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Loeffler J, Hassan M, Qaqish F, Dimachkie R, Dehghani S, Sasso R, Abou Yassine A, Deeb L. Predictors of Renal Replacement Therapy Requirement in Cirrhotic Patients with Acute Kidney Injury. Dig Dis Sci 2025:10.1007/s10620-025-08881-8. [PMID: 39954191 DOI: 10.1007/s10620-025-08881-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Accepted: 01/17/2025] [Indexed: 02/17/2025]
Abstract
BACKGROUND Renal failure is a well-known and often devastating complication in patients with liver cirrhosis and contributes to significant morbidity and mortality. AIMS This study aimed to evaluate the clinical profile and factors associated with the utilization of renal replacement therapy (RRT) requirement in cirrhotic patients presenting with AKI. METHODS We conducted a retrospective cohort study of cirrhotic inpatient visits across all Northwell Health hospitals between January 1, 2019 and December 31, 2020. Patients meeting inclusion criteria were identified using the International Classification of Disease, tenth revision clinical modification (ICD-10-CM) codes. Clinical variables, including demographics, medical history, laboratory data, and outcomes, were collected. Statistical analyses were performed to compare variables between patients requiring RRT and those not requiring RRT. RESULTS Of 701 cirrhotic patient encounters, 516 met inclusion criteria. The most common etiology of AKI was pre-renal (45.3%), followed by hepatorenal syndrome (18.6%) and acute tubular necrosis (14.7%). Sixty patients (11.6%) required RRT, with worse outcomes observed in this group. Independent predictors of RRT requirement included hepatorenal syndrome, acute tubular necrosis, and pneumonia. Pre-renal AKI was associated with decreased likelihood of requiring RRT. CONCLUSION This study identified clinical and laboratory factors predicting RRT requirement in cirrhotic patients with AKI. Hepatorenal syndrome, acute tubular necrosis, and pneumonia were associated with increased likelihood of RRT. Understanding these predictors may aid in prognostication and management decisions for cirrhotic patients presenting with AKI, warranting further prospective validation studies.
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Affiliation(s)
- Jeffrey Loeffler
- Department of Internal Medicine, Staten Island University Hospital, Northwell Health, Staten Island, NY, USA.
| | - Mohammed Hassan
- Department of Internal Medicine, Staten Island University Hospital, Northwell Health, Staten Island, NY, USA
| | - Faris Qaqish
- Department of Internal Medicine, Staten Island University Hospital, Northwell Health, Staten Island, NY, USA
| | - Reem Dimachkie
- Department of Internal Medicine, Staten Island University Hospital, Northwell Health, Staten Island, NY, USA
| | - Shabnam Dehghani
- Department of Internal Medicine, Staten Island University Hospital, Northwell Health, Staten Island, NY, USA
| | - Roula Sasso
- Department of Internal Medicine, Staten Island University Hospital, Northwell Health, Staten Island, NY, USA
| | - Ahmad Abou Yassine
- Department of Internal Medicine, Staten Island University Hospital, Northwell Health, Staten Island, NY, USA
| | - Liliane Deeb
- Department of Gastroenterology and Hepatology, Staten Island University Hospital, Northwell Health, Staten Island, NY, USA
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Sohail A, Chaudhary AJ, Bhinder MM, Zahid K, Brown K. Readmission Rate, Predictors, Outcomes, and Burden of Readmission of Hepatorenal Syndrome in the United States: A Nationwide Analysis. JGH Open 2024; 8:e70062. [PMID: 39600414 PMCID: PMC11588588 DOI: 10.1002/jgh3.70062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2024] [Revised: 10/13/2024] [Accepted: 11/11/2024] [Indexed: 11/29/2024]
Abstract
Background Nationwide US data on readmission rates for patients with cirrhosis admitted with hepatorenal syndrome (HRS) is lacking. We reviewed 30-day readmission rates after HRS-related hospitalizations, the associated predictors of readmissions, and their impact on resource utilization and mortality in the United States. Methods We identified all adults admitted with HRS between 2016 and 2019 using the Nationwide Readmission database of the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project. The primary outcome was all-cause 30-day readmission rate. Secondary outcomes were inpatient mortality rate, predictors of readmission, and resource utilization. Results We identified 245 850 hospitalizations of patients admitted for HRS in the United States from 2016 to 2019. Of these, 214 890 met the inclusion criteria. Mean age was 59.16 years, and 61.31% were males. Medicare was the most common primary payer (44.82%) followed by Medicaid (25.58%). The readmission rate was 24.6% within 30 days of discharge from index hospitalization. The most common cause of readmission was alcoholic cirrhosis with ascites (14.87%), followed by sepsis (9.32%) and unspecified hepatic failure (9%). The in-hospital mortality rate for index hospitalization was 29.52% and 14.35% among those readmitted within 30 days. The mean length of stay (12.33 days vs. 7.15 days, p < 0.01) and hospitalization costs ($44 903 vs. $22 353, p < 0.01) were higher for index hospitalizations than readmissions. Conclusions Our study demonstrated that all-cause 30-day readmission and in-hospital mortality rates after the development of HRS were strikingly high. This warrants health policies and interventions at the institutional level, including close post-hospital discharge follow-up, to decrease readmission rates, improve patient outcomes, and reduce cost burden.
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Affiliation(s)
- Abdullah Sohail
- Department of Internal MedicineUniversity of Iowa Hospitals and ClinicsIowa CityIowaUSA
| | | | | | | | - Kyle Brown
- Department of Internal Medicine, Gastroenterology and HepatologyUniversity of Iowa Hospitals and ClinicsIowa CityIowaUSA
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3
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Jan MY, Patidar KR, Ghabril MS, Kubal CA. Optimization of Kidney Health in Liver Transplant Candidates: Pretransplant Considerations and Modalities. Transplantation 2024; 108:1542-1550. [PMID: 38192019 PMCID: PMC11188627 DOI: 10.1097/tp.0000000000004851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Revised: 08/11/2023] [Accepted: 08/24/2023] [Indexed: 01/10/2024]
Abstract
Patients with decompensated end-stage liver disease (ESLD) are at increased risk for mortality, and only liver transplantation (LT) offers meaningful hope for survival. These patients are at risk for kidney dysfunction through the continuum of care for ESLD including LT. We discuss the role of accurate estimation and measurement of baseline glomerular filtration rate in assessment of kidney dysfunction among those with ESLD. Optimizing kidney function is a vital goal in the management of these patients before LT. In this review, we summarize salient aspects of assessing and optimizing kidney function in this patient population. Precipitating factors and different causes of acute kidney injury are discussed, including hepatorenal syndrome. We further review treatment options for acute kidney injury including volume management. The role of vasopressor therapy, renal replacement therapy, and transjugular intrahepatic portosystemic shunting are discussed.
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Affiliation(s)
- Muhammad Y. Jan
- Division of Transplant Nephrology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN
| | - Kavish R. Patidar
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX
| | - Marwan S. Ghabril
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX
| | - Chandrashekhar A. Kubal
- Division of Transplant Surgery, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN
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4
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Bielawski AM, Frishman WH. A Review of Terlipressin in Hepatorenal Syndrome: Targeting Endothelial Dysfunction and Subsequent Cardiovascular Adverse Events. Cardiol Rev 2024:00045415-990000000-00249. [PMID: 38832784 DOI: 10.1097/crd.0000000000000697] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/05/2024]
Abstract
Hepatorenal syndrome (HRS) is a serious complication of decompensated liver cirrhosis that results in acute kidney injury (AKI). The mortality rate is high. Endothelial dysfunction secondary to liver cirrhosis is a key driver of the development of portal hypertension, which is eventually complicated by ascites and HRS. Ultimately, splanchnic vasodilation and excess gut lymph production result in ascites, low effective arterial blood volume, and maladaptive compensatory mechanisms that contribute to renal hypoperfusion and injury. While the only curative treatment is liver transplantation, vasoconstrictors and albumin have been the mainstay of treatment for candidates who are ineligible or waiting for transplantation. On September 14, 2022, terlipressin, a V1 vasopressin receptor agonist, was approved by the Food and Drug Administration for the treatment of HRS-AKI. In clinical trials, terlipressin plus albumin have been superior to albumin alone and equivocal to noradrenaline plus albumin in renal function improvement. Terlipressin, however, does not improve survival, is costly, and is associated with severe adverse events-including severe cardiac and vascular complications. The aim of this review is to provide an overview of terlipressin pharmacology, adverse events-with a focus on cardiovascular complications-and comparative randomized controlled trials that resulted in the Food and Drug Administration's approval of terlipressin. New literature since its approval and ongoing clinical trials will also be highlighted.
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Affiliation(s)
- Adrienne M Bielawski
- From the Department of Medicine, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY
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5
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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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Allegretti AS, Patidar KR, Ma AT, Cullaro G. From past to present to future: Terlipressin and hepatorenal syndrome-acute kidney injury. Hepatology 2024:01515467-990000000-00741. [PMID: 38353565 PMCID: PMC11322426 DOI: 10.1097/hep.0000000000000790] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Accepted: 10/11/2023] [Indexed: 03/01/2024]
Abstract
Hepatorenal syndrome (HRS) is a rare and highly morbid form of kidney injury unique to patients with decompensated cirrhosis. HRS is a physiologic consequence of portal hypertension, leading to a functional kidney injury that can be reversed by restoring effective circulating volume and renal perfusion. While liver transplantation is the only definitive "cure" for HRS, medical management with vasoconstrictors and i.v. albumin is a cornerstone of supportive care. Terlipressin, a V1a receptor agonist that acts on the splanchnic circulation, has been used for many years outside the United States for the treatment of HRS. However, its recent Food and Drug Administration approval has generated new interest in this population, as a new base of prescribers now work to incorporate the drug into clinical practice. In this article, we review HRS pathophysiology and diagnostic criteria, the clinical use of terlipressin and alternative therapies, and identify areas of future research in the space of HRS and kidney injury in cirrhosis.
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Affiliation(s)
- Andrew S. Allegretti
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Kavish R. Patidar
- Section of Gastroenterology, Department of Medicine, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston TX, USA
| | - Ann T. Ma
- Toronto Centre for Liver Disease, University Health Network, Toronto, Canada
| | - Giuseppe Cullaro
- Division of Gastroenterology, Department of Medicine, University of California-San Francisco, San Francisco CA, USA
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Wu HHL, Rakisheva A, Ponnusamy A, Chinnadurai R. Hepatocardiorenal syndrome in liver cirrhosis: Recognition of a new entity? World J Gastroenterol 2024; 30:128-136. [PMID: 38312119 PMCID: PMC10835518 DOI: 10.3748/wjg.v30.i2.128] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Revised: 12/05/2023] [Accepted: 12/28/2023] [Indexed: 01/12/2024] Open
Abstract
Emerging evidence and perspectives have pointed towards the heart playing an important role in hepatorenal syndrome (HRS), outside of conventional understanding that liver cirrhosis is traditionally considered the sole origin of a cascade of pathophysiological mechanisms directly affecting the kidneys in this context. In the absence of established heart disease, cirrhotic cardiomyopathy may occur more frequently in those with liver cirrhosis and kidney disease. It is a specific form of cardiac dysfunction characterized by blunted contractile responsiveness to stress stimuli and altered diastolic relaxation with electrophysiological abnormalities. Despite the clinical description of these potential cardiac-related complications of the liver, the role of the heart has traditionally been an overlooked aspect of circulatory dysfunction in HRS. Yet from a physiological sense, temporality (prior onset) of cardiorenal interactions in HRS and positive effects stemming from portosystemic shunting demonstrated an important role of the heart in the development and progression of kidney dysfunction in cirrhotic patients. In this review, we discuss current concepts surrounding how the heart may influence the development and progression of HRS, and the role of systemic inflammation and endothelial dysfunction causing circulatory dysfunction within this setting. The temporality of heart and kidney dysfunction in HRS will be discussed. For a subgroup of patients who receive portosystemic shunting, the dynamics of cardiorenal interactions following treatment is reviewed. Continued research to determine the unknowns in this topic is anticipated, hopefully to further clarify the intricacies surrounding the liver-heart-kidney connection and improve strategies for management.
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Affiliation(s)
- Henry H L Wu
- Renal Research, Kolling Institute of Medical Research, Royal North Shore Hospital & The University of Sydney, St. Leonards (Sydney) 2065, New South Wales, Australia
| | - Amina Rakisheva
- Department of Cardiology, City Cardiological Center, Almaty 050000, Kazakhstan
| | - Arvind Ponnusamy
- Department of Renal Medicine, Royal Preston Hospital, Preston PR2 9HT, United Kingdom
| | - Rajkumar Chinnadurai
- Donal O’Donoghue Renal Research Centre & Department of Renal Medicine, Northern Care Alliance National Health Service Foundation Trust, Salford M6 8HD, United Kingdom
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8
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Badura K, Frąk W, Hajdys J, Majchrowicz G, Młynarska E, Rysz J, Franczyk B. Hepatorenal Syndrome-Novel Insights into Diagnostics and Treatment. Int J Mol Sci 2023; 24:17469. [PMID: 38139297 PMCID: PMC10744165 DOI: 10.3390/ijms242417469] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 12/09/2023] [Accepted: 12/11/2023] [Indexed: 12/24/2023] Open
Abstract
Hepatorenal syndrome (HRS) is a disorder associated with cirrhosis and renal impairment, with portal hypertension as its major underlying cause. Moreover, HRS is the third most common cause of acute kidney injury, thus creating a major public health concern. This review summarizes the available information on the pathophysiological implications of HRS. We discuss pathogenesis associated with HRS. Mechanisms such as dysfunction of the circulatory system, bacterial infection, inflammation, impaired renal autoregulation, circulatory, and others, which have been identified as critical pathways for development of HRS, have become easier to diagnose in recent years. Additionally, relatively recently, renal dysfunction biomarkers have been found indicating renal injury, which are involved in the pathophysiology of HRS. This review also summarizes the available information on the management of HRS, focusing on vasoconstrictive drugs, renal replacement therapy, and liver transplant together with currently being investigated novel therapies. Analyzing new discoveries for the underlying causes of this condition assists the general research to improve understanding of the mechanism of pathophysiology and thus prevention of HRS.
