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Berger O, Choi W, Ko CH, Thompson MP, Avram MJ, Scott DJ, Hoare BL, Cridge R, Wheatley M, Bathgate RAD, Batlle D, Gianneschi NC. Long-Circulating Vasoactive 1,18-Octadecanedioic Acid-Terlipressin Conjugate. ACS Pharmacol Transl Sci 2024; 7:1252-1261. [PMID: 38751631 PMCID: PMC11092119 DOI: 10.1021/acsptsci.3c00305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2023] [Revised: 03/29/2024] [Accepted: 04/15/2024] [Indexed: 05/18/2024]
Abstract
Hepatorenal syndrome (HRS) is a life-threatening complication of end-stage liver disease first reported over a century ago, but its management still poses an unmet challenge. A therapeutic agent found to stabilize the condition is a short cyclic peptide, vasopressin analogue, terlipressin (TP). While TP is commonly prescribed for HRS patients in most parts of the world, it was only recently approved for use in the United States. TP exhibits short circulation half-lives and adverse side effects associated with the dose required. Herein, we present a 1,18-octadecanedioic acid (ODDA) conjugate of the cyclic peptide (ODDA-TP), which enables noncovalent binding to serum albumin via native fatty acid binding modes. ODDA-TP is demonstrated to outperform TP alone in studies including in vitro cellular receptor activation, stability in plasma, pharmacokinetics, and performance in vivo in rats. Specifically, ODDA-TP had an elimination half-life 20 times that of TP alone while exhibiting a superior safety profile.
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Affiliation(s)
- Or Berger
- Department
of Chemistry, Northwestern University, Evanston, Illinois 60208, United States
| | - Wonmin Choi
- Department
of Chemistry, Northwestern University, Evanston, Illinois 60208, United States
| | - Caroline H. Ko
- NewCures,
Innovation and Ventures Office, Northwestern
University, Evanston, Illinois 60208, United States
| | - Matthew P. Thompson
- Department
of Chemistry, Northwestern University, Evanston, Illinois 60208, United States
| | - Michael J. Avram
- Feinberg
Medical School, Northwestern University, Chicago, Illinois 60611, United States
- Department
of Anesthesiology, Northwestern University, Chicago, Illinois 60611, United States
| | - Daniel J. Scott
- The
Florey,Parkville, Victoria 3010, Australia
- Department
of Biochemistry and Pharmacology, The University
of Melbourne, Parkville, Victoria 3010, Australia
| | | | | | - Mark Wheatley
- Centre
for Sport, Exercise and Life Sciences, Coventry
University, Coventry CV1 5FB, U.K.
- Centre
of Membrane Proteins and Receptors (COMPARE), University of Birmingham and University of Nottingham, Midlands B15 2TT, U.K.
| | - Ross A. D. Bathgate
- The
Florey,Parkville, Victoria 3010, Australia
- Department
of Biochemistry and Pharmacology, The University
of Melbourne, Parkville, Victoria 3010, Australia
| | - Daniel Batlle
- Feinberg
Medical School, Northwestern University, Chicago, Illinois 60611, United States
- Department
of Medicine Division of Nephrology and Hypertension, Chicago, Illinois 60611, United States
| | - Nathan C. Gianneschi
- Department
of Chemistry, Northwestern University, Evanston, Illinois 60208, United States
- Department
of Materials Science and Engineering, Northwestern
University, Evanston, Illinois 60208, United States
- Department of Biomedical Engineering, Northwestern
University, Evanston, Illinois 60208, United States
- Department of Pharmacology, Northwestern
University, Chicago, Illinois 60611, United States
- International Institute for Nanotechnology, Northwestern University, Evanston, Illinois 60208, United States
- Simpson-Querrey Institute, Northwestern
University, Chicago, Illinois 60611, United States
- Chemistry of Life Processes Institute, Northwestern University, Evanston, Illinois 60208, United States
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Lusnig L, Sagingalieva A, Surmach M, Protasevich T, Michiu O, McLoughlin J, Mansell C, De' Petris G, Bonazza D, Zanconati F, Melnikov A, Cavalli F. Hybrid Quantum Image Classification and Federated Learning for Hepatic Steatosis Diagnosis. Diagnostics (Basel) 2024; 14:558. [PMID: 38473030 DOI: 10.3390/diagnostics14050558] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Revised: 02/17/2024] [Accepted: 02/26/2024] [Indexed: 03/14/2024] Open
Abstract
In the realm of liver transplantation, accurately determining hepatic steatosis levels is crucial. Recognizing the essential need for improved diagnostic precision, particularly for optimizing diagnosis time by swiftly handling easy-to-solve cases and allowing the expert time to focus on more complex cases, this study aims to develop cutting-edge algorithms that enhance the classification of liver biopsy images. Additionally, the challenge of maintaining data privacy arises when creating automated algorithmic solutions, as sharing patient data between hospitals is restricted, further complicating the development and validation process. This research tackles diagnostic accuracy by leveraging novel techniques from the rapidly evolving field of quantum machine learning, known for their superior generalization abilities. Concurrently, it addresses privacy concerns through the implementation of privacy-conscious collaborative machine learning with federated learning. We introduce a hybrid quantum neural network model that leverages real-world clinical data to assess non-alcoholic liver steatosis accurately. This model achieves an image classification accuracy of 97%, surpassing traditional methods by 1.8%. Moreover, by employing a federated learning approach that allows data from different clients to be shared while ensuring privacy, we maintain an accuracy rate exceeding 90%. This initiative marks a significant step towards a scalable, collaborative, efficient, and dependable computational framework that aids clinical pathologists in their daily diagnostic tasks.
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Affiliation(s)
- Luca Lusnig
- Terra Quantum AG, 9000 St. Gallen, Switzerland
- Research Unit of Paleoradiology and Allied Sciences, Laboratorio di Telematica Sanitaria-Struttura Complessa Informatica e Telecomunicazioni, Azienda Sanitaria Universitaria Giuliana Isontina, 34149 Trieste, Italy
| | | | | | | | | | | | | | - Graziano De' Petris
- Laboratorio di Telematica Sanitaria-Struttura Complessa Informatica e Telecomunicazioni, Azienda Sanitaria Universitaria Giuliana Isontina, 34149 Trieste, Italy
| | - Deborah Bonazza
- Department of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Academic Hospital, 34149 Trieste, Italy
| | - Fabrizio Zanconati
- Department of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Academic Hospital, 34149 Trieste, Italy
| | | | - Fabio Cavalli
- Research Unit of Paleoradiology and Allied Sciences, Laboratorio di Telematica Sanitaria-Struttura Complessa Informatica e Telecomunicazioni, Azienda Sanitaria Universitaria Giuliana Isontina, 34149 Trieste, Italy
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Wang S, Zhou Z, Xu C, Chen H, Ren W, Yang X, Yin Q, Zheng W, Pan H. Establishment and evaluation of an early prediction model of hepatorenal syndrome in patients with decompensated hepatitis B cirrhosis. BMC Gastroenterol 2023; 23:1. [PMID: 36593456 PMCID: PMC9809024 DOI: 10.1186/s12876-022-02618-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Accepted: 12/12/2022] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND AND AIM In China, hepatorenal syndrome is a serious complication in the decompensated stage of hepatitis B cirrhosis, which requires early clinical intervention, so the early diagnosis of hepatorenal syndrome is crucial. This study establishes a new predictive model based on serum biomarkers for the early diagnosis of hepatorenal syndrome. METHODS Patients with decompensated hepatitis B cirrhosis who met the inclusion and exclusion criteria were retrospectively enrolled. Patients were randomly assigned to the training dataset and validation dataset at a 7:3 ratio. Univariate and multivariate logistic regression analyses were used to screen the risk factors for hepatorenal syndrome. The identified risk factors were used to establish and verify a model. RESULTS This study included 255 patients with decompensated hepatitis B cirrhosis, including 184 in the training group and 71 in the validation group. The multivariate logistic regression model was established in the training group and verified in the validation group. Logistic regression showed that hemoglobin (OR 0.938, 95% CI 0.908-0.969), total bilirubin (OR 1.014, 95% CI 1.008-1.021) and creatinine (OR 1.079, 95% CI 1.043-1.117) were independent risk factors for hepatorenal syndrome (P < 0.05). These were used to establish the model. In the training group and the validation group, the area under the ROC curve of the nomogram for the diagnosis of hepatorenal syndrome was 0.968 and 0.980, respectively. CONCLUSION The three serum biomarkers, including hemoglobin, total bilirubin and creatinine, can be used as independent early predictors of hepatorenal syndrome in patients with decompensated hepatitis B cirrhosis.
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Affiliation(s)
- Shouhao Wang
- grid.410645.20000 0001 0455 0905Department of Infectious Diseases, Zhejiang Provincial People’s Hospital, Qingdao University, 310014 Hangzhou, Zhejiang China ,grid.417401.70000 0004 1798 6507Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), No. 158 Shangtang Road, Hangzhou, 310014 Zhejiang China
| | - Zhewen Zhou
- grid.417401.70000 0004 1798 6507Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), No. 158 Shangtang Road, Hangzhou, 310014 Zhejiang China
| | - Chengan Xu
- grid.417401.70000 0004 1798 6507Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), No. 158 Shangtang Road, Hangzhou, 310014 Zhejiang China
| | - Hanzhu Chen
- grid.417401.70000 0004 1798 6507Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), No. 158 Shangtang Road, Hangzhou, 310014 Zhejiang China
| | - Wenya Ren
- grid.417401.70000 0004 1798 6507Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), No. 158 Shangtang Road, Hangzhou, 310014 Zhejiang China
| | - Xingdi Yang
- grid.417401.70000 0004 1798 6507Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), No. 158 Shangtang Road, Hangzhou, 310014 Zhejiang China
| | - Qiaoqiao Yin
- grid.417401.70000 0004 1798 6507Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), No. 158 Shangtang Road, Hangzhou, 310014 Zhejiang China
| | - Wei Zheng
- grid.417401.70000 0004 1798 6507Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), No. 158 Shangtang Road, Hangzhou, 310014 Zhejiang China
| | - Hongying Pan
- grid.417401.70000 0004 1798 6507Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), No. 158 Shangtang Road, Hangzhou, 310014 Zhejiang China
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Mahfoz AM, Gawish AY. Insight into the hepatoprotective, hypolipidemic, and antidiabetic impacts of aliskiren in streptozotocin-induced diabetic liver disease in mice. Diabetol Metab Syndr 2022; 14:163. [PMID: 36316746 PMCID: PMC9620647 DOI: 10.1186/s13098-022-00935-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2022] [Accepted: 10/19/2022] [Indexed: 12/03/2022] Open
Abstract
BACKGROUND Diabetic hepatopathy is a serious complication of poorly controlled diabetes mellitus. An efficient antidiabetic drug which keeps normal liver tissues is not available. The renin-angiotensin system has been reported to be involved in both diabetic state and liver function. Aliskiren is a direct renin inhibitor and a recently antihypertensive drug with poly-pharmacological properties. The aim of the current study is to explore the possible hepatoprotective effects and mechanisms of action of aliskiren against streptozotocin (STZ) induced liver toxicity. METHODS Mice were distributed to 3 groups; first: the normal control group, second: the diabetic control group, third: the diabetic group which received aliskiren (25 mg/kg; oral) for 4 weeks. At the end of the treatment period, plasma glucose, insulin, lipid profile, oxidative stress, and liver function tests were evaluated spectrophotometrically. ELISA technique was used to measure the expression levels of TNF-α and adiponectin. Furthermore, a Histopathological examination of liver samples was done. RESULTS It was shown that aliskiren treatment ameliorated the STZ-induced oxidative stress and elevated inflammatory biomarkers, hypercholesterolemia, serum aminotransferases and alkaline phosphatase levels in diabetic mice. In addition, hepatocellular necrosis, and fibrosis were improved by aliskiren treatment. CONCLUSION aliskiren protects against the liver damage caused by STZ-induced diabetes. This can be explained by its ability to block angiotensin-II, and its anti-diabetic, hypocholesterolemic, antioxidant and anti-inflammatory effects. Aliskiren could be a novel therapeutic strategy to prevent liver diseases associated with hypertension and diabetes mellitus.
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Affiliation(s)
- Amal M Mahfoz
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Modern University for Technology and Information, Cairo, Egypt.
| | - Aya Y Gawish
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Modern University for Technology and Information, Cairo, Egypt
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Rodríguez S, Motta FD, Balbinotto Neto G, Brandão A. WAITING LIST FOR LIVER TRANSPLANTATION: CLINICAL AND ECONOMIC BURDEN. ARQUIVOS DE GASTROENTEROLOGIA 2022; 59:488-493. [PMID: 36515344 DOI: 10.1590/s0004-2803.202204000-87] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Accepted: 08/03/2022] [Indexed: 11/16/2022]
Abstract
BACKGROUND Burden of disease is an indicator that relates to health status. United States and European epidemiological data have shown that the burden of chronic liver disease has increased significantly in recent decades. There are no studies evaluating the impact of complications of chronic liver disease on the waiting list for deceased donor liver transplantation (LTx). OBJECTIVE To determine the clinical and economic burden of complications of liver disease in wait-listed patients from the perspective of a transplant center. METHODS The study retrospectively analyzed medical records of 104 patients wait-listed for deceased donor LTx from October 2012 to May 2016 and whose treatment was fully provided at the study transplant center. Clinical data were obtained from electronic medical records, while economic data were collected from a hospital management software. To allocate all direct medical costs, two methods were used: full absorption costing and micro-costing. RESULTS The most common complication was refractory ascites (20.2%), followed by portosystemic encephalopathy (12.5%). The mean number of admissions per patient was 1.37±3.42. Variceal hemorrhage was the complication with longest median length of stay (18 days), followed by hepatorenal syndrome (13.5 days). Hepatorenal syndrome was the costliest complication (mean cost of $3,565), followed by portosystemic encephalopathy ($2,576) and variceal hemorrhage ($1,530). CONCLUSION The burden of chronic liver disease includes a great cost for health systems. In addition, it is likely to be even greater as a result of the insidious course of the disease.
