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1
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Yang JX, Peng YM, Zeng HT, Lin XM, Xu ZL. Drainage of ascites in cirrhosis. World J Hepatol 2024; 16:1245-1257. [PMID: 39351514 PMCID: PMC11438587 DOI: 10.4254/wjh.v16.i9.1245] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 07/20/2024] [Accepted: 07/29/2024] [Indexed: 09/23/2024] Open
Abstract
For cirrhotic refractory ascites, diuretics combined with albumin and vasoactive drugs are the first-line choice for ascites management. However, their therapeutic effects are limited, and most refractory ascites do not respond to medication treatment, necessitating consideration of drainage or surgical interventions. Consequently, numerous drainage methods for cirrhotic ascites have emerged, including large-volume paracentesis, transjugular intrahepatic portosystemic shunt, peritoneovenous shunt, automated low-flow ascites pump, cell-free and concentrated ascites reinfusion therapy, and peritoneal catheter drainage. This review introduces the advantages and disadvantages of these methods in different aspects, as well as indications and contraindications for this disease.
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Affiliation(s)
- Jia-Xing Yang
- Department of Gastroenterology, The Second Clinical Medical College, Jinan University, Shenzhen 518000, Guangdong Province, China
| | - Yue-Ming Peng
- Department of Nursing, Shenzhen People's Hospital, The Second Clinical Medical College, Jinan University, Shenzhen 518000, Guangdong Province, China
| | - Hao-Tian Zeng
- Department of Gastroenterology, The Second Clinical Medical College, Jinan University, Shenzhen 518000, Guangdong Province, China
| | - Xi-Min Lin
- Department of Gastroenterology, The Second Clinical Medical College, Jinan University, Shenzhen 518000, Guangdong Province, China
| | - Zheng-Lei Xu
- Department of Gastroenterology, Shenzhen People's Hospital, The Second Clinical Medical College, Jinan University, Shenzhen 518000, Guangdong Province, China.
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2
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Mendez-Guerrero O, Carranza-Carrasco A, Chi-Cervera LA, Torre A, Navarro-Alvarez N. Optimizing nutrition in hepatic cirrhosis: A comprehensive assessment and care approach. World J Gastroenterol 2024; 30:1313-1328. [PMID: 38596498 PMCID: PMC11000076 DOI: 10.3748/wjg.v30.i10.1313] [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: 11/28/2023] [Revised: 01/23/2024] [Accepted: 02/25/2024] [Indexed: 03/14/2024] Open
Abstract
Cirrhosis is considered a growing cause of morbidity and mortality, which represents a significant public health problem. Currently, there is no effective treatment to reverse cirrhosis. Treatment primarily centers on addressing the underlying liver condition, monitoring, and managing portal hypertension-related complications, and evaluating the potential for liver transplantation in cases of decompensated cirrhosis, marked by rapid progression and the emergence of complications like variceal bleeding, hepatic encephalopathy, ascites, malnutrition, and more. Malnutrition, a prevalent complication across all disease stages, is often underdiagnosed in cirrhosis due to the complexities of nutritional assessment in patients with fluid retention and/or obesity, despite its crucial impact on prognosis. Increasing emphasis has been placed on the collaboration of nutritionists within hepatology and Liver transplant teams to deliver comprehensive care, a practice that has shown to improve outcomes. This review covers appropriate screening and assessment methods for evaluating the nutritional status of this population, diagnostic approaches for malnutrition, and context-specific nutrition treatments. It also discusses evidence-based recommendations for supplementation and physical exercise, both essential elements of the standard care provided to cirrhotic patients.
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Affiliation(s)
- Osvely Mendez-Guerrero
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, Mexico
| | - Anaisa Carranza-Carrasco
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, Mexico
| | - Luis Alberto Chi-Cervera
- Clínica de Especialidades Gastrointestinales y Hepáticas, Hospital Star Medica, Merida 97133, Yucatan, Mexico
| | - Aldo Torre
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, Mexico
| | - Nalu Navarro-Alvarez
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, Mexico
- Molecular Biology, Universidad Panamericana School of Medicine, Campus México, Mexico City 03920, Mexico
- Department of Surgery, University of Colorado Anschutz Medical Campus, Denver, CO 80045, United States
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3
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Ahmadi S, Rohani S. Overcoming the Hydrophobic Nature of Zinc Phenylacetate Through Co-Crystallization with Isonicotinamide. J Pharm Sci 2023; 112:1929-1938. [PMID: 36893962 DOI: 10.1016/j.xphs.2023.02.026] [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: 11/23/2022] [Revised: 02/28/2023] [Accepted: 02/28/2023] [Indexed: 03/09/2023]
Abstract
Zinc phenylacetate (Zn-PA), a substitute for sodium phenylacetate as an ammonia-scavenging drug is hydrophobic, which poses problems for drug dissolution and solubility. We were able to co-crystallize the zinc phenylacetate with isonicotinamide (INAM) and produce a novel crystalline compound (Zn-PA-INAM). The single crystal of this new crystal was obtained, and its structure is reported here for the first time. Zn-PA-INAM was characterized computationally by ab initio, Hirshfeld calculations, CLP-PIXEL lattice energy calculation, and BFDH morphology analysis, and experimentally by PXRD, Sc-XRD, FTIR, DSC, and TGA analyses. Structural and vibrational analyses showed a major modification in intermolecular interaction of Zn-PA-INAM compared to Zn-PA. The dispersion-based pi-stacking in Zn-PA is replaced by coulomb-polarization effect of hydrogen bonds. As a result, Zn-PA-INAM is hydrophilic, improving the wettability and powder dissolution of the target compound in an aqueous solution. Morphology analysis revealed, unlike Zn-PA, Zn-PA-INAM has polar groups exposed on its prominent crystalline faces, reducing the hydrophobicity of the crystal. The shift in average water droplet contact angle from 128.1° (Zn-PA) to 27.1° (Zn-PA-INAM) is strong evidence of a marked decrease in hydrophobicity of the target compound. Finally, HPLC was used to obtain the dissolution profile and solubility of Zn-PA-INAM compared to Zn-PA.
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Affiliation(s)
- Soroush Ahmadi
- Chemical and Biochemical Engineering, Western University, London, Ontario, N6A 5B9, Canada
| | - Sohrab Rohani
- Chemical and Biochemical Engineering, Western University, London, Ontario, N6A 5B9, Canada.
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Pashayee-Khamene F, Hajimohammadebrahim-Ketabforoush M, Saber-Firoozi M, Hatami B, Naseri K, Karimi S, Ahmadzadeh S, Kord H, Saadati S, Hekmatdoost A. Salt consumption and mortality risk in cirrhotic patients: results from a cohort study. J Nutr Sci 2022; 11:e99. [PMID: 36405096 PMCID: PMC9672831 DOI: 10.1017/jns.2022.69] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Accepted: 07/29/2022] [Indexed: 11/10/2022] Open
Abstract
Since conducting a long-term randomised clinical trial is not logical and feasible to find the optimum dosage of salt intake in patients with cirrhosis, cohort studies are the best design to assess the long-term effects of dietary salt on the survival of cirrhotic patients. This cohort study aimed to evaluate the association between dietary intake of salt and mortality risk in cirrhotic patients. The present study was designed as a cohort in three referral hospitals in Iran in 2018. One hundred and twenty-one patients aged between 20 and 70 years with established cirrhosis were recruited. Dietary intakes, demographic data and disease severity were evaluated at the baseline. Participants were followed up annually. Crude survival was greater in patients with low-to-moderate salt consumption rather than in those with high consumption, and in non-consumers [34⋅26 (95 % CI 33⋅04, 35⋅49) v. 30⋅41 (95 % CI 27⋅13, 33⋅69) v. 32⋅72 (95 % CI 30⋅63, 34⋅80), P = 0⋅028; log-rank test]. Using the Cox proportional hazard model, it was shown that the risk of mortality in the high-salt consumption category was approximately 126 % higher than that of the reference category (non-consumers) [HR value 2⋅26, (95 % CI 0⋅91, 5⋅63)], while this risk for the low-to-moderate consumption group was about 28 % lower than the reference category [HR value 0⋅72, (95 % CI 0⋅26, 1⋅99), P-trend = 0⋅04]. In conclusion, a high daily dietary intake of salt might increase the rate of mortality and moderate salt restriction (instead of elimination of salt) decreases the risk of death.
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Affiliation(s)
- Fereshteh Pashayee-Khamene
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Melika Hajimohammadebrahim-Ketabforoush
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahdi Saber-Firoozi
- Digestive Disease Research Center, Digestive Disease Research Institute, Tehran University of Medical Science, Tehran, Iran
| | - Behzad Hatami
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Kaveh Naseri
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sara Karimi
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Saleheh Ahmadzadeh
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamed Kord
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Saeede Saadati
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Azita Hekmatdoost
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Nobbe AM, McCurdy HM. Management of the Adult Patient with Cirrhosis Complicated by Ascites. Crit Care Nurs Clin North Am 2022; 34:311-320. [DOI: 10.1016/j.cnc.2022.04.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Hatami B, Asadi F, Bayani A, Zali MR, Kavousi K. Machine learning-based system for prediction of ascites grades in patients with liver cirrhosis using laboratory and clinical data: design and implementation study. Clin Chem Lab Med 2022; 60:1946-1954. [PMID: 35607284 DOI: 10.1515/cclm-2022-0454] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Accepted: 05/06/2022] [Indexed: 11/15/2022]
Abstract
OBJECTIVES The aim of the study was to implement a non-invasive model to predict ascites grades among patients with cirrhosis. METHODS In the present study, we used modern machine learning (ML) methods to develop a scoring system solely based on routine laboratory and clinical data to help physicians accurately diagnose and predict different degrees of ascites. We used ANACONDA3-5.2.0 64 bit, free and open-source platform distribution of Python programming language with numerous modules, packages, and rich libraries that provide various methods for classification problems. Through the 10-fold cross-validation, we employed three common learning models on our dataset, k-nearest neighbors (KNN), support vector machine (SVM), and neural network classification algorithms. RESULTS According to the data received from the research institute, three types of data analysis have been performed. The algorithms used to predict ascites were KNN, cross-validation (CV), and multilayer perceptron neural networks (MLPNN), which achieved an average accuracy of 94, 91, and 90%, respectively. Also, in the average accuracy of the algorithms, KNN had the highest accuracy of 94%. CONCLUSIONS We applied well-known ML approaches to predict ascites. The findings showed a strong performance compared to the classical statistical approaches. This ML-based approach can help to avoid unnecessary risks and costs for patients with acute stages of the disease.
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Affiliation(s)
- Behzad Hatami
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Farkhondeh Asadi
- Department of Health Information Technology and Management, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Azadeh Bayani
- Department of Health Information Technology and Management, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Kaveh Kavousi
- Laboratory of Complex Biological Systems and Bioinformatics (CBB), Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran
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Cisterna chyli as an optimal marker of tolvaptan response in severe cirrhotic ascites. Sci Rep 2022; 12:8124. [PMID: 35581243 PMCID: PMC9114325 DOI: 10.1038/s41598-022-11889-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Accepted: 05/03/2022] [Indexed: 12/13/2022] Open
Abstract
For patients with cirrhosis, no definitive predictor of the efficacy and prognosis of tolvaptan treatment exists. We assessed the cisterna chyli's utility as an optimal marker. We retrospectively enrolled 172 patients with cirrhosis. The effect of tolvaptan was evaluated using post-treatment survival time. The overall response to tolvaptan was 52.3%. The median cisterna chyli diameter was 4.1 mm. Of 172 patients, 100 were included in the pilot set and 72 in the validation set. According to the Youden index, the cisterna chyli diameter's cutoff value was 4 mm, with a sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio of 92%, 83%, 86%, 91%, 5.43, and 0.09, respectively, in the pilot set. The area under the curve of the cisterna chyli diameter for evaluating tolvaptan's effect was 0.911 and 0.988 in the pilot and validation sets, respectively. During multivariate analysis, cisterna chyli narrowing and furosemide treatment were significant predictive factors for tolvaptan's insufficient effect. Cumulative liver transplantation-free survival rates were significantly higher in patients with cisterna chyli dilatation than in those without (p = 0.028). Our findings suggest a strong association of cisterna chyli with tolvaptan treatment response in patients with cirrhosis and hepatic edema.