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Affiliation(s)
- Krzysztof Badura
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Weronika Frąk
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Joanna Hajdys
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Gabriela Majchrowicz
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Ewelina Młynarska
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Jacek Rysz
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Beata Franczyk
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
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Ayyad A, Al-Horani RA. Terlipressin for the Prevention and Treatment of Renal Decline in Hepatorenal Syndrome: A Drug Profile. GASTROENTEROLOGY INSIGHTS 2023; 14:420-430. [PMID: 37873544 PMCID: PMC10587779 DOI: 10.3390/gastroent14040031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/25/2023] Open
Abstract
Hepatorenal syndrome stands as one of several potential triggers of acute kidney injury in individuals grappling with either acute or persistent liver ailments. The nature of the decline in kidney function has led to the identification of two variants of hepatorenal syndrome. In cases where terlipressin therapy is accessible, the initial approach involves administering terlipressin alongside albumin. Terlipressin, a synthetic analog of vasopressin, boasts double the preference for vasopressin V1 receptors compared to V2 receptors. The FDA granted approval to terlipressin in September 2022, demonstrating its intrinsic activity, although a significant portion of its function arises from its transformation into lysine vasopressin. This article provides a comprehensive examination of terlipressin's various pharmacodynamic and pharmacokinetic facets, as well as its clinical utility, aiming to keep the scientific community well informed about its safe and efficient utilization.
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Affiliation(s)
- Ahlam Ayyad
- Division of Clinical and Administrative Sciences, College of Pharmacy, Xavier University of Louisiana, New Orleans, LA 70125, USA
| | - Rami A. Al-Horani
- Division of Basic Pharmaceutical Sciences, College of Pharmacy, Xavier University of Louisiana, New Orleans, LA 70125, USA
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10
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Choi JC, Yoo JJ. [Hepatorenal Syndrome]. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2023; 82:224-232. [PMID: 37997218 DOI: 10.4166/kjg.2023.108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Revised: 09/16/2023] [Accepted: 09/19/2023] [Indexed: 11/25/2023]
Abstract
Hepatorenal syndrome (HRS) is a critical and potentially life-threatening complication of advanced liver disease, including cirrhosis. It is characterized by the development of renal dysfunction in the absence of underlying structural kidney pathology. The pathophysiology of HRS involves complex interactions between systemic and renal hemodynamics, neurohormonal imbalances, and the intricate role of vasoconstrictor substances. Understanding these mechanisms is crucial for the timely identification and management of HRS. The diagnosis of HRS is primarily clinical and relies on specific criteria that consider the exclusion of other causes of renal dysfunction. The management of HRS comprises two main approaches: vasoconstrictor therapy and albumin infusion, which aim to improve renal perfusion and mitigate the hyperdynamic circulation often seen in advanced liver disease. Additionally, strategies such as liver transplantation and renal replacement therapy are essential considerations based on individual patient characteristics and disease severity. This review article provides a comprehensive overview of hepatorenal syndrome, focusing on its pathophysiology, diagnostic criteria, and current management strategies.
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Affiliation(s)
- Jun Cheol Choi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea
| | - Jeong-Ju Yoo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea
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11
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Trautman CL, Khan M, Baker LW, Aslam N, Fitzpatrick P, Porter I, Mao M, Wadei H, Ball CT, Hickson LJ. Kidney Outcomes Following Utilization of Molecular Adsorbent Recirculating System. Kidney Int Rep 2023; 8:2100-2106. [PMID: 37850016 PMCID: PMC10577361 DOI: 10.1016/j.ekir.2023.07.035] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Revised: 07/24/2023] [Accepted: 07/31/2023] [Indexed: 10/19/2023] Open
Abstract
Introduction Molecular adsorbent recirculating system (MARS) is an extracorporeal system combining conventional veno-venous hemodiafiltration and adsorption to provide rescue support in fulminant hepatic failure. Acute kidney injury (AKI) is common in patients with hepatic failure warranting continuous kidney replacement therapy (CKRT). Our primary aim was to characterize a cohort of patients who received MARS therapy and examine kidney events given the current paucity of available data. Methods Patients initiating MARS in a tertiary care setting from January 2014 through December 2020 were assessed for treatment indications, transplantation, CKRT, kidney recovery, and death. Data was collected using the REDCAP software. Results A total of 49 patients (67% female; 75% White) received MARS therapy with 29 patients (59%) requiring concomitant CKRT. Hepatic encephalopathy (HE) was the most common indication for MARS initiation (55%). In-hospital mortality was 41% (12/29) among patients who received CKRT versus 10% (2/20) among those not requiring CKRT (relative risk [RR] 4.15, 95% confidence interval [CI] 1.04 to 16.52, P = 0.044); this persisted following adjustment for prespecified patient characteristics (all RR ≥ 3.76, all P ≤ 0.060). One-year mortality post-MARS initiation was high overall but highest among the CKRT group (59% [17/29] vs. 25% [5/20] unadjusted RR 2.92, 95% CI 1.08 to 7.94, P = 0.035). Liver transplant after MARS occurred in 41% of patients (20/49). After CKRT, 39% of patients (9/29) recovered kidney function prior to hospital discharge. Conclusions Patients requiring MARS frequently have AKI warranting the use of concomitant CKRT, which is associated with a high rate of in-hospital and 1-year mortality.
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Affiliation(s)
- Christopher L. Trautman
- Division of Nephrology and Hypertension, Department of Medicine; Mayo Clinic Jacksonville, Florida, USA
| | - Mahnoor Khan
- Division of Nephrology and Hypertension, Department of Medicine; Mayo Clinic Jacksonville, Florida, USA
| | - Lyle W. Baker
- Division of Nephrology and Hypertension, Department of Medicine; Mayo Clinic Jacksonville, Florida, USA
| | - Nabeel Aslam
- Division of Nephrology and Hypertension, Department of Medicine; Mayo Clinic Jacksonville, Florida, USA
| | - Peter Fitzpatrick
- Division of Nephrology and Hypertension, Department of Medicine; Mayo Clinic Jacksonville, Florida, USA
| | - Ivan Porter
- Division of Nephrology and Hypertension, Department of Medicine; Mayo Clinic Jacksonville, Florida, USA
| | - Michael Mao
- Division of Nephrology and Hypertension, Department of Medicine; Mayo Clinic Jacksonville, Florida, USA
| | - Hani Wadei
- Department of Transplantation; Mayo Clinic Jacksonville, Florida, USA
| | - Colleen T. Ball
- Division of Biomedical Statistics and Informatics, Mayo Clinic Jacksonville, Florida, USA
| | - LaTonya J. Hickson
- Division of Nephrology and Hypertension, Department of Medicine; Mayo Clinic Jacksonville, Florida, USA
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12
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Arnold J, Avila E, Idalsoaga F, Diaz LA, Ayala Valverde M, Ayares G, Arrese M, Roessler E, Huidobro JP, Hudson D, Khan MQ, Arab JP. Advances in the diagnosis and management of hepatorenal syndrome: insights into HRS-AKI and liver transplantation. EGASTROENTEROLOGY 2023; 1:e100009. [PMID: 39943997 PMCID: PMC11770447 DOI: 10.1136/egastro-2023-100009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Accepted: 09/27/2023] [Indexed: 01/04/2025]
Abstract
In hepatorenal syndrome-acute kidney injury (HRS-AKI), accurate and early diagnosis is crucial. HRS is a severe condition seen in advanced cirrhosis, requiring prompt recognition and proper management to enhance patient outcomes. Diagnosis of HRS-AKI relies on serum creatinine elevations, similar to other AKI cases in cirrhosis. However, distinguishing HRS-AKI from other renal impairments in these patients can be challenging. Biomarkers and clinical criteria aid in diagnosis and guide treatment. The management of HRS-AKI initially involves improving the haemodynamic profile using albumin and vasoconstrictors like terlipressin, a synthetic vasopressin analogue. Despite some reports linking terlipressin to increased adverse events compared with norepinephrine, it remains the preferred choice in HRS-AKI and acute-on-chronic liver failure due to its faster, stronger response and improved survival. Additional therapies like midodrine (alpha-1 adrenergic agonist), octreotide (somatostatin analogue) and transjugular intrahepatic portosystemic shunt are proposed as adjuvant treatments for HRS-AKI, aiming to improve vasoconstriction and renal blood flow. However, these adjunctive therapies cannot replace the definitive treatment for HRS-AKI-liver transplantation (LT). In cases unresponsive to medical management, LT is the only option to restore liver function and improve renal outcomes. Current evidence favours combined liver and kidney transplantation (CLKT) in certain situations. This review aims to evaluate the present evidence and recommendations on AKI in patients with cirrhosis, the pathophysiology of HRS-AKI, different treatments and indications for LT and CLKT. Understanding the complexities of managing HRS-AKI is crucial for optimising patient care and achieving better outcomes in this challenging clinical setting.
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Affiliation(s)
- Jorge Arnold
- Departamento de Gastroenterología, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Eduardo Avila
- Departamento de Nefrología, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Francisco Idalsoaga
- Departamento de Gastroenterología, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Luis Antonio Diaz
- Departamento de Gastroenterología, Pontificia Universidad Católica de Chile, Santiago, Chile
| | | | - Gustavo Ayares
- Departamento de Gastroenterología, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Marco Arrese
- Departamento de Gastroenterología, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Eric Roessler
- Departamento de Nefrología, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Juan Pablo Huidobro
- Departamento de Nefrología, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - David Hudson
- Department of Medicine, London Health Sciences Centre, London, Ontario, Canada
| | - Mohammad Qasim Khan
- Department of Medicine, London Health Sciences Centre, London, Ontario, Canada
| | - Juan Pablo Arab
- Departamento de Gastroenterología, Pontificia Universidad Católica de Chile, Santiago, Chile
- Department of Medicine, London Health Sciences Centre, London, Ontario, Canada
- Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada
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Attieh RM, Wadei HM. Acute Kidney Injury in Liver Cirrhosis. Diagnostics (Basel) 2023; 13:2361. [PMID: 37510105 PMCID: PMC10377915 DOI: 10.3390/diagnostics13142361] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Revised: 07/01/2023] [Accepted: 07/11/2023] [Indexed: 07/30/2023] Open
Abstract
Acute kidney injury (AKI) is common in cirrhotic patients affecting almost 20% of these patients. While multiple etiologies can lead to AKI, pre-renal azotemia seems to be the most common cause of AKI. Irrespective of the cause, AKI is associated with worse survival with the poorest outcomes observed in those with hepatorenal syndrome (HRS) and acute tubular necrosis (ATN). In recent years, new definitions, and classifications of AKI in cirrhosis have emerged. More knowledge has also become available regarding the benefits and drawbacks of albumin and terlipressin use in these patients. Diagnostic tools such as urinary biomarkers and point-of-care ultrasound (POCUS) became available and they will be used in the near future to differentiate between different causes of AKI and direct management of AKI in these patients. In this update, we will review these new classifications, treatment recommendations, and diagnostic tools for AKI in cirrhotic patients.
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Affiliation(s)
- Rose Mary Attieh
- Department of Transplant, Division of Kidney and Pancreas Transplant, Mayo Clinic, Jacksonville, FL 32224, USA
| | - Hani M Wadei
- Department of Transplant, Division of Kidney and Pancreas Transplant, Mayo Clinic, Jacksonville, FL 32224, USA
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14
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Thangaraj SR, Srinivasan M, Arzoun H, Thomas SS. A Systematic Review of the Emerging Treatment for Hepatorenal Syndrome With a Principal Focus on Terlipressin: A Recent FDA-Approved Drug. Cureus 2023; 15:e42367. [PMID: 37621788 PMCID: PMC10445509 DOI: 10.7759/cureus.42367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/23/2023] [Indexed: 08/26/2023] Open
Abstract
BACKGROUND Hepatorenal syndrome (HRS), a consequence of liver cirrhosis, is the development of renal failure, which carries a grave prognosis. Reversing acute renal failure with various vasoconstrictor therapies at an appropriate time favors a good prognosis, especially when a liver transplant is not feasible. OBJECTIVE This study aims to compare various treatment modalities to deduce an effective way to manage HRS. METHODS The authors conducted a literature search in PubMed, Google Scholar, the Cochrane Library, and Science Direct in October 2022, using regular and MeSH keywords. A total of 1072 articles were identified. The PRISMA guidelines were used, the PICO framework was addressed, and the inclusion criteria were set based on studies from the past 10 years. After quality assessment, 14 studies were included for in-depth analysis in this review. Results: A total of 14 studies were included after quality assessment, including randomized controlled trials, systematic reviews, meta-analyses, and observational cohort studies. Nine hundred and forty-one patients represented this review's experimental and observational studies, apart from the other systematic reviews analyzed. Nine studies discovered that Terlipressin, especially when administered with albumin, was more effective than other conventional treatment modalities, including norepinephrine and midodrine, in terms of improving mortality and reversing the HRS. Four studies suggested that terlipressin exhibited similar effectiveness but found no significant difference. In contrast, one study found that norepinephrine was superior to terlipressin when particularly considering the adverse effects. CONCLUSION Terlipressin, one of the most widely used vasoconstrictor agents across the world, seems to be effective in reversing renal failure in HRS. Although adverse effects are seen with this agent, it is still beneficial when compared to other medications. Further studies with larger sample sizes may be warranted.
