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Malakar S, Rungta S, Samanta A, Shamsul Hoda U, Mishra P, Pande G, Roy A, Giri S, Rai P, Mohindra S, Ghoshal UC. Understanding acute kidney injury in cirrhosis: Current perspective. World J Hepatol 2025; 17:104724. [DOI: 10.4254/wjh.v17.i5.104724] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2024] [Revised: 03/13/2025] [Accepted: 04/15/2025] [Indexed: 05/27/2025] Open
Abstract
Acute kidney injury (AKI) is present in 30%-40% of hospitalized patients with cirrhosis. Its incidence is higher in patients with severe alcoholic hepatitis, spontaneous bacterial peritonitis, and acute-on-chronic-liver failure (ACLF). Kidney injury is an important landmark event in the natural history of cirrhosis as it is associated with higher mortality. Overwhelming systemic vasodilation, cardiac dysfunction, hypoperfusion, endotoxemia, and direct nephrotoxicity predispose patients with cirrhosis to kidney injury. Infection is present in 25% of patients with decompensated cirrhosis and 35%-40% of patients with ACLF. Advanced cirrhosis with portal hypertension leads to a sluggish portal flow, leading to increased gut congestion, altered gut permeability and bacterial translocations. They drive infection and endotoxemia in such patients. Pathogen-associated molecular patterns activate inflammatory cascades, which leads to further deterioration in hemodynamics and reduced glomerular filtration rate. Infections and pro-inflammatory cytokines like interleukin 6 (IL-6), IL-1, and tumor necrosis factor alpha may directly cause kidney parenchymal injury. The combined effect of dysfunctional albumin and systemic and splanchnic vasodilatation leads to low effective blood volume, activating the renin-angiotensin-aldosterone system. This causes renal vasoconstriction, water retention, and ascites, which progresses to hepatorenal physiology and AKI development. Vasoconstriction and volume expansion effectively improve arterial blood volume and systemic hemodynamics, thereby improving renal blood flow. It is of paramount importance to predict, detect, and treat AKI in its early state, as progressive renal dysfunction is invariably associated with higher mortality in patients with decompensated cirrhosis and ACLF. This comprehensive review will focus on the recent evolving concepts of the pathophysiology, diagnosis, and management of AKI in patients with cirrhosis.
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Affiliation(s)
- Sayan Malakar
- Department of Gastroenterology, King George's Medical University, Lucknow 226003, Uttar Pradesh, India
| | - Sumit Rungta
- Department of Medical Gastroenterology, King George's Medical University, Lucknow 226003, Uttar Pradesh, India
| | - Arghya Samanta
- Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
| | - Umair Shamsul Hoda
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
| | - Piyush Mishra
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
| | - Gaurav Pande
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
| | - Akash Roy
- Department of Gastrosciences and Liver Transplantation, Apollo Multispeciality Hospitals, Kolkata 700054, West Bengal, India
| | - Suprabhat Giri
- Department of Gastroenterology and Hepatology, Kalinga Institute of Medical Sciences, Bhubaneswar 751024, Odisha, India
| | - Praveer Rai
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
| | - Samir Mohindra
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
| | - Uday C Ghoshal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
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Reuken PA, Franz A, Wirtz TH, Ripoll C, Aschenbach R, Teichgräber U, Pollmanns MR, Kiehntopf M, Keil S, Kuhl C, Schulze PC, Trautwein C, Bruns T, Stallmach A, Zipprich A. Early Dynamics of Portal Pressure Gradient After TIPS Insertion Predict Mortality. Aliment Pharmacol Ther 2025; 61:1175-1182. [PMID: 39817366 PMCID: PMC11908110 DOI: 10.1111/apt.18503] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Revised: 08/28/2024] [Accepted: 01/03/2025] [Indexed: 01/18/2025]
Abstract
BACKGROUND Transjugular intrahepatic portosystemic shunt (TIPS) placement leads to a reduction in portal pressure and an improvement in survival in patients with recurrent and refractory ascites and variceal haemorrhage. Prediction of post-TIPS survival is primarily determined by factors identified before the TIPS procedure, as data collected during or after TIPS implantation are limited. The aim of the study was to evaluate the influence of early hemodynamic changes after TIPS placement on survival, in order to refine post TIPS management. METHODS In this prospective bicentric study, consecutive patients (n = 105) undergoing TIPS placement for ascites or variceal haemorrhage underwent measurement of portal pressure gradient (PPG) immediately at TIPS insertion (PPG0) and 24 h later (PPG24h) and the ΔPPG was calculated from PPG24h and PPG0 (ΔPPG = PPG24h-PPG0). Kaplan-Meier survival analysis and uni- and multivariable regression analyses were conducted to identify survival predictors. RESULTS Patients with lack of increased ΔPPG exhibited poorer 90-day and 1-year survival compared to patients with increased ΔPPG. This worse survival was independent of The Model for End-Stage Liver Disease (MELD) score, Child-Pugh score, bilirubin levels, creatinine and the Freiburg index of post-TIPS survival (FIPS) > 0.92. Among these patients with poorer outcome, elevated bilirubin (> 25 μmol/L) further distinguished survivors from non-survivors. CONCLUSION Lack of increased ΔPPG post-TIPS insertion identifies a high-risk patient group with worse survival. We propose incorporating this second PPG measurement and determining ΔPPG into clinical practice to identify these patients early and tailor post-TIPS patient care.
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Affiliation(s)
- P. A. Reuken
- Department of Internal Medicine IV (Gastroenterology, Hepatology and Infectious Diseases), Jena University HospitalFriedrich‐Schiller‐UniversityJenaGermany
| | - A. Franz
- Department of Internal Medicine IV (Gastroenterology, Hepatology and Infectious Diseases), Jena University HospitalFriedrich‐Schiller‐UniversityJenaGermany
| | - T. H. Wirtz
- Medical Department IIIUniversity Hospital RWTH AachenAachenGermany
| | - C. Ripoll
- Department of Internal Medicine IV (Gastroenterology, Hepatology and Infectious Diseases), Jena University HospitalFriedrich‐Schiller‐UniversityJenaGermany
| | - R. Aschenbach
- Department of RadiologyJena University Hospital, Friedrich‐Schiller‐UniversityJenaGermany
| | - U. Teichgräber
- Department of RadiologyJena University Hospital, Friedrich‐Schiller‐UniversityJenaGermany
| | - M. R. Pollmanns
- Medical Department IIIUniversity Hospital RWTH AachenAachenGermany
| | - M. Kiehntopf
- Institute of Clinical Chemistry and Laboratory DiagnosticsJena University Hospital, Friedrich‐Schiller UniversityJenaGermany
| | - S. Keil
- Department of Diagnostic and Interventional RadiologyUniversity Hospital RWTH AachenAachenGermany
| | - C. Kuhl
- Department of Diagnostic and Interventional RadiologyUniversity Hospital RWTH AachenAachenGermany
| | - P. C. Schulze
- Division of Cardiology, Angiology and Intensive Medical Care, Department of Internal Medicine I, Jena University HospitalFriedrich‐Schiller‐UniversityJenaGermany
| | - C. Trautwein
- Medical Department IIIUniversity Hospital RWTH AachenAachenGermany
| | - T. Bruns
- Medical Department IIIUniversity Hospital RWTH AachenAachenGermany
| | - A. Stallmach
- Department of Internal Medicine IV (Gastroenterology, Hepatology and Infectious Diseases), Jena University HospitalFriedrich‐Schiller‐UniversityJenaGermany
| | - A. Zipprich
- Department of Internal Medicine IV (Gastroenterology, Hepatology and Infectious Diseases), Jena University HospitalFriedrich‐Schiller‐UniversityJenaGermany
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Koratala A, Ronco C, Kazory A. Hepatocardiorenal Syndrome: Integrating Pathophysiology with Clinical Decision-Making via Point-Of-Care Ultrasound. Cardiorenal Med 2025; 15:184-197. [PMID: 39933496 DOI: 10.1159/000543681] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2024] [Accepted: 01/16/2025] [Indexed: 02/13/2025] Open
Abstract
BACKGROUND Accumulating evidence has challenged the traditional model of the liver-kidney connection in hepatorenal syndrome. Cirrhosis can significantly impact cardiac function, leading to cirrhotic cardiomyopathy. Recent understanding reveals how cardiac dysfunction plays a pivotal role in the development of renal dysfunction in this setting, suggesting that disturbances traditionally categorized under hepatorenal syndrome may actually represent a hepatic form of cardiorenal syndrome - hepatocardiorenal syndrome - where the liver affects the kidney through cardiorenal pathways. SUMMARY Effective management of hepatocardiorenal syndrome and acute kidney injury in cirrhosis relies on accurately assessing a patient's hemodynamic and volume status. Point-of-care ultrasound, including lung and focused cardiac ultrasound, is a valuable diagnostic tool that provides crucial data on fluid tolerance, subclinical pulmonary congestion, and left ventricular filling pressures. This objective, bedside approach offers a comprehensive assessment that directly influences patient management and therapeutic decisions. KEY MESSAGES Point-of-care ultrasound plays an essential role in evaluating and managing hepatocardiorenal syndrome, providing insights into the underlying pathophysiology. By assessing hemodynamic parameters, it helps guide therapy and monitor patient responses, ensuring more accurate and effective treatment of patients with cirrhosis and acute kidney injury.
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Affiliation(s)
- Abhilash Koratala
- Division of Nephrology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Claudio Ronco
- International Renal Research Institute of Vicenza (IRRIV), Vicenza, Italy
- Department of Medicine, University of Padova, Padova, Italy
| | - Amir Kazory
- Division of Nephrology, Hypertension and Renal Transplantation, University of Florida, Gainesville, Florida, USA
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Yao F, Luo J, Zhou Q, Wang L, He Z. Development and validation of a machine learning-based prediction model for hepatorenal syndrome in liver cirrhosis patients using MIMIC-IV and eICU databases. Sci Rep 2025; 15:2743. [PMID: 39837961 PMCID: PMC11751441 DOI: 10.1038/s41598-025-86674-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Accepted: 01/13/2025] [Indexed: 01/23/2025] Open
Abstract
Hepatorenal syndrome (HRS) is a key contributor to poor prognosis in liver cirrhosis. This study aims to leverage the database to build a predictive model for early identification of high-risk patients. From two sizable public databases, we retrieved pertinent information about the cirrhosis patients' therapies, comorbidities, laboratory results, and demographics. Patients from the eICU database served as a test set for external validation, while patients from the MIMIC database were divided into training and validation groups. Variables were screened using LASSO regression, Extreme Gradient Boosting (XG Boost), and Random Forest (RF). Core risk factors were determined from the intersection of the three methods. A predictive model was constructed using multivariable logistic regression and visualized via a nomogram. Model performance was assessed using ROC curves, decision curve analysis (DCA), clinical impact curves (CIC), and calibration curves. Eight critical variables associated with HRS were identified using machine learning methods. The final predictive model, based on five key variables-spontaneous bacterial peritonitis, red blood cell count, creatinine, activated partial thromboplastin time, and total bilirubin-showed excellent discrimination, with AUCs of 0.832 (95% CI 0.8069-0.8563) in the training set and 0.8415 (95% CI 0.8042-0.8789) in the validation set. The AUC in the external test set was 0.8212 (95% CI 0.7784-0.864). By integrating the MIMIC-IV database and machine learning algorithms, we developed an effective predictive model for HRS in liver cirrhosis patients, providing a robust tool for early clinical intervention.
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Affiliation(s)
- Fengwei Yao
- Department of Gastrointestinal Surgery, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, People's Republic of China
| | - Ji Luo
- Department of Gastrointestinal Surgery, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, People's Republic of China
| | - Qian Zhou
- Department of Gastrointestinal Surgery, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, People's Republic of China
| | - Luhua Wang
- Department of Gastrointestinal Surgery, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, People's Republic of China
| | - Zhijun He
- Department of Gastrointestinal Surgery, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, People's Republic of China.
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Matovic Zaric V, Pantic I, Lugonja S, Glisic T, Konjikusic S, Lolic I, Baljosevic N, Zgradic S, El Mezeni J, Vojnovic M, Brankovic M, Milovanovic T. Survival of Patients with Alcohol-Related Liver Disease Cirrhosis-Usefulness of the New Liver Mortality Inpatients Prognostic Score. Diagnostics (Basel) 2024; 14:2508. [PMID: 39594174 PMCID: PMC11592997 DOI: 10.3390/diagnostics14222508] [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: 09/29/2024] [Revised: 11/03/2024] [Accepted: 11/04/2024] [Indexed: 11/28/2024] Open
Abstract
Background/Objectives: Alcohol can directly damage the liver, causing steatosis, steatohepatitis, cirrhosis, and hepatocellular cancer. The aim of this study was to examine 28-day survival in hospitalized patients with alcohol-related liver disease (ALD) cirrhosis, as well as to develop and validate a new survival prediction model. Methods: A total of 145 patients with ALD cirrhosis were included; 107 were diagnosed with acute decompensation (AD) and 38 with acute-on-chronic liver failure (ACLF). The new liver mortality inpatients (LIV-IN) score was calculated using the following variables: hepatic encephalopathy (HE), hepatorenal syndrome (HRS), ascites, systemic inflammatory response syndrome (SIRS), community-acquired infection (CAI), and fibrinogen. The diagnostic accuracy of the LIV-IN score was tested, along with the model for end-stage liver disease (MELD), model for end-stage liver disease-sodium (MELD-Na), albumin-bilirubin (ALBI), neutrophil-to-lymphocyte ratio (NLR), chronic liver failure consortium-C acute decompensation (CLIF-C AD), and chronic liver failure consortium-acute-on-chronic liver failure (CLIF-C ACLF). Results: Lethal outcome occurred in 46 (31.7%) patients. The mortality rate was higher in the ACLF group (n = 22, 57.9%) compared to the AD group (n = 24, 22.4%) (p < 0.01). The highest predictive power for short-term mortality was observed for the LIV-IN score (AUC 73.4%, p < 0.01). In patients with AD, the diagnostic accuracy of the CLIF-C AD score was better than for the LIV-IN score (AUC 0.699; p = 0.004, AUC 0.686; p = 0.007, respectively). In patients with ACLF, only the LIV-IN score had statistically significant discriminative power in predicting 28-day survival. Conclusions: The liver mortality inpatients prognostic score is a new, reliable prognostic model in predicting 28-day mortality.
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Affiliation(s)
- Vera Matovic Zaric
- Emergency Center, Gastroenterology and Hepatology Department, University Clinical Center of Serbia, 11000 Belgrade, Serbia; (I.L.); (N.B.)
| | - Ivana Pantic
- Clinic of Gastroenterology and Hepatology, University Clinical Center of Serbia, 11000 Belgrade, Serbia; (I.P.); (T.G.); (S.Z.); (J.E.M.); (M.V.); (T.M.)
| | - Sofija Lugonja
- Department of Internal Medicine, Division of Gastroenterology, General Hospital “Djordje Joanovic”, 23000 Zrenjanin, Serbia;
| | - Tijana Glisic
- Clinic of Gastroenterology and Hepatology, University Clinical Center of Serbia, 11000 Belgrade, Serbia; (I.P.); (T.G.); (S.Z.); (J.E.M.); (M.V.); (T.M.)
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia;
| | | | - Iva Lolic
- Emergency Center, Gastroenterology and Hepatology Department, University Clinical Center of Serbia, 11000 Belgrade, Serbia; (I.L.); (N.B.)
| | - Nevena Baljosevic
- Emergency Center, Gastroenterology and Hepatology Department, University Clinical Center of Serbia, 11000 Belgrade, Serbia; (I.L.); (N.B.)
| | - Sanja Zgradic
- Clinic of Gastroenterology and Hepatology, University Clinical Center of Serbia, 11000 Belgrade, Serbia; (I.P.); (T.G.); (S.Z.); (J.E.M.); (M.V.); (T.M.)
| | - Jasna El Mezeni
- Clinic of Gastroenterology and Hepatology, University Clinical Center of Serbia, 11000 Belgrade, Serbia; (I.P.); (T.G.); (S.Z.); (J.E.M.); (M.V.); (T.M.)
| | - Marko Vojnovic
- Clinic of Gastroenterology and Hepatology, University Clinical Center of Serbia, 11000 Belgrade, Serbia; (I.P.); (T.G.); (S.Z.); (J.E.M.); (M.V.); (T.M.)
| | - Marija Brankovic
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia;
- University Hospital Medical Center Bežanijska Kosa, 11000 Belgrade, Serbia
| | - Tamara Milovanovic
- Clinic of Gastroenterology and Hepatology, University Clinical Center of Serbia, 11000 Belgrade, Serbia; (I.P.); (T.G.); (S.Z.); (J.E.M.); (M.V.); (T.M.)
