|
1
|
Wu PS, Lee KC, Li CY, Hsieh YC, Huo TI, Lin HC, Hou MC. Paracentesis exceeding three liters increases risks of acute kidney injury even in cirrhotic patients with albumin infused refractory ascites. J Formos Med Assoc 2025:S0929-6646(25)00002-6. [PMID: 39779410 DOI: 10.1016/j.jfma.2025.01.002] [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: 06/27/2024] [Revised: 12/05/2024] [Accepted: 01/02/2025] [Indexed: 01/11/2025] Open
Abstract
BACKGROUND Cirrhotic patients with refractory ascites exhibit severe portal hypertension and hemodynamic disturbances. The risks associated modest-volume paracentesis (<5 L) for refractory ascites remains unclear. We aimed to explore the impact of modest-volume paracentesis in refractory ascites. METHODS Cirrhotic patients with refractory ascites undergoing paracentesis <5 L with albumin infusion were retrospectively enrolled. Patients were categorized into two groups based on the volume of paracentesis: ≥3 L and <3 L. Logistic regression analyses were used to determine risk factors for post-paracentesis complications, while Kaplan-Meier analysis was used to assess 28-day survival rates. RESULTS Among 116 patients, 40 (34.5%) experienced post-paracentesis complications within one week, predominantly acute kidney injury (AKI) (19.8%). Twenty patients had paracentesis ≥3 L and 96 patients had <3 L. Overall complications were comparable between two groups (50% vs. 31.3%, p = 0.109), but ≥3 L group had more AKI (40% vs. 15.6%, p = 0.013). Additionally, paracentesis ≥3 L is an independent risk factor for AKI [Odds ratio (OR) = 4.15, p = 0.012], while higher MELD scores (OR = 1.14, p = 0.001) and older age (OR = 1.03, p = 0.047) are risk factors for overall complications. Furthermore, patients with post-paracentesis complications had significantly poorer 28-day survival. CONCLUSION Cirrhotic patients with refractory ascites face a high risk of complications from modest-volume paracentesis, even with albumin infusion. Paracentesis ≥3 L increases AKI risks, while higher MELD scores are linked to greater overall complications, leading to poor short-term survival.
Collapse
Affiliation(s)
- Pei-Shan Wu
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan; Therapeutic and Research Center of Liver Cirrhosis and Portal Hypertension, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Institute of Pharmacology, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Kuei-Chuan Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Therapeutic and Research Center of Liver Cirrhosis and Portal Hypertension, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
| | - Chih-Yu Li
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Yun-Cheng Hsieh
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Therapeutic and Research Center of Liver Cirrhosis and Portal Hypertension, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Teh-Ia Huo
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Institute of Pharmacology, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
| | - Ming-Chih Hou
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan; Therapeutic and Research Center of Liver Cirrhosis and Portal Hypertension, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| |
Collapse
|
|
2
|
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.
Collapse
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.
| |
Collapse
|
|
3
|
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.
Collapse
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)
| |
Collapse
|
|
4
|
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] [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.
Collapse
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
| |
Collapse
|
|
5
|
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.
Collapse
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
| |
Collapse
|
|
6
|
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: 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: 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.
Collapse
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.
| |
Collapse
|
|
7
|
Maia AG, Palhares LFN, Maia IG, Braulino PDM, Pereira LMMB. NON-SELECTIVE BETA-BLOCKERS IN CIRRHOTIC PATIENTS WITH REFRACTORY ASCITES: WHERE ARE WE? ARQUIVOS DE GASTROENTEROLOGIA 2024; 61:e23157. [PMID: 39046001 DOI: 10.1590/s0004-2803.24612023157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Accepted: 04/24/2024] [Indexed: 07/25/2024]
Abstract
BACKGROUND The established use of non-selective beta-blockers (NSBB) in the primary and secondary prevention of esophageal varices has recently been questioned in the subgroup of patients with diuretic-refractory ascites. OBJECTIVE Critically analyze the body of evidence on the topic in order to assist clinical decisions. METHODS A literature review was carried out in the Pubmed® and Scielo® databases. In total, 20 articles between 2010 and 2023 were read by independent researchers. CONCLUSION It remains doubtful whether the use of NSBB is deleterious in cirrhotic patients with refractory ascites, however our literature review allows us to conclude that these drugs should not be proscribed in these patients. On the contrary, a doctor-patient decision based on tolerability and hemodynamic parameters certainly seems to be a safe conduct.
Collapse
|
|
8
|
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.
Collapse
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
| |
Collapse
|
|
9
|
Ostojic A, Mahmud N, Reddy KR. Surgical risk stratification in patients with cirrhosis. Hepatol Int 2024; 18:876-891. [PMID: 38472607 PMCID: PMC11864775 DOI: 10.1007/s12072-024-10644-y] [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: 11/05/2023] [Accepted: 01/15/2024] [Indexed: 03/14/2024]
Abstract
Individuals with cirrhosis experience higher morbidity and mortality rates than the general population, irrespective of the type or scope of surgery. This increased risk is attributed to adverse effects of liver disease, encompassing coagulation dysfunction, altered metabolism of anesthesia and sedatives, immunologic dysfunction, hemorrhage related to varices, malnutrition and frailty, impaired wound healing, as well as diminished portal blood flow, overall hepatic circulation, and hepatic oxygen supply during surgical procedures. Therefore, a frequent clinical dilemma is whether surgical interventions should be pursued in patients with cirrhosis. Several risk scores are widely used to aid in the decision-making process, each with specific advantages and limitations. This review aims to discuss the preoperative risk factors in patients with cirrhosis, describe and compare surgical risk assessment models used in everyday practice, provide insights into the surgical risk according to the type of surgery and present recommendations for optimizing those with cirrhosis for surgical procedures. As the primary focus is on currently available risk models, the review describes the predictive value of each model, highlighting its specific advantages and limitations. Furthermore, for models that do not account for the type of surgical procedure to be performed, the review suggests incorporating both patient-related and surgery-related risks into the decision-making process. Finally, we provide an algorithm for the preoperative assessment of patients with cirrhosis before elective surgery as well as guidance perioperative management.
Collapse
Affiliation(s)
- Ana Ostojic
- Division of Gastroenterology, Department of Internal Medicine, University Hospital Center Zagreb, Kispaticeva 12, Zagreb, 10000, Croatia
| | - Nadim Mahmud
- Division of Gastroenterology and Hepatology, University of Pennsylvania, 2 Dulles, 3400 Spruce Street, HUP, Philadelphia, PA, 19104, USA
| | - K Rajender Reddy
- Division of Gastroenterology and Hepatology, University of Pennsylvania, 2 Dulles, 3400 Spruce Street, HUP, Philadelphia, PA, 19104, USA.
| |
Collapse
|
|
10
|
Boudabbous M, Hammemi R, Gdoura H, Chtourou L, Moalla M, Mnif L, Amouri A, Abid L, Tahri N. Cirrhotic cardiomyopathy: a subject that's always topical. Future Sci OA 2024; 10:FSO954. [PMID: 38817353 PMCID: PMC11137786 DOI: 10.2144/fsoa-2023-0110] [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: 06/13/2023] [Accepted: 12/13/2023] [Indexed: 06/01/2024] Open
Abstract
Cirrhosis is the final stage in the development of hepatic fibrosis in chronic liver disease. It is associated with major hemodynamic disturbances defining the hyperdynamic circulation and may be complicated by specific cardiac involvement or cirrhotic cardiomyopathy which is a silent clinical condition that typically remains asymptomatic until the late stages of liver disease. Recently, new criteria defining CC, based on modern concepts and knowledge of heart failure, have been proposed. Despite knowledge of the main mechanisms behind this entity, there is no specific treatment available for cirrhotic cardiomyopathy. The management approach for symptomatic cardiomyopathy in cirrhotic patients is similar to that for left ventricular failure in non-cirrhotic individuals.
Collapse
Affiliation(s)
- Mona Boudabbous
- Gastroenterology Department, Hédi Chaker Hospital, Sfax, Tunisia
- Medecin sfax university, Sfax university, Tunisia
| | - Rania Hammemi
- Cardiology, Department, Hédi Chaker Hospital, Sfax, Tunisia
- Medecin sfax university, Sfax university, Tunisia
| | - Hela Gdoura
- Gastroenterology Department, Hédi Chaker Hospital, Sfax, Tunisia
- Medecin sfax university, Sfax university, Tunisia
| | - Lassad Chtourou
- Gastroenterology Department, Hédi Chaker Hospital, Sfax, Tunisia
- Medecin sfax university, Sfax university, Tunisia
| | - Manel Moalla
- Gastroenterology Department, Hédi Chaker Hospital, Sfax, Tunisia
- Medecin sfax university, Sfax university, Tunisia
| | - Leila Mnif
- Gastroenterology Department, Hédi Chaker Hospital, Sfax, Tunisia
- Medecin sfax university, Sfax university, Tunisia
| | - Ali Amouri
- Gastroenterology Department, Hédi Chaker Hospital, Sfax, Tunisia
- Medecin sfax university, Sfax university, Tunisia
| | - Leila Abid
- Cardiology, Department, Hédi Chaker Hospital, Sfax, Tunisia
- Medecin sfax university, Sfax university, Tunisia
| | - Nabil Tahri
- Gastroenterology Department, Hédi Chaker Hospital, Sfax, Tunisia
- Medecin sfax university, Sfax university, Tunisia
| |
Collapse
|
|
11
|
Lee MY, Heo KN, Lee S, Ah YM, Shin J, Lee JY. Development and validation of a medication-based risk prediction model for acute kidney injury in older outpatients. Arch Gerontol Geriatr 2024; 120:105332. [PMID: 38382232 DOI: 10.1016/j.archger.2024.105332] [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: 10/05/2023] [Revised: 01/06/2024] [Accepted: 01/13/2024] [Indexed: 02/23/2024]
Abstract
BACKGROUND Older adults are at an increased risk of acute kidney injury (AKI), particularly in community settings, often due to medications. Effective prevention hinges on identifying high-risk patients, yet existing models for predicting AKI risk in older outpatients are scarce, particularly those incorporating medication variables. We aimed to develop an AKI risk prediction model that included medication-related variables for older outpatients. METHODS We constructed a cohort of 2,272,257 outpatients aged ≥65 years using a national claims database. This cohort was split into a development (70%) and validation (30%) groups. Our primary goal was to identify newly diagnosed AKI within one month of cohort entry in an outpatient context. We screened 170 variables and developed a risk prediction model using logistic regression. RESULTS The final model integrated 12 variables: 2 demographic, 4 comorbid, and 6 medication-related. It showed good performance with acceptable calibration. In the validation cohort, the area under the receiver operating characteristic curve value was 0.720 (95% confidence interval, 0.692-0.748). Sensitivity and specificity were 69.9% and 61.9%, respectively. Notably, the model identified high-risk patients as having a 27-fold increased AKI risk compared with low-risk individuals. CONCLUSION We have developed a new AKI risk prediction model for older outpatients, incorporating critical medication-related variables with good discrimination. This tool may be useful in identifying and targeting patients who may require interventions to prevent AKI in an outpatient setting.