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Affiliation(s)
| | - Mirra Srinivasan
- Internal Medicine, St. Bernards Medical Center, Jonesboro, USA
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Hadia Arzoun
- Internal Medicine, St. Bernards Medical Center, Jonesboro, USA
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Siji S Thomas
- Internal Medicine, St. Bernards Medical Center, Jonesboro, USA
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15
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Kiani C, Zori AG. Recent advances in pathophysiology, diagnosis and management of hepatorenal syndrome: A review. World J Hepatol 2023; 15:741-754. [PMID: 37397940 PMCID: PMC10308288 DOI: 10.4254/wjh.v15.i6.741] [Citation(s) in RCA: 2] [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: 02/28/2023] [Revised: 04/18/2023] [Accepted: 05/06/2023] [Indexed: 06/25/2023] Open
Abstract
Hepatorenal syndrome with acute kidney injury (HRS-AKI) is a form of rapidly progressive kidney dysfunction in patients with decompensated cirrhosis and/or acute severe liver injury such as acute liver failure. Current data suggest that HRS-AKI occurs secondary to circulatory dysfunction characterized by marked splanchnic vasodilation, leading to reduction of effective arterial blood volume and glomerular filtration rate. Thus, volume expansion and splanchnic vasoconstriction constitute the mainstay of medical therapy. However, a significant proportion of patients do not respond to medical management. These patients often require renal replacement therapy and may be eligible for liver or combined liver-kidney transplantation. Although there have been advances in the management of patients with HRS-AKI including novel biomarkers and medications, better-calibrated studies, more widely available biomarkers, and improved prognostic models are sorely needed to further improve diagnosis and treatment of HRS-AKI.
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Affiliation(s)
- Calvin Kiani
- Department of Internal Medicine, Section of Gastroenterology and Hepatology, University of Florida, Gainesville, FL 32610, United States
| | - Andreas G Zori
- Department of Internal Medicine, Section of Gastroenterology and Hepatology, University of Florida, Gainesville, FL 32610, United States
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16
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Gheitasi I, Doustimotlagh AH, Kokhdan EP, Akbari G, Barmak MJ. Renoprotective effects of zinc sulfate against transient liver ischemia/reperfusion injury in rats. Heliyon 2023; 9:e15505. [PMID: 37153414 PMCID: PMC10160695 DOI: 10.1016/j.heliyon.2023.e15505] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 03/29/2023] [Accepted: 04/11/2023] [Indexed: 05/09/2023] Open
Abstract
Objectives Liver ischemia/reperfusion damage frequently occurs in setting of hepatic resection and liver transplantation. It leads to disturbance in remote organs such as heart, lung and kidneys. This study explored the consequences of hepatic ischemia/reperfusion on the oxidative stress parameters, biochemical factors, and histopathological alterations in the kidney's rats, as well as evaluated the role of zinc sulfate on above-mentioned parameters. Materials and methods Twenty-eight male Wistar rats were accidently assigned into four groups (n = 7). They were Sham, ischemia/reperfusion, zinc sulfate pretreatment, and zinc sulfate pretreatment + ischemia/reperfusion groups. Sham group: obtained normal saline (2 ml/day, seven consecutive days), intraperitoneally, zinc sulfate pretreatment group: obtained zinc sulfate (5 mg/kg, seven consecutive days, intraperitoneally). Ischemia/reperfusion group: obtained normal saline as mentioned previous, then rats experienced the partial ischemia (%70) for 45 min followed by 60 min reperfusion. Zinc sulfate pretreatment group: obtained zinc sulfate as mentioned previous, then rats experience the partial ischemia/reperfusion as presented earlier. At the end of investigation, blood was withdrawn, liver and renal tissues were removed. Then, biochemical and oxidative stress parameters, and histological changes were evaluated in the mentioned tissues. Results The findings of this experiment indicated that zinc sulfate markedly reduced the serum levels of liver and kidney function tests in relative to ischemia/reperfusion group. Also, antioxidant enzymes activity, ferric reducing antioxidant power, and nitric oxide significantly increased, while malondialdehyde level declined in the renal tissue of zinc sulfate + ischemia/reperfusion group compared to ischemia/reperfusion rats. Furthermore, zinc sulfate alleviated the liver and kidneys histopathological alterations following ischemia/reperfusion. Conclusion Zinc sulfate ameliorated liver and kidney function, and improved oxidant-antioxidant balance in favor of antioxidants. It is suggested that zinc sulfate may be beneficial effects on hepato-renal injury after ischemia/reperfusion.
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Affiliation(s)
- Izadpanah Gheitasi
- Medicinal Plants Research Center, Yasuj University of Medical Sciences, Yasuj, Iran
| | | | | | - Ghaidafeh Akbari
- Medicinal Plants Research Center, Yasuj University of Medical Sciences, Yasuj, Iran
- Corresponding author. Medical Physiology, Yasuj University of Medical Sciences, Yasuj, Iran.
| | - Mehrzad Jafari Barmak
- Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran
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17
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Analysis of Native Kidney Function Recovery With Renal Scintigraphy Following Simultaneous Liver-Kidney Transplantation. Transplantation 2023; 107:540-547. [PMID: 36228323 DOI: 10.1097/tp.0000000000004310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
BACKGROUND Patients undergoing simultaneous liver-kidney transplantation (SLK) have impaired native kidney function. The relative contribution of allograft versus native function after SLK is unknown. We sought to characterize the return of native kidney function following SLK. METHODS Following SLK, patients underwent technetium-99 m-mercaptoacetyltriglycine renal scintigraphy following serum creatinine nadir. Kidney contributions to estimated glomerular filtration rate (eGFR) were determined. Patients with native kidney function at serum creatinine nadir contributing eGFR ≥30 versus <30 mL/min/1.73 m 2 were compared, and multiple linear regression analysis for native eGFR improvement was performed. RESULTS Thirty-one patients were included in this analysis. Average native kidney contribution to overall kidney function following SLK was 51.1% corresponding to native kidney eGFR of 44.5 mL/min/1.73 m 2 and native kidney function eGFR improvement of 30.3 mL/min/1.73 m 2 ( P < 0.001). Twenty-six of 31 patients had native kidney contribution of eGFR ≥30 mL/min/1.73 m 2 . Hepatorenal syndrome as the sole primary etiology of kidney dysfunction was 100% specific for native kidney eGFR >30 mL/min/1.73 m 2 and predicted native eGFR improvement ( P = 0.03). CONCLUSIONS Substantial improvement in native kidney function follows SLK, and hepatorenal syndrome as the sole primary etiology of kidney dysfunction is predictive of improvement. Whether such patients are suitable for liver transplant followed by surveillance with option for subsequent kidney transplants requires investigation.
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18
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Distinct Subtypes of Hepatorenal Syndrome and Associated Outcomes as Identified by Machine Learning Consensus Clustering. Diseases 2023; 11:diseases11010018. [PMID: 36810532 PMCID: PMC9944494 DOI: 10.3390/diseases11010018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2022] [Revised: 01/15/2023] [Accepted: 01/20/2023] [Indexed: 01/31/2023] Open
Abstract
BACKGROUND The utilization of multi-dimensional patient data to subtype hepatorenal syndrome (HRS) can individualize patient care. Machine learning (ML) consensus clustering may identify HRS subgroups with unique clinical profiles. In this study, we aim to identify clinically meaningful clusters of hospitalized patients for HRS using an unsupervised ML clustering approach. METHODS Consensus clustering analysis was performed based on patient characteristics in 5564 patients primarily admitted for HRS in the National Inpatient Sample from 2003-2014 to identify clinically distinct HRS subgroups. We applied standardized mean difference to evaluate key subgroup features, and compared in-hospital mortality between assigned clusters. RESULTS The algorithm revealed four best distinct HRS subgroups based on patient characteristics. Cluster 1 patients (n = 1617) were older, and more likely to have non-alcoholic fatty liver disease, cardiovascular comorbidities, hypertension, and diabetes. Cluster 2 patients (n = 1577) were younger and more likely to have hepatitis C, and less likely to have acute liver failure. Cluster 3 patients (n = 642) were younger, and more likely to have non-elective admission, acetaminophen overdose, acute liver failure, to develop in-hospital medical complications and organ system failure, and to require supporting therapies, including renal replacement therapy, and mechanical ventilation. Cluster 4 patients (n = 1728) were younger, and more likely to have alcoholic cirrhosis and to smoke. Thirty-three percent of patients died in hospital. In-hospital mortality was higher in cluster 1 (OR 1.53; 95% CI 1.31-1.79) and cluster 3 (OR 7.03; 95% CI 5.73-8.62), compared to cluster 2, while cluster 4 had comparable in-hospital mortality (OR 1.13; 95% CI 0.97-1.32). CONCLUSIONS Consensus clustering analysis provides the pattern of clinical characteristics and clinically distinct HRS phenotypes with different outcomes.
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19
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Venkataraj M, Morisetti PP. A Case of Fibrillary Glomerulonephritis. Cureus 2022; 14:e28250. [PMID: 36158379 PMCID: PMC9490443 DOI: 10.7759/cureus.28250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/22/2022] [Indexed: 11/05/2022] Open
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20
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Boike JR, Thornburg BG, Asrani SK, Fallon MB, Fortune BE, Izzy MJ, Verna EC, Abraldes JG, Allegretti AS, Bajaj JS, Biggins SW, Darcy MD, Farr MA, Farsad K, Garcia-Tsao G, Hall SA, Jadlowiec CC, Krowka MJ, Laberge J, Lee EW, Mulligan DC, Nadim MK, Northup PG, Salem R, Shatzel JJ, Shaw CJ, Simonetto DA, Susman J, Kolli KP, VanWagner LB. North American Practice-Based Recommendations for Transjugular Intrahepatic Portosystemic Shunts in Portal Hypertension. Clin Gastroenterol Hepatol 2022; 20:1636-1662.e36. [PMID: 34274511 PMCID: PMC8760361 DOI: 10.1016/j.cgh.2021.07.018] [Citation(s) in RCA: 123] [Impact Index Per Article: 41.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 07/01/2021] [Accepted: 07/13/2021] [Indexed: 02/07/2023]
Abstract
Complications of portal hypertension, including ascites, gastrointestinal bleeding, hepatic hydrothorax, and hepatic encephalopathy, are associated with significant morbidity and mortality. Despite few high-quality randomized controlled trials to guide therapeutic decisions, transjugular intrahepatic portosystemic shunt (TIPS) creation has emerged as a crucial therapeutic option to treat complications of portal hypertension. In North America, the decision to perform TIPS involves gastroenterologists, hepatologists, and interventional radiologists, but TIPS creation is performed by interventional radiologists. This is in contrast to other parts of the world where TIPS creation is performed primarily by hepatologists. Thus, the successful use of TIPS in North America is dependent on a multidisciplinary approach and technical expertise, so as to optimize outcomes. Recently, new procedural techniques, TIPS stent technology, and indications for TIPS have emerged. As a result, practices and outcomes vary greatly across institutions and significant knowledge gaps exist. In this consensus statement, the Advancing Liver Therapeutic Approaches group critically reviews the application of TIPS in the management of portal hypertension. Advancing Liver Therapeutic Approaches convened a multidisciplinary group of North American experts from hepatology, interventional radiology, transplant surgery, nephrology, cardiology, pulmonology, and hematology to critically review existing literature and develop practice-based recommendations for the use of TIPS in patients with any cause of portal hypertension in terms of candidate selection, procedural best practices and, post-TIPS management; and to develop areas of consensus for TIPS indications and the prevention of complications. Finally, future research directions are identified related to TIPS for the management of portal hypertension.
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Affiliation(s)
- Justin R. Boike
- Department of Medicine, Division of Gastroenterology & Hepatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Bartley G. Thornburg
- Department of Radiology, Division of Vascular and Interventional Radiology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | | | - Michael B. Fallon
- Department of Medicine, Division of Gastroenterology and Hepatology, Banner - University Medical Center Phoenix, Phoenix, AZ, USA
| | - Brett E. Fortune
- Department of Medicine, Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York, NY, USA
| | - Manhal J. Izzy
- Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Elizabeth C. Verna
- Department of Medicine, Division of Digestive and Liver Diseases, Columbia University College of Physicians & Surgeons, New York, NY, USA
| | - Juan G. Abraldes
- Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, AB, Canada
| | - Andrew S. Allegretti
- Department of Medicine, Division of Nephrology, Massachusetts General Hospital, Boston, MA, USA
| | - Jasmohan S. Bajaj
- Department of Internal Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and Central Virginia Veterans Healthcare System, Richmond, VA, USA
| | - Scott W. Biggins
- Department of Medicine, Division of Gastroenterology & Hepatology, University of Washington Medical Center, Seattle, WA, USA
| | - Michael D. Darcy
- Department of Radiology, Division of Interventional Radiology, Washington University School of Medicine, St. Louis, MO, USA
| | - Maryjane A. Farr
- Department of Medicine, Division of Cardiology, Columbia University College of Physicians & Surgeons, New York, NY, USA
| | - Khashayar Farsad
- Dotter Department of Interventional Radiology, Oregon Health and Science University, Portland, OR, USA
| | - Guadalupe Garcia-Tsao
- Department of Digestive Diseases, Yale University, Yale University School of Medicine, and VA-CT Healthcare System, CT, USA
| | - Shelley A. Hall
- Department of Internal Medicine, Division of Cardiology, Baylor University Medical Center, Dallas, TX, USA
| | - Caroline C. Jadlowiec
- Department of Surgery, Division of Transplant Surgery, Mayo Clinic, Phoenix, AZ, USA
| | - Michael J. Krowka
- Department of Pulmonary and Critical Care Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Jeanne Laberge
- Department of Radiology and Biomedical Imaging, Division of Interventional Radiology, University of California San Francisco, San Francisco, CA, USA
| | - Edward W. Lee
- Department of Radiology, Division of Interventional Radiology, University of California-Los Angeles David Geffen School of Medicine, Los Angeles, CA, USA
| | - David C. Mulligan
- Department of Surgery, Division of Transplantation, Yale University School of Medicine, New Haven, CT, USA
| | - Mitra K. Nadim
- Department of Medicine, Division of Nephrology and Hypertension, University of Southern California, Los Angeles, California, USA
| | - Patrick G. Northup
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Virginia, Charlottesville, VA, USA
| | - Riad Salem
- Department of Radiology, Division of Vascular and Interventional Radiology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Joseph J. Shatzel
- Division of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR, USA
| | - Cathryn J. Shaw
- Department of Radiology, Division of Interventional Radiology, Baylor University Medical Center, Dallas, TX, USA
| | - Douglas A. Simonetto
- Department of Physiology, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Jonathan Susman
- Department of Radiology, Division of Interventional Radiology, Columbia University Irving Medical Center, New York, NY, USA
| | - K. Pallav Kolli
- Department of Radiology and Biomedical Imaging, Division of Interventional Radiology, University of California San Francisco, San Francisco, CA, USA
| | - Lisa B. VanWagner
- Department of Medicine, Division of Gastroenterology & Hepatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA,Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA,Address for correspondence: Lisa B. VanWagner MD MSc FAST FAHA, Assistant Professor of Medicine and Preventive Medicine, Divisions of Gastroenterology & Hepatology and Epidemiology, Northwestern University Feinberg School of Medicine, 676 N. St Clair St - Suite 1400, Chicago, Illinois 60611 USA, Phone: 312 695 1632, Fax: 312 695 0036,
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Lee YT, Lin CS, Fang WH, Lee CC, Ho CL, Wang CH, Tsai DJ, Lin C. Artificial Intelligence-Enabled Electrocardiography Detects Hypoalbuminemia and Identifies the Mechanism of Hepatorenal and Cardiovascular Events. Front Cardiovasc Med 2022; 9:895201. [PMID: 35770216 PMCID: PMC9234125 DOI: 10.3389/fcvm.2022.895201] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2022] [Accepted: 05/23/2022] [Indexed: 11/17/2022] Open
Abstract
Background Albumin, an important component of fluid balance, is associated with kidney, liver, nutritional, and cardiovascular diseases (CVD) and is measured by blood tests. Since fluid balance is associated with electrocardiography (ECG) changes, we established a deep learning model (DLM) to estimate albumin via ECG. Objective This study aimed to develop a DLM to estimate albumin via ECG and explored its contribution to future complications. Materials and Methods A DLM was trained for estimating ECG-based albumin (ECG-Alb) using 155,078 ECGs corresponding to albumin from 79,111 patients, and another independent 13,335 patients from an academic medical center and 11,370 patients from a community hospital were used for internal and external validation. The primary analysis focused on distinguishing patients with mild to severe hypoalbuminemia, and the secondary analysis aimed to provide additional prognostic value from ECG-Alb for future complications, which included mortality, new-onset hypoalbuminemia, chronic kidney disease (CKD), new onset hepatitis, CVD mortality, new-onset acute myocardial infarction (AMI), new-onset stroke (STK), new-onset coronary artery disease (CAD), new-onset heart failure (HF), and new-onset atrial fibrillation (Afib). Results The AUC to identify hypoalbuminemia was 0.8771 with a sensitivity of 56.0% and a specificity of 90.7% in the internal validation set, and the Pearson correlation coefficient was 0.69 in the continuous analysis. The most important ECG features contributing to ECG-Alb were ordered in terms of heart rate, corrected QT interval, T wave axis, sinus rhythm, P wave axis, etc. The group with severely low ECG-Alb had a higher risk of all-cause mortality [hazard ratio (HR): 2.45, 95% CI: 1.81-3.33] and the other hepatorenal and cardiovascular events in the internal validation set. The external validation set yielded similar results. Conclusion Hypoalbuminemia and its complications can be predicted using ECG-Alb as a novel biomarker, which may be a non-invasive tool to warn asymptomatic patients.