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia;
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Diaz PM, Saly DL, Horick N, Petrosyan R, Gitto Z, Indriolo T, Li L, Kahn-Boesel O, Donlan J, Robinson B, Dow L, Liu A, El-Jawahri A, Parada XV, Combs S, Teixeira J, Chung R, Allegretti AS, Ufere NN. Prognosis of Transplant-Ineligible Patients with Cirrhosis and Acute Kidney Injury Who Initiate Renal Replacement Therapy. Dig Dis Sci 2024; 69:3710-3720. [PMID: 39215868 PMCID: PMC11647743 DOI: 10.1007/s10620-024-08623-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Accepted: 08/25/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND Data to guide dialysis decision-making for transplant-ineligible patients with cirrhosis are lacking. AIMS We aimed to describe the processes, predictors, and outcomes of renal replacement therapy (RRT) initiation for transplant-ineligible patients with cirrhosis at a single liver transplantation center. METHODS We conducted a mixed-methods study of a retrospective cohort of 372 transplant-ineligible inpatients with cirrhosis with acute kidney injury (AKI) due to hepatorenal syndrome (HRS-AKI) or acute tubular necrosis (ATN) between 2008 and 2015. We performed survival analyses to evaluate 6-month survival and renal recovery and examined end-of-life care outcomes. We used a consensus-driven medical record review to characterize processes leading to RRT initiation. RESULTS We identified 266 (71.5%) patients who received RRT and 106 (28.5%) who did not receive RRT (non-RRT). Median survival was 12.5 days (RRT) vs. 2.0 days (non-RRT) (HR 0.36, 95%CI 0.28-0.46); 6-month survival was 15% (RRT) vs. 0% (non-RRT). RRT patients were more likely to die in the intensive care unit (88% vs. 32%, p < 0.001). HRS-AKI patients were more likely to be RRT dependent at 6 months than ATN patients (86% vs. 27%, p = 0.007). The most common reasons for RRT initiation were unclear etiology of AKI on presentation (32%) and belief of likely reversibility of ATN (82%). CONCLUSION Most transplant-ineligible patients who were initiated on RRT experienced very short-term mortality and received intensive end-of-life care. However, approximately 1 in 6 were alive at 6 months. Our findings underscore the critical need for structured clinical processes to support high-quality serious illness communication and RRT decision-making for this population.
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Affiliation(s)
- Paige McLean Diaz
- Department of Gastroenterology, Hepatology & Nutrition, Center for Liver Disease, University of Chicago Medicine, Chicago, IL, USA
| | - Danielle L Saly
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Nora Horick
- MGH Biostatistics, Massachusetts General Hospital, Boston, MA, USA
| | - Romela Petrosyan
- Division of Renal Medicine, Brigham and Women's Hospital, Boston, MA, USA
| | - Zachary Gitto
- Division of Gastroenterology and Hepatology, University of South Carolina School of Medicine, Columbia, SC, USA
| | - Teresa Indriolo
- Gastrointestinal Unit, Gastrointestinal Division, Department of Medicine, Liver Center, Massachusetts General Hospital, Boston, MA, USA
| | - Lucinda Li
- Gastrointestinal Unit, Gastrointestinal Division, Department of Medicine, Liver Center, Massachusetts General Hospital, Boston, MA, USA
| | - Olivia Kahn-Boesel
- Department of Internal Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - John Donlan
- Department of Internal Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Blair Robinson
- Division of Palliative Care and Geriatric Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Lindsay Dow
- Division of Palliative Care and Geriatric Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Annie Liu
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Areej El-Jawahri
- Division of Hematology and Oncology, Massachusetts General Hospital, Boston, MA, USA
| | - Xavier Vela Parada
- Division of Nephrology, UMass Memorial Medical Center, Worcester, MA, USA
| | - Sara Combs
- Divisions of Nephrology and Palliative Medicine, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM, USA
| | - Joao Teixeira
- Divisions of Nephrology and Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM, USA
| | - Raymond Chung
- Gastrointestinal Unit, Gastrointestinal Division, Department of Medicine, Liver Center, Massachusetts General Hospital, Boston, MA, USA
| | - Andrew S Allegretti
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Nneka N Ufere
- Gastrointestinal Unit, Gastrointestinal Division, Department of Medicine, Liver Center, Massachusetts General Hospital, Boston, MA, USA.
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Akbas MM, Uzunlulu M, Torun C, Bahadir O. Comparison of hepatorenal syndrome incidence and outcomes using previous and current diagnostic criteria in cirrhotic patients. HEPATOLOGY FORUM 2024; 6:5-10. [PMID: 40255954 PMCID: PMC12008459 DOI: 10.14744/hf.2023.2023.0067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Revised: 05/30/2024] [Accepted: 06/29/2024] [Indexed: 04/22/2025]
Abstract
Background and Aim Hepatorenal syndrome (HRS) is a severe complication of liver cirrhosis with evolving diagnostic criteria. This study aimed to examine HRS prevalence, subtypes, and outcomes while comparing previous and current diagnostic criteria. Materials and Methods This is a retrospective observational clinical study conducted on hospitalized patients with decompensated cirrhosis. Demographic characteristics, comorbidities, disease duration, disease severity, length of hospitalization, number of rehospitalizations, cirrhosis etiologies, laboratory data, and clinical outcomes were reviewed. The criteria from 2007 by the International Club of Ascites were the previous ones, with the 2015 criteria being the current criteria for diagnosing HRS. The incidence of HRS and its subtypes was determined, and the clinical characteristics of patients with and without HRS were compared using the Mann-Whitney U test. Results The study enrolled 212 patients, with a male predominance (57.5%) and a mean age of 63.4±14.5 years. A total of 32.1% of patients developed acute kidney injury (AKI), with prerenal azotemia being the most common type (76.5%), followed by intrinsic renal AKI (23.5%). Under the current criteria, 27 patients (12.7%) received an HRS diagnosis, while under the previous criteria, 16 patients (7.5%) received an HRS diagnosis, and the difference in diagnostic frequencies was statistically significant (p=0.046). In HRS cases, the MELD score (p=0.001), being classified as Child-Pugh C (p=0.043), rehospitalization (p=0.011), requiring intensive care (p=0.001), and creatinine levels (p<0.001) were higher. Conclusion AKI is common in hospitalized cirrhotic patients. The current HRS criteria identify more cases that need close monitoring compared to the previous criteria.
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Affiliation(s)
- Muhammet Mikdat Akbas
- Department of Internal Medicine, Istanbul Medeniyet University, Goztepe Training and Research Hospital, Istanbul, Turkiye
| | - Mehmet Uzunlulu
- Department of Internal Medicine, Istanbul Medeniyet University, Goztepe Training and Research Hospital, Istanbul, Turkiye
| | - Cundullah Torun
- Department of Internal Medicine, Istanbul Medeniyet University, Goztepe Training and Research Hospital, Istanbul, Turkiye
| | - Ozgur Bahadir
- Department of Internal Medicine, Istanbul Medeniyet University, Goztepe Training and Research Hospital, Istanbul, Turkiye
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Abdelhafez MO, Alhroob AA, Abu Hawilla MO, Rjoob AA, Abualia NM, Gorman EF, Hamadah AM, Gharaibeh KA. Utility of fractional excretion of urea in acute kidney injury with comparison to fractional excretion of sodium: A systematic review and meta-analysis. Am J Med Sci 2024; 368:224-234. [PMID: 38768779 DOI: 10.1016/j.amjms.2024.04.021] [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: 09/13/2023] [Revised: 02/28/2024] [Accepted: 04/18/2024] [Indexed: 05/22/2024]
Abstract
BACKGROUND Differentiating between intrinsic and prerenal acute kidney injury (AKI) presents a challenge. Here, we assessed the performance of the fractional excretion of urea (FEUrea) and compared it to the fractional excretion of sodium (FENa) in distinguishing intrinsic from prerenal AKI. METHODS A thorough search was conducted in several databases until January 16, 2024. We included studies evaluating FEUrea, with or without FENa, for differentiating AKI etiologies in adults. We assessed the methodological quality using the QUADAS-2 and QUADAS-C tools. We performed a meta-analysis using the bivariate random effects model, with subgroup analyses to explore the impact of diuretic therapy on FEUrea, and direct statistical comparisons between FEUrea and FENa involving the subgroups with and without diuretics. RESULTS We included 11 studies with 1108 hospitalized patients. Among eight studies (915 patients) evaluating FEUrea >35% for distinguishing intrinsic from prerenal AKI, the pooled sensitivity and specificity were 66% (95% CI, 49%-79%) and 75% (95% CI, 60%-85%), respectively. In a subset of six studies (302 patients) comparing FEUrea at 35% to FENa at 1% in patients not receiving diuretics, there were no significant differences in sensitivity (77% versus 89%, P = 0.410) or specificity (80% versus 79%, P = 0.956). In four studies, 244 patients on diuretics, FEUrea demonstrated lower sensitivity (52% versus 92%, P < 0.001) but higher specificity (82% versus 44%, P < 0.001) compared to FENa for the diagnosis of intrinsic AKI. CONCLUSIONS FEUrea has limited utility in differentiating intrinsic from prerenal AKI. FEUrea does not provide a superior alternative to FENa, even in patients receiving diuretics.
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Affiliation(s)
- Mohammad O Abdelhafez
- Department of Internal Medicine, Al-Quds University, Abu Dis, Jerusalem, State of Palestine
| | - Asil A Alhroob
- Department of Internal Medicine, Al-Quds University, Abu Dis, Jerusalem, State of Palestine
| | - Mustafa O Abu Hawilla
- Department of Internal Medicine, Al-Quds University, Abu Dis, Jerusalem, State of Palestine
| | - Asmaa A Rjoob
- Department of Internal Medicine, Al-Quds University, Abu Dis, Jerusalem, State of Palestine
| | - Nasser M Abualia
- Department of Internal Medicine, Al-Quds University, Abu Dis, Jerusalem, State of Palestine
| | - Emily F Gorman
- Health Sciences and Human Services Library, University of Maryland, Baltimore, MD, USA
| | | | - Kamel A Gharaibeh
- Department of Internal Medicine, Al-Quds University, Abu Dis, Jerusalem, State of Palestine; Division of Pulmonary & Critical Care Medicine, University of Maryland, School of Medicine, Baltimore, MD, USA.
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Borle A, Kanitkar S, Bagare PC, Ahlawat M, Ande SP. A Study of the Clinical Profiles of Patients With Hepatorenal Syndrome. Cureus 2024; 16:e66778. [PMID: 39268272 PMCID: PMC11392026 DOI: 10.7759/cureus.66778] [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: 08/13/2024] [Indexed: 09/15/2024] Open
Abstract
Background and objective Hepatorenal syndrome (HRS) is a systemic disorder that affects both the kidneys and the liver. HRS refers to the occurrence of kidney failure in individuals with advanced liver cirrhosis, portal hypertension, and ascites, without any underlying kidney disease. The interplay of systemic and portal hemodynamics causes severe constriction of blood vessels in the kidneys, which defines HRS. The study aims to illuminate the demographic profiles, etiology, and outcomes of patients with HRS. Material and methods The study was designed as a prospective, cross-sectional, hospital-based observational study conducted at Dr. D.Y. Patil Medical College, Hospital, and Research Centre in Pimpri, Pune. The study period spans from September 2022 to June 2024. Before commencement, approval was obtained from the institutional ethics committee, and informed written consent was secured from all participating patients. The sample size consists of 100 patients diagnosed with HRS, selected from the general medicine outpatient department, wards, and ICU of Dr. D.Y. Patil Hospital and Research Centre. A comprehensive clinical history was recorded for all patients, focusing on the symptoms of cirrhosis and HRS, followed by a thorough examination for related signs and symptoms. Results Among the 100 patients included in this study on HRS, 25% (N=25) fell within the age range of 18-30 years, and 76% (N=76) were identified as male. Alcoholic cirrhosis accounted for 78% (N=78) of cases, with hepatitis B infection being the subsequent leading cause. The mortality rate was 12% (N=12) while the survival rate was 88% (N=88). Conclusion This study provides insights into the demographic profile, etiology, and outcomes of HRS. The results of this study contribute valuable insights into the complex nature of HRS, highlighting the importance of early detection and monitoring to optimize patient care.
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Affiliation(s)
- Akshata Borle
- Internal Medicine, Dr. D.Y. Patil Medical College, Hospital and Research Centre, Pune, IND
| | - Shubhangi Kanitkar
- Internal Medicine, Dr. D.Y. Patil Medical College, Hospital and Research Centre, Pune, IND
| | - Prasad C Bagare
- Medicine, Dr. D.Y. Patil Medical College, Hospital and Research Centre, Pune, IND
| | - Muskaan Ahlawat
- Medicine, Dr. D.Y. Patil Medical College, Hospital and Research Centre, Pune, IND
| | - Sai Priya Ande
- Internal Medicine, Dr. D.Y. Patil Medical College, Hospital and Research Centre, Pune, IND
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Malik A, Malik MI, Qureshi S, Nadir A. Efficacy and safety of terlipressin and albumin vs. noradrenaline and albumin in adult patients with hepatorenal syndrome: A systematic review and meta-analysis. Ann Hepatol 2024; 29:101495. [PMID: 38460713 DOI: 10.1016/j.aohep.2024.101495] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Revised: 12/10/2023] [Accepted: 01/03/2024] [Indexed: 03/11/2024]
Abstract
INTRODUCTION AND OBJECTIVES Hepatorenal syndrome (HRS) is a serious complication of cirrhosis treated with various medications. We aim to evaluate terlipressin and albumin's effectiveness and safety compared to albumin and noradrenaline in adult hepatorenal disease patients. MATERIALS AND METHODS Clinical trials from four databases were included. Cochrane's approach for calculating bias risk was utilized. We rated the quality evaluation by Grading of Recommendations Assessment, Development, and Evaluation (GRADE). We included the following outcomes: serum creatinine (mg/dl), urine output (ml/24 h), mean arterial pressure (mmHg), reversal rate of HRS, mortality rate, blood plasma renin activity (ng/ml/h), plasma aldosterone concentration (pg/ml), urine sodium (mEq/l), and creatinine clearance (ml/min). RESULTS Our analysis of nine clinical studies revealed that the noradrenaline group was associated with higher creatinine clearance (MD = 4.22 [0.40, 8.05]), (P = 0.03). There were no significant differences in serum creatinine levels (MD = 0.03 [-0.07, 0.13]), urinary sodium (MD = -1.02 [-5.15, 3.11]), urine output (MD = 32.75 [-93.94, 159.44]), mean arterial pressure (MD = 1.40 [-1.17, 3.96]), plasma renin activity (MD = 1.35 [-0.17, 2.87]), plasma aldosterone concentration (MD = 55.35 [-24.59, 135.29]), reversal rate of HRS (RR = 1.15 [0.96, 1.37]), or mortality rate (RR = 0.87 [0.74, 1.01]) between the two groups (p-values > 0.05). CONCLUSIONS Noradrenaline is a safe alternative medical therapy for HRS.