Collapse
Affiliation(s)
- Mee Yeon Lee
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 1, Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea
| | - Kyu-Nam Heo
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 1, Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea
| | - Suhyun Lee
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 1, Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea
| | - Young-Mi Ah
- College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea
| | - Jaekyu Shin
- Department of Clinical Pharmacy, School of Pharmacy, University of California, San Francisco, CA, United States
| | - Ju-Yeun Lee
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 1, Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea.
| |
Collapse
|
|
12
|
Mingpun W, Sobhonslidsuk A, Chumnumwat S. Optimal resting heart rate and ascites-related death in patients with cirrhosis and ascites using nonselective beta-blockers (ORCA). Clin Transl Sci 2024; 17:e13681. [PMID: 37950532 PMCID: PMC10766015 DOI: 10.1111/cts.13681] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 09/09/2023] [Accepted: 11/05/2023] [Indexed: 11/12/2023] Open
Abstract
Nonselective beta-blockers (NSBBs) may exacerbate ascites by impairing cardiac function. This study evaluated the impact of achieving a heart rate target of 55-60 beats per minute (bpm) on ascites-related death and complications from worsening ascites in patients with cirrhosis and diuretic-responsive ascites using NSBBs. A retrospective study was conducted at the Faculty of Medicine Ramathibodi Hospital, Mahidol University (2012-2022) and analyzed patients with cirrhosis and diuretic-responsive ascites using NSBBs (propranolol/carvedilol) for variceal bleeding prophylaxis. The outcomes were incidence of ascites-related death and complications from worsening ascites, comparing the achievable target group (heart rate 55-60 bpm) and the unachievable target group (heart rate >60 bpm). A total of 206 patients were included in the study, with a median follow-up time of 20 months. The patients were divided into an achievable target group (n = 75, median heart rate = 58.0 bpm) and an unachievable target group (n = 131, median heart rate = 73.6 bpm). Propranolol was the most used NSBB (95.1%). The adjusted hazard ratio (HR) for ascites-related death from spontaneous bacterial peritonitis (SBP) or refractory ascites (RA) or hepatorenal syndrome (HRS) or hepatic encephalopathy (HE) showed no difference between the groups (adjusted HR 0.59 [0.23-1.54]; p = 0.28). Additionally, no significant difference was found in the incidence of complications between groups, including SBP, RA, HRS, and HE. Achieving a heart rate target of 55-60 bpm with NSBBs for variceal bleeding prophylaxis is safe in patients with diuretic-responsive ascites and cirrhosis.
Collapse
Affiliation(s)
- Warunee Mingpun
- Department of Pharmacy, Faculty of PharmacyMahidol UniversityBangkokThailand
- Department of Pharmaceutical Care, Faculty of PharmacyChiang Mai UniversityChiang MaiThailand
| | - Abhasnee Sobhonslidsuk
- Division of Gastroenterology and Hepatology, Faculty of Medicine, Ramathibodi HospitalMahidol UniversityBangkokThailand
| | - Supatat Chumnumwat
- Department of Pharmacy, Faculty of PharmacyMahidol UniversityBangkokThailand
| |
Collapse
|
|
13
|
He X, Zhao Z, Jiang X, Sun Y. Non-selective beta-blockers and the incidence of hepatocellular carcinoma in patients with cirrhosis: a meta-analysis. Front Pharmacol 2023; 14:1216059. [PMID: 37538177 PMCID: PMC10394622 DOI: 10.3389/fphar.2023.1216059] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Accepted: 07/04/2023] [Indexed: 08/05/2023] Open
Abstract
Background: Hepatocellular carcinoma (HCC) is a serious complication of cirrhosis. Currently, non-selective beta-blockers (NSBBs) are commonly used to treat portal hypertension in patients with cirrhosis. The latest research shows that NSBBs can induce apoptosis and S-phase arrest in liver cancer cells and inhibit the development of hepatic vascular endothelial cells, which may be effective in preventing HCC in cirrhosis patients. Aim: To determine the relationship between different NSBBs and HCC incidence in patients with cirrhosis. Methods: We searched the Cochrane database, MEDLINE, EMBASE, PubMed, and Web of Science. Cohort studies, case‒control studies, and randomized controlled trials were included if they involved cirrhosis patients who were divided into an experimental group using NSBBs and a control group with any intervention. Based on heterogeneity, we calculated odds ratio (OR) and 95% confidence interval (CI) using random-effect models. We also conducted subgroup analysis to explore the source of heterogeneity. Sensitivity analysis and publication bias detection were performed. Results: A total of 47 studies included 38 reporting HCC incidence, 26 reporting HCC-related mortality, and 39 reporting overall mortality. The HCC incidence between the experimental group and the control group was OR = 0.87 (0.69 and 1.10), p = 0.000, and I2 = 81.8%. There was no significant association between propranolol (OR = 0.94 and 95%CI 0.62-1.44) or timolol (OR = 1.32 and 95%CI 0.44-3.95) and HCC incidence, while the risk of HCC decreased by 26% and 38% with nadolol (OR = 0.74 and 95%CI 0.64-0.86) and carvedilol (OR = 0.62 and 95%CI 0.52-0.74), respectively. Conclusion: Different types of NSBB have different effects on the incidence of patients with cirrhosis of the liver, where nadolol and carvedilol can reduce the risk. Also, the effect of NSBBs may vary in ethnicity. Propranolol can reduce HCC incidence in Europe and America. Systematic Review Registration: identifier https://CRD42023434175, https://www.crd.york.ac.uk/PROSPERO/.
Collapse
Affiliation(s)
- Xinyi He
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
- Clinical Department I, China Medical University, Shenyang, Liaoning, China
| | - Zimo Zhao
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
- First Clinical Medical College, China Medical University, Shenyang, Liaoning, China
| | - Xi Jiang
- Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Yan Sun
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| |
Collapse
|
|
14
|
Gu W, Kimmann M, Laleman W, Praktiknjo M, Trebicka J. To TIPS or Not to TIPS in High Risk of Variceal Rebleeding and Acute-on-Chronic Liver Failure. Semin Liver Dis 2023; 43:189-205. [PMID: 37286178 DOI: 10.1055/a-2107-0576] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
Variceal bleeding is a consequence of severe portal hypertension in patients with liver cirrhosis. Although the rate of bleeding has decreased over time, variceal bleeding in the presence of acute-on-chronic liver failure (ACLF) carries a high risk of treatment failure and short-term mortality. Treatment and/or removal of precipitating events (mainly bacterial infection and alcoholic hepatitis) and decrease of portal pressure may improve outcome of patients with acute decompensation or ACLF. Transjugular intrahepatic portosystemic shunts (TIPSs), especially in the preemptive situation, have been found to efficiently control bleeding, prevent rebleeding, and reduce short-term mortality. Therefore, TIPS placement should be considered as an option in the management of ACLF patients with variceal bleeding.
Collapse
Affiliation(s)
- Wenyi Gu
- Department of Medical Clinic B, University Hospital Muenster, Muenster, Germany
- Medical Department I, Frankfurt University Hospital, Frankfurt am Main, Germany
| | - Markus Kimmann
- Department of Medical Clinic B, University Hospital Muenster, Muenster, Germany
| | - Wim Laleman
- Department of Medical Clinic B, University Hospital Muenster, Muenster, Germany
- Department of Gastroenterology and Hepatology, Section of Liver and Biliopancreatic Disorders, University Hospitals Leuven, KU Leuven, Leuven, Belgium
| | - Michael Praktiknjo
- Department of Medical Clinic B, University Hospital Muenster, Muenster, Germany
| | - Jonel Trebicka
- Department of Medical Clinic B, University Hospital Muenster, Muenster, Germany
- European Foundation for Study of Chronic Liver Failure, Barcelona, Spain
- Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark
| |
Collapse
|
|
15
|
Kaltenbach MG, Mahmud N. Assessing the risk of surgery in patients with cirrhosis. Hepatol Commun 2023; 7:e0086. [PMID: 36996004 PMCID: PMC10069843 DOI: 10.1097/hc9.0000000000000086] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Accepted: 01/17/2023] [Indexed: 03/31/2023] Open
Abstract
Patients with cirrhosis have an increased perioperative risk relative to patients without cirrhosis. This is related to numerous cirrhosis-specific factors, including severity of liver disease, impaired synthetic function, sarcopenia and malnutrition, and portal hypertension, among others. Nonhepatic comorbidities and surgery-related factors further modify the surgical risk, adding to the complexity of the preoperative assessment. In this review, we discuss the pathophysiological contributors to surgical risk in cirrhosis, key elements of the preoperative risk assessment, and application of risk prediction tools including the Child-Turcotte-Pugh score, Model for End-Stage Liver Disease-Sodium, Mayo Risk Score, and the VOCAL-Penn Score. We also detail the limitations of current approaches to risk assessment and highlight areas for future research.