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Affiliation(s)
- Yung-Tsai Lee
- Division of Cardiovascular Surgery, Cheng Hsin Rehabilitation and Medical Center, Taipei City, Taiwan
| | - Chin-Sheng Lin
- Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei City, Taiwan
| | - Wen-Hui Fang
- Department of Family and Community Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei City, Taiwan
- Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei City, Taiwan
- Artificial Intelligence of Things Center, Tri-Service General Hospital, National Defense Medical Center, Taipei City, Taiwan
| | - Chia-Cheng Lee
- Medical Informatics Office, Tri-Service General Hospital, National Defense Medical Center, Taipei City, Taiwan
- Division of Colorectal Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei City, Taiwan
| | - Ching-Liang Ho
- Division of Hematology and Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei City, Taiwan
| | - Chih-Hung Wang
- Department of Otolaryngology-Head and Neck Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei City, Taiwan
- Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei City, Taiwan
| | - Dung-Jang Tsai
- Artificial Intelligence of Things Center, Tri-Service General Hospital, National Defense Medical Center, Taipei City, Taiwan
- School of Public Health, National Defense Medical Center, Taipei City, Taiwan
| | - Chin Lin
- Artificial Intelligence of Things Center, Tri-Service General Hospital, National Defense Medical Center, Taipei City, Taiwan
- School of Public Health, National Defense Medical Center, Taipei City, Taiwan
- Medical Technology Education Center, School of Medicine, National Defense Medical Center, Taipei City, Taiwan
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22
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Abstract
Hepatorenal syndrome (HRS) is defined as a functional renal failure without major histologic changes in individuals with severe liver disease and it is associated with a high mortality rate. Renal hypoperfusion due to marked vasoconstriction as a result of complex circulatory dysfunction has been suggested to be the cornerstone of HRS. Splanchnic and peripheral arterial vasodilation and cirrhotic cardiomyopathy result in effective arterial hypovolemia and compensatory activation of vasoconstrictor mechanisms. The efficacy of current therapeutic strategies targeting this circulatory dysfunction is limited. Increasing evidence suggests a substantial role of systemic inflammation in HRS via either vascular or direct renal effects. Here we summarize the current understanding of HRS pathophysiology.
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Affiliation(s)
- Timea Csak
- Sandra Atlas Bass Center for Liver Diseases, Northwell Health, 400 Community Drive, Manhasset, NY 11030, USA.
| | - David Bernstein
- Division of Hepatology and Sandra Atlas Bass Center for Liver Diseases, Northwell Health, Zucker School of Medicine at Hofstra/Northwell, 400 Community Drive, Manhasset, NY 11030, USA
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23
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Ferreira LM, Terrabuio DR, Ferreira CM, Mazo DFDC, Haddad LBDP. COST EFFECTIVENESS OF USING TERLIPRESSIN TO TREAT HEPATORENAL SYNDROME. ARQUIVOS DE GASTROENTEROLOGIA 2022; 59:268-274. [PMID: 35830040 DOI: 10.1590/s0004-2803.202202000-48] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Accepted: 03/28/2022] [Indexed: 06/15/2023]
Abstract
BACKGROUND Hepatorenal syndrome (HRS) is the most severe form of acute kidney injury in patients with advanced cirrhosis, and it is associated with high mortality. It is usually diagnosed according to criteria defined by the International Ascites Club. Currently, the most frequently indicated pharmacological therapy for the treatment of HRS is a combination of splanchnic vasoconstrictors (terlipressin or norepinephrine) in combination with albumin. With the progressive increase in healthcare spending, it is important to conduct a cost-effectiveness analysis of pharmacological treatment in patients who are diagnosed with HRS. OBJECTIVE To perform a cost-effectiveness assessment for the use of terlipressin in combination with albumin to treat HRS in patients with cirrhosis. METHODS Economic evaluation of cost-effectiveness based on secondary data from studies showed the efficacy of terlipressin therapy compared with norepinephrine combined with albumin or albumin alone. The cost-effectiveness analysis was calculated using an incremental cost-effectiveness ratio (ICER), and a sensitivity analysis was developed by varying the values of therapies and probabilities. The Brazilian real was the currency used in the analysis, and the results were converted to US dollars. RESULTS After selection, eligibility, and evaluation of the quality of publications, the results demonstrated that administration of terlipressin or norepinephrine in combination with albumin in patients diagnosed with HRS type 1 was efficacious. The cost of treatment with terlipressin in combination with albumin was USD $1,644.06, administration of albumin alone was USD $912.02, and norepinephrine plus albumin was USD $2,310.78. Considering that the combination therapies demonstrated effectiveness, the incremental cost of terlipressin and norepinephrine in combination with albumin was USD $666.73, and an effectiveness of 0.570 was found for terlipressin in combination with albumin and 0.200 for norepinephrine in combination with albumin. The incremental effectiveness was 0.370, and the ICER was USD $1,801.97. Thus, the parameters of increasing cost per therapy and ICER indicated that the combined therapy of terlipressin plus albumin was cost effective compared to albumin alone or norepinephrine plus albumin in a public single-payer healthcare system. CONCLUSION A cost-effectiveness analysis showed that terlipressin in combination with albumin when administered concomitantly to patients who were diagnosed with type 1 HRS is cost-effective compared to norepinephrine in combination with albumin administered in a controlled environment.
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Affiliation(s)
- Luciana Marcondes Ferreira
- Universidade de São Paulo, Faculdade de Medicina, Departamento de Gastroenterologia, São Paulo, SP, Brasil
| | - Débora Raquel Terrabuio
- Universidade de São Paulo, Faculdade de Medicina, Departamento de Gastroenterologia, São Paulo, SP, Brasil
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El-Makarem MAERA, Mahmoud YZ, Moussa MM, El-Saghir SMM, Keryakos HKH. Do old urinary biomarkers have a place in the new definition of hepatorenal syndrome in the Egyptian cirrhotic patients? A single-center experience. EGYPTIAN LIVER JOURNAL 2022. [DOI: 10.1186/s43066-022-00185-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Hepatorenal syndrome is still a diagnosis of exclusion despite new classification.
Aims
To validate the accuracy of urinary neutrophil gelatinase-associated lipocalin, interleukin-18, and kidney injury molecule-1 in the new diagnostic criteria of hepatorenal syndrome in Egyptian patients with hepatitis C virus-related liver cirrhosis using serum creatinine as a gold standard test for acute kidney injury.
Methods
One-hundred twenty cirrhotic patients with ascites were recruited and divided into two groups depending on the presence or absence of renal impairment, and 40 age- and sex-matched cirrhotic patients without ascites used as controls participated in the study. Urinary biomarkers were measured and compared with conventional biomarkers used to assess kidney function (serum creatinine, estimated glomerular filtration rate).
Results
The mean urinary neutrophil gelatinase-associated lipocalin, interleukin-18, and kidney injury molecule-1 were statistically significantly higher in patients with hepatorenal syndrome and were found to be helpful in the early detection with cutoff values of 125 ng/ml, 34.8 pg/ml, and 3.1 pg/ml, respectively.
Conclusions
Urinary neutrophil gelatinase-associated lipocalin, interleukin-18, and kidney injury molecule-1 levels are higher in patients with cirrhotic ascites complicated by HRS-AKI using the new definition of HRS, but IL-18 has lower sensitivity and specificity for the prediction of HRS-AKI as compared to NGAL and KIM-1.
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Jamil K, Huang X, Hayashida D, Lodaya K. The Hepatorenal Syndrome (HRS) Patient Pathway: Retrospective Analysis of Electronic Health Records. Curr Ther Res Clin Exp 2022; 96:100663. [PMID: 35399809 PMCID: PMC8987804 DOI: 10.1016/j.curtheres.2022.100663] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Accepted: 02/04/2022] [Indexed: 11/16/2022] Open
Abstract
Background Hepatorenal syndrome (HRS) is among the leading causes of hospitalization and mortality in patients with chronic liver disease. Objective To assess the HRS patient journey from preadmission to postdischarge to understand patient characteristics, disease progression, treatment patterns, and outcomes. Methods We conducted a retrospective study using real-world data from a nationwide electronic health record database (Cerner Health Facts, Kansas City, Missouri). We used ICD-9/10 diagnosis codes to identify patients hospitalized with HRS between January 1, 2009, and January 31, 2018. We assessed patient characteristics and history, clinical presentation, treatment, and outcomes. Regression analysis was conducted to assess the association between patient characteristics and survival while adjusting for demographic and clinical covariates. Results The study included 3563 patients (62% men). Precipitants of HRS included gastrointestinal bleeding (18%), diuretics and infections (30%), and paracentesis (26%). Although 21% of patients had liver injury exclusively associated with alcohol use, 20% had hepatitis C, 8% had nonalcoholic steatohepatitis, and the etiology of the remainder (51%) was either some combination of conditions or unknown. A total of 42% of patients received vasopressors, including octreotide and midodrine (10%), other combinations of vasopressors (11%), or another single vasopressor (21%). In-hospital mortality was 34%, and 14% of patients were discharged to hospice. Regression analysis showed patients with acute-on-chronic liver failure had higher mortality in acute-on-chronic liver failure grades 1 (odds ratio = 1.59), 2 (odds ratio = 2.49), and 3 (odds ratio = 4.53) versus no acute-on-chronic liver failure. Among survivor patients, 38% were readmitted within 90 days of discharge; 23% of readmissions were HRS-related. Conclusions The HRS patient journey presented in this study highlights inconsistencies in, and provides insight into, associated hospital-based treatment strategies. A mortality rate of 34% along with a readmission rate of 23% associated with HRS-related complications warrant more disease awareness and effective treatment. Further research is needed to examine the interactions between the etiology of cirrhosis, precipitants, treatment, and outcomes. (Curr Ther Res Clin Exp. 2022; 82:XXX–XXX)
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Affiliation(s)
| | | | | | - Kunal Lodaya
- Boston Strategic Partners Inc, Boston, Massachusetts
- Address correspondence to: Kunal Lodaya, MD, Boston Strategic Partners, Inc, 4 Wellington St, Suite 3, Boston, MA 02118.
