1
|
Sikerwar S, Yao L, Elfarra Y, Jesudian A. Optimal Management of the Inpatient With Decompensated Cirrhosis. J Clin Gastroenterol 2025:00004836-990000000-00414. [PMID: 39889207 DOI: 10.1097/mcg.0000000000002143] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Accepted: 01/14/2025] [Indexed: 02/02/2025]
Abstract
Over the past several years, there has been a wealth of new data pertaining to the management of complications of cirrhosis, resulting in several important updates to best practices and consensus guidelines. Despite these advancements and numerous recent targeted quality initiatives, hospitalizations resulting from complications of cirrhosis remain frequent, costly and associated with poor patient outcomes. An emphasis on evidence-based management of hospitalized patients with decompensated cirrhosis has the potential to decrease readmission rates and length of stay while improving overall patient outcomes. Herein, we provide an updated, evidence-based overview of the optimal inpatient management of the most frequently encountered complications associated with cirrhosis.
Collapse
Affiliation(s)
- Sandeep Sikerwar
- NewYork-Presbyterian Hospital/Columbia University Medical Center
| | - Leah Yao
- NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY
| | - Yasmine Elfarra
- NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY
| | - Arun Jesudian
- NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY
| |
Collapse
|
2
|
Liu Q, He Y, Yang F, Guo G, Yang W, Wu L, Sun C. Development and external validation of Global Leadership Initiative on Malnutrition-dictated nomograms predicting long-term mortality in hospitalized patients with cirrhosis. Sci Prog 2025; 108:368504251320157. [PMID: 39967253 DOI: 10.1177/00368504251320157] [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: 02/20/2025]
Abstract
OBJECTIVES Global Leadership Initiative on Malnutrition (GLIM) criteria have gradually accounted for the mainstay evaluating nutritional status. We sought to establish GLIM-dictated nomograms with other prognostic factors influencing long-term mortality and externally validate their predictive performance in decompensated cirrhosis. METHODS The derivation cohort comprised 301 patients presenting with cirrhosis-associated acute insults, while the validation cohort encompassed 101 subjects from another tertiary hospital. Two nomograms were constructed to predict the 1-year all-cause mortality by integrating the GLIM criteria. The study population was stratified into low-, moderate- and high-risk mortality groups according to aforesaid proposed models. RESULTS Adjusting Child-Turcotte-Pugh classification (Nomo#1) or Model for End-stage Liver Disease-Sodium score (Nomo#2) separately, the GLIM criteria were independently associated with 1-year mortality in the multivariate Cox regression analysis (Nomo#1 hazard ratio (HR) = 3.139, p < 0.001; Nomo#2 HR = 3.456, p < 0.001). The C-index and time AUC for Nomo#1 and Nomo#2 performed significantly better than those of the GLIM criteria or conventional scoring systems alone. The survival rate of the low-risk group was significantly higher than those of the moderate- or high-risk groups (Nomo#1: 95% vs 65.8% vs 33.3%, p < 0.001; Nomo#2: 94.3% vs 64.5% vs 25%, p < 0.001). Furthermore, our proposed models exhibited moderate prediction accuracy and may identify malnourished patients with poor survival conditions in the external validation cohort. CONCLUSION GLIM criteria-defined malnutrition negatively impacted long-term mortality in the context of decompensated cirrhosis. Our established nomograms may predict survival status with sufficient discriminatory ability, alongside good consistency and clinical benefits, supporting their effectiveness in daily practice.
Collapse
Affiliation(s)
- Qing Liu
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
| | - Yumei He
- Department of Gastroenterology, The Third People's Hospital of Chengdu, Chengdu, China
| | - Fang Yang
- Department of Digestive System, Baodi Clinical College of Tianjin Medical University, Tianjin, China
| | - Gaoyue Guo
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
| | - Wanting Yang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
| | - Liping Wu
- Department of Gastroenterology, The Third People's Hospital of Chengdu, Chengdu, China
| | - Chao Sun
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
| |
Collapse
|
3
|
Trebicka J, Garcia-Tsao G. Controversies regarding albumin therapy in cirrhosis. Hepatology 2025; 81:288-303. [PMID: 37540192 PMCID: PMC11643133 DOI: 10.1097/hep.0000000000000521] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Accepted: 05/26/2023] [Indexed: 08/05/2023]
Abstract
Albumin is the most abundant protein in the human body and is synthetized exclusively by the liver. Therefore, serum albumin levels are reduced in acute and/or chronic liver disease. In cirrhosis, low levels of albumin predict the outcome. In advanced cirrhosis, the quality of albumin is decreased due to high oxidative stress and a proinflammatory state. Therefore, the administration of i.v. albumin would seem to be of pathophysiological relevance and benefit. Yet, the questions that remain are who, when, how much, and how often. While albumin infusion is recommended after large-volume paracentesis, at diagnosis of spontaneous bacterial peritonitis, in acute kidney injury, and in hepatorenal syndrome, the amount and schedule of albumin to be administered require refinement, particularly given complications related to volume overload that have become increasingly apparent. Other indications for albumin such as infections other than spontaneous bacterial peritonitis, hyponatremia, HE, prevention of poor outcomes in hospitalized, and in outpatients with cirrhosis are still debated. The results of studies in these settings are either negative, controversial, or inconclusive. This sheds some doubts regarding the use of albumin as a "one size fits all" strategy. The indication and patient selection are crucial and not always intuitive. The amount and frequency also seem to play a role in the success or failure of albumin. This review will critically discuss the evidence and underline areas where there are indications for albumin use and others where evidence is still insufficient and will have to await the development/results of randomized controlled trials.
Collapse
Affiliation(s)
- Jonel Trebicka
- Department of Internal Medicine B, University of Münster, Münster, Germany
- European Foundation for Study of Chronic Liver Failure, EASL-CLIF-Consortium, Barcelona, Spain
- Department of Gastroenterology and Hepatology, University of Southern Denmark, Odense, Denmark
| | - Guadalupe Garcia-Tsao
- Digestive Diseases Section, Department of Medicine, Yale University, New Haven, Connecticut, USA
- Digestive Diseases Section, Department of Medicine, VA-CT Healthcare System, West Haven, Connecticut, USA
| |
Collapse
|
4
|
Kalo E, Read S, Baig A, Marshall K, Ma WS, Crowther H, Gofton C, Lynch KD, Sood S, Holmes J, Lubel J, Wigg A, McCaughan G, Roberts SK, Caraceni P, Ahlenstiel G, Majumdar A. Efficacy of albumin use in decompensated cirrhosis and real-world adoption in Australia. JGH Open 2024; 8:e70029. [PMID: 39301299 PMCID: PMC11410680 DOI: 10.1002/jgh3.70029] [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: 05/01/2024] [Revised: 08/26/2024] [Accepted: 09/03/2024] [Indexed: 09/22/2024]
Abstract
The current treatment approach to patients with liver cirrhosis relies on the individual management of complications. Consequently, there is an unmet need for an overall therapeutic strategy for primary and secondary prevention of complications. The clinical potential of long-term albumin infusions supported by recent clinical trials has expanded its indications and holds promise to transform the management and secondary prevention of cirrhosis-related complications. This renewed interest in albumin comes with inherent controversies, compounding challenges and pressing need for rigorous evaluation of its clinical potential to capitalize on its therapeutic breakthroughs. Australia is among a few countries worldwide to adopt outpatient human albumin infusion. Here, we summarize currently available evidence of the potential benefits of human albumin for the management of multiple liver cirrhosis-related complications and discuss key challenges for wide application of long-term albumin administration strategy in Australian clinical practice. Australian Gastroenterological week (AGW), organised by the Gastroenterological Society of Australia (GESA), was held between 9-11 September 2022. A panel of hepatologists, advanced liver nurses and one haematologist, were invited to a roundtable meeting to discuss the use of long-term albumin infusions for liver cirrhosis. management in Australia. In this review, we summarise the proceedings of this meeting in context of the current literature.
Collapse
Affiliation(s)
- Eric Kalo
- Blacktown Clinical School and Research Centre, School of Medicine Western Sydney University Blacktown New South Wales Australia
- Blacktown Hospital, Western Sydney Local Health District Blacktown New South Wales Australia
| | - Scott Read
- Blacktown Clinical School and Research Centre, School of Medicine Western Sydney University Blacktown New South Wales Australia
- Blacktown Hospital, Western Sydney Local Health District Blacktown New South Wales Australia
- Storr Liver Centre, The Westmead Institute for Medical Research University of Sydney Westmead New South Wales Australia
| | - Asma Baig
- Blacktown Hospital, Western Sydney Local Health District Blacktown New South Wales Australia
| | - Kate Marshall
- Royal Prince Alfred Hospital Sydney New South Wales Australia
| | - Wai-See Ma
- Blacktown Hospital, Western Sydney Local Health District Blacktown New South Wales Australia
| | - Helen Crowther
- Blacktown Hospital, Western Sydney Local Health District Blacktown New South Wales Australia
| | - Cameron Gofton
- Storr Liver Centre, The Westmead Institute for Medical Research University of Sydney Westmead New South Wales Australia
- Department of Gastroenterology and Hepatology Royal North Shore Hospital St Leonards New South Wales Australia
| | - Kate D Lynch
- Department of Gastroenterology and Hepatology Royal Adelaide Hospital, Central Adelaide Local Health Network Adelaide South Australia Australia
- Faculty of Health and Medical Sciences University of Adelaide Adelaide South Australia Australia
| | - Siddharth Sood
- Department of Gastroenterology Northern Health Melbourne Victoria Australia
- Department of Medicine The University of Melbourne Parkville Victoria Australia
| | - Jacinta Holmes
- Department of Medicine The University of Melbourne Parkville Victoria Australia
- Department of Gastroenterology St Vincent's Hospital Fitzroy Victoria Australia
| | - John Lubel
- Department of Gastroenterology Alfred Health Melbourne Victoria Australia
- Central Clinical School Monash University Melbourne Victoria Australia
| | - Alan Wigg
- Hepatology and Liver Transplant Medicine Unit Southern Adelaide Local Health Network Adelaide South Australia Australia
- Flinders University of South Australia Adelaide South Australia Australia
| | - Geoff McCaughan
- A.W. Morrow Gastroenterology and Liver Centre Centenary Research Institute for Cancer Research and Cell Biology Camperdown New South Wales Australia
- Australian National Liver Transplant Unit Royal Prince Alfred Hospital Sydney New South Wales Australia
- Faculty of Medicine and Health University of Sydney Sydney New South Wales Australia
| | - Stuart K Roberts
- Department of Gastroenterology Alfred Health Melbourne Victoria Australia
- Central Clinical School Monash University Melbourne Victoria Australia
| | - Paolo Caraceni
- Unit of Semeiotics, Liver and Alcohol-Related Diseases IRCCS Azienda-Ospedaliera Universitaria di Bologna, EMR Bologna Italy
- Department of Medical and Surgical Sciences University of Bologna, EMR Bologna Italy
| | - Golo Ahlenstiel
- Blacktown Clinical School and Research Centre, School of Medicine Western Sydney University Blacktown New South Wales Australia
- Blacktown Hospital, Western Sydney Local Health District Blacktown New South Wales Australia
- Storr Liver Centre, The Westmead Institute for Medical Research University of Sydney Westmead New South Wales Australia
| | - Avik Majumdar
- Department of Medicine The University of Melbourne Parkville Victoria Australia
- Victorian Liver transplant Unit Austin Health Heidelberg Victoria Australia
| |
Collapse
|
5
|
Abedi F, Zarei B, Elyasi S. Albumin: a comprehensive review and practical guideline for clinical use. Eur J Clin Pharmacol 2024; 80:1151-1169. [PMID: 38607390 DOI: 10.1007/s00228-024-03664-y] [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: 07/25/2023] [Accepted: 03/04/2024] [Indexed: 04/13/2024]
Abstract
PURPOSE Nowadays, it is largely accepted that albumin should not be used in hypoalbuminemia or for nutritional purpose. The most discussed indication of albumin at present is the resuscitation in shock states, especially distributive shocks such as septic shock. The main evidence-based indication is also liver disease. In this review, we provided updated evidence-based instruction for definite and potential indications of albumin administration in clinical practice, with appropriate dosing and duration. METHODS Data collection was carried out until November 2023 by search of electronic databases including PubMed, Google Scholar, Scopus, and Web of Science. GRADE system has been used to determine the quality of evidence and strength of recommendations for each albumin indication. RESULTS A total of 165 relevant studies were included in this review. Fluid replacement in plasmapheresis and liver diseases, including hepatorenal syndrome, spontaneous bacterial peritonitis, and large-volume paracentesis, have a moderate to high quality of evidence and a strong recommendation for administering albumin. Moreover, albumin is used as a second-line and adjunctive to crystalloids for fluid resuscitation in hypovolemic shock, sepsis and septic shock, severe burns, toxic epidermal necrolysis, intradialytic hypotension, ovarian hyperstimulation syndrome, major surgery, non-traumatic brain injury, extracorporeal membrane oxygenation, acute respiratory distress syndrome, and severe and refractory edema with hypoalbuminemia has a low to moderate quality of evidence and weak recommendation to use. Also, in modest volume paracentesis, severe hyponatremia in cirrhosis has a low to moderate quality of evidence and a weak recommendation. CONCLUSION Albumin administration is most indicated in management of cirrhosis complications. Fluid resuscitation or treatment of severe and refractory edema, especially in patients with hypoalbuminemia and not responding to other treatments, is another rational use for albumin. Implementation of evidence-based guidelines in hospitals can be an effective measure to reduce inappropriate uses of albumin.
