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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.
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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
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Jagdish RK, Roy A, Kumar K, Premkumar M, Sharma M, Rao PN, Reddy DN, Kulkarni AV. Pathophysiology and management of liver cirrhosis: from portal hypertension to acute-on-chronic liver failure. Front Med (Lausanne) 2023; 10:1060073. [PMID: 37396918 PMCID: PMC10311004 DOI: 10.3389/fmed.2023.1060073] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2022] [Accepted: 05/19/2023] [Indexed: 07/04/2023] Open
Abstract
Cirrhosis transcends various progressive stages from compensation to decompensation driven by the severity of portal hypertension. The downstream effect of increasing portal hypertension severity leads to various pathophysiological pathways, which result in the cardinal complications of cirrhosis, including ascites, variceal hemorrhage, and hepatic encephalopathy. Additionally, the severity of portal hypertension is the central driver for further advanced complications of hyperdynamic circulation, hepatorenal syndrome, and cirrhotic cardiomyopathy. The management of these individual complications has specific nuances which have undergone significant developments. In contrast to the classical natural history of cirrhosis and its complications which follows an insidious trajectory, acute-on-chronic failure (ACLF) leads to a rapidly downhill course with high short-term mortality unless intervened at the early stages. The management of ACLF involves specific interventions, which have quickly evolved in recent years. In this review, we focus on complications of portal hypertension and delve into an approach toward ACLF.
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Affiliation(s)
- Rakesh Kumar Jagdish
- Department of Hepatology, Gastroenterology and Liver Transplant Medicine, Metro Hospital, Noida, India
| | - Akash Roy
- Department of Gastroenterology, Institute of Gastrosciences and Liver Transplantation, Apollo Hospitals, Kolkata, India
| | - Karan Kumar
- Department of Hepatology, Mahatma Gandhi Medical College and Hospital, Jaipur, India
| | - Madhumita Premkumar
- Department of Hepatology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Mithun Sharma
- Department of Hepatology, Asian Institute of Gastroenterology (AIG) Hospitals, Hyderabad, India
| | - Padaki Nagaraja Rao
- Department of Hepatology, Asian Institute of Gastroenterology (AIG) Hospitals, Hyderabad, India
| | - Duvvur Nageshwar Reddy
- Department of Hepatology, Asian Institute of Gastroenterology (AIG) Hospitals, Hyderabad, India
| | - Anand V. Kulkarni
- Department of Hepatology, Asian Institute of Gastroenterology (AIG) Hospitals, Hyderabad, India
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Bikheet MM, Mahmoud ME, Yassien EE, Hassan HM. Effect of lactic acid bacteria isolated from some fermented dairy products on carbon tetrachloride-induced hepatotoxicity and nephrotoxicity of albino rats. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2022; 29:11790-11800. [PMID: 34553279 DOI: 10.1007/s11356-021-16524-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Accepted: 09/09/2021] [Indexed: 06/13/2023]
Abstract
The current research was performed to evaluate the potential protective effect of Lactobacillus paracasei ssp. paracasei, Pediococcus acidilactici, Lactococcus lactis ssp. lactis, and silymarin in the alleviation of health (hepatic and renal) complications caused by carbon tetrachloride (CCl4) in rats. Healthy sixty albino rats were divided into six groups, the first group was control (negative), the second group (control positive) was injected CCl4 (1 ml/kg, 1:1 v/v paraffin oil mixture, i.p. every third day for 8 weeks), the third group (CCl4 + silymarin group) receiving both CCl4 and daily silymarin therapy (50 mg/kg, oral), and the fourth group: CCl4 + Lactobacillus paracasei (1 ml orally). The fifth group (CCl4 + Pediococcus acidilactici 1 ml orally) and the sixth group (CCl4 + Lactococcus lactis 1 ml orally) for 8 weeks per day. Biochemical markers were tested for blood, liver, and kidney tissue. Histopathological examination of the liver and kidney tissues was performed. The findings obtained have shown that Lactobacillus paracasei ssp. paracasei, Pediococcus acidilactici, and Lactococcus lactis ssp. lactis improved the disrupted biochemical parameters caused by CCl4 therapy. Besides, the findings of the histopathology are in consistent with biochemical parameters and the protective ability of lactic acid bacteria suggesting that the best lactic acid bacteria were Pediococcus acidilactici that helped strengthen liver fibrosis caused by CCl4 therapy, while the best bacterium for improving renal damage was Lactococcus lactis.
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Affiliation(s)
- Maha M Bikheet
- Department of Dairy Science, Faculty of Agriculture, Minia University, El-Minia, Egypt
| | - Magda E Mahmoud
- Department of Agricultural Chemistry, Faculty of Agriculture, Minia University, El-Minia, Egypt
| | - Eman E Yassien
- Department of Agricultural Chemistry, Faculty of Agriculture, Minia University, El-Minia, Egypt
| | - Hanaa M Hassan
- Department of Agricultural Chemistry, Faculty of Agriculture, Minia University, El-Minia, Egypt.
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Butt AK, Patel J, Shirwany H, Mirza Q, Hoover J, Khouzam RN. Beneficial Extracardiac Effects of Cardiovascular Medications. Curr Cardiol Rev 2022; 18:e151021197270. [PMID: 34779371 PMCID: PMC9413730 DOI: 10.2174/1573403x17666211015145132] [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: 01/05/2021] [Revised: 08/10/2021] [Accepted: 08/25/2021] [Indexed: 11/22/2022] Open
Abstract
Cardiovascular diseases are the most common cause of death worldwide, with cardiovascular medications being amongst the most common medications prescribed. These medications have diverse effects on the heart, vascular system, as well as other tissues and organ systems. The extra cardiovascular effects have been found to be of use in the treatment of non-cardiovascular diseases and pathologies. Minoxidil is used to manage systemic hypertension with its well-known side effect of hirsutism used to treat alopecia and baldness. Sildenafil was originally investigated as a treatment option for systemic hypertension; however, its side effect of penile erection led to it being widely used for erectile dysfunction. Alpha-1 blockers such as terazosin are indicated to treat systemic hypertension but are more commonly used for benign prostatic hyperplasia and post-traumatic stress disorder. Beta blockers are the mainstay treatment for congestive heart failure and systemic hypertension but have been found useful to help in patients with intention tremors as well as prophylaxis of migraines. Similarly, calcium channel blockers are indicated in medical expulsion therapy for ureteric calculi in addition to their cardiovascular indications. Thiazides are commonly used for treating systemic hypertension and as diuretics. Thiazides can cause hypocalciuria and hypercalcemia. This side effect has led to thiazides being used to treat idiopathic hypercalciuria and associated nephrolithiasis. Spironolactone is commonly utilized in treating heart failure and as a diuretic for edema. It's well described anti-androgen side effects have been used for acne vulgaris and hirsutism in polycystic ovarian syndrome. This review article discusses how the various extracardiovascular effects of commonly used cardiovascular medications are put to use in managing non-cardiovascular conditions.
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Affiliation(s)
- Asra K. Butt
- Department of Internal Medicine, Veteran Affairs Medical Center, Memphis, TN 38104, USA
| | - Jay Patel
- Department of Internal Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA
| | - Hamid Shirwany
- University of Tennessee Health Science Center, College of Medicine, Memphis, TN 38163, USA
| | - Qasim Mirza
- Department of Medicine, Division of Pulmonary, Critical Care & Sleep Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA
| | - Jonathan Hoover
- Department of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA
| | - Rami N. Khouzam
- Department of Medicine, Division of Cardiovascular Diseases, University of Tennessee Health Science Center, Memphis, TN 38163, USA
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Dourakis SP, Geladari E, Geladari C, Vallianou N. Cirrhotic Cardiomyopathy: The Interplay Between Liver and Cardiac Muscle. How Does the Cardiovascular System React When the Liver is Diseased? Curr Cardiol Rev 2021; 17:78-84. [PMID: 31072296 PMCID: PMC8142364 DOI: 10.2174/1573403x15666190509084519] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2019] [Revised: 04/21/2019] [Accepted: 04/22/2019] [Indexed: 12/03/2022] Open
Abstract
It is widely known that liver cirrhosis, regardless of the etiologies is accompanied by severe hemodynamic changes. The principal pathophysiological mechanisms are the hyperdynamic circulation with increased cardiac output, heart rate along with reduced systemic vascular resistance. Thus, counteractive mechanisms may develop that eventually lead to systolic as well as diastolic dysfunction and rhythm disturbances, in order to keep a steady homeostasis in the human body. Literally, blunted contractile responsiveness to physical or pharmacological stress, impaired diastolic relaxation and electrophysiological changes, primarily QT interval prolongation, do occur progressively in a cirrhotic patient with no known preexisting cardiac disease. This condition is identified as cirrhotic cardiomyopathy (CCM), an entity different from that seen in alcoholic cardiac muscle disease. For the past decades, clinicians did study and attempt to understand the pathophysiology and clinical significance of this process. Indeed, various factors have been identified acting at the molecular and cellular level. Electrocardiography, echocardiography and various serum biomarkers are the main tools that help healthcare practitioners to point to the correct diagnosis. Noteworthy, the subjects that suffer from cirrhotic cardiomyopathy may progress to heart failure during invasive procedures such as surgery, insertion of a transjugular intrahepatic portosystemic shunting (TIPS) and liver transplantation. Besides, several studies have illustrated that CCM is a contributing factor, or even a precipitant, of hepatorenal syndrome (HRS), a conceivable reversible kidney failure in patients with liver cirrhosis and ascites. The treatment is the same as it is in the patients with liver cirrhosis and heart failure and there is no particular treatment for cirrhotic cardiomyopathy. Hence, it is of utmost importance to clearly comprehend the pathophysiology of this disease in order to design more accurate diagnostic tools and definitive treatments in a way to prevent the complications of cirrhosis and overt heart failure. The objective of this review is to describe in a comprehensive way the pathological alterations that occur in the cardiovascular system of cirrhotic patients. It will also point the limitations that remain in the diagnosis and treatment strategies and more importantly, this review will alert the clinicians in the modern era to further observe and record additional pathological changes in this subset of patients.