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Gupta MM, Deng X. Hepatorenal Syndrome. APPROACHES TO CHRONIC KIDNEY DISEASE 2022:151-168. [DOI: 10.1007/978-3-030-83082-3_9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Alves RDC, Ferreira CGM, Ferreira de Melo IM, Baptista MGP, Lima de Albuquerque YM, do Nascimento BJ, dos Santos YB, Wanderley-Teixeira V, Teixeira ÁAC. Renal and hepatic changes in the offspring of rats that received biological insecticides during pregnancy and lactation. Acta Histochem 2021; 123:151799. [PMID: 34656827 DOI: 10.1016/j.acthis.2021.151799] [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: 07/29/2020] [Revised: 09/27/2021] [Accepted: 10/08/2021] [Indexed: 10/20/2022]
Abstract
Bacillus thuringiensis insecticides have been considered safe, being an alternative to the use of synthetic insecticides. However, studies have shown the effects of Bt Cry toxins on various organs, compromising their functions. The objective of this work was to test whether the administration of biological insecticides based on B. thuringiensis in pregnant rats will cause histopathological changes in the liver and kidneys, as well as in the levels of toxicity biomarkers, of their puppies in adulthood. Twenty rats, 90 days old, were used, divided into four groups: GC - Pregnant rats, GX - Pregnant rats that received XenTari®, GDi - Pregnant rats that received Dipel® and GDe - Pregnant rats that received deltamethrin. Insecticides were administered by gavage at a dosage of 1 mg/100 g/day (GX and GDi), and 2 mg/Kg/day (GDe) during pregnancy and lactation. In the animals of the groups whose matrices received the insecticides, there was a reduction in the levels of the biomarkers of toxicity alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea and creatinine, about the control group. The biological insecticides promoted histopathological changes in the liver, with the presence of portal vein, centrilobular and sinusoidal capillaries congestion, and in the kidney, presence of cortical congestion and reduction of the subcapsular space. Histochemical evaluation in the liver demonstrated a significant reduction in glycogen in the groups that received insecticides when compared to the control group, whereas for collagen fibers in both the liver and the kidneys, no differences were observed between the experimental groups. The morphometry of the liver revealed a significant reduction in the lobular parenchyma and an increase in the non-lobular parenchyma, and in the kidney, there was a reduction in the diameter and volume of the glomerulus and Bowman's capsule of the animals whose matrices received both biological and synthetic insecticides. Thus, it is concluded that the biological insecticides XenTari® and Dipel® in sublethal doses in pregnant rats promote changes in the liver and kidney of the offspring similar to the insecticide deltamethrin, which extend into adulthood.
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He HM, He C, Zhang SC, You ZB, Lin XQ, Luo MQ, Lin MQ, Guo YS, Zheng WP, Lin KY. Predictive value of aspartate aminotransferase-to-alanine aminotransferase ratio for contrast-associated acute kidney injury in patients undergoing elective percutaneous coronary intervention. J Cardiol 2021; 79:618-625. [PMID: 34857433 DOI: 10.1016/j.jjcc.2021.11.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Revised: 10/24/2021] [Accepted: 11/03/2021] [Indexed: 12/28/2022]
Abstract
BACKGROUND Pre-procedure liver insufficiency has been demonstrated as a poor prognostic factor after percutaneous coronary intervention (PCI). Recent research discovered that the aspartate aminotransferase-to-alanine aminotransferase ratio (De-Ritis ratio) reflects the severity of liver insufficiency and was associated with adverse outcomes. We aim to evaluate the predictive value of the De-Ritis ratio for contrast-associated acute kidney injury (CA-AKI) and long-term mortality in patients undergoing elective PCI. METHODS We retrospectively enrolled 5780 consenting patients undergoing elective PCI between January 2012 and December 2018. CA-AKI was defined as an increase in serum creatinine ≥0.3 mg/dl or ≥50% within 48 h after the administration of contrast media. RESULTS The incidence of CA-AKI was 6.3% (n = 363). The De-Ritis ratio >1.30 was identified as the best cut-off value for CA-AKI prediction. The De-Ritis ratio showed an area under the curve (AUC) of 0.636 [95% confidence interval (CI): 0.605-0.667] in predicting CA-AKI, which was significantly greater than alanine aminotransferase (p<0.001) and aspartate aminotransferase (p = 0.012) alone. Furthermore, compared to currently recognized liver function assessment tools, the predictive value of the De-Ritis ratio on CA-AKI was similar to the MELD score (AUC: 0.636 vs 0.626, p = 0.631) and higher than the MELD-XI score (AUC: 0.636 vs 0.561, p<0.001). Multivariate logistic analysis showed that the De-Ritis ratio >1.30 was independently associated with CA-AKI (odds ratio=1.551, 95% CI: 1.185-2.030, p = 0.001). The addition of the De-Ritis ratio to the fully adjusted logistic regression model has significant incremental effects on the risk prediction for CA-AKI with a continuous net reclassification improvement of 0.395 (p<0.001) and an integrated discrimination improvement of 0.005 (p = 0.018). Additionally, the De-Ritis ratio >1.30 was significantly associated with long-term mortality (hazard ratio=1.285, 95% CI: 1.007-1.641, p = 0.044). CONCLUSIONS The De-Ritis ratio was an independent risk factor for CA-AKI and long-term mortality in patients undergoing elective PCI.
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Affiliation(s)
- Hao-Ming He
- Department of Cardiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, China; Fujian Provincial Key Laboratory of Cardiovascular Disease, Fujian Cardiovascular Institute, Fujian Provincial Center for Geriatrics, Fujian Clinical Medical Research Center for Cardiovascular Diseases, Fuzhou, China; Fujian Heart Failure Center Alliance, Fuzhou, China
| | - Chen He
- Department of Cardiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, China; Fujian Provincial Key Laboratory of Cardiovascular Disease, Fujian Cardiovascular Institute, Fujian Provincial Center for Geriatrics, Fujian Clinical Medical Research Center for Cardiovascular Diseases, Fuzhou, China; Fujian Heart Failure Center Alliance, Fuzhou, China
| | - Si-Cheng Zhang
- Department of Cardiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, China; Fujian Provincial Key Laboratory of Cardiovascular Disease, Fujian Cardiovascular Institute, Fujian Provincial Center for Geriatrics, Fujian Clinical Medical Research Center for Cardiovascular Diseases, Fuzhou, China; Fujian Heart Failure Center Alliance, Fuzhou, China
| | - Zhe-Bin You
- Department of Geriatric Medicine, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fujian Provincial Center for Geriatrics, Fuzhou, China
| | - Xue-Qin Lin
- Department of Cardiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, China; Fujian Provincial Key Laboratory of Cardiovascular Disease, Fujian Cardiovascular Institute, Fujian Provincial Center for Geriatrics, Fujian Clinical Medical Research Center for Cardiovascular Diseases, Fuzhou, China; Fujian Heart Failure Center Alliance, Fuzhou, China
| | - Man-Qing Luo
- Department of Cardiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, China; Fujian Provincial Key Laboratory of Cardiovascular Disease, Fujian Cardiovascular Institute, Fujian Provincial Center for Geriatrics, Fujian Clinical Medical Research Center for Cardiovascular Diseases, Fuzhou, China; Fujian Heart Failure Center Alliance, Fuzhou, China
| | - Mao-Qing Lin
- Department of Cardiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, China; Fujian Provincial Key Laboratory of Cardiovascular Disease, Fujian Cardiovascular Institute, Fujian Provincial Center for Geriatrics, Fujian Clinical Medical Research Center for Cardiovascular Diseases, Fuzhou, China; Fujian Heart Failure Center Alliance, Fuzhou, China
| | - Yan-Song Guo
- Department of Cardiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, China; Fujian Provincial Key Laboratory of Cardiovascular Disease, Fujian Cardiovascular Institute, Fujian Provincial Center for Geriatrics, Fujian Clinical Medical Research Center for Cardiovascular Diseases, Fuzhou, China; Fujian Heart Failure Center Alliance, Fuzhou, China.
| | - Wei-Ping Zheng
- Department of Cardiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, China; Fujian Provincial Key Laboratory of Cardiovascular Disease, Fujian Cardiovascular Institute, Fujian Provincial Center for Geriatrics, Fujian Clinical Medical Research Center for Cardiovascular Diseases, Fuzhou, China; Fujian Heart Failure Center Alliance, Fuzhou, China.
| | - Kai-Yang Lin
- Department of Cardiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, China; Fujian Provincial Key Laboratory of Cardiovascular Disease, Fujian Cardiovascular Institute, Fujian Provincial Center for Geriatrics, Fujian Clinical Medical Research Center for Cardiovascular Diseases, Fuzhou, China; Fujian Heart Failure Center Alliance, Fuzhou, China.
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Kollaras V, Valsami G, Lambropoulou M, Konstandi O, Kostomistsopoulos N, Pikoulis E, Simopoulos C, Tsaroucha A. Effect of silibinin on the expression of MMP2, MMP3, MMP9 and TIMP2 in kidney and lung after hepatic ischemia/reperfusion injury in an experimental rat model. Acta Cir Bras 2021; 36:e360904. [PMID: 34755764 PMCID: PMC8580512 DOI: 10.1590/acb360904] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Accepted: 08/12/2021] [Indexed: 11/22/2022] Open
Abstract
PURPOSE The protective effect of silibinin on kidney and lung parenchyma during hepatic ischemia/reperfusion injury (IRI) is explored. METHODS Sixty-three Wistar rats were separated into three groups: sham; control (45 min IRI); and silibinin (200 μL silibinin administration after 45 min of ischemia and before reperfusion). Immunohistochemistry and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to evaluate the expression levels of MMP2, MMP3, MMP9, and TIMP2 on kidney and lung. RESULTS Comparing sham vs. control groups, confirmed that hepatic IRI increased both renal and lung MMP2, MMP3, MMP9 and TIMP2 expressions starting at 180 min (p<0.001). Comparison of the control vs. silibinin groups showed a statistically significant decrease in the expression levels of MMP2, MMP3, and MMP9 and increase of TIMP2 in kidney and lung parenchyma. The starting point of this decrease was at 120 min after reperfusion, both for kidney and lung parameters, and it was statistically significant at 240 min (p<0.001) for kidney, while silibinin showed a peak of lung protection at 180 min after hepatic reperfusion (p<0.001). CONCLUSIONS Hepatic IRI causes distant kidney and lung damage, while a statistically significant protective action, both on kidney and lung parenchyma, is conveyed by the intravenous administration of silibinin.
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Chaney A. A Review for the Practicing Clinician: Hepatorenal Syndrome, a Form of Acute Kidney Injury, in Patients with Cirrhosis. Clin Exp Gastroenterol 2021; 14:385-396. [PMID: 34675586 PMCID: PMC8502008 DOI: 10.2147/ceg.s323778] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Accepted: 09/04/2021] [Indexed: 12/15/2022] Open
Abstract
The hepatorenal syndrome type of acute kidney injury (HRS-AKI), formerly known as type 1 hepatorenal syndrome, is a rapidly progressing renal failure that occurs in many patients with advanced cirrhosis and ascites. Accumulating evidence has led to a recent evolution of diagnostic criteria for this serious complication of end-stage liver disease. The aim of this review is to provide an overview of disease-related characteristics and therapeutic management of patients with HRS-AKI. Relevant literature was compiled to support discussion of the pathophysiology, diagnosis, prognosis, associated conditions, prevention, treatment, and management of HRS-AKI. Onset of HRS-AKI is characterized by sudden severe renal vasoconstriction, leading to an acute reduction in glomerular filtration rate and rapid, potentially life-threatening, renal deterioration. Although our understanding of disease pathophysiology continues to evolve, etiology of HRS-AKI likely involves systemic hemodynamic changes caused by liver disease, inflammation, and damage to renal parenchyma. There is currently no gold standard for diagnosis, which typically involves a clinical workup, abdominal imaging, and laboratory assessments. The current consensus definition of HRS-AKI includes proposed diagnostic criteria based on changes in serum creatinine levels tailored for high sensitivity, and rapid detection to accelerate diagnosis and treatment initiation. The only potential cure for HRS-AKI is liver transplantation; however, vasoconstrictive agents and other supportive measures are used as needed to help maintain survival for patients who are awaiting or are ineligible for transplantation. The severity of HRS-AKI, complex pathology, limited treatment options, and range of associated conditions pose significant challenges for both patients and care providers.
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Affiliation(s)
- Amanda Chaney
- Department of Transplant, College of Medicine, Mayo Clinic, Jacksonville, FL, USA
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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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Hepatorenal syndrome: pathophysiology and evidence-based management update. ROMANIAN JOURNAL OF INTERNAL MEDICINE 2021; 59:227-261. [DOI: 10.2478/rjim-2021-0006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Indexed: 11/20/2022] Open
Abstract
Abstract
Hepatorenal syndrome (HRS) is a functional renal failure that develops in patients with advanced hepatic cirrhosis with ascites and in those with fulminant hepatic failure. The prevalence of HRS varies among studies but in general it is the third most common cause of acute kidney injury (AKI) in cirrhotic patients after pre-renal azotemia and acute tubular necrosis. HRS carries a grim prognosis with a mortality rate approaching 90% three months after disease diagnosis. Fortunately, different strategies have been proven to be successful in preventing HRS. Although treatment options are available, they are not universally effective in restoring renal function but they might prolong survival long enough for liver transplantation, which is the ultimate treatment. Much has been learned in the last two decades regarding the pathophysiology and management of this disease which lead to notable evolution in the HRS definition and better understanding on how best to manage HRS patients. In the current review, we will summarize the recent advancement in epidemiology, pathophysiology, and management of HRS.
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El-Haddad HM, Sabry AA, Shehata GM. Endoscopic versus percutaneous biliary drainage for resectable pancreatic head cancer with hyperbilirubinemia and impact on pancreaticoduodenectomy: A randomized controlled study. Int J Surg 2021; 93:106043. [PMID: 34371176 DOI: 10.1016/j.ijsu.2021.106043] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Revised: 07/09/2021] [Accepted: 07/29/2021] [Indexed: 02/02/2023]
Abstract
BACKGROUND We hypothesized that percutaneous biliary drainage provides more short-term advantages over endoscopic stenting before pancreaticoduodenectomy. METHODS Between January 2019 and December 2010, a prospective cohort study was conducted. Sixty patients with potentially resectable pancreatic head cancers and high bilirubin levels were stratified into two equal groups according to the method of biliary drainage: endoscopic stenting or percutaneous drainage. The primary outcome measures were operative difficulties and early postoperative morbidity, the secondary outcome was post-drainage complications. RESULTS Both groups were comparable in age; gender; presenting symptoms, type of malignancy, post-drainage complications, and time intervals between drainage and surgery. Key preoperative significant differences were technically higher but clinical success rates was better in the PTD cohort. ERCP patients had significantly more difficult dissections, more blood loss, longer resection time, more postoperative bile leak, and longer hospital stay. CONCLUSION From the operative perspective, patients who underwent PTD in the preoperative setting had fewer morbidities and shorter hospital stay. Large scale studies are required to support the validity of these findings in surgical practice.