Collapse
Affiliation(s)
- Farshad Abedi
- Department of Clinical Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, P.O. Box, Mashhad, 91775-1365, Iran
| | - Batool Zarei
- Department of Clinical Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, P.O. Box, Mashhad, 91775-1365, Iran.
| | - Sepideh Elyasi
- Department of Clinical Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, P.O. Box, Mashhad, 91775-1365, Iran.
| |
Collapse
|
6
|
Velarde-Ruiz Velasco JA, Crespo J, Montaño-Loza A, Aldana-Ledesma JM, Cano-Contreras AD, Cerda-Reyes E, Fernández Pérez NJ, Castro-Narro GE, García-Jiménez ES, Lira-Vera JE, López-Méndez YI, Meza-Cardona J, Moreno-Alcántar R, Pérez-Escobar J, Pérez-Hernández JL, Tapia-Calderón DK, Higuera-de-la-Tijera F. Position paper on perioperative management and surgical risk in the patient with cirrhosis. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2024; 89:418-441. [PMID: 39003101 DOI: 10.1016/j.rgmxen.2024.05.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Accepted: 05/02/2024] [Indexed: 07/15/2024]
Abstract
INTRODUCTION Management of the patient with cirrhosis of the liver that requires surgical treatment has been relatively unexplored. In Mexico, there is currently no formal stance or expert recommendations to guide clinical decision-making in this context. AIMS The present position paper reviews the existing evidence on risks, prognoses, precautions, special care, and specific management or procedures for patients with cirrhosis that require surgical interventions or invasive procedures. Our aim is to provide recommendations by an expert panel, based on the best published evidence, and consequently ensure timely, quality, efficient, and low-risk care for this specific group of patients. RESULTS Twenty-seven recommendations were developed that address preoperative considerations, intraoperative settings, and postoperative follow-up and care. CONCLUSIONS The assessment and care of patients with cirrhosis that require major surgical or invasive procedures should be overseen by a multidisciplinary team that includes the anesthesiologist, hepatologist, gastroenterologist, and clinical nutritionist. With respect to decompensated patients, a nephrology specialist may be required, given that kidney function is also a parameter involved in the prognosis of these patients.
Collapse
Affiliation(s)
- J A Velarde-Ruiz Velasco
- Servicio de Gastroenterología, Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Jalisco, Mexico
| | - J Crespo
- Servicio de Aparato Digestivo, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain
| | - A Montaño-Loza
- División de Gastroenterología y Hepatología, Hospital de la Universidad de Alberta, Alberta, Canada
| | - J M Aldana-Ledesma
- Servicio de Gastroenterología, Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Jalisco, Mexico
| | - A D Cano-Contreras
- Instituto de Investigaciones Médico Biológicas, Universidad Veracruzana, Veracruz, Veracruz, Mexico
| | | | | | - G E Castro-Narro
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - E S García-Jiménez
- Servicio de Gastroenterología, Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Jalisco, Mexico
| | - J E Lira-Vera
- Servicio de Gastroenterología y Hepatología, Hospital Central «Dr. Ignacio Morones Prieto», San Luis Potosí, San Luis Potosí, Mexico
| | - Y I López-Méndez
- Departamento de Gastroenterología, Medica Sur, Mexico City, Mexico
| | - J Meza-Cardona
- Departamento de Gastroenterología, Hospital Español, Mexico City, Mexico
| | - R Moreno-Alcántar
- Departamento de Gastroenterología, Hospital de Especialidades «Dr. Bernando Sepúlveda», UMAE Centro Médico Nacional Siglo XXI, IMSS, Mexico City, Mexico
| | - J Pérez-Escobar
- Servicio de Gastroenterología y Unidad de Trasplante Hepático, Hospital Juárez de México, Mexico City, Mexico
| | - J L Pérez-Hernández
- Servicio de Gastroenterología y Hepatología, Hospital General de México «Dr. Eduardo Liceaga», Mexico City, Mexico
| | - D K Tapia-Calderón
- Servicio de Gastroenterología, Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Jalisco, Mexico
| | - F Higuera-de-la-Tijera
- Servicio de Gastroenterología y Hepatología, Hospital General de México «Dr. Eduardo Liceaga», Mexico City, Mexico.
| |
Collapse
|
7
|
Roy A, Giri S, Sharma S, Singh S, De A, Jalal P, Goenka M. Effectiveness of albumin infusion for the management of hyponatremia in decompensated cirrhosis: a systematic review. EGYPTIAN LIVER JOURNAL 2024; 14:41. [DOI: 10.1186/s43066-024-00350-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Accepted: 05/26/2024] [Indexed: 10/07/2024] Open
Abstract
Abstract
Background
Hyponatremia portends a poor prognosis in decompensated cirrhosis and is an independent predictor of mortality. Multiple modalities have been evaluated in the management of hyponatremia, including albumin infusion. However, the effect of albumin infusion on the resolution of hyponatremia is unclear. We conducted a systematic review to explore the available literature on the use of albumin infusion in hyponatremia.
Methods
We performed a comprehensive search up to 31st December 2022 using MEDLINE, EMBASE, and Scopus for studies reporting the effectiveness of albumin infusion in the resolution of hyponatremia. The impact of albumin infusion of any dose, administration frequency, and duration of therapy was recorded. The study protocol was prospectively registered (CRD42021245914).
Results
The literature search yielded 1322 references after duplicate removal. Only seven studies (three randomized trials, three cohort studies, and one case series) satisfied the predefined selection criteria after a full-text review. While hyponatremia was clearly defined as serum sodium < 130 meEq/L in all studies, two studies explicitly defined hyponatremia resolution (serum sodium > 135 mEq/L). No differentiation was made between the types of hyponatremia. The strength of the albumin infusion used was 5% and 20%. All but one study reported significant improvement in hyponatremia with albumin infusion. A subgroup analysis showed albumin infusion improved 30-day survival (odds ratio 0.43, 95% CI 0.25–0.74, I2 = 0.) No studies reported adverse events or the impact of concomitant associations (diuretic withdrawal, lactulose use, sepsis).
Conclusion
Despite available literature on the use of albumin infusion for the resolution of hyponatremia, the level of evidence remains low. Large prospective studies with pre-defined selection criteria and endpoints are required to generate the evidence.
Collapse
|
8
|
Khanna D, Kar P, Sahu P. Efficacy of long-term albumin therapy in the treatment of decompensated cirrhosis. Indian J Gastroenterol 2024; 43:494-504. [PMID: 38722510 DOI: 10.1007/s12664-024-01566-6] [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: 09/18/2023] [Accepted: 03/04/2024] [Indexed: 05/28/2024]
Abstract
BACKGROUND AND AIMS Decompensated liver cirrhosis has a poor prognosis, with a median overall survival of two to four years, which is worse than for many oncological disorders. These patients are highly susceptible to infections due to increased systemic inflammation leading to kidney failure and death. The aim was to study the efficacy of albumin in reducing episodes of decompensation, preventing bacterial infection, kidney dysfunction and mortality. METHOD Study involved patients with Child B or C cirrhosis with an albumin level below 3.0 g/dL, who were administered 20% human albumin weekly with standard medical treatment (SMT) for three months or till serum albumin levels were 4.0 g/dL (whichever is earlier) and compared with age and sex-matched controls who received only SMT. The primary end-point was six-month mortality and the secondary end-points were reduction in infections, kidney dysfunction, ascites recurrence, hepatic encephalopathy (HE), gastrointestinal (GI) bleed and complications of cirrhosis. RESULTS From September 2021 to January 2023, 88 cases and 86 controls were taken and followed up for six months. Overall, six-month survival was not statistically significant between groups (95.1% vs. 91.9%; p = 0·330). The incidence of recurrence of ascites (34.09% vs. 59.3%, p < 0.001), kidney dysfunction (6.8% vs. 24.4%, p < 0.001), HE (15.9% vs, 37.2%, p = 0.015), spontaneous bacterial peritonitis (SBP) (3.4% vs 17.4%, p = 0.002) and non-SBP infections (7.9% vs. 18.6%, p = 0.038) were significantly less in cases as compared with controls; however, GI bleed (14.8% vs. 17.4%, p = 0.632) was not statistically significant. CONCLUSION Long-term human albumin acts as a disease-modifying treatment in patients with decompensated cirrhosis.
Collapse
Affiliation(s)
- Deepanshu Khanna
- Department of Gastroenterology, Max Superspeciality Hospital, Vaishali, 201 012, India
| | - Premashis Kar
- Department of Gastroenterology, Max Superspeciality Hospital, Vaishali, 201 012, India.
| | - Pabitra Sahu
- Department of Gastroenterology, Max Superspeciality Hospital, Vaishali, 201 012, India
| |
Collapse
|
9
|
Kulkarni AV, Zuberi AA, Chaitanya K, Doolam H, Reddy S, Lakshmi PK, Godbole S, Shantan V, Iyengar S, Alla M, Sharma M, Reddy DN, Rao PN. Human albumin infusion is safe and effective even in patients without acute kidney injury and spontaneous bacterial peritonitis. Indian J Gastroenterol 2024; 43:485-493. [PMID: 38085502 DOI: 10.1007/s12664-023-01475-0] [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: 08/17/2023] [Accepted: 10/21/2023] [Indexed: 05/28/2024]
Abstract
BACKGROUND AND OBJECTIVES Human albumin (HA) solution is currently recommended only for patients with spontaneous bacterial peritonitis (SBP) and acute kidney injury (AKI). However, its use in hospitalized patients is quite frequent. The objective was to compare the outcomes of patients receiving HA in recommended (Gr. A) vs. non-recommended (Gr. B) indications. METHODS In this prospective study, consecutive hospitalized patients who received HA were included. Apart from comparing the proportion of patients achieving resolution of hyponatremia, infection and hepatic encephalopathy among Gr. A and Gr. B, we also compared the in-hospital survival and performed a sub-group analysis of patients with the European Association for the Study of the Liver (EASL) acute-on-chronic liver failure (ACLF) and decompensated cirrhosis (DC). RESULTS Of the 396 hospitalized patients who received HA, 180 had AKI and/or SBP (Gr. A), and 216 received albumin for non-recommended indications (Gr. B). The mean age, sex and etiology distribution were similar. The total dose of HA was higher (88 ± 61.62 g vs. 71.31 ± 488.17 g; p = 0.003) and the duration longer (4 ± 2.37 vs. 3.4 ± 1.82 days; p = 0.005) in Gr. A than B. The resolution of infection and HE was similar among both groups, while hyponatremia resolution was significantly higher in Gr. B (94.7%) than Gr. A (75.6%; p < 0.001). On Kaplan-Meier analysis, survival was significantly higher in Gr. B (94%) than Gr. A (78.9%; p < 0.001). The incidence of albumin-induced fluid overload was comparable (2.8% vs. 1.4%; p = 0.32). Patients with ACLF were sicker with a higher incidence of microbiologically proven infection, hepatic encephalopathy (HE) and hyponatremia than in the DC group. Resolution of infection and hyponatremia and in-hospital survival was significantly lower in the ACLF group (72.5%) than in the DC group (92.7%; p < 0.001). Eighty-six per cent of patients achieved resolution of ACLF. CONCLUSIONS HA infusion is safe and effective even in patients without AKI and SBP and leads to the resolution of infection, hyponatremia, HE and ACLF.
Collapse
Affiliation(s)
- Anand V Kulkarni
- Department of Hepatology, AIG Hospitals, Hyderabad, 500 032, India.
| | - Asim Ahmed Zuberi
- Department of Clinical Pharmacy, AIG Hospitals, Hyderabad, 500 032, India
| | - K Chaitanya
- Department of Clinical Pharmacy, AIG Hospitals, Hyderabad, 500 032, India
| | - Harshitha Doolam
- Department of Clinical Pharmacy, AIG Hospitals, Hyderabad, 500 032, India
| | - Santhosh Reddy
- Department of Clinical Pharmacy, AIG Hospitals, Hyderabad, 500 032, India
| | - P K Lakshmi
- Department of Pharmacy Practice, G. Pulla Reddy College of Pharmacy, Hyderabad, 500 028, India
| | | | | | - Sowmya Iyengar
- Department of Hepatology, AIG Hospitals, Hyderabad, 500 032, India
| | - Manasa Alla
- Department of Hepatology, AIG Hospitals, Hyderabad, 500 032, India
| | - Mithun Sharma
- Department of Hepatology, AIG Hospitals, Hyderabad, 500 032, India
| | | | - P N Rao
- Department of Hepatology, AIG Hospitals, Hyderabad, 500 032, India
| |
Collapse
|
10
|
Bolia R, Srivastava A. Ascites and Chronic Liver Disease in Children. Indian J Pediatr 2024; 91:270-279. [PMID: 37310583 DOI: 10.1007/s12098-023-04596-8] [Citation(s) in RCA: 2] [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: 11/30/2022] [Accepted: 03/17/2023] [Indexed: 06/14/2023]
Abstract
Development of ascites in children with chronic liver disease is the most common form of decompensation. It is associated with a poor prognosis and increased risk of mortality. A diagnostic paracentesis should be performed in liver disease patients with- new-onset ascites, at the beginning of each hospital admission and when ascitic fluid infection (AFI) is suspected. The routine analysis includes cell count with differential, bacterial culture, ascitic fluid total protein and albumin. A serum albumin-ascitic fluid albumin gradient of ≥1.1 g/dL confirms the diagnosis of portal hypertension. Ascites has been reported in children with non-cirrhotic liver disease like acute viral hepatitis, acute liver failure and extrahepatic portal venous obstruction. The main steps in management of cirrhotic ascites include dietary sodium restriction, diuretics and large-volume paracentesis. Sodium should be restricted to maximum of 2 mEq/kg/d (max 90 mEq/d) of sodium/day. Oral diuretic therapy comprises of aldosterone antagonists (e.g., spironolactone) with or without loop-diuretics (e.g., furosemide). Once the ascites is mobilized, the diuretics should be gradually tapered to the minimum effective dosage. Tense ascites should be managed with a large-volume paracentesis (LVP) preferably with albumin infusion. Therapeutic options for refractory ascites include recurrent LVP, transjugular intrahepatic porto-systemic shunt and liver transplantation. AFI (fluid neutrophil count ≥250/mm3) is an important complication, and requires prompt antibiotic therapy. Hyponatremia, acute kidney injury, hepatic hydrothorax and hernias are the other complications.