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Affiliation(s)
- Adnan Malik
- Division of Gastroenterology, Mountain Vista Medical Center, Mesa, AZ, United States.
| | | | - Shahbaz Qureshi
- Division of Gastroenterology, Mountain Vista Medical Center, Mesa, AZ, United States
| | - Abdul Nadir
- Division of Gastroenterology, Mountain Vista Medical Center, Mesa, AZ, United States
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Lekakis V, Gkoufa A, Vlachogiannakos J, Papatheodoridis GV, Cholongitas E. Incidence and risk factors of acute kidney injury in cirrhosis: a systematic review and meta-analysis of 5,202,232 outpatients, inpatients, and ICU-admitted patients. Expert Rev Gastroenterol Hepatol 2024; 18:377-388. [PMID: 39001566 DOI: 10.1080/17474124.2024.2380299] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Accepted: 07/11/2024] [Indexed: 07/18/2024]
Abstract
INTRODUCTION Acute kidney injury (AKI) is a commonly seen condition in the natural course of cirrhosis. The aim of this study was to evaluate the pooled incidence and risk factors of AKI in different clinical stages and situations in patients with cirrhosis. METHODS Search was conducted on 13 December 2023 across MEDLINE (PubMed), Embase, and Cochrane databases. Meta-analysis was performed using a generalized linear mixed model. RESULTS In total, 73 studies with 5,202,232 patients were finally enrolled in the meta-analysis. AKI commonly occurs among hospitalized cirrhotics experiencing any decompensation event (29%) as well as among stable outpatients (28%) throughout a 1-year follow-up period. On admission, patients with infection or sepsis/septic shock had the highest AKI rate (47%), followed by those with hepatic encephalopathy (41%). Furthermore, the severity of liver disease proved to be a substantial driver for AKI development, while patients at intensive care unit had the greatest AKI incidence (61%). CONCLUSIONS Both hospitalized patients and stable outpatients with cirrhosis exhibited an elevated susceptibility to AKI. Patients at intensive care unit and those with severe liver disease, infection, sepsis/septic shock, hepatic encephalopathy, or acute on chronic liver failure upon admission are at higher risk for AKI. TRIAL REGISTRATION PROSPERO, registered 09/12/23, CRD42023487736.
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Affiliation(s)
- Vasileios Lekakis
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | - Aikaterini Gkoufa
- First Department of Internal Medicine, "Laiko", General Hospital, Medical School of National and Kapodistrian University of Athens, Athens, Greece
| | - John Vlachogiannakos
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | - George V Papatheodoridis
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | - Evangelos Cholongitas
- First Department of Internal Medicine, "Laiko", General Hospital, Medical School of National and Kapodistrian University of Athens, Athens, Greece
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12
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L'Écuyer S, Charbonney E, Carrier FM, Rose CF. Implication of Hypotension in the Pathogenesis of Cognitive Impairment and Brain Injury in Chronic Liver Disease. Neurochem Res 2024; 49:1437-1449. [PMID: 36635437 DOI: 10.1007/s11064-022-03854-z] [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: 07/25/2022] [Revised: 09/23/2022] [Accepted: 12/26/2022] [Indexed: 01/14/2023]
Abstract
The incidence of chronic liver disease is on the rise. One of the primary causes of hospital admissions for patients with cirrhosis is hepatic encephalopathy (HE), a debilitating neurological complication. HE is defined as a reversible syndrome, yet there is growing evidence stating that, under certain conditions, HE is associated with permanent neuronal injury and irreversibility. The pathophysiology of HE primarily implicates a strong role for hyperammonemia, but it is believed other pathogenic factors are involved. The fibrotic scarring of the liver during the progression of chronic liver disease (cirrhosis) consequently leads to increased hepatic resistance and circulatory anomalies characterized by portal hypertension, hyperdynamic circulatory state and systemic hypotension. The possible repercussions of these circulatory anomalies on brain perfusion, including impaired cerebral blood flow (CBF) autoregulation, could be implicated in the development of HE and/or permanent brain injury. Furthermore, hypotensive insults incurring during gastrointestinal bleed, infection, or liver transplantation may also trigger or exacerbate brain dysfunction and cell damage. This review will focus on the role of hypotension in the onset of HE as well as in the occurrence of neuronal cell loss in cirrhosis.
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Affiliation(s)
- Sydnée L'Écuyer
- Hepato-Neuro Laboratory, Centre de recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), 900, rue Saint-Denis - Pavillon R, R08.422 Montréal (Québec), Québec, H2X 0A9, Canada
| | - Emmanuel Charbonney
- Department of Medicine, Critical Care Division, Centre Hospitalier de l'Université de Montréal, Montréal, Canada
| | - François Martin Carrier
- Department of Medicine, Critical Care Division, Centre Hospitalier de l'Université de Montréal, Montréal, Canada
- Department of Anesthesiology, Centre Hospitalier de l'Université de Montréal, Montréal, Canada
- Carrefour de l'innovation et santé des populations , Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montréal, Canada
| | - Christopher F Rose
- Hepato-Neuro Laboratory, Centre de recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), 900, rue Saint-Denis - Pavillon R, R08.422 Montréal (Québec), Québec, H2X 0A9, Canada.
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Banegas-Deras EJ, Mazón-Ruiz J, Romero-González G, Ruiz-Cobo JC, Sanz-García C, Serrano-Soto M, Sánchez E, Argaiz ER. Acute kidney injury and point-of-care ultrasound in liver cirrhosis: redefining hepatorenal syndrome. Clin Kidney J 2024; 17:sfae112. [PMID: 38726210 PMCID: PMC11079671 DOI: 10.1093/ckj/sfae112] [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: 01/04/2024] [Indexed: 05/12/2024] Open
Abstract
Acute kidney injury (AKI) in patients with cirrhosis is a diagnostic challenge due to multiple and sometimes overlapping possible etiologies. Many times, diagnosis cannot be made based on case history, physical examination or laboratory data, especially when the nephrologist is faced with AKI with a hemodynamic basis, such as hepatorenal syndrome. In addition, the guidelines still include generalized recommendations regarding withdrawal of diuretics and plasma volume expansion with albumin for 48 h, which may be ineffective and counterproductive and may have iatrogenic effects, such as fluid overload and acute cardiogenic pulmonary edema. For this reason, the use of new tools, such as hemodynamic point-of-care ultrasound (PoCUS), allows us to phenotype volume status more accurately and ultimately guide medical treatment in a noninvasive, rapid and individualized manner.
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Affiliation(s)
| | - Jaime Mazón-Ruiz
- Nephrology Department, Central University Hospital of Asturias, Oviedo, Spain
| | - Gregorio Romero-González
- Nephrology Department, Germans Trias i Pujol University Hospital, Badalona, Spain
- International Renal Research Institute of Vicenza, Vicenza, Italy
| | - Juan Carlos Ruiz-Cobo
- Liver Unit, Vall d'Hebron University Hospital, Barcelona, Spain
- Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Clara Sanz-García
- Nephrology Department, Grande Covián de Arriondas Hospital, Arriondas, Spain
| | - Mara Serrano-Soto
- International Renal Research Institute of Vicenza, Vicenza, Italy
- Nephrology Department, Marqués de Valdecilla University Hospital, Santander, Spain
| | - Emilio Sánchez
- Nephrology Department, Cabueñes University Hospital, Gijón, Spain
| | - Eduardo R Argaiz
- Tecnológico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Mexico City, Mexico
- Departamento de Nefrología y Metabolismo Mineral, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
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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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15
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Rudyk DV, Tutchenko MI, Chub SL, Besedinsky MS. Portal hypertension and emergency care. WIADOMOSCI LEKARSKIE (WARSAW, POLAND : 1960) 2024; 77:1485-1489. [PMID: 39241149 DOI: 10.36740/wlek202407125] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/08/2024]
Abstract
OBJECTIVE Aim: To evaluate the peculiarities of the course of complications and the provision of care for portal hypertension associated with the development of diureticresistant ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, and variceal bleeding. PATIENTS AND METHODS Materials and Methods: This research is based on a review of the literature in PubMed, CrossRef, Google Scholar sources on complicated portal hypertension. Such complications of portal hypertension as spontaneous bacterial peritonitis, ascites, hepatorenal sуndrome, variceal bleeding caused by sinistral portal hypertension are considered. The effectiveness of interventional treatment methods and laparoscopic surgical interventions has been demonstrated. CONCLUSION Conclusions: Diagnosis and treatment of patients with complicated portal hypertension requires a multidisciplinary approach, which is due to the diverse pathophysiological process of portal hypertension. The possibilities of providing emergency care to this category of patients depend on the level of medical training of the staff, the possibilities of medical and technical support in the provision of interventional care, the ineffectiveness of which necessitates surgical treatment using minimally invasive technologies.
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Affiliation(s)
- Diana V Rudyk
- BOGOMOLETS NATIONAL MEDICAL UNIVERSITY, KYIV, UKRAINE
| | | | - Sergiy L Chub
- BOGOMOLETS NATIONAL MEDICAL UNIVERSITY, KYIV, UKRAINE
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Narayanan V, Devadas K, Sreesh S, Varghese J, Solanki R, Mohapatra SD, Pal R, Madhu D, Chakravorty A. Novel predictors of response to therapy with terlipressin and albumin in hepatorenal syndrome-acute kidney injury. Ann Gastroenterol 2024; 37:81-88. [PMID: 38223250 PMCID: PMC10785019 DOI: 10.20524/aog.2023.0853] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2023] [Accepted: 11/27/2023] [Indexed: 01/16/2024] Open
Abstract
Background A combination of terlipressin and albumin is the first-line pharmacologic treatment for hepatorenal syndrome-acute kidney injury (HRS-AKI). We assessed the response rates to terlipressin-albumin therapy in patients with HRS-AKI and determined early predictors of treatment response and survival. Methods A total of 84 patients with HRS-AKI (International Club of Ascites definition 2015) treated with terlipressin-albumin were included. Predictors of HRS reversal were identified by logistic regression analysis. Survival analysis was performed using the Kaplan-Meier method, and Cox regression models were used to determine independent predictors of mortality. Results Complete response to therapy was observed in 54.8%, partial response in 14.3%, and no response in 31% of patients. The factors associated with complete treatment response were the presence of systemic inflammatory response syndrome (SIRS), baseline serum creatinine, a rise in mean arterial pressure by day 3, and a reduction in the renal resistive index (ΔRRI) by day 3 of treatment. Independent predictors of HRS reversal were the presence of SIRS at baseline (P=0.022; odds ratio [OR] 15.74, 95% confidence interval [CI] 1.47-167.82) and ΔRRI ≥5% by day 3 of treatment (P=0.048; OR 6.67, 95%CI 1.021-43.62). Mean transplant-free survival at 6 months was significantly better in treatment responders (148 vs. 90 days, P<0.001). Independent predictors of 6-month mortality were response to treatment (P=0.004) and model for end-stage liver disease-sodium >23 (P=0.018). Conclusions SIRS and ΔRRI are simple parameters to predict treatment response in HRS-AKI. Non-responders have higher mortality and should be identified early to expedite liver transplantation.
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Affiliation(s)
- Vijay Narayanan
- Department of Medical Gastroenterology, Government Medical College, Thiruvananthapuram, Kerala, India (Vijay Narayanan, Krishnadas Devadas, Srijaya Sreesh, Jijo Varghese, Rushil Solanki, Shivabrata Dhal Mohapatra, Ravindra Pal, Devika Madhu, Avisek Chakravorty)
| | - Krishnadas Devadas
- Department of Medical Gastroenterology, Government Medical College, Thiruvananthapuram, Kerala, India (Vijay Narayanan, Krishnadas Devadas, Srijaya Sreesh, Jijo Varghese, Rushil Solanki, Shivabrata Dhal Mohapatra, Ravindra Pal, Devika Madhu, Avisek Chakravorty)
| | - Srijaya Sreesh
- Department of Medical Gastroenterology, Government Medical College, Thiruvananthapuram, Kerala, India (Vijay Narayanan, Krishnadas Devadas, Srijaya Sreesh, Jijo Varghese, Rushil Solanki, Shivabrata Dhal Mohapatra, Ravindra Pal, Devika Madhu, Avisek Chakravorty)
| | - Jijo Varghese
- Department of Medical Gastroenterology, Government Medical College, Thiruvananthapuram, Kerala, India (Vijay Narayanan, Krishnadas Devadas, Srijaya Sreesh, Jijo Varghese, Rushil Solanki, Shivabrata Dhal Mohapatra, Ravindra Pal, Devika Madhu, Avisek Chakravorty)
| | - Rushil Solanki
- Department of Medical Gastroenterology, Government Medical College, Thiruvananthapuram, Kerala, India (Vijay Narayanan, Krishnadas Devadas, Srijaya Sreesh, Jijo Varghese, Rushil Solanki, Shivabrata Dhal Mohapatra, Ravindra Pal, Devika Madhu, Avisek Chakravorty)
| | - Shivabrata Dhal Mohapatra
- Department of Medical Gastroenterology, Government Medical College, Thiruvananthapuram, Kerala, India (Vijay Narayanan, Krishnadas Devadas, Srijaya Sreesh, Jijo Varghese, Rushil Solanki, Shivabrata Dhal Mohapatra, Ravindra Pal, Devika Madhu, Avisek Chakravorty)
| | - Ravindra Pal
- Department of Medical Gastroenterology, Government Medical College, Thiruvananthapuram, Kerala, India (Vijay Narayanan, Krishnadas Devadas, Srijaya Sreesh, Jijo Varghese, Rushil Solanki, Shivabrata Dhal Mohapatra, Ravindra Pal, Devika Madhu, Avisek Chakravorty)
| | - Devika Madhu
- Department of Medical Gastroenterology, Government Medical College, Thiruvananthapuram, Kerala, India (Vijay Narayanan, Krishnadas Devadas, Srijaya Sreesh, Jijo Varghese, Rushil Solanki, Shivabrata Dhal Mohapatra, Ravindra Pal, Devika Madhu, Avisek Chakravorty)
| | - Avisek Chakravorty
- Department of Medical Gastroenterology, Government Medical College, Thiruvananthapuram, Kerala, India (Vijay Narayanan, Krishnadas Devadas, Srijaya Sreesh, Jijo Varghese, Rushil Solanki, Shivabrata Dhal Mohapatra, Ravindra Pal, Devika Madhu, Avisek Chakravorty)
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Salim T, Maindad D. Role of oral Midodrine in preventing hepatorenal syndrome in Child-Turcotte-Pugh class C cirrhotics: a pilot study. GASTROENTEROLOGY AND HEPATOLOGY FROM BED TO BENCH 2024; 17:438-449. [PMID: 40406430 PMCID: PMC12094511 DOI: 10.22037/ghfbb.v17i4.3019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 05/26/2025]
Abstract
Aim The purpose of the study was to assess benefits of oral midodrine in the role of primary prevention of hepatorenal syndrome (HRS) in Child-Turcotte-Pugh Class C (CTP-C) cirrhotics. Background The present non-randomized pilot study was designed for primary prevention of HRS as there is absence of an effective and definite treatment for this complication of cirrhosis to date other than liver transplant (LT). Methods This study effectively involved 30 patients each enrolled in interventional and control arms suffering from liver cirrhosis CTP-C with normal renal function and having a mean arterial pressure (MAP) < 80 mmHg who were subjected to clinical examination and baseline blood investigations. The mean daily dosage of midodrine used across the study group was 16.75 mg. Results At the end of 4 months of study, 11 individuals completed the study without attaining any endpoints from the control group while 23 accomplished it from the interventional arm. Nearly 50 % patients required a midodrine dose of 7.5 mg 8th hourly while the rest attained the targeted MAP with lower doses. By increasing MAP, the rate of HRS development during the study period (i.e. 4 months) was found to be significantly reduced in patients from interventional arm. The number needed to treat (NNT) observed in survival analysis to prevent one death was found to be 7.6. Conclusion This study successfully established the role oral midodrine in primary prevention of HRS in cirrhotics at high risk. Midodrine was well tolerated with no significant adverse effects in patients under study.