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Affiliation(s)
- Hany M El-Haddad
- Department of Gastrointestinal Surgery, Faculty of Medicine, Alexandria University, Egypt.
| | - Ahmed A Sabry
- Department of Gastrointestinal Surgery, Faculty of Medicine, Alexandria University, Egypt
| | - Gihan M Shehata
- Biomedical Informatics and Medical Statistics Department, Medical Research Institute, Alexandria University, Egypt
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Lamanna A, Mitreski G, Maingard J, Owen A, Schelleman T, Goodwin M, Ranatunga D. Ultrasound-guided portal vein puncture during Transjugular Intrahepatic Portosystemic Shunt: Technique and experience of a quaternary liver transplant hospital. J Med Imaging Radiat Oncol 2021; 66:60-67. [PMID: 34278730 DOI: 10.1111/1754-9485.13288] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 06/24/2021] [Accepted: 07/02/2021] [Indexed: 10/20/2022]
Abstract
INTRODUCTION Portal hypertension (PH) is associated with complications including refractory ascites and variceal haemorrhage and can be treated endovascularly with a Transjugular Intrahepatic Portosystemic Shunt (TIPS). Portal vein puncture during TIPS using real-time transabdominal ultrasound guidance is one of many portal vein puncture techniques and is seldom used compared with other methods. The purpose of this manuscript is to describe this technique and its associated procedural outcomes at a quaternary liver transplant hospital. METHODS Clinical data of all patients who underwent ultrasound-guided TIPS at our institution between 1 January 2009 and 1 January 2019 were retrospectively obtained from electronic medical records and reviewed. Patient demographics, indications, procedural outcomes and complications were recorded. RESULTS Forty-four ultrasound-guided TIPS procedures were performed during the study period. The most common indication for TIPS was refractory ascites (n = 26; 57%) and variceal haemorrhage (n = 12; 26%). Technical success rate was 100%. No intraprocedural complications occurred. Periprocedural complication rate was 35% (n = 16) with encephalopathy (n = 8; 17%) and sepsis (n = 5; 11%) the most common. One patient with sepsis died. No other TIPS-related deaths occurred. Median fluoroscopy time, contrast volume, air kerma and dose area product values for all procedures were 35 minutes (IQR 24-51), 100 ml (IQR 70-160), 0.95 Gy (IQR 0.50-1.53) and 127 Gycm2 (IQR 68.75-206), respectively. CONCLUSION Transabdominal ultrasound-guided portal vein puncture during TIPS is safe and technically feasible. When compared to fluoroscopically guided methods, it is associated with lower intraprocedural complication rates, fluoroscopy times, contrast volumes and radiation doses in our experience. Radiation doses, FTs and contrast volumes were also considerably lower than recommended limits.
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Affiliation(s)
- Anthony Lamanna
- Interventional Radiology Service - Department of Radiology, Austin Hospital, Melbourne, Victoria, Australia
| | - Goran Mitreski
- Interventional Radiology Service - Department of Radiology, Austin Hospital, Melbourne, Victoria, Australia
| | - Julian Maingard
- Department of Imaging, Monash Health, Melbourne, Victoria, Australia.,School of Medicine, Deakin University, Geelong, Victoria, Australia
| | - Andrew Owen
- Interventional Radiology Service - Department of Radiology, Austin Hospital, Melbourne, Victoria, Australia.,Interventional Radiology Service - Department of Radiology, Barwon Health, Geelong, Victoria, Australia
| | - Tony Schelleman
- Interventional Radiology Service - Department of Radiology, Austin Hospital, Melbourne, Victoria, Australia
| | - Mark Goodwin
- Interventional Radiology Service - Department of Radiology, Austin Hospital, Melbourne, Victoria, Australia
| | - Dinesh Ranatunga
- Interventional Radiology Service - Department of Radiology, Austin Hospital, Melbourne, Victoria, Australia
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Onwuka CC, Ayoola OO, Adekanle O, Famurewa OC, Abidoye IA. Renal arterial resistance index among subjects with liver cirrhosis in a Nigerian population. JOURNAL OF CLINICAL ULTRASOUND : JCU 2021; 49:538-545. [PMID: 33527436 DOI: 10.1002/jcu.22985] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Revised: 01/05/2021] [Accepted: 01/17/2021] [Indexed: 06/12/2023]
Abstract
PURPOSE To describe the relationship between renal artery resistance index (RARI) and liver function based on Child-Pugh system among patients with liver cirrhosis (LC) in Southwest Nigeria. METHODS About 50 patients with LC and 50 controls were consecutively recruited into this prospective comparative case control study. Each LC patient was classed based on Child-Turcotte-Pugh (CTP) system after relevant tests. Subjects underwent abdominal ultrasonography with triplex Doppler examination of the right kidney to obtain RARI. RESULTS About 50 cirrhotic and 50 controls completed the study. Age range of cirrhotic subjects was 19-69 years (mean ± SD = 47.5 ± 13.3) while that of controls was 18-69 years (46.9 ± 15.0). RARI was higher (P = <.001) in patients with LC (0.68) than in controls (0.57). RARI was also significantly higher (P = <.001) in cirrhotic subjects in CTP class C (0.72) than in those in classes B (0.66) and A (0.58). Additionally, RARI showed significant correlation with CTP total score (r = .662; P = <.001), serum bilirubin (r = .297; P = .036), serum albumin (r = -.494; P = <.001), serum sodium (r = -.369; P = .008), Model for End Stage Liver Disease (MELD) score (r = .316; P = .026) and MELD-Na score (r = .470; P = .001). RARI showed no significant relationship with serum creatinine (r = .110; P = .445) and blood urea nitrogen (r = .112; P = .437). CONCLUSION Liver cirrhosis is associated with renovascular changes which manifest as increased resistance in the renal arteries. RARI is a useful noninvasive tool for the assessment of these changes and should be done routinely in the evaluation of patients with LC.
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Affiliation(s)
| | - Oluwagbemiga Oluwole Ayoola
- Department of Radiology, Faculty of Clinical Sciences, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria
| | - Olusegun Adekanle
- Department of Medicine, Obafemi Awolowo University, Obafemi Awolowo University Teaching Hospitals, Ile-Ife, Osun State, Nigeria
| | - Olusola Comfort Famurewa
- Department of Radiology, Faculty of Clinical Sciences, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria
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Albumin administration in patients with decompensated liver cirrhosis: a meta-analytic update. Eur J Gastroenterol Hepatol 2021; 33:479-486. [PMID: 32976190 DOI: 10.1097/meg.0000000000001932] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
End-stage liver disease and its related complications exert a huge disease burden and reduce the survival rates of many patients. Albumin administration for patients with decompensated liver cirrhosis has been a controversial topic of discussion. The aim of this study is to investigate whether albumin reduces the mortality and complications of liver cirrhosis compared to standard medical therapy (SMT) alone. Clinical trials in which albumin administration was compared to SMT in patients with liver cirrhosis were included in this meta-analysis. The primary outcome of this study was to evaluate the effect on reducing all-cause mortality. Ascites control, renal failure and hepatic encephalopathy were evaluated as secondary outcomes. Nine clinical trials with 1231 patients were recruited and analyzed using the quality effect model. Mortality rate was significantly reduced in the albumin group [relative risk (RR) 0.73, 95% confidence interval (CI) 0.56-0.96]. Heterogeneity was mild across all studies (I2 23.3%). Studies reporting long-term albumin (LTA) administration were found to have a significant decrease in mortality (RR 0.57, 95% CI 0.44-0.73). However, studies reporting short-term albumin administration were found to have no effect on mortality (RR 0.90, 95% CI 0.56-1.45). Furthermore, there was a significant decrease in the incidence of all secondary outcomes. This meta-analysis provides evidence that LTA administration is significantly effective in reducing the mortality of liver cirrhosis compared to SMT. Albumin administration was also shown to reduce the occurrence of ascites, renal failure and hepatic encephalopathy as complications of liver cirrhosis.
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Does Anemia Have a Potential Effect on Type 2 Hepatorenal Syndrome? Can J Gastroenterol Hepatol 2020; 2020:1134744. [PMID: 33381474 PMCID: PMC7762663 DOI: 10.1155/2020/1134744] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Revised: 11/19/2020] [Accepted: 12/10/2020] [Indexed: 11/17/2022] Open
Abstract
Background/Aims. Hepatorenal syndrome (HRS) is a form of functional renal failure arising in advanced cirrhosis and is characterized by a poor survival rate. Anemia is frequently observed during the clinical course of cirrhosis. Our study aimed to investigate the hematologic findings in patients with cirrhosis to determine the effects of anemia on renal functions in type 2 HRS and if it was a potential aggravating factor. Materials and Methods. This prospective study, in which all consecutive patients with cirrhosis were enrolled, was performed at a tertiary-level hospital (Military Hospital of Tunis) from January 2019 to June 2019. A total of 9 patients with HRS fulfilled the type 2 HRS diagnostic criteria, and 41 patients with cirrhosis without HRS were included. All data regarding patients were obtained from the medical record. Demographic data, routine hemograms, biochemical, and urinary test results were collected. Models of end-stage liver disease (MELD) and Child-Turcotte-Pugh (CTP) scores were calculated. Results. The most common etiology of cirrhosis was viral hepatitis (66%). According to the CTP score, 23 patients were in the CTP-A stage, 13 in the CTP-B stage, and 14 patients were in the CTP-C stage. Patients with type 2 HRS had significantly lower hemoglobin levels compared with non-HRS stable cirrhosis patients. As hemoglobin levels decreased, renal function worsened on patients with type 2 HRS. Patients with lower hemoglobin levels had poor prognosis and survival compared with patients with higher hemoglobin levels. Logistic regression analysis showed that lower hemoglobin levels and higher MELD and CTP scores were statistically significant for an onset of type 2 HRS. Conclusion. Renal dysfunction is a frequent complication in patients with end-stage chronic liver disease. The role of anemia in aggravating HRS in patients with cirrhosis is explained by hypoxia that can lead to microcirculatory renal ischemia. Other studies are required to determine if anemia is a precipitant factor for HRS or not.
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Krishna R, Raj J, Dev D, Prasad SC, Reghu R, V SO. A study on clinical outcomes of combination of terlipressin and albumin in Hepatorenal Syndrome. Scand J Gastroenterol 2020; 55:860-864. [PMID: 32634332 DOI: 10.1080/00365521.2020.1786851] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Hepatorenal Syndrome (HRS) is a reversible functional renal impairment that occurs in patients with advanced liver cirrhosis or those with fulminant hepatic failure. AIM To evaluate the effect of terlipressin and albumin combination in various clinical outcomes in Hepatorenal Syndrome patientsMethods and Material: It was a prospective study involving 50 patients with HRS. The effectiveness parameters of the treatments were: confirmed HRS reversal, Recurrence of HRS within 90 days of treatment and mortality rate up to 90 days. The safety assessment includes adverse events collected up to 14 days of post-treatment. The quality of life of HRS patients was assessed using SF-12 questionnaire. RESULTS In the present study the mean age of patients was found to be 55.10 ± 9.35 years. Mean serum creatinine values were found to be reduced (1.22 ± 0.96) by 10th day in type 1 HRS which indicated improved renal function. Study patients showed a marked improvement in liver function throughout the observation period. 74% of patients did not have HRS recurrence and 79.48% of patients had completely relieved from HRS. Loose stool (14.2%) and hyponatremia (14.2%) were the prominent side effects of the therapy. The quality of life of patients also showed a statistically significant betterment in both physical and mental functioning. CONCLUSIONS Our study concluded that terlipressin and albumin combination was safe and effective in successfully stabilising cirrhosis patients with Hepatorenal Syndrome and bridging eligible patients to liver transplantation by restoring the liver and renal function with minimal adverse effects.
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Affiliation(s)
- Rakhi Krishna
- Department of Pharmacy Practice, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India
| | - Jina Raj
- Department of Pharmacy Practice, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India
| | - Drishya Dev
- Department of Pharmacy Practice, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India
| | - Sruthy C Prasad
- Department of Pharmacy Practice, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India
| | - Remya Reghu
- Department of Pharmacy Practice, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India
| | - Sudheer O V
- Department of GI surgery, Amrita Institute of Medical Sciences and Research Center, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India
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Brunetti L, Song JH, Suh D, Kim HJ, Seong YH, Lee DS, Lee SM, Suh DC. The risk of vancomycin toxicity in patients with liver impairment. Ann Clin Microbiol Antimicrob 2020; 19:13. [PMID: 32234065 PMCID: PMC7110653 DOI: 10.1186/s12941-020-00354-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Accepted: 03/25/2020] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND The influence of liver disease on the pharmacokinetic profile, the risk of acute kidney injury, and excessive drug exposure in patients treated with vancomycin was examined. METHODS A retrospective cohort study was performed with patients discharged from a medical center between January 2011 and June 2018 who received vancomycin therapy. Patients were stratified according to liver dysfunction (no to mild liver dysfunction (NMLD) and moderate to severe liver dysfunction (MSLD) based on the Child-Pugh score. The risk of acute kidney injury was compared between patients who were stratified by the attainment of a target serum trough concentration (10 mg/dL to 20 mg/dL) and the vancomycin ratio formed between the area under the curve and minimum inhibitory concentration. The impact of liver dysfunction and a daily dose of vancomycin on the risk of acute kidney injury and vancomycin AUC:MIC > 600 were tested using logistic regression with and without adjusting for the study variables. RESULTS A total of 408 patients empirically treated with vancomycin were included in this study (237 with NMLD and 171 with MSLD). Mean vancomycin trough concentrations (17.5 ± 8.4 mg/dL versus 15.3 ± 5.2 mg/dL, p = 0.0049) and AUC:MIC ratios (549.4 ± 217.2 versus 497.5 ± 117.3, 0.0065) were significantly higher in the MSLD group when compared to the NMLD group, respectively. Vancomycin clearance was also lower in the MSLD group and corresponded to a longer half-life. The proportion of patients who developed acute kidney injury was greater in patients with MSLD when compared to NMLD (7.6% versus 3.8%, respectively; p = 0.0932); however, the difference was statistically insignificant. Furthermore, supratherapeutic serum trough concentrations and AUC:MIC ratios were more common in the MSLD group versus the NMLD group (27.5% versus 13.9%, p = 0.0007 and 28.7% versus 17.3%, respectively; p = 0.0063). CONCLUSIONS MSLD correlates with an increased risk of supratherapeutic vancomycin exposure. Although patients with MSLD had a higher risk of acute kidney injury, the difference was not significant.