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8
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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.
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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
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9
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Yatsuhashi H, Sano H, Hirano T, Shibasaki Y. Real-world hospital mortality of liver cirrhosis inpatients in Japan: a large-scale cohort study using a medical claims database: Prognosis of liver cirrhosis. Hepatol Res 2021; 51:682-693. [PMID: 33710718 DOI: 10.1111/hepr.13635] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Revised: 02/08/2021] [Accepted: 02/23/2021] [Indexed: 12/13/2022]
Abstract
AIM Prognosis of liver cirrhosis patients is poor when ascites is present and liver function is impaired, but such up-to-date information from a large-scale, real-world setting is limited in Japan. We aimed to investigate the hospital mortality of Japanese liver cirrhosis inpatients. METHODS This retrospective cohort study included data on liver cirrhosis inpatients between January 2011 and September 2018 extracted from an administrative claims database. The outcome was in-hospital mortality. The 1- and 3-year cumulative survival rates were examined for liver cirrhosis etiology, Child-Pugh classification, or ascites presence/absence using Kaplan-Meier analysis. The survival up to 1 year for tolvaptan prescription/nonprescription was examined. RESULTS We analyzed the data of 57 769 inpatients. Survival rates did not substantially differ among etiologies, with a better prognosis for alcohol etiology and poorer prognosis for hepatitis C virus. According to the Child-Pugh classification, the 1- and 3-year survival rates were 90.2% and 75.3% for grade A, 73.5% and 53.9% for grade B, and 41.9% and 28.9% for grade C, respectively. Patients without ascites had a higher survival rate (83.2% and 67.0% at 1 and 3 years, respectively) than those with ascites (51.9% and 36.3%, respectively). Based on examining matched patients with ascites using a propensity score, prognosis was poor in general but was better at 6 months (58.1%) or similar at 1 year (47.1%) in patients prescribed tolvaptan compared to those not prescribed tolvaptan (54.8% and 47.5%, respectively). CONCLUSIONS Poorer prognosis was suggested in inpatients with cirrhosis who had a worse Child-Pugh grade and ascites.
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Affiliation(s)
| | - Hiromi Sano
- Medical Affairs, Otsuka Pharmaceutical Co., Ltd., Osaka, Japan
| | - Takahiro Hirano
- Medical Affairs, Otsuka Pharmaceutical Co., Ltd., Tokyo, Japan
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10
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Pinchot JW, Kalva SP, Majdalany BS, Kim CY, Ahmed O, Asrani SK, Cash BD, Eldrup-Jorgensen J, Kendi AT, Scheidt MJ, Sella DM, Dill KE, Hohenwalter EJ. ACR Appropriateness Criteria® Radiologic Management of Portal Hypertension. J Am Coll Radiol 2021; 18:S153-S173. [PMID: 33958110 DOI: 10.1016/j.jacr.2021.02.013] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Accepted: 02/10/2021] [Indexed: 12/17/2022]
Abstract
Cirrhosis is a heterogeneous disease that cannot be studied as a single entity and is classified in two main prognostic stages: compensated and decompensated cirrhosis. Portal hypertension, characterized by a pathological increase of the portal pressure and by the formation of portal-systemic collaterals that bypass the liver, is the initial and main consequence of cirrhosis and is responsible for the majority of its complications. A myriad of treatment options exists for appropriately managing the most common complications of portal hypertension, including acute variceal bleeding and refractory ascites. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.
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Affiliation(s)
| | - Sanjeeva P Kalva
- Panel Chair, Massachusetts General Hospital, Boston, Massachusetts, Chief, Division of Interventional Radiology, Massachusetts General Hospital
| | | | - Charles Y Kim
- Panel Vice-Chair, Duke University Medical Center, Durham, North Carolina, Chief, Division of Interventional Radiology, Duke University Medical Center
| | | | - Sumeet K Asrani
- Baylor University Medical Center, Dallas, Texas, American Association for the Study of Liver Diseases
| | - Brooks D Cash
- University of Texas Health Science Center at Houston and McGovern Medical School, Houston, Texas, American Gastroenterological Association
| | - Jens Eldrup-Jorgensen
- Tufts University School of Medicine, Boston, Massachusetts, Society for Vascular Surgery
| | - A Tuba Kendi
- Mayo Clinic, Rochester, Minnesota, Director of Nuclear Medicine Therapy at Mayo Clinic Rochester
| | | | | | - Karin E Dill
- Specialty Chair, Emory University Hospital, Atlanta, Georgia
| | - Eric J Hohenwalter
- Specialty Chair, Froedtert & The Medical College of Wisconsin, Milwaukee, Wisconsin, Chair, FMLH credentials committee, Division chief of IR at Medical College of Wisconsin
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11
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Atsukawa M, Tsubota A, Takaguchi K, Toyoda H, Iwasa M, Ikegami T, Chuma M, Nozaki A, Uojima H, Hiraoka A, Fukunishi S, Yokohama K, Tada T, Kato K, Abe H, Tani J, Okubo H, Watanabe T, Hattori N, Tsutsui A, Senoh T, Yoshida Y, Okubo T, Itokawa N, Nakagawa-Iwashita A, Kondo C, Arai T, Michitaka K, Iio E, Kumada T, Tanaka Y, Takei Y, Iwakiri K. Analysis of factors associated with the prognosis of cirrhotic patients who were treated with tolvaptan for hepatic edema. J Gastroenterol Hepatol 2020; 35:1229-1237. [PMID: 31881554 DOI: 10.1111/jgh.14965] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2019] [Revised: 11/26/2019] [Accepted: 12/22/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIM The prognosis of cirrhotic patients with hepatic edema is poor. Although several short-term predictors of tolvaptan (novel diuretic agent) treatment for such patients have been reported, the factors related to long-term survival are still unclear. METHODS Among 459 patients with hepatic edema enrolled in a retrospective, multicenter collaborative study, we analyzed 407 patients who received tolvaptan. RESULTS Patients consisted of 266 men and 141 women, with the median age of 68 years (range, 28-93 years). The frequency of short-term responders to tolvaptan was 59.7% (243/407). In the Cox regression analysis, short-term response to tolvaptan, low average dosages of furosemide and spironolactone during tolvaptan treatment, Child-Pugh classification A and B, and absence of hepatocellular carcinoma were independent factors contributed to 1-year survival. The 1-year and long-term cumulative survival rates in short-term responders were significantly higher than those in non-responders (P = 0.011 and 0.010, respectively). Using a receiver operating characteristic curve analysis, the optimal cut-off values of average daily dosages of furosemide and spironolactone for predicting 1-year survival were 19 and 23 mg/day, respectively. The long-term cumulative survival rates in patients who received a mean dosage of spironolactone < 23 mg/day during tolvaptan treatment were significantly higher than those receiving a mean dosage of ≥ 23 mg/day (P = 0.001). CONCLUSIONS The present study suggests that the short-term response to tolvaptan and low dosages of conventional diuretics during tolvaptan treatment might improve the 1-year and long-term survival rates in cirrhotic patients with hepatic edema.
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Affiliation(s)
- Masanori Atsukawa
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Akihito Tsubota
- Core Research Facilities, The Jikei University School of Medicine, Tokyo, Japan
| | - Koichi Takaguchi
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Motoh Iwasa
- Department of Gastroenterology and Hepatology, Mie University School of Medicine, Tsu, Mie, Japan
| | - Tadashi Ikegami
- Tokyo Medical University Ibaraki Medical Center, Inashiki, Ibaraki, Japan
| | - Makoto Chuma
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Akito Nozaki
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Haruki Uojima
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
| | - Atsushi Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Shinya Fukunishi
- Second Department of Internal Medicine, Osaka Medical College, Osaka, Japan
| | - Keisuke Yokohama
- Second Department of Internal Medicine, Osaka Medical College, Osaka, Japan
| | - Toshifumi Tada
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Keizo Kato
- Division of Gastroenterology and Hepatology, Shinmatusdo Central General Hospital, Matsudo, Japan
| | - Hiroshi Abe
- Division of Gastroenterology and Hepatology, Shinmatusdo Central General Hospital, Matsudo, Japan
| | - Joji Tani
- Department of Internal Medicine, Yashima General Hospital, Takamatsu, Japan
| | - Hironao Okubo
- Department of Gastroenterology, Juntendo Nerima University Hospital, Tokyo, Japan
| | - Tsunamasa Watanabe
- Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Nobuhiro Hattori
- Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Akemi Tsutsui
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Tomonori Senoh
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Yuji Yoshida
- Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan
| | - Tomomi Okubo
- Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan
| | - Norio Itokawa
- Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan
| | - Ai Nakagawa-Iwashita
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Chisa Kondo
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Taeang Arai
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Kojiro Michitaka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Etsuko Iio
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan
| | - Takashi Kumada
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Yasushito Tanaka
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan
| | - Yoshiyuki Takei
- Department of Gastroenterology and Hepatology, Mie University School of Medicine, Tsu, Mie, Japan
| | - Katsuhiko Iwakiri
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
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12
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Hingwala J, Whitlock R, Dunsmore S, Armstrong S, Tangri N, Komenda P. Peritoneal Dialysis Catheters to Treat Refractory Non-Malignant Ascites. Perit Dial Int 2020; 37:481-482. [DOI: 10.3747/pdi.2016.00282] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Refractory non-malignant ascites is associated with significant morbidity. Serial, large-volume paracentesis is a common treatment. Tunneled peritoneal dialysis (PD) catheters are an effective treatment for refractory malignant ascites, but there are limited data on complications and effectiveness for non-malignant ascites. We reviewed all 13 PD catheter insertions between 2010 - 2015 for this indication at our center. The median catheter survival time was 146 days. No complications occurred during catheter insertion, and no mechanical complications occurred after catheter insertion. One case of peritonitis developed over 217 catheter months. Peritoneal dialysis catheters may be a safe and effective option to manage refractory non-malignant ascites. Prospective, randomized trials are needed to better evaluate potential risks and benefits.
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Affiliation(s)
- Jay Hingwala
- Section of Nephrology Department of Medicine, University of Manitoba Winnipeg, Canada
- Health Sciences Center Winnipeg, Canada
| | - Reid Whitlock
- Chronic Disease Innovation Centre Seven Oaks General Hospital, Winnipeg, Canada
| | - Sara Dunsmore
- Section of Nephrology Department of Medicine, University of Manitoba Winnipeg, Canada
- Chronic Disease Innovation Centre Seven Oaks General Hospital, Winnipeg, Canada
| | - Sean Armstrong
- Section of Nephrology Department of Medicine, University of Manitoba Winnipeg, Canada
- Chronic Disease Innovation Centre Seven Oaks General Hospital, Winnipeg, Canada
| | - Navdeep Tangri
- Section of Nephrology Department of Medicine, University of Manitoba Winnipeg, Canada
- Chronic Disease Innovation Centre Seven Oaks General Hospital, Winnipeg, Canada
| | - Paul Komenda
- Section of Nephrology Department of Medicine, University of Manitoba Winnipeg, Canada
- Chronic Disease Innovation Centre Seven Oaks General Hospital, Winnipeg, Canada
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Abstract
Ascites occurs in up to 70% of patients during the natural history of cirrhosis. Management of uncomplicated ascites includes sodium restriction and diuretic therapy, whereas that for refractory ascites (RA) is regular large-volume paracentesis with transjugular intrahepatic portosystemic shunt being offered in appropriate patients. Renal impairment occurs in up to 50% of patients with RA with type 1 hepatorenal syndrome (HRS) being most severe. Liver transplant remains the definitive treatment of eligible candidates with HRS, whereas combined liver and kidney transplant should be considered in patients requiring dialysis for more than 4 to 6 weeks or those with underlying chronic kidney disease.