Collapse
Affiliation(s)
- Rishi Bolia
- Department of Gastroenterology, Hepatology and Liver Transplant, Queensland Children's Hospital, 501, Stanley Street, South Brisbane, Queensland, 4101, Australia
| | - Anshu Srivastava
- Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, 226014, India.
| |
Collapse
|
11
|
Yau AA, Buchkremer F. Hyponatremia in the Context of Liver Disease. ADVANCES IN KIDNEY DISEASE AND HEALTH 2024; 31:139-146. [PMID: 38649218 DOI: 10.1053/j.akdh.2023.12.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/16/2022] [Revised: 11/22/2023] [Accepted: 12/15/2023] [Indexed: 04/25/2024]
Abstract
Hyponatremia is common in patients with liver disease and is associated with increased mortality, morbidity, and a reduced quality of life. In liver transplantation, the inclusion of hyponatremia in organ allocation scores has reduced waitlist mortality. Portal hypertension and the resulting lowering of the effective arterial blood volume are important pathogenetic factors, but in most patients with liver disease, hyponatremia is multifactorial. Treatment requires a multifaceted approach that tries to reduce electrolyte-free water intake, restore urinary dilution, and increase nonelectrolyte solute excretion. Albumin therapy for hyponatremia is a peculiarity of advanced liver disease. Its use appears to be increasing, while the vaptans are currently only given in selected cases. Osmotic demyelination is a special concern in patients with liver disease. Serial checks of serum sodium concentrations and urine volume monitoring are mandatory.
Collapse
Affiliation(s)
- Amy A Yau
- Division of Nephrology, The Ohio State University, Columbus, OH
| | | |
Collapse
|
12
|
Schwarz C, Lindner G, Windpessl M, Knechtelsdorfer M, Saemann MD. [Consensus recommendations on the diagnosis and treatment of hyponatremia from the Austrian Society for Nephrology 2024]. Wien Klin Wochenschr 2024; 136:1-33. [PMID: 38421476 PMCID: PMC10904443 DOI: 10.1007/s00508-024-02325-5] [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] [Accepted: 01/03/2024] [Indexed: 03/02/2024]
Abstract
Hyponatremia is a disorder of water homeostasis. Water balance is maintained by the collaboration of renal function and cerebral structures, which regulate thirst mechanisms and secretion of the antidiuretic hormone. Measurement of serum-osmolality, urine osmolality and urine-sodium concentration help to diagnose the different reasons for hyponatremia. Hyponatremia induces cerebral edema and might lead to severe neurological symptoms, which need acute therapy. Also, mild forms of hyponatremia should be treated causally, or at least symptomatically. An inadequate fast increase of the serum sodium level should be avoided, because it raises the risk of cerebral osmotic demyelination. Basic pathophysiological knowledge is necessary to identify the different reasons for hyponatremia which need different therapeutic procedures.
Collapse
Affiliation(s)
- Christoph Schwarz
- Innere Medizin 1, Pyhrn-Eisenwurzenklinikum, Sierningerstr. 170, 4400, Steyr, Österreich.
| | - Gregor Lindner
- Zentrale Notaufnahme, Kepler Universitätsklinikum GmbH, Johannes-Kepler-Universität, Linz, Österreich
| | | | | | - Marcus D Saemann
- 6.Medizinische Abteilung mit Nephrologie und Dialyse, Klinik Ottakring, Wien, Österreich
- Medizinische Fakultät, Sigmund-Freud Universität, Wien, Österreich
| |
Collapse
|
13
|
Sikerwar S, Zand S, Steel P, Jesudian A. Management of patients with cirrhosis in the emergency department: Implications for hospitalization outcomes. Liver Transpl 2024; 30:94-102. [PMID: 37851401 DOI: 10.1097/lvt.0000000000000285] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Accepted: 10/11/2023] [Indexed: 10/19/2023]
Affiliation(s)
- Sandeep Sikerwar
- New York Presbyterian Weill Cornell Medical Center New York, New York, USA
- Columbia University Irving Medical Center, New York, New York, USA
| | - Sohrab Zand
- New York Presbyterian Weill Cornell Medical Center New York, New York, USA
| | - Peter Steel
- New York Presbyterian Weill Cornell Medical Center New York, New York, USA
| | - Arun Jesudian
- New York Presbyterian Weill Cornell Medical Center New York, New York, USA
| |
Collapse
|
14
|
Janičko M, Dražilová S, Gazda J, Tomáš M, Kučera M, Šuchová Ž, Jarčuška P. Clinical Significance and Management of Hyponatremia in Liver Cirrhosis. GASTROENTEROLOGY INSIGHTS 2023; 14:446-462. [DOI: 10.3390/gastroent14040033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2025] Open
Abstract
The overall prevalence of hyponatremia in cirrhotics is around 50%. Hypovolemic hyponatremia is a result of excessive fluid loss caused mostly by diuretic treatment or diarrhea. More common is hypervolemic hyponatremia, which results from excessive activation of water and sodium-retaining mechanisms caused by effective arterial hypovolemia. This review focuses on the associations of hyponatremia with clinical outcomes and reviews the available data on its management. Hyponatremia is a strong predictor of mortality and is also associated with an increased probability of hepatorenal syndrome, disturbance of consciousness, infections, and unfavorable post-transplant outcomes. In the management of hyponatremia, it is crucial to distinguish between hypovolemic and hypervolemic hyponatremia. The treatment of hypervolemic hyponatremia should be started only in symptomatic patients. The cessation of the treatment with traditional diuretics and fluid restriction may prevent further decrease in natremia. Pharmacological treatment is directed towards cirrhosis itself, precipitating factor, or hyponatremia directly. Currently, only albumin infusions can be recommended routinely. Other possibilities, such as vaptans, splanchnic vasoconstrictors, niravoline, or osmotic diuretics, are restricted to specific use cases (e.g., imminent liver transplantation) or need more research to determine their efficacy. We tried to summarize the management of hyponatremia into a concise flowchart.
Collapse
Affiliation(s)
- Martin Janičko
- 2nd Department of Internal Medicine, L. Pasteur University Hospital and PJ Safarik University in Kosice, Trieda SNP 1, 04011 Kosice, Slovakia
| | - Sylvia Dražilová
- 2nd Department of Internal Medicine, L. Pasteur University Hospital and PJ Safarik University in Kosice, Trieda SNP 1, 04011 Kosice, Slovakia
| | - Jakub Gazda
- 2nd Department of Internal Medicine, L. Pasteur University Hospital and PJ Safarik University in Kosice, Trieda SNP 1, 04011 Kosice, Slovakia
| | - Martin Tomáš
- 2nd Department of Internal Medicine, L. Pasteur University Hospital and PJ Safarik University in Kosice, Trieda SNP 1, 04011 Kosice, Slovakia
| | - Martin Kučera
- 2nd Department of Internal Medicine, L. Pasteur University Hospital and PJ Safarik University in Kosice, Trieda SNP 1, 04011 Kosice, Slovakia
| | - Želmíra Šuchová
- 2nd Department of Internal Medicine, L. Pasteur University Hospital and PJ Safarik University in Kosice, Trieda SNP 1, 04011 Kosice, Slovakia
| | - Peter Jarčuška
- 2nd Department of Internal Medicine, L. Pasteur University Hospital and PJ Safarik University in Kosice, Trieda SNP 1, 04011 Kosice, Slovakia
| |
Collapse
|
15
|
Ryu JY, Baek SH, Kim S. Evidence-based hyponatremia management in liver disease. Clin Mol Hepatol 2023; 29:924-944. [PMID: 37280091 PMCID: PMC10577348 DOI: 10.3350/cmh.2023.0090] [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: 03/03/2023] [Revised: 06/05/2023] [Accepted: 06/05/2023] [Indexed: 06/08/2023] Open
Abstract
Hyponatremia is primarily a water balance disorder associated with high morbidity and mortality. The pathophysiological mechanisms behind hyponatremia are multifactorial, and diagnosing and treating this disorder remains challenging. In this review, the classification, pathogenesis, and step-by-step management approaches for hyponatremia in patients with liver disease are described based on recent evidence. We summarize the five sequential steps of the traditional diagnostic approach: 1) confirm true hypotonic hyponatremia, 2) assess the severity of hyponatremia symptoms, 3) measure urine osmolality, 4) classify hyponatremia based on the urine sodium concentration and extracellular fluid status, and 5) rule out any coexisting endocrine disorder and renal failure. Distinct treatment strategies for hyponatremia in liver disease should be applied according to the symptoms, duration, and etiology of disease. Symptomatic hyponatremia requires immediate correction with 3% saline. Asymptomatic chronic hyponatremia in liver disease is prevalent and treatment plans should be individualized based on diagnosis. Treatment options for correcting hyponatremia in advanced liver disease may include water restriction; hypokalemia correction; and administration of vasopressin antagonists, albumin, and 3% saline. Safety concerns for patients with liver disease include a higher risk of osmotic demyelination syndrome.
Collapse
Affiliation(s)
- Ji Young Ryu
- Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Korea
| | - Seon Ha Baek
- Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Korea
| | - Sejoong Kim
- Department of Internal Medicine, Seoul University Bundang Hospital, Seongnam, Korea
- Center for Artificial Intelligence in Healthcare, Seoul University Bundang Hospital, Seongnam, Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| |
Collapse
|
16
|
Fatima I, Jahagirdar V, Kulkarni AV, Reddy R, Sharma M, Menon B, Reddy DN, Rao PN. Liver Transplantation: Protocol for Recipient Selection, Evaluation, and Assessment. J Clin Exp Hepatol 2023; 13:841-853. [PMID: 37693258 PMCID: PMC10483012 DOI: 10.1016/j.jceh.2023.04.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Accepted: 04/13/2023] [Indexed: 09/12/2023] Open
Abstract
Liver transplantation (LT) is the definitive therapy for patients with end-stage liver disease, acute liver failure, acute-on-chronic liver failure, hepatocellular carcinoma, and metabolic liver diseases. The acceptance of LT in Asia has been gradually increasing and so is the expertise to perform LT. Preparing a patient with cirrhosis for LT is the most important aspect of a successful LT. The preparation for LT begins with the first index decompensation for a patient with cirrhosis. Patients planned for LT should undergo a thorough screening for infections, and a complete cardiac, pulmonology, and psychosocial evaluation pre-LT. In this review, we discuss the indications and contraindications of LT and the evaluation and assessment of patients with liver disease planned for LT.
Collapse
Affiliation(s)
- Ifrah Fatima
- University of Missouri-Kansas City School of Medicine, MO, USA
| | | | | | - Raghuram Reddy
- Department of Liver Transplantation Surgery, AIG Hospitals, Hyderabad, India
| | - Mithun Sharma
- Department of Hepatology, AIG Hospitals, Hyderabad, India
| | - Balchandran Menon
- Department of Liver Transplantation Surgery, AIG Hospitals, Hyderabad, India
| | | | | |
Collapse
|
17
|
Singh V, De A, Mehtani R, Angeli P, Maiwall R, Satapathy S, Singal AK, Saraya A, Sharma BC, Eapen CE, Rao PN, Shukla A, Shalimar, Choudhary NS, Alcantara-Payawal D, Arora V, Aithal G, Kulkarni A, Roy A, Shrestha A, Mamun Al Mahtab, Niriella MA, Siam TS, Zhang CQ, Huei LG, Yu ML, Roberts SK, Peng CY, Chen T, George J, Wong V, Yilmaz Y, Treeprasertsuk S, Kurniawan J, Kim SU, Younossi ZM, Sarin SK. Asia-Pacific association for study of liver guidelines on management of ascites in liver disease. Hepatol Int 2023; 17:792-826. [PMID: 37237088 DOI: 10.1007/s12072-023-10536-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2022] [Accepted: 04/08/2023] [Indexed: 05/28/2023]
Affiliation(s)
- Virendra Singh
- Punjab Institute of Liver and Biliary Sciences, Mohali, Punjab, India.
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
| | - Arka De
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Rohit Mehtani
- Department of Hepatology, Amrita Institute of Medical Sciences and Research, Faridabad, India
| | - Paolo Angeli
- Department of Internal Medicine and Hepatology, University of Padova, Padua, Italy
| | - Rakhi Maiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Sanjaya Satapathy
- Division of Hepatology, Sandra Atlas Bass Center for Liver Diseases and Transplantation, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Health, Manhasset, NY, USA
| | - Ashwini K Singal
- University of South Dakota Sanford School of Medicine, Sioux Falls, USA
| | - Anoop Saraya
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - B C Sharma
- Department of Gastroenterology, G.B. Pant Hospital, New Delhi, Delhi, India
| | - C E Eapen
- Department of Hepatology, Christian Medical College, Vellore, India
| | - P N Rao
- Department of Hepatology, AIG Hospitals, Hyderabad, India
| | - Akash Shukla
- Department of Gastroenterology, Lokmanya Tilak Municipal General Hospital and Lokmanya Tilak Municipal Medical College, Sion, Mumbai, India
| | - Shalimar
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | | | | | - Vinod Arora
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Guru Aithal
- Biomedical Research Unit, NIHR Nottingham Digestive Diseases, Nottingham, UK
| | - Anand Kulkarni
- Department of Hepatology, AIG Hospitals, Hyderabad, India
| | - Akash Roy
- Institute of Gastrosciences and Liver Transplantation, Apollo Multispeciality Hospitals, Kolkata, India
| | - Ananta Shrestha
- Department of Hepatology, The Liver Clinic, Liver Foundation, Kathmandu, Nepal
| | - Mamun Al Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Madunil A Niriella
- Department of Medicine, Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka
| | - Tan Soek Siam
- Department of Hepatology, Hospital Selayang, Selangor Darul Ehsan, Malaysia
| | - Chun-Qing Zhang
- Department of Gastroenterology, Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Lee Guan Huei
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Ming-Lung Yu
- School of Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-Sen University, Kaohsiung, Taiwan
| | | | - Cheng-Yuan Peng
- Centre for Digestive Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan
| | - Tao Chen
- Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jacob George
- University of Sydney School of Medicine, Sydney, Australia
| | - Vincent Wong
- Mok Hing Yiu Professor of Medicine, Department of Medicine and Therapeutics, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China
| | - Yusuf Yilmaz
- Liver Research Unit, Institute of Gastroenterology, Marmara University, Istanbul, Turkey
- Department of Gastroenterology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey
| | | | - Juferdy Kurniawan
- Hepatobiliary Division, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Hospital Jakarta, Jakarta, Indonesia
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | | | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| |
Collapse
|
18
|
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. 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: 10] [Impact Index Per Article: 5.0] [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.