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Affiliation(s)
- Spyros P Dourakis
- 2nd Department of Internal Medicine and Research Laboratory, Medical School, National and Kapodistrian University of Athens, Hippokration Hospital, Athens, Greece
| | - Eleni Geladari
- Internal Medicine Department, Evaggelismos General Hospital, Athens, Greece
| | | | - Natalia Vallianou
- Internal Medicine Department, Evaggelismos General Hospital, Athens, Greece
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Wang SF, Huang YT, Huang CH, Chang SH, Lin CY. Fibrosis index predicts variceal bleeding and reduces need for nonselective beta-blocker in compensated cirrhosis with initial small esophageal varices without red-color sign. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:1223. [PMID: 33178755 PMCID: PMC7607085 DOI: 10.21037/atm-20-2444] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/12/2020] [Accepted: 08/07/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Various non-invasive markers predicting hepatic fibrosis are poor predictors of esophageal variceal bleeding (EVB). Elastography performs well but resource-limited. Controversy for small EV prevention also exists. We aim to investigate if a non-invasive marker could predict subsequent EVB within 1 and 2 years in patients with compensated liver cirrhosis (CLC), initial small EV without red-color sign (RCS), without use of non-selective beta-blockers (NSBB) and endoscopic variceal ligation (EVL). This marker would also be tested if it could help reduce use of NSBB, thereby avoiding potential side effects and saving medical costs. METHODS In this retrospective cohort study, 6,803 CLC patients fulfilling the inclusion-exclusion criteria were enrolled between 2001 and 2018, and were followed-up for 1 year, 2 years. The primary outcomes were subsequent EVB within 1 and 2 years of enrollment. Another 281 CLC patients with NSBB use were compared for additional outcome analysis. RESULTS In total, 539 patients and 710 patients experienced EVB within 1 year and 2 years, respectively. The fibrosis index (FI) with cut-off value of 3.95 showed a negative predictive value (NPV) of 94.3% and an area under receiver operating characteristic (AUROC) of 62.95% for predicting subsequent EVB within 1 year. The EVB and mortality of patients with FI <3.95 and not taking NSBB were significantly lower than those of the other 3 groups. Similar results were demonstrated within 2 years. CONCLUSIONS In CLC patients with initial small EV and no RCS, low FI scores showed a high NPV and moderate AUROC in predicting subsequent EVB and mortalities, signifying clinically non-significant portal hypertension. Patients with low FI scores and not taking NSBB had significantly lowest EVB and mortality. The medical cost savings for cutting NSBB in these patients would be estimated at least $3 million per year in the U.S. Further randomized control trial study needed to validate this screening tool.
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Affiliation(s)
- Sheng-Fu Wang
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital, Linkou Medical Center, Taoyuan
| | - Yu-Tung Huang
- Center for Big Data Analytics and Statistics, Department of Medical Research and Development, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan
| | - Chien-Hao Huang
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital, Linkou Medical Center, Taoyuan
- Center for Big Data Analytics and Statistics, Department of Medical Research and Development, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan
- School of Medicine, College of Medicine, Chang-Gung University, Taoyuan
- Cardiovascular Division, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan
| | - Shang-Hung Chang
- Center for Big Data Analytics and Statistics, Department of Medical Research and Development, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan
- School of Medicine, College of Medicine, Chang-Gung University, Taoyuan
- Cardiovascular Division, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan
| | - Chun-Yen Lin
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital, Linkou Medical Center, Taoyuan
- School of Medicine, College of Medicine, Chang-Gung University, Taoyuan
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Yoo JJ, Kim SG, Kim YS, Lee B, Jeong SW, Jang JY, Lee SH, Kim HS, Jun BG, Kim YD, Cheon GJ. Propranolol plus endoscopic ligation for variceal bleeding in patients with significant ascites: Propensity score matching analysis. Medicine (Baltimore) 2020; 99:e18913. [PMID: 32000397 PMCID: PMC7004788 DOI: 10.1097/md.0000000000018913] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
The use of beta-blockers in decompensated cirrhosis accompanying ascites is still under debate. The aim of this study was to compare overall survival (OS) and incidence of cirrhotic complications between endoscopic variceal ligation (EVL) only and EVL + non-selective beta-blocker (NSBB) combination therapy in cirrhotic patients with significant ascites (≥grade 2).This retrospective study included 271 consecutive cirrhotic patients with ascites who were treated with EVL only or EVL + NSBB combination therapy as a primary prophylaxis of esophageal varices. The primary outcome was all-cause mortality. Propensity score matching was performed between the 2 groups to minimize baseline difference.Median observation period was 42.1 months (interquartile range, 18.4-75.1 months). All patients had deteriorated liver function: 81.1% Child-Pugh class B and 18.9% Child-Pugh class C. All-cause mortality was significantly higher in the EVL + NSBB group than in the EVL only group not only in non-matched cohort, but also in matched cohort (48.9% vs 31.2%; P = .039). More people died from hepatic failure in the EVL + NSBB group than that in the EVL only group (40.5% vs 20.0%; P = .020). However, the incidence of variceal bleeding, hepatorenal syndrome (HRS), or spontaneous bacterial peritonitis (SBP) was not significantly different between the 2 groups.The use of NSBB might worsen the prognosis of cirrhotic patients with significant ascites. These results suggest that EVL alone is a more appropriate treatment option for prophylaxis of esophageal varices than propranolol combination therapy when patients have significant ascites.
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Affiliation(s)
- Jeong-Ju Yoo
- Department of Gastroenterology and Hepatology, Soon Chun Hyang University School of Medicine
| | - Sang Gyune Kim
- Department of Gastroenterology and Hepatology, Soon Chun Hyang University School of Medicine
| | - Young Seok Kim
- Department of Gastroenterology and Hepatology, Soon Chun Hyang University School of Medicine
| | - Bora Lee
- Department of Statistics, Graduate School, Chung-Ang University, Seoul
| | - Soung Won Jeong
- Department of Gastroenterology and Hepatology, Soon Chun Hyang University School of Medicine
| | - Jae Young Jang
- Department of Gastroenterology and Hepatology, Soon Chun Hyang University School of Medicine
| | - Sae Hwan Lee
- Department of Gastroenterology and Hepatology, Soon Chun Hyang University School of Medicine
| | - Hong Soo Kim
- Department of Gastroenterology and Hepatology, Soon Chun Hyang University School of Medicine
| | - Baek-Gyu Jun
- Department of Internal Medicine, Gangneug Asan Hospital, Republic of Korea
| | - Young Don Kim
- Department of Internal Medicine, Gangneug Asan Hospital, Republic of Korea
| | - Gab Jin Cheon
- Department of Internal Medicine, Gangneug Asan Hospital, Republic of Korea
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Abstract
Terlipressin, somatostatin, or octreotide are recommended as pharmacologic treatment of acute variceal hemorrhage. Nonselective β-blockers decrease the risk of variceal hemorrhage and hepatic decompensation, particularly in those 30% to 40% of patients with good hemodynamic response. Carvedilol, statins, and anticoagulants are promising agents in the management of portal hypertension. Recent advances in the pharmacologic treatment of portal hypertension have mainly focused on modifying an increased intrahepatic resistance through nitric oxide and/or modulation of vasoactive substances. Several novel pharmacologic agents for portal hypertension are being evaluated in humans.
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Affiliation(s)
- Chalermrat Bunchorntavakul
- Division of Gastroenterology and Hepatology, Department of Medicine, Rajavithi Hospital, College of Medicine, Rangsit University, Rajavithi Road, Ratchathewi, Bangkok 10400, Thailand; Division of Gastroenterology and Hepatology, Department of Medicine, University of Pennsylvania, 2 Dulles, 3400 Spruce Street, Philadelphia, PA 19104, USA
| | - K Rajender Reddy
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Pennsylvania, 2 Dulles, 3400 Spruce Street, Philadelphia, PA 19104, USA.
