOI: 10.1002/cld.699] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2017] [Revised: 01/24/2018] [Accepted: 02/02/2018] [Indexed: 02/04/2023] Open
Affiliation(s)
- Ariel W. Aday
- Department of Internal Medicine, Division of Digestive and Liver DiseasesUT Southwestern Medical CenterDallasTX
| | - Nicole E. Rich
- Department of Internal Medicine, Division of Digestive and Liver DiseasesUT Southwestern Medical CenterDallasTX
| | - Arjmand R. Mufti
- Department of Internal Medicine, Division of Digestive and Liver DiseasesUT Southwestern Medical CenterDallasTX
| | - Shannan R. Tujios
- Department of Internal Medicine, Division of Digestive and Liver DiseasesUT Southwestern Medical CenterDallasTX
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44
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Role of diuretics in the harmful effects of beta blockers in patients with ascites. Dig Liver Dis 2018; 50:101-102. [PMID: 28967631 DOI: 10.1016/j.dld.2017.09.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2017] [Accepted: 09/05/2017] [Indexed: 12/11/2022]
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Moctezuma-Velazquez C, Kalainy S, Abraldes JG. Beta-blockers in patients with advanced liver disease: Has the dust settled? Liver Transpl 2017; 23:1058-1069. [PMID: 28590564 DOI: 10.1002/lt.24794] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2017] [Accepted: 05/16/2017] [Indexed: 12/14/2022]
Abstract
Nonselective beta-blockers (NSBBs) have been the backbone for the treatment of portal hypertension in cirrhosis for the last 3 decades. A publication in 2010 of a prospective observational study suggested that NSBBs could increase mortality in patients with refractory ascites. This opened a controversy about the safety and efficacy of NSBBs in patients with advanced liver disease and led to the publication of a large corpus of observational data assessing the safety of NSBBs in patients with advanced cirrhosis. In this article, we briefly review the clinical pharmacology of NSBBs, the pathophysiological basis for the underlying benefits and harms of NSBBs in advanced cirrhosis, and the evidence in favor and against the use of NSBBs in specific scenarios. Finally, we summarize the current recommendations and propose areas of opportunity for future research. Liver Transplantation 23 1058-1069 2017 AASLD.
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Affiliation(s)
- Carlos Moctezuma-Velazquez
- Cirrhosis Care Clinic, Liver Unit, Division of Gastroenterology, Centre of Excellence for Gastrointestinal Inflammation and Immunity Research, University of Alberta, Edmonton, Canada
| | - Sylvia Kalainy
- Cirrhosis Care Clinic, Liver Unit, Division of Gastroenterology, Centre of Excellence for Gastrointestinal Inflammation and Immunity Research, University of Alberta, Edmonton, Canada
| | - Juan G Abraldes
- Cirrhosis Care Clinic, Liver Unit, Division of Gastroenterology, Centre of Excellence for Gastrointestinal Inflammation and Immunity Research, University of Alberta, Edmonton, Canada
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Peeraphatdit TB, Kamath PS, Shah VH. Beta-blockers in patients with advanced cirrhosis: Red light, green light, yellow light…. Liver Transpl 2017; 23:725-726. [PMID: 28452116 DOI: 10.1002/lt.24780] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2017] [Accepted: 04/03/2017] [Indexed: 12/14/2022]
Affiliation(s)
| | - Patrick S Kamath
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Vijay H Shah
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
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