Collapse
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
| |
Collapse
|
19
|
Urushima H, Matsubara T, Miyakoshi M, Kimura S, Yuasa H, Yoshizato K, Ikeda K. Hypo-osmolarity induces apoptosis resistance via TRPV2-mediated AKT-Bcl-2 pathway. Am J Physiol Gastrointest Liver Physiol 2023; 324:G219-G230. [PMID: 36719093 PMCID: PMC9988531 DOI: 10.1152/ajpgi.00138.2022] [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: 05/27/2022] [Revised: 12/30/2022] [Accepted: 01/23/2023] [Indexed: 02/01/2023]
Abstract
In cirrhosis, several molecular alterations such as resistance to apoptosis could accelerate carcinogenesis. Recently, mechanotransduction has been attracting attention as one of the causes of these disturbances. In patients with cirrhosis, the serum sodium levels progressively decrease in the later stage of cirrhosis, and hyponatremia leads to serum hypo-osmolality. Since serum sodium levels in patients with cirrhosis with liver cancer are inversely related to cancer's number, size, stage, and cumulative survival, we hypothesized that hypo-osmolality-induced mechanotransduction under cirrhotic conditions might contribute to oncogenesis and/or progression of hepatocellular carcinoma (HCC). In this study, we adjusted osmosis of culture medium by changing the sodium chloride concentration and investigated the influence of hypotonic conditions on the apoptosis resistance of an HCC cell line, HepG2, using a serum-deprivation-induced apoptosis model. By culturing the cells in a serum-free medium, the levels of an antiapoptotic protein Bcl-2 were downregulated. In contrast, the hypotonic conditions caused apoptosis resistance by upregulation of Bcl-2. Next, we examined which pathway was involved in the apoptosis resistance. Hypotonic conditions enhanced AKT signaling, and constitutive activation of AKT in HepG2 cells led to upregulation of Bcl-2. Moreover, we revealed that the enhancement of AKT signaling was caused by intracellular calcium influx via a mechanosensor, TRPV2. Our findings suggested that hyponatremia-induced serum hypotonic in patients with cirrhosis promoted the progression of hepatocellular carcinoma.NEW & NOTEWORTHY Our study first revealed that hypo-osmolarity-induced mechanotransduction enhanced calcium-mediated AKT signaling via TRPV2 activation, resulting in contributing to apoptosis resistance. The finding indicates a possible view that liver cirrhosis-induced hyponatremia promotes hepatocellular carcinogenesis.
Collapse
Affiliation(s)
- Hayato Urushima
- Department of Anatomy and Regenerative Biology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Tsutomu Matsubara
- Department of Anatomy and Regenerative Biology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Masaaki Miyakoshi
- Department of Maxillofacial Radiology, Graduate School of Medical and Dental Sciences Field of Oncology, Kagoshima University, Kagoshima, Japan
| | - Shioko Kimura
- Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States
| | - Hideto Yuasa
- Department of Anatomy and Regenerative Biology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Katsutoshi Yoshizato
- Endowed Laboratory of Synthetic Biology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Kazuo Ikeda
- Department of Anatomy and Regenerative Biology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| |
Collapse
|
20
|
Correction and Prevention of Hyponatremia in Patients With Cirrhosis and Ascites: Post Hoc Analysis of the ANSWER Study Database. Am J Gastroenterol 2023; 118:168-173. [PMID: 36087106 DOI: 10.14309/ajg.0000000000001995] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Accepted: 08/15/2022] [Indexed: 01/28/2023]
Abstract
INTRODUCTION We assessed the impact of long-term albumin administration to hyponatremic patients with ascites enrolled in the ANSWER trial. METHODS The normalization rate of baseline hyponatremia and the 18-month incidence rate of at least moderate hyponatremia were evaluated. RESULTS The hyponatremia normalization rate was higher with albumin than with standard medical treatment (45% vs 28%, P = 0.042 at 1 month). Long-term albumin ensured a lower incidence of at least moderate hyponatremia than standard medical treatment (incidence rate ratio: 0.245 [CI 0.167-0.359], P < 0.001). DISCUSSION Long-term albumin administration improves hyponatremia and reduces episodes of at least moderate hyponatremia in outpatients with cirrhosis and ascites.
Collapse
|
21
|
Bai Z, Xu W, Chai L, Zheng X, Méndez-Sánchez N, Philips CA, Cheng G, Qi X. Effects of Short-Term Human Albumin Infusion for the Prevention and Treatment of Hyponatremia in Patients with Liver Cirrhosis. J Clin Med 2022; 12:jcm12010107. [PMID: 36614908 PMCID: PMC9821044 DOI: 10.3390/jcm12010107] [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: 11/21/2022] [Revised: 12/10/2022] [Accepted: 12/16/2022] [Indexed: 12/24/2022] Open
Abstract
Background: Human albumin (HA) infusion is potentially effective for the management of hyponatremia in liver cirrhosis, but the current evidence is very limited. Methods: In this retrospective study, 2414 cirrhotic patients who were consecutively admitted to our hospital between January 2010 and June 2014 were included in the Hospitalization outcome cohort, and 339 cirrhotic patients without malignancy who were consecutively admitted to our department between December 2014 and April 2021 were included in the Long-term outcome cohort. The development and improvement of hyponatremia were compared between patients who received HA infusion during hospitalizations and did not. Logistic and Cox regression analyses were performed to evaluate the association of development and improvement of hyponatremia during hospitalizations with the outcomes. Odds ratios (ORs) and hazard ratios (HRs) were calculated. Results: In the two cohorts, HA infusion significantly decreased the incidence of hyponatremia and increased the rate of improvement of hyponatremia in cirrhotic patients during hospitalizations. In the Hospitalization outcome cohort, the development of hyponatremia during hospitalizations was significantly associated with increased in-hospital mortality (OR = 2.493, p < 0.001), and the improvement of hyponatremia during hospitalizations was significantly associated with decreased in-hospital mortality (OR = 0.599, p = 0.014). In the Long-term outcome cohort, the development of hyponatremia during hospitalizations was significantly associated with decreased long-term survival (HR = 0.400, p < 0.001), and the improvement of hyponatremia during hospitalizations was not significantly associated with long-term survival (HR = 1.085, p = 0.813). Conclusions: HA infusion can effectively prevent the development of hyponatremia and improve hyponatremia in cirrhotic patients during hospitalizations, which may influence the patients’ outcomes.
Collapse
Affiliation(s)
- Zhaohui Bai
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, China
- NMPA Key Laboratory for Research and Evaluation of Drug Regulatory Technology, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Wentao Xu
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, China
- NMPA Key Laboratory for Research and Evaluation of Drug Regulatory Technology, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Lu Chai
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, China
- NMPA Key Laboratory for Research and Evaluation of Drug Regulatory Technology, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Xiaojie Zheng
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, China
| | - Nahum Méndez-Sánchez
- Medica Sur Clinic, National Autonomous University of Mexico, Mexico City 14050, Mexico
| | - Cyriac Abby Philips
- Clinical and Translational Hepatology, The Liver Institute, Center of Excellence in GI Sciences, Rajagiri Hospital, Aluva 683112, India
| | - Gang Cheng
- NMPA Key Laboratory for Research and Evaluation of Drug Regulatory Technology, Shenyang Pharmaceutical University, Shenyang 110016, China
- Correspondence: (G.C.); (X.Q.)
| | - Xingshun Qi
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, China
- NMPA Key Laboratory for Research and Evaluation of Drug Regulatory Technology, Shenyang Pharmaceutical University, Shenyang 110016, China
- Correspondence: (G.C.); (X.Q.)
| |
Collapse
|
22
|
Bai Z, Wang L, Lin H, Tacke F, Cheng G, Qi X. Use of Human Albumin Administration for the Prevention and Treatment of Hyponatremia in Patients with Liver Cirrhosis: A Systematic Review and Meta-Analysis. J Clin Med 2022; 11:jcm11195928. [PMID: 36233795 PMCID: PMC9572637 DOI: 10.3390/jcm11195928] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2022] [Revised: 09/15/2022] [Accepted: 09/28/2022] [Indexed: 11/16/2022] Open
Abstract
Background. Hyponatremia is a common complication of liver cirrhosis and aggravates patients’ outcomes. It may be corrected by human albumin (HA) infusion. Herein, we have conducted a systematic review and meta-analysis to evaluate the efficacy of intravenous HA administration for the prevention and treatment of hyponatremia in liver cirrhosis. Methods. Literature was searched in the PubMed, EMBASE, and Cochrane Library databases. If possible, a meta-analysis would be conducted. Incidence of hyponatremia, rate of resolution of hyponatremia, and serum sodium level were compared between cirrhotic patients who received and did not receive HA infusion. Odds ratios (ORs) or mean differences (MDs) with 95% confidence intervals (CIs) were calculated. The quality of evidence was assessed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Results. Initially, 3231 papers were identified. Among them, 30 studies, including 25 randomized controlled trials (RCTs) and 5 cohort studies, were eligible. Among cirrhotic patients without hyponatremia, the HA infusion group had significantly lower incidence of hyponatremia (OR = 0.55, 95%CI = 0.38–0.80, p = 0.001) and higher serum sodium level (MD = 0.95, 95%CI = 0.47–1.43, p = 0.0001) as compared to the control group. Among cirrhotic patients with hyponatremia, the HA infusion group had a significantly higher rate of resolution of hyponatremia (OR = 1.50, 95%CI = 1.17–1.92, p = 0.001) as compared to the control group. Generally, the quality of available evidence is low. Conclusions. Based on the current evidence, HA may be considered for preventing the development of hyponatremia in liver cirrhosis, especially in those undergoing LVP, and treating hyponatremia. Well-designed studies are required to clarify the effects of HA infusion on hyponatremia in liver cirrhosis.
Collapse
Affiliation(s)
- Zhaohui Bai
- NMPA Key Laboratory for Research and Evaluation of Drug Regulatory Technology, Shenyang Pharmaceutical University, Shenyang 110016, China
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, China
| | - Le Wang
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, China
| | - Hanyang Lin
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, China
| | - Frank Tacke
- Department of Hepatology & Gastroenterology, Charité University Medical Center, 10117 Berlin, Germany
| | - Gang Cheng
- NMPA Key Laboratory for Research and Evaluation of Drug Regulatory Technology, Shenyang Pharmaceutical University, Shenyang 110016, China
- Correspondence: (G.C.); (X.Q.)
| | - Xingshun Qi
- NMPA Key Laboratory for Research and Evaluation of Drug Regulatory Technology, Shenyang Pharmaceutical University, Shenyang 110016, China
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, China
- Correspondence: (G.C.); (X.Q.)
| |
Collapse
|
23
|
de Mattos ÂZ, Simonetto DA, Terra C, Farias AQ, Bittencourt PL, Pase THS, Toazza MR, de Mattos AA. Albumin administration in patients with cirrhosis: Current role and novel perspectives. World J Gastroenterol 2022; 28:4773-4786. [PMID: 36156923 PMCID: PMC9476855 DOI: 10.3748/wjg.v28.i33.4773] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2022] [Revised: 06/05/2022] [Accepted: 07/06/2022] [Indexed: 02/06/2023] Open
Abstract
Mortality in cirrhosis is mostly associated with the development of clinical decompensation, characterized by ascites, hepatic encephalopathy, variceal bleeding, or jaundice. Therefore, it is important to prevent and manage such complications. Traditionally, the pathophysiology of decompensated cirrhosis was explained by the peripheral arterial vasodilation hypothesis, but it is currently understood that decompensation might also be driven by a systemic inflammatory state (the systemic inflammation hypothesis). Considering its oncotic and nononcotic properties, albumin has been thoroughly evaluated in the prevention and management of several of these decompensating events. There are formal evidence-based recommendations from international medical societies proposing that albumin be administered in individuals with cirrhosis undergoing large-volume paracentesis, patients with spontaneous bacterial peritonitis, those with acute kidney injury (even before the etiological diagnosis), and those with hepatorenal syndrome. Moreover, there are a few randomized controlled trials and meta-analyses suggesting a possible role for albumin infusion in patients with cirrhosis and ascites (long-term albumin administration), individuals with hepatic encephalopathy, and those with acute-on-chronic liver failure undergoing modest-volume paracentesis. Further studies are necessary to elucidate whether albumin administration also benefits patients with cirrhosis and other complications, such as individuals with extraperitoneal infections, those hospitalized with decompensated cirrhosis and hypoalbuminemia, and patients with hyponatremia.