Collapse
Affiliation(s)
- Melissa G. Kaltenbach
- Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Nadim Mahmud
- Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Department of Medicine, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania, USA
- Leonard David Institute of Health Economics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
- Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics, Epidemiology & Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| |
Collapse
|
|
16
|
Miceli G, Calvaruso V, Casuccio A, Pennisi G, Licata M, Pintus C, Basso MG, Velardo M, Daidone M, Amodio E, Petta S, Simone F, Cabibbo G, Di Raimondo D, Craxì A, Pinto A, Tuttolomondo A. Heart rate variability is associated with disease severity and portal hypertension in cirrhosis. Hepatol Commun 2023; 7:e0050. [PMID: 36757394 PMCID: PMC9916116 DOI: 10.1097/hc9.0000000000000050] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Accepted: 11/22/2022] [Indexed: 02/10/2023] Open
Abstract
INTRODUCTION Autonomic nervous system activity in cirrhotic portal hypertension is linked to hyperdynamic circulation. Heart rate variability (HRV) is a validated noninvasive method to assess the sympathovagal balance. To investigate the correlation between HRV parameters and degree of portal hypertension, we studied a cohort of patients with cirrhosis accounting for etiology and treatments. PATIENTS AND METHODS In this cross-sectional, observational cohort study, 157 outpatients of both sex with nonalcoholic cirrhosis were assessed by upper gastrointestinal endoscopy to search for esophagogastric varices. Twenty-four-hour electrocardiogram Holter monitoring with 3 HRV parameters measurement [SD of the NN intervals, root mean square successive difference of NN intervals, and SD of the averages of NN intervals (SDANN)] according to time-domain analysis were performed in all patients. Sixteen patients with large esophagogastric varices underwent measurements of the HVPG and assessment of HRV parameters at baseline and after 45 days on carvedilol. RESULTS The liver dysfunction, expressed by Child-Pugh class or MELD score, was directly related to root mean square successive difference of NN intervals and inversely related to SDANN. Presence of ascites was inversely related to SDANN and to SD of the NN intervals. Treatment with carvedilol had an inverse relation with SDANN. Presence and size of esophagogastric varices had an inverse relation to SDANN and SD of the NN intervals. Upon multivariate analysis the associations between SDANN and Child-Pugh class, size of varices and ascites were confirmed. In the subgroup of 16 patients undergoing HVPG measurement, pressure gradient was unrelated to heart rate and HRV parameters. CONCLUSIONS Time-domain HRV parameters in patients with cirrhosis, confirm the autonomic nervous system alteration, and their correlation to the degree of portal hypertension suggesting a role of the ANS in hepatic decompensation.
Collapse
Affiliation(s)
- Giuseppe Miceli
- Department of Health promotion, Mother and Child Care, Internal Medicine and Medical specialties (ProMISE) University of Palermo, Piazza delle Cliniche, Palermo, Italy
- Internal Medicine and Stroke Care Ward, University Hospital, Policlinico “P. Giaccone,” Palermo, Italy
| | - Vincenza Calvaruso
- Department of Health promotion, Mother and Child Care, Internal Medicine and Medical specialties (ProMISE) University of Palermo, Piazza delle Cliniche, Palermo, Italy
| | - Alessandra Casuccio
- Department of Health promotion, Mother and Child Care, Internal Medicine and Medical specialties (ProMISE) University of Palermo, Piazza delle Cliniche, Palermo, Italy
| | - Grazia Pennisi
- Department of Health promotion, Mother and Child Care, Internal Medicine and Medical specialties (ProMISE) University of Palermo, Piazza delle Cliniche, Palermo, Italy
| | - Massimo Licata
- Department of Health promotion, Mother and Child Care, Internal Medicine and Medical specialties (ProMISE) University of Palermo, Piazza delle Cliniche, Palermo, Italy
| | - Chiara Pintus
- Department of Health promotion, Mother and Child Care, Internal Medicine and Medical specialties (ProMISE) University of Palermo, Piazza delle Cliniche, Palermo, Italy
- Internal Medicine and Stroke Care Ward, University Hospital, Policlinico “P. Giaccone,” Palermo, Italy
| | - Maria G. Basso
- Department of Health promotion, Mother and Child Care, Internal Medicine and Medical specialties (ProMISE) University of Palermo, Piazza delle Cliniche, Palermo, Italy
- Internal Medicine and Stroke Care Ward, University Hospital, Policlinico “P. Giaccone,” Palermo, Italy
| | - Mariachiara Velardo
- Department of Health promotion, Mother and Child Care, Internal Medicine and Medical specialties (ProMISE) University of Palermo, Piazza delle Cliniche, Palermo, Italy
| | - Mario Daidone
- Department of Health promotion, Mother and Child Care, Internal Medicine and Medical specialties (ProMISE) University of Palermo, Piazza delle Cliniche, Palermo, Italy
- Internal Medicine and Stroke Care Ward, University Hospital, Policlinico “P. Giaccone,” Palermo, Italy
| | - Emanuele Amodio
- Department of Health promotion, Mother and Child Care, Internal Medicine and Medical specialties (ProMISE) University of Palermo, Piazza delle Cliniche, Palermo, Italy
| | - Salvatore Petta
- Department of Health promotion, Mother and Child Care, Internal Medicine and Medical specialties (ProMISE) University of Palermo, Piazza delle Cliniche, Palermo, Italy
| | - Fabio Simone
- Department of Health promotion, Mother and Child Care, Internal Medicine and Medical specialties (ProMISE) University of Palermo, Piazza delle Cliniche, Palermo, Italy
| | - Giuseppe Cabibbo
- Department of Health promotion, Mother and Child Care, Internal Medicine and Medical specialties (ProMISE) University of Palermo, Piazza delle Cliniche, Palermo, Italy
| | - Domenico Di Raimondo
- Department of Health promotion, Mother and Child Care, Internal Medicine and Medical specialties (ProMISE) University of Palermo, Piazza delle Cliniche, Palermo, Italy
- Internal Medicine and Stroke Care Ward, University Hospital, Policlinico “P. Giaccone,” Palermo, Italy
| | - Antonio Craxì
- Department of Health promotion, Mother and Child Care, Internal Medicine and Medical specialties (ProMISE) University of Palermo, Piazza delle Cliniche, Palermo, Italy
| | - Antonio Pinto
- Department of Health promotion, Mother and Child Care, Internal Medicine and Medical specialties (ProMISE) University of Palermo, Piazza delle Cliniche, Palermo, Italy
| | - Antonino Tuttolomondo
- Department of Health promotion, Mother and Child Care, Internal Medicine and Medical specialties (ProMISE) University of Palermo, Piazza delle Cliniche, Palermo, Italy
- Internal Medicine and Stroke Care Ward, University Hospital, Policlinico “P. Giaccone,” Palermo, Italy
| |
Collapse
|
|
17
|
Abstract
The development of refractory ascites in approximately 10% of patients with decompensated cirrhosis heralds the progression to a more advanced stage of cirrhosis. Its pathogenesis is related to significant hemodynamic changes, initiated by portal hypertension, but ultimately leading to renal hypoperfusion and avid sodium retention. Inflammation can also contribute to the pathogenesis of refractory ascites by causing portal microthrombi, perpetuating the portal hypertension. Many complications accompany the development of refractory ascites, but renal dysfunction is most common. Management starts with continuation of sodium restriction, which needs frequent reviews for adherence; and regular large volume paracentesis of 5 L or more with albumin infusions to prevent the development of paracentesisinduced circulatory dysfunction. Albumin infusions independent of paracentesis may have a role in the management of these patients. The insertion of a covered, smaller diameter, transjugular intrahepatic porto-systemic stent shunt (TIPS) in the appropriate patients with reasonable liver reserve can bring about improvement in quality of life and improved survival after ascites clearance. Devices such as an automated low-flow ascites pump may be available in the future for ascites treatment. Patients with refractory ascites should be referred for liver transplant, as their prognosis is poor. In patients with refractory ascites and concomitant chronic kidney disease of more than stage 3b, assessment should be referred for dual liver-kidney transplants. In patients with very advanced cirrhosis not suitable for any definitive treatment for ascites control, palliative care should be involved to improve the quality of life of these patients.
Collapse
Affiliation(s)
- Florence Wong
- Division of Gastroenterology and Hepatology, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Canada,Corresponding author : Florence Wong Division of Gastroenterology and Hepatology, Toronto General Hospital, University Health Network, University of Toronto, 200 Elizabeth Street, Toronto Ontario M5G2C4, Canada Tel: +1-416-3403834, Fax: +1-416-3405019, E-mail:
| |
Collapse
|
|
18
|
Garcia-Saenz-de-Sicilia M, Al-Obaid L, Hughes DL, Duarte-Rojo A. Mastering Core Recommendations during HEPAtology ROUNDS in Patients with Advanced Chronic Liver Disease. Semin Liver Dis 2022; 42:341-361. [PMID: 35764316 DOI: 10.1055/a-1886-5909] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Efficient and thorough care of hospitalized patients with advanced chronic liver disease is of utter importance to improve outcomes and optimize quality of life. This requires understanding current evidence and best practices. To facilitate focus on up-to-date knowledge and a practical approach, we have created the HEPA-ROUNDS mnemonic while outlining a practical review of the literature with critical appraisal for the busy clinician. The HEPA-ROUNDS mnemonic provides a structured approach that incorporates critical concepts in terms of prevention, management, and prognostication of the most common complications frequently encountered in patients with advanced chronic liver disease. In addition, implementing the HEPA-ROUNDS mnemonic can facilitate education for trainees and staff caring for patients with advanced chronic liver disease.
Collapse
Affiliation(s)
| | - Lolwa Al-Obaid
- Division of Gastroenterology, Washington University School of Medicine in St. Louis, St. Louis, Missouri
| | - Dempsey L Hughes
- Division of Gastroenterology, Hepatology and Nutrition, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Andrés Duarte-Rojo
- Division of Gastroenterology, Hepatology and Nutrition, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
| |
Collapse
|
|
19
|
Kulkarni AV, Rabiee A, Mohanty A. Management of Portal Hypertension. J Clin Exp Hepatol 2022; 12:1184-1199. [PMID: 35814519 PMCID: PMC9257868 DOI: 10.1016/j.jceh.2022.03.002] [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: 01/05/2022] [Accepted: 03/07/2022] [Indexed: 12/12/2022] Open
Abstract
Portal hypertension is the cause of the clinical complications associated with cirrhosis. The primary complications of portal hypertension are ascites, acute variceal bleed, and hepatic encephalopathy. Hepatic venous pressure gradient measurement remains the gold standard test for diagnosing cirrhosis-related portal hypertension. Hepatic venous pressure gradient more than 10 mmHg is associated with an increased risk of complications and is termed clinically significant portal hypertension (CSPH). Clinical, laboratory, and imaging methods can also aid in diagnosing CSPH non-invasively. Recently, deep learning methods have been demonstrated to diagnose CSPH effectively. The management of portal hypertension is always individualized and is dependent on the etiology, the availability of therapies, and the degree of portal hypertension complications. In this review, we discuss the diagnosis and management of cirrhosis-related portal hypertension in detail. Also, we highlight the history of portal hypertension and future research areas in portal hypertension.