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Affiliation(s)
- Tariq Salim
- Department of Medical Gastroenterology, Bharati Vidyapeeth University Medical College, Pune - 411043 (Maharashtra), India
| | - Dadasaheb Maindad
- Department of Medical Gastroenterology, Bharati Vidyapeeth University Medical College, Pune - 411043 (Maharashtra), India
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Nall S, Arshad H, Contractor B, Sunina F, Raja F, Chaudhari SS, Batool S, Amin A. Predictors of Acute Kidney Injury in Patients Hospitalized With Liver Cirrhosis: A Systematic Review and Meta-Analysis. Cureus 2024; 16:e52386. [PMID: 38361702 PMCID: PMC10868655 DOI: 10.7759/cureus.52386] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/16/2024] [Indexed: 01/27/2024] Open
Abstract
Acute kidney injury (AKI) frequently occurs in hospitalized individuals with liver cirrhosis and represents a significant risk factor for early in-hospital mortality, holding crucial clinical and prognostic importance. The objective of this meta-analysis was to assess the risk factors associated with AKI in hospitalized individuals with cirrhosis. This systematic review and meta-analysis was conducted in concordance with guidelines provided by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. Two independent researchers systematically searched major databases, including MEDLINE/PubMed, Web of Science, and EMBASE, from January 2015 until December 2023. A total of 14 studies were included in this meta-analysis, of which six were prospective, and the remaining were retrospective. Of the 9,659 cirrhosis patients in the 14 included studies, 3,968 had developed AKI with a pooled incidence of 41% (95% confidence interval = 34-47%). Our findings showed that a high Model for End-Stage Liver Disease (MELD) score, infection, high Child-Pugh-Turcotte stage score, high serum creatinine, high serum bilirubin, and low serum albumin were significantly associated with high incidence of AKI in liver cirrhosis patients. The results emphasize the importance of vigilant monitoring in cirrhosis patients to detect any indications of AKI, followed by meticulous and attentive management.
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Affiliation(s)
- Scott Nall
- Medicine, Central Michigan University School of Medicine, Saginaw, USA
| | | | - Bianca Contractor
- Internal Medicine, Smt. Nathiba Hargovandas Lakhmichand (NHL) Municipal Medical College, Ahmedabad, IND
| | - Fnu Sunina
- Medicine, Jinnah Postgraduate Medical Centre, Karachi, PAK
| | - Fnu Raja
- Pathology, MetroHealth Medical Center, Cleveland, USA
| | - Sandipkumar S Chaudhari
- Cardiothoracic Surgery, University of Alabama at Birmingham, Birmingham, USA
- Family Medicine, University of North Dakota School of Medicine and Health Sciences, Fargo, USA
| | - Saima Batool
- Internal Medicine, Hameed Latif Hospital, Lahore, PAK
| | - Adil Amin
- Cardiology, Pakistan Navy Ship (PNS) Shifa, Karachi, PAK
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Petiunin O, Shevchenko R, Brek O, Kolomenskyi O. Clinical classification of liver cirrhosis - a way to plan individual definitive treatment. WIADOMOSCI LEKARSKIE (WARSAW, POLAND : 1960) 2024; 77:160-165. [PMID: 38431821 DOI: 10.36740/wlek202401120] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/05/2024]
Abstract
OBJECTIVE Aim: To develop clinical classification of liver cirrhosis, which can aid individualization and planning definitive treatment for this group of patients. PATIENTS AND METHODS Materials and Methods: Computerized search of the literature was performed via PubMed using the following medical subject headings or keywords: "liver", "cirrhosis" and "classification"; or "liver", "cirrhosis" and "complications"; or "liver", "cirrhosis" and "treatment"; or "portal" ", "hypertension" and "complications". Articles were independently evaluated by each author, the etiological, morphological and current clinical classifications of LC were analyzed, their advantages and disadvantages identified, and after discussion classification of LC was developed by consensus. CONCLUSION Conclusions: The developed clinical classification of liver cirrhosis will facilitate the planning of therapeutic tactics for each patient, allow to personalize the treatment of patients with this pathology.
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Affiliation(s)
| | | | - Ostap Brek
- KHARKIV NATIONAL MEDICAL UNIVERSITY, KHARKIV, UKRAINE
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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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Mohanty A, Cárdenas A. Securing the diagnosis of HRS-AKI: implications for current therapies. Expert Rev Gastroenterol Hepatol 2023; 17:1233-1239. [PMID: 37982156 DOI: 10.1080/17474124.2023.2284189] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Accepted: 11/13/2023] [Indexed: 11/21/2023]
Abstract
INTRODUCTION Hepatorenal syndrome (HRS)-acute kidney injury (HRS-AKI) is a specific type of kidney injury seen in patients with cirrhosis and ascites and is associated with high mortality and morbidity. It is characterized by rapid deterioration of renal function due to reduced renal blood flow secondary to portal hypertensive splanchnic and systemic vasodilation. Early diagnosis and treatment of HRS-AKI are associated with greater likelihood of improvement in renal function, lower need for dialysis, and better post-transplant outcomes. AREAS COVERED This review discusses the diagnostic criteria for HRS-AKI, which has undergone several key changes over the last decade, with an aim to secure an early diagnosis and aid swift treatment initiation. Additionally, this review outlines the current treatment paradigms for HRS-AKI. EXPERT OPINION In the last 20 years, there have been several advances in understanding the pathophysiology and natural course of HRS-AKI. These have led to critical changes in its definition and diagnostic algorithm. However, prognosis of HRS-AKI remains dismal with no significant improvement in HRS-AKI reversal or HRS-related mortality over this time. We discuss several gaps in the current understanding and management of HRS-AKI that will benefit from further research.
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Affiliation(s)
- Arpan Mohanty
- Boston University Chobanian and Avedisian School of Medicine and Boston Medical Center, United States
| | - Andrés Cárdenas
- GI and Liver Unit, Institut de Malalties Digestives, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi-Sunyer (IDIBAPS), Barcelona and Ciber de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain
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22
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Huang X, Bindra J, Chopra I, Niewoehner J, Wan GJ. Treatment-Related Cost Analysis of Terlipressin for Adults with Hepatorenal Syndrome with Rapid Reduction in Kidney Function. Adv Ther 2023; 40:5432-5446. [PMID: 37812332 PMCID: PMC10611877 DOI: 10.1007/s12325-023-02674-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2023] [Accepted: 08/31/2023] [Indexed: 10/10/2023]
Abstract
INTRODUCTION Hepatorenal syndrome (HRS), a special form of acute kidney failure, is a rare, acute, life-threatening complication of cirrhosis and has a very poor prognosis. Terlipressin (TERLIVAZ®) is the first and only pharmacological treatment approved by Food and Drug Administration (September 2022) to improve kidney function for adults with HRS with rapid reduction in kidney function. We constructed a decision analytic economic model to estimate the cost per complete response/HRS reversal of terlipressin + albumin from a United States hospital perspective. METHODS A decision analytic model was developed to estimate the HRS treatment-related cost per response over an HRS hospitalization (assuming 14 days). Patients can experience either HRS reversal (complete response) or no HRS reversal (partial/no response) upon receipt of treatment. The efficacy, safety, and treatment duration data were from published head-to-head randomized international trials. Total treatment cost comprised drug acquisition and treatment-related costs (intensive care unit [ICU], dialysis [intermittent or continuous], pulse oximetry monitoring for terlipressin, and adverse events) sourced from the published literature. Cost per response, defined as the total treatment cost per HRS reversal was estimated for each treatment. The number needed to treat (NNT), defined as the number of patients treated to achieve HRS reversal in 1 additional patient, was estimated. RESULTS Cost per response of terlipressin + albumin was lower than midodrine and octreotide + albumin (M&O) (US$85,315 vs. $467,794) and norepinephrine + albumin ($81,614 vs. $139,324). NNT for HRS reversal was 2 patients with terlipressin + albumin vs. M&O + albumin and 4 patients with terlipressin + albumin vs. norepinephrine + albumin, respectively. CONCLUSIONS The analysis shows that terlipressin is a cost-effective treatment due to its higher efficacy and administration in the non-ICU setting. Terlipressin is a value-based treatment option for appropriate adults with HRS with rapid reduction in kidney function.
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Affiliation(s)
- Xingyue Huang
- Mallinckrodt Pharmaceuticals, 440 Route 22 East, Bridgewater, NJ, USA.
| | - Jas Bindra
- Falcon Research Group, North Potomac, MD, USA
| | | | - John Niewoehner
- Mallinckrodt Pharmaceuticals, 440 Route 22 East, Bridgewater, NJ, USA
| | - George J Wan
- Mallinckrodt Pharmaceuticals, 440 Route 22 East, Bridgewater, NJ, USA
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23
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Weinberg E, Rahematpura S, Gonzalez SA, Izzy MJ, Simonetto DA, Frederick RT, Rubin RA, Ikahihifo-Bender J, Harte M, Kim-Lee G, Witkiewicz S, Tobin W, Jamil K, Fricker Z, Reddy KR. INFUSE: Rationale and design of a multi-center, open label, collaborative study to treat HRS-AKI with continuous terlipressin infusion. Contemp Clin Trials Commun 2023; 36:101211. [PMID: 37953795 PMCID: PMC10632660 DOI: 10.1016/j.conctc.2023.101211] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Revised: 08/25/2023] [Accepted: 10/01/2023] [Indexed: 11/14/2023] Open
Abstract
Background Hepatorenal syndrome-acute kidney injury (HRS-AKI) carries significant morbidity and mortality among those with end-stage liver disease. Bolus terlipressin for treatment of HRS-AKI received FDA approval in September 2022. US implementation of terlipressin, however, is hindered by the paucity of local data on the optimal patient population and administration mode, as well as the effect on transplant priority. The INFUSE study is designed to evaluate the use of continuous terlipressin infusion among transplant candidates with advanced liver disease and HRS-AKI. Methods Fifty prospective patients with HRS-AKI will receive a single bolus of terlipressin 0.5 mg followed by continuous infusions of terlipressin from 2 to 8 mg/day for up to 14 days. The cohort will be enriched with those listed, in evaluation, or eligible for liver transplantation, while those with ACLF grade 3, MELD ≥35, and serum creatinine >5.0 mg/dL will be excluded. Fifty patients who received midodrine plus octreotide or norepinephrine for HRS-AKI will serve as a retrospective comparator cohort. Conclusion The INFUSE study aims to assess the safety and efficacy of continuous terlipressin infusion among largely transplant-eligible patients with HRS-AKI, and to provide US-based data on transplant outcomes. This novel study design simultaneously mitigates terlipressin adverse events while providing renal benefits to patients, thus addressing the unmet medical need of those with HRS-AKI who have limited treatment options and are awaiting liver transplantation in the US.
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Affiliation(s)
- Ethan Weinberg
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Suditi Rahematpura
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Stevan A. Gonzalez
- Division of Hepatology, Simmons Transplant Institute, Baylor Scott and White All Saints Medical Center, Fort Worth, TX, USA
| | - Manhal J. Izzy
- Department of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, TN, USA
| | | | - R. Todd Frederick
- Department of Hepatology and Liver Transplantation, California Pacific Medical Center, San Francisco, CA, USA
| | - Raymond A. Rubin
- Department of Transplantation, Piedmont Transplant Institute, Atlanta, GA, USA
| | - Jade Ikahihifo-Bender
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Maggie Harte
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Grace Kim-Lee
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | | | | | - Khurram Jamil
- Mallinckrodt Ltd, Scientific Affairs, Hampton, NJ, USA
| | - Zachary Fricker
- Division of Gastroenterology, Hepatology, and Nutrition, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - K. Rajender Reddy
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
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Liu H, Nguyen HH, Hwang SY, Lee SS. Oxidative Mechanisms and Cardiovascular Abnormalities of Cirrhosis and Portal Hypertension. Int J Mol Sci 2023; 24:16805. [PMID: 38069125 PMCID: PMC10706054 DOI: 10.3390/ijms242316805] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Revised: 11/19/2023] [Accepted: 11/24/2023] [Indexed: 12/18/2023] Open
Abstract
In patients with portal hypertension, there are many complications including cardiovascular abnormalities, hepatorenal syndrome, ascites, variceal bleeding, and hepatic encephalopathy. The underlying mechanisms are not yet completely clarified. It is well known that portal hypertension causes mesenteric congestion which produces reactive oxygen species (ROS). ROS has been associated with intestinal mucosal injury, increased intestinal permeability, enhanced gut bacterial overgrowth, and translocation; all these changes result in increased endotoxin and inflammation. Portal hypertension also results in the development of collateral circulation and reduces liver mass resulting in an overall increase in endotoxin/bacteria bypassing detoxication and immune clearance in the liver. Endotoxemia can in turn aggravate oxidative stress and inflammation, leading to a cycle of gut barrier dysfunction → endotoxemia → organ injury. The phenotype of cardiovascular abnormalities includes hyperdynamic circulation and cirrhotic cardiomyopathy. Oxidative stress is often accompanied by inflammation; thus, blocking oxidative stress can minimize the systemic inflammatory response and alleviate the severity of cardiovascular diseases. The present review aims to elucidate the role of oxidative stress in cirrhosis-associated cardiovascular abnormalities and discusses possible therapeutic effects of antioxidants on cardiovascular complications of cirrhosis including hyperdynamic circulation, cirrhotic cardiomyopathy, and hepatorenal syndrome.
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Affiliation(s)
| | | | | | - Samuel S. Lee
- Liver Unit, University of Calgary Cumming School of Medicine, Calgary, AB T2N 4N1, Canada (H.H.N.); (S.Y.H.)
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25
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Jung CY, Chang JW. Hepatorenal syndrome: Current concepts and future perspectives. Clin Mol Hepatol 2023; 29:891-908. [PMID: 37050843 PMCID: PMC10577351 DOI: 10.3350/cmh.2023.0024] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Revised: 04/10/2023] [Accepted: 04/10/2023] [Indexed: 04/14/2023] Open
Abstract
Hepatorenal syndrome (HRS), a progressive but potentially reversible deterioration of kidney function, remains a major complication in patients with advanced cirrhosis, often leading to death before liver transplantation (LT). Recent updates in the pathophysiology, definition, and classification of HRS have led to a complete revision of the nomenclature and diagnostic criteria for HRS type 1, which was renamed HRS-acute kidney injury (AKI). HRS is characterized by severe impairment of kidney function due to increased splanchnic blood flow, activation of several vasoconstriction factors, severe vasoconstriction of the renal arteries in the absence of kidney histologic abnormalities, nitric oxide dysfunction, and systemic inflammation. Diagnosis of HRS remains a challenge because of the lack of specific diagnostic biomarkers that accurately distinguishes structural from functional AKI, and mainly involves the differential diagnosis from other forms of AKI, particularly acute tubular necrosis. The optimal treatment of HRS is LT. While awaiting LT, treatment options include vasoconstrictor drugs to counteract splanchnic arterial vasodilation and plasma volume expansion by intravenous albumin infusion. In patients with HRS unresponsive to pharmacological treatment and with conventional indications for kidney replacement therapy (KRT), such as volume overload, uremia, or electrolyte imbalances, KRT may be applied as a bridging therapy to transplantation. Other interventions, such as transjugular intrahepatic portosystemic shunt, and artificial liver support systems have a very limited role in improving outcomes in HRS. Although recently developed novel therapies have potential to improve outcomes of patients with HRS, further studies are warranted to validate the efficacy of these novel agents.
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Affiliation(s)
- Chan-Young Jung
- Division of Nephrology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jai Won Chang
- Division of Nephrology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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26
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Scheinberg AR, Martin P, Turkeltaub JA. Terlipressin in the management of liver disease. Expert Opin Pharmacother 2023; 24:1665-1671. [PMID: 37535437 DOI: 10.1080/14656566.2023.2244427] [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: 06/11/2023] [Revised: 07/26/2023] [Accepted: 08/01/2023] [Indexed: 08/05/2023]
Abstract
INTRODUCTION Terlipressin is a synthetic vasopressin analog which has been recently approved in the United States by the Food and Drug Administration for the treatment of hepatorenal syndrome. Terlipressin stimulates vasopressin receptors located on the smooth muscle vasculature of the splanchnic circulation and renal tubules which results in splanchnic vasoconstriction with improved renal perfusion and antidiuretic activity, respectively. AREAS COVERED In this review, we discuss available data regarding the FDA approved use of terlipressin, safety, and tolerability, as well as highlight alternative uses in chronic liver disease currently still under investigation. EXPERT OPINION Terlipressin is more efficacious compared to other vasoactive agents including midodrine octreotide and norepinephrine in reversal of hepatorenal syndrome and improves short-term survival. Other potential applications of terlipressin's vasoconstrictor actions reported in the literature include management of variceal hemorrhage and other complications of portal hypertension.