Collapse
Affiliation(s)
- Ângelo Zambam de Mattos
- Graduate Program in Medicine: Hepatology, Federal University of Health Sciences of Porto Alegre, Porto Alegre 90050-170, Brazil
| | - Douglas Alano Simonetto
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55902, United States
| | - Carlos Terra
- Department of Gastroenterology, State University of Rio de Janeiro, Rio de Janeiro 20550-170, Brazil
| | | | | | - Tales Henrique Soares Pase
- Internal Medicine Unit, Irmandade Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90020-090, Brazil
| | - Marlon Rubini Toazza
- Gastroenterology and Hepatology Unit, Irmandade Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90020-090, Brazil
| | - Angelo Alves de Mattos
- Graduate Program in Medicine: Hepatology, Federal University of Health Sciences of Porto Alegre, Porto Alegre 90050-170, Brazil
| | | |
Collapse
|
24
|
Abstract
IMPORTANCE Hyponatremia is the most common electrolyte disorder and it affects approximately 5% of adults and 35% of hospitalized patients. Hyponatremia is defined by a serum sodium level of less than 135 mEq/L and most commonly results from water retention. Even mild hyponatremia is associated with increased hospital stay and mortality. OBSERVATIONS Symptoms and signs of hyponatremia range from mild and nonspecific (such as weakness or nausea) to severe and life-threatening (such as seizures or coma). Symptom severity depends on the rapidity of development, duration, and severity of hyponatremia. Mild chronic hyponatremia is associated with cognitive impairment, gait disturbances, and increased rates of falls and fractures. In a prospective study, patients with hyponatremia more frequently reported a history of falling compared with people with normal serum sodium levels (23.8% vs 16.4%, respectively; P < .01) and had a higher rate of new fractures over a mean follow-up of 7.4 years (23.3% vs 17.3%; P < .004). Hyponatremia is a secondary cause of osteoporosis. When evaluating patients, clinicians should categorize them according to their fluid volume status (hypovolemic hyponatremia, euvolemic hyponatremia, or hypervolemic hyponatremia). For most patients, the approach to managing hyponatremia should consist of treating the underlying cause. Urea and vaptans can be effective treatments for the syndrome of inappropriate antidiuresis and hyponatremia in patients with heart failure, but have adverse effects (eg, poor palatability and gastric intolerance with urea; and overly rapid correction of hyponatremia and increased thirst with vaptans). Severely symptomatic hyponatremia (with signs of somnolence, obtundation, coma, seizures, or cardiorespiratory distress) is a medical emergency. US and European guidelines recommend treating severely symptomatic hyponatremia with bolus hypertonic saline to reverse hyponatremic encephalopathy by increasing the serum sodium level by 4 mEq/L to 6 mEq/L within 1 to 2 hours but by no more than 10 mEq/L (correction limit) within the first 24 hours. This treatment approach exceeds the correction limit in about 4.5% to 28% of people. Overly rapid correction of chronic hyponatremia may cause osmotic demyelination, a rare but severe neurological condition, which can result in parkinsonism, quadriparesis, or even death. CONCLUSIONS AND RELEVANCE Hyponatremia affects approximately 5% of adults and 35% of patients who are hospitalized. Most patients should be managed by treating their underlying disease and according to whether they have hypovolemic, euvolemic, or hypervolemic hyponatremia. Urea and vaptans can be effective in managing the syndrome of inappropriate antidiuresis and hyponatremia in patients with heart failure; hypertonic saline is reserved for patients with severely symptomatic hyponatremia.
Collapse
Affiliation(s)
- Horacio J Adrogué
- Section of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, Texas
- Division of Nephrology, Department of Medicine, Houston Methodist Hospital, Houston, Texas
| | - Bryan M Tucker
- Section of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, Texas
- Division of Nephrology, Department of Medicine, Houston Methodist Hospital, Houston, Texas
| | - Nicolaos E Madias
- Department of Medicine, Tufts University School of Medicine, Boston, Massachusetts
- Division of Nephrology, Department of Medicine, St Elizabeth's Medical Center, Boston, Massachusetts
| |
Collapse
|
25
|
Kulkarni AV, Rabiee A, Mohanty A. Management of Portal Hypertension. J Clin Exp Hepatol 2022; 12:1184-1199. [PMID: 35814519 PMCID: PMC9257868 DOI: 10.1016/j.jceh.2022.03.002] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Accepted: 03/07/2022] [Indexed: 12/12/2022] Open
Abstract
Portal hypertension is the cause of the clinical complications associated with cirrhosis. The primary complications of portal hypertension are ascites, acute variceal bleed, and hepatic encephalopathy. Hepatic venous pressure gradient measurement remains the gold standard test for diagnosing cirrhosis-related portal hypertension. Hepatic venous pressure gradient more than 10 mmHg is associated with an increased risk of complications and is termed clinically significant portal hypertension (CSPH). Clinical, laboratory, and imaging methods can also aid in diagnosing CSPH non-invasively. Recently, deep learning methods have been demonstrated to diagnose CSPH effectively. The management of portal hypertension is always individualized and is dependent on the etiology, the availability of therapies, and the degree of portal hypertension complications. In this review, we discuss the diagnosis and management of cirrhosis-related portal hypertension in detail. Also, we highlight the history of portal hypertension and future research areas in portal hypertension.
Collapse
Key Words
- ACLF, acute-on-chronic liver failure
- AKI, acute kidney injury
- APRI, AST to platelet ratio
- AST, aspartate transaminase
- BB, Beta blocker
- BRTO, balloon occluded retrograde transvenous obliteration
- CKD, chronic kidney disease
- CSPH, clinically significant portal hypertension
- CT, computed tomography
- GFR, glomerular filtration rate
- GOV, gastrpoesopahegal varices
- HE, hepatic encephalopathy
- HRS, hepatorenal syndrome
- HVPG, hepatic venous pressure gradient
- ICG, indocyanine green
- LOLA, l-ornithine l-aspartate
- NAFLD, Non-alcoholic fatty liver disease
- SBP, spontaneous bacterial peritonitis
- SGLT2I, sodium glucose co-transporter 2 inhibitors
- SSM, splenic stiffness measurement
- TE, transient elastography
- TIPS, transjugular intrahepatic portosystemic shunt
- VITRO, von Willebrand factor to platelet counts
- acute kidney injury
- ascites
- hemodynamics
- history
- vasoconstrictors
Collapse
Affiliation(s)
| | | | - Arpan Mohanty
- Boston University School of Medicine, Boston, MA, USA
| |
Collapse
|
26
|
Thuluvath PJ, Alukal JJ, Zhang T. A model to predict inhospital mortality in patients with cirrhosis, ascites and hyponatremia. Eur J Gastroenterol Hepatol 2022; 34:591-597. [PMID: 35170534 DOI: 10.1097/meg.0000000000002357] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
BACKGROUND AND OBJECTIVE Hypervolemic hyponatremia is a late complication of portal hypertension. Hyponatremia is associated with a higher mortality in hospitalized patients. In this study, we evaluated the risk factors for inhospital mortality and developed a mortality prediction model in patients with cirrhosis and hyponatremia. METHODS Using the national inpatient sample data for years 2016 and 2017, we identified cirrhotic patients hospitalized with ascites and hyponatremia (n = 9153). We identified independent risk factors of inhospital mortality and developed a prediction model in a training group and assessed its accuracy in a validation group. To enhance the clinical utility, we further stratified patients into low-, intermediate-, and high-risk mortality risk groups using cutoff points selected by decision tree analysis. RESULTS The inhospital mortality in our cohort was 10.2% (n = 846). Multivariable analysis showed that age at least 65 years, variceal bleeding, sepsis, coagulopathy, and acute-on-chronic liver failure (ACLF defined as two or more organ failures) were independent risk factors for mortality. The prediction model using these five risk factors had an AUROC of 0.80 [95% confidence interval (CI), 0.78-0.82] for the training data and 0.83 (95% CI, 0.80-0.86) for the validation data. The mortality risks in the low-, intermediate-, and high-risk groups were 4% (95% CI, 3-4), 29% (95% CI, 28-33), and 43% (95% CI, 37-50), respectively. CONCLUSION We have developed a clinically meaningful inhospital prognostic model with excellent discrimination that will enable clinicians to risk stratify hospitalized patients with hyponatremia, ascites, and cirrhosis.
Collapse
Affiliation(s)
- Paul J Thuluvath
- Institute of Digestive Health & Liver Diseases, Mercy Medical Center
- Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA
| | - Joseph J Alukal
- Institute of Digestive Health & Liver Diseases, Mercy Medical Center
| | - Talan Zhang
- Institute of Digestive Health & Liver Diseases, Mercy Medical Center
| |
Collapse
|
27
|
Evaluation and management of emergencies in the patient with cirrhosis. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2022; 87:198-215. [PMID: 35570104 DOI: 10.1016/j.rgmxen.2022.05.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Accepted: 11/28/2021] [Indexed: 01/10/2023] Open
Abstract
The approach to and management of critically ill patients is one of the most versatile themes in emergency medicine. Patients with cirrhosis of the liver have characteristics that are inherent to their disease that can condition modification in acute emergency treatment. Pathophysiologic changes that occur in cirrhosis merit the implementation of an analysis as to whether the overall management of a critically ill patient can generally be applied to patients with cirrhosis of the liver or if they should be treated in a special manner. Through a review of the medical literature, the available information was examined, and the evidence found on the special management required by those patients was narratively synthesized, selecting the most representative decompensations within chronic disease that require emergency treatment.
Collapse
|
28
|
Abstract
Hyponatremia is the most common electrolyte disorder encountered in clinical practice, and it is a common complication of cirrhosis reflecting an increase in nonosmotic secretion of arginine vasopressin as a result of of the circulatory dysfunction that is characteristic of advanced liver disease. Hyponatremia in cirrhosis has been associated with poor clinical outcomes including increased risk of morbidity and mortality, poor quality of life, and heightened health care utilization. Despite this, the treatment of hyponatremia in cirrhosis remains challenging as conventional therapies such as fluid restriction are frequently ineffective. In this review, we discuss the epidemiology, clinical outcomes, pathogenesis, etiology, evaluation, and management of hyponatremia in cirrhosis.
Collapse
Affiliation(s)
- Helbert Rondon-Berrios
- Department of Medicine, Renal-Electrolyte Division, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Juan Carlos Q. Velez
- Ochsner Clinical School/The University of Queensland, Brisbane, Queensland, Australia AND Department of Nephrology, Ochsner Health, New Orleans, Louisiana, USA
| |
Collapse
|
29
|
Verbeek TA, Saner FH, Bezinover D. Hyponatremia and Liver Transplantation: A Narrative Review. J Cardiothorac Vasc Anesth 2022; 36:1458-1466. [PMID: 34144870 DOI: 10.1053/j.jvca.2021.05.027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Revised: 04/28/2021] [Accepted: 05/12/2021] [Indexed: 11/11/2022]
Abstract
Hyponatremia is a common electrolyte disorder in patients with end-stage liver disease (ESLD) and is associated with increased mortality on the liver transplantation (LT) waiting list. The impact of hyponatremia on outcomes after LT is unclear. Ninety-day and one-year mortality may be increased, but the data are conflicting. Hyponatremic patients have an increased rate of complications and longer hospital stays after transplant. Although rare, osmotic demyelination syndrome (ODS) is a feared complication after LT in the hyponatremic patient. The condition may occur when the serum sodium (sNa) concentration increases excessively during or after LT. This increase in sNa concentration correlates with the degree of preoperative hyponatremia, the amount of intraoperative blood loss, and the volume of intravenous fluid administration. The risk of developing ODS after LT can be mitigated by avoiding large perioperative increases in sNa concentration . This can be achieved through measures such as carefully increasing the sNa pretransplant, and by limiting the intravenous intra- and postoperative amounts of sodium infused. SNa concentrations should be monitored regularly throughout the entire perioperative period.
Collapse
Affiliation(s)
- Thomas A Verbeek
- Department of Anesthesiology and Perioperative Medicine, Penn State Health, Milton S. Hershey Medical Center/Penn State College of Medicine, Hershey, PA.
| | - Fuat H Saner
- Department of General, Visceral, and Transplantation Surgery, Essen University Medical Center, Essen, Germany
| | - Dmitri Bezinover
- Department of Anesthesiology and Perioperative Medicine, Penn State Health, Milton S. Hershey Medical Center/Penn State College of Medicine, Hershey, PA
| |
Collapse
|
30
|
Velarde-Ruiz Velasco JA, García-Jiménez ES, Aldana-Ledesma JM, Tapia-Calderón DK, Tornel-Avelar AI, Lazcano-Becerra M, Chávez-Ramírez RM, Cano-Contreras AD, Remes-Troche JM, Colunga-Lozano LE, Montaño-Loza A. Evaluation and management of emergencies in the patient with cirrhosis. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2022; 87:198-215. [PMID: 35570104 DOI: 10.1016/j.rgmx.2021.11.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Accepted: 11/28/2021] [Indexed: 01/04/2025]
Abstract
The approach to and management of critically ill patients is one of the most versatile themes in emergency medicine. Patients with cirrhosis of the liver have characteristics that are inherent to their disease that can condition modification in acute emergency treatment. Pathophysiologic changes that occur in cirrhosis merit the implementation of an analysis as to whether the overall management of a critically ill patient can generally be applied to patients with cirrhosis of the liver or if they should be treated in a special manner. Through a review of the medical literature, the available information was examined, and the evidence found on the special management required by those patients was narratively synthesized, selecting the most representative decompensations within chronic disease that require emergency treatment.
Collapse
Affiliation(s)
- J A Velarde-Ruiz Velasco
- Servicio de Gastroenterología, Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Jalisco, Mexico; Instituto de Investigaciones Médico Biológicas, Universidad Veracruzana, Veracruz, Mexico.
| | - E S García-Jiménez
- Servicio de Gastroenterología, Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Jalisco, Mexico
| | - J M Aldana-Ledesma
- Servicio de Gastroenterología, Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Jalisco, Mexico
| | - D K Tapia-Calderón
- Servicio de Gastroenterología, Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Jalisco, Mexico
| | - A I Tornel-Avelar
- Servicio de Gastroenterología, Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Jalisco, Mexico
| | - M Lazcano-Becerra
- Servicio de Gastroenterología, Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Jalisco, Mexico
| | - R M Chávez-Ramírez
- Unidad de Cuidados Intensivos, Hospital de Gineco-obstetricia, UMAE CMNO IMSS, Guadalajara, Jalisco, Mexico
| | - A D Cano-Contreras
- Instituto de Investigaciones Médico Biológicas, Universidad Veracruzana, Veracruz, Mexico
| | - J M Remes-Troche
- Instituto de Investigaciones Médico Biológicas, Universidad Veracruzana, Veracruz, Mexico
| | - L E Colunga-Lozano
- Departamento de Clínicas Médicas, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico
| | - A Montaño-Loza
- División of Gastroenterología y Unidad de Hígado, University of Alberta Hospital, Edmonton, Alberta, Canada
| |
Collapse
|
31
|
Abstract
In patients with cirrhosis and chronic liver disease, acute-on-chronic liver failure is emerging as a major cause of mortality. These guidelines indicate the preferred approach to the management of patients with acute-on-chronic liver failure and represent the official practice recommendations of the American College of Gastroenterology. The scientific evidence for these guidelines was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation process. In instances where the evidence was not appropriate for Grading of Recommendations, Assessment, Development, and Evaluation, but there was consensus of significant clinical merit, key concept statements were developed using expert consensus. These guidelines are meant to be broadly applicable and should be viewed as the preferred, but not only, approach to clinical scenarios.