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Affiliation(s)
- Santiago Rodríguez
- Universidade Federal de Ciências da Saúde de Porto Alegre, Programa de Pós-Graduação em Medicina: Hepatologia, Porto Alegre, RS, Brasil.,Department of He patology, Hospital Vozandes, Quito, Ecuador
| | - Fabio Da Motta
- Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, RS, Brasil
| | - Giácomo Balbinotto Neto
- Universidade Federal do Rio Grande do Sul, Programa de Pós-Graduação em Economia, Porto Alegre, RS, Brasil.,Instituto de Avaliações de Tecnologias e Saúde - IATS/UFRGS, Porto Alegre, RS, Brasil
| | - Ajácio Brandão
- Universidade Federal de Ciências da Saúde de Porto Alegre, Programa de Pós-Graduação em Medicina: Hepatologia, Porto Alegre, RS, Brasil.,Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, RS, Brasil
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Habas E, Ibrahim AR, Moursi MO, Shraim BA, Elgamal ME, Elzouki AN. Update on hepatorenal Syndrome: Definition, Pathogenesis, and management. Arab J Gastroenterol 2022; 23:125-133. [PMID: 35473682 DOI: 10.1016/j.ajg.2022.01.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 12/25/2021] [Accepted: 01/27/2022] [Indexed: 12/18/2022]
Abstract
Hepatorenal syndrome (HRS) is acute kidney injury (AKI) that occurs without evidence of structural abnormalities in the kidneys in patients with liver disease. It is thought to be due to splanchnic vasculature dilatation that is associated with intense increase of renal arteries' tone, leading to renal cortex ischemia and AKI. Nitric oxide, endotoxins, neurohormonal changes, bacterial infection, high serum bilirubin and bile acids are examples for factors contributing to HRS development. Nevertheless, other unknown factors may have role in HRS pathophysiology. Hence, further discussion and research are needed to clearly understand HRS. Plasma volume restoration and vasoconstrictors are the cornerstone of HRS treatment. Others such as octreotide, noradrenaline, infection control, systemic inflammatory response prevention, shunting, and renal replacement therapy are currently used to manage HRS. Liver or combined liver and kidney transplantation is currently the ultimate cure for HRS. This review was written to help in better understanding the pathogenesis, diagnosis, and treatment options for HRS.
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Affiliation(s)
- Elmukhtar Habas
- Department of Medicine, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar
| | - Ayman R Ibrahim
- College of Medicine, QU Health, Qatar University, Doha, Qatar
| | - Moaz O Moursi
- College of Medicine, QU Health, Qatar University, Doha, Qatar
| | - Bara A Shraim
- College of Medicine, QU Health, Qatar University, Doha, Qatar
| | | | - Abdel-Naser Elzouki
- Department of Medicine, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar; College of Medicine, QU Health, Qatar University, Doha, Qatar; Weill Cornell Medical College, Qatar.
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Wadei HM, Burcin Taner C, Keaveny AP, Mai ML, Hodge DO, White LJ, Harnois DM, Mao SA, Jarmi T, Croome KP. The changing impact of pre-liver transplant renal dysfunction on post-transplant survival: results of 2 decades from a single center. Ann Hepatol 2022; 24:100317. [PMID: 33545403 DOI: 10.1016/j.aohep.2021.100317] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Revised: 12/27/2020] [Accepted: 01/04/2021] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND OBJECTIVES Renal dysfunction before liver transplantation (LT) is associated with higher post-LT mortality. We aimed to study if this association still persisted in the contemporary transplant era. MATERIALS AND METHODS We retrospectively reviewed data on 2871 primary LT performed at our center from 1998 to 2018. All patients were listed for LT alone and were not considered to be simultaneous liver-kidney (SLK) transplant candidates. SLK recipients and those with previous LT were excluded. Patients were grouped into 4 eras: era-1 (1998-2002, n = 488), era-2 (2003-2007, n = 889), era-3 (2008-2012, n = 703) and era-4 (2013-2018, n = 791). Pre-LT renal dysfunction was defined as creatinine (Cr) >1.5 mg/dl or on dialysis at LT. The effect of pre-LT renal dysfunction on post-LT patient survival in each era was examined using Kaplan Meier estimates and univariate and multivariate Cox proportional hazard analyses. RESULTS Pre-LT renal dysfunction was present in 594 (20%) recipients. Compared to patients in era-1, patients in era-4 had higher Cr, lower eGFR and were more likely to be on dialysis at LT (P < 0.001). Pre-LT renal dysfunction was associated with worse 1, 3 and 5-year survival in era-1 and era-2 (P < 0.005) but not in era-3 or era-4 (P = 0.13 and P = 0.08, respectively). Multivariate analysis demonstrated the lack of independent effect of pre-LT renal dysfunction on post-LT mortality in era-3 and era-4. A separate analysis using eGFR <60 mL/min/1.73 m2 at LT to define renal dysfunction showed similar results. CONCLUSIONS Pre-LT renal dysfunction had less impact on post-LT survival in the contemporary transplant era.
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Affiliation(s)
- Hani M Wadei
- Department of Transplant, Mayo Clinic Florida, United States.
| | - C Burcin Taner
- Department of Transplant, Mayo Clinic Florida, United States
| | | | - Martin L Mai
- Department of Transplant, Mayo Clinic Florida, United States
| | - David O Hodge
- Department of Health Sciences Research, Mayo Clinic Florida, United States
| | - Launia J White
- Department of Health Sciences Research, Mayo Clinic Florida, United States
| | - Denis M Harnois
- Department of Transplant, Mayo Clinic Florida, United States
| | - Shennen A Mao
- Department of Transplant, Mayo Clinic Florida, United States
| | - Tambi Jarmi
- Department of Transplant, Mayo Clinic Florida, United States
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Terres AZ, Balbinot RS, Muscope ALF, Longen ML, Schena B, Cini BT, Luis Rost G, Balensiefer JIL, Eberhardt LZ, Balbinot RA, Balbinot SS, Soldera J. Evidence-based protocol for diagnosis and treatment of hepatorenal syndrome is independently associated with lower mortality. GASTROENTEROLOGIA Y HEPATOLOGIA 2022; 45:25-39. [PMID: 33746028 DOI: 10.1016/j.gastrohep.2021.02.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Revised: 01/22/2021] [Accepted: 02/05/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Hepatorenal syndrome (HRS) is the deadliest complication of cirrhosis. The purpose of this study is to analyze if the use of a protocol for HRS is associated with higher survival in these patients. METHODS An evidence-based protocol for the diagnosis and treatment of HRS was instituted in 2013. Data from medical records from 2010 to 2016 were obtained by searching the hospital database for patients who received terlipressin, in the three years before and after the institution of the protocol. Data were reviewed to confirm the diagnosis of HRS and multiple variables were collected. Liver-specific scores were calculated and a stepwise Cox regression approach was used for univariate and multivariate analysis. RESULTS The study included 46 patients, 20 from the pre-protocol period and 26 from the post-protocol period. Respectively, mortality at 30 days, 90 days and 365 days was 75%, 75% and 90% for the pre-protocol period, and 61%, 69% and 80% for the post-protocol period. In the multivariate analysis, an aspartate aminotransferase (AST) of <40U/L, the pre-protocol period and higher Child-Turcotte-Pugh scores were associated with higher 30-day and 90-day mortality. The total mean dose of terlipressin and human albumin used per patient was reduced from 27mg to 22mg and from 236g to 144g, respectively, after the institution of the protocol. This was not associated with higher mortality. CONCLUSION The use of an evidence-based protocol for the treatment of HRS translated into a higher survival. The authors suggest that the use of evidence-based protocols for the diagnosis and treatment of HRS could reduce cost and mortality in tertiary hospitals.
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Affiliation(s)
- Alana Zulian Terres
- Internal Medicine, Hospital Pompeia, Caxias do Sul, RS, Brazil; Gastroenterology, Hospital Geral de Caxias do Sul (RS), Brazil
| | - Rafael Sartori Balbinot
- Residency in Internal Medicine, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil; Faculty of Medicine, Universidade de Caxias do Sul, Caxias do Sul, RS, Brazil
| | | | | | - Bruna Schena
- Faculty of Medicine, Universidade de Caxias do Sul, Caxias do Sul, RS, Brazil
| | - Bruna Teston Cini
- Faculty of Medicine, Universidade de Caxias do Sul, Caxias do Sul, RS, Brazil
| | - Gilberto Luis Rost
- Faculty of Medicine, Universidade de Caxias do Sul, Caxias do Sul, RS, Brazil
| | | | | | - Raul Angelo Balbinot
- Clinical Gastroenterology, Universidade de Caxias do Sul (UCS), Caxias do Sul, RS, Brazil; Department of Gastroenterology, Universidade de São Paulo (USP), São Paulo, SP, Brazil
| | - Silvana Sartori Balbinot
- Clinical Gastroenterology, Universidade de Caxias do Sul (UCS), Caxias do Sul, RS, Brazil; Department of Gastroenterology, Universidade de São Paulo (USP), São Paulo, SP, Brazil
| | - Jonathan Soldera
- Clinical Gastroenterology, Universidade de Caxias do Sul (UCS), Caxias do Sul, RS, Brazil; Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil.
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Nassar M, Nso N, Medina L, Ghernautan V, Novikov A, El-Ijla A, Soliman KM, Kim Y, Alfishawy M, Rizzo V, Daoud A. Liver Kidney Crosstalk: Hepatorenal Syndrome. World J Hepatol 2021; 13:1058-1068. [PMID: 34630874 PMCID: PMC8473490 DOI: 10.4254/wjh.v13.i9.1058] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 05/12/2021] [Accepted: 07/30/2021] [Indexed: 02/06/2023] Open
Abstract
The dying liver causes the suffocation of the kidneys, which is a simplified way of describing the pathophysiology of hepatorenal syndrome (HRS). HRS is characterized by reversible functional renal impairment due to reduced blood supply and glomerular filtration rate, secondary to increased vasodilators. Over the years, HRS has gained much attention and focus among hepatologists and nephrologists. HRS is a diagnosis of exclusion, and in some cases, it carries a poor prognosis. Different classifications have emerged to better understand, diagnose, and promptly treat this condition. This targeted review aims to provide substantial insight into the epidemiology, pathophysiology, diagnosis, and management of HRS, shed light on the various milestones of this condition, and add to our current understanding.
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Affiliation(s)
- Mahmoud Nassar
- Department of Medicine, Icahn School of Medicine at Mount Sinai / NYC Health + Hospitals / Queens, New York, NY 11432, United States
| | - Nso Nso
- Department of Medicine, Icahn School of Medicine at Mount Sinai / NYC Health + Hospitals / Queens, New York, NY 11432, United States
| | - Luis Medina
- Department of Medicine, Icahn School of Medicine at Mount Sinai / NYC Health + Hospitals / Queens, New York, NY 11432, United States
| | - Victoria Ghernautan
- Department of Medicine, Icahn School of Medicine at Mount Sinai / NYC Health + Hospitals / Queens, New York, NY 11432, United States
| | - Anastasia Novikov
- Department of Medicine, Icahn School of Medicine at Mount Sinai / NYC Health + Hospitals / Queens, New York, NY 11432, United States
| | - Alli El-Ijla
- Department of Medicine, Icahn School of Medicine at Mount Sinai / NYC Health + Hospitals / Queens, New York, NY 11432, United States
| | - Karim M Soliman
- Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, United States
| | - Yungmin Kim
- Department of Medicine, Icahn School of Medicine at Mount Sinai / NYC Health + Hospitals / Queens, New York, NY 11432, United States
| | - Mostafa Alfishawy
- Department of Infectious Diseases, Infectious Diseases Consultants and Academic Researchers of Egypt IDCARE, Cairo 11562, Egypt
| | - Vincent Rizzo
- Department of Medicine, Icahn School of Medicine at Mount Sinai / NYC Health + Hospitals / Queens, New York, NY 11432, United States
| | - Ahmed Daoud
- Department of Medicine, Kasr Alainy Medical School, Cairo University, Cairo 11211, Egypt.
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10
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Liu PMF, de Carvalho ST, Fradico PF, Cazumbá MLB, Campos RGB, Simões E Silva AC. Hepatorenal syndrome in children: a review. Pediatr Nephrol 2021; 36:2203-2215. [PMID: 33001296 PMCID: PMC7527294 DOI: 10.1007/s00467-020-04762-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Revised: 08/01/2020] [Accepted: 09/05/2020] [Indexed: 02/07/2023]
Abstract
Hepatorenal syndrome (HRS) occurs in patients with cirrhosis or fulminant hepatic failure and is a kind of pre-renal failure due to intense reduction of kidney perfusion induced by severe hepatic injury. While other causes of pre-renal acute kidney injury (AKI) respond to fluid infusion, HRS does not. HRS incidence is 5% in children with chronic liver conditions before liver transplantation. Type 1 HRS is an acute and rapidly progressive form that often develops after a precipitating factor, including gastrointestinal bleeding or spontaneous bacterial peritonitis, while type 2 is considered a slowly progressive form of kidney failure that often occurs spontaneously in chronic ascites settings. HRS pathogenesis is multifactorial. Cirrhosis causes portal hypertension; therefore, stasis and release of vasodilator substances occur in the hepatic vascular bed, leading to vasodilatation of splanchnic arteries and systemic hypotension. Many mechanisms seem to work together to cause this imbalance: splanchnic vasodilatation; vasoactive mediators; hyperdynamic circulation states and subsequent cardiac dysfunction; neuro-hormonal mechanisms; changes in sympathetic nervous system, renin-angiotensin system, and vasopressin. In patients with AKI and cirrhosis, fluid expansion therapy needs to be initiated as soon as possible and nephrotoxic drugs discontinued. Once HRS is diagnosed, pharmacological treatment with vasoconstrictors, mainly terlipressin plus albumin, should be initiated. If there is no response, other options can include surgical venous shunts and kidney replacement therapy. In this regard, extracorporeal liver support can be a bridge for liver transplantation, which remains as the ideal treatment. Further studies are necessary to investigate early biomarkers and alternative treatments for HRS.