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Affiliation(s)
- Luigi Brunetti
- Department of Pharmacy Practice and Administration, Ernest Mario School of Pharmacy, Piscataway, NJ, USA.,Department of Pharmacy, RWJ Barnabas Health-Robert Wood Johnson University Hospital Somerset, Somerville, NJ, USA
| | - Jong Hwa Song
- Department of Pharmacy Administration, Chung-Ang University College of Pharmacy, Seoul, South Korea
| | - David Suh
- School of Public Health, University of Michigan, Ann Arbor, MI, USA
| | - Heui Jae Kim
- Department of Pharmacy Administration, Chung-Ang University College of Pharmacy, Seoul, South Korea
| | - Yeon Hee Seong
- Department of Pharmacy Administration, Chung-Ang University College of Pharmacy, Seoul, South Korea
| | - Dae Song Lee
- Department of Pharmacy Administration, Chung-Ang University College of Pharmacy, Seoul, South Korea
| | - Seung-Mi Lee
- Department of Pharmacy, College of Pharmacy, Daegu Catholic University, Gyeongsan-si, Gyeongsangbuk-do, South Korea.
| | - Dong-Churl Suh
- Department of Pharmacy Administration, Chung-Ang University College of Pharmacy, Seoul, South Korea.
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Abstract
AbstractKidney injury is a common finding in patients with liver disease. Bile cast nephropathy (also known as cholemic nephropathy) is an overlooked cause of renal injury in patients with hyperbilirubinemia. It can occur as a result of the toxic effects of bilirubin and bile acids on the renal tubules via several mechanisms. Bile cast nephropathy has characteristic histopathological changes consisting of bilirubin cast deposition in the distal nephron along with tubular epithelial cell injury. Treatment is based on the reversal of liver injury. This review aims to describe bile cast nephropathy in terms of its clinical and morphological features and to shed light on diagnostic techniques. In addition, we present data on management of such nephropathy while reviewing all the reported cases of bile cast nephropathy.
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Milanez MI, Cabral AM, Pires JG, Bergamaschi CT, Campos RR, Futuro Neto HA, Silva NF. Impairment of natriuresis and diuresis induced by intrarenal adrenoceptor mechanisms in an experimental model of cirrhosis in rats. Heliyon 2019; 5:e03066. [PMID: 31890977 PMCID: PMC6931082 DOI: 10.1016/j.heliyon.2019.e03066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Revised: 11/13/2019] [Accepted: 12/13/2019] [Indexed: 02/07/2023] Open
Abstract
The contribution of intrarenal alpha-2 adrenergic receptors in mediating the enhanced renal excretory responses evoked by the alpha-2-agonist xylazine was examined in a model of cirrhosis in rats. In sham-operated rats, xylazine (0.2 mg/kg, i.v.) increased diuresis and natriuresis (urine flow, control: 78 ± 12.1, 10 min: 155 ± 17, 20 min: 194 ± 19, 30 min: 146 ± 16, 40 min: 114 ± 13, 50 min: 95 ± 10.5 μl/min/g; urinary sodium excretion, control: 6.75 ± 2.08, 10 min: 7.12 ± 2.1, 20 min: 13.4 ± 4.6, 30 min: 14.6 ± 4.02, 40 min: 12.05 ± 2.35, 50 min: 12.7 ± 2.45 μeq/min/g), which was accompanied by a significant reduction in renal sympathetic nerve activity (RSNA) (control: 100, 10 min: 39.5 ± 5.8, 20 min: 53 ± 8.8, 30 min: 72 ± 7.0, 40 min: 83 ± 5.0, 50 min: 94 ± 6.1 AU). Xylazine (0.2 mg/kg) in cirrhotic animals, despite resulting in a significant reduction in RSNA (control: 100, 10 min: 73 ± 4.3*, 20 min: 70 ± 5.0*, 30 min: 76 ± 7.0*, 40 min: 85 ± 5.5*, 50 min: 92 ± 4.8* AU), was unable to increase natriuresis. A higher dose (20 mg/kg) of xylazine was not capable of increasing natriuresis and diuresis, even in the presence of a robust reduction in RSNA. Renal denervation did not alter the onset and time course of cirrhosis. The results indicated that during the development of cirrhosis, there is an adaptive process that disables the intrarenal alpha-2 adrenoceptor mechanisms that selectively promote water and urinary sodium excretion via a sympathetic renal nerve-independent mechanism. Thus, in cirrhotic rats, the diuresis/natriuresis induced by xylazine is independent on RSNA. Intrarenal and/or hormonal changes are probably involved in the impairment of xylazine-induced diuresis/natriuresis in cirrhosis.
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Adler M, Tang I, Gach MW, MacFaul G. Recurrent metastatic breast cancer presenting with portal hypertension and pseudocirrhosis. BMJ Case Rep 2019; 12:12/11/e231044. [PMID: 31767605 DOI: 10.1136/bcr-2019-231044] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Abstract
We present a case of a 63-year-old woman with an acute history of abdominal distension and shortness of breath. She had no risk factors for liver disease though her prior medical history was positive for breast carcinoma, in remission for 14 years. Examination and investigations were initially consistent with decompensated cirrhosis, thought to be due to subclinical autoimmune hepatitis. Imaging revealed hepatic contour irregularity, atrophy of the liver parenchyma and numerous lesions highly suggestive for multifocal hepatocellular carcinoma. Surprisingly, tissue histology revealed no evidence of cirrhosis, but recurrence of breast cancer which had mimicked cirrhosis. Pseudocirrhosis may be indistinguishable from true cirrhosis without histopathology. It has previously been linked to chemotherapy-induced hepatic injury and nodular regenerative hyperplasia, although our case illustrates an uncommon pathophysiology. Pseudocirrhosis often represents a poor prognosis even with a good baseline performance status, and early involvement of palliative care specialists may be advisable.
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Affiliation(s)
- Maciej Adler
- Department of Medicine, Milton Keynes University Hospital NHS Foundation Trust, Milton Keynes, UK
| | - Ivan Tang
- Department of Medicine, Milton Keynes University Hospital NHS Foundation Trust, Milton Keynes, UK
| | - Michael William Gach
- Department of Medicine, Milton Keynes University Hospital NHS Foundation Trust, Milton Keynes, UK
| | - George MacFaul
- Department of Gastroenterology, Milton Keynes University Hospital NHS Foundation Trust, Milton Keynes, UK
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Ayoola OO, Bolarinwa RA, Aderibigbe AS, Onigbinde SO, Oguntade BO. Portal hypertension evolving from sickled hepatopathy: Could hepatic venous Doppler ultrasound be beneficial in its evaluation? Med Hypotheses 2019; 135:109450. [PMID: 31751874 DOI: 10.1016/j.mehy.2019.109450] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2019] [Revised: 10/20/2019] [Accepted: 10/23/2019] [Indexed: 11/27/2022]
Abstract
PURPOSE Sickle cell intrahepatic cholestasis involves sickling within hepatic sinusoids leading to vascular stasis and localized hypoxia resulting in ballooning of the hepatocytes causing a direct back pressure effect with resultant intracanalicular cholestasis. Vascular stasis may ultimately lead to portal hypertension. We proposed to document findings suggestive of portal hypertension evolving from hepatopathy in steady-state sickle cell disease (SCD) patients using hepatic venous Doppler ultrasound. METHODS This is a prospective case series of 6 SCD subjects in steady-state (median age, 30 years; range, 19-43), comprising of 3 males and 3 females, who underwent a routine Doppler ultrasound evaluation of their hepatic veins and were discovered to have an abnormal biphasic waveform pattern. Venous blood was obtained from all subjects to evaluate for P-selectin, homocysteine, foetal haemoglobin, haematocrit levels, white cell and platelet counts. Doppler ultrasound was also carried out on all subjects to evaluate for the hepatic waveform, right renal artery RI and PI along with the hepatic artery velocities. RESULTS All the 6 subjects had reduced haematocrit (median value of 21.5%; range, 18-25%) and some degree of renal dysfunction (plasma cystatin-C ranged from 1.6 to 12.2 mg/L). Elevated white cell count, hyperhomocysteinemia, reduced SpO2(<94.0%) and reduced estimated GFR (eGFR < 90 ml/min) was also noted in 4 subjects (66.7%). Similarly, 4 subjects (66.7%) had elevated RI in the right kidneys while 3 subjects (50.0%) had elevated PI in the right kidney. CONCLUSION Doppler ultrasound Hepatic vein waveform analysis may be a useful examination in the evaluation of patients with SCD as it may elicit feature of portal hypertension. Further studies are suggested to confirm this in a larger population of SCD patients using the gold standard.
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Affiliation(s)
- O O Ayoola
- Department of Radiology, Faculty of Clinical Sciences, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria; Department of Radiology, Obafemi Awolowo University Teaching Hospital, Ile-Ife, Osun State, Nigeria.
| | - R A Bolarinwa
- Department of Haematology and Blood Transfusion, Faculty of Basic Sciences, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria.
| | - A S Aderibigbe
- Department of Radiology, Faculty of Clinical Sciences, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria; Department of Radiology, Obafemi Awolowo University Teaching Hospital, Ile-Ife, Osun State, Nigeria.
| | - S O Onigbinde
- Department of Radiology, Obafemi Awolowo University Teaching Hospital, Ile-Ife, Osun State, Nigeria.
| | - B O Oguntade
- Department of Radiology, Obafemi Awolowo University Teaching Hospital, Ile-Ife, Osun State, Nigeria.
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Bolm L, Petrova E, Woehrmann L, Werner J, Uhl W, Nuessler N, Ghadimi M, Bausch D, Lapshyn H, Gaedcke J, Belyaev O, D'Haese JG, Klier T, Keck T, Wellner UF. The impact of preoperative biliary stenting in pancreatic cancer: A case-matched study from the German nationwide pancreatic surgery registry (DGAV StuDoQ|Pancreas). Pancreatology 2019; 19:985-993. [PMID: 31563328 DOI: 10.1016/j.pan.2019.09.007] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2019] [Revised: 08/29/2019] [Accepted: 09/17/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND/OBJECTIVE The impact of preoperative biliary stenting (PBS) before pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) is controversial. METHODS Patients undergoing PD with or without PBS for PDAC were identified from the German DGAV-StuDoQlPancreas registry. The impact of PBS on perioperative complications was analyzed. RESULTS 1133 patients undergoing PD for PDAC were identified from the registry. After matching, 480 PBS patients vs. 480 patients without PBS were analyzed. Postoperative complications Clavien-Dindo classification (CDC) grade IIIa-IVb were higher in PBS patients (PBS 27% vs. no PBS 22%, p = 0.027). 320 PBS patients (66%) had no history of jaundice. In these patients, PBS was associated with higher morbidity. In contrast, PBS was not associated with higher complication rates in patients with history of jaundice. Serum bilirubin levels of 15 mg/dl and higher lead to more CDC IIIa-IVb (24% vs. 28%, p = 0.053) and higher mortality (3% vs. 7%, p < 0.001). PBS in patients with serum bilirubin levels of >15 mg/dl increased CDC IIa-IVb complications (21% vs. 50%, p = 0.001), mortality was equivalent. CONCLUSION Most PBS procedures were performed in patients with no history of jaundice and increased morbidity. Serum bilirubin levels >15 mg/dl lead to higher morbidity and mortality. PBS correlated with higher complication rates in these patients.
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Affiliation(s)
- Louisa Bolm
- Department of Surgery, University Medical Center Luebeck, Germany
| | | | - Lukas Woehrmann
- Department of Surgery, University Medical Center Luebeck, Germany
| | - Jens Werner
- DGAV STuDoQ
- Pancreas Registry of the German Association for General and Visceral Surgery, Germany; Department of General, Visceral and Transplantation Surgery, Ludwig-Maximilians University Munich, Germany
| | - Waldemar Uhl
- DGAV STuDoQ
- Pancreas Registry of the German Association for General and Visceral Surgery, Germany; Department of Surgery, St. Josef Hospital, Ruhr University Bochum, Germany
| | - Natascha Nuessler
- DGAV STuDoQ
- Pancreas Registry of the German Association for General and Visceral Surgery, Germany; Department of Surgery, Municipal Hospital Munich, Germany
| | - Michael Ghadimi
- DGAV STuDoQ
- Pancreas Registry of the German Association for General and Visceral Surgery, Germany; Department of General, Visceral and Pediatric Surgery, University Medical Center Göttingen, Germany
| | - Dirk Bausch
- Department of Surgery, University Medical Center Luebeck, Germany
| | - Hryhoriy Lapshyn
- Department of Surgery, University Medical Center Luebeck, Germany
| | - Jochen Gaedcke
- DGAV STuDoQ
- Pancreas Registry of the German Association for General and Visceral Surgery, Germany; Department of General, Visceral and Pediatric Surgery, University Medical Center Göttingen, Germany
| | - Orlin Belyaev
- DGAV STuDoQ
- Pancreas Registry of the German Association for General and Visceral Surgery, Germany; Department of Surgery, St. Josef Hospital, Ruhr University Bochum, Germany
| | - Jan G D'Haese
- DGAV STuDoQ
- Pancreas Registry of the German Association for General and Visceral Surgery, Germany; Department of General, Visceral and Transplantation Surgery, Ludwig-Maximilians University Munich, Germany
| | - Thomas Klier
- DGAV STuDoQ
- Pancreas Registry of the German Association for General and Visceral Surgery, Germany; Department of Surgery, Municipal Hospital Munich, Germany
| | - Tobias Keck
- Department of Surgery, University Medical Center Luebeck, Germany; DGAV STuDoQ
- Pancreas Registry of the German Association for General and Visceral Surgery, Germany.
| | - Ulrich F Wellner
- Department of Surgery, University Medical Center Luebeck, Germany; DGAV STuDoQ
- Pancreas Registry of the German Association for General and Visceral Surgery, Germany
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Yager A, Khorsand S, Chokshi R, Cheruku S. Combined Thoracic and Abdominal Organ Transplantation: Special Considerations. Semin Cardiothorac Vasc Anesth 2019; 24:84-95. [PMID: 31455153 DOI: 10.1177/1089253219870631] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Combined thoracic-abdominal organ transplants are infrequently performed procedures indicated for patients with failure of two or more transplantable organs. In this review, we discuss recipient selection, surgical considerations, anesthetic management, and outcomes associated with common combinations of thoracic-abdominal transplant operations. General principles regarding the postoperative care of these patients are also discussed. These procedures present a unique challenge requiring specialized knowledge, technical expertise, and leadership from the anesthesiology team throughout the perioperative period.