Collapse
|
32
|
Bai Z, Zou M, Zhang X, Cheng G. Human Serum Albumin Infusion in Liver Cirrhosis. PHARMACOTHERAPY FOR LIVER CIRRHOSIS AND ITS COMPLICATIONS 2022:113-125. [DOI: 10.1007/978-981-19-2615-0_7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
|
33
|
Praharaj DL, Anand AC. Clinical Implications, Evaluation, and Management of Hyponatremia in Cirrhosis. J Clin Exp Hepatol 2022; 12:575-594. [PMID: 35535075 PMCID: PMC9077240 DOI: 10.1016/j.jceh.2021.09.008] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Accepted: 09/06/2021] [Indexed: 02/06/2023] Open
Abstract
Hyponatremia is the most common electrolyte abnormality in patients with decompensated cirrhosis on Liver Transplantation (LT) waiting list. Most of these patients have dilutional or hypervolemic hyponatremia secondary to splanchnic vasodilatation. Excessive secretion of the antidiuretic hormone also plays an important role. Hypervolemic hyponatremia is commonly associated with refractory ascites, spontaneous bacterial peritonitis, and hepatic encephalopathy. Although uncommon, the use of diuretics and laxatives can cause hypovolemic hyponatremia that is characterized by the striking absence of ascites or pedal edema. Clinical features are often nonspecific and depend on the acuity of onset rather than the absolute value of serum sodium. Symptoms may be subtle, including nausea, lethargy, weakness, or anorexia. However, rarely patients may present with confusion, seizures, psychosis, or coma. Treatment includes discontinuation of diuretics, beta-blockers, and albumin infusion. Hypertonic saline (3%) infusion may be used in patients with very low serum sodium (<110 mmol/L) or when patients present with seizures or coma. Short-term use of Vasopressin (V2) receptor antagonists may also be used to normalize sodium levels prior to LT. However, all these measures may be futile, and LT remains the definite treatment in these patients to improve survival. In this review, we describe the classification, pathogenesis of hyponatremia, and its clinical implications in patients with cirrhosis. Approach to these patients along with management will also be discussed briefly.
Collapse
Key Words
- ACE, angiotensin-converting enzyme
- ACLF, acute-on-chronic liver failure
- ACTH, adrenocorticotropic hormone
- ADH
- ADH, antidiuretic hormone
- AKI, acute kidney injury
- AVP, arginine vasopressin
- CLIF, chronic liver failure
- CNS, central nervous system
- CTP, Child-Turcotte-Pugh
- CVVHD, continuous venovenous hemofiltration
- DAMP, damage-associated molecular patterns
- EABV, effective arterial blood volume
- FENa, fractional excretion of sodium
- HE, hepatic encephalopathy
- HRS, hepatorenal syndrome
- LT, liver transplantation
- LVP, large volume paracentesis
- MAP, mean arterial pressure
- MELD, model of end-stage liver disease
- NO, nitric oxide
- NSBB, nonselective beta-blockers
- PAMP, pathogen-associated molecular patterns
- PICD, paracentesis-induced circulatory dysfunction
- PPCD, post-paracentesis circulatory dysfunction
- PRA, plasma renin activity
- RA, refractory ascites
- RAAS, renin-angiotensin-aldosterone-system
- RAI, relative adrenal insufficiency
- RBF, renal blood flow
- SBP, spontaneous bacterial peritonitis
- SIADH, syndrome of inappropriate ADH secretion
- SMT, standard medical treatment
- SNS, sympathetic nervous system
- TBW, total body water
- TIPS, transjugular intrahepatic portosystemic shunt
- advanced cirrhosis
- albumin
- hyponatremia
- liver transplantation
- sNa, serum sodium
Collapse
Affiliation(s)
- Dibya L. Praharaj
- Address for correspondence. Dibya L Praharaj, Assistant Professor, Department of Gastroenterology and Hepatology, Kalinga Institute of Medical Science, Bhubaneswar, India
| | | |
Collapse
|
34
|
Kim WR, Mannalithara A, Heimbach JK, Kamath PS, Asrani SK, Biggins SW, Wood NL, Gentry SE, Kwong AJ. MELD 3.0: The Model for End-Stage Liver Disease Updated for the Modern Era. Gastroenterology 2021; 161:1887-1895.e4. [PMID: 34481845 PMCID: PMC8608337 DOI: 10.1053/j.gastro.2021.08.050] [Citation(s) in RCA: 279] [Impact Index Per Article: 69.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Revised: 08/06/2021] [Accepted: 08/18/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND & AIMS The Model for End-Stage Liver Disease (MELD) has been established as a reliable indicator of short-term survival in patients with end-stage liver disease. The current version (MELDNa), consisting of the international normalized ratio and serum bilirubin, creatinine, and sodium, has been used to determine organ allocation priorities for liver transplantation in the United States. The objective was to optimize MELD further by taking into account additional variables and updating coefficients with contemporary data. METHODS All candidates registered on the liver transplant wait list in the US national registry from January 2016 through December 2018 were included. Uni- and multivariable Cox models were developed to predict survival up to 90 days after wait list registration. Model fit was tested using the concordance statistic (C-statistic) and reclassification, and the Liver Simulated Allocation Model was used to estimate the impact of replacing MELDNa with the new model. RESULTS The final multivariable model was characterized by (1) additional variables of female sex and serum albumin, (2) interactions between bilirubin and sodium and between albumin and creatinine, and (3) an upper bound for creatinine at 3.0 mg/dL. The final model (MELD 3.0) had better discrimination than MELDNa (C-statistic, 0.869 vs 0.862; P < .01). Importantly, MELD 3.0 correctly reclassified a net of 8.8% of decedents to a higher MELD tier, affording them a meaningfully higher chance of transplantation, particularly in women. In the Liver Simulated Allocation Model analysis, MELD 3.0 resulted in fewer wait list deaths compared to MELDNa (7788 vs 7850; P = .02). CONCLUSION MELD 3.0 affords more accurate mortality prediction in general than MELDNa and addresses determinants of wait list outcomes, including the sex disparity.
Collapse
Affiliation(s)
- W Ray Kim
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California.
| | - Ajitha Mannalithara
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California
| | | | | | | | | | - Nicholas L Wood
- Department of Mathematics, United States Naval Academy, Annapolis, Maryland
| | - Sommer E Gentry
- Department of Mathematics, United States Naval Academy, Annapolis, Maryland
| | - Allison J Kwong
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California
| |
Collapse
|
35
|
Sata SS, Sanders OO, Curley CA. Clinical Progress Note: Intravenous Human Albumin in Patients With Cirrhosis. J Hosp Med 2021; 16:738-741. [PMID: 34730505 DOI: 10.12788/jhm.3695] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Accepted: 07/27/2021] [Indexed: 11/20/2022]
Affiliation(s)
- Suchita Shah Sata
- Division of General Internal Medicine, Duke University Hospital, Duke University School of Medicine, Durham, North Carolina
| | | | - Catherine A Curley
- Division of Hospital Medicine, MetroHealth Medical Center, Case Western Reserve University School of Medicine, Cleveland, Ohio
| |
Collapse
|
36
|
Targeted Albumin Therapy Does Not Improve Short-Term Outcome in Hyponatremic Patients Hospitalized With Complications of Cirrhosis: Data From the ATTIRE Trial. Am J Gastroenterol 2021; 116:2292-2295. [PMID: 34520431 DOI: 10.14309/ajg.0000000000001488] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Accepted: 07/19/2021] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Patients with decompensated cirrhosis and hyponatremia have a poor prognosis. We investigated Albumin to Prevent Infection in Chronic Liver Failure trial data to determine whether targeted albumin infusions improved outcome in patients with hyponatremia at baseline. METHODS We examined the interaction between targeted albumin and standard care for the composite primary end point, stratifying by baseline sodium ≥ and <130 mmol/L. RESULTS Randomization to albumin was associated with a significant increase in sodium; however, there was no interaction between sodium category and treatment for the trial primary end point. DISCUSSION Targeted intravenous albumin infusions increased serum sodium level in hospitalized hyponatremic patients with cirrhosis, but this did not improve outcome.
Collapse
|
37
|
Biggins SW, Angeli P, Garcia-Tsao G, Ginès P, Ling SC, Nadim MK, Wong F, Kim WR. Diagnosis, Evaluation, and Management of Ascites, Spontaneous Bacterial Peritonitis and Hepatorenal Syndrome: 2021 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology 2021; 74:1014-1048. [PMID: 33942342 DOI: 10.1002/hep.31884] [Citation(s) in RCA: 392] [Impact Index Per Article: 98.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Accepted: 04/07/2021] [Indexed: 12/13/2022]
Affiliation(s)
- Scott W Biggins
- Division of Gastroenterology and Hepatology, and Center for Liver Investigation Fostering discovEryUniversity of WashingtonSeattleWA
| | - Paulo Angeli
- Unit of Hepatic Emergencies and Liver TransplantationDepartment of MedicineDIMEDUniversity of PadovaPaduaItaly
| | - Guadalupe Garcia-Tsao
- Department of Internal MedicineSection of Digestive DiseasesYale UniversityNew HavenCT.,VA-CT Healthcare SystemWest HavenCT
| | - Pere Ginès
- Liver Unit, Hospital Clinic, and Institut d'Investigacions Biomèdiques August Pi i SunyerUniversity of BarcelonaBarcelonaSpain.,Centro de Investigación Biomèdica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)MadridSpain
| | - Simon C Ling
- The Hospital for Sick Children, Division of Gastroenterology, Hepatology and Nutrition, and Department of PaediatricsUniversity of TorontoTorontoOntarioCanada
| | - Mitra K Nadim
- Division of NephrologyUniversity of Southern CaliforniaLos AngelesCA
| | - Florence Wong
- Division of Gastroenterology and HepatologyUniversity Health NetworkUniversity of TorontoTorontoOntarioCanada
| | - W Ray Kim
- Division of Gastroenterology and HepatologyStanford UniversityPalo AltoCA
| |
Collapse
|
38
|
China L, Freemantle N, Forrest E, Kallis Y, Ryder SD, Wright G, Portal AJ, Becares Salles N, Gilroy DW, O'Brien A. A Randomized Trial of Albumin Infusions in Hospitalized Patients with Cirrhosis. N Engl J Med 2021; 384:808-817. [PMID: 33657293 DOI: 10.1056/nejmoa2022166] [Citation(s) in RCA: 195] [Impact Index Per Article: 48.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Infection and increased systemic inflammation cause organ dysfunction and death in patients with decompensated cirrhosis. Preclinical studies provide support for an antiinflammatory role of albumin, but confirmatory large-scale clinical trials are lacking. Whether targeting a serum albumin level of 30 g per liter or greater in these patients with repeated daily infusions of 20% human albumin solution, as compared with standard care, would reduce the incidences of infection, kidney dysfunction, and death is unknown. METHODS We conducted a randomized, multicenter, open-label, parallel-group trial involving hospitalized patients with decompensated cirrhosis who had a serum albumin level of less than 30 g per liter at enrollment. Patients were randomly assigned to receive either targeted 20% human albumin solution for up to 14 days or until discharge, whichever came first, or standard care. Treatment commenced within 3 days after admission. The composite primary end point was new infection, kidney dysfunction, or death between days 3 and 15 after the initiation of treatment. RESULTS A total of 777 patients underwent randomization, and alcohol was reported to be a cause of cirrhosis in most of these patients. A median total infusion of albumin of 200 g (interquartile range, 140 to 280) per patient was administered to the targeted albumin group (increasing the albumin level to ≥30 g per liter), as compared with a median of 20 g (interquartile range, 0 to 120) per patient administered to the standard-care group (adjusted mean difference, 143 g; 95% confidence interval [CI], 127 to 158.2). The percentage of patients with a primary end-point event did not differ significantly between the targeted albumin group (113 of 380 patients [29.7%]) and the standard-care group (120 of 397 patients [30.2%]) (adjusted odds ratio, 0.98; 95% CI, 0.71 to 1.33; P = 0.87). A time-to-event analysis in which data were censored at the time of discharge or at day 15 also showed no significant between-group difference (hazard ratio, 1.04; 95% CI, 0.81 to 1.35). More severe or life-threatening serious adverse events occurred in the albumin group than in the standard-care group. CONCLUSIONS In patients hospitalized with decompensated cirrhosis, albumin infusions to increase the albumin level to a target of 30 g per liter or more was not more beneficial than the current standard care in the United Kingdom. (Funded by the Health Innovation Challenge Fund; ATTIRE EudraCT number, 2014-002300-24; ISRCT number, N14174793.).