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Affiliation(s)
- Priscila Menezes Ferri Liu
- Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Federal University of Minas Gerais, UFMG, Avenida Alfredo Balena, 190, 2nd floor, #281 room, Belo Horizonte, Minas Gerais, 30130-100, Brazil
| | - Sarah Tayná de Carvalho
- Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Federal University of Minas Gerais, UFMG, Avenida Alfredo Balena, 190, 2nd floor, #281 room, Belo Horizonte, Minas Gerais, 30130-100, Brazil
| | - Pollyanna Faria Fradico
- Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Federal University of Minas Gerais, UFMG, Avenida Alfredo Balena, 190, 2nd floor, #281 room, Belo Horizonte, Minas Gerais, 30130-100, Brazil
| | - Maria Luiza Barreto Cazumbá
- Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Federal University of Minas Gerais, UFMG, Avenida Alfredo Balena, 190, 2nd floor, #281 room, Belo Horizonte, Minas Gerais, 30130-100, Brazil
| | - Ramon Gustavo Bernardino Campos
- Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Federal University of Minas Gerais, UFMG, Avenida Alfredo Balena, 190, 2nd floor, #281 room, Belo Horizonte, Minas Gerais, 30130-100, Brazil
| | - Ana Cristina Simões E Silva
- Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Federal University of Minas Gerais, UFMG, Avenida Alfredo Balena, 190, 2nd floor, #281 room, Belo Horizonte, Minas Gerais, 30130-100, Brazil.
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11
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Pampalone M, Corrao S, Amico G, Vitale G, Alduino R, Conaldi PG, Pietrosi G. Human Amnion-Derived Mesenchymal Stromal Cells in Cirrhotic Patients with Refractory Ascites: A Possible Anti-Inflammatory Therapy for Preventing Spontaneous Bacterial Peritonitis. Stem Cell Rev Rep 2021; 17:981-998. [PMID: 33389680 PMCID: PMC8166706 DOI: 10.1007/s12015-020-10104-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/01/2020] [Indexed: 12/24/2022]
Abstract
Cirrhosis is associated with dysregulated immune cell activation and immune dysfunction. These conditions modify gut flora, facilitate bacterial translocation, and increase susceptibility to bacterial peritonitis and consequent systemic infections by dramatically affecting long-term patient survival. Human amnion-derived mesenchymal stromal cells (hA-MSCs) exert immunomodulatory potential benefit, and have the ability to modulate their actions, especially in situations requiring immune activation through mechanisms not fully understood. In this study, we aimed to investigate, in vitro, the immunostimulant or immunosuppressive effects of hA-MSCs on cellular components of ascitic fluid obtained from cirrhotic patients with refractory ascites. We found that hA-MSCs viability is not affected by ascitic fluid and, interestingly, hA-MSCs diminished the pro-inflammatory cytokine production, and promoted anti-inflammatory M2 macrophage polarization. Moreover, we found that there was no simultaneous significant decrease in the M1-like component, allowing a continual phagocytosis activity of macrophages and NK cells to restore a physiological condition. These data highlight the plasticity of hA-MSCs' immunomodulatory capacity, and pave the way to further understanding their role in conditions such as spontaneous bacterial peritonitis.
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Affiliation(s)
- Mariangela Pampalone
- Ri.MED Foundation, Palermo, Italy
- Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), Palermo, Italy
| | - Simona Corrao
- Ri.MED Foundation, Palermo, Italy
- Section of Histology and Embryology, Department of Biomedicine Neurosciences and Advanced Diagnostics (BiND), University of Palermo, Palermo, Italy
| | - Giandomenico Amico
- Ri.MED Foundation, Palermo, Italy
- Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), Palermo, Italy
| | - Giampiero Vitale
- Ri.MED Foundation, Palermo, Italy
- Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), Palermo, Italy
| | - Rossella Alduino
- Ri.MED Foundation, Palermo, Italy
- Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), Palermo, Italy
| | - Pier Giulio Conaldi
- Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), Palermo, Italy
| | - Giada Pietrosi
- Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), Palermo, Italy
- Hepatology Unit, Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, IRCCS-ISMETT, Palermo, Italy
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12
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Juanola A, Solé C, Toapanta D, Ginès P, Solà E. Monitoring Renal Function and Therapy of Hepatorenal Syndrome Patients with Cirrhosis. Clin Liver Dis 2021; 25:441-460. [PMID: 33838860 DOI: 10.1016/j.cld.2021.01.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Acute kidney injury (AKI) is a frequent complication in patients with cirrhosis. Patients with cirrhosis can develop AKI due to different causes. Hepatorenal syndrome (HRS) is a unique cause of AKI occurring in patients with advanced cirrhosis and is associated with high short-term mortality. The differential diagnosis between different causes of AKI may be challenging. In this regard, new urine biomarkers may be helpful. Liver transplantation is the definitive treatment of patients with HRS-AKI. Vasoconstrictors and albumin represent the first-line pharmacologic treatment of HRS-AKI. This review summarizes current knowledge for the diagnosis and management of HRS in cirrhosis.
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Affiliation(s)
- Adrià Juanola
- Liver Unit, Hospital Clínic de Barcelona, 08036 Barcelona, Catalonia, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Catalonia, Spain
| | - Cristina Solé
- Liver Unit, Hospital Clínic de Barcelona, 08036 Barcelona, Catalonia, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Catalonia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain
| | - David Toapanta
- Liver Unit, Hospital Clínic de Barcelona, 08036 Barcelona, Catalonia, Spain
| | - Pere Ginès
- Liver Unit, Hospital Clínic de Barcelona, 08036 Barcelona, Catalonia, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Catalonia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain; Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Catalonia, Spain.
| | - Elsa Solà
- Liver Unit, Hospital Clínic de Barcelona, 08036 Barcelona, Catalonia, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Catalonia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain; Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Catalonia, Spain
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13
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Dourakis SP, Geladari E, Geladari C, Vallianou N. Cirrhotic Cardiomyopathy: The Interplay Between Liver and Cardiac Muscle. How Does the Cardiovascular System React When the Liver is Diseased? Curr Cardiol Rev 2021; 17:78-84. [PMID: 31072296 PMCID: PMC8142364 DOI: 10.2174/1573403x15666190509084519] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2019] [Revised: 04/21/2019] [Accepted: 04/22/2019] [Indexed: 12/03/2022] Open
Abstract
It is widely known that liver cirrhosis, regardless of the etiologies is accompanied by severe hemodynamic changes. The principal pathophysiological mechanisms are the hyperdynamic circulation with increased cardiac output, heart rate along with reduced systemic vascular resistance. Thus, counteractive mechanisms may develop that eventually lead to systolic as well as diastolic dysfunction and rhythm disturbances, in order to keep a steady homeostasis in the human body. Literally, blunted contractile responsiveness to physical or pharmacological stress, impaired diastolic relaxation and electrophysiological changes, primarily QT interval prolongation, do occur progressively in a cirrhotic patient with no known preexisting cardiac disease. This condition is identified as cirrhotic cardiomyopathy (CCM), an entity different from that seen in alcoholic cardiac muscle disease. For the past decades, clinicians did study and attempt to understand the pathophysiology and clinical significance of this process. Indeed, various factors have been identified acting at the molecular and cellular level. Electrocardiography, echocardiography and various serum biomarkers are the main tools that help healthcare practitioners to point to the correct diagnosis. Noteworthy, the subjects that suffer from cirrhotic cardiomyopathy may progress to heart failure during invasive procedures such as surgery, insertion of a transjugular intrahepatic portosystemic shunting (TIPS) and liver transplantation. Besides, several studies have illustrated that CCM is a contributing factor, or even a precipitant, of hepatorenal syndrome (HRS), a conceivable reversible kidney failure in patients with liver cirrhosis and ascites. The treatment is the same as it is in the patients with liver cirrhosis and heart failure and there is no particular treatment for cirrhotic cardiomyopathy. Hence, it is of utmost importance to clearly comprehend the pathophysiology of this disease in order to design more accurate diagnostic tools and definitive treatments in a way to prevent the complications of cirrhosis and overt heart failure. The objective of this review is to describe in a comprehensive way the pathological alterations that occur in the cardiovascular system of cirrhotic patients. It will also point the limitations that remain in the diagnosis and treatment strategies and more importantly, this review will alert the clinicians in the modern era to further observe and record additional pathological changes in this subset of patients.
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Affiliation(s)
- Spyros P Dourakis
- 2nd Department of Internal Medicine and Research Laboratory, Medical School, National and Kapodistrian University of Athens, Hippokration Hospital, Athens, Greece
| | - Eleni Geladari
- Internal Medicine Department, Evaggelismos General Hospital, Athens, Greece
| | | | - Natalia Vallianou
- Internal Medicine Department, Evaggelismos General Hospital, Athens, Greece
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14
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Rajakumar A, Appuswamy E, Kaliamoorthy I, Rela M. Renal Dysfunction in Cirrhosis: Critical Care Management. Indian J Crit Care Med 2021; 25:207-214. [PMID: 33707901 PMCID: PMC7922436 DOI: 10.5005/jp-journals-10071-23721] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Cirrhotic patients with manifestations of the end-stage liver disease have a high risk for developing renal dysfunction even with minor insults. The development of renal dysfunction increases the morbidity and mortality of these patients. Causes of renal dysfunction in cirrhotics can be due to hepatorenal syndrome (HRS) or acute kidney injury (AKI) resulting from prerenal, renal, and postrenal causes. Development of pretransplant renal dysfunction has been shown to affect post-liver transplantation outcomes. Early detection and aggressive strategies for the prevention of further progression of renal dysfunction seem to decrease the morbidity and improve survival in this group of patients. This article aims to outline the pathogenesis of renal dysfunction in cirrhosis, etiological factors, and evaluation of renal dysfunction, strategies for aggressive therapy for renal dysfunction, the indications of renal replacement therapy (RRT) in this group of patients, and the various modalities of RRT with their merits and demerits. A thorough understanding of the pathogenesis, early detection, and aggressive corrective measures for AKI can prevent further progression. In conclusion, a good knowledge of treatment modalities available for renal dysfunction in cirrhosis and institution of timely interventions can significantly improve survival in this group of patients.
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Affiliation(s)
- Akila Rajakumar
- Department of Liver Anaesthesia and Intensive Care, Dr. Rela Institute and Medical Centre, Chennai, Tamil Nadu, India
| | - Ellango Appuswamy
- Department of Liver Anaesthesia and Intensive Care, Gleneagles Global Health City, Chennai, Tamil Nadu, India
| | - Ilankumaran Kaliamoorthy
- Department of Liver Anaesthesia and Intensive Care, Dr. Rela Institute and Medical Centre, Chennai, Tamil Nadu, India
| | - Mohamed Rela
- Department of Liver Transplantation and HPB Surgery, Dr. Rela Institute and Medical Centre, Chennai, Tamil Nadu, India
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15
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Standardized approach of albumin, midodrine and octreotide on hepatorenal syndrome treatment response rate. Eur J Gastroenterol Hepatol 2021; 33:102-106. [PMID: 32243349 DOI: 10.1097/meg.0000000000001700] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Hepatorenal syndrome (HRS) remains a serious complication of cirrhosis with a high mortality rate. There is little information on the effect of standardizing albumin, midodrine and octreotide combination on treatment response in patients with HRS. OBJECTIVE The aim of the study was to determine the impact of a standardized HRS treatment regimen on renal function recovery. The primary outcome was full response rate. Secondary outcomes included partial and no response rates, 30-day all-cause mortality, ICU length of stay (LOS), hospital LOS, liver transplantation and total dose of albumin. METHODS This retrospective study evaluated the impact of using a standardized approach with albumin, midodrine and octreotide on treatment response rates compared to a historical group. RESULTS Of the patients with HRS, 28 received a standardized approach with albumin, midodrine and octreotide while 60 received a nonstandardized approach. Ten percent of patients achieved full response in the prestandardization group compared with 25% in the poststandardization group (P = 0.07). Renal replacement therapy was significantly more prevalent in the prestandardization group vs. poststandardization group (45% vs. 21.4%, P = 0.03). Liver transplantation was performed significantly more often in the prestandardization group compared the poststandardization group (23% vs. 3.6%, P = 0.02). Amount of albumin used was statistically lower in the poststandardization group (425 vs. 332 g, P = 0.05). No significant differences in days of HRS treatment, mortality rate, hospital and ICU LOS were observed. CONCLUSION A trend towards improved treatment response rate was observed after standardizing the HRS treatment regimen. Standardized therapy led to significantly lower rates of renal replacement therapy and liver transplantation, suggesting patients in poststandardization were effectively managed medically without requiring further intervention.
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16
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Gallo A, Dedionigi C, Civitelli C, Panzeri A, Corradi C, Squizzato A. Optimal Management of Cirrhotic Ascites: A Review for Internal Medicine Physicians. J Transl Int Med 2020; 8:220-236. [PMID: 33511049 PMCID: PMC7805288 DOI: 10.2478/jtim-2020-0035] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Clinical history of liver cirrhosis is characterised by two phases: the asymptomatic phase, also termed 'compensated cirrhosis', and the phase of complications due to the development of portal hypertension and liver dysfunction, also termed 'decompensated cirrhosis', in which patients may develop ascites, the most frequent and clinically relevant complication of liver cirrhosis. Ascites can be classified into uncomplicated and complicated according to the development of refractoriness, spontaneous bacterial peritonitis (SBP) or the association with hepatorenal syndrome (HRS). In this narrative review, we will extensively discuss the optimal pharmacological and non-pharmacological management of cirrhotic ascites with the aim to offer an updated practical guide to Internal Medicine physicians. According to the amount of fluid in the abdominal cavity, uncomplicated ascites is graded from 1 to 3, and the cornerstone of its management consists of restriction of salt intake, diuretics and large-volume paracentesis (LVP); in recent years, long-term administration of human albumin has acquired a new interesting role. Refractory ascites is primarily managed with LVP and transjugular intrahepatic portosystemic shunt (TIPS) placement in selected patients. The occurrence of renal impairment, especially HRS, worsens the prognosis of patients with cirrhotic ascites and deserves a specific treatment. Also, the management of SBP faces the rising and alarming spread of antibiotic resistance. Hepatic hydrothorax may even complicate the course of the disease and its management is a challenge. Last but not least, liver transplantation (LT) is the ultimate and more effective measure to offer to patients with cirrhotic ascites, particularly when complications occur.