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Affiliation(s)
- Andrew R Scheinberg
- Department of Medicine, Division of Digestive Health and Liver Diseases, University of Miami, Miami, FL, USA
| | - Paul Martin
- Department of Medicine, Division of Digestive Health and Liver Diseases, University of Miami, Miami, FL, USA
| | - Joshua A Turkeltaub
- Department of Medicine, Division of Digestive Health and Liver Diseases, University of Miami, Miami, FL, USA
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27
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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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28
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Hannah N, Tjandra D, Patwardhan A, Rutland K, Halliday J, Sood S. Outpatient albumin infusions reduce hospitalizations and improve outcomes in decompensated cirrhosis: A real-world cohort study. JGH Open 2023; 7:537-544. [PMID: 37649856 PMCID: PMC10463019 DOI: 10.1002/jgh3.12944] [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: 03/09/2023] [Revised: 06/25/2023] [Accepted: 06/30/2023] [Indexed: 09/01/2023]
Abstract
Background and Aim Long-term human albumin (HA) infusions improve survival in cirrhotic patients with diuretic resistant ascites. We aimed to determine whether there is a significant benefit in a more unwell real-world cohort. Methods This is a single-center retrospective cohort study. Patients received outpatient HA between April 2017 and June 2021. Inclusion criteria were age ≥18 years, cirrhosis with ascites, and received at least 1 month of HA. Patients with significant comorbidities and ongoing alcohol use were not excluded. Outcomes assessed were transjugular intrahepatic portosystemic shunt (TIPS)/transplant-free survival (TTFS), and biochemical and prognostic outcomes. Results Twenty-four patients were included. Median age was 59.5 years. Seven were female (29.2%). Etiology included were alcohol (50%), non-alcoholic steatohepatitis (16.7%), and viral/alcohol (12.5%). Median model for end-stage liver disease-sodium (MELD-Na) was 18.5, with Child-Pugh scores (CPS) A (4.2%), B (50%), and C (45.8%). Improvements in serum sodium (P = 0.014), albumin (P = 0.003), and CPS (P = 0.017) were observed. Reduction in hospitalizations (P = 0.001), particularly portal hypertensive related admissions was observed (relative risk 0.39; 95% confidence interval [CI] 0.21-0.69, P = 0.003), needed to treat 2.09 (95% CI 1.25-3.67). There was a reduction in total paracentesis requirements (P = 0.005). On multivariate analysis, type 2 diabetes mellitus significantly increased risk of TIPS/transplant/death (hazard ratio 6.16; 95% CI 1.23-30.84, P = 0.027). Median TTFS improved in patients with a change in MELD-Na ≤1 at 1 month: 29.4 months versus 7.7 months (P = 0.011). Conclusion Outpatient HA infusions decrease portal hypertensive related hospital admissions, improve serum sodium, albumin levels, and CPS. Type 2 diabetes mellitus and change in MELD-Na score help discriminate those likely to benefit most.
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Affiliation(s)
- Nicholas Hannah
- Department of Gastroenterology and HepatologyRoyal Melbourne HospitalMelbourneVictoriaAustralia
- Melbourne Medical School, Faculty of Medicine, Dentistry and Health SciencesUniversity of MelbourneMelbourneVictoriaAustralia
- Department of GastroenterologyNorthern HealthMelbourneVictoriaAustralia
| | - Douglas Tjandra
- Department of GastroenterologyAlfred HealthMelbourneVictoriaAustralia
- Monash Medical School, Faculty of Medicine, Nursing and Health SciencesMelbourneVictoriaAustralia
| | - Ashwin Patwardhan
- Department of Gastroenterology and HepatologyRoyal Melbourne HospitalMelbourneVictoriaAustralia
| | - Kelsey Rutland
- Department of Gastroenterology and HepatologyRoyal Melbourne HospitalMelbourneVictoriaAustralia
| | - John Halliday
- Department of Gastroenterology and HepatologyRoyal Melbourne HospitalMelbourneVictoriaAustralia
| | - Siddharth Sood
- Melbourne Medical School, Faculty of Medicine, Dentistry and Health SciencesUniversity of MelbourneMelbourneVictoriaAustralia
- Department of GastroenterologyNorthern HealthMelbourneVictoriaAustralia
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29
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Calleri A, Alessandria C. Renal damage in Hepatorenal Syndrome: A still unsolved issue. Clin Res Hepatol Gastroenterol 2023; 47:102178. [PMID: 37453679 DOI: 10.1016/j.clinre.2023.102178] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 07/02/2023] [Accepted: 07/12/2023] [Indexed: 07/18/2023]
Abstract
Acute kidney injury (AKI) is a common complication of cirrhosis, burdened by high morbidity and mortality rates and progression to chronic kidney disease. Hepatorenal syndrome (HRS) is a peculiar type of functional AKI observed in cirrhotic patients with ascites. HRS diagnosis is still clinical, once pre-renal azotemia and intrinsic kidney damage have been excluded by applying well-established and internationally adopted criteria. HRS is considered reversible because of the absence of intrinsic renal damage. However, HRS reversibility has been questioned, due to the lack of response to treatment with vasoconstrictors plus albumin in a relevant percentage of patients and to the persistence of renal dysfunction in HRS patients who underwent liver transplantation (LT). Indeed, LT is the only ultimate treatment, as it solves both liver failure and portal hypertension. Thus, the presence of renal damage in HRS can be hypothesized. In this scenario, neutrophil gelatinase-associated lipocalin (NGAL), one of the most promising biomarkers, may help in characterizing the type of renal injury, distinguishing between HRS and acute tubular necrosis. This review gathers the available evidence in favor and against the presence of structural lesions in HRS in terms of either renal histology and urinary biomarkers with a particular focus on NGAL. The ability to properly characterize which component of renal dysfunction prevails - functional rather than structural - entails a relevant clinical impact for the treatment of these patients, both in terms of medical therapy and liver vs. combined liver-kidney transplantation.
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Affiliation(s)
- Alberto Calleri
- Division of Gastroenterology and Hepatology, Città della Salute e della Scienza Hospital, University of Turin, Italy
| | - Carlo Alessandria
- Division of Gastroenterology and Hepatology, Città della Salute e della Scienza Hospital, University of Turin, Italy.
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30
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Bai Z, Méndez-Sánchez N, Romeiro FG, Mancuso A, Philips CA, Tacke F, Basaranoglu M, Primignani M, Ibrahim M, Wong YJ, Nery FG, Teschke R, Ferreira CN, Muñoz AE, Pinyopornpanish K, Thevenot T, Singh SP, Mohanty A, Satapathy SK, Ridola L, Maruyama H, Cholongitas E, Levi Sandri GB, Yang L, Shalimar, Yang Y, Villa E, Krag A, Wong F, Jalan R, O’Brien A, Bernardi M, Qi X, the Liver Cirrhosis-related Complications (LCC)-International Special Interest Group. Use of albumin infusion for cirrhosis-related complications: An international position statement. JHEP Rep 2023; 5:100785. [PMID: 37456673 PMCID: PMC10339261 DOI: 10.1016/j.jhepr.2023.100785] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Revised: 04/06/2023] [Accepted: 04/18/2023] [Indexed: 07/18/2023] Open
Abstract
BACKGROUND & AIMS Numerous studies have evaluated the role of human albumin (HA) in managing various liver cirrhosis-related complications. However, their conclusions remain partially controversial, probably because HA was evaluated in different settings, including indications, patient characteristics, and dosage and duration of therapy. METHODS Thirty-three investigators from 19 countries with expertise in the management of liver cirrhosis-related complications were invited to organise an International Special Interest Group. A three-round Delphi consensus process was conducted to complete the international position statement on the use of HA for treatment of liver cirrhosis-related complications. RESULTS Twelve clinically significant position statements were proposed. Short-term infusion of HA should be recommended for the management of hepatorenal syndrome, large volume paracentesis, and spontaneous bacterial peritonitis in liver cirrhosis. Its effects on the prevention or treatment of other liver cirrhosis-related complications should be further elucidated. Long-term HA administration can be considered in specific settings. Pulmonary oedema should be closely monitored as a potential adverse effect in cirrhotic patients receiving HA infusion. CONCLUSIONS Based on the currently available evidence, the international position statement suggests the potential benefits of HA for the management of multiple liver cirrhosis-related complications and summarises its safety profile. However, its optimal timing and infusion strategy remain to be further elucidated. IMPACT AND IMPLICATIONS Thirty-three investigators from 19 countries proposed 12 position statements on the use of human albumin (HA) infusion in liver cirrhosis-related complications. Based on current evidence, short-term HA infusion should be recommended for the management of HRS, LVP, and SBP; whereas, long-term HA administration can be considered in the setting where budget and logistical issues can be resolved. However, pulmonary oedema should be closely monitored in cirrhotic patients who receive HA infusion.
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Affiliation(s)
- Zhaohui Bai
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
- Department of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, China
| | - Nahum Méndez-Sánchez
- Liver Research Unit, Medica Sur Clinic and Foundation, National Autonomous University of Mexico, Mexico City, Mexico
| | | | - Andrea Mancuso
- Medicina Interna 1, Azienda di Rilievo Nazionale ad Alta Specializzazione Civico-Di Cristina-Benfratelli, Palermo, Italy
| | - Cyriac Abby Philips
- Clinical and Translational Hepatology, The Liver Institute, Center of Excellence in GI Sciences, Rajagiri Hospital, Aluva, India
| | - Frank Tacke
- Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Metin Basaranoglu
- Division of Gastroenterology, Department of Internal Medicine, Bezmialem Vakif University, Istanbul, Turkey
| | - Massimo Primignani
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Mostafa Ibrahim
- Department of Gastroenterology and Hepatology, Theodor Bilharz Research Institute, Cairo, Egypt
| | - Yu Jun Wong
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
| | - Filipe Gaio Nery
- Serviço de Cuidados Intensivos, Unidade de Cuidados Intermédios Médico-Cirúrgica, Centro Hospitalar Universitário do Porto, Porto, Portugal
| | - Rolf Teschke
- Department of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, Germany
| | - Carlos Noronha Ferreira
- Serviço de Gastrenterologia e Hepatologia, Hospital de Santa Maria-Centro Hospitalar Universitário Lisboa Norte, Lisboa, Portugal
| | - Alberto E. Muñoz
- Sección Hepatología, Hospital Dr. Carlos B. Udaondo. Ciudad Autónoma de Buenos Aires, Argentina
| | - Kanokwan Pinyopornpanish
- Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Thierry Thevenot
- Centre Hospitalier Universitaire de Besançon, Hôpital Jean Minjoz, Service d’Hépatologie et de Soins Intensifs Digestifs, Besançon, France
| | | | - Arpan Mohanty
- Section of Gastroenterology, Boston Medical Center, Boston, MA, USA
| | - Sanjaya K. Satapathy
- Department of Internal Medicine, Division of Hepatology, Sandra Atlas Bass Center for Liver Diseases & Transplantation, Donald and Barbara Zucker School of Medicine for Hofstra/Northwell Health, Manhasset, New York, USA
| | - Lorenzo Ridola
- Department of Translational and Precision Medicine, “Sapienza” University of Rome, Rome, Italy
| | - Hitoshi Maruyama
- Department of Gastroenterology, Juntendo University, Hongo, Bunkyo-ku, Tokyo, Japan
| | - Evangelos Cholongitas
- First Department of Internal Medicine, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | | | - Li Yang
- Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, China
| | - Shalimar
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Yongping Yang
- Senior Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Erica Villa
- Department of Gastroenterology, University of Modena & Reggio Emilia and Azienda Ospedaliero-Universitaria di Modena, Italy
| | - Aleksander Krag
- Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Florence Wong
- Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - Rajiv Jalan
- Liver Failure Group, UCL Institute for Liver and Digestive Health, The Royal Free Hospital, University College London, London, UK
| | | | - Mauro Bernardi
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Xingshun Qi
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
- Department of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, China
| | - the Liver Cirrhosis-related Complications (LCC)-International Special Interest Group
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
- Department of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, China
- Liver Research Unit, Medica Sur Clinic and Foundation, National Autonomous University of Mexico, Mexico City, Mexico
- Internal Medicine Department, Botucatu Medical School, São Paulo, Brazil
- Medicina Interna 1, Azienda di Rilievo Nazionale ad Alta Specializzazione Civico-Di Cristina-Benfratelli, Palermo, Italy
- Clinical and Translational Hepatology, The Liver Institute, Center of Excellence in GI Sciences, Rajagiri Hospital, Aluva, India
- Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Berlin, Germany
- Division of Gastroenterology, Department of Internal Medicine, Bezmialem Vakif University, Istanbul, Turkey
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Gastroenterology and Hepatology, Theodor Bilharz Research Institute, Cairo, Egypt
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
- Serviço de Cuidados Intensivos, Unidade de Cuidados Intermédios Médico-Cirúrgica, Centro Hospitalar Universitário do Porto, Porto, Portugal
- Department of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, Germany
- Serviço de Gastrenterologia e Hepatologia, Hospital de Santa Maria-Centro Hospitalar Universitário Lisboa Norte, Lisboa, Portugal
- Sección Hepatología, Hospital Dr. Carlos B. Udaondo. Ciudad Autónoma de Buenos Aires, Argentina
- Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
- Centre Hospitalier Universitaire de Besançon, Hôpital Jean Minjoz, Service d’Hépatologie et de Soins Intensifs Digestifs, Besançon, France
- Kalinga Gastroenterology Foundation, Odisha, India
- Section of Gastroenterology, Boston Medical Center, Boston, MA, USA
- Department of Internal Medicine, Division of Hepatology, Sandra Atlas Bass Center for Liver Diseases & Transplantation, Donald and Barbara Zucker School of Medicine for Hofstra/Northwell Health, Manhasset, New York, USA
- Department of Translational and Precision Medicine, “Sapienza” University of Rome, Rome, Italy
- Department of Gastroenterology, Juntendo University, Hongo, Bunkyo-ku, Tokyo, Japan
- First Department of Internal Medicine, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
- Division of General Surgery and Liver Transplantation, San Camillo Hospital, Rome, Italy
- Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, China
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
- Senior Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
- Department of Gastroenterology, University of Modena & Reggio Emilia and Azienda Ospedaliero-Universitaria di Modena, Italy
- Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
- Department of Medicine, University of Toronto, Toronto, ON, Canada
- Liver Failure Group, UCL Institute for Liver and Digestive Health, The Royal Free Hospital, University College London, London, UK
- Division of Medicine, Royal Free Campus, London, UK
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
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Okushin K, Yamana H, Tateishi R, Sato M, Tsutsumi T, Matsui H, Fushimi K, Yasunaga H, Koike K, Fujishiro M. Treatment and outcome of hepatorenal syndrome in Japan: a retrospective cohort study using a national inpatient database. BMC Gastroenterol 2023; 23:218. [PMID: 37353737 DOI: 10.1186/s12876-023-02858-5] [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: 03/01/2023] [Accepted: 06/18/2023] [Indexed: 06/25/2023] Open
Abstract
BACKGROUND Hepatorenal syndrome (HRS) is a life-threatening complication of end-stage liver disease. This study aimed to clarify the status of HRS in Japan by analyzing the Japanese Diagnosis Procedure Combination database. METHODS Patients hospitalized for cirrhosis and HRS from July 2010 to March 2019 were sampled. They were divided into two groups according to their prognosis upon discharge: the transplant-free survival group and the death or liver transplantation group. The two groups' baseline patient characteristics and treatments were compared. RESULTS The mean age of the 1,412 participants was 67.3 years (standard deviation: 12.3 years), and 65.4% were male. The Child-Pugh grades was B and C in 18.8% and 81.2%, respectively. Hepatocellular carcinoma was present in 27.1% of the patients, and the proportion of spontaneous bacterial peritonitis was 2.3%. Albumin, noradrenaline, and dopamine were administered to 57.9%, 8.0%, and 14.9% of the patients, respectively; 7.0% of the patients underwent renal replacement therapy; and 5.0% were admitted to the intensive care unit. Intravenous antibiotics were administered to 30.8% of the patients. A total of 925 patients (65.5%) died or underwent liver transplantation. In addition to a higher proportion of patients with poor baseline liver function, the death or liver transplantation group included more males, patients with hepatocellular carcinoma, and those with spontaneous bacterial peritonitis. CONCLUSIONS HRS in Japan has a high mortality rate. Albumin was administered to over 50% of participants. Although noradrenaline is recommended in Japanese clinical guidelines, dopamine was more frequently used as a vasoconstrictor in clinical practice.