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Stundiene I, Sarnelyte J, Norkute A, Aidietiene S, Liakina V, Masalaite L, Valantinas J. Liver cirrhosis and left ventricle diastolic dysfunction: Systematic review. World J Gastroenterol 2019; 25:4779-4795. [PMID: 31528101 PMCID: PMC6718042 DOI: 10.3748/wjg.v25.i32.4779] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2019] [Revised: 06/10/2019] [Accepted: 07/19/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Liver cirrhosis is a chronic hepatic disease which is associated with cardiovascular abnormalities. Hyperdynamic circulation in liver cirrhosis causes functional and structural cardiac alterations. The prevalence of left ventricle diastolic dysfunction (LVDD) in cirrhotic patients ranges from 25.7% to as high as 81.4% as reported in different studies. In several studies the severity of diastolic dysfunction (DD) correlated with a degree of liver failure and the rate of dysfunction was higher in patients with decompensated cirrhosis compared with compensated. Future directions of comprehensive assessment of cardiac function in cirrhotic patients might provide a better prognosis for these patients. AIM To clarify the correlation between the severity of liver cirrhosis and left ventricle diastolic dysfunction in the existing literature. METHODS Through January and February of 2019 at Vilnius University we conducted a systematic review of the global existing literature on the prevalence of left ventricle diastolic dysfunction in patients with liver cirrhosis. We searched for articles in PubMed, Medline and Web of science databases. Articles were selected by using adequate inclusion and exclusion criteria. Our interest was the outcome of likely correlation between the severity of cirrhosis [evaluated by Child-Pugh classes, Model For End-Stage Liver Disease (MELD) scores] and left ventricle diastolic dysfunction [classified according to American Society of Echocardiography (ASE) guidelines (2009, 2016)], as well as relative risk of dysfunction in cirrhotic patients. Subgroup analyses were performed to evaluate the ratio and grades of left ventricle diastolic dysfunction with respect to cirrhosis severity. RESULTS A total of 1149 articles and abstracts met the initial search criteria. Sixteen articles which met the predefined eligibility criteria were included in the final analysis. Overall, 1067 patients (out of them 723 men) with liver cirrhosis were evaluated for left ventricle diastolic dysfunction. In our systemic analysis we have found that 51.2% of cirrhotic patients had left ventricle diastolic dysfunction diagnosed and the grade 1 was the most prevalent (59.2%, P < 0.001) among them, the grade 3 had been rarely diagnosed - only 5.1%. The data about the prevalence of diastolic dysfunction in cirrhotic patients depending on Child-Pugh Classes was available from 5 studies (365 patients overall) and only in 1 research diastolic dysfunction was found being associated with severity of liver cirrhosis (P < 0.005). We established that diastolic dysfunction was diagnosed in 44.6% of Child-Pugh A class patients, in 62% of Child B class and in 63.3% of Child C patients (P = 0.028). The proportion of patients with higher diastolic dysfunction grades increases in more severe cirrhosis presentation (P < 0.001). There was no difference between mean MELD scores in patients with and without diastolic dysfunction and in different diastolic dysfunction groups. In all studies diastolic dysfunction was more frequent in patients with ascites. CONCLUSION This systemic analysis suggests that left ventricle diastolic dysfunction is an attribute of liver cirrhosis which has not received sufficient attention from clinicians so far. Future suggestions of a comprehensive assessment of cardiac function in cirrhotic patients might provide a better prognosis for these patients and give hint for better understanding of the left ventricle diastolic dysfunction pathogenesis in liver cirrhosis.
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Affiliation(s)
- Ieva Stundiene
- Vilnius University, Institute of Clinical Medicine, Clinic of Gastroenterology, Nephrourology and Surgery, Vilnius University, Vilnius LT-03101, Lithuania
| | - Julija Sarnelyte
- Vilnius University, Institute of Clinical Medicine, Clinic of Gastroenterology, Nephrourology and Surgery, Vilnius University, Vilnius LT-03101, Lithuania
| | - Ausma Norkute
- Vilnius University, Institute of Clinical Medicine, Clinic of Internal diseases, Family medicine and Oncology, Vilnius University, Vilnius LT-03101, Lithuania
| | - Sigita Aidietiene
- Vilnius University, Institute of Clinical Medicine, Clinic of Cardiology and Angiology, Vilnius University, Vilnius LT-03101, Lithuania
| | - Valentina Liakina
- Vilnius University, Institute of Clinical Medicine, Clinic of Gastroenterology, Nephrourology and Surgery, Vilnius University, Vilnius LT-03101, Lithuania
- Vilnius Gediminas Technical University, Faculty of Fundamental Sciences, Department of Chemistry and Bioengineering, Vilnius LT-10223, Lithuania
| | - Laura Masalaite
- Vilnius University, Institute of Clinical Medicine, Clinic of Gastroenterology, Nephrourology and Surgery, Vilnius University, Vilnius LT-03101, Lithuania
| | - Jonas Valantinas
- Vilnius University, Institute of Clinical Medicine, Clinic of Gastroenterology, Nephrourology and Surgery, Vilnius University, Vilnius LT-03101, Lithuania
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Xanthopoulos A, Starling RC, Kitai T, Triposkiadis F. Heart Failure and Liver Disease: Cardiohepatic Interactions. JACC-HEART FAILURE 2018; 7:87-97. [PMID: 30553904 DOI: 10.1016/j.jchf.2018.10.007] [Citation(s) in RCA: 185] [Impact Index Per Article: 26.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/20/2018] [Accepted: 10/04/2018] [Indexed: 02/07/2023]
Abstract
Heart failure (HF) and liver disease often co-exist. This is because systemic disorders and diseases affect both organs (alcohol abuse, drugs, inflammation, autoimmunity, infections) and because of complex cardiohepatic interactions. The latter, which are the focus of this review, include the development of acute cardiogenic liver injury and congestive hepatopathy in HF as well as cardiac dysfunction and failure in the setting of liver cirrhosis, nonalcoholic fatty liver disease, and sequelae following liver transplantation. The emerging role of altered liver X receptor signaling in the pathogenesis of HF comorbidities as well as of the intestinal microbiome and its metabolites in HF and liver disease are fruitful areas for future research.
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Affiliation(s)
- Andrew Xanthopoulos
- Department of Cardiovascular Medicine, Heart and Vascular Institute, Kaufman Center for Heart Failure, Cleveland Clinic, Cleveland, Ohio
| | - Randall C Starling
- Department of Cardiovascular Medicine, Heart and Vascular Institute, Kaufman Center for Heart Failure, Cleveland Clinic, Cleveland, Ohio
| | - Takeshi Kitai
- Department of Cardiovascular Medicine, Kobe City Medical Center General Hospital, Kobe, Japan
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Sinha R, Lockman KA, Mallawaarachchi N, Robertson M, Plevris JN, Hayes PC. Carvedilol use is associated with improved survival in patients with liver cirrhosis and ascites. J Hepatol 2017; 67:40-46. [PMID: 28213164 DOI: 10.1016/j.jhep.2017.02.005] [Citation(s) in RCA: 74] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2016] [Revised: 01/20/2017] [Accepted: 02/06/2017] [Indexed: 12/24/2022]
Abstract
BACKGROUND & AIMS Carvedilol, a non-selective beta-blocker (NSBB) with additional anti-alpha 1 receptor activity, is a potent portal hypotensive agent and has been used as prophylaxis against variceal bleeding. However, its safety in patients with decompensated liver cirrhosis and ascites is still disputed. In this study, we examined whether long-term use of carvedilol in patients with ascites is a risk factor for mortality. METHODS A single-centre retrospective analysis of 325 consecutive patients with liver cirrhosis and ascites presenting to our Liver Unit between 1st of January 2009 to 31st August 2012 was carried out. The primary outcome was all-cause and liver-specific mortality in patients receiving or not receiving carvedilol as prophylaxis against variceal bleeding. RESULTS The final cohort after propensity score matching comprised 264 patients. Baseline ascites severity and UK end-stage liver disease (UKELD) score between carvedilol (n=132) and non-carvedilol (n=132) treated patient groups were comparable. Median follow-up time was 2.3years. Survival at the end of the follow-up was 24% and 2% for the carvedilol and the non-carvedilol groups respectively (log-rank p<0.0001). The long-term survival was significantly better in carvedilol than non-carvedilol group (log-rank p<0.001). The survival difference remained significant after adjusting for age, gender, ascites severity, aetiology of cirrhosis, previous variceal bleed, spontaneous bacterial peritonitis prophylaxis, serum albumin and UKELD with hazard ratio of 0.59 (95% confidence interval [CI]: 0.44, 0.80; p=0.001), suggesting a 41% reduction in mortality risk. When stratified by the severity of ascites, carvedilol therapy resulted in hazard ratio of 0.47 (95% CI: 0.29, 0.77; p=0.003) in those with mild ascites. Even with moderate or severe ascites, carvedilol use was not associated with increased mortality risk. CONCLUSION Long-term carvedilol therapy is not harmful in patients with decompensated cirrhosis and ascites. LAY SUMMARY The safety of carvedilol and other non-selective beta-blocker drugs in patients with liver cirrhosis and ascites is still debated. In this study, we have shown that carvedilol therapy in these patients was associated with reduced risk of mortality, particularly in those with mild ascites. We concluded that low dose, chronic treatment with carvedilol in patients with liver cirrhosis and ascites is not detrimental.