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14
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Role of Transjugular Intrahepatic Portosystemic Shunt in the Management of Portal Hypertension: Review and Update of the Literature. Clin Liver Dis 2019; 23:737-754. [PMID: 31563220 DOI: 10.1016/j.cld.2019.07.004] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Transjugular intrahepatic portosystemic shunt (TIPS) is a well-established procedure used in the management of complications of portal hypertension. Although the most robust evidence supports the use of TIPS as salvage therapy in variceal hemorrhage, secondary prophylaxis of variceal bleeding, and treatment of refractory ascites, there is also data to suggest its efficacy in other indications such as hepatic hydrothorax, hepatorenal syndrome, and Budd-Chiari syndrome. Recent literature also suggests that TIPS may improve survival for certain subpopulations if placed early after variceal bleeding. This article provides an updated evidence-based review of the indications for TIPS. Outcomes, complications, and adequate patient selection are also discussed.
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15
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Robinson G. How to care for patients undergoing paracentesis for the drainage of ascites. Nurs Stand 2019; 35:e11344. [PMID: 31657173 DOI: 10.7748/ns.2019.e11344] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/25/2019] [Indexed: 11/09/2022]
Abstract
RATIONALE AND KEY POINTS Ascites is the excessive accumulation of extracellular fluid within the peritoneal cavity, which usually develops as a result of cirrhosis of the liver. Paracentesis is the procedure for removing ascitic fluid from the transabdominal peritoneal cavity via a temporary ascitic drain. This article aims to support nurses in providing safe and effective care for patients undergoing paracentesis. • Paracentesis is used to reduce intra-abdominal pressure and to relieve the symptoms of abdominal ascites, such as severe abdominal distention, pain and dyspnoea (difficulty breathing). The removal of at least 5L of ascitic fluid is considered large-volume paracentesis.• The role of the nurse is usually to monitor the patient throughout the procedure, administer treatment as directed by the medical team and, depending on local policy, remove the drain at the end of the procedure.• Knowledge of the benefits and risks of this procedure is essential to provide safe, evidence-based care for patients undergoing paracentesis. REFLECTIVE ACTIVITY: 'How to' articles can help to update your practice and ensure it remains evidence-based. Apply this article to your practice. Reflect on and write a short account of: 1. How reading this article will change your practice in caring for patients undergoing paracentesis.2. How this article could be used to educate patients who are due to undergo paracentesis.
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Affiliation(s)
- Grace Robinson
- Acute Medicine, Northern General Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, South Yorkshire, England
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16
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Abdolrazaghnejad A, Rajabpour-Sanati A, Rastegari-Najafabadi H, Ziaei M, Pakniyat A. The Role of Ultrasonography in Patients Referring to the Emergency Department with Acute Abdominal Pain. ADVANCED JOURNAL OF EMERGENCY MEDICINE 2019; 3:e43. [PMID: 31633098 PMCID: PMC6789065 DOI: 10.22114/ajem.v0i0.152] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
CONTEXT Acute abdominal pain is a common clinical problem in emergency and non-emergency cases accounting for 5 to 10% of all referrals to the emergency department. Studies have indicated that these widely differentiated diagnoses are common to these complaints. Considering the high prevalence of this complaint in the patients and the wide range of its differential diagnosis, this review study was designed and evaluated aiming at investigating the causes of acute abdominal pain with a focus on assessing the position of ultrasound as a diagnostic tool in the emergency department. EVIDENCE ACQUISITION This article was conducted as a narrative review of selected articles from 2005 through 2019. By comparing them, a comprehensive review of ultrasound role was conducted in patients with acute abdominal pain referring to the emergency department. RESULTS In this review study, we attempted to use the articles of the clinical approach, the required laboratory tests, the disadvantages and advantages of each imaging technique, the differential diagnosis for acute abdominal pain according to the location of the pain, and the position of ultrasound as a diagnostic aid tool. Eventually, the proposed protrusion will be considered in dealing with a patient with acute abdominal pain. CONCLUSION Regarding the wide range of causes providing multiple differential diagnosis, as well as the limited time of the health team in the emergency department for diagnostic and therapeutic measures, particularly in time-sensitive clinical conditions, ultrasound offered by emergency medicine specialists as a diagnostic aid is considered to improve the overall diagnosis and treatment of patients, thereby reducing complications.
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Affiliation(s)
- Ali Abdolrazaghnejad
- Department of Emergency Medicine, Khatam-Al-Anbia Hospital, Zahedan University of Medical Sciences, Zahedan, Iran
| | | | - Hojjat Rastegari-Najafabadi
- Department of Emergency Medicine, Khatam-Al-Anbia Hospital, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Maryam Ziaei
- Department of Emergency Medicine, Khatam-Al-Anbia Hospital, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Abdolghader Pakniyat
- Department of Emergency Medicine, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
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17
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Abstract
Portal hypertension, a consequence of end-stage liver disease and liver cirrhosis can lead to significant morbidity and mortality for patients through abnormal fluid accumulation as well as the formation of portosystemic shunts and varices. Treatment of the sequelae of portal hypertension can be achieved through endovascular management by referral to an interventional radiologist on an outpatient or emergent basis as required. Current techniques include the placement of peritoneovenous shunts and tunneled peritoneal drains, the creation of transjugular intrahepatic portosystemic shunts, or the obliteration of shunts via balloon-occluded retrograde transvenous obliteration (BRTO). In addition, newer procedural techniques utilizing vascular plugs and coils have reduced risks of the traditional BRTO procedure. Modified-BRTO procedures, known as plug-assisted and coil-assisted retrograde transvenous obliteration (PARTO and CARTO, respectively) have become the standard of care at many institutions for the treatment of gastric varices and portosystemic shunt-induced hepatic encephalopathy. This review examines the most recent literature of the management of portal hypertension by interventional radiologists, evaluating treatment options as well as the clinical and technical outcomes of TIPS, peritoneovenous shunts, tunneled peritoneal drains, BRTOs, and modified-BRTOs as well as future directions in the development of procedural techniques.
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Neong SF, Adebayo D, Wong F. An update on the pathogenesis and clinical management of cirrhosis with refractory ascites. Expert Rev Gastroenterol Hepatol 2019; 13:293-305. [PMID: 30791777 DOI: 10.1080/17474124.2018.1555469] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Ascites commonly complicates cirrhosis, becoming refractory to treatment with diuretics and sodium restriction in approximately 10% of patients. Pathogenesis of refractory ascites (RA) is multifactorial, the common final pathway being renal hypoperfusion and avid sodium retention. Refractory ascites has a negative prognostic implication in the natural history of cirrhosis. Management of RA include sodium restriction and regular large volume paracentesis (LVP) with albumin infusions, preventing paracentesis-induced circulatory dysfunction. In appropriate setting, transjugular intrahepatic porto-systemic shunt (TIPS) can be considered. Ascites clearance with TIPS can lead to nutritional improvement, avoiding sarcopenia. Liver transplantation (LT) remains the definitive treatment for eligible candidates. Areas covered: Our review summarizes current updates on pathogenesis and clinical management of RA including potential future therapeutic options such as the automated slow-flow ascites pump, chronic outpatient albumin infusion and cell-free and concentrated ascites reinfusion therapy. Expert commentary: Standard of care in patients with RA include LVP with albumin replacement and prompt referral for LT where indicated. Other novel therapeutic options on the horizon include automated low-flow ascites pump and cell-free, concentrated albumin reinfusion therapy.
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Affiliation(s)
- Shuet Fong Neong
- a Division of Gastroenterology, Department of Medicine, Toronto General Hospital , University of Toronto , Toronto , Ontario , Canada
| | - Danielle Adebayo
- a Division of Gastroenterology, Department of Medicine, Toronto General Hospital , University of Toronto , Toronto , Ontario , Canada
| | - Florence Wong
- a Division of Gastroenterology, Department of Medicine, Toronto General Hospital , University of Toronto , Toronto , Ontario , Canada
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Abstract
Ascites, a common complication of liver cirrhosis, eventually becomes refractory to diuretic therapy and sodium restriction in ∼10% of patients. Multiple pathogenetic factors are involved in the development of refractory ascites, which ultimately lead to renal hypoperfusion and avid sodium retention. Therefore, renal dysfunction commonly accompanies refractory ascites. Management includes 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 paracentesis-induced circulatory dysfunction. In the appropriate patients with reasonable liver reserve, the insertion of a transjugular intrahepatic portosystemic stent shunt (TIPS) can be considered, especially if the patient is relatively young and has no previous hepatic encephalopathy or anatomical contraindications, and no past history of renal or cardiopulmonary disease. Response to TIPS with ascites clearance can lead to nutritional improvement. Devices such as an automated low-flow ascites pump may be available in the future for ascites treatment. Patients with refractory ascites and poor liver function and/or renal dysfunction, should be referred for liver transplant, as this will eliminate the portal hypertension and liver dysfunction. Renal dysfunction prior to liver transplant largely improves after transplant without affecting post-transplant survival.
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Affiliation(s)
- Danielle Adebayo
- Division of Gastroenterology, Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, ON, Canada. These authors contributed equally: Danielle Adebayo, Shuet Fong Neong
| | - Shuet Fong Neong
- Division of Gastroenterology, Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, ON, Canada. These authors contributed equally: Danielle Adebayo, Shuet Fong Neong
| | - Florence Wong
- Division of Gastroenterology, Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, ON, Canada. These authors contributed equally: Danielle Adebayo, Shuet Fong Neong
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20
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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
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21
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Refractory Hepatic Hydrothorax: A Rare Complication of Systemic Sclerosis and Presinusoidal Portal Hypertension. Case Reports Hepatol 2018; 2018:2704949. [PMID: 29854501 PMCID: PMC5952433 DOI: 10.1155/2018/2704949] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2018] [Accepted: 03/22/2018] [Indexed: 01/15/2023] Open
Abstract
We report on a rare case of refractory hepatic hydrothorax in an individual with Scleroderma/CREST syndrome and noncirrhotic portal hypertension. Portal pressure measurements revealed a normal transjugular hepatic venous portal pressure gradient, mild pulmonary hypertension, and an unremarkable liver biopsy except for mild sinusoidal dilation. Pulmonary hypertension, cardiac diastolic dysfunction, and chronic kidney disease were determined to be the causes of his refractory pleural effusions and ascites. Over the year, he underwent 50 thoracenteses and 20 paracenteses averaging 10-12 liters/week. Repeat pulmonary evaluation determined his pulmonary pressures to be normal and a secondary review of the "unremarkable" liver biopsy noted mild venous outflow obstruction and possibly Nodular Regenerative Hyperplasia (NRH). Repeat portal pressures indirectly and directly confirmed the existence of presinusoidal portal hypertension that has been associated with NRH. A transjugular intrahepatic portal systemic shunt (TIPS) was placed and he has not required thoracentesis or paracentesis over the past 18 months.