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Affiliation(s)
- Kazuya Okushin
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
- Department of Infection Control and Prevention, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hayato Yamana
- Data Science Center, Jichi Medical University, Shimotsuke, Japan
- Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan
| | - Ryosuke Tateishi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
| | - Masaya Sato
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Takeya Tsutsumi
- Department of Infection Control and Prevention, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hiroki Matsui
- Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan
| | - Kiyohide Fushimi
- Department of Health Policy and Informatics, Tokyo Medical and Dental University Graduate School, Tokyo, Japan
| | - Hideo Yasunaga
- Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan
| | - Kazuhiko Koike
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
- Kanto Central Hospital, Tokyo, Japan
| | - Mitsuhiro Fujishiro
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
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Cooper KM, Colletta A, Moulton K, Ralto KM, Devuni D. Kidney disease in patients with chronic liver disease: Does sex matter? World J Clin Cases 2023; 11:3980-3992. [PMID: 37388789 PMCID: PMC10303604 DOI: 10.12998/wjcc.v11.i17.3980] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Revised: 04/30/2023] [Accepted: 05/16/2023] [Indexed: 06/12/2023] Open
Abstract
Kidney disease in patients with liver disease is serious and increases mortality. Up to 50% of patients hospitalized experience an episode of acute kidney injury. In general, men with liver disease are thought to be at increased risk of kidney disease. However, this association should be considered with caution because most studies use creatinine-based inclusion criteria, which is negatively biased against women. In this review, we synthesize data on sex differences in kidney disease in patients with chronic liver disease in the clinical setting and discuss potential physiologic underpinnings.
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Affiliation(s)
- Katherine M Cooper
- Department of Medicine, UMass Chan Medical School, Worcester, MA 01665, United States
| | - Alessandro Colletta
- Department of Medicine, UMass Chan Medical School, Worcester, MA 01665, United States
| | - Kristen Moulton
- Department of Medicine, Division of Gastroenterology, UMass Chan Medical School, Worcester, MA 01665, United States
| | - Kenneth M Ralto
- Department of Medicine, Division of Renal Medicine, UMass Chan Medical School, Worcester, MA 01665, United States
| | - Deepika Devuni
- Department of Medicine, Division of Gastroenterology, UMass Chan Medical School, Worcester, MA 01665, United States
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33
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Terres AZ, Balbinot RS, Muscope ALF, Longen ML, Schena B, Cini BT, Rost Jr GL, Balensiefer JIL, Eberhardt LZ, Balbinot RA, Balbinot SS, Soldera J. Acute-on-chronic liver failure is independently associated with higher mortality for cirrhotic patients with acute esophageal variceal hemorrhage: Retrospective cohort study. World J Clin Cases 2023; 11:4003-4018. [PMID: 37388802 PMCID: PMC10303600 DOI: 10.12998/wjcc.v11.i17.4003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Revised: 04/15/2023] [Accepted: 05/12/2023] [Indexed: 06/12/2023] Open
Abstract
BACKGROUND Acute esophageal variceal hemorrhage (AEVH) is a common complication of cirrhosis and might precipitate multi-organ failure, causing acute-on-chronic liver failure (ACLF). AIM To analyze if the presence and grading of ACLF as defined by European Society for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) is able to predict mortality in cirrhotic patients presenting AEVH. METHODS Retrospective cohort study executed in Hospital Geral de Caxias do Sul. Data from medical records from 2010 to 2016 were obtained by searching the hospital electronic database for patients who received terlipressin. Medical records were reviewed in order to determine the diagnosis of cirrhosis and AEVH, including 97 patients. Kaplan-Meier survival analysis was used for univariate analysis and a stepwise approach to the Cox regression for multivariate analysis. RESULTS All- cause mortality for AEVH patients was 36%, 40.2% and 49.4% for 30-, 90- and 365-day, respectively. The prevalence of ACLF was 41.3%. Of these, 35% grade 1, 50% grade 2 and 15% grade 3. In multivariate analysis, the non-use of non-selective beta-blockers, presence and higher grading of ACLF and higher Model for End-Stage Liver Disease scores were independently associated with higher mortality for 30-day with the addition of higher Child-Pugh scores for 90-day period. CONCLUSION Presence and grading of ACLF according to the EASL-CLIF criteria was independently associated with higher 30- and 90-day mortality in cirrhotic patients admitted due to AEVH.
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Affiliation(s)
- Alana Zulian Terres
- Clinical Gastroenterology, Universidade de Caxias do Sul, Caxias do Sul 95020-002, Brazil
| | | | | | - Morgana Luisa Longen
- School of Medicine, Universidade de Caxias do Sul, Caxias do Sul 95020-002, Brazil
| | - Bruna Schena
- School of Medicine, Universidade de Caxias do Sul, Caxias do Sul 95020-002, Brazil
| | - Bruna Teston Cini
- School of Medicine, Universidade de Caxias do Sul, Caxias do Sul 95020-002, Brazil
| | | | | | | | - Raul Angelo Balbinot
- Clinical Gastroenterology, Universidade de Caxias do Sul, Caxias do Sul 95020-002, Brazil
| | | | - Jonathan Soldera
- Department of Gastroenterology, University of South Wales, Cardiff CF37 1DL, United Kingdom
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Ibáñez-Samaniego L, Baines A, Bañares R. Afectación renal en la enfermedad hepática crónica avanzada. Síndrome hepatorrenal. MEDICINE - PROGRAMA DE FORMACIÓN MÉDICA CONTINUADA ACREDITADO 2023; 13:4841-4849. [DOI: 10.1016/j.med.2023.06.010] [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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Long B, Gottlieb M. Emergency medicine updates: Spontaneous bacterial peritonitis. Am J Emerg Med 2023; 70:84-89. [PMID: 37244043 DOI: 10.1016/j.ajem.2023.05.015] [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: 03/30/2023] [Revised: 05/11/2023] [Accepted: 05/12/2023] [Indexed: 05/29/2023] Open
Abstract
INTRODUCTION Spontaneous bacterial peritonitis (SBP) is a common infection in patients with cirrhosis and ascites and is associated with significant risk of mortality. Therefore, it is important for emergency medicine clinicians to be aware of the current evidence regarding the diagnosis and management of this condition. OBJECTIVE This paper evaluates key evidence-based updates concerning SBP for the emergency clinician. DISCUSSION SBP is commonly due to Gram-negative bacteria, but infections due to Gram-positive bacteria and multidrug resistant bacteria are increasing. The typical presentation of SBP includes abdominal pain, worsening ascites, fever, or altered mental status in a patient with known liver disease; however, some patients may be asymptomatic or present with only mild symptoms. Paracentesis is the diagnostic modality of choice and should be performed in any patient with ascites and concern for SBP or upper gastrointestinal bleeding, or in those being admitted for a complication of cirrhosis. Ultrasound should be used to optimize the procedure. An ascites absolute neutrophil count (ANC) ≥ 250 cells/mm3 is diagnostic of SBP. Ascitic fluid should be placed in blood culture bottles to improve the culture yield. Leukocyte esterase reagent strips can be used for rapid diagnosis if available. While many patients will demonstrate coagulation panel abnormalities, routine transfusion is not recommended. Management traditionally includes a third-generation cephalosporin, but specific patient populations may require more broad-spectrum coverage with a carbapenem or piperacillin-tazobactam. Albumin infusion is associated with reduced risk of renal impairment and mortality. CONCLUSIONS An understanding of literature updates can improve the care of patients with suspected SBP.
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Affiliation(s)
- Brit Long
- SAUSHEC, Emergency Medicine, Brooke Army Medical Center, United States of America.
| | - Michael Gottlieb
- Department of Emergency Medicine, Rush University Medical Center, Chicago, IL, United States of America
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Yoo JJ, Park MY, Kim SG. Acute kidney injury in patients with acute-on-chronic liver failure: clinical significance and management. Kidney Res Clin Pract 2023; 42:286-297. [PMID: 37313610 DOI: 10.23876/j.krcp.22.264] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Accepted: 02/06/2023] [Indexed: 06/15/2023] Open
Abstract
Acute-on-chronic-liver failure (ACLF) refers to a phenomenon in which patients with chronic liver disease develop multiple organ failure due to acute exacerbation of underlying liver disease. More than 10 definitions of ACLF are extant around the world, and there is lack of consensus on whether extrahepatic organ failure is a main component or a consequence of ACLF. Asian and European consortiums have their own definitions of ACLF. The Asian Pacific Association for the Study of the Liver ACLF Research Consortium does not consider kidney failure as a diagnostic criterion for ACLF. Meanwhile, the European Association for the Study of the Liver Chronic Liver Failure and the North American Consortium for the Study of End-stage Liver Disease do consider kidney failure as an important factor in diagnosing and assessing the severity of ACLF. When kidney failure occurs in ACLF patients, treatment varies depending on the presence and stage of acute kidney injury (AKI). In general, the diagnosis of AKI in cirrhotic patients is based on the International Club of Ascites criteria: an increase of 0.3 mg/dL or more within 48 hours or a serum creatinine increase of 50% or more within one week. This study underscores the importance of kidney failure or AKI in patients with ACLF by reviewing its pathophysiology, prevention methods, and treatment approaches.
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Affiliation(s)
- Jeong-Ju Yoo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University School of Medicine, Bucheon, Republic of Korea
| | - Moo Yong Park
- Division of Nephrology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University School of Medicine, Bucheon, Republic of Korea
| | - Sang Gyune Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University School of Medicine, Bucheon, Republic of Korea
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Coxeter-Smith C, Al-Adhami A, Alrubaiy L. The Usefulness of Mayo End-stage Liver Disease (MELD) and MELD-Sodium (MELD-Na) Scores for Predicting Mortality in Cirrhotic Patients With Spontaneous Bacterial Peritonitis. Cureus 2023; 15:e38343. [PMID: 37143642 PMCID: PMC10151207 DOI: 10.7759/cureus.38343] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/30/2023] [Indexed: 05/06/2023] Open
Abstract
BACKGROUND Spontaneous bacterial peritonitis (SBP) is a common infection in patients with cirrhosis and ascites. Currently, the accuracy of the model for end-stage liver disease (MELD) and MELD-sodium (MELD-Na) as prognostic scores in this cohort is unclear. This study aimed to evaluate and compare the accuracy of MELD and MELD-Na for predicting 90-day mortality and determine whether the mortality risk estimates they provide accurately reflect the poor prognosis of patients with SBP Methods: Patients with cirrhosis and SBP were retrospectively identified from ascitic fluid samples sent for microscopy, culture and sensitivity analysis (1/1/18-31/12/20) and a previous audit. MELD and MELD-Na scores at diagnosis were calculated and associations with 90-day mortality were assessed using univariate analysis. Receiver operator characteristic curves were compared, and standardised mortality ratios (SMRs) were calculated by comparing the number of deaths observed to the number predicted by MELD and MELD-Na. RESULTS Of the 567 patients identified, 15 patients with cirrhosis and SBP were included. The 90-day mortality rate was 66.7% (10/15). Only concurrent hyponatremia (<135mmol/L) was associated with mortality (6/10 non-survivors vs 0/5 survivors, p=0.04). The difference in MELD and MELD-Na's C-statistic was not significant: 0.66 (95% Cl:0.35-0.98) vs 0.74 (95% Cl:0.47-1.0) respectively (p=0.72). Patients with a MELD-Na >18.5 had significantly higher 90-day mortality than patients with MELD-Na ≤18.5 (88.9% (8/9) vs. 33.3% (2/6), p=0.05). The SMR (95% Cl) for each MELD decile evaluated was 33.3 (0-79.5), 11.1 (0.2-22.0) and 3.4 (0-7.0) for scores ≤9,10-19 and 20-29 respectively. For each MELD-Na tertile, these were: 25 (0-59.6), 5.2 (0.1-10.3) and 2.7 (0.1-8.1) for scores <17,17-26, ≥27 respectively. CONCLUSION In a small cohort of patients with cirrhosis and SBP, the MELD's accuracy in predicting 90-day mortality was limited. MELD-Na's accuracy was higher but not significantly. Both scores consistently underestimated participants' mortality, therefore future studies could evaluate the accuracy of alternative prognostic scores in this patient group.
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Affiliation(s)
| | - Ali Al-Adhami
- Gastroenterology and Hepatology, St Mark's Hospital, London, GBR
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38
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Fuochi E, Anastasio L, Lynch EN, Campani C, Dragoni G, Milani S, Galli A, Innocenti T. Main factors influencing long-term outcomes of liver transplantation in 2022. World J Hepatol 2023; 15:321-352. [PMID: 37034235 PMCID: PMC10075010 DOI: 10.4254/wjh.v15.i3.321] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 11/24/2022] [Accepted: 02/22/2023] [Indexed: 04/11/2023] Open
Abstract
Liver transplant (LT) outcomes have markedly improved in the recent decades, even if long-term morbidity and mortality are still considerable. Most of late deaths are independent from graft function and different comorbidities, including complications of metabolic syndrome and de novo neoplasms, seem to play a key role in determining long-term outcomes in LT recipients. This review discusses the main factors associated with late mortality and suggests possible strategies to improve long-term management and follow-up after liver transplantation. In particular, the reduction of drug toxicity, the use of tools to identify high-risk patients, and setting up a multidisciplinary team also for long-term management of LT recipients may further improve survival after liver transplantation.
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Affiliation(s)
- Elisa Fuochi
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Lorenzo Anastasio
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Erica Nicola Lynch
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Claudia Campani
- Department of Experimental and Clinical Medicine, University of Florence, Florence 50134, Italy
| | - Gabriele Dragoni
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
- Department of Medical Biotechnologies, University of Siena, Siena 53100, Italy
| | - Stefano Milani
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Andrea Galli
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Tommaso Innocenti
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
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Singu BS, Ndeunyema MN, Ette EI, Pieper CH, Verbeeck RK. Plasma concentration and eGFR in preterm and term neonates receiving gentamicin or successive amikacin therapy. BMC Pediatr 2023; 23:24. [PMID: 36647065 PMCID: PMC9841723 DOI: 10.1186/s12887-023-03834-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Accepted: 01/02/2023] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND Gentamicin and amikacin are aminoglycoside antibiotics which are renally excreted and known to be nephrotoxic. Estimate of glomerular filtration rate (eGFR) per body surface area is lower in neonates than in adults and exposure to these drugs could lead to more suppression in kidney function. The aim of this study was to determine maximum and minimum plasma concentrations (Cmax and Cmin), time to reach Cmin levels of gentamicin and amikacin, and to assess eGFR in preterm and term neonates. METHODS Two groups of patients were recruited, 44 neonates receiving gentamicin (5 mg/kg/24 h) and 35 neonates receiving amikacin (15 mg/kg/24 h) by slow intravenous injection. Patients on amikacin had been on gentamicin before being switched to amikacin. Two blood samples were drawn for the determination of the maximum and minimum plasma concentration. Primary outcomes were determination of Cmax, Cmin, and the time it took to clear the aminoglycoside to a plasma concentration below the toxicity threshold (gentamicin: < 1 mcg/mL; amikacin: < 5 mcg/mL. RESULTS Therapeutic range for Cmax of gentamicin (15-25 mcg/mL) or amikacin (30-40 mcg/mL) was achieved in only 27.3 and 2.9% of neonates, respectively. Percentage of neonates reaching plasma concentrations below the toxicity threshold within the 24-hour dosing interval was 72.7% for gentamicin and 97.1% for amikacin. Positive correlation between gentamicin clearance and postnatal age borderline statistical significance (p = 0.007), while the correlation between amikacin clearance and postnatal age was poor and not statistically significant (r2 = - 0.30, p = 0.971). CONCLUSION Although eGFR decreased significantly as a function of postnatal age in neonates receiving amikacin, the majority (91.4%) of these neonates were able to clear the drug to < 5 mcg/mL within a 24-hour dosing interval.