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Affiliation(s)
- Rohit Sinha
- Liver Unit, The Royal Infirmary of Edinburgh and The University of Edinburgh, Edinburgh, United Kingdom; Hepatology Laboratory, The Royal Infirmary of Edinburgh and The University of Edinburgh, Edinburgh, United Kingdom.
| | - Khalida A Lockman
- Hepatology Laboratory, The Royal Infirmary of Edinburgh and The University of Edinburgh, Edinburgh, United Kingdom
| | - Nethmee Mallawaarachchi
- Hepatology Laboratory, The Royal Infirmary of Edinburgh and The University of Edinburgh, Edinburgh, United Kingdom
| | - Marcus Robertson
- Liver Unit, The Royal Infirmary of Edinburgh and The University of Edinburgh, Edinburgh, United Kingdom
| | - John N Plevris
- Liver Unit, The Royal Infirmary of Edinburgh and The University of Edinburgh, Edinburgh, United Kingdom; Hepatology Laboratory, The Royal Infirmary of Edinburgh and The University of Edinburgh, Edinburgh, United Kingdom
| | - Peter C Hayes
- Liver Unit, The Royal Infirmary of Edinburgh and The University of Edinburgh, Edinburgh, United Kingdom; Hepatology Laboratory, The Royal Infirmary of Edinburgh and The University of Edinburgh, Edinburgh, United Kingdom
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12
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Blasco-Algora S, Masegosa-Ataz J, Alonso S, Gutiérrez ML, Fernández-Rodriguez C. Non-selective β-blockers in advanced cirrhosis: a critical review of the effects on overall survival and renal function. BMJ Open Gastroenterol 2016; 3:e000104. [PMID: 28074149 PMCID: PMC5174812 DOI: 10.1136/bmjgast-2016-000104] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2016] [Revised: 07/23/2016] [Accepted: 07/29/2016] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION Non-selective β-blockers (NSBBs) are widely prescribed in patients with cirrhosis for primary and secondary prophylaxis of bleeding oesophageal varices. Furthermore, it has been suggested that the clinical benefits of NSBBs may extend beyond their haemodynamic effects. Recently, a potentially harmful effect has been described in patients with refractory ascites or spontaneous bacterial peritonitis. METHODOLOGY A comprehensive literature search on β-blockers and cirrhosis survival using the electronic databases PubMed/MEDLINE, AMED, CINAHL and the Cochrane Central Register of Controlled Trials. Full-text manuscripts published over more than 35 years, from 1980 to April 2016 were reviewed for relevance and reference lists were cross-checked for additional pertinent studies regarding potential NSBB effects, especially focused on those concerned with survival and/or acute kidney injury (AKI). DISCUSSION The proposed review will be able to provide valuable evidence to help decision making in the use of NSBB for the treatment of advanced cirrhosis and highlights some limitations in existing evidence to direct future research.
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Affiliation(s)
- Sara Blasco-Algora
- Gastroenterology Unit, Hospital Universitario Fundación Alcorcon, Madrid, Spain; University Rey Juan Carlos, Madrid, Spain
| | - José Masegosa-Ataz
- Gastroenterology Unit, Hospital Universitario Fundación Alcorcon, Madrid, Spain; University Rey Juan Carlos, Madrid, Spain
| | - Sonia Alonso
- Gastroenterology Unit, Hospital Universitario Fundación Alcorcon, Madrid, Spain; University Rey Juan Carlos, Madrid, Spain
| | - Maria-Luisa Gutiérrez
- Gastroenterology Unit, Hospital Universitario Fundación Alcorcon, Madrid, Spain; University Rey Juan Carlos, Madrid, Spain
| | - Conrado Fernández-Rodriguez
- Gastroenterology Unit, Hospital Universitario Fundación Alcorcon, Madrid, Spain; University Rey Juan Carlos, Madrid, Spain
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13
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Ferrarese A, Zanetto A, Germani G, Burra P, Senzolo M. Rethinking the role of non-selective beta blockers in patients with cirrhosis and portal hypertension. World J Hepatol 2016; 8:1012-1018. [PMID: 27648153 PMCID: PMC5002497 DOI: 10.4254/wjh.v8.i24.1012] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2016] [Revised: 07/01/2016] [Accepted: 07/14/2016] [Indexed: 02/06/2023] Open
Abstract
Non-selective beta blockers (NSBB) are commonly used to prevent portal hypertensive bleeding in cirrhotics. Nevertheless, in the last years, the use of NSBB in critically decompensated patients, especially in those with refractory ascites, has been questioned, mainly for an increased risk of mortality and worsening of systemic hemodynamics. Moreover, even if NSBB have been reported to correlate with a higher risk of renal failure and severe infection in patients with advanced liver disease and hypotension, their use has been associated with a reduction of risk of spontaneous bacterial peritonitis, modification of gut permeability and reduction of bacterial translocation. This manuscript systematically reviews the published evidences about harms and benefits of the use of NSBB in patients with decompensated cirrhosis.
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Affiliation(s)
- Alberto Ferrarese
- Alberto Ferrarese, Alberto Zanetto, Giacomo Germani, Patrizia Burra, Marco Senzolo, Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, 35128 Padua, Italy
| | - Alberto Zanetto
- Alberto Ferrarese, Alberto Zanetto, Giacomo Germani, Patrizia Burra, Marco Senzolo, Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, 35128 Padua, Italy
| | - Giacomo Germani
- Alberto Ferrarese, Alberto Zanetto, Giacomo Germani, Patrizia Burra, Marco Senzolo, Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, 35128 Padua, Italy
| | - Patrizia Burra
- Alberto Ferrarese, Alberto Zanetto, Giacomo Germani, Patrizia Burra, Marco Senzolo, Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, 35128 Padua, Italy
| | - Marco Senzolo
- Alberto Ferrarese, Alberto Zanetto, Giacomo Germani, Patrizia Burra, Marco Senzolo, Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, 35128 Padua, Italy
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14
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Bossen L, Krag A, Vilstrup H, Watson H, Jepsen P. Nonselective β-blockers do not affect mortality in cirrhosis patients with ascites: Post Hoc analysis of three randomized controlled trials with 1198 patients. Hepatology 2016; 63:1968-76. [PMID: 26599983 DOI: 10.1002/hep.28352] [Citation(s) in RCA: 94] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2015] [Revised: 10/22/2015] [Accepted: 11/13/2015] [Indexed: 12/15/2022]
Abstract
UNLABELLED The safety of nonselective β-blockers (NSBBs) in advanced cirrhosis has been questioned. We used data from three satavaptan trials to examine whether NSBBs increase mortality in cirrhosis patients with ascites. The trials were conducted in 2006-2008 and included 1198 cirrhosis patients with ascites followed for 1 year. We used Cox regression to compare all-cause mortality and cirrhosis-related mortality between patients who did and those who did not use NSBBs at randomization, controlling for age, gender, Model for End-Stage Liver Disease score, Child-Pugh score, serum sodium, previous variceal bleeding, cirrhosis etiology, and ascites severity. Moreover, we identified clinical events predicting that a patient would stop NSBB treatment. At randomization, the 559 NSBB users were more likely than the 629 nonusers to have a history of variceal bleeding but less likely to have Child-Pugh class C cirrhosis, hyponatremia, or refractory ascites. The 52-week cumulative all-cause mortality was similar in the NSBB user and nonuser groups (23.2% versus 25.3%, adjusted hazard ratio = 0.92, 95% confidence interval 0.72-1.18), and NSBBs also did not increase mortality in the subgroup of patients with refractory ascites (588 patients, adjusted hazard ratio = 1.02, 95% confidence interval 0.74-1.40) or in any other subgroup. Similarly, NSBBs did not increase cirrhosis-related mortality (adjusted hazard ratio = 1.00, 95% confidence interval 0.76-1.31). During follow-up, 29% of initial NSBB users stopped taking NSBBs, and the decision to stop NSBB treatment marked a sharp rise in mortality and coincided with hospitalization, variceal bleeding, bacterial infection, and/or development of hepatorenal syndrome. CONCLUSION This large and detailed data set on worldwide nonprotocol use of NSBBs in cirrhosis patients with ascites shows that NSBBs did not increase mortality; the decision to stop NSBB treatment in relation to stressful events may have added to the safety. (Hepatology 2016;63:1968-1976).