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22
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Atsukawa M, Tsubota A, Kato K, Abe H, Shimada N, Asano T, Ikegami T, Koeda M, Okubo T, Arai T, Nakagawa-Iwashita A, Yoshida Y, Hayama K, Itokawa N, Kondo C, Chuganji Y, Matsuzaki Y, Iwakiri K. Analysis of factors predicting the response to tolvaptan in patients with liver cirrhosis and hepatic edema. J Gastroenterol Hepatol 2018; 33:1256-1263. [PMID: 29215154 DOI: 10.1111/jgh.14047] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2017] [Revised: 11/02/2017] [Accepted: 11/04/2017] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIM This study aimed to clarify the factors predictive of treatment response to tolvaptan (V2-receptor antagonist) for cirrhotic patients with hepatic edema in a real-world setting. METHODS In this retrospective, multicenter study, tolvaptan was orally administered at a dose of 7.5 mg once a day. Patients with a decrease in body weight of 1.5 kg or greater from baseline were characterized as responders at day 7. RESULTS Of 229 patients, 210 were subjected to this analysis. Patients consisted of 133 men and 77 women, with the median age of 67 years (range, 40-89 years). According to the Child-Pugh classification, five patients were classified as class A, 90 as class B, and 115 as class C. The frequencies of responders and nonresponders were 55.2% and 44.8%, respectively. Blood urea nitrogen (BUN) level was significantly lower in responders compared with nonresponders (P = 3.77 × 10-3 ). Using the receiver operating characteristic curve, the cutoff value of 28.2 mg/dL was the most useful in discriminating responders from nonresponders. Among 154 patients with BUN level of less than 28.2 mg/dL, 95 (61.7%) were responders. By contrast, among 56 patients with BUN level of 28.2 mg/dL or more, 21 (37.5%) were nonresponders (P = 2.70 × 10-3 ). On multivariate analysis, BUN level of <28.2 mg/dL and urine sodium >51 mEq/day were found to be independent factors associated with the response to tolvaptan. CONCLUSIONS This study suggests that BUN level and urinary sodium excretion are closely associated with the response to tolvaptan in cirrhotic patients with hepatic edema.
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Affiliation(s)
- Masanori Atsukawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.,Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Tokyo, Japan
| | - Akihito Tsubota
- Core Research Facilities for Basic Science, The Jikei University School of Medicine, Tokyo, Japan
| | - Keizo Kato
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Shinmatsudo Central General Hospital, Chiba, Japan
| | - Hiroshi Abe
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Shinmatsudo Central General Hospital, Chiba, Japan
| | - Noritomo Shimada
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Otakanomori Hospital, Chiba, Japan
| | - Toru Asano
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokyo Metropolitan Bokutoh Hospital, Tokyo, Japan
| | - Tadashi Ikegami
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokyo Medical University Ibaraki Medical Center, Ibaraki, Japan
| | - Mai Koeda
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Tokyo, Japan
| | - Tomomi Okubo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Tokyo, Japan
| | - Taeang Arai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Tokyo, Japan
| | - Ai Nakagawa-Iwashita
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Tokyo, Japan
| | - Yuji Yoshida
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
| | - Korenobu Hayama
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
| | - Norio Itokawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Tokyo, Japan
| | - Chisa Kondo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
| | - Yoshimichi Chuganji
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokyo Metropolitan Bokutoh Hospital, Tokyo, Japan
| | - Yasushi Matsuzaki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokyo Medical University Ibaraki Medical Center, Ibaraki, Japan
| | - Katsuhiko Iwakiri
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
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Wang YF, Tang JT, Han T, Ding HG, Ye WJ, Wang MR, Cheng J, Yang YP, Chen CW, Xie Q, Mao Q, Niu JQ, Wang ZH, Wei Z, Chen YX, Zeng MD, Mao YM. Tolvaptan in Chinese cirrhotic patients with ascites: A randomized, placebo-controlled phase 2 trial. J Dig Dis 2018; 19:144-154. [PMID: 29389068 DOI: 10.1111/1751-2980.12583] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2017] [Revised: 01/25/2018] [Accepted: 01/29/2018] [Indexed: 12/15/2022]
Abstract
OBJECTIVE To evaluate tolvaptan as a novel therapeutic option for Chinese patients with liver cirrhosis-associated ascites in a phase 2 clinical trial. METHODS This randomized, double-blind, placebo-controlled, multicenter trial was conducted in patients with insufficient responses to combination therapies of an oral loop diuretic and an aldosterone antagonist. Reduction in body weight and abdominal circumference, increase in 24-h cumulative urine volume and improvement in serum sodium level from baseline to the end of treatment in the tolvaptan groups (15 mg/day or 30 mg/day orally) were compared with those in the placebo group. Drug safety was also assessed. RESULTS Sixty-two patients were allocated to the placebo group, 56 to the tolvaptan 15-mg group and 63 to the tolvaptan 30-mg group. Their mean changes in body weight were -0.5 ± 1.6 kg, -2.1 ± 2.0 kg and -1.9 ± 2.0 kg, respectively. Body weight reductions in both tolvaptan groups were significantly greater than that in the placebo group (difference -1.6, 95% confidence interval [CI] -2.5 to -0.8, and difference -1.4, 95% CI, -2.2 to -0.7, both P < 0.0001). The administration of tolvaptan also significantly reduced the abdominal circumference, increased 24-h cumulative urine volume and serum sodium level compared with placebo. The most common adverse events in the tolvaptan groups were constipation, diarrhea, dry mouth and thirst, with no severe adverse events observed. CONCLUSION Tolvaptan at 15 mg/day significantly reduced the body weight and abdominal circumference in patients with liver cirrhosis-associated ascites, which needs to be confirmed in a phase 3 trial.
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Affiliation(s)
- Yong Feng Wang
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Jie Ting Tang
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Tao Han
- Division of Hepatology, Tianjin Third Hospital, Tianjin, China
| | - Hui Guo Ding
- Division of Gastroenterology and Hepatology, Beijing You'an Hospital, Capital Medical University, Beijing, China
| | - Wei Jiang Ye
- Department of Infectious Diseases, Xixi Hospital of Hangzhou, Hangzhou, Zhejiang Province, China
| | - Mao Rong Wang
- Department of Infectious Diseases, Nanjing Bayi Hospital, Nanjing, Jiangsu Province, China
| | - Jun Cheng
- Department of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yong Ping Yang
- Department of Infectious Diseases, 302 Military Hospital of China, Beijing, China
| | - Cheng Wei Chen
- Division of Hepatology, 85 Hospital of People's Liberation Army, Shanghai, China
| | - Qing Xie
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qing Mao
- Department of Infectious Diseases, Southwest Hospital, Chongqing, China
| | - Jun Qi Niu
- Department of Infectious Diseases, First Hospital of Jilin University, Changchun, Jilin Province, China
| | - Zheng Hua Wang
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Zhong Wei
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Ying Xuan Chen
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Min De Zeng
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Yi Min Mao
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
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Abstract
Liver transplantation (LT) is a unique surgical procedure that has major hemodynamic and cardiovascular implications. Recently, there has been significant interest focused on cardiovascular issues that affect LT patients in all phases of the perioperative period. The preoperative cardiac evaluation is a major step in the selection of LT candidates. LT candidates are aging in concordance with the general population; cardiovascular disease and their risk factors are highly associated with older age. Underlying cardiovascular disease has the potential to affect outcomes in LT patients and has a major impact on candidate selection. The prolonged hemodynamic and metabolic instability during LT may contribute to adverse outcomes, especially in patients with underlying cardiovascular disease. Cardiovascular events are not unusual during LT; transplant anesthesiologists must be prepared for these events. Advanced cardiovascular monitoring techniques and treatment modalities are now routinely used during LT. Postoperative cardiovascular complications are common in both the early and late posttransplant periods. The impact of cardiac complications on posttransplant mortality is well recognized. Emerging knowledge regarding cardiovascular disease in LT patients and its impact on posttransplant outcomes will have an important role in guiding the future perioperative management of LT patients.
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25
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Kamimura H, Watanabe T, Sugano T, Nakajima N, Yokoyama J, Kamimura K, Tsuchiya A, Takamura M, Kawai H, Kato T, Watanabe G, Yamagiwa S, Terai S. A Case of Hepatorenal Syndrome and Abdominal Compartment Syndrome with High Renal Congestion. AMERICAN JOURNAL OF CASE REPORTS 2017; 18:1000-1004. [PMID: 28919595 PMCID: PMC5616135 DOI: 10.12659/ajcr.904663] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2017] [Accepted: 06/21/2017] [Indexed: 12/26/2022]
Abstract
BACKGROUND Hepatorenal syndrome (HRS) is a reversible renal impairment that occurs in patients with acute liver failure and advanced liver cirrhosis. HRS is due to a renal vasoconstriction that results from extreme vasodilatation. It is therefore a functional disorder, not associated with structural kidney damage. On the other hand, end-stage liver diseases are often complicated by massive ascites. Massive ascites may cause abdominal compartment syndrome (ACS), which includes impairment of renal blood flow, but there are no reports indicating that kidney lesions caused by ACS may pathologically contribute to end-stage liver diseases. CASE REPORT A 40-year-old man with acute liver failure was admitted to our hospital. He was diagnosed with type 1 HRS and showed ACS at the same time. He died 30 days after admission. There were signs of congestion in the kidneys upon dissection and advanced erythroid fullness in the renal tubules. CONCLUSIONS We report an autopsy case with HRS and ACS diagnosed with a clinical and histopathological consideration of liver and kidney. Further clinical studies are needed to improve management of renal failure in patients with acute liver failure and advanced liver cirrhosis.
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Affiliation(s)
- Hiroteru Kamimura
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata City, Niigata, Japan
| | - Takayuki Watanabe
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata City, Niigata, Japan
| | - Tomoyuki Sugano
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata City, Niigata, Japan
| | - Nao Nakajima
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata City, Niigata, Japan
| | - Junji Yokoyama
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata City, Niigata, Japan
| | - Kenya Kamimura
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata City, Niigata, Japan
| | - Atsunori Tsuchiya
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata City, Niigata, Japan
| | - Masaaki Takamura
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata City, Niigata, Japan
| | - Hirokazu Kawai
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata City, Niigata, Japan
| | - Takashi Kato
- Division of Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata City, Niigata, Japan
| | - Gen Watanabe
- Division of Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata City, Niigata, Japan
| | - Satoshi Yamagiwa
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata City, Niigata, Japan
| | - Shuji Terai
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata City, Niigata, Japan
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Tanabe N, Takami T, Fujisawa K, Matsumoto T, Yamamoto N, Sakaida I. Effectiveness of tolvaptan monotherapy and low-dose furosemide/tolvaptan combination therapy for hepatoprotection and diuresis in a rat cirrhotic model. J Clin Biochem Nutr 2017; 61:53-59. [PMID: 28751810 PMCID: PMC5525014 DOI: 10.3164/jcbn.16-122] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2016] [Accepted: 01/25/2017] [Indexed: 12/30/2022] Open
Abstract
Spironolactone and furosemide, which are used to treat ascites associated with decompensated cirrhosis, are ineffective in treating refractory ascites. Hence, combination therapy with tolvaptan, a vasopressin V2 receptor antagonist, has been approved in Japan. Tolvaptan monotherapy and combination therapy with furosemide inhibit fibrosis in cardiac remodeling; hence, we examined these therapies in a rat cirrhotic model, including their usefulness in inhibiting hepatic fibrosis. In the present study, we used a model of hepatic fibrosis induced by a choline-deficient l-amino-acid-defined diet + diethylnitrosamine. Rats were divided into a low-dose furosemide group (15 mg/kg/day), a high-dose furosemide group (100 mg/kg/day), a tolvaptan monotherapy group (10 mg/kg/day), a low-dose furosemide/tolvaptan combination therapy group, and a control group which received neither furosemide nor tolvaptan; we then assessed diuretic effects and hepatic fibrosis. The tolvaptan monotherapy group and the furosemide/tolvaptan combination therapy group demonstrated significantly higher urine volume than the control group and the low-dose furosemide group. In addition, tolvaptan monotherapy and low-dose furosemide/tolvaptan combination therapy were found to inhibit hepatic fibrosis and yield a hepatoprotective effect by an antioxidative mechanism. The results of the present study suggest that tolvaptan monotherapy and low-dose furosemide/tolvaptan combination therapy are highly effective for hepatoprotection and diuresis.