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Affiliation(s)
- Bonifasius Siyuka Singu
- School of Pharmacy, Faculty of Health Sciences, University of Namibia, Private Bag, Windhoek, 13301 Namibia
| | - Milka Ndapandula Ndeunyema
- School of Pharmacy, Faculty of Health Sciences, University of Namibia, Private Bag, Windhoek, 13301 Namibia
| | - Ene I. Ette
- School of Pharmacy, Faculty of Health Sciences, University of Namibia, Private Bag, Windhoek, 13301 Namibia
| | | | - Roger Karel Verbeeck
- School of Pharmacy, Faculty of Health Sciences, University of Namibia, Private Bag, Windhoek, 13301 Namibia
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Abstract
The development of refractory ascites in approximately 10% of patients with decompensated cirrhosis heralds the progression to a more advanced stage of cirrhosis. Its pathogenesis is related to significant hemodynamic changes, initiated by portal hypertension, but ultimately leading to renal hypoperfusion and avid sodium retention. Inflammation can also contribute to the pathogenesis of refractory ascites by causing portal microthrombi, perpetuating the portal hypertension. Many complications accompany the development of refractory ascites, but renal dysfunction is most common. Management starts with continuation of sodium restriction, which needs frequent reviews for adherence; and regular large volume paracentesis of 5 L or more with albumin infusions to prevent the development of paracentesisinduced circulatory dysfunction. Albumin infusions independent of paracentesis may have a role in the management of these patients. The insertion of a covered, smaller diameter, transjugular intrahepatic porto-systemic stent shunt (TIPS) in the appropriate patients with reasonable liver reserve can bring about improvement in quality of life and improved survival after ascites clearance. Devices such as an automated low-flow ascites pump may be available in the future for ascites treatment. Patients with refractory ascites should be referred for liver transplant, as their prognosis is poor. In patients with refractory ascites and concomitant chronic kidney disease of more than stage 3b, assessment should be referred for dual liver-kidney transplants. In patients with very advanced cirrhosis not suitable for any definitive treatment for ascites control, palliative care should be involved to improve the quality of life of these patients.
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Affiliation(s)
- Florence Wong
- Division of Gastroenterology and Hepatology, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Canada,Corresponding author : Florence Wong Division of Gastroenterology and Hepatology, Toronto General Hospital, University Health Network, University of Toronto, 200 Elizabeth Street, Toronto Ontario M5G2C4, Canada Tel: +1-416-3403834, Fax: +1-416-3405019, E-mail:
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Early Albumin Infusion Is Associated With Greater Survival to Discharge Among Patients With Sepsis/Septic Shock Who Develop Severe Acute Kidney Injury Among Patients With Sepsis/Septic Shock Who Develop Severe Acute Kidney Injury. Crit Care Explor 2022; 4:e0793. [PMID: 36583206 PMCID: PMC9750554 DOI: 10.1097/cce.0000000000000793] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Adults hospitalized with sepsis/septic shock commonly develop acute kidney injury (AKI) which imposes a significant burden on the healthcare system. The administration of early human albumin in this patient population may yield more efficient healthcare resource utilization. Objectives To examine the association between early use of albumin and time to discharge in adults who develop severe AKI while hospitalized with sepsis/septic shock. Design Retrospective cohort study using de-identified electronic health records from a national database (Cerner Health Facts; Cerner Corp., Kansas City, MO). Setting and Participants Patients (n = 2,829) hospitalized between January 2013 and April 2018 with a diagnosis of sepsis/septic shock (identified using International Classification of Diseases, 9th Revision and 10th Revision codes) who developed severe AKI (stage 3 according to Kidney Disease Improving Global Outcomes criteria) during hospitalization (n = 2,845 unique encounters). Main Outcomes and Measures Patients were grouped according to timing of albumin exposure: within less than or equal to 24 hours of admission ("early albumin") or unexposed/exposed late ("nonearly albumin"). A cause-specific hazard model, censoring for death/discharge to hospice, was used to examine the association between "early albumin" and the rate of hospital discharge with clinical stability. Results Albumin was administered early in 8.6% of cases. Cases with early albumin administration had a median time to discharge of 13.2 days compared with 17.0 in the nonearly group (Log-rank p < 0.0001). An adjusted analysis showed that the rate of hospital discharge with clinical stability increased by 83% in the early albumin group compared with the nonearly group (hazard ratio, 1.832; 95% CI, 1.564-2.146; p < 0.001 nonearly group. Conclusions and Relevance The use of albumin within 24 hours of hospital admission was associated with a shorter time to discharge and a higher rate of discharge with clinical stability, suggesting an improvement in healthcare resource utilization among patients with sepsis/septic shock who developed stage 3 AKI during hospitalization.
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Tayek JA, Stolz AA, Nguyen DV, Fleischman MW, Donovan JA, Alcorn JM, Chao DCK, Asghar A, Morgan TR. A phase II, multicenter, open-label, randomized trial of pegfilgrastim for patients with alcohol-associated hepatitis. EClinicalMedicine 2022; 54:101689. [PMID: 36267499 PMCID: PMC9576807 DOI: 10.1016/j.eclinm.2022.101689] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Revised: 09/15/2022] [Accepted: 09/16/2022] [Indexed: 11/20/2022] Open
Abstract
Background In trials conducted in India, recombinant granulocyte colony stimulating factor (GCSF) improved survival in alcohol-associated hepatitis (AH). The aim of this trial was to determine the safety and efficacy of pegfilgrastim, a long-acting recombinant GCSF, in patients with AH in the United States. Methods This prospective, randomized, open label trial conducted between March 2017 and March 2020 randomized patients with a clinical diagnosis of AH and a Maddrey discriminant function score ≥32 to standard of care (SOC) or SOC+pegfilgrastim (0.6 mg subcutaneously) on Day 1 and Day 8 (clinicaltrials.gov NCT02776059). SOC was 28 days of either pentoxifylline or prednisolone, as determined by the patient's primary physician. The second injection of pegfilgrastim was not administered if the white blood cell count exceeded 30,000/mm3 on Day 8. Primary outcome was survival at Day 90. Secondary outcomes included the incidence of acute kidney injury (AKI), hepatorenal syndrome (HRS), hepatic encephalopathy, or infections. Findings The study was terminated early due to COVID19 pandemic. Eighteen patients were randomized to SOC and 16 to SOC+pegfilgrastim. All patients received prednisolone as SOC. Nine patients failed to receive a second dose of pegfilgrastin due to WBC > 30,000/mm3 on Day 8. Survival at 90 days was similar in both groups (SOC: 0.83 [95% confidence interval [CI]: 0.57-0.94] vs. pegfilgrastim: 0.73 [95% CI: 0.44-0.89]; p > 0.05; CI for difference: -0.18-0.38). The incidences of AKI, HRS, hepatic encephalopathy, and infections were similar in both treatment arms and there were no serious adverse events attributed to pegfilgrastim. Interpretation This phase II trial found no survival benefit at 90 days among subjects with AH who received pegfilgrastim+prednisolone compared with subjects receiving prednisolone alone. Funding was provided by the United States National Institutes of Health and National Institute on Alcohol Abuse and Alcoholism U01-AA021886 and U01-AA021884.
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Key Words
- ACLF, acute on chronic liver failure
- AH, alcohol-related hepatitis
- AKI, acute kidney injury
- Alcoholic hepatitis
- CTCAE, common terminology criteria for adverse events
- DF, discriminant function
- DSMB, data safety monitoring board
- FDA, food and drug administration
- FU, follow-up
- GCSF, granulocyte colony stimulating factor
- HIV, human immunodeficiency virus
- HRS, hepatorenal syndrome
- INR, international normalized ratio
- NIAAA, national institute on alcohol abuse and alcoholism
- Pegfilgrastim
- Phase II
- Randomized clinical trial
- SD, standard deviation
- SOC, standard of care
- WBC, white blood cell count
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Affiliation(s)
- John A. Tayek
- Department of Medicine, Harbor-UCLA Medical Center and Lundquist Institute, Torrance, CA, United States
| | - Andrew A. Stolz
- LAC-USC Medical Center, Los Angeles, CA and the Hepatology Section, Division of Medicine, University of Southern California, Los Angeles, CA, United States
| | - Danh V. Nguyen
- Division of General Internal Medicine, Department of Medicine, University of California, Irvine, CA, United States
| | - M. Wayne Fleischman
- Department of Medicine, Harbor-UCLA Medical Center and Lundquist Institute, Torrance, CA, United States
| | - John A. Donovan
- LAC-USC Medical Center, Los Angeles, CA and the Hepatology Section, Division of Medicine, University of Southern California, Los Angeles, CA, United States
| | - Joseph M. Alcorn
- Division of Gastroenterology, Department of Medicine University of New Mexico, Albuquerque, New Mexico and Medical Service, Raymond G. Murphy VA Medical Center, Albuquerque, NM, United States
| | - Daniel C-K. Chao
- Gastroenterology Section, Medical Service, VA Healthcare System, Loma Linda, CA, United States
| | - Aliya Asghar
- Research Service, VA Healthcare System, Long Beach, CA, United States
| | - Timothy R. Morgan
- Gastroenterology Section, Medical Service, VA Healthcare System, Long Beach, CA, United States
- Division of Gastroenterology, Department of Medicine, University of California, Irvine, CA, United States
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Allegretti AS, Subramanian RM, Francoz C, Olson JC, Cárdenas A. Respiratory events with terlipressin and albumin in hepatorenal syndrome: A review and clinical guidance. Liver Int 2022; 42:2124-2130. [PMID: 35838488 PMCID: PMC9762017 DOI: 10.1111/liv.15367] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Revised: 07/06/2022] [Accepted: 07/12/2022] [Indexed: 12/13/2022]
Abstract
Hepatorenal syndrome-acute kidney injury (HRS-AKI) is a serious complication of severe liver disease with a clinically poor prognosis. Supportive care using vasoconstrictors and intravenous albumin are the current mainstays of therapy. Terlipressin is an efficacious vasoconstrictor that has been used for 2 decades as the first-line treatment for HRS-AKI in Europe and has demonstrated greater efficacy in improving renal function compared to placebo and other vasoconstrictors. One of the challenges associated with terlipressin use is monitoring and mitigating serious adverse events, specifically adverse respiratory events, which were noted in a subset of patients in the recently published CONFIRM trial, the largest randomized trial examining terlipressin use for HRS-AKI. In this article, we review terlipressin's pharmacology, hypothesize how its mechanism contributes to the risk of respiratory compromise and propose strategies that will decrease the frequency of these events by rationally selecting patients at lower risk for these events.
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Affiliation(s)
- Andrew S. Allegretti
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Ram M. Subramanian
- Divisions of Gastroenterology and Hepatology and Pulmonary and Critical Care Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Claire Francoz
- Hepatology and Liver intensive Care Unit, Hospital Beaujon, Clichy, France
| | - Jody C. Olson
- Divisions of Gastroenterology, Hepatology, Pulmonary and Critical Care Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA
| | - Andrés Cárdenas
- GI and Liver Unit, Institut de Malalties Digestives, Hospital Clinic, Barcelona, Spain. Institut d'Investigacions Biomèdiques August Pi-Sunyer (IDIBAPS), Barcelona and Ciber de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain
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Shimada S, Shamaa T, Ivanics T, Kitajima T, Collins K, Rizzari M, Yoshida A, Abouljoud M, Moonka D, Lu M, Nagai S. Liver Transplant Recipient Characteristics Associated With Worse Post-Transplant Outcomes in Using Elderly Donors. Transpl Int 2022; 35:10489. [PMID: 36090776 PMCID: PMC9452632 DOI: 10.3389/ti.2022.10489] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Accepted: 08/10/2022] [Indexed: 12/03/2022]
Abstract
Advanced age of liver donor is a risk factor for graft loss after transplant. We sought to identify recipient characteristics associated with negative post-liver transplant (LT) outcomes in the context of elderly donors. Using 2014–2019 OPTN/UNOS data, LT recipients were classified by donor age: ≥70, 40–69, and <40 years. Recipient risk factors for one-year graft loss were identified and created a risk stratification system and validated it using 2020 OPTN/UNOS data set. At transplant, significant recipient risk factors for one-year graft loss were: previous liver transplant (adjusted hazard ratio [aHR] 4.37, 95%CI 1.98–9.65); mechanical ventilation (aHR 4.28, 95%CI 1.95–9.43); portal thrombus (aHR 1.87, 95%CI 1.26–2.77); serum sodium <125 mEq/L (aHR 2.88, 95%CI 1.34–6.20); and Karnofsky score 10–30% (aHR 2.03, 95%CI 1.13–3.65), 40–60% (aHR 1.65, 95%CI 1.08–2.51). Using those risk factors and multiplying HRs, recipients were divided into low-risk (n = 931) and high-risk (n = 294). Adjusted risk of one-year graft loss in the low-risk recipient group was similar to that of patients with younger donors; results were consistent using validation dataset. Our results show that a system of careful recipient selection can reduce the risks of graft loss associated with older donor age.
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Affiliation(s)
- Shingo Shimada
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Health System, Detroit, MI, United States
| | - Tayseer Shamaa
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Health System, Detroit, MI, United States
| | - Tommy Ivanics
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Health System, Detroit, MI, United States
| | - Toshihiro Kitajima
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Health System, Detroit, MI, United States
| | - Kelly Collins
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Health System, Detroit, MI, United States
| | - Michael Rizzari
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Health System, Detroit, MI, United States
| | - Atsushi Yoshida
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Health System, Detroit, MI, United States
| | - Marwan Abouljoud
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Health System, Detroit, MI, United States
| | - Dilip Moonka
- Division of Gastroenterology and Hepatology, Henry Ford Health System, Detroit, MI, United States
| | - Mei Lu
- Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, United States
| | - Shunji Nagai
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Health System, Detroit, MI, United States
- *Correspondence: Shunji Nagai,
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Martin SS, Kolaneci J, Czwikla R, Booz C, Gruenewald LD, Albrecht MH, Thompson ZM, Lenga L, Yel I, Vogl TJ, Wichmann JL, Koch V. Dual-Energy CT for the Detection of Portal Vein Thrombosis: Improved Diagnostic Performance Using Virtual Monoenergetic Reconstructions. Diagnostics (Basel) 2022; 12:1682. [PMID: 35885585 PMCID: PMC9317258 DOI: 10.3390/diagnostics12071682] [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: 06/08/2022] [Revised: 06/26/2022] [Accepted: 07/07/2022] [Indexed: 11/16/2022] Open
Abstract
Purpose: To investigate the diagnostic performance of noise-optimized virtual monoenergetic images (VMI+) in dual-energy CT (DECT) of portal vein thrombosis (PVT) compared to standard reconstructions. Method: This retrospective, single-center study included 107 patients (68 men; mean age, 60.1 ± 10.7 years) with malignant or cirrhotic liver disease and suspected PVT who had undergone contrast-enhanced portal-phase DECT of the abdomen. Linearly blended (M_0.6) and virtual monoenergetic images were calculated using both standard VMI and noise-optimized VMI+ algorithms in 20 keV increments from 40 to 100 keV. Quantitative measurements were performed in the portal vein for objective contrast-to-noise ratio (CNR) calculation. The image series showing the greatest CNR were further assessed for subjective image quality and diagnostic accuracy of PVT detection by two blinded radiologists. Results: PVT was present in 38 subjects. VMI+ reconstructions at 40 keV revealed the best objective image quality (CNR, 9.6 ± 4.3) compared to all other image reconstructions (p < 0.01). In the standard VMI series, CNR peaked at 60 keV (CNR, 4.7 ± 2.1). Qualitative image parameters showed the highest image quality rating scores for the 60 keV VMI+ series (median, 4) (p ≤ 0.03). The greatest diagnostic accuracy for the diagnosis of PVT was found for the 40 keV VMI+ series (sensitivity, 96%; specificity, 96%) compared to M_0.6 images (sensitivity, 87%; specificity, 92%), 60 keV VMI (sensitivity, 87%; specificity, 97%), and 60 keV VMI+ reconstructions (sensitivity, 92%; specificity, 97%) (p ≤ 0.01). Conclusions: Low-keV VMI+ reconstructions resulted in significantly improved diagnostic performance for the detection of PVT compared to other DECT reconstruction algorithms.