Collapse
Key Words
- ACLF, acute-on-chronic liver failure
- AKI, acute kidney injury
- APRI, AST to platelet ratio
- AST, aspartate transaminase
- BB, Beta blocker
- BRTO, balloon occluded retrograde transvenous obliteration
- CKD, chronic kidney disease
- CSPH, clinically significant portal hypertension
- CT, computed tomography
- GFR, glomerular filtration rate
- GOV, gastrpoesopahegal varices
- HE, hepatic encephalopathy
- HRS, hepatorenal syndrome
- HVPG, hepatic venous pressure gradient
- ICG, indocyanine green
- LOLA, l-ornithine l-aspartate
- NAFLD, Non-alcoholic fatty liver disease
- SBP, spontaneous bacterial peritonitis
- SGLT2I, sodium glucose co-transporter 2 inhibitors
- SSM, splenic stiffness measurement
- TE, transient elastography
- TIPS, transjugular intrahepatic portosystemic shunt
- VITRO, von Willebrand factor to platelet counts
- acute kidney injury
- ascites
- hemodynamics
- history
- vasoconstrictors
Collapse
Affiliation(s)
| | | | - Arpan Mohanty
- Boston University School of Medicine, Boston, MA, USA
| |
Collapse
|
|
20
|
Kimer N, Hobolth L. Editorial: timing of carvedilol - promoting survivors in cirrhosis. Aliment Pharmacol Ther 2022; 56:172-173. [PMID: 35689324 DOI: 10.1111/apt.16942] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Affiliation(s)
- Nina Kimer
- Gastro Unit, Medical Division, Hvidovre University Hospital, Hvidovre, Denmark
| | - Lise Hobolth
- Gastro Unit, Medical Division, Hvidovre University Hospital, Hvidovre, Denmark
| |
Collapse
|
|
21
|
Nabilou P, Danielsen KV, Kimer N, Hove JD, Bendtsen F, Møller S. Blunted cardiovascular effects of beta-blockers in patients with cirrhosis: Relation to severity? PLoS One 2022; 17:e0270603. [PMID: 35763518 PMCID: PMC9239488 DOI: 10.1371/journal.pone.0270603] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2022] [Accepted: 06/13/2022] [Indexed: 11/22/2022] Open
Abstract
Aims Patients with cirrhosis and portal hypertension are at high risk of developing complications such as variceal hemorrhage, ascites, and cardiac dysfunction, the latter of which is known as cirrhotic cardiomyopathy. Since non-selective beta-blockers (NSBB) may aggravate hemodynamic complications we investigated the effect of real-time propranolol infusion on cardiac function in patients with varying degrees of cirrhosis. Methods Thirty-eight patients with Child-Pugh A (n = 17), B (n = 17) and C (n = 4) underwent liver vein catheterization and cardiac magnetic resonance imaging. We assessed the effect of real-time propranolol infusion on the hepatic venous pressure gradient, cardiac index, stroke volume, ejection fraction, heart rate, and contractility. Results Nineteen patients were classified as responders to beta-blocker therapy. In pooling Child-Pugh B and C patients, the reduction in cardiac index by beta-blockade was weaker than in Child-Pugh A patients (-8.5% vs. -20.5%, p = 0.043). The effect of NSBB on portal pressure was inversely correlated to changes in the left atrium where the left atrial volume changed by 4 mL±18 in responders compared to 15 mL±11 in non-responders (p = 0.03). Finally, the baseline ejection fraction correlated inversely with the reduction in portal pressure (r = -0.39, p = 0.02). Conclusion We found the effect of beta-blockade on cardiac index in patients with advanced cirrhosis to be less potent than in patients with early cirrhosis, indicating that underlying cirrhotic cardiomyopathy increases, and the cardiac compensatory reserve becomes more compromised, with disease progression. The differential effects of beta-blockade in the left atrium may be used to predict the effect of beta-blockers on portal pressure, but further studies are needed to investigate this possibility.
Collapse
Affiliation(s)
- Puria Nabilou
- Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
- * E-mail:
| | - Karen Vagner Danielsen
- Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
| | - Nina Kimer
- Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
| | - Jens Dahlgaard Hove
- Department of Cardiology, Copenhagen University Hospital, Hvidovre, Denmark
- Department of Clinical Medicine, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
| | - Flemming Bendtsen
- Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
- Department of Clinical Medicine, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
| | - Søren Møller
- Department of Clinical Medicine, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
- Dept. Clinical Physiology and Nuclear Medicine, Center for Functional and Diagnostic Imaging and Research, Hvidovre Hospital, Faculty of Health Sciences, University of Copenhagen, København, Denmark
| |
Collapse
|
|
22
|
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.
Collapse
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
| |
Collapse
|
|
23
|
Chen YC, Li YD, Lu CM, Huang WC, Kao SS, Chen WC. Propranolol use in patients with cirrhosis and refractory ascites: A nationwide study. Saudi J Gastroenterol 2022; 28:108-114. [PMID: 35295067 PMCID: PMC9007076 DOI: 10.4103/sjg.sjg_586_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
Abstract
BACKGROUND The impact of propranolol on patients with cirrhosis and refractory ascites is controversial. We conducted a nationwide longitudinal cohort study to compare the survival between patients with cirrhosis and refractory ascites, with and without using propranolol. METHODS Data of patients with cirrhosis and refractory ascites using propranolol, and controls matched by age and gender, were extracted from The National Health Insurance Research Database of Taiwan. The baseline demographic characteristics were compared between groups. Cox regression analysis was used to examine the predictors of mortality. RESULTS In this study, 1788 patients were enrolled in each group; 1304 patients (72.9%) in the propranolol group and 1445 patients (80.8%) in the control group died (P < 0.001). The mean survival was 34.3 ± 31.2 months in the propranolol group and 20.8 ± 26.6 months in the control group (P < 0.001). Propranolol (hazard ratio [HR]: 0.60, 95% confidence interval [CI]: 0.55-0.64, P < 0.001), statins (HR: 0.43, 95% CI: 0.34-0.56, P < 0.001), age (HR: 1.02, 95% CI: 1.01-1.02, P < 0.001), and diabetes mellitus (HR: 1.14, 95% CI: 1.05-1.24, P = 0.002) were the independent predictors for mortality. CONCLUSIONS Use of propanolol was associated with reduced mortality, compared with controls, in this nationwide cohort of patients with cirrhosis and refractory ascites.
Collapse
Affiliation(s)
- Yen-Chun Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan,Division of Gastroenterology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi, Taiwan
| | - Yun-Da Li
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Chia-Ming Lu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Wei-Chun Huang
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan,Division of Cardiology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan,Institute of Biomedical Sciences, College of Science, National Sun Yat-sen University, Kaohsiung, Taiwan
| | - Sung-Shuo Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan,Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Wen-Chi Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan,Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan,Institute of Biomedical Sciences, College of Science, National Sun Yat-sen University, Kaohsiung, Taiwan,Address for correspondence: Dr. Wen-Chi Chen, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, No. 386, Ta-Chung 1st. Rd., Kaohsiung City 813, Taiwan. E-mail:
| |
Collapse
|
|
24
|
Gerber LD, Sgro G, Cyr JE, Conlin S. An Academic Hospitalist-Run Outpatient Paracentesis Clinic. Fed Pract 2022; 39:114-119. [PMID: 35444390 PMCID: PMC9014930 DOI: 10.12788/fp.0235] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/21/2024]
Abstract
BACKGROUND Patients needing large-volume paracenteses (LVPs) can occupy inpatient hospital beds and unnecessarily use inpatient resources. METHODS We describe an outpatient paracentesis clinic that was part of a quality assurance initiative at the Veterans Affairs Pittsburgh Healthcare System in Pennsylvania. A retrospective review was conducted that included patient age, sex, etiology of ascites, amount of ascites removed, time of the procedure, complications, and results of ascites cell count and cultures abstracted from the electronic health record. RESULTS Over 74 months, 506 paracenteses were performed on 82 patients. The mean volume removed was 7.9 L, and the mean time of the procedure was 33.3 minutes. There were 5 episodes of postprocedure hypotension that required admission for 3 patients. One episode of abdominal wall hematoma occurred that required admission. Two patients developed incarceration of an umbilical hernia after the paracentesis; both required surgical repair. Without the clinic, almost all the 506 outpatient LVPs we performed would have resulted in a hospital admission. CONCLUSION An outpatient paracentesis clinic run by academic hospitalists can safely and quickly remove large volumes of ascites and minimize hospitalizations.
Collapse
Affiliation(s)
- Lawrence D Gerber
- Veterans Affairs Pittsburgh Healthcare System, Pennsylvania
- University of Pittsburgh School of Medicine, Pennsylvania
| | - Gaetan Sgro
- Veterans Affairs Pittsburgh Healthcare System, Pennsylvania
- University of Pittsburgh School of Medicine, Pennsylvania
| | - Jessica E Cyr
- Veterans Affairs Pittsburgh Healthcare System, Pennsylvania
- University of Pittsburgh School of Medicine, Pennsylvania
| | - Sharon Conlin
- Veterans Affairs Pittsburgh Healthcare System, Pennsylvania
| |
Collapse
|
|
25
|
Bouzbib C, Cluzel P, Sultanik P, Bernard-Chabert B, Massard J, Benosman H, Mallet M, Tripon S, Conti F, Thabut D, Rudler M. Prognosis of patients undergoing salvage TIPS is still poor in the preemptive TIPS era. Clin Res Hepatol Gastroenterol 2021; 45:101593. [PMID: 33667917 DOI: 10.1016/j.clinre.2020.101593] [Citation(s) in RCA: 8] [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: 06/30/2020] [Revised: 11/19/2020] [Accepted: 12/02/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND Salvage transjugular intrahepatic portosystemic shunts (TIPS) are associated with poor prognosis, especially in patients with Child-Pugh C cirrhosis. Since preemptive TIPS improved prophylaxis of variceal bleeding in those patients, recourse to salvage TIPS may now affect patients with a better prognosis. AIM To assess the impact of the preemptive TIPS policy on outcomes after salvage TIPS placement. METHODS We conducted a retrospective monocentric study on cirrhotic patients undergoing salvage TIPS with polytetrafluoroethylene-covered stents from 2002 to 2017 (period 1 until February 2011; period 2 after the preemptive TIPS policy in March 2011). The primary endpoint was one-year transplant-free survival. RESULTS We included 106 patients (period 1/2 = 53/53 patients, male gender 82%, age 54 ± 9 years, alcoholic cirrhosis 70%, Child-Pugh score B/C 94%). One-year transplant-free survival was 46.0% during period 1 compared to 40.2% during period 2 (p = 0.65). Amongst 61 patients with history of variceal bleeding, 32 (52.5%) had an inadequate secondary prophylaxis, including 19 (59.4%) with a previous indication of preemptive TIPS. One-year transplant-free survival was 33.2% if inadequate secondary prophylaxis vs 65.2% if adequate (p = 0.008). Independent factors associated with survival were a lower Child-Pugh or MELD score, infection, failure to control bleeding, and hepatic encephalopathy after TIPS. CONCLUSION Prognosis after salvage TIPS remained poor in our series. Optimizing secondary prophylaxis, including preemptive TIPS placement, should be the main concern to improve prognosis.