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Affiliation(s)
- Norikazu Tanabe
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami Kogushi, Ube, Yamaguchi 755-8505, Japan
| | - Taro Takami
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami Kogushi, Ube, Yamaguchi 755-8505, Japan
| | - Koichi Fujisawa
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami Kogushi, Ube, Yamaguchi 755-8505, Japan.,Center of Research and Education for Regenerative Medicine, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami Kogushi, Ube, Yamaguchi 755-8505, Japan
| | - Toshihiko Matsumoto
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami Kogushi, Ube, Yamaguchi 755-8505, Japan.,Department of Oncology & Laboratory Medicine, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami Kogushi, Ube, Yamaguchi 755-8505, Japan
| | - Naoki Yamamoto
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami Kogushi, Ube, Yamaguchi 755-8505, Japan.,Yamaguchi University Health Administration Center, 1677-1 Yoshida, Yamaguchi, Yamaguchi 753-8511, Japan
| | - Isao Sakaida
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami Kogushi, Ube, Yamaguchi 755-8505, Japan
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Cakir OO, Toker A, Ataseven H, Demir A, Polat H. The Importance of Liver-Fatty Acid Binding Protein in Diagnosis of Liver Damage in Patients with Acute Hepatitis. J Clin Diagn Res 2017; 11:OC17-OC21. [PMID: 28571184 DOI: 10.7860/jcdr/2017/24958.9621] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2016] [Accepted: 01/06/2017] [Indexed: 12/25/2022]
Abstract
INTRODUCTION Acute hepatitis is acute inflammation of liver elicited by a large number of causes. It sometimes spontaneously recovers, sometimes may progress to chronic hepatitis. Liver- Fatty Acid Binding Protein (L-FABP) is a small protein that is abundant in hepatocytes, and which binds most of the long-chain fatty acids present in the cytosol. AIM The present study was aimed to investigate the levels of serum and urine L-FABP in acute hepatitis and diagnostic value of serum and urine L-FABP levels in patients with acute hepatitis. MATERIALS AND METHODS The present study included a total of 85 patients. Total number of patients with acute hepatitis were 17 (five of acute hepatitis B, one of acute hepatitis A, two of acute hepatitis C, five of autoimmune hepatitis and four of toxic hepatitis), 19 of hepatic encephalopathy, 29 of liver cirrhosis, and 20 controls were included. Serum and urinary L-FABP levels were analyzed by the Enzyme-Linked Immunosorbent Assay (ELISA). RESULTS Serum L-FABP levels were 9110±3352.5, 9410±1355, 9715±2462 and 3672±982.5 ng/l in patients with acute hepatitis, hepatic encephalopathy and cirrhosis and control subjects, respectively. There were statistically significant positive correlations between serum levels of L-FABP and Aspartate Aminotransferases (AST), Alanine Aminotransferases (ALT), Creatinine (Cre) and Gamma Glutamyl Transferases (GGT) (p<0.001, p<0.001, p<0.001 and p<0.001, respectively). While the cut-off value of serum L-FABP for all of the patients was 5183 ng/l {p<0.001 and Area Under Curve (AUC) 0.985}, the sensitivity and specificity were 95.4% and 100%, respectively. Positive and negative predictive values for serum L-FABP were 100% and 87%, respectively. CONCLUSION Serum and urine L-FABP may be a new diagnostic marker for liver damage in patients with acute hepatitis. However, our study showed that except of aminotransferases, L-FABP should be used for diagnosis of liver damage in patients with acute hepatitis, chronic hepatitis and also cirrhosis.
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Affiliation(s)
- Ozlem Ozer Cakir
- Associate Professor, Department of Gastroenterology and Hepatology, Konya Education and Research Hospital, Konya, Meram, Turkey
| | - Aysun Toker
- Associate Professor, Department of Biochemistry, Necmettin Erbakan University, Meram School of Medicine, Konya, Meram, Turkey
| | - Huseyin Ataseven
- Professor, Department of Gastroenterology and Hepatology, Necmettin Erbakan University, Meram School of Medicine, Konya, Meram, Turkey
| | - Ali Demir
- Professor, Department of Gastroenterology and Hepatology, Necmettin Erbakan University, Meram School of Medicine, Konya, Meram, Turkey
| | - Hakki Polat
- Professor, Department of Gastroenterology and Hepatology, Necmettin Erbakan University, Meram School of Medicine, Konya, Meram, Turkey
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Uojima H, Kinbara T, Hidaka H, Sung JH, Ichida M, Tokoro S, Masuda S, Takizawa S, Sasaki A, Koizumi K, Egashira H, Kako M. Close correlation between urinary sodium excretion and response to tolvaptan in liver cirrhosis patients with ascites. Hepatol Res 2017; 47:E14-E21. [PMID: 27059410 DOI: 10.1111/hepr.12716] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2015] [Revised: 03/18/2016] [Accepted: 03/29/2016] [Indexed: 02/08/2023]
Abstract
AIM To assess the correlation between response to tolvaptan and treatment-related factors in liver cirrhosis patients. METHODS This single-center retrospective study was carried out at Shonan Kamakura General Hospital in Kanagawa, Japan, between October 2013 and September 2015. Forty-three liver cirrhosis patients (mean age, 65.7 years) with insufficient responses to conventional diuretics for at least 7 days were enrolled. All patients received oral tolvaptan (7.5 mg/day for 7 days) and guideline-directed medical therapy including sodium intake restrictions. A responder to tolvaptan was defined as a patient having a ≥2-kg decrease in body weight 1 week after commencing drug treatment, and a non-responder was defined as a patient not losing ≥2 kg in body weight 1 week after commencing treatment. We investigated the correlation of change in body weight for 1 week after drug administration compared to baseline clinical characteristics. RESULTS The mean body weight change from the baseline on the final dosing day was -2.47 ± 3.34 kg (P < 0.0001). There were 20 (46.5%) responders to tolvaptan. Urinary sodium and volume excretion was higher in responders than in non-responders (108.2 ± 70.5 vs 42.6 ± 36.7, P = 0.0003; 1462.8 ± 625.7 vs 960.9 ± 600.6, P = 0.0073). Logistic regression analyses for responders to tolvaptan were carried out, and independent correlation of the responders was urinary sodium excretion (P = 0.0114; hazard ratio, 0.9418; 95% confidence interval, 0.8768-0.9896) in the multivariate analyses. CONCLUSION In decompensated liver cirrhosis patients, urinary excretion sodium showed good correlation with tolvaptan response.
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Affiliation(s)
- Haruki Uojima
- Department of Gastroenterology, Shonan Kamakura General Hospital, Kamakura, Kanagawa, Japan.,Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
| | - Takeshi Kinbara
- Department of Gastroenterology, Shonan Kamakura General Hospital, Kamakura, Kanagawa, Japan
| | - Hisashi Hidaka
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
| | - Ji Hyun Sung
- Department of Gastroenterology, Shonan Kamakura General Hospital, Kamakura, Kanagawa, Japan
| | - Masachika Ichida
- Department of Gastroenterology, Shonan Kamakura General Hospital, Kamakura, Kanagawa, Japan
| | - Shinnosuke Tokoro
- Department of Gastroenterology, Shonan Kamakura General Hospital, Kamakura, Kanagawa, Japan
| | - Sakue Masuda
- Department of Gastroenterology, Shonan Kamakura General Hospital, Kamakura, Kanagawa, Japan
| | - Satoshi Takizawa
- Department of Gastroenterology, Shonan Kamakura General Hospital, Kamakura, Kanagawa, Japan
| | - Akiko Sasaki
- Department of Gastroenterology, Shonan Kamakura General Hospital, Kamakura, Kanagawa, Japan
| | - Kazuya Koizumi
- Department of Gastroenterology, Shonan Kamakura General Hospital, Kamakura, Kanagawa, Japan
| | - Hideto Egashira
- Department of Gastroenterology, Shonan Kamakura General Hospital, Kamakura, Kanagawa, Japan
| | - Makoto Kako
- Department of Gastroenterology, Shonan Kamakura General Hospital, Kamakura, Kanagawa, Japan
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Sakaida I, Terai S, Nakajima K, Shibasaki Y, Tachikawa S, Tsubouchi H. Predictive factors of the pharmacological action of tolvaptan in patients with liver cirrhosis: a post hoc analysis. J Gastroenterol 2017; 52:229-236. [PMID: 27379386 PMCID: PMC5281662 DOI: 10.1007/s00535-016-1233-x] [Citation(s) in RCA: 16] [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: 03/27/2016] [Accepted: 06/08/2016] [Indexed: 02/04/2023]
Abstract
BACKGROUND Tolvaptan has been approved in Japan for the treatment of hepatic edema. An important consideration in providing a clinical benefit to patients with liver cirrhosis is the improvement of ascites-related clinical symptoms. In the present post hoc analysis, we aimed to identify factors that were predictive of the potency of tolvaptan, and to examine the relationship between changes in initial urine volume and improvement in ascites-related clinical symptoms. METHODS This post hoc analysis was based on three previous phase 2 and 3 clinical trials of tolvaptan in patients with liver cirrhosis. Predictive factors associated with a change in initial urine volume were identified. A change of ≥500 mL from baseline confirmed the pharmacological action of tolvaptan treatment. The relationship between the change in initial urine volume and improvement in ascites-related clinical symptoms was also examined. RESULTS A total of 152 patients were enrolled in this study. Body weight and BUN were identified as predictive parameters. Among patients with a change in initial urine volume of ≥500 mL, 75 % demonstrated improvement in ascites-related clinical symptoms, while no improvement was seen in those with a change of <500 mL. None of the patients with initial urine volume of <500 mL showed resolution of symptoms. CONCLUSIONS Change in urine volume was affected by both baseline body weight and BUN in tolvaptan-treated subjects. Higher urine output was associated with improvements in ascites-related clinical symptoms.