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Affiliation(s)
- Simon S. Martin
- Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, 60590 Frankfurt, Germany; (J.K.); (R.C.); (C.B.); (L.D.G.); (M.H.A.); (L.L.); (I.Y.); (T.J.V.); (J.L.W.); (V.K.)
- Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC 29425, USA;
| | - Jetlir Kolaneci
- Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, 60590 Frankfurt, Germany; (J.K.); (R.C.); (C.B.); (L.D.G.); (M.H.A.); (L.L.); (I.Y.); (T.J.V.); (J.L.W.); (V.K.)
| | - Rouben Czwikla
- Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, 60590 Frankfurt, Germany; (J.K.); (R.C.); (C.B.); (L.D.G.); (M.H.A.); (L.L.); (I.Y.); (T.J.V.); (J.L.W.); (V.K.)
| | - Christian Booz
- Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, 60590 Frankfurt, Germany; (J.K.); (R.C.); (C.B.); (L.D.G.); (M.H.A.); (L.L.); (I.Y.); (T.J.V.); (J.L.W.); (V.K.)
| | - Leon D. Gruenewald
- Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, 60590 Frankfurt, Germany; (J.K.); (R.C.); (C.B.); (L.D.G.); (M.H.A.); (L.L.); (I.Y.); (T.J.V.); (J.L.W.); (V.K.)
| | - Moritz H. Albrecht
- Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, 60590 Frankfurt, Germany; (J.K.); (R.C.); (C.B.); (L.D.G.); (M.H.A.); (L.L.); (I.Y.); (T.J.V.); (J.L.W.); (V.K.)
| | - Zachary M. Thompson
- Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC 29425, USA;
| | - Lukas Lenga
- Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, 60590 Frankfurt, Germany; (J.K.); (R.C.); (C.B.); (L.D.G.); (M.H.A.); (L.L.); (I.Y.); (T.J.V.); (J.L.W.); (V.K.)
| | - Ibrahim Yel
- Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, 60590 Frankfurt, Germany; (J.K.); (R.C.); (C.B.); (L.D.G.); (M.H.A.); (L.L.); (I.Y.); (T.J.V.); (J.L.W.); (V.K.)
| | - Thomas J. Vogl
- Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, 60590 Frankfurt, Germany; (J.K.); (R.C.); (C.B.); (L.D.G.); (M.H.A.); (L.L.); (I.Y.); (T.J.V.); (J.L.W.); (V.K.)
| | - Julian L. Wichmann
- Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, 60590 Frankfurt, Germany; (J.K.); (R.C.); (C.B.); (L.D.G.); (M.H.A.); (L.L.); (I.Y.); (T.J.V.); (J.L.W.); (V.K.)
| | - Vitali Koch
- Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, 60590 Frankfurt, Germany; (J.K.); (R.C.); (C.B.); (L.D.G.); (M.H.A.); (L.L.); (I.Y.); (T.J.V.); (J.L.W.); (V.K.)
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Duan Z, Jiang M, Huang X, Liu H, Yu H, Meng Q. Urinary Neutrophil Gelatinase-Associated Lipocalin Can Predict the Efficacy of Volume Expansion Therapy in Patients With Hepatitis B Cirrhosis and AKI. Front Pharmacol 2022; 13:839250. [PMID: 35784735 PMCID: PMC9240615 DOI: 10.3389/fphar.2022.839250] [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: 12/19/2021] [Accepted: 05/11/2022] [Indexed: 11/19/2022] Open
Abstract
Backgrounds: Kidney biomarkers in urine appear to be useful in differential diagnosis between acute tubular necrosis and other types of acute kidney injury (AKI) in cirrhosis. In clinical practice, prerenal azotemia (PRA) is often distinguished from other types of AKI by volume expansion therapy. The aim of the current study was to investigate the accuracy of urinary biomarkers in the differential diagnosis between PRA and other types of AKI. Methods: A total of 65 patients with hepatitis B cirrhosis were prospectively included and divided into AKI and non-AKI groups. Patients with hepatitis B cirrhosis and AKI discontinue diuretics, vasodilators, and nephrotoxic drugs and give volume expansion therapy. The efficacy was judged after 48 h of treatment. Urinary biomarkers were measured at the time of diagnosis of AKI and 48 h after volume expansion therapy. Univariate and multivariate analyses were used to identify independent risk factors for nonresponse to volume expansion therapy. Results: Of the 65 patients, 49 patients with newly diagnosed AKI were screened in the study, and 16 hospitalized patients with hepatitis B cirrhosis without AKI at the same period were screened as the control group. In patients with cirrhosis and AKI, 29 (59.18%) patients were in the response group and 20 (40.81%) patients were in the nonresponse group. The mortality rate in the nonresponse group was significantly higher than that in the response group (75% vs. 13.8% p < 0.001). After logistic regression analysis, urinary neutrophil gelatinase-associated lipocalin (NGAL) and serum creatinine (SCr) at diagnosis of AKI showed significant association with nonresponse to volume expansion therapy. The cutoff values for SCr and urinary NGAL were 128.50 µmol/L and 90.75 ng/ml, respectively. The area under the receiver operating curve (AUC) for SCr and urinary NGAL was 0.815 and 0.831. Conclusion: Elevated urinary NGAL can reflect the degree of kidney injury and is an independent risk factor for nonresponse to volume expansion therapy in patients with hepatitis B cirrhosis and AKI.
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Affiliation(s)
- Zhonghui Duan
- Department of Emergency, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Minjie Jiang
- Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Xiaojie Huang
- Department of Infectious Disease, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Haixia Liu
- Department of Intensive Care Medicine, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Hongwei Yu
- Department of Outpatient, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Qinghua Meng
- Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
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Abdelhafez M, Nayfeh T, Atieh A, AbuShamma O, Babaa B, Baniowda M, Hrizat A, Hasan B, Hassett L, Hamadah A, Gharaibeh K. Diagnostic Performance of Fractional Excretion of Sodium for the Differential Diagnosis of Acute Kidney Injury: A Systematic Review and Meta-Analysis. Clin J Am Soc Nephrol 2022; 17:785-797. [PMID: 35545442 PMCID: PMC9269645 DOI: 10.2215/cjn.14561121] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Accepted: 04/06/2022] [Indexed: 11/23/2022]
Abstract
BACKGROUND AND OBJECTIVES AKI is classified as prerenal, intrinsic, and postrenal. Prerenal AKI and intrinsic AKI represent the most common causes for AKI in hospitalized patients. This study aimed to examine the accuracy of the fractional excretion of sodium for distinguishing intrinsic from prerenal AKI. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, the Cochrane Library, and Scopus for all available studies that met the criteria until December 31, 2021. We included studies that evaluated fractional excretion of sodium in differentiating AKI etiologies in adults, whereas studies that did not have sufficient data to extract a 2×2 table were excluded. We assessed the methodologic quality using the Quality Assessment of Diagnostic Accuracy Studies-2 tool and extracted the diagnostic accuracy data for all included studies. We conducted a meta-analysis using the bivariate random effects model. We performed subgroup analysis to investigate sources of heterogeneity and the effect of the relevant confounders on fractional excretion of sodium accuracy. RESULTS We included 19 studies with 1287 patients. In a subset of 15 studies (872 patients) that used a threshold of 1%, the pooled sensitivity and specificity for differentiating intrinsic from prerenal AKI were 90% (95% confidence interval, 81% to 95%) and 82% (95% confidence interval, 70% to 90%), respectively. In a subgroup of six studies (511 patients) that included CKD or patients on diuretics, the pooled sensitivity and specificity were 83% (95% confidence interval, 64% to 93%) and 66% (95% confidence interval, 51% to 78%), respectively. In five studies with 238 patients on diuretics, the pooled sensitivity and specificity were 80% (95% confidence interval, 69% to 87%) and 54% (95% confidence interval, 31% to 75%), respectively. In eight studies with 264 oliguric patients with no history of CKD or diuretic therapy, the pooled sensitivity and specificity were 95% (95% confidence interval, 82% to 99%) and 91% (95% confidence interval, 83% to 95%), respectively. CONCLUSIONS Fractional excretion of sodium has a limited role for AKI differentiation in patients with a history of CKD or those on diuretic therapy. It is most valuable when oliguria is present.
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Affiliation(s)
- Mohammad Abdelhafez
- Department of Internal Medicine, Al-Quds University, Jerusalem, State of Palestine
| | - Tarek Nayfeh
- Evidence-Based Practice Research Program, Mayo Clinic, Rochester, Minnesota.,Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, Minnesota
| | - Anwar Atieh
- Department of Internal Medicine, Al-Quds University, Jerusalem, State of Palestine
| | - Omar AbuShamma
- Department of Internal Medicine, Al-Quds University, Jerusalem, State of Palestine
| | - Basheer Babaa
- Department of Internal Medicine, Al-Quds University, Jerusalem, State of Palestine
| | - Muath Baniowda
- Department of Internal Medicine, Al-Quds University, Jerusalem, State of Palestine
| | - Alaa Hrizat
- Department of Internal Medicine, Al-Quds University, Jerusalem, State of Palestine
| | - Bashar Hasan
- Evidence-Based Practice Research Program, Mayo Clinic, Rochester, Minnesota.,Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, Minnesota
| | - Leslie Hassett
- Mayo Clinic Libraries, Mayo Clinic, Rochester, Minnesota
| | | | - Kamel Gharaibeh
- Department of Internal Medicine, Al-Quds University, Jerusalem, State of Palestine .,Division of Pulmonary & Critical Care, University of Maryland, Baltimore, Maryland
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Heda R, Kovalic AJ, Satapathy SK. Peritransplant Renal Dysfunction in Liver Transplant Candidates. Clin Liver Dis 2022; 26:255-268. [PMID: 35487609 DOI: 10.1016/j.cld.2022.01.010] [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] [Indexed: 01/31/2023]
Abstract
Renal function is intricately tied to Model for End-Stage Liver Disease score and overall prognosis among patients with cirrhosis. The estimation of glomerular filtration rate (GFR) and etiology of renal impairment are even more magnified among cirrhotic patients in the period surrounding liver transplantation. Novel biomarkers including cystatin C and urinary neutrophil gelatinase-associated lipocalin have been demonstrated to more accurately assess renal dysfunction and aid in the diagnosis of competing etiologies. Accurately identifying the severity and chronicity of renal dysfunction among transplant candidates is an imperative component with respect to stratifying patients toward simultaneous liver-kidney transplantation versus liver transplantation alone.
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Affiliation(s)
- Rajiv Heda
- Department of Internal Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA
| | - Alexander J Kovalic
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health, Manhasset, NY 11030, USA
| | - Sanjaya K Satapathy
- Department of Medicine, Division of Hepatology, Sandra Atlas Bass Center for Liver Diseases and Transplantation, Manhasset, NY 11030, USA; Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Health, 400 Community Drive, Manhasset, NY 11030, USA.
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Velez JCQ. Hepatorenal Syndrome Type 1: From Diagnosis Ascertainment to Goal-Oriented Pharmacologic Therapy. KIDNEY360 2022; 3:382-395. [PMID: 35373127 PMCID: PMC8967638 DOI: 10.34067/kid.0006722021] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 12/02/2021] [Indexed: 05/05/2023]
Abstract
Hepatorenal syndrome type 1 (HRS-1) is a serious form of AKI that affects individuals with advanced cirrhosis with ascites. Prompt and accurate diagnosis is essential for effective implementation of therapeutic measures that can favorably alter its clinical course. Despite decades of investigation, HRS-1 continues to be primarily a diagnosis of exclusion. Although the diagnostic criteria dictated by the International Club of Ascites provide a useful framework to approach the diagnosis of HRS-1, they do not fully reflect the complexity of clinical scenarios that is often encountered in patients with cirrhosis and AKI. Thus, diagnostic uncertainty is often faced. In particular, the distinction between HRS-1 and acute tubular injury is challenging with the currently available clinical tools. Because treatment of HRS-1 differs from that of acute tubular injury, distinguishing these two causes of AKI has direct implications in management. Therefore, the use of the International Club of Ascites criteria should be enhanced with a more individualized approach and attention to the other phenotypic aspects of HRS-1 and other types of AKI. Liver transplantation is the most effective treatment for HRS-1, but it is only available to a small fraction of the affected patients worldwide. Thus, pharmacologic therapy is necessary. Vasoconstrictors aimed to increase mean arterial pressure constitute the most effective approach. Administration of intravenous albumin is an established co-adjuvant therapy. However, the risk for fluid overload in patients with cirrhosis with AKI is not negligible, and interventions intended to expand or remove volume should be tailored to the specific needs of the patient. Norepinephrine and terlipressin are the most effective vasoconstrictors, and their use should be determined by availability, ease of administration, and attention to optimal risk-benefit balance for each clinical scenario.
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Affiliation(s)
- Juan Carlos Q. Velez
- Department of Nephrology, Ochsner Health, New Orleans, Louisiana
- Ochsner Clinical School, University of Queensland, Brisbane, Australia
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Acute Kidney Injury in Patients with Liver Cirrhosis: Prevalence, Predictors, and In-Hospital Mortality at a District Hospital in Ghana. BIOMED RESEARCH INTERNATIONAL 2022; 2022:4589767. [PMID: 35237687 PMCID: PMC8885249 DOI: 10.1155/2022/4589767] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Revised: 11/30/2021] [Accepted: 02/11/2022] [Indexed: 12/16/2022]
Abstract
Background Acute kidney injury (AKI) is one of the most severe complications of cirrhosis and portends an ominous prognosis with an estimated mortality of about 50% in a month and 65% within a year. Infection and hypovolemia have been found to be the main precipitating factors of AKI in liver cirrhosis. Early detection and treatment of AKI may improve outcomes. AKI in patients with liver cirrhosis in Ghana and their impact on inpatient mortality are largely unknown. This study was aimed at determining the prevalence, precipitating factors, predictors, and in-hospital mortality of AKI in patients with liver cirrhosis admitted to a district hospital in Ghana. Methods Consecutive hospitalized patients with liver cirrhosis from 1 January 2018 to 30 April 2020 were recruited. Patient's demographic data and clinical features were collected using a standardized questionnaire. Biochemical and haematological tests as well as abdominal ultrasound scans were done for all patients. All patients were then followed up until discharge or death. Results There were 117 (65.4%) males out of the 179 patients with a mean age of 49.94 and 45.84 years for those with and without AKI, respectively. The prevalence of AKI was 27.9% (50/179). Out of 50 participants with AKI, 64.0% (32/50) died, contributing 41.0% of all in-patient mortality amongst participants. There was a significant association between AKI and death (p ≤ 0.001). The major precipitating factors of AKI were infections (60.0%), hypovolemia (20.0%) due to gastrointestinal bleeding and gastroenteritis, and refractory ascites (16.0%). Alkaline phosphatase, INR, model for end-stage liver disease sodium, sodium, and blood urea nitrogen were independent predictors of AKI. Conclusion AKI was common among patients with liver cirrhosis with high in-patient mortality. Identification of these precipitants and independent predictors of AKI may lead to prompt and targeted treatment with reduction in patient mortality.
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