Collapse
Affiliation(s)
- Charlotte Bouzbib
- Hepatology Intensive Care Unit, Hepatology Department, Pitié-Salpêtrière Hospital, 47-83 boulevard de l'Hôpital, 75013 Paris, France
| | - Philippe Cluzel
- Sorbonne Universities, UPMC University Paris 06, AP-HP, Pitié-Salpêtrière Hospital, F-75013 Paris, France; Interventional Radiology Unit, Radiology Department, Pitié-Salpêtrière Hospital, 47-83 boulevard de l'Hôpital, 75013 Paris, France
| | - Philippe Sultanik
- Hepatology Intensive Care Unit, Hepatology Department, Pitié-Salpêtrière Hospital, 47-83 boulevard de l'Hôpital, 75013 Paris, France
| | - Brigitte Bernard-Chabert
- Hepatology Intensive Care Unit, Hepatology Department, Pitié-Salpêtrière Hospital, 47-83 boulevard de l'Hôpital, 75013 Paris, France
| | - Julien Massard
- Hepatology Intensive Care Unit, Hepatology Department, Pitié-Salpêtrière Hospital, 47-83 boulevard de l'Hôpital, 75013 Paris, France
| | - Hedi Benosman
- Hepatology Intensive Care Unit, Hepatology Department, Pitié-Salpêtrière Hospital, 47-83 boulevard de l'Hôpital, 75013 Paris, France
| | - Maxime Mallet
- Hepatology Intensive Care Unit, Hepatology Department, Pitié-Salpêtrière Hospital, 47-83 boulevard de l'Hôpital, 75013 Paris, France
| | - Simona Tripon
- Hepatology Intensive Care Unit, Hepatology Department, Pitié-Salpêtrière Hospital, 47-83 boulevard de l'Hôpital, 75013 Paris, France
| | - Filomena Conti
- Liver Transplantation Unit, Hepatology Department, Pitié-Salpêtrière Hospital, 47-83 boulevard de l'Hôpital 75013, Paris, France
| | - Dominique Thabut
- Hepatology Intensive Care Unit, Hepatology Department, Pitié-Salpêtrière Hospital, 47-83 boulevard de l'Hôpital, 75013 Paris, France; Sorbonne Universities, UPMC University Paris 06, AP-HP, Pitié-Salpêtrière Hospital, F-75013 Paris, France
| | - Marika Rudler
- Hepatology Intensive Care Unit, Hepatology Department, Pitié-Salpêtrière Hospital, 47-83 boulevard de l'Hôpital, 75013 Paris, France.
| |
Collapse
|
|
26
|
Biggins SW, Angeli P, Garcia-Tsao G, Ginès P, Ling SC, Nadim MK, Wong F, Kim WR. Diagnosis, Evaluation, and Management of Ascites, Spontaneous Bacterial Peritonitis and Hepatorenal Syndrome: 2021 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology 2021; 74:1014-1048. [PMID: 33942342 DOI: 10.1002/hep.31884] [Citation(s) in RCA: 408] [Impact Index Per Article: 102.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Accepted: 04/07/2021] [Indexed: 12/13/2022]
Affiliation(s)
- Scott W Biggins
- Division of Gastroenterology and Hepatology, and Center for Liver Investigation Fostering discovEryUniversity of WashingtonSeattleWA
| | - Paulo Angeli
- Unit of Hepatic Emergencies and Liver TransplantationDepartment of MedicineDIMEDUniversity of PadovaPaduaItaly
| | - Guadalupe Garcia-Tsao
- Department of Internal MedicineSection of Digestive DiseasesYale UniversityNew HavenCT.,VA-CT Healthcare SystemWest HavenCT
| | - Pere Ginès
- Liver Unit, Hospital Clinic, and Institut d'Investigacions Biomèdiques August Pi i SunyerUniversity of BarcelonaBarcelonaSpain.,Centro de Investigación Biomèdica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)MadridSpain
| | - Simon C Ling
- The Hospital for Sick Children, Division of Gastroenterology, Hepatology and Nutrition, and Department of PaediatricsUniversity of TorontoTorontoOntarioCanada
| | - Mitra K Nadim
- Division of NephrologyUniversity of Southern CaliforniaLos AngelesCA
| | - Florence Wong
- Division of Gastroenterology and HepatologyUniversity Health NetworkUniversity of TorontoTorontoOntarioCanada
| | - W Ray Kim
- Division of Gastroenterology and HepatologyStanford UniversityPalo AltoCA
| |
Collapse
|
|
27
|
Pfisterer N, Unger LW, Reiberger T. Clinical algorithms for the prevention of variceal bleeding and rebleeding in patients with liver cirrhosis. World J Hepatol 2021; 13:731-746. [PMID: 34367495 PMCID: PMC8326161 DOI: 10.4254/wjh.v13.i7.731] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Revised: 05/14/2021] [Accepted: 07/07/2021] [Indexed: 02/06/2023] Open
Abstract
Portal hypertension (PH), a common complication of liver cirrhosis, results in development of esophageal varices. When esophageal varices rupture, they cause significant upper gastrointestinal bleeding with mortality rates up to 20% despite state-of-the-art treatment. Thus, prophylactic measures are of utmost importance to improve outcomes of patients with PH. Several high-quality studies have demonstrated that non-selective beta blockers (NSBBs) or endoscopic band ligation (EBL) are effective for primary prophylaxis of variceal bleeding. In secondary prophylaxis, a combination of NSBB + EBL should be routinely used. Once esophageal varices develop and variceal bleeding occurs, standardized treatment algorithms should be followed to minimize bleeding-associated mortality. Special attention should be paid to avoidance of overtransfusion, early initiation of vasoconstrictive therapy, prophylactic antibiotics and early endoscopic therapy. Pre-emptive transjugular intrahepatic portosystemic shunt should be used in all Child C10-C13 patients experiencing variceal bleeding, and potentially in Child B patients with active bleeding at endoscopy. The use of carvedilol, safety of NSBBs in advanced cirrhosis (i.e. with refractory ascites) and assessment of hepatic venous pressure gradient response to NSBB is discussed. In the present review, we give an overview on the rationale behind the latest guidelines and summarize key papers that have led to significant advances in the field.
Collapse
Affiliation(s)
- Nikolaus Pfisterer
- Medizinische Abteilung für Gastroenterologie und Hepatologie, Klinik Landstraße/Krankenanstalt Rudolfstiftung, Vienna 1030, Austria
- Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna 1090, Austria
| | - Lukas W Unger
- Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna, Vienna 1090, Austria
- Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, United Kingdom.
| | - Thomas Reiberger
- Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna 1090, Austria
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna 1090, Austria
- Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna 1090, Austria
| |
Collapse
|
|
28
|
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.
Collapse
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
| |
Collapse
|
|
29
|
Garcia-Pagan JC, Francoz C, Montagnese S, Senzolo M, Mookerjee RP. Management of the major complications of cirrhosis: Beyond guidelines. J Hepatol 2021; 75 Suppl 1:S135-S146. [PMID: 34039484 DOI: 10.1016/j.jhep.2021.01.027] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Revised: 01/17/2021] [Accepted: 01/20/2021] [Indexed: 02/07/2023]
Abstract
Along with a growing understanding of the pathophysiology of cirrhosis and its complications, new therapies and management strategies have emerged in recent years. Many of these advances have helped inform the current EASL clinical practice guidelines1 on the management of some of the key complications of cirrhosis, such as ascites, variceal bleeding and infection. However, there are still some aspects of management where the evidence base is less clear, and/or where opinions amongst practitioners remain divided. Some of these more controversial areas are explored in this section, wherein we present evidence culminating in a suggested management approach based on expert opinion and extending beyond the current guidelines.
Collapse
Affiliation(s)
- Juan Carlos Garcia-Pagan
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Universitat de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain; Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Spain
| | - Claire Francoz
- Hepatology and Liver Intensive Care Unit, Hôpital Beaujon, INSERM. Clichy; France
| | | | - Marco Senzolo
- Gastroenterology, Multi-visceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padua, Italy
| | - Rajeshwar P Mookerjee
- Institute for Liver and Digestive Health, University College London, UK; Department of Hepatology and Gastroenterology, Aarhus University, Denmark.
| |
Collapse
|
|
30
|
Carrion AF, Martin P. Keeping Patients with End-Stage Liver Disease Alive While Awaiting Transplant: Management of Complications of Portal Hypertension. Clin Liver Dis 2021; 25:103-120. [PMID: 33978573 DOI: 10.1016/j.cld.2020.08.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Complications of portal hypertension such as gastroesophageal variceal hemorrhage, ascites, and spontaneous bacterial peritonitis, as well as pulmonary complications, are often responsible for diminished quality of life, excess morbidity and mortality, increased health care resource use and expenditure, and dropout from the liver transplant (LT) waiting list. Therefore, the care of LT candidates on the waiting list must be centered on anticipation and prompt intervention for these complications.
Collapse
Affiliation(s)
- Andres F Carrion
- Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine, 1120 Northwest 14th Street, Office 1189, Miami, FL 33136, USA.
| | - Paul Martin
- Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine, 1120 Northwest 14th #1115, Miami, FL 33136, USA
| |
Collapse
|
|
31
|
Gallo A, Dedionigi C, Civitelli C, Panzeri A, Corradi C, Squizzato A. Optimal Management of Cirrhotic Ascites: A Review for Internal Medicine Physicians. J Transl Int Med 2020; 8:220-236. [PMID: 33511049 PMCID: PMC7805288 DOI: 10.2478/jtim-2020-0035] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Clinical history of liver cirrhosis is characterised by two phases: the asymptomatic phase, also termed 'compensated cirrhosis', and the phase of complications due to the development of portal hypertension and liver dysfunction, also termed 'decompensated cirrhosis', in which patients may develop ascites, the most frequent and clinically relevant complication of liver cirrhosis. Ascites can be classified into uncomplicated and complicated according to the development of refractoriness, spontaneous bacterial peritonitis (SBP) or the association with hepatorenal syndrome (HRS). In this narrative review, we will extensively discuss the optimal pharmacological and non-pharmacological management of cirrhotic ascites with the aim to offer an updated practical guide to Internal Medicine physicians. According to the amount of fluid in the abdominal cavity, uncomplicated ascites is graded from 1 to 3, and the cornerstone of its management consists of restriction of salt intake, diuretics and large-volume paracentesis (LVP); in recent years, long-term administration of human albumin has acquired a new interesting role. Refractory ascites is primarily managed with LVP and transjugular intrahepatic portosystemic shunt (TIPS) placement in selected patients. The occurrence of renal impairment, especially HRS, worsens the prognosis of patients with cirrhotic ascites and deserves a specific treatment. Also, the management of SBP faces the rising and alarming spread of antibiotic resistance. Hepatic hydrothorax may even complicate the course of the disease and its management is a challenge. Last but not least, liver transplantation (LT) is the ultimate and more effective measure to offer to patients with cirrhotic ascites, particularly when complications occur.