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Affiliation(s)
- Lars Bossen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.,Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark
| | - Aleksander Krag
- Department of Gastroenterology, Odense University Hospital, Odense, Denmark
| | - Hendrik Vilstrup
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | | | - Peter Jepsen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.,Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark
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15
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Tapper EB, Bonder A, Cardenas A. Preventing and Treating Acute Kidney Injury Among Hospitalized Patients with Cirrhosis and Ascites: A Narrative Review. Am J Med 2016; 129:461-7. [PMID: 26724589 DOI: 10.1016/j.amjmed.2015.12.006] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2015] [Revised: 12/15/2015] [Accepted: 12/15/2015] [Indexed: 02/07/2023]
Abstract
Acute kidney injury in the setting of ascites and cirrhosis is a medical emergency characterized by significant morbidity and mortality. Clinicians other than gastroenterologists are often the front line against acute kidney injury for patients with ascites. Owing to the specifics of cirrhotic physiology, the treatment and prevention of acute kidney injury in the setting of ascites has unique features, widespread knowledge of which will benefit our patients with cirrhosis. Early detection and treatment of infection, maximization of cardiac output, and avoidance of medications that limit cardiorenal adaptations to arterial underfilling are part of a multipronged strategy to protect the renal function of our patients with cirrhosis and ascites.
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Affiliation(s)
- Elliot B Tapper
- Division of Gastroenterology/Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass.
| | - Alan Bonder
- Division of Gastroenterology/Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass
| | - Andres Cardenas
- GI/Liver Unit, Hospital Clinic, Institut de Malalties Digestives i Metaboliques, University of Barcelona, Spain
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16
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Ruiz-del-Árbol L, Serradilla R. Cirrhotic cardiomyopathy. World J Gastroenterol 2015; 21:11502-11521. [PMID: 26556983 PMCID: PMC4631957 DOI: 10.3748/wjg.v21.i41.11502] [Citation(s) in RCA: 91] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2015] [Revised: 06/17/2015] [Accepted: 09/14/2015] [Indexed: 02/06/2023] Open
Abstract
During the course of cirrhosis, there is a progressive deterioration of cardiac function manifested by the disappearance of the hyperdynamic circulation due to a failure in heart function with decreased cardiac output. This is due to a deterioration in inotropic and chronotropic function which takes place in parallel with a diastolic dysfunction and cardiac hypertrophy in the absence of other known cardiac disease. Other findings of this specific cardiomyopathy include impaired contractile responsiveness to stress stimuli and electrophysiological abnormalities with prolonged QT interval. The pathogenic mechanisms of cirrhotic cardiomyopathy include impairment of the b-adrenergic receptor signalling, abnormal cardiomyocyte membrane lipid composition and biophysical properties, ion channel defects and overactivity of humoral cardiodepressant factors. Cirrhotic cardiomyopathy may be difficult to determine due to the lack of a specific diagnosis test. However, an echocardiogram allows the detection of the diastolic dysfunction and the E/e′ ratio may be used in the follow-up progression of the illness. Cirrhotic cardiomyopathy plays an important role in the pathogenesis of the impairment of effective arterial blood volume and correlates with the degree of liver failure. A clinical consequence of cardiac dysfunction is an inadequate cardiac response in the setting of vascular stress that may result in renal hypoperfusion leading to renal failure. The prognosis is difficult to establish but the severity of diastolic dysfunction may be a marker of mortality risk. Treatment is non-specific and liver transplantation may normalize the cardiac function.
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17
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Sersté T, Njimi H, Degré D, Deltenre P, Schreiber J, Lepida A, Trépo E, Gustot T, Moreno C. The use of beta-blockers is associated with the occurrence of acute kidney injury in severe alcoholic hepatitis. Liver Int 2015; 35:1974-82. [PMID: 25611961 DOI: 10.1111/liv.12786] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2014] [Accepted: 01/14/2015] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS The beneficial effect of nonselective beta-blockers (NSBB) has recently been questioned in patients with end-stage cirrhosis. We analysed the impact of NSBB on outcomes in severe alcoholic hepatitis (AH). METHODS This study was based on a prospective database of patients with severe, biopsy-proven AH. Patients admitted from July, 2006 to July, 2014 were retrospectively studied. Patients were divided into two groups (with and without NSBB) and assessed for the occurrence of Acute Kidney Injury (AKI) and transplant-free mortality during a 168-day follow-up period. RESULTS One hundred thirty-nine patients were included, the mean Maddrey score was 71 ± 34 and 86 patients (61.9%) developed AKI. Forty-eight patients (34.5%) received NSBB. The overall 168-day transplant-free mortality was 50.5% (95%CI, 41.3-60.0%). The overall 168-day cumulative incidence of AKI was 61.9% (95%CI, 53.2-69.4%). When compared, patients with NSBB had a lower heart rate (65 ± 13 vs 92 ± 12, P < 0.0001) and a lower mean arterial pressure (MAP, 78 ± 3 vs 87 ± 5, P < 0.0001). Patients with NSBB had comparable MELD scores, Maddrey scores, and medical histories. The 168-day transplant-free mortality was 56.8% (95%CI, 41.3-69.7%) in patients with NSBB and 46.7% (95%CI, 35.0-57.6%) without NSBB (P = 0.25). The 168-day cumulative incidence of AKI was 89.6% (95%CI, 74.9-95.9%) with NSBB compared to 50.4% (95%CI: 39.0-60.7) for no NSBB (P = 0.0001). The independent factors predicting AKI were a higher MELD score and the presence of NSBB. CONCLUSIONS The use of NSBB in patients with severe AH is independently associated with a higher cumulative incidence of AKI.
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Affiliation(s)
- Thomas Sersté
- Liver Unit, Department of Gastroenterology and Hepatopancreatology, CUB Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium.,Department of Hepatogastroenterology, CHU Saint-Pierre, Bruxelles, Belgium
| | - Hassane Njimi
- Biomedical Statistics, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Delphine Degré
- Liver Unit, Department of Gastroenterology and Hepatopancreatology, CUB Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Pierre Deltenre
- Service de Gastroentérologie et d'Hépatologie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
| | - Jonas Schreiber
- Liver Unit, Department of Gastroenterology and Hepatopancreatology, CUB Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Antonia Lepida
- Liver Unit, Department of Gastroenterology and Hepatopancreatology, CUB Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Eric Trépo
- Liver Unit, Department of Gastroenterology and Hepatopancreatology, CUB Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium.,Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Thierry Gustot
- Liver Unit, Department of Gastroenterology and Hepatopancreatology, CUB Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium.,Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Christophe Moreno
- Liver Unit, Department of Gastroenterology and Hepatopancreatology, CUB Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium.,Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Bruxelles, Belgium
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Abstract
Cirrhotic cardiomyopathy is a cardiac condition observed in patients with cirrhotic regardless of the etiologies. It is characterized by the impaired systolic response to physical stress, diastolic dysfunction, and electrophysiological abnormalities, especially QT interval prolongation. Its pathophysiology and clinical significance has been a focus of various researchers for the past decades. The impairment of β-adrenergic receptor, the increase in endogenous cannabinoids, the presence of cardiosuppressants such as nitric oxide and inflammatory cytokines are the proposed mechanisms of systolic dysfunction. The activation of cardiac renin-angiotensin system and salt retention play the role in the development of cardiac hypertrophy and impaired diastolic function. QT interval prolongation, which is observed in 40-50 % of cirrhotic patients, occurs as a result of the derangement in membrane fluidity and ion channel defect. The increased recognition of this disease will prevent the complications of overt heart failure after procedures such as transjugular intrahepatic portosystemic shunt (TIPS) and liver transplantation. Better understandings of the pathogenesis and pathology of cirrhotic cardiomyopathy is crucial in developing more accurate diagnostic tools and specific treatments of this condition.
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Affiliation(s)
| | - Suthat Liangpunsakul
- Division of Gastroenterology/Hepatology, Department of Medicine, Indiana University Hospital, 550 University Boulevard, UH 4100, Indianapolis, IN 46202-5149, USA; Roudebush Veterans Administration Medical Center, Indiana University, Indianapolis, IN, USA
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19
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Abstract
Cirrhotic cardiomyopathy is a cardiac condition observed in patients with cirrhotic regardless of the etiologies. It is characterized by the impaired systolic response to physical stress, diastolic dysfunction, and electrophysiological abnormalities, especially QT interval prolongation. Its pathophysiology and clinical significance has been a focus of various researchers for the past decades. The impairment of β-adrenergic receptor, the increase in endogenous cannabinoids, the presence of cardiosuppressants such as nitric oxide and inflammatory cytokines are the proposed mechanisms of systolic dysfunction. The activation of cardiac renin-angiotensin system and salt retention play the role in the development of cardiac hypertrophy and impaired diastolic function. QT interval prolongation, which is observed in 40-50 % of cirrhotic patients, occurs as a result of the derangement in membrane fluidity and ion channel defect. The increased recognition of this disease will prevent the complications of overt heart failure after procedures such as transjugular intrahepatic portosystemic shunt (TIPS) and liver transplantation. Better understandings of the pathogenesis and pathology of cirrhotic cardiomyopathy is crucial in developing more accurate diagnostic tools and specific treatments of this condition.