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Affiliation(s)
- Andrea Gallo
- Department of Medicine and Surgery, University of Insubria, Como/Varese, Italy
| | - Cristina Dedionigi
- Department of Medicine and Surgery, University of Insubria, Como/Varese, Italy
| | - Chiara Civitelli
- Department of Medicine and Surgery, University of Insubria, Como/Varese, Italy
| | - Anna Panzeri
- Department of Medicine and Surgery, University of Insubria, Como/Varese, Italy
- Hepatology Center, Ospedale Sant’Anna, Como, Italy
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17
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Tufoni M, Baldassarre M, Zaccherini G, Antognoli A, Caraceni P. Hemodynamic and Systemic Effects of Albumin in Patients with Advanced Liver Disease. CURRENT HEPATOLOGY REPORTS 2020; 19:147-158. [PMID: 32837825 PMCID: PMC7326530 DOI: 10.1007/s11901-020-00521-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Purpose of Review Albumin administration is recommended to prevent or treat specific complications of decompensated cirrhosis based on its capacity to expand plasma volume. However, the molecule also has many other biological properties that are unrelated to the oncotic activity. The purpose of this review is to examine the hemodynamic and systemic effects of albumin administration in patients with decompensated cirrhosis. Recent Findings Besides plasma expansion, albumin appears to act against inflammation, facilitate immunocompetence, and improve cardiac and endothelial function, thus antagonizing critical steps in the pathophysiological cascade underlying decompensated cirrhosis. Summary Increasing knowledge of the pathophysiological mechanisms of the disease, as well the pleiotropic properties of the molecule, provides the rationale for considering albumin as a multi-target disease-modifying agent in decompensated cirrhosis. Both oncotic and non-oncotic properties likely concur with the clinical benefits of long-term albumin administration recently demonstrated in these patients.
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Affiliation(s)
- Manuel Tufoni
- Department of Medical and Surgical Sciences, S. Orsola-Malpighi University Hospital, Alma Mater Studiorum University of Bologna, Via Albertoni 15, 40138 Bologna, Italy
| | - Maurizio Baldassarre
- Department of Medical and Surgical Sciences, S. Orsola-Malpighi University Hospital, Alma Mater Studiorum University of Bologna, Via Albertoni 15, 40138 Bologna, Italy
- Center for Applied Medical Research (CRBA), Alma Mater Studiorum University of Bologna, Bologna, Italy
| | - Giacomo Zaccherini
- Department of Medical and Surgical Sciences, S. Orsola-Malpighi University Hospital, Alma Mater Studiorum University of Bologna, Via Albertoni 15, 40138 Bologna, Italy
| | - Agnese Antognoli
- Department of Medical and Surgical Sciences, S. Orsola-Malpighi University Hospital, Alma Mater Studiorum University of Bologna, Via Albertoni 15, 40138 Bologna, Italy
- Center for Applied Medical Research (CRBA), Alma Mater Studiorum University of Bologna, Bologna, Italy
| | - Paolo Caraceni
- Department of Medical and Surgical Sciences, S. Orsola-Malpighi University Hospital, Alma Mater Studiorum University of Bologna, Via Albertoni 15, 40138 Bologna, Italy
- Center for Applied Medical Research (CRBA), Alma Mater Studiorum University of Bologna, Bologna, Italy
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18
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Bernardi M, Angeli P, Claria J, Moreau R, Gines P, Jalan R, Caraceni P, Fernandez J, Gerbes AL, O'Brien AJ, Trebicka J, Thevenot T, Arroyo V. Albumin in decompensated cirrhosis: new concepts and perspectives. Gut 2020; 69:1127-1138. [PMID: 32102926 PMCID: PMC7282556 DOI: 10.1136/gutjnl-2019-318843] [Citation(s) in RCA: 214] [Impact Index Per Article: 42.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2019] [Revised: 02/03/2020] [Accepted: 02/03/2020] [Indexed: 12/12/2022]
Abstract
The pathophysiological background of decompensated cirrhosis is characterised by a systemic proinflammatory and pro-oxidant milieu that plays a major role in the development of multiorgan dysfunction. Such abnormality is mainly due to the systemic spread of bacteria and/or bacterial products from the gut and danger-associated molecular patterns from the diseased liver triggering the release of proinflammatory mediators by activating immune cells. The exacerbation of these processes underlies the development of acute-on-chronic liver failure. A further mechanism promoting multiorgan dysfunction and failure likely consists with a mitochondrial oxidative phosphorylation dysfunction responsible for systemic cellular energy crisis. The systemic proinflammatory and pro-oxidant state of patients with decompensated cirrhosis is also responsible for structural and functional changes in the albumin molecule, which spoil its pleiotropic non-oncotic properties such as antioxidant, scavenging, immune-modulating and endothelium protective functions. The knowledge of these abnormalities provides novel targets for mechanistic treatments. In this respect, the oncotic and non-oncotic properties of albumin make it a potential multitarget agent. This would expand the well-established indications to the use of albumin in decompensated cirrhosis, which mainly aim at improving effective volaemia or preventing its deterioration. Evidence has been recently provided that long-term albumin administration to patients with cirrhosis and ascites improves survival, prevents complications, eases the management of ascites and reduces hospitalisations. However, variant results indicate that further investigations are needed, aiming at confirming the beneficial effects of albumin, clarifying its optimal dosage and administration schedule and identify patients who would benefit most from long-term albumin administration.
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Affiliation(s)
- Mauro Bernardi
- Department of Medical and Surgical Sciences, Alma Mater Studiorum - University of Bologna, Bologna, Italy
| | - Paolo Angeli
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy,EF Clif, EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain
| | - Joan Claria
- EF Clif, EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain,Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi-Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red (CIBERehd) and Universitat de Barcelona, Barcelona, Spain
| | - Richard Moreau
- EF Clif, EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain,Service d'Hépatologie, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France; Inserm, Université de Paris, Centre de Recherche sur l'Inflammation (CRI), Paris, France
| | - Pere Gines
- Liver Unit, Hospital Clínic, Universitat de Barcelona, Institut d’Investigacions Biomèdiques August Pi-Sunyer (IDIBAPS) and Centro de Investigación Biomèdica en Red (CIBEREHD), Barcelona, Spain
| | - Rajiv Jalan
- Liver Failure Group, Institute for Liver Disease Health, University College London, Royal Free Hospital, London, UK
| | - Paolo Caraceni
- Unit of Semeiotica Medica, Policlinico S Orsola, Bologna; Department of Medical and Surgical Sciences, Alma Mater Studiorum – University of Bologna, Bologna, Italy
| | - Javier Fernandez
- EF Clif, EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain,Liver Unit, Hospital Clínic, Universitat de Barcelona, Institut d’Investigacions Biomèdiques August Pi-Sunyer (IDIBAPS) and Centro de Investigación Biomèdica en Red (CIBEREHD), Barcelona, Spain
| | - Alexander L Gerbes
- Department of Medicine II, Liver Centre Munich, University Hospital, LMU Munich, Munich, Germany
| | - Alastair J O'Brien
- Institute for Liver Disease Health, University College London, Royal Free Hospital, London, UK
| | - Jonel Trebicka
- EF Clif, EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain,Department of Internal Medicine I, Goethe University Frankfurt, Frankfurt, Germany
| | - Thierry Thevenot
- Centre Hospitalier Universitaire de Besançon, Hôpital Jean Minjoz, Service d'Hépatologie et de Soins Intensifs Digestifs, Besançon, France
| | - Vicente Arroyo
- EF Clif, EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain
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19
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Impact of cardiac function, refractory ascites and beta blockers on the outcome of patients with cirrhosis listed for liver transplantation. J Hepatol 2020; 72:463-471. [PMID: 31622697 DOI: 10.1016/j.jhep.2019.10.002] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2019] [Revised: 09/27/2019] [Accepted: 10/07/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Whether non-selective beta blockers (NSBBs) are deleterious in patients with end-stage cirrhosis and refractory ascites has been widely debated. We hypothesized that only the subset of patients on the liver transplant waiting list who had impaired cardiac performance would be at increased risk of mortality if receiving NSBBs. METHODS This study included 584 consecutive patients with cirrhosis evaluated for transplantation between 1999 and 2014. All patients had right heart catheterization with hemodynamic measurements at evaluation. Fifty percent received NSBBs. Refractory ascites was present in 33%. Cardiac performance was assessed by left ventricular stroke work index (LVSWI). Waiting list mortality without liver transplantation was explored using competing risk analysis. RESULTS LVSWI was significantly lower in patients with refractory ascites. In multivariate analysis using competing risk, refractory ascites, NSBBs and LVSWI were associated with waiting list mortality in the whole population, with a statistically significant interaction between NSBBs and LVSWI. The most discriminant value of LVSWI was 64.1 g-m/m2. In the final model, refractory ascites (subdistribution hazard ratio 1.52; 95% CI1.01-2.28; p = 0.0083) and treatment by NSBBs with LVSWI <64.1 g-m/m2 (subdistribution hazard ratio 1.96; 95% CI 1.32-2.90; p = 0.0009) were significantly associated with waiting list mortality, taking into account serum sodium and the model for end-stage liver disease score. CONCLUSIONS This study suggests that compromised cardiac performance is more common in patients with refractory ascites and that NSBBs are deleterious in cirrhotic patients with compromised cardiac performance. These results highlight the prognostic value of cardiac function in patients with end-stage cirrhosis. LAY SUMMARY There are still controversies concerning the impact of non-selective beta blockers on outcomes in patients with decompensated cirrhosis, especially in those with refractory ascites. In this study of 584 cirrhotic patients evaluated for liver transplantation, who underwent right heart catheterization, we have shown that global cardiac performance measured by left ventricular stroke work index is lower in patients with refractory ascites. Administration of non-selective beta blockers in patients with compromised cardiac performance may increase waiting list mortality. These results highlight the prognostic value of global cardiac performance in patients with end-stage cirrhosis.
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Schiavon LDL, Ejima FH, Menezes MRD, Bittencourt PL, Moreira AM, Farias AQ, Chagas AL, Assis AMD, Mattos ÂZD, Salomão BC, Terra C, Martins FPB, Carnevale FC, Rezende GFDM, Paulo GAD, Pereira GHS, Leal Filho JMDM, Meneses JD, Costa LSND, Carneiro MDV, Álvares-DA-Silva MR, Soares MVA, Pereira OI, Ximenes RO, Durante RFS, Ferreira VA, Lima VMD. RECOMMENDATIONS FOR INVASIVE PROCEDURES IN PATIENTS WITH DISEASES OF THE LIVER AND BILIARY TRACT: REPORT OF A JOINT MEETING OF THE BRAZILIAN SOCIETY OF HEPATOLOGY (SBH), BRAZILIAN SOCIETY OF DIGESTIVE ENDOSCOPY (SOBED) AND BRAZILIAN SOCIETY OF INTERVENTIONAL RADIOLOGY AND ENDOVASCULAR SURGERY (SOBRICE). ARQUIVOS DE GASTROENTEROLOGIA 2019; 56:213-231. [PMID: 31460590 DOI: 10.1590/s0004-2803.201900000-42] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/08/2019] [Accepted: 04/12/2019] [Indexed: 12/12/2022]
Abstract
Liver and biliary tract diseases are common causes of morbidity and mortality worldwide. Invasive procedures are usually performed in those patients with hepatobiliary diseases for both diagnostic and therapeutic purposes. Defining proper indications and restraints of commonly used techniques is crucial for proper patient selection, maximizing positive results and limiting complications. In 2018, the Brazilian Society of Hepato-logy (SBH) in cooperation with the Brazilian Society of Interventional Radiology and Endovascular surgery (SOBRICE) and the Brazilian Society of Digestive Endoscopy (SOBED) sponsored a joint single-topic meeting on invasive procedures in patients with hepatobiliary diseases. This paper summarizes the proceedings of the aforementioned meeting. It is intended to guide clinicians, gastroenterologists, hepatologists, radiologists, and endoscopists for the proper use of invasive procedures for management of patients with hepatobiliary diseases.