Collapse
Affiliation(s)
- Andrea Gallo
- Department of Medicine and Surgery, University of Insubria, Como/Varese, Italy
| | - Cristina Dedionigi
- Department of Medicine and Surgery, University of Insubria, Como/Varese, Italy
| | - Chiara Civitelli
- Department of Medicine and Surgery, University of Insubria, Como/Varese, Italy
| | - Anna Panzeri
- Department of Medicine and Surgery, University of Insubria, Como/Varese, Italy
- Hepatology Center, Ospedale Sant’Anna, Como, Italy
| | | | | |
Collapse
|
|
32
|
Alvarado-Tapias E, Ardevol A, Garcia-Guix M, Montañés R, Pavel O, Cuyas B, Graupera I, Brujats A, Vilades D, Colomo A, Poca M, Torras X, Guarner C, Concepción M, Aracil C, Torres F, Villanueva C. Short-term hemodynamic effects of β-blockers influence survival of patients with decompensated cirrhosis. J Hepatol 2020; 73:829-841. [PMID: 32298768 DOI: 10.1016/j.jhep.2020.03.048] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Revised: 03/30/2020] [Accepted: 03/31/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND & AIMS Whether the effect of β-blockers on arterial pressure and/or cardiac function may offset the benefit of reducing portal pressure in advanced cirrhosis is controversial. Herein, we aimed to evaluate the systemic and splanchnic hemodynamic effects of β-blockers in decompensated vs. compensated cirrhosis and to investigate the influence of systemic hemodynamic changes on survival times in decompensated cirrhosis. METHODS Patients with cirrhosis and high-risk esophageal varices, without previous bleeding, were consecutively included and grouped according to the presence or absence of decompensation (ascites with or without overt encephalopathy). Systemic and hepatic hemodynamic measurements were performed before starting β-blockers and again after 1 to 3 months of treatment (short-term). RESULTS Four hundred and three patients were included (190 decompensated and 213 compensated). At baseline, decompensated patients had higher portal pressure than compensated patients and were more hyperdynamic, with higher cardiac output (CO) and lower arterial pressure. Under β-blockers, decompensated patients had lower portal pressure decrease (10 ± 18% vs. 15 ± 12%; p <0.05) and had greater reductions in heart rate (p <0.001) and CO (17 ± 15% vs. 10 ± 21%; p <0.01). Among patients with decompensated cirrhosis, those who died had a greater decrease in CO with β-blockers than survivors (21 ± 14% vs. 15 ± 16%; p <0.05) and CO under β-blockers independently predicted death by competing-risk regression analysis, with good diagnostic accuracy (C-index 0.74; 95% CI 0.66-0.83). Death risk was higher in decompensated patients with CO <5 L/min vs. CO ≥5 L/min (subdistribution hazard ratio 0.44; 95% CI 0.25-0.77; p = 0.004). CONCLUSIONS In patients with high-risk varices treated to prevent first bleeding, the systemic hemodynamic response to β-blockers is greater and the portal pressure decrease is smaller in those with decompensated cirrhosis. The short-term effect of β-blockers on CO might adversely influence survival in decompensated cirrhosis. LAY SUMMARY β-blockers are often used to reduce the risk of variceal bleeding in patients with cirrhosis. However, it is not known whether the effect of β-blockers on arterial pressure and/or cardiac function may offset the benefit of reducing portal pressure. Herein, we show that in patients with decompensated cirrhosis the potentially detrimental systemic effects of β-blockers are greater than in compensated patients, while the beneficial pressure lowering effects are reduced. The short-term effect of β-blockers on cardiac output may adversely influence survival in patients with decompensated cirrhosis.
Collapse
Affiliation(s)
- Edilmar Alvarado-Tapias
- Department of Gastroenterology, Hospital Santa Creu i Sant Pau, Barcelona, Spain; Institut de Recerca, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Barcelona, Spain
| | - Alba Ardevol
- Department of Gastroenterology, Hospital Santa Creu i Sant Pau, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Barcelona, Spain
| | - Marta Garcia-Guix
- Department of Gastroenterology, Hospital Santa Creu i Sant Pau, Barcelona, Spain; Institut de Recerca, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Rosa Montañés
- Department of Gastroenterology, Hospital Santa Creu i Sant Pau, Barcelona, Spain; Institut de Recerca, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Oana Pavel
- Department of Gastroenterology, Hospital Santa Creu i Sant Pau, Barcelona, Spain; Institut de Recerca, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Berta Cuyas
- Department of Gastroenterology, Hospital Santa Creu i Sant Pau, Barcelona, Spain; Institut de Recerca, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Isabel Graupera
- Department of Gastroenterology, Hospital Santa Creu i Sant Pau, Barcelona, Spain; Institut de Recerca, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Anna Brujats
- Department of Gastroenterology, Hospital Santa Creu i Sant Pau, Barcelona, Spain; Institut de Recerca, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - David Vilades
- Institut de Recerca, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Barcelona, Spain; Cardiac imaging unit, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Alan Colomo
- Department of Gastroenterology, Hospital Santa Creu i Sant Pau, Barcelona, Spain; Institut de Recerca, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Maria Poca
- Department of Gastroenterology, Hospital Santa Creu i Sant Pau, Barcelona, Spain; Institut de Recerca, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Xavier Torras
- Department of Gastroenterology, Hospital Santa Creu i Sant Pau, Barcelona, Spain; Institut de Recerca, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Barcelona, Spain
| | - Carlos Guarner
- Department of Gastroenterology, Hospital Santa Creu i Sant Pau, Barcelona, Spain; Institut de Recerca, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Barcelona, Spain
| | - Mar Concepción
- Department of Gastroenterology, Hospital Santa Creu i Sant Pau, Barcelona, Spain; Institut de Recerca, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Carles Aracil
- Hospital Universitari Arnau de Vilanova, Lleida, Institut de Recerca Biomèdica (IRBLleida)
| | - Ferran Torres
- Medical Statistics Core Facility, IDIBAPS, Hospital Clinic, Barcelona; and Biostatistics Unit, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Càndid Villanueva
- Department of Gastroenterology, Hospital Santa Creu i Sant Pau, Barcelona, Spain; Institut de Recerca, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Barcelona, Spain.
| |
Collapse
|
|
33
|
Alsebaey A, Rewisha E, Waked I. Paracentesis-induced circulatory dysfunction: are there albumin alternatives? EGYPTIAN LIVER JOURNAL 2020. [DOI: 10.1186/s43066-020-00047-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Abstract
Background
Ascites is one of the main complications of advanced liver cirrhosis. It is defined as a pathological accumulation if free fluid in the peritoneal cavity.
Main body of the abstract
Ascites is a sign of decompensation in patients with liver cirrhosis and is associated with decreased survival. Ascites is associated with bad cosmetic figure and poor quality of life. Ascites is a predisposing factor for developing hydrothorax, hernias, diastolic dysfunction, spontaneous bacterial peritonitis, and renal impairment especially hepatorenal syndrome. The main treatment is salt restriction and diuretics. By the time the patient become non-responder and develop tense ascites, abdominal large volume paracentesis is the treatment of choice. Its advantages are rapid, cheap, and 1 day hospitalization. The main drawback is the development of paracentesis-induced circulatory dysfunction (PICD) if no volume expanding drugs are used. PICD is associated with dilutional hyponatremia, renal impairment, so it is considered the silent killer. Albumin infusion is the standard preventive measure but since costly to other alternatives such as colloids, vasoconstrictors or lowering the standard doses of the albumin was studied and is promising.
Conclusions
This review summarized the effectiveness of other alternative drugs.
Collapse
|
|
34
|
Alsebaey A, Rewisha E, Waked I. High efficacy of low-dose albumin infusion in the prevention of paracentesis-induced circulatory dysfunction. EGYPTIAN LIVER JOURNAL 2020. [DOI: 10.1186/s43066-020-0024-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Abstract
Background
Large-volume paracentesis (LVP) is a main pillar in treating patients with tense ascites. Without plasma expanders use, paracentesis-induced circulatory dysfunction (PICD) is a common complication with decreased survival. The aim was to compare low-dose albumin (2 g/L ascitic fluid removed n = 85) with standard-dose albumin (6 g/L ascitic fluid removed, n = 25) for prevention of PICD. Liver function tests, urea, creatinine, CBC, and abdominal ultrasonography were done. Plasma renin activity (PRA) was measured at baseline and on the 6th day post-LVP. The delta change (Δ) = day 6 variable minus baseline variable value. PICD was defined as increase in PRA of > 50% of the baseline value.
Results
Patients in low-dose albumin group were mainly Child B compared with Child C (85.9% vs. 52%; p = 0.001), underwent less paracentesis volume (9.78 ± 3.56 vs. 12.52 ± 3.6 L; p = 0.001), but had higher baseline PRA (859.62 ± 1151.34 vs. 165.93 ± 95.34 pg/mL; p = 0.001). In both groups, the PRA increased at day 6 compared with the baseline (1141.57 ± 1433.01 vs. 859.62 ± 1151.34 pg/mL; p = 0.01) and (192.21 ± 80.99 vs. 165.93 ± 95.34 pg/mL; p = 0.01) respectively. Both groups were comparable for Δ PRA (281.95 ± 851.4 vs. 26.28 ± 30.2 pg/mL; p = 0.102) and PRA percent increase (10.97 ± 30.77 vs. 12.57 ± 14.87; p = 0.844). They had comparable PICD incidence (24.7% vs. 12%; p = 0.27). Females were more liable for PICD occurrence than males (OR 2.91, 95% CI 1.125–7.547, p = 0.028) and so Child B patients than Child C (OR 8.4, 95% CI 1.072–65.767, p = 0.043).
Conclusion
Low-dose albumin infusion is comparable to the standard-dose albumin for the prevention of PICD.