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Affiliation(s)
| | - Suthat Liangpunsakul
- Division of Gastroenterology/Hepatology, Department of Medicine, Indiana University Hospital, 550 University Boulevard, UH 4100, Indianapolis, IN 46202-5149, USA; Roudebush Veterans Administration Medical Center, Indiana University, Indianapolis, IN, USA
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20
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Leithead JA, Rajoriya N, Tehami N, Hodson J, Gunson BK, Tripathi D, Ferguson JW. Non-selective β-blockers are associated with improved survival in patients with ascites listed for liver transplantation. Gut 2015; 64:1111-1119. [PMID: 25281417 DOI: 10.1136/gutjnl-2013-306502] [Citation(s) in RCA: 139] [Impact Index Per Article: 13.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2013] [Accepted: 09/11/2014] [Indexed: 12/14/2022]
Abstract
OBJECTIVE Recent data have suggested that non-selective β-blockers (NSBB) are associated with increased mortality in patients with cirrhosis and refractory ascites. However, other evidence implies that NSBB may be beneficial in this setting by reducing bacterial translocation. Our aim was to determine whether NSBB use was a risk factor for mortality in patients with end-stage chronic liver disease and ascites awaiting liver transplantation. DESIGN This was a single-centre retrospective study of 322 patients with ascites listed January 2007 to July 2011. RESULTS NSBB patients (n=159) and non-NSBB patients (n=163) were comparable with regards to listing model for end-stage liver disease score (p=0.168), frequency of hepatocellular carcinoma (p=0.193) and refractory ascites (35.2% vs. 37.4%, p=0.681). 82 patients died, 221 patients were transplanted and 19 patients were removed from the list during a median follow-up duration of 72 days; the median time to death was 150 and 54 days in the NSBB and non-NSBB groups, respectively. In a multivariate competing risk Cox model, patients on NSBB had reduced mortality compared with propensity risk score-matched non-NSBB patients (HR 0.55; 95% CI 0.32 to 0.95, p=0.032). Similarly, in the subgroup of patients with refractory ascites (n=117), NSBB remained independently associated with less waitlist death (adjusted HR 0.35; 95% CI 0.14 to 0.86, p=0.022). CONCLUSIONS NSBB in patients with ascites and refractory ascites listed for liver transplantation are not detrimental, and instead are associated with reduced waitlist death. Our findings argue that NSBB are safe and may confer benefit in patients with ascites complicating end-stage liver disease.
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Affiliation(s)
- Joanna A Leithead
- Liver Unit, Queen Elizabeth Hospital, Birmingham, UK NIHR Biomedical Research Unit and Centre for Liver Research, University of Birmingham, Birmingham, UK
| | - Neil Rajoriya
- Liver Unit, Queen Elizabeth Hospital, Birmingham, UK
| | - Nadeem Tehami
- Liver Unit, Queen Elizabeth Hospital, Birmingham, UK
| | - James Hodson
- Department of Statistics, Wolfson Building, Queen Elizabeth Hospital, Birmingham, UK
| | - Bridget K Gunson
- Liver Unit, Queen Elizabeth Hospital, Birmingham, UK NIHR Biomedical Research Unit and Centre for Liver Research, University of Birmingham, Birmingham, UK
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21
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Bernsmeier C, Singanayagam A, Patel VC, Wendon J, Antoniades CG. Immunotherapy in the treatment and prevention of infection in acute-on-chronic liver failure. Immunotherapy 2015; 7:641-54. [PMID: 26065379 DOI: 10.2217/imt.15.27] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Chronic liver disease, depicted by gradual destruction and fibrosis of the liver, is a condition with high and probably increasing prevalence worldwide. Its deterioration, acute-on-chronic liver failure (ACLF), is characterized by an in-hospital mortality of up to 65%. Infectious complications are the main precipitants eliciting ACLF and concurrently the main cause of death from ACLF. Patients have a marked susceptibility to bacterial infections, which is thought to arise a consequence of an inadequate immune response to microbial challenge, termed immuneparesis. The pathophysiologic mechanisms remain poorly understood. Treatments aimed at restoring the patients' immune function may prevent onset of ACLF and death from secondary infections. A number of drugs approved for patients with liver disease bear immunomodulatory potential such as albumin, glucocorticoids, N-acetylcysteine. Specific targets have been defined that may lead to development of new immunotherapeutic agents. Here, we summarize the pathophysiology of immuneparesis in ACLF and drug candidates to restore immune function and improve survival in the future.
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Affiliation(s)
- Christine Bernsmeier
- Institute of Liver Studies, King's College Hospital, King's College London, London SE5 9RS, UK
| | - Arjuna Singanayagam
- Institute of Liver Studies, King's College Hospital, King's College London, London SE5 9RS, UK
| | - Vishal C Patel
- Institute of Liver Studies, King's College Hospital, King's College London, London SE5 9RS, UK
| | - Julia Wendon
- Institute of Liver Studies, King's College Hospital, King's College London, London SE5 9RS, UK
| | - Charalambos G Antoniades
- Institute of Liver Studies, King's College Hospital, King's College London, London SE5 9RS, UK.,Section of Hepatology, St Mary's Hospital, Imperial College London, London W2 1NY, UK
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Abstract
OBJECTIVE To investigate the subclinical cardiac morphological and functional modifications in cirrhotic patients according to the stage of liver disease. PATIENTS AND METHODS One hundred and thirteen cirrhotic patients underwent standard Doppler echocardiography and were compared with healthy individuals. Left ventricular (LV) geometry, systolic/diastolic function, and the main hemodynamic parameters were assessed according to current guidelines. RESULTS Cirrhotic patients showed a reduction in the peripheral vascular resistance (PVR), a compensatory hyperdynamic syndrome, and a significant increase in cardiac index (CI), cardiac output (CO), and cardiac work, with a consequent increase in the prevalence of LV hypertrophy and associated diastolic dysfunction (DD). Age (P=0.005) and LV mass index (P=0.03) were the strongest predictors of DD. Even though all the systolic parameters assessed were similar between patients and controls, in patients with refractory ascites, the reduction of the PVR and mean blood pressure was not balanced by a further increase in cardiac work and therefore the CI and CO were supported only by the increase in heart rate. CONCLUSION In cirrhotic patients, DD is strongly related to the increase in LV mass, not related to the stage of the liver disease, and can be correctly detectable only by the use of tissue Doppler imaging. For systolic dysfunction, along with the development and worsening of ascites, CO and CI do not increase further to compensate the continuous reduction of PVR and mean blood pressure, and their maintenance becomes critically dependent on the heart rate, thus suggesting a possible detrimental effect of β-blockers in these patients.
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23
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Mura VL, Tosetti G, Primignani M, Salerno F. Use of non-selective beta blockers in cirrhosis: the evidence we need before closing (or not) the window. World J Gastroenterol 2015; 21:2265-2268. [PMID: 25741132 PMCID: PMC4342901 DOI: 10.3748/wjg.v21.i8.2265] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2014] [Revised: 12/17/2014] [Accepted: 01/30/2015] [Indexed: 02/06/2023] Open
Abstract
Non selective beta blockers (NSBBs) are used in primary and secondary prophylaxis of portal hypertension-related bleeding in patients with cirrhosis. The efficacy of NSBBs treatment is predicted by hemodynamic response in term of reduction of the hepatic venous pressure gradient (HVPG) below 12 mmHg or at least 20% of the basal value. Nevertheless a relevant number of patients who do not achieve this HVPG reduction during NSBBs therapy do not bleed during follow up; this evidence suggests an additional non-hemodynamic advantage of NSBBs treatment to modify the natural history of cirrhosis. Recent studies have questioned the efficacy and safety of NSBBs in patients with advanced stage of liver disease characterized by refractory ascites and/or spontaneous bacterial peritonitis. These studies have suggested the existence of a defined and limited period to modify the natural history of cirrhosis by NSBBs: the "window hypothesis". According with this hypothesis, patients with cirrhosis benefit from the use of NSBBs from the appearance of varices up to the development of an advanced stage of cirrhosis. Indeed, in patients with refractory ascites and/or spontaneous bacterial peritonitis the hemodynamic effects of NSBBs may expose to a high risk of further complications such as renal insufficiency and/or death. Methodological concerns and contrasting results counterbalance the evidence produced up to now on this issue and are the main topic of this editorial.