Collapse
Affiliation(s)
- Louise China
- From the Institute for Liver and Digestive Health (L.C., N.B.S., A.O.), the Comprehensive Clinical Trials Unit (N.F.), and the Division of Medicine, University College London (D.W.G.), Barts and the London School of Medicine and Dentistry, Queen Mary University of London (Y.K.), London, the Glasgow Royal Infirmary and the University of Glagow, Glasgow (E.F.), the National Institute for Health Research Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust and the University of Nottingham, Queens Medical Centre, Nottingham (S.D.R.), the Mid and South Essex NHS Foundation Trust and the Basildon and Thurrock University Hospitals NHS Foundation Trust, Basildon (G.W.), and the Bristol Royal Infirmary, Bristol (A.J.P.) - all in the United Kingdom
| | - Nick Freemantle
- From the Institute for Liver and Digestive Health (L.C., N.B.S., A.O.), the Comprehensive Clinical Trials Unit (N.F.), and the Division of Medicine, University College London (D.W.G.), Barts and the London School of Medicine and Dentistry, Queen Mary University of London (Y.K.), London, the Glasgow Royal Infirmary and the University of Glagow, Glasgow (E.F.), the National Institute for Health Research Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust and the University of Nottingham, Queens Medical Centre, Nottingham (S.D.R.), the Mid and South Essex NHS Foundation Trust and the Basildon and Thurrock University Hospitals NHS Foundation Trust, Basildon (G.W.), and the Bristol Royal Infirmary, Bristol (A.J.P.) - all in the United Kingdom
| | - Ewan Forrest
- From the Institute for Liver and Digestive Health (L.C., N.B.S., A.O.), the Comprehensive Clinical Trials Unit (N.F.), and the Division of Medicine, University College London (D.W.G.), Barts and the London School of Medicine and Dentistry, Queen Mary University of London (Y.K.), London, the Glasgow Royal Infirmary and the University of Glagow, Glasgow (E.F.), the National Institute for Health Research Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust and the University of Nottingham, Queens Medical Centre, Nottingham (S.D.R.), the Mid and South Essex NHS Foundation Trust and the Basildon and Thurrock University Hospitals NHS Foundation Trust, Basildon (G.W.), and the Bristol Royal Infirmary, Bristol (A.J.P.) - all in the United Kingdom
| | - Yiannis Kallis
- From the Institute for Liver and Digestive Health (L.C., N.B.S., A.O.), the Comprehensive Clinical Trials Unit (N.F.), and the Division of Medicine, University College London (D.W.G.), Barts and the London School of Medicine and Dentistry, Queen Mary University of London (Y.K.), London, the Glasgow Royal Infirmary and the University of Glagow, Glasgow (E.F.), the National Institute for Health Research Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust and the University of Nottingham, Queens Medical Centre, Nottingham (S.D.R.), the Mid and South Essex NHS Foundation Trust and the Basildon and Thurrock University Hospitals NHS Foundation Trust, Basildon (G.W.), and the Bristol Royal Infirmary, Bristol (A.J.P.) - all in the United Kingdom
| | - Stephen D Ryder
- From the Institute for Liver and Digestive Health (L.C., N.B.S., A.O.), the Comprehensive Clinical Trials Unit (N.F.), and the Division of Medicine, University College London (D.W.G.), Barts and the London School of Medicine and Dentistry, Queen Mary University of London (Y.K.), London, the Glasgow Royal Infirmary and the University of Glagow, Glasgow (E.F.), the National Institute for Health Research Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust and the University of Nottingham, Queens Medical Centre, Nottingham (S.D.R.), the Mid and South Essex NHS Foundation Trust and the Basildon and Thurrock University Hospitals NHS Foundation Trust, Basildon (G.W.), and the Bristol Royal Infirmary, Bristol (A.J.P.) - all in the United Kingdom
| | - Gavin Wright
- From the Institute for Liver and Digestive Health (L.C., N.B.S., A.O.), the Comprehensive Clinical Trials Unit (N.F.), and the Division of Medicine, University College London (D.W.G.), Barts and the London School of Medicine and Dentistry, Queen Mary University of London (Y.K.), London, the Glasgow Royal Infirmary and the University of Glagow, Glasgow (E.F.), the National Institute for Health Research Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust and the University of Nottingham, Queens Medical Centre, Nottingham (S.D.R.), the Mid and South Essex NHS Foundation Trust and the Basildon and Thurrock University Hospitals NHS Foundation Trust, Basildon (G.W.), and the Bristol Royal Infirmary, Bristol (A.J.P.) - all in the United Kingdom
| | - Andrew J Portal
- From the Institute for Liver and Digestive Health (L.C., N.B.S., A.O.), the Comprehensive Clinical Trials Unit (N.F.), and the Division of Medicine, University College London (D.W.G.), Barts and the London School of Medicine and Dentistry, Queen Mary University of London (Y.K.), London, the Glasgow Royal Infirmary and the University of Glagow, Glasgow (E.F.), the National Institute for Health Research Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust and the University of Nottingham, Queens Medical Centre, Nottingham (S.D.R.), the Mid and South Essex NHS Foundation Trust and the Basildon and Thurrock University Hospitals NHS Foundation Trust, Basildon (G.W.), and the Bristol Royal Infirmary, Bristol (A.J.P.) - all in the United Kingdom
| | - Natalia Becares Salles
- From the Institute for Liver and Digestive Health (L.C., N.B.S., A.O.), the Comprehensive Clinical Trials Unit (N.F.), and the Division of Medicine, University College London (D.W.G.), Barts and the London School of Medicine and Dentistry, Queen Mary University of London (Y.K.), London, the Glasgow Royal Infirmary and the University of Glagow, Glasgow (E.F.), the National Institute for Health Research Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust and the University of Nottingham, Queens Medical Centre, Nottingham (S.D.R.), the Mid and South Essex NHS Foundation Trust and the Basildon and Thurrock University Hospitals NHS Foundation Trust, Basildon (G.W.), and the Bristol Royal Infirmary, Bristol (A.J.P.) - all in the United Kingdom
| | - Derek W Gilroy
- From the Institute for Liver and Digestive Health (L.C., N.B.S., A.O.), the Comprehensive Clinical Trials Unit (N.F.), and the Division of Medicine, University College London (D.W.G.), Barts and the London School of Medicine and Dentistry, Queen Mary University of London (Y.K.), London, the Glasgow Royal Infirmary and the University of Glagow, Glasgow (E.F.), the National Institute for Health Research Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust and the University of Nottingham, Queens Medical Centre, Nottingham (S.D.R.), the Mid and South Essex NHS Foundation Trust and the Basildon and Thurrock University Hospitals NHS Foundation Trust, Basildon (G.W.), and the Bristol Royal Infirmary, Bristol (A.J.P.) - all in the United Kingdom
| | - Alastair O'Brien
- From the Institute for Liver and Digestive Health (L.C., N.B.S., A.O.), the Comprehensive Clinical Trials Unit (N.F.), and the Division of Medicine, University College London (D.W.G.), Barts and the London School of Medicine and Dentistry, Queen Mary University of London (Y.K.), London, the Glasgow Royal Infirmary and the University of Glagow, Glasgow (E.F.), the National Institute for Health Research Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust and the University of Nottingham, Queens Medical Centre, Nottingham (S.D.R.), the Mid and South Essex NHS Foundation Trust and the Basildon and Thurrock University Hospitals NHS Foundation Trust, Basildon (G.W.), and the Bristol Royal Infirmary, Bristol (A.J.P.) - all in the United Kingdom
| |
Collapse
|
39
|
Aithal GP, Palaniyappan N, China L, Härmälä S, Macken L, Ryan JM, Wilkes EA, Moore K, Leithead JA, Hayes PC, O'Brien AJ, Verma S. Guidelines on the management of ascites in cirrhosis. Gut 2021; 70:9-29. [PMID: 33067334 PMCID: PMC7788190 DOI: 10.1136/gutjnl-2020-321790] [Citation(s) in RCA: 200] [Impact Index Per Article: 50.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Revised: 08/27/2020] [Accepted: 09/04/2020] [Indexed: 12/15/2022]
Abstract
The British Society of Gastroenterology in collaboration with British Association for the Study of the Liver has prepared this document. The aim of this guideline is to review and summarise the evidence that guides clinical diagnosis and management of ascites in patients with cirrhosis. Substantial advances have been made in this area since the publication of the last guideline in 2007. These guidelines are based on a comprehensive literature search and comprise systematic reviews in the key areas, including the diagnostic tests, diuretic use, therapeutic paracentesis, use of albumin, transjugular intrahepatic portosystemic stent shunt, spontaneous bacterial peritonitis and beta-blockers in patients with ascites. Where recent systematic reviews and meta-analysis are available, these have been updated with additional studies. In addition, the results of prospective and retrospective studies, evidence obtained from expert committee reports and, in some instances, reports from case series have been included. Where possible, judgement has been made on the quality of information used to generate the guidelines and the specific recommendations have been made according to the 'Grading of Recommendations Assessment, Development and Evaluation (GRADE)' system. These guidelines are intended to inform practising clinicians, and it is expected that these guidelines will be revised in 3 years' time.
Collapse
Affiliation(s)
- Guruprasad P Aithal
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
- Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK
| | - Naaventhan Palaniyappan
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
- Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK
| | - Louise China
- Institute of Liver Disease and Digestive Health, University College London, London, UK
| | - Suvi Härmälä
- Institute of Health Informatics, University College London, London, UK
| | - Lucia Macken
- Department of Clinical and Experimental Medicine, Brighton and Sussex Medical School, Brighton, UK
- Department of Gastroenterology and Hepatology, Brighton and Sussex University Hospitals NHS Trust, Brighton, UK
| | - Jennifer M Ryan
- Institute of Liver Disease and Digestive Health, University College London, London, UK
- Royal Free London NHS Foundation Trust, London, UK
| | - Emilie A Wilkes
- Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK
- Nottingham University Hospitals NHS Trust, Nottingham, UK
| | - Kevin Moore
- Institute of Liver Disease and Digestive Health, University College London, London, UK
| | - Joanna A Leithead
- Liver Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Peter C Hayes
- Hepatology Department, Royal Infirmary of Edinburgh, Edinburgh, UK
| | - Alastair J O'Brien
- Institute of Liver Disease and Digestive Health, University College London, London, UK
| | - Sumita Verma
- Department of Clinical and Experimental Medicine, Brighton and Sussex Medical School, Brighton, UK
- Department of Gastroenterology and Hepatology, Brighton and Sussex University Hospitals NHS Trust, Brighton, UK
| |
Collapse
|
40
|
Lenci I, Milana M, Grassi G, Signorello A, Aglitti A, Baiocchi L. Natremia and liver transplantation: The right amount of salt for a good recipe. World J Hepatol 2020; 12:919-930. [PMID: 33312419 PMCID: PMC7701977 DOI: 10.4254/wjh.v12.i11.919] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2020] [Revised: 09/19/2020] [Accepted: 09/28/2020] [Indexed: 02/06/2023] Open
Abstract
An adequate balance between electrolytes and clear water is of paramount importance to maintaining physiologic homeostasis. Natremia imbalance and, in particular, hyponatremia is the most frequent electrolyte abnormality observed in hospitalized subjects, involving approximately one-fourth of them. Pathological changes occurring during liver cirrhosis predispose patients to an increased risk of sodium imbalance, and hypervolemic hyponatremia has been reported in nearly 50% of subjects with severe liver disease and ascites. Splanchnic vasodilatation, portal-systemic collaterals’ opening and increased excretion of vasoactive modulators are all factors impairing clear water handling during liver cirrhosis. Of concern, sodium imbalance has been consistently reported to be associated with increased risk of complications and reduced survival in liver disease patients. In the last decades clinical interest in sodium levels has been also extended in the field of liver transplantation. Evidence that [Na+] in blood is an independent risk factor for in-list mortality led to the incorporation of sodium value in prognostic scores employed for transplant priority, such as model for end-stage liver disease-Na and UKELD. On the other hand, severe hyponatremic cirrhotic patients are frequently delisted by transplant centers due to the elevated risk of mortality after grafting. In this review, we describe in detail the relationship between sodium imbalance and liver cirrhosis, focusing on its impact on peritransplant phases. The possible therapeutic approaches, in order to improve transplant outcome, are also discussed.
Collapse
Affiliation(s)
- Ilaria Lenci
- Department of Internal Medicine, Hepatology Unit, Tor Vergata University, Rome 00133, Italy
| | - Martina Milana
- Department of Internal Medicine, Hepatology Unit, Tor Vergata University, Rome 00133, Italy
| | - Giuseppe Grassi
- Department of Internal Medicine, Hepatology Unit, Tor Vergata University, Rome 00133, Italy
| | - Alessandro Signorello
- Department of Internal Medicine, Hepatology Unit, Tor Vergata University, Rome 00133, Italy
| | - Andrea Aglitti
- Department of Internal Medicine, Hepatology Unit, Tor Vergata University, Rome 00133, Italy
| | - Leonardo Baiocchi
- Department of Internal Medicine, Hepatology Unit, Tor Vergata University, Rome 00133, Italy
| |
Collapse
|
41
|
Abstract
Hyponatremia is frequently seen in patients with ascites secondary to advanced cirrhosis and portal hypertension. Although not apparent in the early stages of cirrhosis, the progression of cirrhosis and portal hypertension leads to splanchnic vasodilation, and this leads to the activation of compensatory mechanisms such as renin-angiotensin-aldosterone system (RAAS), sympathetic nervous system, and antidiuretic hormone (ADH) to ameliorate low circulatory volume. The net effect is the avid retention of sodium and water to compensate for the low effective circulatory volume, resulting in the development of ascites. These compensatory mechanisms lead to impairment of the kidneys to eliminate solute-free water in decompensated cirrhosis. Nonosmotic secretion of antidiuretic hormone (ADH), also known as arginine vasopressin, further worsens excess water retention and thereby hyponatremia. The management of hyponatremia in this setting is a challenge as conventional therapies for hyponatremia including fluid restriction and correction of hypokalemia are frequently inefficacious. In this review, we discuss the pathophysiology, complications, and various treatment modalities, including albumin infusion, selective vasopressin receptor antagonists, or hypertonic saline for patients with severe hyponatremia and those awaiting liver transplantation.
Collapse
Affiliation(s)
- Joseph J Alukal
- Institute of Digestive Health and Liver Diseases, Mercy Medical Center, Baltimore, Maryland, USA
| | - Savio John
- Division of Gastroenterology, Department of Medicine, SUNY Upstate Medical University, Syracuse, New York, USA
| | - Paul J Thuluvath
- Institute of Digestive Health and Liver Diseases, Mercy Medical Center, Baltimore, Maryland, USA
- Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA
| |
Collapse
|
42
|
Abstract
Acute on chronic liver failure (ACLF) is an inflammation-based disorder that occurs in patients with underlying liver disease and is characterized by hepatic and extrahepatic organ failure. Morbidity and mortality are high in patients with ACLF, and therefore prevention and early identification are critical to improve outcome. The purpose of this article is to define ACLF, describe ways to identify the expected outcome of ACLF after development, and illustrate interventions to prevent it and when it is not preventable reduce associated morbidity and mortality.