Collapse
|
|
35
|
KASL clinical practice guidelines for liver cirrhosis: Varices, hepatic encephalopathy, and related complications. Clin Mol Hepatol 2020; 26:83-127. [PMID: 31918536 PMCID: PMC7160350 DOI: 10.3350/cmh.2019.0010n] [Citation(s) in RCA: 69] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Accepted: 10/23/2019] [Indexed: 02/06/2023] Open
|
|
36
|
Magaz M, Baiges A, Hernández-Gea V. Precision medicine in variceal bleeding: Are we there yet? J Hepatol 2020; 72:774-784. [PMID: 31981725 DOI: 10.1016/j.jhep.2020.01.008] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2019] [Revised: 01/13/2020] [Accepted: 01/14/2020] [Indexed: 12/14/2022]
Abstract
Variceal bleeding is one of the most feared complications of portal hypertension in patients with cirrhosis because of its deleterious impact on prognosis. Adequate management of patients at risk of developing variceal bleeding includes the prevention of the first episode of variceal bleeding and rebleeding, and is crucial in modifying prognosis. The presence of clinically significant portal hypertension is the main factor determining the risk of development of varices and other liver-related decompensations; therefore, it should be carefully screened for and monitored. Treating patients with clinically significant portal hypertension based on their individual risk of portal hypertension-related bleeding undoubtedly improves prognosis. The evaluation of liver haemodynamics and liver function can stratify patients according to their risk of bleeding and are no question useful tools to guide therapy in an individualised manner. That said, recent data support the idea that tailoring therapy to patient characteristics may effectively impact on prognosis and increase survival in all clinical scenarios. This review will focus on evaluating the available evidence supporting the use of individual risk characteristics for clinical decision-making and their impact on clinical outcome and survival. In primary prophylaxis, identification and treatment of patients with clinically significant portal hypertension improves decompensation-free survival. In the setting of acute variceal bleeding, the risk of failure and rebleeding can be easily predicted, allowing for early escalation of treatment (i.e. pre-emptive transjugular intrahepatic portosystemic shunt) which can improve survival in appropriate candidates. Stratifying the risk of recurrent variceal bleeding based on liver function and haemodynamic response to non-selective beta-blockers allows for tailored treatment, thereby increasing survival and avoiding adverse events.
Collapse
Affiliation(s)
- Marta Magaz
- Unidad de Hemodinámica Hepática, Servicio de Hepatología, Hospital Clínic, Universidad de Barcelona, Instituto de Investigaciones Biomédicas Augusto Pi Suñer (IDIBAPS), Barcelona, Spain
| | - Anna Baiges
- Unidad de Hemodinámica Hepática, Servicio de Hepatología, Hospital Clínic, Universidad de Barcelona, Instituto de Investigaciones Biomédicas Augusto Pi Suñer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Barcelona, Spain
| | - Virginia Hernández-Gea
- Unidad de Hemodinámica Hepática, Servicio de Hepatología, Hospital Clínic, Universidad de Barcelona, Instituto de Investigaciones Biomédicas Augusto Pi Suñer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Barcelona, Spain.
| |
Collapse
|
|
37
|
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.
Collapse
|
|
38
|
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: 93] [Impact Index Per Article: 18.6] [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.
Collapse
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
Collapse
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.
| |
Collapse
|
|
39
|
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.
Collapse
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.
| |
Collapse
|
|
40
|
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.
Collapse
Affiliation(s)
| | | | | | | | - Emily Cooke
- Barnes-Jewish Hospital, Saint Louis, MO, USA
| | | |
Collapse
|
|
41
|
Facciorusso A. Hepatorenal Syndrome Type 1: Current Challenges And Future Prospects. Ther Clin Risk Manag 2019; 15:1383-1391. [PMID: 31819465 PMCID: PMC6886557 DOI: 10.2147/tcrm.s205328] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2019] [Accepted: 11/05/2019] [Indexed: 12/13/2022] Open
Abstract
Renal dysfunction represents a dreadful complication of advanced liver cirrhosis. In addition to the traditional types of acute kidney injury (AKI) that can occur in the general population, cirrhotics might experience a different kind of renal dysfunction, called hepatorenal syndrome (HRS). The exact definition of HRS is a functional renal dysfunction caused by overactivity of the endogenous vasoactive systems (in particular intrarenal circulation) which lead to reduced renal perfusion. Type I HRS (HRS-1) is characterized by an abrupt deterioration in renal function (in less than 2 weeks), defined by a doubling of baseline sCr to >2.5 mg/dL or a 50% reduction in the initial 24 hrs creatinine clearance to <20 mL/min. Frequent precipitating events leading to HRS-1 are bacterial infections, gastrointestinal hemorrhage, or large-volume paracentesis without adequate albumin administration as well as massive diuretic use. In 2015, the international club of ascites (ICA) revised the definitions and recommendations concerning HRS. The revised definition allows to adopt effective pharmacological therapy based on albumin and vasoconstrictors in an earlier stage thus not influenced anymore by a rigid sCr cut-off value as by the previous definition of HRS-1. The aim of this article was to provide an updated overview of the latest advancements in the field of hepatorenal syndrome and of the recent amendments of the previous definitions of kidney injury in cirrhotic patients.
Collapse
|
|
42
|
Snoga JL, Lusk KA, Attridge RT, Attridge RL. Effect of Nonselective β-Blockers on Mortality in Patients With End-Stage Cirrhosis. Ann Pharmacother 2019; 54:322-330. [PMID: 31701773 DOI: 10.1177/1060028019886529] [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: 11/16/2022] Open
Abstract
Background: Data regarding safety of nonselective β-blockers (NSBBs) in patients with end-stage cirrhosis are conflicting, making it difficult for practitioners to justify if benefits outweigh the risks. Objective: Evaluate the effect of NSBB use on mortality in patients with end-stage cirrhosis. Methods: We performed a dual-center retrospective study of patients who received octreotide for a variceal bleed. Patients were stratified into 2 groups based on whether or not a NSBB was prescribed at hospital discharge. The primary outcome was 24-month mortality. Multivariable logistic regression, with 24-month mortality as the dependent variable, was performed to identify independent risk factors for the primary outcome. Results: 255 patients met inclusion criteria; 24-month mortality was 32.8%. The NSBB and no-NSBB groups had similar mortality rates at 24 months (32.0% vs 38.5%, P = 0.51). Mortality at 3 months (11.6% vs 23.3%, P = 0.08) and 12 months (22.2% vs 30.0%, P = 0.36) were similar, and there were no differences in rate of variceal bleeding (22.7% vs 13.3%, P = 0.34) or cirrhosis-related cause of death (20.4% vs 23.3%, P = 0.81). In the multivariable model, age, model for end-stage liver disease with sodium and hepatocellular carcinoma were independent risk factors for 24-month mortality. NSBB therapy had no effect on 24-month mortality (adjusted odds ratio = 1.05; 95% CI = 0.32 to 3.40). Conclusion and Relevance: In patients with end-stage cirrhosis, use of NSBBs did not affect 24-month mortality. More research is needed to determine when, and if, NSBBs should be discontinued in end-stage cirrhosis.
Collapse
Affiliation(s)
- Jenna L Snoga
- University of the Incarnate Word Feik School of Pharmacy, San Antonio, TX, USA.,South Texas Veterans Healthcare System, San Antonio, TX, USA
| | - Kathleen A Lusk
- University of the Incarnate Word Feik School of Pharmacy, San Antonio, TX, USA.,UT Health San Antonio, TX, USA.,University Health System, San Antonio, TX, USA
| | - Russell T Attridge
- University of the Incarnate Word Feik School of Pharmacy, San Antonio, TX, USA.,South Texas Veterans Healthcare System, San Antonio, TX, USA
| | - Rebecca L Attridge
- University of the Incarnate Word Feik School of Pharmacy, San Antonio, TX, USA.,UT Health San Antonio, TX, USA.,University Health System, San Antonio, TX, USA
| |
Collapse
|
|
43
|
Kasztelan-Szczerbinska B, Cichoz-Lach H. Refractory ascites-the contemporary view on pathogenesis and therapy. PeerJ 2019; 7:e7855. [PMID: 31637125 PMCID: PMC6798865 DOI: 10.7717/peerj.7855] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Accepted: 09/09/2019] [Indexed: 12/14/2022] Open
Abstract
Refractory ascites (RA) refers to ascites that cannot be mobilized or that has an early recurrence that cannot be prevented by medical therapy. Every year, 5-10% of patients with liver cirrhosis and with an accumulation of fluid in the peritoneal cavity develop RA while undergoing standard treatment (low sodium diet and diuretic dose up to 400 mg/day of spironolactone and 160 mg/day of furosemide). Liver cirrhosis accounts for marked alterations in the splanchnic and systemic hemodynamics, causing hypovolemia and arterial hypotension. The consequent activation of renin-angiotensin and sympathetic systems and increased renal sodium re-absorption occurs during the course of the disease. Cirrhotic patients with RA have poor prognoses and are at risk of developing serious complications. Different treatment options are available, but only liver transplantation may improve the survival of such patients.
Collapse
Affiliation(s)
| | - Halina Cichoz-Lach
- Department of Gastroenterology with Endoscopy Unit, Medical University of Lublin, Poland
| |
Collapse
|
|
44
|
Tergast TL, Kimmann M, Laser H, Gerbel S, Manns MP, Cornberg M, Maasoumy B. Systemic arterial blood pressure determines the therapeutic window of non-selective beta blockers in decompensated cirrhosis. Aliment Pharmacol Ther 2019; 50:696-706. [PMID: 31373713 DOI: 10.1111/apt.15439] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2019] [Revised: 05/10/2019] [Accepted: 07/05/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND The safety of non-selective β-blockers in patients with advanced cirrhosis has been questioned in recent years. It was hypothesised that there is a particular therapeutic window. However, the specific limits still need to be determined. AIM To evaluate potential limits of the therapeutic window of non-selective β-blocker therapy in patients with cirrhosis and ascites METHODS: The impact of non-selective β-blockers on 28-day transplant-free survival was analysed in a cohort of 624 consecutive patients with decompensated cirrhosis and ascites. Three potential limits were investigated: spontaneous bacterial peritonitis, acute-on-chronic liver failure, mean arterial blood pressure ≤ 82 and < 65 mm Hg. RESULTS Treatment with non-selective β-blockers was associated with a higher 28-day transplant-free survival in the overall cohort (hazard ratio: 0.621; P = .035) as well as in patients with acute-on-chronic liver failure (hazard ratio: 0.578; P = .031) and those with spontaneous bacterial peritonitis (hazard ratio: 0.594; P = .073). In contrast, survival benefits were markedly attenuated in patients with a mean arterial blood pressure ≤ 82 mm Hg and completely lost in those with mean arterial blood pressure < 65 mm Hg (P = .536). In spontaneous bacterial peritonitis patients with a mean arterial blood pressure < 65 mm Hg non-selective β-blocker treatment was associated with renal impairment. Of note, among those with a mean arterial blood pressure ≥ 65 mm Hg non-selective β-blocker intake was consistently associated with superior transplant-free survival (hazard ratio: 0.582; P = .029) irrespective of the presence of spontaneous bacterial peritonitis (hazard ratio: 0.435; P = .028) or acute-on-chronic liver failure (hazard ratio: 0.480 P = .034). CONCLUSIONS Ascites, acute-on-chronic liver failure and spontaneous bacterial peritonitis do not limit the safe use of non-selective β-blockers in patients with cirrhosis. Mean arterial blood pressure might represent a better indicator to determine the therapeutic window of non-selective β-blocker treatment.