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Affiliation(s)
- Isao Sakaida
- 0000 0001 0660 7960grid.268397.1Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi Japan
| | - Shuji Terai
- 0000 0001 0671 5144grid.260975.fDivision of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Koji Nakajima
- grid.419953.3Department of Medical Affairs, Otsuka Pharmaceutical Co., Ltd., 2-16-4 Konan, Minato-ku, Tokyo, 108-8242 Japan
| | - Yoshiyuki Shibasaki
- grid.419953.3Department of Medical Affairs, Otsuka Pharmaceutical Co., Ltd., 2-16-4 Konan, Minato-ku, Tokyo, 108-8242 Japan
| | - Sayaka Tachikawa
- grid.419953.3Department of Medical Affairs, Otsuka Pharmaceutical Co., Ltd., 2-16-4 Konan, Minato-ku, Tokyo, 108-8242 Japan
| | - Hidetsugu Tsubouchi
- grid.419953.3Department of Medical Affairs, Otsuka Pharmaceutical Co., Ltd., 2-16-4 Konan, Minato-ku, Tokyo, 108-8242 Japan
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Albumin May Prevent the Morbidity of Paracentesis-Induced Circulatory Dysfunction in Cirrhosis and Refractory Ascites: A Pilot Study. Dig Dis Sci 2016; 61:3084-3092. [PMID: 27048451 DOI: 10.1007/s10620-016-4140-3] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2015] [Accepted: 03/21/2016] [Indexed: 12/13/2022]
Abstract
BACKGROUND Large-volume total paracentesis may result in paracentesis-induced circulatory dysfunction, which is associated with poor outcomes. AIMS To explore the short- and long-term effects of paracentesis-induced circulatory dysfunction on systemic hemodynamics, renal function and other cirrhosis-related complications in patients with refractory ascites, following subtotal large-volume paracentesis. METHODS Patients with cirrhosis and refractory ascites without renal dysfunction had systemic hemodynamics, renal function, and neurohormones (plasma active renin, aldosterone, norepinephrine and angiotensin II) measured pre- and 6 days post-paracentesis. Paracentesis was limited to ≤8 L with 6-8 g of albumin per liter ascites drained. Patients were followed up until transjugular intrahepatic portosystemic shunt insertion, liver transplantation, or death. Paracentesis-induced circulatory dysfunction was defined as >50 % increase in plasma active renin 6 days post-paracentesis. RESULTS Fifty-seven patients (mean age 59.0 ± 9.4 years) had mean 6.8 ± 1.8 L of ascites removed with 9 ± 3 g of albumin given/L of ascites drained. Patients were followed up for 715 ± 104 days. Twenty-three patients (40.4 %) developed paracentesis-induced circulatory dysfunction with unchanged serum creatinine on day six, despite worsening of hemodynamics (mean arterial pressure 90 ± 10 mmHg at baseline vs. 84 ± 8 mmHg on day six, p < 0.05). Similar hemodynamic changes were observed among patients without paracentesis-induced circulatory dysfunction. There was no significant difference in the long-term renal function or cirrhosis-related complications between the groups. CONCLUSION The occurrence of paracentesis-induced circulatory dysfunction, as defined by plasma active renin, may not have a significant short- and long-term impact on renal function or cirrhosis-related complications in patients with refractory ascites who undergo subtotal paracentesis with albumin infusion.
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Yamada T, Ohki T, Hayata Y, Karasawa Y, Kawamura S, Ito D, Kojima K, Seki M, Toda N, Tagawa K. Potential Effectiveness of Tolvaptan to Improve Ascites Unresponsive to Standard Diuretics and Overall Survival in Patients with Decompensated Liver Cirrhosis. Clin Drug Investig 2016; 36:829-35. [DOI: 10.1007/s40261-016-0434-7] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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Nakagawa A, Atsukawa M, Tsubota A, Kondo C, Okubo T, Arai T, Itokawa N, Narahara Y, Iwakiri K. Usefulness of portal vein pressure for predicting the effects of tolvaptan in cirrhotic patients. World J Gastroenterol 2016; 22:5104-5113. [PMID: 27275103 PMCID: PMC4886386 DOI: 10.3748/wjg.v22.i21.5104] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2016] [Revised: 03/19/2016] [Accepted: 03/30/2016] [Indexed: 02/06/2023] Open
Abstract
AIM: To elucidate influencing factors of treatment response, then tolvaptan has been approved in Japan for liquid retention.
METHODS: We herein conducted this study to clarify the influencing factors in 40 patients with decompensated liver cirrhosis complicated by liquid retention. Tolvaptan was administered at a dosage of 7.5 mg once a day for patients with conventional diuretic-resistant hepatic edema for 7 d. At the initiation of tolvaptan, the estimated hepatic venous pressure gradient (HVPG) value which was estimated portal vein pressure was measured using hepatic venous catheterization. We analyzed the effects of tolvaptan and influencing factors associated with treatment response.
RESULTS: Subjects comprised patients with a median age of 65 (range, 40-82) years. According to the Child-Pugh classification, class A was 3 patients, class B was 19, and class C was 18. Changes from the baseline in body weight were -1.0 kg (P = 2.04 × 10-6) and -1.3 kg (P = 1.83 × 10-5), respectively. The median HVPG value was 240 (range, 105-580) mmH2O. HVPG was only significant influencing factor of the weight loss effect. When patients with body weight loss of 2 kg or greater from the baseline was defined as responders, receiver operating characteristic curve analysis showed that the optimal HVPG cutoff value was 190 mmH2O in predicting treatment response. The response rate was 87.5% (7/8) in patients with HVPG of 190 mmH2O or less, whereas it was only 12.5% (2/16) in those with HVPG of greater than 190 mmH2O (P = 7.46 × 10-4). We compared each characteristics factors between responders and non-responders. As a result, HVPG (P = 0.045) and serum hyaluronic acid (P = 0.017) were detected as useful factors.
CONCLUSION: The present study suggests that tolvaptan in the treatment of liquid retention could be more effective for patients with lower portal vein pressure.
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Ferral H, Gomez-Reyes E, Fimmel CJ. Post-Transjugular Intrahepatic Portosystemic Shunt Follow-Up and Management in the VIATORR Era. Tech Vasc Interv Radiol 2016; 19:82-8. [PMID: 26997092 DOI: 10.1053/j.tvir.2016.01.009] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The transjugular intrahepatic portosystemic shunt (TIPS) is a non-selective portosystemic shunt created using endovascular techniques. The first TIPS was performed in Germany in 1988. The VIATORR self-expandable PTFE covered stent-graft (WL Gore, Flagstaff AZ) was approved by the FDA for a TIPS application in December of 2004. This stent-graft offers excellent shunt patency rates and it is possible that it has a beneficial effect on patient survival. Patient surveillance and post-procedural management have changed after the introduction of this stent-graft. This article presents the current management strategies that are followed at our Institution for patients who have undergone a TIPS procedure with a VIATORR stent graft including imaging follow-up, management of encephalopathy, medical management and nutritional aspects.
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Affiliation(s)
- Hector Ferral
- The Department of Radiology, Section of Interventional Radiology, NorthShore University HealthSystem, Evanston, IL.
| | - Elisa Gomez-Reyes
- Departamento de Gastroenterologia, Instituto Nacional de la Nutricion Salvador Zubiran, Tlalpan, Mexico City, Mexico
| | - Claus J Fimmel
- University of Chicago Pritzker School of Medicine, Section Chief of Hepatology, Division of Gastroenterology, NorthShore University HealthSystem, Evanston, IL
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Abstract
Renal dysfunction is prevalent in patients with advanced cirrhosis and decompensation. The presence of type 1 hepatorenal syndrome (HRS) has traditionally been defined by a set of stringent criteria based on serum creatinine levels. These diagnostic criteria have been found to be too stringent to be widely applicable to patients with cirrhosis, leading to underdiagnosis of renal failure in this population. Acute kidney injury (AKI) has now been proposed to characterize renal dysfunction in patients with cirrhosis and is defined as an increase in serum creatinine by 0.3 mg/dl in <48 h or an increase in serum creatinine by 50% from a stable baseline reading within 3 months. Type 1 HRS is renamed HRS-AKI. Stage 1 AKI is defined by 0.3 mg/dl serum creatinine or a 50% increase, stages 2 and 3 AKI are defined by a two-fold and three-fold increase in serum creatinine levels, respectively. Data collected so far suggests that even stage 1 AKI is associated with worse prognosis in patients with cirrhosis. The progression of AKI usually indicates substantially worse outcomes. A panel of biomarkers, including inflammatory markers, are envisaged to complement and enhance our current diagnostic criteria in the future and provide aetiology of the AKI.
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Affiliation(s)
- Florence Wong
- Department of Medicine, Division of Gastroenterology, Toronto General Hospital, University Health Network, University of Toronto, 200 Elizabeth Street, Toronto, ON M5G2C4, Canada
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Siramolpiwat S. Transjugular intrahepatic portosystemic shunts and portal hypertension-related complications. World J Gastroenterol 2014; 20:16996-17010. [PMID: 25493012 PMCID: PMC4258568 DOI: 10.3748/wjg.v20.i45.16996] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2014] [Revised: 07/09/2014] [Accepted: 08/28/2014] [Indexed: 02/06/2023] Open
Abstract
Portal hypertension (PH) plays an important role in the natural history of cirrhosis, and is associated with several clinical consequences. The introduction of transjugular intrahepatic portosystemic shunts (TIPS) in the 1980s has been regarded as a major technical advance in the management of the PH-related complications. At present, polytetrafluoroethylene-covered stents are the preferred option over traditional bare metal stents. TIPS is currently indicated as a salvage therapy in patients with bleeding esophageal varices who fail standard treatment. Recently, applying TIPS early (within 72 h after admission) has been shown to be an effective and life-saving treatment in those with high-risk variceal bleeding. In addition, TIPS is recommended as the second-line treatment for secondary prophylaxis. For bleeding gastric varices, applying TIPS was able to achieve hemostasis in more than 90% of patients. More trials are needed to clarify the efficacy of TIPS compared with other treatment modalities, including cyanoacrylate injection and balloon retrograde transvenous obliteration of gastric varices. TIPS should also be considered in bleeding ectopic varices and refractory portal hypertensive gastropathy. In patients with refractory ascites, there is growing evidence that TIPS not only results in better control of ascites, but also improves long-term survival in appropriately selected candidates. In addition, TIPS is a promising treatment for refractory hepatic hydrothorax. However, the role of TIPS in the treatment of hepatorenal and hepatopulmonary syndrome is not well defined. The advantage of TIPS is offset by a risk of developing hepatic encephalopathy, the most relevant post-procedural complication. Emerging data are addressing the determination the optimal time and patient selection for TIPS placement aiming at improving long-term treatment outcome. This review is aimed at summarizing the published data regarding the application of TIPS in the management of complications related to PH.
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Sakaida I, Okita K. Correlation between changes in bodyweight and changes in ascites volume in liver cirrhosis patients with hepatic edema in short-term diuretic therapy. Hepatol Res 2014; 44:735-9. [PMID: 23711300 DOI: 10.1111/hepr.12171] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2013] [Revised: 05/21/2013] [Accepted: 05/22/2013] [Indexed: 12/16/2022]
Abstract
AIM Although it is an important treatment challenge to treat ascites with diuretic therapy, no objective markers have been established to assess improvement of ascites. However, change in bodyweight has been used as a marker of change in ascites volume. Thus, we evaluated the relationship between changes in bodyweight and changes in ascites volume in liver cirrhosis patients with ascites. METHODS We calculated ascites volume in patients using the simple 5-point method by conventional computed tomography and conducted a correlation analysis between changes in bodyweight and changes in ascites volume as a part of our double-blind phase 3 trial of tolvaptan. RESULT Change in bodyweight (x-axis) was correlated with change in ascites volume (y-axis) in all included patients (r = 0.52). A strong correlation were observed between the changes in patients without lower limb edema (r = 0.61). These correlations between the changes were expressed by the following linear regression equations: y = -0.102 + 0.206x or y = -0.033 + 0.292x, respectively. Proportions of change in ascites volume to change in bodyweight were estimated to be nearly 30%. Therefore, bodyweight reduction was confirmed to lead to improvement in ascites. CONCLUSION Change in bodyweight can be an objective marker to assess improvement of hepatic edema in the short-term diuretic therapy in everyday clinical practice. Decrease in ascites volume was estimated to account for nearly 30% of bodyweight reduction.
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Affiliation(s)
- Isao Sakaida
- Yamaguchi University Graduate School of Medicine, Ube
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Yang J, Xu SN, Wang M, Peng LP, Zhou Q. Effects of sodium ferulate on liver fibrosis in experimental cirrhotic rats. Shijie Huaren Xiaohua Zazhi 2014; 22:1676-1681. [DOI: 10.11569/wcjd.v22.i12.1676] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To assess the effects of sodium ferulate on liver fibrosis in rats with experimental cirrhosis induced by bile duct ligation.