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Kreisel W, Deibert P, Kupcinskas L, Sumskiene J, Appenrodt B, Roth S, Neagu M, Rössle M, Zipprich A, Caca K, Ferlitsch A, Dilger K, Mohrbacher R, Greinwald R, Sauerbruch T. The phosphodiesterase-5-inhibitor udenafil lowers portal pressure in compensated preascitic liver cirrhosis. A dose-finding phase-II-study. Dig Liver Dis 2015; 47:144-150. [PMID: 25483910 DOI: 10.1016/j.dld.2014.10.018] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2014] [Revised: 10/15/2014] [Accepted: 10/26/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND Phosphodiesterase-5-inhibitors may lower portal pressure. AIMS To investigate the effect of the phosphodiesterase-5-inhibitor udenafil on hepatic and systemic haemodynamics in liver cirrhosis. METHODS In an open-label phase-II-study, patients with liver cirrhosis Child A/B and hepatic venous pressure-gradient ≥ 12 mmHg received 12.5mg/day, 25mg/day, 50mg/day, 75 mg/day (n = 5, each), or 100mg/day (n = 10) udenafil p.o. for one week. On days 0 and 6, hepatic venous pressure-gradient was measured prior to and one hour after drug ingestion. Endpoints were reduction of hepatic venous pressure-gradient from day 0 pre to day 6 post intake and reduction in the acute setting. Pharmacokinetics were measured in the two lowest dosage groups. RESULTS Combining the 75 and 100mg/day groups hepatic venous pressure-gradient reduction after drug intake was 19.9% (p = 0.0006) on day 0. From day 0 pre-dose to day 6 post-dose hepatic venous pressure-gradient decreased by 15.7% (p = 0.040) and in 5/15 patients by ≥ 20% or to <12 mmHg. In the 100mg/day group, mean arterial pressure decreased from 98.9 mmHg by 6.2 mmHg (p = 0.037) from day 0 pre-dose to day 6 post-dose. Heart rates or electrocardiograms were unchanged. Udenafil was eliminated with t1/2 = 25 h. CONCLUSIONS Oral application of 75-100mg of the phosphodiesterase-5-inhibitor udenafil lowers portal pressure in the acute setting by about 20% without relevant systemic cardiovascular side effects.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Karel Caca
- Klinikum Ludwigsburg, Ludwigsburg, Germany
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Kimer N, Feineis M, Møller S, Bendtsen F. Beta-blockers in cirrhosis and refractory ascites: a retrospective cohort study and review of the literature. Scand J Gastroenterol 2015; 50:129-37. [PMID: 25113796 DOI: 10.3109/00365521.2014.948053] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE It is currently discussed if beta-blockers exert harmful effects and increase mortality in patients with cirrhosis and refractory ascites. In this study, we provide an overview of the available literature in this field in combination with a retrospective analysis of 61 patients with cirrhosis and refractory ascites in a tertiary unit. MATERIAL AND METHODS We performed a systematic search of literature in May 2014. In addition, 61 patients with cirrhosis and ascites were identified and followed from development of refractory ascites until death or end of follow-up. RESULTS Fourteen trials (9 trials on propranolol, 1 case-control study and 4 retrospective analyses) were identified. One trial suggested an increased mortality in patients treated with beta-blockers and refractory ascites. The results of the remaining trials were inconclusive. No increase in mortality among beta-blocker-treated patients was found in the present retrospective analysis. CONCLUSIONS Treatment with beta-blockers may increase mortality in patients with cirrhosis and refractory ascites. However, the current evidence is sparse and high-quality studies are warranted to clarify the matter.
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Affiliation(s)
- Nina Kimer
- Gastrounit, Medical Division, Copenhagen University Hospital Hvidovre , Hvidovre , Denmark
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Mandorfer M, Bota S, Schwabl P, Bucsics T, Pfisterer N, Kruzik M, Hagmann M, Blacky A, Ferlitsch A, Sieghart W, Trauner M, Peck-Radosavljevic M, Reiberger T. Nonselective β blockers increase risk for hepatorenal syndrome and death in patients with cirrhosis and spontaneous bacterial peritonitis. Gastroenterology 2014; 146:1680-90.e1. [PMID: 24631577 DOI: 10.1053/j.gastro.2014.03.005] [Citation(s) in RCA: 280] [Impact Index Per Article: 25.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2013] [Revised: 03/07/2014] [Accepted: 03/07/2014] [Indexed: 02/08/2023]
Abstract
BACKGROUND & AIMS Nonselective β blockers (NSBBs) reduce portal pressure and the risk for variceal hemorrhage in patients with cirrhosis. However, development of spontaneous bacterial peritonitis (SBP) in these patients could preclude treatment with NSBBs because of their effects on the circulatory reserve. We investigated the effects of NSBBs in patients with cirrhosis and ascites with and without SBP. METHODS We performed a retrospective analysis of data from 607 consecutive patients with cirrhosis who had their first paracentesis at the Medical University of Vienna from 2006 through 2011. Cox models were calculated to investigate the effect of NSBBs on transplant-free survival time and adjusted for Child-Pugh stage and presence of varices. RESULTS NSBBs increased transplant-free survival in patients without SBP (hazard ratio = 0.75; 95% confidence interval: 0.581-0.968; P = .027) and reduced days of nonelective hospitalization (19.4 days/year for patients on NSBBs vs 23.9 days/year for patients not taking NSBBs). NSBBs had only moderate effects on systemic hemodynamics at patients' first paracentesis. However, at the first diagnosis of SBP, the proportion of hemodynamically compromised patients with systolic arterial pressure <100 mm Hg was higher among those who received NSBBs (38% vs 18% of those not taking NSBBs; P = .002), as was the proportion of patients with arterial pressure <82 mm Hg (64% of those taking NSBBs vs 44% of those not taking NSBBs; P = .006). Among patients with SBP, NSBBs reduced transplant-free survival (hazard ratio = 1.58; 95% confidence interval: 1.098-2.274; P = .014) and increased days of nonelective hospitalization (29.6 days/person-year in patients on NSBBs vs 23.7 days/person-year in those not taking NSBBs). A higher proportion of patients on NSBBs had hepatorenal syndrome (24% vs 11% in those not taking NSBBs; P = .027) and grade C acute kidney injury (20% vs 8% for those not taking NSBBs; P = .021). CONCLUSIONS Among patients with cirrhosis and SBP, NSBBs increase the proportion who are hemodynamically compromised, time of hospitalization, and risks for hepatorenal syndrome and acute kidney injury. They also reduce transplant-free survival. Patients with cirrhosis and SBP should not receive NSBBs.
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Affiliation(s)
- Mattias Mandorfer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Vienna, Austria
| | - Simona Bota
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Vienna, Austria
| | - Philipp Schwabl
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Vienna, Austria
| | - Theresa Bucsics
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Vienna, Austria
| | - Nikolaus Pfisterer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Vienna, Austria
| | - Matthias Kruzik
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Vienna, Austria
| | - Michael Hagmann
- Section for Medical Statistics, Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria
| | - Alexander Blacky
- Clinical Institute of Hospital Hygiene, Vienna General Hospital, Vienna, Austria
| | - Arnulf Ferlitsch
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Vienna, Austria
| | - Wolfgang Sieghart
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Vienna, Austria
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Vienna, Austria
| | - Markus Peck-Radosavljevic
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Vienna, Austria
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Vienna, Austria.
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Affiliation(s)
- Phillip S Ge
- Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, California
| | - Bruce A Runyon
- Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, California.
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Robins A, Bowden A, Watson W, Smith F, Gelson W, Griffiths W. Beta-blockers in cirrhosis patients with refractory ascites. Hepatology 2014; 59:2054-5. [PMID: 23929786 DOI: 10.1002/hep.26676] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2013] [Revised: 07/26/2013] [Accepted: 07/31/2013] [Indexed: 01/05/2023]
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Ge PS, Runyon BA. The changing role of beta-blocker therapy in patients with cirrhosis. J Hepatol 2014; 60:643-53. [PMID: 24076364 DOI: 10.1016/j.jhep.2013.09.016] [Citation(s) in RCA: 92] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2013] [Revised: 09/13/2013] [Accepted: 09/17/2013] [Indexed: 12/11/2022]
Abstract
Cirrhosis is a leading cause of death in the United States and worldwide. Beta-blockers have been established in numerous studies as part of the cornerstone of the medical management of cirrhosis, particularly in the primary and secondary prevention of variceal hemorrhage. However, new evidence has cautioned the use of beta-blockers in patients with end-stage cirrhosis and refractory ascites. In this article, we review the beneficial effects of beta-blocker therapy, the potential harms of aggressive beta-blocker therapy, and provide suggestions regarding the appropriate use of this class of medications in patients with cirrhosis.
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Affiliation(s)
- Phillip S Ge
- Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States
| | - Bruce A Runyon
- Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States.
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Heebøll S, Villadsen GE, Aagaard NK, Grønbæk H, Vilstrup H, Keiding S. Propranolol treatment of portal hypertension in cirrhosis patients is better the higher the untreated pressure: a single-centre prospective experience. Scand J Gastroenterol 2013; 48:969-73. [PMID: 23755897 DOI: 10.3109/00365521.2013.805811] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE To assess the effect of propranolol treatment on the hepatic venous pressure gradient (HVPG) and the relationship between native HVPG and the effect of propranolol in patients with cirrhosis and portal hypertension in a prospective, observational, single-center study. MATERIAL AND METHODS The HVPG was registered prospectively in 124 consecutive cirrhosis patients with and without treatment with propranolol 80 mg daily. Results. 41% of the patients responded to the treatment with the intended reduction of HVPG to <12 mm Hg and/or by >20%. The HVPG reduction was larger for higher native HVPG values (p < 0.001). There was no significant relation between changes in heart rate and changes in HVPG (p = 0.8). CONCLUSIONS The high fraction of hemodynamic non-responders supports the rationale of measuring the HVPG with and without propranolol treatment to assist the clinical assessment and avoid meaningless and potentially harmful treatment. The positive association between a high native HVPG and propranolol-induced HVPG reduction indicates that pharmacological treatment also benefits patients with advanced portal hypertension.