Collapse
Affiliation(s)
- Tammo L Tergast
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Markus Kimmann
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Hans Laser
- Hannover Medical School, Centre for Information Management (ZIMt), Hannover, Germany
| | - Svetlana Gerbel
- Hannover Medical School, Centre for Information Management (ZIMt), Hannover, Germany
| | - Michael P Manns
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.,German Centre for Infection Research (Deutsches Zentrum für Infektionsforschung DZIF), Partner-site Hannover-Braunschweig, Hannover, Germany.,Centre for Individualised Infection Medicine (CIIM), Hannover, Germany
| | - Markus Cornberg
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.,German Centre for Infection Research (Deutsches Zentrum für Infektionsforschung DZIF), Partner-site Hannover-Braunschweig, Hannover, Germany.,Centre for Individualised Infection Medicine (CIIM), Hannover, Germany
| | - Benjamin Maasoumy
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.,German Centre for Infection Research (Deutsches Zentrum für Infektionsforschung DZIF), Partner-site Hannover-Braunschweig, Hannover, Germany
| |
Collapse
|
|
45
|
Facciorusso A, Antonino M, Orsitto E, Sacco R. Primary and secondary prophylaxis of spontaneous bacterial peritonitis: current state of the art. Expert Rev Gastroenterol Hepatol 2019; 13:751-759. [PMID: 31304804 DOI: 10.1080/17474124.2019.1644167] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Introduction: Spontaneous bacterial peritonitis represents a frequent and severe complication in cirrhotic patients with ascites. In daily practice, the diagnosis of spontaneous bacterial peritonitis might be challenging in the absence of the typical signs and symptoms of infection such as fever or leukocytosis. Areas covered: Aim of this review is to revise the current state of the art on primary and secondary spontaneous bacterial peritonitis. Literature search in Medline/Pubmed was performed. Expert opinion: Historically, gram-negative bacteria were the most frequent etiologic agents of spontaneous bacterial peritonitis, with Escherichia coli and Klebsiella spp. being the most frequently isolated bacteria. However, major changes in this regard occurred over the last few decades with an increasing prevalence of gram-positive, quinolone-resistant, and multidrug-resistant bacteria. In particular, the increasing prevalence of quinolone-resistant bacteria challenged the prominent role of norfloxacin in spontaneous bacterial peritonitis prevention. Given the high mortality rate and the risk of developing the hepatorenal syndrome, prophylaxis of spontaneous bacterial peritonitis is indicated in three high-risk populations: patients with acute gastrointestinal hemorrhage, patients with low total protein content in ascitic fluid and advanced cirrhosis, and patients with a previous history of spontaneous bacterial peritonitis (secondary prophylaxis).
Collapse
Affiliation(s)
- Antonio Facciorusso
- a Department of Medical Sciences, Ospedali Riuniti di Foggia , Foggia , Italy
| | - Matteo Antonino
- a Department of Medical Sciences, Ospedali Riuniti di Foggia , Foggia , Italy
| | - Eugenio Orsitto
- b Department of Radiology, Azienda Ospedaliero-Universitaria Pisana , Pisa , Italy
| | - Rodolfo Sacco
- a Department of Medical Sciences, Ospedali Riuniti di Foggia , Foggia , Italy
| |
Collapse
|
|
46
|
Brito-Azevedo A. Diuretic window hypothesis in cirrhosis: Changing the point of view. World J Gastroenterol 2019; 25:3283-3290. [PMID: 31341355 PMCID: PMC6639551 DOI: 10.3748/wjg.v25.i26.3283] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Revised: 05/09/2019] [Accepted: 06/01/2019] [Indexed: 02/06/2023] Open
Abstract
Since the 1970s, non-selective beta-blockers (NSBB) have been used to prevent variceal upper bleeding in advanced cirrhotic patients. However, several recent studies have raised the doubt about the benefit of NSBB in end-stage cirrhotic patients. In fact, they suggested a detrimental effect in these patients that even reduced survival. All of these studies have been assembled to compose the “window therapy hypothesis”, in which NSBB would have traditional indication to be initiated to prevent variceal upper bleeding; however, treatment should be stopped (or not be initiated) in patients with end-stage cirrhosis. NSBB would reduce the cardiac reserve of these patients, worsening systemic perfusion and prognosis. However, it should be emphasized that these studies present important bias issues, and their results also suggested that diuretic treatment may also be behind the effects observed. In this opinion review, we changed the point of view from NSBB to diuretic treatment, based on a physiopathogenic approach of circulatory parameters of cirrhotic patients studied, and based on diuretic effect in blood pressure lowering and in other hypervolemic disease, as heart failure. We suggest a “diuretic window hypothesis”, composed by an open window in hypervolemic phase, an attention window when patient present in a normal plasma volume phase, and a closed window during the plasma hypovolemic phase.
Collapse
Affiliation(s)
- Anderson Brito-Azevedo
- Liver Transplant Unit, São Lucas Hospital, Rio de Janeiro 22061-080, Brazil
- Liver Transplant Unit, São Francisco na Providência de Deus Hospital, Rio de Janeiro 20520-053, Brazil
- Liver Transplant Unit, Adventist Silvestre Hospital, Rio de Janeiro 22241-280, Brazil
| |
Collapse
|
|
47
|
Low-Dose Propranolol as Secondary Prophylaxis for Varix Bleeding Decreases Mortality and Rebleeding Rate in Patients with Tense Ascites. J Clin Med 2019; 8:jcm8050573. [PMID: 31035484 PMCID: PMC6571569 DOI: 10.3390/jcm8050573] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2019] [Revised: 04/20/2019] [Accepted: 04/24/2019] [Indexed: 12/25/2022] Open
Abstract
Background and Aim: The risk and benefit of non-selective propranolol in patients with tense ascites are controversial. This study aimed to investigate the effect of propranolol as secondary prophylaxis on varix rebleeding and overall mortality in patients with tense ascites. Methods: This study used a database of the Health Insurance Review and Assessment Service (HIRAS), which provides health insurance to 97.2% of the total population in Korea. A total of 80,071 patients first variceal bleeding as the first decompensated complication enrolled from 2007 to 2014. Results: There were 2274 patients with large-volume ascites prescribed propranolol as secondary prophylaxis after first varix bleeding. The average prescription dose of propranolol as secondary prophylaxis was 74 mg/day in patients with large-volume ascites. The mean duration of rebleeding was 22.8 months. Result of analysis showed that low-dose propranolol (40–120 mg/day) compared to inadequate propranolol dose (<40 mg/day) as secondary prophylaxis decreased overall mortality and varix rebleeding in patients with tense ascites. Conclusions: Low-dose propranolol (40–120 mg/day) as secondary prophylaxis for variceal re-bleeding decreased overall mortality and varix rebleeding recurrence in patients with tense ascites.
Collapse
|
|
48
|
Tripathi D, Hayes PC, Richardson P, Rowe I, Ferguson J, Devine P, Mathers J, Poyner C, Jowett S, Handley K, Grant M, Slinn G, Ahmed K, Brocklehurst P. Study protocol for a randomised controlled trial of carvedilol versus variceal band ligation in primary prevention of variceal bleeding in liver cirrhosis (CALIBRE trial). BMJ Open Gastroenterol 2019; 6:e000290. [PMID: 31139428 PMCID: PMC6506059 DOI: 10.1136/bmjgast-2019-000290] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2019] [Revised: 03/27/2019] [Accepted: 04/03/2019] [Indexed: 12/12/2022] Open
Abstract
Introduction Liver cirrhosis is the fifth largest cause of adult deaths, and a major complication, variceal bleeding is associated with a 1-year mortality of 40%. There is uncertainty on the first-line therapy for prevention of variceal bleeding owing to a lack of adequately powered trials comparing non-selective beta blockers, in particular carvedilol, with variceal band ligation. Methods and analysis CALIBRE is a multicentre, pragmatic, randomised controlled, open-label trial with an internal pilot. The two interventions are carvedilol 12.5 mg od or variceal band ligation (VBL). Patients with liver cirrhosis and medium to large oesophageal varices that have never bled are eligible for inclusion. The primary outcome is any variceal bleeding within 1 year of randomisation. Secondary endpoints include time to variceal bleed, mortality, transplant-free survival, adverse events, complications of cirrhosis, health-related quality of life, use of healthcare resources, patient preference and use of alternative or crossover therapies. The sample size is 2630 patients over a 4-year recruitment period, across 66 hospitals in the UK. Ethics and dissemination The study has been approved by a National Health Service (NHS) Research Ethics Committee (REC) (reference number 18/NE/0296). The results of this trial will be submitted for publication in a peer reviewed journal. Participants will be informed via a link to a preview of the publication. A lay summary will also be provided via email or posted to participants prior to publication (ISRCTN reference number: 73887615).
Collapse
Affiliation(s)
- Dhiraj Tripathi
- Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.,NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | | | - Paul Richardson
- Gastroenterology and Hepatology, Royal Liverpool University Hospital, Liverpool, UK
| | - Ian Rowe
- Hepatology and Liver Transplantation, University of Leeds, Leeds, UK
| | - James Ferguson
- Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.,NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Peter Devine
- Birmingham Liver Public and Patient Involvement Group, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Jonathan Mathers
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Christopher Poyner
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Sue Jowett
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Kelly Handley
- Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, UK
| | - Margaret Grant
- Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, UK
| | - Gemma Slinn
- Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, UK
| | - Khaled Ahmed
- Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, UK
| | - Peter Brocklehurst
- Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, UK
| |
Collapse
|
|
49
|
|
|
50
|
KASL clinical practice guidelines for liver cirrhosis: Ascites and related complications. Clin Mol Hepatol 2018; 24:230-277. [PMID: 29991196 PMCID: PMC6166105 DOI: 10.3350/cmh.2018.1005] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Accepted: 04/06/2018] [Indexed: 02/07/2023] Open
|