METHODS: Liver cirrhosis was experimentally induced in rats by bile duct ligation. Rats were divided into three groups: a control group, a model group and a treatment group, which were treated by sham-operation, bile duct ligation, and sodium ferulate injection after bile duct ligation, respectively. Biochemical parameters were measured. Body weight, liver weight and liver index were compared between groups. Pathological characteristics of liver tissues were observed by optical microscopy and transmission electron microscopy, and the integrated absorbance of hepatic α-smooth muscle actin was determined by immunohistochemistry.
RESULTS: Biochemical parameters did not differ between the model group and treatment group. Liver index in the model group increased compared with control rats (7.83% ± 0.57% vs 4.05% ± 0.17%, P < 0.01); after treatment, the index decreased significantly (7.08% ± 0.68% vs 7.83% ± 0.57%, P < 0.05). Pathological observation revealed that the degree of fibrosis and severity of hepatocyte damage in the treatment group were lower than those in the model group. Hepatic α-SMA content in the model group was significantly higher than that in the control group (113224.74 ± 45518.79 vs 4197.80 ± 1364.97, P < 0.01). After treatment with sodium ferulate, hepatic α-SMA content decreased in the treatment group compared with the model group (46451.65 ± 15600.56 vs 113224.74 ± 45518.79, P < 0.05).
CONCLUSION: Sodium ferulate has a therapeutic effect on liver fibrosis in rats with experimental cirrhosis induced by bile duct ligation.
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Chen RP, Zhu Ge XJ, Huang ZM, Ye XH, Hu CY, Lu GR, Lu DY, Phemba IL. Prophylactic use of transjugular intrahepatic portosystemic shunt aids in the treatment of refractory ascites: metaregression and trial sequential meta-analysis. J Clin Gastroenterol 2014; 48:290-299. [PMID: 24030734 DOI: 10.1097/mcg.0b013e3182a115e9] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
GOALS The aim of this study was to explore whether prophylactic use of transjugular intrahepatic portosystemic shunt (TIPS) could aid in the treatment of refractory ascites on the basis of current randomized controlled trials. BACKGROUND TIPS is more effective for refractory ascites versus large-volume paracentesis. At present, however, the survival advantage is not clear within populations of undifferentiated patients. STUDY Correlative studies were searched through online journal databases, and a manual search was done from 1974 to 2012. Six trials involving 390 patients were included. RESULTS TIPS could ameliorate refractory ascites on the basis of short-term analysis [odds ratio (OR) 8.66; 95% confidence interval (CI), 5.27-14.24] and long-term analysis (OR 6.07; 95% CI, 3.60-10.22). Hepatic encephalopathy (HE) appeared more common in the TIPS arm (OR 2.95; 95% CI, 1.87-4.66). Mortality in the 2 groups did not show any difference (OR 0.82; 95% CI, 0.46-1.50). Trial sequential analysis confirmed the effect of TIPS upon ascites control and upon the risk of HE recurrence, whereas insufficient trials were available to distinguish between the arms on mortality. Metaregression analysis showed that the level of urine sodium, serum bilirubin, and portal pressure gradient reduction value could be used as survival predictors. Subgroup analysis showed an elevated survival effect in TIPS (OR 0.45; 95% CI, 0.24-0.81), and patients survived longer with recurrent ascites (OR 0.40; 95% CI, 0.19-0.83). CONCLUSIONS TIPS was confirmed to improve ascites control in both the short term and the long term. Although HE frequently appeared in the TIPS group, patients with better hepatic and renal function survived longer when they were treated with TIPS. Serum bilirubin and urine sodium could be used as pre-TIPS predictors for patient survival. Portal pressure gradient reduction values could be used as post-TIPS predictors of survival.
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Affiliation(s)
- Ren Pin Chen
- Departments of *Gastroenterology and Hepatology †Gastrointestinal Surgery, First Affiliated Hospital of Wenzhou Medical College ‡School of International Studies, Wenzhou Medical College, Wenzhou, China
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40
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Gungor G, Ataseven H, Demir A, Solak Y, Gaipov A, Biyik M, Ozturk B, Polat I, Kiyici A, Cakir OO, Polat H. Neutrophil gelatinase-associated lipocalin in prediction of mortality in patients with hepatorenal syndrome: a prospective observational study. Liver Int 2014; 34:49-57. [PMID: 23799980 DOI: 10.1111/liv.12232] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2012] [Accepted: 05/19/2013] [Indexed: 12/19/2022]
Abstract
BACKGROUND & AIMS Hepatorenal syndrome (HRS) is a severe complication of cirrhosis which is characterized by renal dysfunction and associated with poor survival. Neutrophil gelatinase-associated lipocalin (NGAL) is a troponin-like biomarker for human acute kidney injury. We aimed to investigate levels of plasma and urine NGAL in HRS and predictive ability of these markers for all-cause mortality, in HRS, stable cirrhosis and control subjects. METHODS A total of 64 patients with cirrhosis (8 patients with type 1 HRS, 22 with type 2 HRS, and 34 without HRS) and 23 control subjects were included in the study. Blood and urine samples were measured with Human NGAL sandwich ELISA. Patients were followed up prospectively. RESULTS Patients with type 1 and type 2 HRS had significantly higher plasma and urine NGAL levels compared with stable cirrhosis and control subjects. Cox regression analysis showed that plasma NGAL and MELD-Na scores were independent predictors of mortality. ROC-curve analysis showed that the plot of the plasma NGAL, urine NGAL, MELD-Na and Child-Turcot-Pugh score could predict all-cause mortality in cirrhotic patients' area under the curve (AUC 0.819, 0.686, 0.807 and 0.795 respectively). CONCLUSIONS NGAL could predict mortality in patients with HRS independent of other commonly used risk factors.
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Affiliation(s)
- Gokhan Gungor
- Division of Gastroenterology, Department of Internal Medicine, Meram School of Medicine, Konya University, Meram, Konya, Turkey
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Sundaram V, Manne V, Al-Osaimi AMS. Ascites and spontaneous bacterial peritonitis: recommendations from two United States centers. Saudi J Gastroenterol 2014; 20:279-87. [PMID: 25253362 PMCID: PMC4196342 DOI: 10.4103/1319-3767.141686] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Cirrhosis affects millions of people throughout the world. Two of the most serious complications of liver cirrhosis are ascites and spontaneous bacterial peritonitis (SBP). The development of ascites is related to the severity of portal hypertension and is an indicator of increased mortality. Although sodium restriction and diuretic therapy have proven effective, some patients may not respond appropriately or develop adverse reactions to diuretic therapy. In such cases, interventions such as transjugular intrahepatic portosystemic shunt (TIPS) placement are warranted. SBP is a complication of ascites that confers a very high mortality rate. Recognition and prompt treatment of this condition is essential to prevent serious morbidity and mortality. Initiation of prophylaxis in SBP remains controversial. Given the burden of liver cirrhosis on the health care system, ascites and SBP will continue to provide challenges for the primary care provider, hospitalist, internist, and gastroenterologist alike.
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Affiliation(s)
- Vinay Sundaram
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Vignan Manne
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Abdullah MS Al-Osaimi
- Department of Medicine, Division of Hepatology, Temple University Health System, Philadelphia, Pennsylvania, USA,Address for correspondence: Dr. Abdullah M. S. Al-Osaimi, Associate Professor of Medicine and Surgery, Division Chief of Hepatology, Medical Director of Liver Transplantation, Temple University Health System, 3440 N. Broad Street, Kresge Building West, Room 216, Philadelphia, Pennsylvania - 19103, USA. E-mail:
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Okita K, Kawazoe S, Hasebe C, Kajimura K, Kaneko A, Okada M, Sakaida I. Dose-finding trial of tolvaptan in liver cirrhosis patients with hepatic edema: A randomized, double-blind, placebo-controlled trial. Hepatol Res 2014; 44:83-91. [PMID: 23530991 DOI: 10.1111/hepr.12099] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2013] [Revised: 02/14/2013] [Accepted: 02/17/2013] [Indexed: 01/07/2023]
Abstract
AIM Liver cirrhosis represents the end stage of any chronic liver disease, and it is associated with hepatic edema such as ascites. Many patients with ascites do not respond to diuretic therapy or require administration of diuretics at high doses that can cause adverse events. This 7-day, multicenter, double-blind trial of tolvaptan was designed to determine the optimal dose of tolvaptan for producing the intended pharmacological effect in hepatic edema. METHODS Liver cirrhosis patients with inadequate diuretic response despite having received a conventional diuretic therapy were enrolled in the trial. Participants were stratified randomly to four groups receiving tolvaptan at 7.5, 15 or 30 mg/day, or placebo as an add-on to conventional diuretics once daily for 7 days. Changes in bodyweight and abdominal circumference were analyzed. Serum sodium concentrations were measured. Safety assessment was performed. RESULTS Tolvaptan at 7.5-30 mg/day reduced bodyweight and abdominal circumference compared with placebo. Serum sodium concentrations remained within the normal range in all tolvaptan groups. Serious adverse events were not observed, and most common adverse event was thirst. Tolvaptan at 7.5 mg/day showed the maximum change in bodyweight and abdominal circumference together with preferable tolerability. CONCLUSION Tolvaptan at 7.5 mg/day was considered the optimal dose in liver cirrhosis patients with hepatic edema who showed inadequate response to conventional diuretics.
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Affiliation(s)
- Kiwamu Okita
- Social Insurance Alliance Shimonoseki Kohsei Hospital, Yamaguchi, Japan
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43
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Sakaida I, Kawazoe S, Kajimura K, Saito T, Okuse C, Takaguchi K, Okada M, Okita K. Tolvaptan for improvement of hepatic edema: A phase 3, multicenter, randomized, double-blind, placebo-controlled trial. Hepatol Res 2014; 44:73-82. [PMID: 23551935 DOI: 10.1111/hepr.12098] [Citation(s) in RCA: 98] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2013] [Revised: 02/05/2013] [Accepted: 02/17/2013] [Indexed: 12/11/2022]
Abstract
AIM Hepatic edema is manifested by ascites, lower limb edema and intolerable symptoms. Some patients insufficiently respond to the conventional diuretic therapy. Therefore, a novel therapeutic option is required. We conducted a phase 3 study to confirm therapeutic effect of tolvaptan on hepatic edema associated with liver cirrhosis. METHODS In our multicenter, randomized, double-blind, placebo-controlled trial, liver cirrhosis patients who showed insufficient response to conventional diuretics were randomly assigned to 7-day administration of either tolvaptan at 7.5 mg/day or placebo as an add-on therapy to conventional diuretics. The primary outcome was change in bodyweight from baseline. RESULTS Of 164 eligible patients, 84 were assigned to tolvaptan and 80 to placebo. Change in bodyweight from baseline on the final dosing day was -0.44 kg (standard deviation [SD], 1.93) in the placebo group and -1.95 kg (SD, 1.77) in the tolvaptan group (P < 0.0001). Improvement rates for lower limb edema and ascites-related clinical symptoms were higher with tolvaptan than with placebo. Even in patients with low serum albumin (<2.5 g/dL), decrease in bodyweight was greater with tolvaptan than with placebo (P = 0.0163). In addition, tolvaptan significantly increased serum sodium concentration from baseline. CONCLUSION Add-on therapy with tolvaptan was effective for the treatment of hepatic edema and ascites-related clinical symptoms. Furthermore, tolvaptan is expected to improve low serum sodium concentration and to exert its effect regardless of serum albumin level. Add-on therapy with tolvaptan is therefore considered to be a novel therapeutic option for hepatic edema.