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Affiliation(s)
- Leonardo de Lucca Schiavon
- Universidade Federal de Santa Catarina, Faculdade de Medicina, Departamento de Clínica Médica, Florianópolis, SC, Brasil
| | | | - Marcos Roberto de Menezes
- Instituto do Câncer do Estado de São Paulo, Setor de Diagnóstico por Imagem, São Paulo, SP, Brasil
- Instituto do Câncer do Estado de São Paulo da Faculdade de Medicina da Universidade de São Paulo, Serviço de Radiologia Intervencionista, São Paulo, SP, Brasil
| | | | - Aírton Mota Moreira
- Universidade de São Paulo, Faculdade de Medicina, Serviço de Radiologia Intervencionista do Instituto de Radiologia, São Paulo, SP, Brasil
| | - Alberto Queiroz Farias
- Universidade de São Paulo, Faculdade de Medicina, Departamento de Gastroenterologia, São Paulo, SP, Brasil
| | - Aline Lopes Chagas
- Universidade de São Paulo, Faculdade de Medicina, Departamento de Gastroenterologia, São Paulo, SP, Brasil
| | - André Moreira de Assis
- Universidade de São Paulo, Faculdade de Medicina, Serviço de Radiologia Intervencionista do Instituto de Radiologia, São Paulo, SP, Brasil
- Hospital Sírio-Libanês, São Paulo, SP, Brasil
| | - Ângelo Zambam de Mattos
- Universidade Federal de Ciências da Saúde de Porto Alegre, Programa de Pós-Graduação em Medicina: Hepatologia, RS, Brasil
| | | | - Carlos Terra
- Universidade do Estado do Rio de Janeiro, Faculdade de Medicina, Departamento de Gastroenterologia, RJ, Brasil
- Hospital Federal de Lagoa, Departamento de Gastroenterologia, Rio de Janeiro, RJ, Brasil
| | | | - Francisco Cesar Carnevale
- Instituto de Radiologia da Faculdade de Medicina da Universidade de São Paulo, Serviço de Radiologia Intervencionista, São Paulo, SP, Brasil
| | | | | | | | - Joaquim Maurício da Motta Leal Filho
- Instituto do Câncer do Estado de São Paulo da Faculdade de Medicina da Universidade de São Paulo, Serviço de Radiologia Intervencionista, São Paulo, SP, Brasil
| | - Juliana de Meneses
- Instituto Hospital de Base do Distrito Federal, Brasília, DF, Brasil
- Instituto Nacional do Câncer, Brasília, DF, Brasil
| | - Lucas Santana Nova da Costa
- Instituto Hospital de Base do Distrito Federal, Brasília, DF, Brasil
- Hospital Sírio-Libanês Unidade Brasília, Brasília, DF, Brasil
| | - Marcos de Vasconcelos Carneiro
- Hospital das Forças Armadas, Brasília, DF, Brasil
- Universidade Católica de Brasília, Curso de Medicina, Brasília, DF, Brasil
| | - Mário Reis Álvares-DA-Silva
- Universidade Federal do Rio Grande do Sul, Faculdade de Medicina, Departamento de Medicina Interna, Rio Grande do Sul, RS, Brasil
| | - Mayra Veloso Ayrimoraes Soares
- Hospital Sírio-Libanês Unidade Brasília, Brasília, DF, Brasil
- Universidade de Brasília, Serviço de Radiologia, Brasília, DF, Brasil
| | - Osvaldo Ignácio Pereira
- Instituto de Radiologia da Faculdade de Medicina da Universidade de São Paulo, Serviço de Radiologia Intervencionista, São Paulo, SP, Brasil
| | - Rafael Oliveira Ximenes
- Hospital das Clínicas da Universidade Federal de Goiás, Serviço de Gastroenterologia e Hepatologia, Goiás, GO, Brasil
| | | | - Valério Alves Ferreira
- Instituto Hospital de Base do Distrito Federal, Brasília, DF, Brasil
- Hospital Santa Marta, Brasília, DF, Brasil
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Tan L, Yang Y, Ma G, Zhu T, Yang J, Liu H, Zhang W. Early acute kidney injury after liver transplantation in patients with normal preoperative renal function. Clin Res Hepatol Gastroenterol 2019; 43:475-482. [PMID: 31126850 DOI: 10.1016/j.clinre.2018.07.009] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2018] [Revised: 07/21/2018] [Accepted: 07/24/2018] [Indexed: 02/05/2023]
Abstract
AIM Acute kidney injury (AKI) commonly occurs in patients after liver transplantation (LT). However, few studies have focused on AKI and its correlation with clinical outcomes under the Kidney Disease Improving Global Outcomes (KDIGO) criteria. This study aimed to identity the incidence, risk factors, and impacts of early AKI on outcomes in LT recipients with normal preoperative renal function, according to the KDIGO criteria. METHODS Clinical and laboratory data of 227 patients with normal preoperative renal function who underwent LT from January 2011 to January 2015 were retrospectively analyzed. RESULTS During the first week after LT, 106 patients (46.7%) developed AKI based on the KDIGO criteria. A multivariate analysis revealed that BMI of > 25, prolonged inferior vena cava clamping, prolonged cold ischemia time, and post-operative RBC requirements > 10 units were independent risk factors for AKI after LT. The area under the receiver operating characteristic curve for the predictive ability of AKI under these risk factors was 0.748. The occurrence of AKI was associated with longer mechanical ventilation time and post-operative ICU stay, increased post-operative 30-day mortality and decreased long-term patient survival. CONCLUSIONS Even in patients with normal preoperative renal function, AKI was a frequent complication in LT recipients and had both negative short- or long-term effects on patient outcomes, also the severity of AKI had a dose-response relationship with worse outcomes. Patients with BMI > 25, prolonged inferior vena cava clamping, prolonged cold ischemia time, or post-operative RBC requirement > 10 units should be pay particular attention, which may assist in achieving better clinical outcomes.
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Affiliation(s)
- Lingcan Tan
- Department of Anesthesiology, West China Hospital, Sichuan University, No. 37, Guoxue Street, Chengdu 610041, China.
| | - Yaoxin Yang
- Department of Anesthesiology, West China Hospital, Sichuan University, No. 37, Guoxue Street, Chengdu 610041, China
| | - Gang Ma
- Department of Anesthesiology, West China Hospital, Sichuan University, No. 37, Guoxue Street, Chengdu 610041, China
| | - Tao Zhu
- Department of Anesthesiology, West China Hospital, Sichuan University, No. 37, Guoxue Street, Chengdu 610041, China.
| | - Jiayin Yang
- Department of Liver Surgery, West China Hospital, Sichuan University, No. 37, Guoxue Street, Chengdu 610041, China.
| | - Haibei Liu
- Department of Anesthesiology, West China Hospital, Sichuan University, No. 37, Guoxue Street, Chengdu 610041, China
| | - Weiyi Zhang
- Department of Anesthesiology, West China Hospital, Sichuan University, No. 37, Guoxue Street, Chengdu 610041, China
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Garbuzenko DV, Arefyev NO. Current approaches to the management of patients with cirrhotic ascites. World J Gastroenterol 2019; 25:3738-3752. [PMID: 31391769 PMCID: PMC6676543 DOI: 10.3748/wjg.v25.i28.3738] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2019] [Revised: 05/09/2019] [Accepted: 06/25/2019] [Indexed: 02/06/2023] Open
Abstract
This review describes current approaches to the management of patients with cirrhotic ascites in relation to the severity of its clinical manifestations. The PubMed database, the Google Scholar retrieval system, the Cochrane Database of Systematic Reviews, and the reference lists from related articles were used to search for relevant publications. Articles corresponding to the aim of the review were selected for 1991-2018 using the keywords: "liver cirrhosis," "portal hypertension," "ascites," "pathogenesis," "diagnostics," and "treatment." Uncomplicated and refractory ascites in patients with cirrhosis were the inclusion criteria. The literature analysis has shown that despite the achievements of modern hepatology, the presence of ascites is associated with poor prognosis and high mortality. The key to successful management of patients with ascites may be the stratification of the risk of an adverse outcome and personalized therapy. Pathogenetically based approach to the choice of pharmacotherapy and optimization of minimally invasive methods of treatment may improve the quality of life and increase the survival rate of this category of patients.
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Affiliation(s)
| | - Nikolay Olegovich Arefyev
- Department of Pathological Anatomy and Forensic Medicine, South Ural State Medical University, Chelyabinsk 454092, Russia
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23
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Ning Q. Main Complications of AECHB and Severe Hepatitis B (Liver Failure). ACUTE EXACERBATION OF CHRONIC HEPATITIS B 2019. [PMCID: PMC7498917 DOI: 10.1007/978-94-024-1603-9_2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Qin Ning
- Department of Infectious Disease, Tongji Hospital, Wuhan, China
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24
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Affiliation(s)
- Aluko A. Hope
- RS Morrison (corresponding author) Department of Geriatrics and Palliative Medicine, and Hertzberg Palliative Care Institute, Mount Sinai School of Medicine, 1 Gustave Levy Place, Box 1070, New York, New York, USA
| | - R. Sean Morrison
- Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, and Department of Geriatrics and Palliative Medicine, Mount Sinai School of Medicine, New York, New York, USA
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Bernardi M, Caraceni P. Novel perspectives in the management of decompensated cirrhosis. Nat Rev Gastroenterol Hepatol 2018; 15:753-764. [PMID: 30026556 DOI: 10.1038/s41575-018-0045-2] [Citation(s) in RCA: 50] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The current approaches to the management of patients with decompensated cirrhosis are based on targeted strategies aimed at preventing or treating specific complications of the disease. The improved knowledge of the pathophysiological background of advanced cirrhosis, represented by a sustained systemic inflammation strictly linked to a circulatory dysfunction, provides a novel paradigm for the management of these patients, with the ambitious target of modifying the course of the disease by preventing the onset of complications and multiorgan failure; these interventions will eventually improve patients' quality of life, prolong survival and reduce health-care costs. Besides aetiological treatments, these goals could be achieved by persistently antagonizing key pathophysiological events, such as portal hypertension, abnormal bacterial translocation from the gut, liver damage, systemic inflammation, circulatory dysfunction and altered immunological responses. Interestingly, in addition to strategies based on new therapeutic agents, these targets can be tackled by employing drugs that are already used in patients with cirrhosis for different indications or in other clinical settings, including non-absorbable oral antibiotics, non-selective β-blockers, human albumin and statins. The scope of the present Review includes reporting updated information on the treatments that promise to influence the course of advanced cirrhosis and thus act as disease-modifying agents.
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Affiliation(s)
- Mauro Bernardi
- Department of Medical and Surgical Sciences, Alma Mater Studiorum - University of Bologna, Bologna, Italy.
| | - Paolo Caraceni
- Department of Medical and Surgical Sciences, Alma Mater Studiorum - University of Bologna, Bologna, Italy
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26
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Khaldi M, Lemaitre E, Louvet A, Artru F. Insuffisance rénale aiguë et syndrome hépatorénal chez le patient cirrhotique : actualités diagnostiques et thérapeutiques. MEDECINE INTENSIVE REANIMATION 2018. [DOI: 10.3166/rea-2018-0076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
La survenue d’une insuffisance rénale aiguë ou AKI (acute kidney injury) chez un patient cirrhotique est un événement de mauvais pronostic. Parmi les AKI, une entité spécifique au patient cirrhotique décompensé est le syndrome hépatorénal (SHR) dont la définition ainsi que la stratégie thérapeutique ont été réactualisées récemment. La prise en charge de l’AKI hors SHR n’est pas spécifique au patient cirrhotique. La prise en charge du SHR repose sur l’association d’un traitement vasoconstricteur intraveineux et d’un remplissage vasculaire par sérum d’albumine concentrée. Cette association thérapeutique permet d’améliorer le pronostic des patients répondeurs. En contexte d’AKI chez le patient cirrhotique, l’épuration extrarénale (EER) peut être envisagée en cas de non-réponse au traitement médical. La décision de débuter une prise en charge invasive avec EER dépend principalement de la présence d’un projet de transplantation hépatique (TH). En l’absence d’un tel projet, cette décision devrait être prise après évaluation du pronostic à court terme du patient dépendant du nombre de défaillance d’organes et d’autres variables telles que l’âge ou les comorbidités. L’objectif de cette mise au point est de discuter des récentes modifications de la définition de l’AKI et en particulier du SHR chez les patients cirrhotiques, de détailler la prise en charge spécifique du SHR et d’évoquer les processus décisionnels menant ou non à l’instauration d’une EER chez les patients non répondeurs au traitement médical en milieu réanimatoire.
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27
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Chuang CL, Chang CC, Hsu SJ, Huang HC, Lee FY, Huang LJ, Lee SD. Endotoxemia-enhanced renal vascular reactivity to endothelin-1 in cirrhotic rats. Am J Physiol Gastrointest Liver Physiol 2018; 315:G752-G761. [PMID: 30095297 DOI: 10.1152/ajpgi.00302.2017] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Hepatorenal syndrome (HRS), a severe complication of advanced cirrhosis, is defined as hypoperfusion of kidneys resulting from intense renal vasoconstriction in response to generalized systemic arterial vasodilatation. Nevertheless, the mechanisms have been barely investigated. Cumulative studies demonstrated renal vasodilatation in portal hypertensive and compensated cirrhotic rats. Previously, we identified that blunted renal vascular reactivity of portal hypertensive rats was reversed after lipopolysaccharide (LPS). This study was therefore conducted to delineate the sequence of renal vascular alternation and underlying mechanisms in LPS-treated cirrhotic rats. Sprague-Dawley rats were randomly allocated to receive sham surgery (Sham) or common bile duct ligation (CBDL). LPS was induced on the 28th day after surgery. Kidney perfusion was performed at 0.5 or 3 h after LPS to evaluate renal vascular response to endothelin-1 (ET-1). Endotoxemia increased serum ET-1 levels ( P < 0.0001) and renal arterial blood flow ( P < 0.05) in both Sham and CBDL rats. CBDL rats showed enhanced renal vascular reactivity to ET-1 at 3 h after LPS ( P = 0.026). Pretreatment with endothelin receptor type A (ETA) antagonist abrogated the LPS-enhanced renal vascular response in CBDL rats ( P < 0.001). There were significantly lower inducible nitric oxide synthase (iNOS) expression but higher ETA and phosphorylated extracellular signal-regulated kinase (p-ERK) expressions in renal medulla of endotoxemic CBDL rats ( P < 0.05). We concluded that LPS-induced renal iNOS inhibition, ETA upregulation, and subsequent ERK signaling activation may participate in renal vascular hyperreactivity in cirrhosis. ET-1-targeted therapy may be feasible in the control of HRS. NEW & NOTEWORTHY Hepatorenal syndrome (HRS) occurred in advanced cirrhosis after large-volume paracentesis or bacterial peritonitis. We demonstrated that intraperitoneal lipopolysaccharide (LPS) enhanced renal vascular reactivity to endothelin-1 (ET-1) in cirrhotic rats, accompanied by inducible nitric oxide synthase inhibition, endothelin receptor type A (ETA) upregulation, and subsequent extracellular signal-regulated kinase activation in renal medulla. Pretreatment with ETA antagonist abrogated the LPS-enhanced renal vascular response in common bile duct ligation rats. These findings suggest that further clinical investigation of ET-1-targeted therapy may be feasible in the control of HRS.