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Affiliation(s)
- Sara Heebøll
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
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Bajaj JS, Ratliff SM, Heuman DM, Lapane KL. Non-selective beta-blockers are not associated with serious infections in veterans with cirrhosis. Aliment Pharmacol Ther 2013; 38:407-14. [PMID: 23786291 PMCID: PMC3725127 DOI: 10.1111/apt.12382] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2013] [Revised: 05/20/2013] [Accepted: 06/03/2013] [Indexed: 12/11/2022]
Abstract
BACKGROUND Studies evaluating outcomes associated with non-selective beta-blockers (NSBB) in cirrhosis have yielded mixed results. A major cause of death in decompensated cirrhosis is infection. AIM To determine the effect of NSBB use on serious infections (requiring hospitalisation) in compensated and decompensated cirrhosis. METHODS Using data from the US Veterans Health Administration from 2001-2009, we identified two cohorts: compensated cirrhotics (n = 12,656) and decompensated cirrhotics (n = 4834). From each cohort, we identified new NSBB users and propensity-matched them 1:1 to non-users (n = 1836 each in compensated users/non-users and n = 1462 each in decompensated users/non-users). They were followed up for serious infections (median time: 3.1 years), death and transplant. We estimated adjusted hazard ratios (HR) and 95% confidence intervals (CI) from Cox regression models. RESULTS Death or transplantation occurred in 0.7% compensated and 2.7% of decompensated patients. Among decompensated cirrhotics, death (P = 0.0061) and transplantation (P = 0.0086) occurred earlier in NSBB users compared with non-users. Serious infections were observed in 4.8% of compensated cirrhotics and in 13.7% of decompensated cirrhotics. There was no difference in the rate of serious infection development in new NSBB users compared with non-users in the compensated (adjusted HR: 0.90, CI: 0.59-1.36) or in the decompensated group (adjusted HR: 1.10, CI: 0.96-1.25). CONCLUSION The use of non-selective beta-blockers in U.S. veterans is not associated with an increased rate of serious infections in compensated or decompensated cirrhosis.
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Affiliation(s)
- J S Bajaj
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire Veterans Affairs Medical Center, Richmond, VA 23249, USA.
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Bunchorntavakul C, Chavalitdhamrong D. Bacterial infections other than spontaneous bacterial peritonitis in cirrhosis. World J Hepatol 2012; 4:158-68. [PMID: 22662285 PMCID: PMC3365435 DOI: 10.4254/wjh.v4.i5.158] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2011] [Revised: 09/08/2011] [Accepted: 04/25/2012] [Indexed: 02/06/2023] Open
Abstract
Cirrhotic patients are immunocompromised with a high risk of infection. Proinflammatory cytokines and hemodynamic circulation derangement further facilitate the development of serious consequences of infections. Other than spontaneous bacterial peritonitis, bacteremia and bacterial infections of other organ systems are frequently observed. Gram-negative enteric bacteria are the most common causative organism. Other bacterial infections, such as enterococci, Vibrio spp., Aeromonas spp., Clostridium spp., Listeria monocytogenes, Plesiomonas shigelloides and Mycobacterium tuberculosis are more prevalent and more virulent. Generally, intravenous third generation cephalosporins are recommended as empirical antibiotic therapy. Increased incidences of gram-positive and drug-resistant organisms have been reported, particularly in hospital-acquired infections and in patients receiving quinolones prophylaxis. This review focuses upon epidemiology, microbiology, clinical features and treatment of infections in cirrhosis other than spontaneous bacterial peritonitis, including pathogen-specific and liver disease-specific issues.
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Affiliation(s)
- Chalermrat Bunchorntavakul
- Chalermrat Bunchorntavakul, Division of Gastroenterology and Hepatology, Rajavithi Hospital, College of Medicine, Rangsit University, Bangkok 12000, Thailand
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Abstract
Cirrhosis is the leading cause of portal hypertension worldwide, with the development of bleeding gastroesophageal varices being one of the most life-threatening consequences. Endoscopy plays an indispensible role in the diagnosis, staging, and prophylactic or active management of varices. With the expected future refinements in endoscopic technology, capsule endoscopy may one day replace traditional gastroscopy as a diagnostic modality, whereas endoscopic ultrasound may more precisely guide interventional therapy for gastric varices.
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Effect of propranolol on the relationship between QT interval and vagal modulation of heart rate variability in cirrhotic patients awaiting liver transplantation. Transplant Proc 2011; 43:1654-9. [PMID: 21693252 DOI: 10.1016/j.transproceed.2011.02.017] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2010] [Revised: 01/13/2011] [Accepted: 02/02/2011] [Indexed: 12/13/2022]
Abstract
BACKGROUND Prolonged corrected QT (QT(c)) interval and vagal dysfunction are common occurrences in liver cirrhosis and are determinants of mortality in patients with chronic liver disease. We evaluated whether propranolol can affect the relationship between QT(c) interval and cardiac vagal control of heart rate variability (HRV) in cirrhotic patients awaiting liver transplantation. METHODS We compared 50 cirrhotic patients (M/F = 43/7, 52.6 ± 8.4 years, Child-Pugh class A/B/C: 9/24/17) receiving propranolol with a sex-, age-, and liver disease severity-matched control group of 50 patients (M/F = 43/7, 52.0 ± 8.3 year, Child-Pugh class A/B/C: 9/24/17) not receiving propranolol. Among the parameters evaluated were QT(c) interval and cardiac vagal indices of HRV, including the root mean square of successive differences in R-R intervals (RMSSD); spectral power in the high-frequency range (HF); standard deviation (SD)1 in Poincare plot; and sample entropy. Correlations between QT(c) interval and vagal indices of HRV were analyzed. RESULTS The mean duration of preoperative propranolol treatment in the propranolol group was 19.4 ± 24.7 months. QT(c) interval was significantly lower, whereas RMSSD, HF, SD1, and sample entropy were significantly higher in the propranolol group than in the control group. Correlation coefficients between QT(c) interval and RMSSD, HF, SD1, and sample entropy were higher in the propranolol group than in the control group. CONCLUSIONS The prolonged QT(c) interval observed in cirrhotic patients may be reduced by propranolol administration, an effect attributable to improved vagal cardiac modulation. These findings suggest that propranolol may have a beneficial effect on perioperative mortality in cirrhotic patients awaiting liver transplantation.
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Angeli P. β-blockers and refractory ascites in cirrhosis: the message of a team of true scientists. J Hepatol 2011; 55:743-4. [PMID: 21396970 DOI: 10.1016/j.jhep.2011.02.026] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2011] [Accepted: 02/28/2011] [Indexed: 01/17/2023]
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Bonnel AR, Bunchorntavakul C, Reddy KR. Immune dysfunction and infections in patients with cirrhosis. Clin Gastroenterol Hepatol 2011; 9:727-38. [PMID: 21397731 DOI: 10.1016/j.cgh.2011.02.031] [Citation(s) in RCA: 276] [Impact Index Per Article: 19.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2010] [Revised: 02/22/2011] [Accepted: 02/27/2011] [Indexed: 02/06/2023]
Abstract
Patients with cirrhosis are immunocompromised and susceptible to infections. Although detection and treatment of spontaneous bacterial peritonitis (SBP) have improved, overall survival rates have not increased greatly in recent decades-infection still increases mortality 4-fold among patients with cirrhosis. Hospitalized patients with cirrhosis have the highest risk of developing infections, especially patients with gastrointestinal (GI) hemorrhage. Bacterial infections occur in 32% to 34% of patients with cirrhosis who are admitted to the hospital and 45% of patients with GI hemorrhage. These rates are much higher than the overall rate of infection in hospitalized patients (5%-7%). The most common are SBP (25% of infections), urinary tract infection (20%), and pneumonia (15%). Bacterial overgrowth and translocation from the GI tract are important steps in the pathogenesis of SBP and bacteremia-these processes increase levels of endotoxins and cytokines that induce the inflammatory response and can lead to septic shock, multiorgan dysfunction, and death. A number of other bacterial and fungal pathogens are more common and virulent in patients with cirrhosis than in the overall population. We review the pathogenesis of infections in these patients, along with diagnostic and management strategies.
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Affiliation(s)
- Alexander R Bonnel
- Division of Gastroenterology/Hepatology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
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Thevenot T, Cervoni JP, Di Martino V. [Beta-blockers in portal hypertension: Unexpected limitations!]. Presse Med 2011; 40:227-229. [PMID: 21093210 DOI: 10.1016/j.lpm.2010.10.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2010] [Accepted: 10/04/2010] [Indexed: 11/23/2022] Open
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Garcia-Pagán JC. Portal hypertension: Nonselective β-blockers in patients with refractory ascites. Nat Rev Gastroenterol Hepatol 2011; 8:10-1. [PMID: 21119614 DOI: 10.1038/nrgastro.2010.185] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/08/2022]
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