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Affiliation(s)
- Isao Sakaida
- Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi
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44
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Saffouri GB, Wittich CM. 83-year-old man with abdominal swelling and lower extremity edema. Mayo Clin Proc 2013; 88:e115-8. [PMID: 24079694 DOI: 10.1016/j.mayocp.2013.03.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2012] [Revised: 03/13/2013] [Accepted: 03/15/2013] [Indexed: 10/26/2022]
Affiliation(s)
- George B Saffouri
- Resident in Internal Medicine, Mayo School of Graduate Medical Education, Mayo Clinic, Rochester, MN
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45
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Sakaida I, Yanase M, Kobayashi Y, Yasutake T, Okada M, Okita K. The pharmacokinetics and pharmacodynamics of tolvaptan in patients with liver cirrhosis with insufficient response to conventional diuretics: a multicentre, double-blind, parallel-group, phase III study. J Int Med Res 2013; 40:2381-93. [PMID: 23321196 DOI: 10.1177/030006051204000637] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
OBJECTIVES This study investigated the pharmacokinetic and pharmacodynamic profile of tolvaptan, and verified its efficacy and safety in patients with liver cirrhosis-associated ascites, with insufficient response to conventional diuretic treatment. METHODS This multicentre, double-blind, parallel-group study allocated patients with cirrhosis to receive either 3.75 or 7.5 mg/day tolvaptan orally, once daily, for 7 days. Pharmacokinetic, pharmacodynamic and efficacy variables were measured. RESULTS Tolvaptan was shown to have high plasma concentrations, and prolonged duration of maximum concentration and half life, in these patients with impaired hepatic function. Tolvaptan resulted in dose-dependent decreases in body weight and ascites volume, and increases in urine output. There were no effects on urinary or serum electrolytes. Tolvaptan was well tolerated, with a good safety profile. CONCLUSIONS Tolvaptan at 3.75 mg/day exerts some effects due to the pharmacokinetic profile in patients with liver cirrhosis. Tolvaptan at 7.5 mg/day is a clinically useful option for treating patients who do not respond well to conventional diuretics.
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Affiliation(s)
- I Sakaida
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
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Sakaida I, Yamashita S, Kobayashi T, Komatsu M, Sakai T, Komorizono Y, Okada M, Okita K. Efficacy and safety of a 14-day administration of tolvaptan in the treatment of patients with ascites in hepatic oedema. J Int Med Res 2013; 41:835-47. [PMID: 23685892 DOI: 10.1177/0300060513480089] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
OBJECTIVE To investigate the efficacy and safety of 14 days' orally administered tolvaptan as adjunctive treatment for hepatic oedema in Japanese liver cirrhosis patients with insufficient response to conventional diuretics, with the option to increase dose in those who did not respond initially. METHODS This multicentre, single-arm, phase 3 study allocated patients with liver cirrhosis and persistent ascites to 7-day treatment with 7.5 mg/day tolvaptan followed by an additional 7 days' treatment. Responders at day 7 (achieving ≥ 1 kg body-weight reduction) continued on 7.5 mg/day tolvaptan; nonresponders (<1 kg body-weight reduction) received 15 mg/day tolvaptan. Conventional diuretic treatment continued throughout. The primary endpoint was change in body weight from baseline, as a marker of ascites volume. RESULTS A total of 51 patients received 7.5 mg/day tolvaptan for 7 days, which caused a significant reduction in mean body weight (55% response rate). During the second 7-day treatment period, 30 patients received 7.5 mg/day tolvaptan and 13 patients received tolvaptan 15 mg/day: response rates were 43% and 23%, respectively. Two serious adverse events were observed. Serum sodium was within normal range. CONCLUSIONS Tolvaptan therapy for 14 days (with possible dose increase as necessary), in combination with conventional diuretics, effectively reduced body weight in patients with hepatic oedema.
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Affiliation(s)
- Isao Sakaida
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.
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Singh A, Bajwa A, Shujaat A. Evidence-based review of the management of hepatic hydrothorax. ACTA ACUST UNITED AC 2013; 86:155-73. [PMID: 23571767 DOI: 10.1159/000346996] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2012] [Accepted: 01/08/2013] [Indexed: 12/19/2022]
Abstract
Hepatic hydrothorax (HH) is an example of a porous diaphragm syndrome. Portal hypertension results in the formation of ascitic fluid which moves across defects in the diaphragm and accumulates in the pleural space. Consequently, the treatment approach to HH consists of measures to reduce the formation of ascitic fluid, prevent the movement of ascitic fluid across the diaphragm, and drain or obliterate the pleural space. Approximately 21-26% of cases of HH are refractory to salt and fluid restriction and diuretics and warrant consideration of additional treatment measures. Ideally, liver transplantation is the best treatment option; however, most of the patients are not candidates and most of those who are eligible die while waiting for a transplant. Treatment measures other than liver transplantation may not only provide relief from dyspnea but also improve patient survival and serve as a bridge to liver transplantation.
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Affiliation(s)
- Amita Singh
- Department of Pulmonary and Critical Care, UF College of Medicine at Jacksonville, Jacksonville, FL 32209, USA.
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48
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Blood neutrophil-to-lymphocyte ratio independently predicts survival in patients with liver cirrhosis. Eur J Gastroenterol Hepatol 2013; 25:435-41. [PMID: 23249602 DOI: 10.1097/meg.0b013e32835c2af3] [Citation(s) in RCA: 117] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVES Neutrophil-to-lymphocyte ratio (NLR) is a novel inflammation index that has been shown to independently predict poor clinical outcomes. We aimed to evaluate the role of NLR in the prediction of long-term mortality in patients with stable liver cirrhosis. MATERIALS AND METHODS This is a retrospective observational cohort study in which 145 stable cirrhotic patients without infection, hepatocellular carcinoma, and ongoing steroid therapy were enrolled between January 2009 and December 2011. The primary end point was survival during follow-up. NLR along with Child-Turcotte-Pugh (CTP), Model for End-Stage Liver Disease (MELD) scores, and Charlson comorbidity index were assessed for the prediction of mortality. RESULTS There were 86 men and 59 women, mean age 58.9±13.4 years. The etiologies of liver cirrhosis included viral hepatitis (n=73), cryptogenic (50), alcoholic (12), and other (10). The mean follow-up duration was 27.8±6.8 months, during which 40 patients died. The mean NLRs were 2.08±0.99 and 4.39±3.0 in surviving and nonsurviving patients, respectively (P<0.001). Kaplan-Meier survival analysis was carried out according to the median NLR above and below 2.72. Patients with NLR of at least 2.72 had a significantly lower survival (log rank, P<0.001). NLR was found to be an independent predictor of mortality in all Cox Regression models (odds ratio 1.2; 95% confidence interval 1.2-1.3; P<0.001). Receiver operating characteristic analysis showed that cut-off values of 4.22, 3.07, and 2.96 for NLR predicted 12, 24, and 36-month mortality, respectively (AUC: 0.806, P=0.0029; 0.841, P<0.0001 and 0.783, P<0.0001, respectively). CONCLUSION NLR is a predictor of mortality independent of CTP and MELD scores in patients with liver cirrhosis. NLR could predict mortality in the subgroup of patients with low MELD scores as well.
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Chen SH, Li YF, Lai HC, Kao JT, Peng CY, Chuang PH, Su WP, Chiang IP. Effects of patient factors on noninvasive liver stiffness measurement using acoustic radiation force impulse elastography in patients with chronic hepatitis C. BMC Gastroenterol 2012; 12:105. [PMID: 22877310 PMCID: PMC3462151 DOI: 10.1186/1471-230x-12-105] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2012] [Accepted: 08/02/2012] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Previous research has shown variation in the effects of patient factors, including hepatic necroinflammatory activity, on liver stiffness measurement (LSM). This prospective study attempts to identify explanatory factors for LSM in patients with chronic hepatitis C (CHC) using acoustic radiation force impulse (ARFI) technology. METHODS A cohort of 127 Taiwanese patients with CHC underwent ARFI LSM and immediate percutaneous liver biopsy. This study compares the concurrent diagnostic performances of LSM and FibroTest using receiver operating characteristic (ROC) curves. Three multiple linear regression models were used to evaluate the significance of concurrent patient factors in explaining LSM. RESULTS To classify METAVIR fibrosis (F) stages, the areas under ROC curves (AUCs) were ARFI LSM, 0.847 (95% confidence interval (CI), 0.779-0.914) and FibroTest, 0.823 (95% CI, 0.748-0.898), for F1 versus F2-4; ARFI LSM, 0.902 (95% CI, 0.835-0.970) and FibroTest, 0.812 (95% CI, 0.735-0.888), for F1-2 versus F3-4; ARFI LSM, 0.831 (95% CI, 0.723-0.939) and FibroTest, 0.757 (95% CI, 0.648-0.865), for F1-3 versus F4. After adjusting for other demographic and biological covariates, biochemical and histological necroinflammatory factors consistently explained LSM. Factors included serum alanine aminotransferase (ALT)/upper limit of normal (ULN) categories (model R(2) = 0.661, adjusted R(2) = 0.629), ActiTest A scores (R(2) = 0.662, adjusted R(2) = 0.636), and METAVIR activity (A) grades (R(2) = 0.651, adjusted R(2) = 0.620). METAVIR F stages, body mass index, and platelet count were also independently associated with LSM. Necroinflammatory degrees, including ALT/ULN, ActiTest A scores, and METAVIR A grades, explained the false positivity of liver fibrosis staging using ARFI LSM. CONCLUSIONS The degree of hepatic necroinflammatory activity independently and significantly exaggerated liver fibrosis evaluation using ARFI LSM. However, comparisons with concurrent FibroTest indicate that ARFI LSM may be a promising alternative, or adjunctive single indicator, for liver fibrosis evaluation in patients with CHC.
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Affiliation(s)
- Sheng-Hung Chen
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, No 2 Yuh-Der Road, Taichung, 40402, Taiwan
- China Medical University, Taichung, 40402, Taiwan
| | - Yu-Fen Li
- Institute of Biostatistics Center, China Medical University, Taichung, 40402, Taiwan
| | - Hsueh-Chou Lai
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, No 2 Yuh-Der Road, Taichung, 40402, Taiwan
- College of Chinese Medicine, China Medical University, Taichung, 40402, Taiwan
| | - Jung-Ta Kao
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, No 2 Yuh-Der Road, Taichung, 40402, Taiwan
- China Medical University, Taichung, 40402, Taiwan
| | - Cheng-Yuan Peng
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, No 2 Yuh-Der Road, Taichung, 40402, Taiwan
- School of Medicine, China Medical University, Taichung, 40402, Taiwan
| | - Po-Heng Chuang
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, No 2 Yuh-Der Road, Taichung, 40402, Taiwan
- China Medical University, Taichung, 40402, Taiwan
| | - Wen-Pang Su
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, No 2 Yuh-Der Road, Taichung, 40402, Taiwan
- China Medical University, Taichung, 40402, Taiwan
| | - I-Ping Chiang
- School of Medicine, China Medical University, Taichung, 40402, Taiwan
- Department of Pathology, China Medical University Hospital, Taichung, 40402, Taiwan
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Elsharkawy AM, Hudson M. The future developments in hepatology: no need for a jaundiced view. Frontline Gastroenterol 2012; 3:i47-i52. [PMID: 28839693 PMCID: PMC5551950 DOI: 10.1136/flgastro-2012-100153] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/10/2012] [Indexed: 02/04/2023] Open
Abstract
There have been major advances in the diagnosis and management of all forms of liver disease since the British Society of Gastroenterology first came into existence 75 years ago. In this review some of the exciting developments that are likely to enter into routine clinical practice over the next 5 years are highlighted. It is suggested that some critical changes need to take place in UK hepatology over the next decade to ensure that the management of liver disease in this country continues to be among the best in the world.
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Affiliation(s)
- Ahmed Mohamed Elsharkawy
- Liver Unit, University Hospitals Birmingham, Birmingham, UK,Liver Unit, Freeman Hospital, Newcastle upon Tyne, UK
| | - Mark Hudson
- British Association for the Study of the Liver, London, UK
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