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Affiliation(s)
- Chiao-Lin Chuang
- Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital , Taipei , Taiwan.,Faculty of Medicine, National Yang-Ming University School of Medicine , Taipei , Taiwan
| | - Ching-Chih Chang
- Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital , Taipei , Taiwan.,Faculty of Medicine, National Yang-Ming University School of Medicine , Taipei , Taiwan
| | - Shao-Jung Hsu
- Faculty of Medicine, National Yang-Ming University School of Medicine , Taipei , Taiwan.,Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital , Taipei , Taiwan
| | - Hui-Chun Huang
- Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital , Taipei , Taiwan.,Faculty of Medicine, National Yang-Ming University School of Medicine , Taipei , Taiwan.,Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital , Taipei , Taiwan
| | - Fa-Yauh Lee
- Faculty of Medicine, National Yang-Ming University School of Medicine , Taipei , Taiwan.,Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital , Taipei , Taiwan
| | - Ling-Ju Huang
- Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital , Taipei , Taiwan.,Faculty of Medicine, National Yang-Ming University School of Medicine , Taipei , Taiwan.,Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital , Taipei , Taiwan
| | - Shou-Dong Lee
- Faculty of Medicine, National Yang-Ming University School of Medicine , Taipei , Taiwan.,Division of Gastroenterology, Department of Medicine, Cheng-Hsin General Hospital , Taipei , Taiwan
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Angeli P, Bernardi M, Villanueva C, Francoz C, Mookerjee RP, Trebicka J, Krag A, Laleman W, Gines P. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol 2018; 69:406-460. [PMID: 29653741 DOI: 10.1016/j.jhep.2018.03.024] [Citation(s) in RCA: 1773] [Impact Index Per Article: 253.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Accepted: 03/28/2018] [Indexed: 02/06/2023]
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Bleszynski MS, Bressan AK, Joos E, Morad Hameed S, Ball CG. Acute care and emergency general surgery in patients with chronic liver disease: how can we optimize perioperative care? A review of the literature. World J Emerg Surg 2018; 13:32. [PMID: 30034510 PMCID: PMC6052581 DOI: 10.1186/s13017-018-0194-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2018] [Accepted: 07/10/2018] [Indexed: 12/15/2022] Open
Abstract
The increasing prevalence of advanced cirrhosis among operative candidates poses a major challenge for the acute care surgeon. The severity of hepatic dysfunction, degree of portal hypertension, emergency of surgery, and severity of patients’ comorbidities constitute predictors of postoperative mortality. Comprehensive history taking, physical examination, and thorough review of laboratory and imaging examinations typically elucidate clinical evidence of hepatic dysfunction, portal hypertension, and/or their complications. Utilization of specific scoring systems (Child-Pugh and MELD) adds objectivity to stratifying the severity of hepatic dysfunction. Hypovolemia and coagulopathy often represent major preoperative concerns. Resuscitation mandates judicious use of intravenous fluids and blood products. As a general rule, the most expeditious and least invasive operative procedure should be planned. Laparoscopic approaches, advanced energy devices, mechanical staplers, and topical hemostatics should be considered whenever applicable to improve safety. Precise operative technique must acknowledge common distortions in hepatic anatomy, as well as the risk of massive hemorrhage from porto-systemic collaterals. Preventive measures, as well as both clinical and laboratory vigilance, for postoperative hepatic and renal decompensation are essential.
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Affiliation(s)
| | - Alexsander K Bressan
- 2Department of Surgery, University of Calgary, Foothills Medical Centre, 1403 - 29 Street NW, Calgary, Alberta Canada
| | - Emilie Joos
- 1Department of Surgery, University of British Columbia, Vancouver, Canada
| | - S Morad Hameed
- 1Department of Surgery, University of British Columbia, Vancouver, Canada
| | - Chad G Ball
- 2Department of Surgery, University of Calgary, Foothills Medical Centre, 1403 - 29 Street NW, Calgary, Alberta Canada
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Terra C, Mattos ÂZD, Pereira G, Farias AQ, Kondo M, Mattos AAD, Medeiros Filho JEMD, Strauss E, Dutra FRD, Mazza M, Lopes EP, Pereira TS, Schiavon LL, Carvalho Filho RJD, Fagundes C, Bittencourt PL. RECOMMENDATIONS OF THE BRAZILIAN SOCIETY OF HEPATOLOGY FOR THE MANAGEMENT OF ACUTE KIDNEY INJURY IN PATIENTS WITH CIRRHOSIS. ARQUIVOS DE GASTROENTEROLOGIA 2018; 55:314-320. [PMID: 30540097 DOI: 10.1590/s0004-2803.201800000-71] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/06/2018] [Accepted: 06/11/2018] [Indexed: 12/11/2022]
Abstract
Acute kidney injury is a common complication of cirrhosis, occurring in up to 20% of patients hospitalized with cirrhosis. This field is rapidly changing, with significant advances in classification, biomarkers and therapy over the last few years. On the behalf of the Brazilian Society of Hepatology, a panel of experts in Hepatology and Nephrology reviewed published evidence to integrate findings and develop the recommendations presented in this manuscript.
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Affiliation(s)
- Carlos Terra
- Universidade do Estado do Rio de Janeiro, Faculdade de Medicina, Departamento de Gastroenterologia, RJ, Brasil
- Hospital Federal de Lagoa, Departamento de Gastroenterologia, Rio de Janeiro, RJ, Brasil
| | - Ângelo Zambam de Mattos
- Universidade Federal de Ciências da Saúde de Porto Alegre, Programa de Pós-Graduação em Medicina: Hepatologia, RS, Brasil
| | - Gustavo Pereira
- Hospital Federal de Bonsucesso, Serviço de Gastroenterologia e Hepatologia, Rio de Janeiro, RJ, Brasil
| | - Alberto Queiroz Farias
- Universidade de São Paulo, Faculdade de Medicina, Departamento de Gastroenterologia, SP, Brasil
| | - Mario Kondo
- Universidade Federal de São Paulo, Faculdade de Medicina, Departamento de Gastroenterologia, SP, Brasil
| | - Angelo Alves de Mattos
- Universidade Federal de Ciências da Saúde de Porto Alegre, Programa de Pós-Graduação em Medicina: Hepatologia, RS, Brasil
| | | | - Edna Strauss
- Universidade de São Paulo, Faculdade de Medicina, Departamento de Patologia, SP, Brasil
| | | | - Marcelo Mazza
- Universidade Federal do Paraná, Faculdade de Medicina, Departamento de Nefrologia, Curitiba, PR, Brasil
| | - Edmundo Pessoa Lopes
- Universidade Federal de Pernambuco, Faculdade de Medicina, Departamento de Medicina Clínica, Recife, PE, Brasil
| | - Tiago Sevá Pereira
- Universidade Estadual de Campinas, Faculdade Ciências Médicas, Disciplina de Gastroenterologia, Campinas, SP, Brasil
| | - Leonardo Lucca Schiavon
- Universidade Federal de Santa Catarina, Faculdade de Medicina, Departamento de Clínica Médica, Florianópolis, SC, Brasil
| | | | - Cláudia Fagundes
- Hospital Federal de Bonsucesso, Serviço de Nefrologia, Rio de Janeiro, RJ, Brasil
- Hospital São Francisco, Unidade de Transplante Renal, Rio de Janeiro, RJ, Brasil
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Systemic hemodynamic response to terlipressin predicts development of hepatorenal syndrome and survival in advanced cirrhosis. Eur J Gastroenterol Hepatol 2018; 30:659-667. [PMID: 29432366 DOI: 10.1097/meg.0000000000001088] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND The aim of this study was to predict the occurrence of hepatorenal syndrome (HRS) and death in patients with advanced cirrhosis and ascites. PATIENTS AND METHODS We retrospectively evaluated 2-year data of 78 patients with cirrhosis and ascites (Child-Pugh B/C: 45/43). The mean arterial pressure (MAP) and cardiac output (CO) were measured in all patients just before administration of 2 mg of terlipressin and 30 min later. Systemic vascular resistance (SVR) was calculated as MAP/CO. ΔMAP, and ΔCO, and ΔSVR were defined as the percentage change of MAP, CO, and SVR, respectively, after terlipressin injection. Plasma renin activity (PRA) and plasma aldosterone were evaluated at baseline. Two multivariate models were used: one excluding (model 1) and one including (model 2) the Model of End-stage Liver Disease score. RESULTS Higher ΔSVR, Model of End-stage Liver Disease score, and PRA were related independently to the severity of cirrhosis. Independent predictors of HRS at 12 and 24 months were ΔSVR (models 1/2: P=0.008/0.01 and 0.01/0.02, respectively), ΔCO (models 1/2: P=0.01/0.03 and 0.03/0.04, respectively), and PRA (models 1/2: P=0.04 and model 1: P=0.04, respectively). ΔSVR at 12 and 24 months (models 1/2: P=0.005/0.01 and 0.01/0.03, respectively) and ΔCO at 24 months (models 1/2: P=0.02/0.01, respectively) were related independently to survival. Patient groups with significantly higher probability of HRS and mortality were identified by certain cutoffs of ΔSVR (20.6 and 22.8%, respectively) and ΔCO (-10.6 and -11.8%, respectively). ΔSVR and ΔCO independently predicted survival in patients with the most advanced cirrhosis and infection-related survival. CONCLUSION An increase in SVR by at least 20% and a decrease in CO at least 10% in response to terlipressin could predict HRS and mortality in patients with advanced cirrhosis.
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Davies T, Wythe S, O'Beirne J, Martin D, Gilbert-Kawai E. Review article: the role of the microcirculation in liver cirrhosis. Aliment Pharmacol Ther 2017; 46:825-835. [PMID: 29023881 DOI: 10.1111/apt.14279] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2017] [Revised: 04/11/2017] [Accepted: 08/06/2017] [Indexed: 12/13/2022]
Abstract
BACKGROUND Intrahepatic microvascular derangements and microcirculatory dysfunction are key in the development of liver cirrhosis and its associated complications. While much has been documented relating to cirrhosis and the dysfunction of the microcirculation in the liver parenchyma, far less is known about the state of the extrahepatic microcirculation and the role this may have in the pathogenesis of multiple organ failure in end stage liver cirrhosis. AIM To provide an update on the role of the microcirculation in the pathophysiology of cirrhosis and its associated complications and briefly discuss some of the imaging techniques which may be used to directly investigate the microcirculation. METHODS A Medline literature search was conducted using the following search terms: 'cirrhosis', 'microcirculation', 'circulation', 'systemic', 'inflammation', 'peripheral', 'hepatorenal' and 'hepatopulmonary'. RESULTS Significant heterogeneous microvascular alterations exist in patients with cirrhosis. Data suggest that the systemic inflammation, associated with advanced cirrhosis, induces microcirculatory dysregulation and contributes to haemodynamic derangement. The resultant vasoconstriction and hypoperfusion in the systemic extrahepatic microvasculature, is likely to be instrumental in the pathophysiology of organ failure in decompensated cirrhosis, however the mechanistic action of vasoactive agents used to correct the circulatory disturbance of advanced cirrhosis is poorly understood. CONCLUSIONS Further research into the role of the microcirculation in patients with liver cirrhosis, will improve physicians understanding of the pathophysiology of cirrhosis, and may provide a platform for real time evaluation of an individual's microcirculatory response to vasoactive mediators, thus guiding their therapy.
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Affiliation(s)
- T Davies
- Intensive Care Department, Royal Free Hospital, London, UK.,UCLH NIHR Biomedical Research Centre, Institute of Sport and Exercise Health, University College London Centre for Altitude Space and Extreme Environment Medicine, London, UK
| | - S Wythe
- Intensive Care Department, Royal Free Hospital, London, UK.,UCLH NIHR Biomedical Research Centre, Institute of Sport and Exercise Health, University College London Centre for Altitude Space and Extreme Environment Medicine, London, UK
| | - J O'Beirne
- Department of Hepatology, Nambour General Hospital, Sunshine Coast Hospital and Health Service, Nambour, Qld, Australia
| | - D Martin
- Intensive Care Department, Royal Free Hospital, London, UK.,UCLH NIHR Biomedical Research Centre, Institute of Sport and Exercise Health, University College London Centre for Altitude Space and Extreme Environment Medicine, London, UK
| | - E Gilbert-Kawai
- Intensive Care Department, Royal Free Hospital, London, UK.,UCLH NIHR Biomedical Research Centre, Institute of Sport and Exercise Health, University College London Centre for Altitude Space and Extreme Environment Medicine, London, UK
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Abstract
Acute on chronic liver failure (ACLF) was first described in 1995 as a clinical syndrome distinct to classic acute decompensation. Characterized by complications of decompensation, ACLF occurs on a background of chronic liver dysfunction and is associated with high rates of organ failure and significant short-term mortality estimated between 45% and 90%. Despite the clinical relevance of the condition, it still remains largely undefined with continued disagreement regarding its precise etiological factors, clinical course, prognostic criteria and management pathways. It is concerning that, despite our relative lack of understanding of the condition, the burden of ACLF among cirrhotic patients remains significant with an estimated prevalence of 30.9%. This paper highlights our current understanding of ACLF, including its etiology, diagnostic and prognostic criteria and pathophysiology. It is evident that further refinement of the ACLF classification system is required in order to detect high-risk patients and improve short-term mortality rates. The field of metabolomics certainly warrants investigation to enhance diagnostic and prognostic parameters, while the use of granulocyte-colony stimulating factor is a promising future therapeutic intervention for patients with ACLF.