Collapse
Affiliation(s)
- Ariel Aday
- University of Texas Southwestern, 5323 Harry Hines Blvd, Dallas, TX 75390, USA
| | - Jacqueline G O'Leary
- University of Texas Southwestern, 5323 Harry Hines Blvd, Dallas, TX 75390, USA; Dallas Veterans Affairs Medical Center, 4500 South Lancaster Road, Dallas, TX 75216, USA.
| |
Collapse
|
43
|
Verbeek TA, Stine JG, Saner FH, Bezinover D. Osmotic demyelination syndrome: are patients with end-stage liver disease a special risk group? Minerva Anestesiol 2020; 86:756-767. [DOI: 10.23736/s0375-9393.20.14120-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
|
44
|
Antifibrotic effects of hypocalcemic vitamin D analogs in murine and human hepatic stellate cells and in the CCl 4 mouse model. J Transl Med 2019; 99:1906-1917. [PMID: 31467426 DOI: 10.1038/s41374-019-0310-1] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2018] [Revised: 07/09/2019] [Accepted: 07/16/2019] [Indexed: 01/25/2023] Open
Abstract
Liver cirrhosis is a life-threatening consequence of liver fibrosis. The aim of this study was to investigate the antifibrotic potential of clinically available vitamin D analogs compared to that of calcitriol in vitro and in vivo. Murine hepatic stellate cells, Kupffer cells, and human LX-2 cells were treated with vitamin D analogs, and the profibrotic behavior of these cells was studied. In vivo liver fibrosis was induced using CCl4 until measurable fibrosis was established. Animals were then treated with calcitriol and paricalcitol. Vitamin D and its analogs showed antifibrotic effects in vitro. Treatment with active vitamin D (calcitriol, CAL) and its analogs reduced the protein expression of α-smooth muscle actin (α-SMA) in mHSC. In human LX-2 cells alfacalcidol reduced transforming growth factor-β (TGF-β) induced platelet-derived growth factor receptor-β protein expression and contractility while paricalcitol (PCT), in its equipotent dose to CAL, reduced TGF-β induced α-SMA protein expression, and ACTA2 and TGF-β mRNA expression. No effects of a treatment with vitamin D and its analogs were observed in Kupffer cells. In vivo, PCT-treated mice had significantly lower calcium levels than CAL-treated mice. CAL and PCT reduced the hepatic infiltration of CD11b-positive cells and alanine transaminase levels, while PCT but not CAL significantly inhibited fibrosis progression, with a favorable side effect profile in the CCl4 model. We conclude that hypocalcemic vitamin D analogs should be considered in future studies investigating vitamin D for the treatment of liver fibrosis.
Collapse
|
45
|
Bai Z, Bernardi M, Yoshida EM, Li H, Guo X, Méndez-Sánchez N, Li Y, Wang R, Deng J, Qi X. Albumin infusion may decrease the incidence and severity of overt hepatic encephalopathy in liver cirrhosis. Aging (Albany NY) 2019; 11:8502-8525. [PMID: 31596729 PMCID: PMC6814610 DOI: 10.18632/aging.102335] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2019] [Accepted: 09/22/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND The role of human albumin infusion for the prevention and treatment of overt hepatic encephalopathy (HE) in liver cirrhosis remains unclear. RESULTS Among the 708 patients without pre-existing overt HE, albumin infusion significantly decreased the incidence of overt HE (4.20% versus 12.70%, P<0.001) and in-hospital mortality (1.70% versus 5.40%, P=0.008). Among the 182 patients with overt HE at admission or during hospitalization, albumin infusion significantly improved overt HE (84.60% versus 68.10%, P=0.009) and decreased in-hospital mortality (7.70% versus 19.80%, P=0.018). Meta-analysis of 6 studies found that albumin infusion might decrease the risk of overt HE (OR=1.63, P=0.07), but the difference was not statistically significant. Meta-analysis of 3 studies found that albumin infusion significantly improved overt HE (OR=2.40, P=0.04). CONCLUSIONS Based on the results of our retrospective study and meta-analysis, albumin infusion might prevent from the occurrence of overt HE and improve the severity of overt HE in cirrhosis. Our retrospective study also suggested that albumin infusion improved the outcomes of cirrhotic patients regardless of overt HE. METHODS Cirrhotic patients consecutively admitted between January 2010 and June 2014 were considered in a retrospective study. A 1:1 propensity score matching analysis was performed. Additionally, publications regarding albumin infusion for the management of overt HE were systematically searched. Meta-analyses were performed by random-effect model. Odds ratio (OR) was calculated.
Collapse
Affiliation(s)
- Zhaohui Bai
- Department of Gastroenterology, General Hospital of Northern Theater Command (formerly called General Hospital of Shenyang Military Area), Shenyang, P.R. China
- Postgraduate College, Shenyang Pharmaceutical University, Shenyang, P.R. China
| | - Mauro Bernardi
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Eric M. Yoshida
- Division of Gastroenterology, Vancouver General Hospital, Vancouver, British Columbia, Canada
| | - Hongyu Li
- Department of Gastroenterology, General Hospital of Northern Theater Command (formerly called General Hospital of Shenyang Military Area), Shenyang, P.R. China
| | - Xiaozhong Guo
- Department of Gastroenterology, General Hospital of Northern Theater Command (formerly called General Hospital of Shenyang Military Area), Shenyang, P.R. China
| | - Nahum Méndez-Sánchez
- Liver Research Unit, Medica Sur Clinic and Foundation and Faculty of Medicine, National Autonomous University of Mexico, Mexico
| | - Yingying Li
- Department of Gastroenterology, General Hospital of Northern Theater Command (formerly called General Hospital of Shenyang Military Area), Shenyang, P.R. China
| | - Ran Wang
- Department of Gastroenterology, General Hospital of Northern Theater Command (formerly called General Hospital of Shenyang Military Area), Shenyang, P.R. China
| | - Jiao Deng
- Department of Pharmacology, General Hospital of Northern Theater Command, (formerly called General Hospital of Shenyang Military Area), Shenyang, P.R. China
| | - Xingshun Qi
- Department of Gastroenterology, General Hospital of Northern Theater Command (formerly called General Hospital of Shenyang Military Area), Shenyang, P.R. China
| |
Collapse
|
46
|
Recent developments in the management of acute and chronic hyponatremia. Curr Opin Nephrol Hypertens 2019; 28:424-432. [DOI: 10.1097/mnh.0000000000000528] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
|
47
|
Simonetti RG, Perricone G, Nikolova D, Bjelakovic G, Gluud C. Plasma expanders for people with cirrhosis and large ascites treated with abdominal paracentesis. Cochrane Database Syst Rev 2019; 6:CD004039. [PMID: 31251387 PMCID: PMC6598734 DOI: 10.1002/14651858.cd004039.pub2] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Plasma volume expanders are used in connection to paracentesis in people with cirrhosis to prevent reduction of effective plasma volume, which may trigger deleterious effect on haemodynamic balance, and increase morbidity and mortality. Albumin is considered the standard product against which no plasma expansion or other plasma expanders, e.g. other colloids (polygeline , dextrans, hydroxyethyl starch solutions, fresh frozen plasma), intravenous infusion of ascitic fluid, crystalloids, or mannitol have been compared. However, the benefits and harms of these plasma expanders are not fully clear. OBJECTIVES To assess the benefits and harms of any plasma volume expanders such as albumin, other colloids (polygeline, dextrans, hydroxyethyl starch solutions, fresh frozen plasma), intravenous infusion of ascitic fluid, crystalloids, or mannitol versus no plasma volume expander or versus another plasma volume expander for paracentesis in people with cirrhosis and large ascites. SEARCH METHODS We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS, CNKI, VIP, Wanfang, Science Citation Index Expanded, and Conference Proceedings Citation Index until January 2019. Furthermore, we searched FDA, EMA, WHO (last search January 2019), www.clinicaltrials.gov/, and www.controlled-trials.com/ for ongoing trials. SELECTION CRITERIA Randomised clinical trials, no matter their design or year of publication, publication status, and language, assessing the use of any type of plasma expander versus placebo, no intervention, or a different plasma expander in connection with paracentesis for ascites in people with cirrhosis. We considered quasi-randomised, retrieved with the searches for randomised clinical trials only, for reports on harms. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane. We calculated the risk ratio (RR) or mean difference (MD) using the fixed-effect model and the random-effects model meta-analyses, based on the intention-to-treat principle, whenever possible. If the fixed-effect and random-effects models showed different results, then we made our conclusions based on the analysis with the highest P value (the more conservative result). We assessed risks of bias of the individual trials using predefined bias risk domains. We assessed the certainty of the evidence at an outcome level, using GRADE, and constructed 'Summary of Findings' tables for seven of our review outcomes. MAIN RESULTS We identified 27 randomised clinical trials for inclusion in this review (24 published as full-text articles and 3 as abstracts). Five of the trials, with 271 participants, assessed plasma expanders (albumin in four trials and ascitic fluid in one trial) versus no plasma expander. The remaining 22 trials, with 1321 participants, assessed one type of plasma expander, i.e. dextran, hydroxyethyl starch, polygeline, intravenous infusion of ascitic fluid, crystalloids, or mannitol versus another type of plasma expander, i.e. albumin in 20 of these trials and polygeline in one trial. Twenty-five trials provided data for quantitative meta-analysis. According to the Child-Pugh classification, most participants were at an intermediate to advanced stage of liver disease in the absence of hepatocellular carcinoma, recent gastrointestinal bleeding, infections, and hepatic encephalopathy. All trials were assessed as at overall high risk of bias. Ten trials seemed not to have been funded by industry; twelve trials were considered unclear about funding; and five trials were considered funded by industry or a for-profit institution.We found no evidence of a difference in effect between plasma expansion versus no plasma expansion on mortality (RR 0.52, 95% CI 0.06 to 4.83; 248 participants; 4 trials; very low certainty); renal impairment (RR 0.32, 95% CI 0.02 to 5.88; 181 participants; 4 trials; very low certainty); other liver-related complications (RR 1.61, 95% CI 0.79 to 3.27; 248 participants; 4 trials; very low certainty); and non-serious adverse events (RR 1.04, 95% CI 0.32 to 3.40; 158 participants; 3 trials; very low certainty). Two of the trials stated that no serious adverse events occurred while the remaining trials did not report on this outcome. No trial reported data on health-related quality of life.We found no evidence of a difference in effect between experimental plasma expanders versus albumin on mortality (RR 1.03, 95% CI 0.82 to 1.30; 1014 participants; 14 trials; very low certainty); serious adverse events (RR 0.89, 95% CI 0.10 to 8.30; 118 participants; 2 trials; very low certainty); renal impairment (RR 1.17, 95% CI 0.71 to 1.91; 1107 participants; 17 trials; very low certainty); other liver-related complications (RR 1.10, 95% CI 0.82 to 1.48; 1083 participants; 16 trials; very low certainty); and non-serious adverse events (RR 1.37, 95% CI 0.66 to 2.85; 977 participants; 14 trials; very low certainty). We found no data on heath-related quality of life and refractory ascites. AUTHORS' CONCLUSIONS Our systematic review and meta-analysis did not find any benefits or harms of plasma expanders versus no plasma expander or of one plasma expander such as polygeline, dextrans, hydroxyethyl starch, intravenous infusion of ascitic fluid, crystalloids, or mannitol versus albumin on primary or secondary outcomes. The data originated from few, small, mostly short-term trials at high risks of systematic errors (bias) and high risks of random errors (play of chance). GRADE assessments concluded that the evidence was of very low certainty. Therefore, we can neither demonstrate or discard any benefit of plasma expansion versus no plasma expansion, and differences between one plasma expander versus another plasma expander.Larger trials at low risks of bias are needed to assess the role of plasma expanders in connection with paracentesis. Such trials should be conducted according to the SPIRIT guidelines and reported according to the CONSORT guidelines.
Collapse
Affiliation(s)
- Rosa G Simonetti
- Cochrane Hepato‐Biliary GroupBlegdamsvej 9, 7811CopenhagenDenmark2100
| | - Giovanni Perricone
- Azienda Socio‐Sanitaria Territoriale Grande Ospedale Metropolitano NiguardaS.C. Epatologia e GastroenterologiaPiazza Ospedale Maggiore, 3MilanItaly20162
- UCL Institute for Liver and Digestive Health, UCL Medical School, Royal Free HospitalLiver Failure GroupLondonUK
| | - Dimitrinka Nikolova
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University HospitalCochrane Hepato‐Biliary GroupBlegdamsvej 9CopenhagenDenmarkDK‐2100
| | - Goran Bjelakovic
- Medical Faculty, University of NisDepartment of Internal MedicineZorana Djindjica 81NisSerbia18000
| | - Christian Gluud
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University HospitalCochrane Hepato‐Biliary GroupBlegdamsvej 9CopenhagenDenmarkDK‐2100
| | | |
Collapse
|
48
|
Attar B. Approach to Hyponatremia in Cirrhosis. Clin Liver Dis (Hoboken) 2019; 13:98-101. [PMID: 31061701 PMCID: PMC6491031 DOI: 10.1002/cld.790] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2018] [Accepted: 11/27/2018] [Indexed: 02/04/2023] Open
Affiliation(s)
- Bashar Attar
- Cook County Health and Hospitals SystemChicagoIL
| |
Collapse
|
49
|
Paine CH, Biggins SW, Pichler RH. Albumin in Cirrhosis: More Than a Colloid. ACTA ACUST UNITED AC 2019; 17:231-243. [DOI: 10.1007/s11938-019-00227-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
|
50
|
|