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Nevens F, Bittencourt PL, Coenraad MJ, Ding H, Hou MC, Laterre PF, Mendizabal M, Ortiz-Olvera NX, Vorobioff JD, Zhang W, Angeli P. Recommendations on the Diagnosis and Initial Management of Acute Variceal Bleeding and Hepatorenal Syndrome in Patients with Cirrhosis. Dig Dis Sci 2019; 64:1419-1431. [PMID: 30684079 DOI: 10.1007/s10620-018-5448-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2018] [Accepted: 12/29/2018] [Indexed: 12/14/2022]
Abstract
Cirrhosis is a serious and life-threatening condition which imposes a significant socioeconomic burden on affected individuals and healthcare systems. Cirrhosis can result in portal hypertension, which may lead to major complications, including acute variceal bleeding and hepatorenal syndrome. Without prompt treatment, these complications may be life-threatening. Over the past 2 decades, new treatment modalities and treatment strategies have been introduced, which have improved patients' prognosis, but the initial management of these severe complications continues to present a challenge. The present recommendations aim to increase clinicians' knowledge on the importance of early diagnosis and treatment, and to provide evidence-based management strategies to potentially, further improve patient outcomes. Special attention was given to the role of terlipressin. A comprehensive non-systematic literature search was undertaken to evaluate the evidence for the diagnosis and initial management of acute variceal bleeding and hepatorenal syndrome in patients with cirrhosis. Recommendations on the diagnosis and initial management of acute variceal bleeding and hepatorenal syndrome in patients with cirrhosis have been developed based on the best available evidence and the expert opinion of the consensus panel following a comprehensive review of the available clinical data. Prompt identification and timely treatment of acute variceal bleeding and hepatorenal syndrome are essential to reduce the burden.
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Affiliation(s)
- Frederik Nevens
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Campus Gasthuisberg, Herestraat 49, 3000, Louvain, Belgium.
| | - Paulo Lisboa Bittencourt
- Unit of Gastroenterology and Hepatology, Portuguese Hospital of Salvador, Rua Prof. Clementino Fraga, 220/1901, Salvador, Bahia, Brazil
| | - Minneke J Coenraad
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Albinusdreef 2, 2300 ZC, Leiden, The Netherlands
| | - Huiguo Ding
- Department of Gastroenterology and Hepatology, Beijing You'an Hospital Affiliated with Capital Medical University, No 8, Youan Men Wai Street, Fengtai District, Beijing, 100069, China
| | - Ming-Chih Hou
- Department of Medicine Division of Gastroenterology, Taipei Veterans General Hospital, 201, Sec. II, Shih-Pai Road, Taipei, Taiwan
| | - Pierre-François Laterre
- Medical-surgical Intensive Care Unit, Cliniques Universitaires Saint Luc, Université Catholique de Louvain, Avenue Hippocrate 10, Brussels, Belgium
| | - Manuel Mendizabal
- Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Av. Peron 1500, 1629, Pilar, Provincia de Buenos Aires, Argentina
| | - Nayeli Xochiquetzal Ortiz-Olvera
- Department of Gastroenterology, UMAE, Hospital de Especialidades Dr. Bernardo Sepúlveda, Centro Médico Nacional Siglo XXI, IMSS, Mexico City, Mexico
| | - Julio D Vorobioff
- Department of Gastroenterology and Hepatology, University of Rosario Medical School, Morrison 8750, 2000, Rosario, Argentina
| | - Wenhong Zhang
- Department of Infectious Diseases, Huashan Hospital, Fudan University, 12 Wulumuqi Middle Rd, Jingan Qu, Shanghai Shi, 200000, China
| | - Paolo Angeli
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine - DIMED, University of Padova, Via Giustiniani, 2, 35128, Padua, Italy
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Effect of protocatechuic acid-layered double hydroxide nanoparticles on diethylnitrosamine/phenobarbital-induced hepatocellular carcinoma in mice. PLoS One 2019; 14:e0217009. [PMID: 31141523 PMCID: PMC6541272 DOI: 10.1371/journal.pone.0217009] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2018] [Accepted: 05/02/2019] [Indexed: 01/09/2023] Open
Abstract
Researchers investigating cancer chemotherapy and management continue to search for agents that selectively kill malignant cells and leave healthy neighboring cells intact. Natural products provide relevant resources for anti-cancer drug discovery. However, the physicochemical properties of these compounds limit their efficient uptake and bioavailability. We introduced a nanocarrier system, namely, zinc-aluminum-layered double hydroxide (ZnAl-LDH) intercalated with protocatechuic acid. In this study, the efficacy and toxicity of protocatechuic acid intercalated in zinc aluminum-layered double hydroxide nanoparticles (PCA-ZnAl) against diethylnitrosamine/phenobarbital (DEN/PB)-induced hepatocellular carcinoma (HCC) in BALB/c mice was evaluated. HCC in male mice was induced by a single-dose intraperitoneal administration of DEN and was promoted by the introduction of PB via drinking water for 12 weeks. HCC induction was confirmed after the DEN/PB introduction period by measurement of the elevated level of serum α-feto protein (AFP). The results showed that the level of α-fetoprotein was significantly reduced in PCA-ZnAl (350±43.90 ng/mL), doxorubicin (DOX) (290±20.52 ng/mL) and ZnAl-LDH (390±19.65 ng/mL) treated animals compared to HCC mice treated with normal saline (580.4± 52.04 ng/mL). Superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels were significantly increased, whereas the level of lipid peroxidation was significantly decreased in HCC mice treated with DOX, PCA-ZnAl and ZnAl-LDH compared with those in HCC mice treated with saline. Restoration of hepatocyte morphology was observed following treatment that was comparable to that in the normal control group. Deterioration of hepatic cells and a significant increase of aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) were observed in the cancer-induced untreated group compared with that in the groups treated with nanoparticles. The histopathological features of the liver obtained from PCA-ZnAl-treated mice showed a uniform size with a similar distribution of the nuclear-cytoplasmic ratio and nucleus centrally located in the cytoplasm, similar to the normal liver cells. The results underscored the potential of PCA-ZnAl for the treatment of hepatocellular carcinoma.
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Jamil K, Huang X, Lovelace B, Pham AT, Lodaya K, Wan G. The burden of illness of hepatorenal syndrome (HRS) in the United States: a retrospective analysis of electronic health records. J Med Econ 2019; 22:421-429. [PMID: 30724682 DOI: 10.1080/13696998.2019.1580201] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVES Hepatorenal Syndrome (HRS) is characterized by renal failure in patients with advanced chronic liver disease (CLD) and is the leading cause of hospitalizations in CLD. This study examines the clinical and economic burden, outcomes, and unmet need of HRS treatment in US hospitals. METHOD A retrospective cohort study was conducted based on a large electronic health records database (Cerner HealthFacts) with records for hospitalized HRS patients from January 2009-June 2015. Demographics, clinical characteristics, treatment patterns, and economic outcomes were analyzed. Prognostic indicators of cirrhosis, kidney injury, end-stage liver disease, and acute-on-chronic liver failure were used to determine mortality risk. RESULTS A total of 2,542 patients hospitalized with HRS were identified (average age = 57.9 years, 61.8% males, 74.2% Caucasian), with an average total hospital charge of $91,504 per patient and a mean length of stay (LOS) of 30.5 days. The mortality rate was 36.9% with 8.9% of patients discharged to hospice. Of all patients, 1,660 patients had acute kidney injury, 859 with Stage 3 disease, and 26.7% had dialysis. The 30-day readmission rate was 33.1%, 41% of which were unplanned. Nearly one-third of study patients had commercial insurance (30.2%), followed by Medicare (29.9%); hospital charges varied by LOS, receipt of dialysis, and discharge status. Regression analysis demonstrated that HRS costs are associated with LOS, dialysis, and hospital mortality. CONCLUSION HRS is associated with poor outcomes and high hospital costs. Analysis of HRS cost drivers demonstrated an unmet need for additional treatment options to improve outcomes in this patient population.
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Affiliation(s)
- Khurram Jamil
- a Mallinckrodt Pharmaceuticals, Inc , Bedminster , NJ , USA
| | - Xingyue Huang
- a Mallinckrodt Pharmaceuticals, Inc , Bedminster , NJ , USA
| | - Belinda Lovelace
- b Formerly of Mallinckrodt Pharmaceuticals, Inc , Bedminster , NJ , USA
| | - An T Pham
- b Formerly of Mallinckrodt Pharmaceuticals, Inc , Bedminster , NJ , USA
- c University of Washington School of Pharmacy , Seattle , WA , USA
| | - Kunal Lodaya
- d Boston Strategic Partners, Inc Health Economics and Outcomes Research , Boston , MA , USA
| | - George Wan
- a Mallinckrodt Pharmaceuticals, Inc , Bedminster , NJ , USA
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49
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Varajic B, Cavallazzi R, Mann J, Furmanek S, Guardiola J, Saad M. High versus low mean arterial pressures in hepatorenal syndrome: A randomized controlled pilot trial. J Crit Care 2019; 52:186-192. [PMID: 31096099 DOI: 10.1016/j.jcrc.2019.04.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2018] [Revised: 03/27/2019] [Accepted: 04/01/2019] [Indexed: 11/30/2022]
Abstract
There is controversy regarding the mean arterial pressure (MAP) goals that should be targeted in the treatment of hepatorenal syndrome (HRS.) We conducted a study to assess different MAP targets in HRS in the intensive care unit (ICU). MATERIALS AND METHODS This is a prospective randomized controlled pilot trial. ICU patients had target mean arterial pressure (MAP) ≥ 85 mmHg (control arm) or 65-70 mmHg (study arm). Urine output and serum creatinine were trended and recorded. RESULTS A total of 18 patients were enrolled. The day four urine output in the high and low MAP group was 1194 (SD = 1249) mL/24 h and 920 (SD = 812) mL/24 h, respectively. The difference in day four - day one urine output was -689 (SD = 1684) mL/24 h and 272 (SD = 582) mL/24 h for the high and low MAP groups. The difference in serum creatinine at day four - day one was -0.54 (SD = 0.63) mg/dL and - 0.77 (SD = 1.14) mg/dL in the high and low MAP groups, respectively. CONCLUSION In this study, we failed to prove non-inferiority between a low and high target MAP in patients with HRS. TRIAL REGISTRATION This trial was registered with and approved by the University of Louisville Internal Review Board and hospital research review committees (IRB # 14.1190). The trial was registered with ClinicalTrials.gov (ID # NCT02789150). The IRB committee roster 7/21/2014-2/26/2015 is registered with IORG (IORG # IORG0000147; OMB # 0990-0279) and is available at http://louisville.edu/research/humansubjects/about-the-irb/rosters/RosterEffective20140721thru20150226.pdf.
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Affiliation(s)
- Benadin Varajic
- Department of Internal Medicine, University of Louisville, USA.
| | - Rodrigo Cavallazzi
- Department of Pulmonary, Critical Care, and Sleep Disorders Medicine, University of Louisville, USA
| | - Jason Mann
- Department of Pulmonary, Critical Care, and Sleep Disorders Medicine, University of Louisville, USA
| | | | - Juan Guardiola
- Department of Pulmonary, Critical Care, and Sleep Disorders Medicine, University of Louisville, USA
| | - Mohamed Saad
- Department of Pulmonary, Critical Care, and Sleep Disorders Medicine, University of Louisville, USA
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50
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Kim M, Kiran RP, Li G. Acute kidney injury after hepatectomy can be reasonably predicted after surgery. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2019; 26:144-153. [PMID: 30793845 DOI: 10.1002/jhbp.615] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Hepatectomy presents unique challenges potentially heightening acute kidney injury (AKI) risk, but the full spectrum of risk factors has not been identified. METHODS Data for hepatectomy patients in the 2016 American College of Surgeons National Surgical Quality Improvement Program (n = 3,814) was randomly split into derivation (70%) and validation (30%) cohorts. AKI was defined as an increase in serum creatinine ≥0.3 mg/dl or ≥1.5-fold above the preoperative value within 30 days of surgery. Multivariable logistic regression assessed preoperative and intraoperative risk factors for AKI. RESULTS Of 2,692 patients (derivation cohort), 432 (16%) developed AKI. Risk factors were the following: age (years; adjusted odds ratio [aOR] 1.016 [95% confidence interval 1.006-1.026], female sex (aOR 0.65 [0.51-0.82]), body mass index (kg/m2 ; aOR 1.043 [1.024-1.062]), diabetes (aOR 1.71 [1.31-2.24]), hypertension (aOR 1.66 [1.30-2.13]), hematocrit (%; aOR 0.944 [0.924-0.966]), operative time (min; aOR 1.004 [1.003-1.004]), planned open procedure (aOR 2.00 [1.47-2.73]), and Pringle maneuver (aOR 1.36 [1.07-1.72]). The areas under the curve of the receiver operating characteristic curves were 0.74 (95% CI 0.71-0.76) and 0.71 (95% CI 0.67-0.75) in the derivation and validation cohorts, respectively. CONCLUSIONS Postoperative AKI affects one in six hepatectomy patients; preoperative and intraoperative factors can predict the risk of postoperative AKI.
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Affiliation(s)
- Minjae Kim
- Department of Anesthesiology, Columbia University Medical Center, 622 West 168th Street, PH 5, Suite 505C, New York, NY 10032, USA.,Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA
| | - Ravi P Kiran
- Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.,Department of Surgery, Columbia University Medical Center, New York, NY, USA
| | - Guohua Li
- Department of Anesthesiology, Columbia University Medical Center, 622 West 168th Street, PH 5, Suite 505C, New York, NY 10032, USA.,Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA
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