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Affiliation(s)
- Azeem Alam
- Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, London, SW7 2AZ, UK
| | - Ka Chun Suen
- Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, London, SW7 2AZ, UK
| | - Daqing Ma
- Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, London, SW7 2AZ, UK
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34
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Piano S, Tonon M, Angeli P. Management of ascites and hepatorenal syndrome. Hepatol Int 2017; 12:122-134. [DOI: 10.1007/s12072-017-9815-0] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2017] [Accepted: 07/27/2017] [Indexed: 12/11/2022]
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Arab JP, Claro JC, Arancibia JP, Contreras J, Gómez F, Muñoz C, Nazal L, Roessler E, Wolff R, Arrese M, Benítez C. Therapeutic alternatives for the treatment of type 1 hepatorenal syndrome: A Delphi technique-based consensus. World J Hepatol 2016; 8:1075-1086. [PMID: 27660674 PMCID: PMC5026999 DOI: 10.4254/wjh.v8.i25.1075] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2016] [Revised: 07/07/2016] [Accepted: 08/01/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To propose several alternatives treatment of type 1 hepatorenal syndrome (HRS-1) what is the most severe expression of circulatory dysfunction on patients with portal hypertension.
METHODS A group of eleven gastroenterologists and nephrologists performed a structured analysis of available literature. Each expert was designated to review and answer a question. They generated draft statements for evaluation by all the experts. Additional input was obtained from medical community. In order to reach consensus, a modified three-round Delphi technique method was used. According to United States Preventive Services Task Force criteria, the quality of the evidence and level of recommendation supporting each statement was graded.
RESULTS Nine questions were formulated. The available evidence was evaluated considering its quality, number of patients included in the studies and the consistency of its results. The generated questions were answered by the expert panel with a high level of agreement. Thus, a therapeutic algorithm was generated. The role of terlipressin and norepinephrine was confirmed as the pharmacologic treatment of choice. On the other hand the use of the combination of octreotide, midodrine and albumin without vasoconstrictors was discouraged. The role of several other options was also evaluated and the available evidence was explored and discussed. Liver transplantation is considered the definitive treatment for HRS-1. The present consensus is an important effort that intends to organize the available strategies based on the available evidence in the literature, the quality of the evidence and the benefits, adverse effects and availability of the therapeutic tools described.
CONCLUSION Based on the available evidence the expert panel was able to discriminate the most appropriate therapeutic alternatives for the treatment of HRS-1.
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Mocarzel LO, Bicca J, Jarske L, Oliveira T, Lanzieri P, Gismondi R, Ribeiro ML. Cirrhotic Cardiomyopathy: Another Case of a Successful Approach to Treatment of Hepatorenal Syndrome. Case Rep Gastroenterol 2016; 10:531-537. [PMID: 27843430 PMCID: PMC5091268 DOI: 10.1159/000448885] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2016] [Accepted: 08/02/2016] [Indexed: 12/31/2022] Open
Abstract
Hepatorenal syndrome (HRS) is defined as a failure of renal function, potentially reversible, in patients with liver cirrhosis and ascites. Recently, a component of cardiomyopathy associated with HRS was described, but the use of positive inotropic medicine as part of the treatment of the acute phase has not been extensively evaluated. We report a second case in our hospital of a patient with HRS type I without previous heart disease, with secondary hemodynamic decompensation due to liver disease, in which the abnormalities in systolic function by speckle-tracking echocardiography were observed and could be reversed by the use of inotropes. After partial response to current therapies, the patient presented a clinical and laboratorial response with improvement of renal function after infusion of dobutamine. Clinical studies are needed for the therapy approach to HRS taking into account myocardial dysfunction as a major contributing factor for renal dysfunction.
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Affiliation(s)
- Luis Otávio Mocarzel
- Department of Internal Medicine, Hospital Universitário Antônio Pedro, Universidade Federal Fluminense, Niterói, Brazil
| | - Jessica Bicca
- Department of Internal Medicine, Hospital Universitário Antônio Pedro, Universidade Federal Fluminense, Niterói, Brazil
| | - Luiza Jarske
- Department of Internal Medicine, Hospital Universitário Antônio Pedro, Universidade Federal Fluminense, Niterói, Brazil
| | - Thamires Oliveira
- Department of Internal Medicine, Hospital Universitário Antônio Pedro, Universidade Federal Fluminense, Niterói, Brazil
| | - Pedro Lanzieri
- Department of Internal Medicine, Hospital Universitário Antônio Pedro, Universidade Federal Fluminense, Niterói, Brazil
| | - Ronaldo Gismondi
- Department of Internal Medicine, Hospital Universitário Antônio Pedro, Universidade Federal Fluminense, Niterói, Brazil
| | - Mario Luiz Ribeiro
- Department of Cardiology, Hospital Universitário Antônio Pedro (HUAP), Niterói, Brazil
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Enescu A, Petrescu F, Mitruţ P, Petrescu IO, Pădureanu V, Enescu AŞ. Hepatorenal Syndrome: Diagnosis and Treatment - newsreel. ROMANIAN JOURNAL OF INTERNAL MEDICINE = REVUE ROUMAINE DE MEDECINE INTERNE 2016; 54:143-150. [PMID: 27658161 DOI: 10.1515/rjim-2016-0024] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/03/2016] [Indexed: 01/06/2023]
Abstract
Hepatorenal syndrome (HRS) is defined as renal failure that occurs in the presence of severe acute or chronic liver disease in the absence of underlying renal pathology. Due to the functional nature of the disease and the absence of specific diagnostic markers, HRS diagnosis is determined based on positive criteria associated with excluding other causes of renal failure in patients with liver cirrhosis and ascites. Differentiation from other types of acute or chronic renal disease is extremely difficult and therapeutic options are limited, prophylactic behavior is most appropriate in patients with severe hepatic disease and risk factors for the installation of hepatorenal syndrome. Highlighting all precipitating factors of acute renal insufficiency and therapeutic modalities in order to minimize adverse events is an important step in improving the follow-up of the patients with liver cirrhosis. The prognosis is reserved especially for type 1 HRS. Liver transplantation is the best option for patients without contraindications. The therapies introduced in recent years, such as vasoconstrictor drugs or transjugular intrahepatic portosystemic shunt are effective methods in the renal function improvement.
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Bile Nephropathy in Flucloxacillin-Induced Cholestatic Liver Dysfunction. Case Rep Nephrol 2016; 2016:4162674. [PMID: 27006842 PMCID: PMC4783551 DOI: 10.1155/2016/4162674] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2016] [Accepted: 02/03/2016] [Indexed: 11/23/2022] Open
Abstract
Kidney injury in the context of cholestatic liver dysfunction is not uncommon; this has been historically referred to as cholemic nephrosis implying a direct deleterious renal effect of cholemia. However, scepticism about the exact role that bile and its constituents play in this injury has led to the disappearance of the term. We describe a case of severe AKI due to bile nephropathy with bile casts in flucloxacillin-induced liver dysfunction. We also discuss the recent literature reviving the concept of bile nephropathy.
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Altun R, Korkmaz M, Yıldırım E, Öcal S, Akbaş E, Selçuk H. Terlipressin and albumin for type 1 hepatorenal syndrome: does bacterial infection affect the response? SPRINGERPLUS 2015; 4:806. [PMID: 26722626 PMCID: PMC4689717 DOI: 10.1186/s40064-015-1625-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/20/2015] [Accepted: 12/15/2015] [Indexed: 01/15/2023]
Abstract
Vasoconstrictor therapy with terlipressin and concomitant albumin can improve renal function in patients with hepatorenal syndrome (HRS) type 1, but the efficacy of therapy in patients with active infection is controversial. The aim of this study was to investigate the efficacy, adverse effects, and predictors of terlipressin therapy and to find out whether there was a difference in response rates between the patients with or without active infections. Data of 58 patients with type 1 HRS treated with terlipressin and albumin were retrospectively evaluated. Twenty-six patients (44.8 %) showed complete response to treatment. Response rates of patients with or without active bacterial infection were 47 and 43.9 %, respectively (p > 0.05). Only baseline serum creatinine level was significantly related to response in univariate/multivariate analyses (p < 0.05). Twenty-three patients (39.6 %) developed adverse effects probably related to treatment. In 8.6 % of patients, treatment was discontinued because of adverse effects of therapy. Four patients (6.9 %) developed ischemic adverse events, including nonfatal myocardial infarction, intestinal ischemia, and cutaneous necrosis. Terlipressin plus albumin therapy improved renal function in nearly half of patients with type 1 HRS. Thus, it seems a reasonable treatment for patients with active bacterial infections. Baseline serum creatinine level is a potential predictor of terlipressin response.
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Affiliation(s)
- Reskan Altun
- Department of Gastroenterology, Baskent University, Ankara, Turkey
| | - Murat Korkmaz
- Department of Gastroenterology, Baskent University, Ankara, Turkey
| | - Emre Yıldırım
- Department of Gastroenterology, Baskent University, Ankara, Turkey
| | - Serkan Öcal
- Department of Gastroenterology, Baskent University, Ankara, Turkey
| | - Enver Akbaş
- Department of Gastroenterology, Baskent University, Ankara, Turkey
| | - Haldun Selçuk
- Department of Gastroenterology, Baskent University, Ankara, Turkey
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40
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Srivastava S, Shalimar, Vishnubhatla S, Prakash S, Sharma H, Thakur B, Acharya SK. Randomized Controlled Trial Comparing the Efficacy of Terlipressin and Albumin with a Combination of Concurrent Dopamine, Furosemide, and Albumin in Hepatorenal Syndrome. J Clin Exp Hepatol 2015; 5:276-85. [PMID: 26900268 PMCID: PMC4723649 DOI: 10.1016/j.jceh.2015.08.003] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2015] [Accepted: 08/24/2015] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Terlipressin with albumin is recommended in hepatorenal syndrome (HRS). Terlipressin is expensive and not licensed in many countries. Alternative therapy is necessary. We compared the efficacy of terlipressin and albumin with concurrent low-dose dopamine, furosemide, and albumin in HRS. METHODS In an open-label, randomized trial, forty consecutive patients each with HRS type I and HRS type II received either concurrent infusion of terlipressin 0.5 mg for every 6 hr and albumin 20 g/day for 5 days (n = 20) or a combination of dopamine 2 μg/kg/min, furosemide 0.01 mg/kg/hr, and albumin 20 g/day (triple therapy), in one of two therapeutic arms. Twenty-four-hour urine output, urinary sodium, and plasma renin activity (PRA) were assessed before and after treatment. RESULTS The two groups were comparable at baseline in both HRS-I and II. In HRS-I, 24 hr urine output and urine sodium at the end of 5 days increased in both treatment groups (terlipressin, urine output 278 ± 136 to 765 ± 699 ml/day, P < 0.01; urine sodium 28 ± 25.1 to 39 ± 32.1 meq/l, P = 0.05. Triple therapy: urine output 219 ± 134 to 706 ± 595 ml/day, P < 0.01; urine sodium 25 ± 18.3 to 41 ± 27.5 meq/l, P < 0.01). PRA (ng/ml/hr) decreased from 28.1 ± 9.76 to 24.2 ± 9.5 (P = 0.01) and from 29.5 ± 15.8 to 27.3 ± 17.1 (P = 0.02) in the terlipressin and triple therapy groups, respectively. In HRS-II, similar significant improvement (P < 0.01) was seen in 24 hr urine output and urine sodium; decrease in PRA (P < 0.05) was documented after treatment in both the arms. Post-treatment changes in parameters were comparable between the two arms, in both HRS-I and HRS-II cases. CONCLUSIONS Concurrent triple therapy improved renal function in HRS and was less expensive than terlipressin (Registration: CTRI/2011/07/001860; www.ctri.nic.in).
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Affiliation(s)
- Siddharth Srivastava
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Shalimar
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Sreenivas Vishnubhatla
- Department of Biostatistics, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Shyam Prakash
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Hanish Sharma
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Bhaskar Thakur
- Department of Biostatistics, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Subrat K. Acharya
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi 110029, India,Address for correspondence: Subrat K. Acharya, Professor and Head of the Department, Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India. Tel.: +91 11 26589130/26594934; fax: +91 11 26589130.
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41
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Wiese S, Hove JD, Møller S. Cardiac imaging in patients with chronic liver disease. Clin Physiol Funct Imaging 2015; 37:347-356. [PMID: 26541640 DOI: 10.1111/cpf.12311] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2014] [Accepted: 09/18/2015] [Indexed: 12/15/2022]
Abstract
Cirrhotic cardiomyopathy (CCM) is characterized by an impaired contractile response to stress, diastolic dysfunction and the presence of electrophysiological abnormalities, and it may be diagnosed at rest in some patients or demasked by physiological or pharmacological stress. CCM seems to be involved in the development of hepatic nephropathy and is associated with an impaired survival. In the field of cardiac imaging, CCM is not yet a well-characterized entity, hence various modalities of cardiac imaging have been applied. Stress testing with either physiologically or pharmacologically induced circulatory stress has been used to assess systolic dysfunction. Whereas echocardiography with tissue Doppler is by far the most preferred method to detect diastolic dysfunction with measurement of E/A- and E/E'-ratio. In addition, echocardiography may also possess the potential to evaluate systolic dysfunction at rest by application of new myocardial strain techniques. Experience with other modalities such as cardiac magnetic resonance imaging and cardiac computed tomography is limited. Future studies exploring these imaging modalities are necessary to characterize and monitor the cardiac changes in cirrhotic patients.
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Affiliation(s)
- Signe Wiese
- Centre of Functional and Diagnostic Imaging and Research, Department of Clinical Physiology and Nuclear Medicine 239, Hvidovre Hospital, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.,Gastro Unit, Medical Division, Hvidovre Hospital, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Jens D Hove
- Department of Cardiology, Hvidovre Hospital, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Søren Møller
- Centre of Functional and Diagnostic Imaging and Research, Department of Clinical Physiology and Nuclear Medicine 239, Hvidovre Hospital, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
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42
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Understanding the Complexities of Cirrhosis. Clin Ther 2015; 37:1822-36. [DOI: 10.1016/j.clinthera.2015.05.507] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2015] [Revised: 03/25/2015] [Accepted: 05/08/2015] [Indexed: 12/13/2022]
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Abstract
The most common complication to chronic liver failure is ascites. The formation of ascites in the cirrhotic patient is caused by a complex chain of pathophysiological events involving portal hypertension and progressive vascular dysfunction. Since ascites formation represents a hallmark in the natural history of chronic liver failure it predicts a poor outcome with a 50% mortality rate within 3 years. Patients with ascites are at high risk of developing complications such as spontaneous bacterial peritonitis, hyponatremia and progressive renal impairment. Adequate management of cirrhotic ascites and its complications betters quality of life and increases survival. This paper summarizes the pathophysiology behind cirrhotic ascites and the diagnostic approaches, as well as outlining the current treatment options. Despite improved medical treatment of ascites, liver transplantation remains the ultimate treatment and early referral of the patient to a highly specialized hepatology unit should always be considered.
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Affiliation(s)
- Julie Steen Pedersen
- Centre of Functional Imaging and Research, Department of Clinical Physiology and Nuclear Medicine, and Gastro Unit, Medical Division, Hvidovre Hospital, Faculty of Health Sciences, University of Copenhagen, Denmark
| | - Flemming Bendtsen
- Gastro Unit, Medical Division, Hvidovre Hospital, Faculty of Health Sciences, University of Copenhagen, Denmark
| | - Søren Møller
- Centre of Functional Imaging and Research, Department of Clinical Physiology and Nuclear Medicine 239, Hvidovre Hospital, DK-2650 Hvidovre, Faculty of Health Sciences, University of Copenhagen, Denmark
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44
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Mura VL, Tosetti G, Primignani M, Salerno F. Use of non-selective beta blockers in cirrhosis: the evidence we need before closing (or not) the window. World J Gastroenterol 2015; 21:2265-2268. [PMID: 25741132 PMCID: PMC4342901 DOI: 10.3748/wjg.v21.i8.2265] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2014] [Revised: 12/17/2014] [Accepted: 01/30/2015] [Indexed: 02/06/2023] Open
Abstract
Non selective beta blockers (NSBBs) are used in primary and secondary prophylaxis of portal hypertension-related bleeding in patients with cirrhosis. The efficacy of NSBBs treatment is predicted by hemodynamic response in term of reduction of the hepatic venous pressure gradient (HVPG) below 12 mmHg or at least 20% of the basal value. Nevertheless a relevant number of patients who do not achieve this HVPG reduction during NSBBs therapy do not bleed during follow up; this evidence suggests an additional non-hemodynamic advantage of NSBBs treatment to modify the natural history of cirrhosis. Recent studies have questioned the efficacy and safety of NSBBs in patients with advanced stage of liver disease characterized by refractory ascites and/or spontaneous bacterial peritonitis. These studies have suggested the existence of a defined and limited period to modify the natural history of cirrhosis by NSBBs: the "window hypothesis". According with this hypothesis, patients with cirrhosis benefit from the use of NSBBs from the appearance of varices up to the development of an advanced stage of cirrhosis. Indeed, in patients with refractory ascites and/or spontaneous bacterial peritonitis the hemodynamic effects of NSBBs may expose to a high risk of further complications such as renal insufficiency and/or death. Methodological concerns and contrasting results counterbalance the evidence produced up to now on this issue and are the main topic of this editorial.
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45
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Zaky A, Bendjelid K. Appraising cardiac dysfunction in liver transplantation: an ongoing challenge. Liver Int 2015; 35:12-29. [PMID: 24797833 DOI: 10.1111/liv.12582] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2013] [Accepted: 04/26/2014] [Indexed: 12/26/2022]
Abstract
End-stage liver disease (ESLD) is a multisystemic disease that adversely and mutually aggravates other organs such as the heart. Cardiac dysfunction in ESLD encompasses a spectrum of disease that could be aggravated, precipitated or be occurring hand-in-hand with coexisting aetiological factors precipitating cirrhosis. Additionally and more complexly, liver transplantation, the curative modality of ESLD, is responsible for additional intra- and postoperative short- and long-term cardiac morbidity. The phenotypic distinction of the different forms of cardiac dysfunction in ESLD albeit important prognostically and therapeutically is not allowed by the current societal recommendations, due to conceptual, and methodological limitations in the appraisal of cardiac function and structure in ESLD and in designing studies that are based on this appraisal. This review comprehensively discusses the spectrum of cardiac dysfunction in ESLD, discusses the limitations of the current appraisal of cardiac dysfunction in ESLD, and proposes a hypothetical approach for studying cardiac dysfunction in liver transplant candidates.
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Affiliation(s)
- Ahmed Zaky
- Department of Anesthesiology and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
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46
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Henriksen UL, Hansen HB, Ring-Larsen H, Bendtsen F, Henriksen JH. Total plasma clearance versus urinary plasma clearance of51Cr-EDTA in patients with cirrhosis with and without fluid retention. Scandinavian Journal of Clinical and Laboratory Investigation 2014; 75:64-72. [DOI: 10.3109/00365513.2014.980313] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Licata A, Mazzola A, Ingrassia D, Calvaruso V, Cammà C, Craxì A. Clinical implications of the hyperdynamic syndrome in cirrhosis. Eur J Intern Med 2014; 25:795-802. [PMID: 25245607 DOI: 10.1016/j.ejim.2014.09.004] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2014] [Revised: 09/02/2014] [Accepted: 09/04/2014] [Indexed: 12/24/2022]
Abstract
The hyperdynamic syndrome is a late consequence of portal hypertension in cirrhosis. The principal hemodynamic manifestations of the hyperdynamic syndrome are high cardiac output, and increased heart rate and total blood volume, accompanied by reduced total systemic vascular resistance. Pathophysiology involves a complex of humoral and neural mechanisms that can determine hemodynamic changes, and lead to hyperdynamic circulation. In this review we focus our attention on the manifestations of the hyperdynamic syndrome. Some of these are well described and directly related to portal hypertension (varices, ascites, hepatic encephalopathy, and hepatorenal syndrome), while others, such as hepatopulmonary syndrome, portopulmonary hypertension, and cirrhotic cardiomyopathy, are less known as clinical manifestations related to cirrhosis and, therefore, merit further investigation.
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Affiliation(s)
- Anna Licata
- Sezione di Gastroenterologia & Epatologia, Dipartimento Biomedico di Medicina Interna e Specialistica, DIBIMIS, Università di Palermo, Palermo, Italy
| | - Alessandra Mazzola
- Sezione di Gastroenterologia & Epatologia, Dipartimento Biomedico di Medicina Interna e Specialistica, DIBIMIS, Università di Palermo, Palermo, Italy
| | - Daniela Ingrassia
- Sezione di Gastroenterologia & Epatologia, Dipartimento Biomedico di Medicina Interna e Specialistica, DIBIMIS, Università di Palermo, Palermo, Italy
| | - Vincenza Calvaruso
- Sezione di Gastroenterologia & Epatologia, Dipartimento Biomedico di Medicina Interna e Specialistica, DIBIMIS, Università di Palermo, Palermo, Italy
| | - Calogero Cammà
- Sezione di Gastroenterologia & Epatologia, Dipartimento Biomedico di Medicina Interna e Specialistica, DIBIMIS, Università di Palermo, Palermo, Italy
| | - Antonio Craxì
- Sezione di Gastroenterologia & Epatologia, Dipartimento Biomedico di Medicina Interna e Specialistica, DIBIMIS, Università di Palermo, Palermo, Italy
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Hung TH, Tseng CW, Tseng KC, Hsieh YH, Tsai CC, Tsai CC. Effect of renal function impairment on the mortality of cirrhotic patients with hepatic encephalopathy: a population-based 3-year follow-up study. Medicine (Baltimore) 2014; 93:e79. [PMID: 25255022 PMCID: PMC4616283 DOI: 10.1097/md.0000000000000079] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Kidney is an important organ to clear neurotoxic substance in circulation. However, it is still unknown about the effect of renal function impairment (RFI) on the mortality of cirrhotic patients with hepatic encephalopathy (HE). We used the Taiwan National Health Insurance Database to identify 4932 cirrhotic patients with HE, hospitalized between January 1, 2007 and December 31, 2007. The enrolled patients were followed up individually for 3 years to identify their 3-year mortalities. There were 411 (8.3%) patients with RFI and 4521 (91.7%) patients without RFI. The adjusted hazard ratio (HR) of RFI for 3-year mortality was 2.03 (95% CI, 1.82-2.27). In RFI group, there were 157 (38.2%) patients with acute renal failure (ARF), 61 (14.8%) with hepatorenal syndrome (HRS), 93 (22.6%) with chronic kidney disease (CKD), and 100 (24.3%) with end-stage renal disease (ESRD). Compared with the non-RFI group, the adjusted HR of ARF for 3-year mortality was 2.57 (95% CI, 2.17-3.06), CKD 1.93 (95% CI, 1.55-2.40), ESRD 1.26 (95% CI, 1.01-1.57), and HRS 3.58 (95% CI, 2.78-4.63). Among ESRD patients, there were 99 patients receiving hemodialysis regularly. Compared with the CKD group, the adjusted HR of ESRD with hemodialysis for 3-year mortality was 0.664 (95% CI, 0.466-0.945). RFI increased the 3-year mortality of cirrhotic patients with HE, especially ARF and HRS. HE patients with ESRD receiving hemodialysis had better 3-year survival rate than those with CKD.
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Affiliation(s)
- Tsung-Hsing Hung
- Division of Gastroenterology (T-HH, C-WT, K-CT, Y-HH), Department of Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi; School of Medicine (T-HH, C-WT, K-CT, Y-HH, C-Chi Tsai), Tzu Chi University, Hualien; Department of Mathematics (C-Chun Tsai), Tamkang University, Tamsui; Division of Infectious Disease (C-Chi Tsai), Department of Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
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Could serum nitrate and nitrite levels possibly predict hepatorenal syndrome in hepatitis C virus-related liver cirrhosis? Indian J Gastroenterol 2014; 33:274-80. [PMID: 24287875 DOI: 10.1007/s12664-013-0427-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2013] [Accepted: 10/14/2013] [Indexed: 02/04/2023]
Abstract
PURPOSE This study aimed to determine whether serum levels of nitric oxide metabolites (nitrates and nitrites) correlate with renal dysfunction in patients with liver cirrhosis and, moreover, to assess nitric oxide metabolite (NOx) power for predicting hepatorenal syndrome (HRS) in such patients. METHODS Among patients admitted to the Tropical Medicine Department, Ain Shams University Hospital, a total of 60 patients with chronic hepatitis C-related liver cirrhosis were included in this study. Patients were divided into three groups. Group I included 20 patients with compensated liver cirrhosis (CLC). Group II included 20 patients with decompensated liver cirrhosis (DLC). Group III included 20 patients with decompensated liver cirrhosis and HRS. Twenty healthy subjects with no clinical or laboratory evidence of liver disease were enrolled as a control group (group IV). RESULTS Patients with HRS had a higher mean nitrite levels followed by DLC, then CLC, and then controls. The sensitivity and specificity of NO metabolites (nitrites) were 100 % and 93.3 %, respectively, with accuracy of 95 % at cutoff value of 387 μmol/L for diagnosing patients with HRS. There was a highly significant statistical difference between patients positive and negative for nitrites as regards renal profile (p = 0.000). CONCLUSION A strong relation between nitrite cutoff value and renal dysfunction in liver cirrhosis has been found. Also, patients with HRS had higher mean serum nitrite levels than decompensated liver cirrhosis or compensated liver cirrhosis, raising the possibility of using nitrate and nitrite levels as a predictor for HRS in HCV-related liver cirrhosis.
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Qasem AA, Farag SE, Hamed E, Emara M, Bihery A, Pasha H. Urinary biomarkers of acute kidney injury in patients with liver cirrhosis. ISRN NEPHROLOGY 2014; 2014:376795. [PMID: 24967242 PMCID: PMC4045442 DOI: 10.1155/2014/376795] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/21/2014] [Accepted: 03/12/2014] [Indexed: 02/06/2023]
Abstract
Acute kidney injury (AKI) is a common complication in cirrhotic patients. Serum creatinine is a poor biomarker for detection of renal impairment in cirrhotic patients. This study aimed to evaluate urinary neutrophil gelatinase-associated lipocalin (NGAL) and urinary interleukin-18 (IL-18) as early biomarkers of acute kidney injury in cirrhotic patients. 160 patients with cirrhosis admitted to the Liver Units at Zagazig University Hospitals were classified into three groups: (I) nonascitic patients, (II) ascitic patients without renal impairment, and (III) ascitic patients with renal impairment. Patients with renal impairment were further divided into four subgroups: [A] prerenal azotemia, [B] chronic kidney disease (CKD), [C] hepatorenal syndrome (HRS), and [D] acute tubular necrosis (ATN). Significant elevation of both urinary NGAL and urinary IL-18 in cirrhotic patients with renal impairment especially in patients with ATN was observed. Urinary NGAL and urinary IL-18 have the ability to differentiate between AKI types in patients with cirrhosis. This could improve risk stratification for patients admitted to the hospital with cirrhosis, perhaps leading to early ICU admission, transplant evaluation, and prompt initiation of HRS therapy and early management of AKI.
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Affiliation(s)
- Anass Ahmed Qasem
- Internal Medicine Department, Faculty of Medicine, Zagazig University, Zagazig 44511, Egypt
| | - Salama Elsayed Farag
- Internal Medicine Department, Faculty of Medicine, Zagazig University, Zagazig 44511, Egypt
| | - Emad Hamed
- Internal Medicine Department, Faculty of Medicine, Zagazig University, Zagazig 44511, Egypt
| | - Mohamed Emara
- Tropical Medicine Department, Faculty of Medicine, Zagazig University, Zagazig 44511, Egypt
| | - Ahmed Bihery
- Tropical Medicine Department, Faculty of Medicine, Zagazig University, Zagazig 44511, Egypt
| | - Heba Pasha
- Medical Biochemistry Department, Faculty of Medicine, Zagazig University, Zagazig 44511, Egypt
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