|
1
|
Rajakumar A, Paulin S, Sam AF, Jothimani D, Rammohan A, Rela M. Impact of Perioperative Serum Sodium Levels on Outcomes Following Living Donor Liver Transplantation. J Clin Exp Hepatol 2025; 15:102511. [PMID: 40093507 PMCID: PMC11908579 DOI: 10.1016/j.jceh.2025.102511] [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: 09/07/2024] [Accepted: 01/29/2025] [Indexed: 03/19/2025] Open
Abstract
Background & objectives Preoperative hyponatremia has been shown to be associated with poor outcomes post-liver transplantation. We analyzed the impact of preoperative hyponatremia and perioperative sodium (Na) changes on outcomes following adult living donor liver transplantation. Methods After obtaining clearance from Institutional ethical Committee, a retrospective review of electronic database and medical records of all adult patients who underwent LDLT between January 2019 and September 2022 was done and relevant perioperative data were collected. Results The study cohort of 520 recipients was divided into four groups based on preoperative serum Na levels in mmol/L; 12 patients (2.3%) in Group A (<125); 66 patients (12.6%) in Group B (125-129); 216 patients (41.5%) in Group C (130-135) and 226 patients (43.4%) in Group D (136-145). MELD score, preoperative AKI, SBP, intraoperative ascites volume, volume of packed blood cells (PRC), other blood products and 25% albumin were significantly associated with the degree of hyponatremia. No other outcomes including mortality was associated any grade of hyponatremia. The delta sodium on postoperative day 1 was largest in Group A. The level of Na rise post-transplant on POD1 had an inverse correlation with preoperative Na levels [ r (520) -0.6, P < 0.001]. High delta sodium was not associated with neurological complications in this cohort. Group A patients had higher incidence of postoperative AKI requiring dialysis followed by groups B, C and D. Eighty-six (16.5%) patients had large delta-Na of >10 mmol/L. On univariate analysis, low pretransplant Na (<130mEq/L), preoperative AKI, SBP, higher MELD and ascitic volumes, intraoperative transfusions of PRC, blood products and 25% albumin, early allograft dysfunction and need for dialysis, were associated with larger delta-Na. On multivariate analysis, preoperative Na levels ≤130 mmol/L, intraoperative ascites and PRC transfusion were found to be independent risk factors for a large delta-Na. Conclusion Hyponatremia, being a factor associated with liver disease, might not by itself contribute to poor survival when the deleterious effects of large delta changes can be avoided. The results from this study reinforces the fact that with a cautious perioperative approach, patients with hyponatremia can be transplanted safely in LDLT settings.
Collapse
Affiliation(s)
- Akila Rajakumar
- Department of Liver Intensive Care and Anaesthesia, Dr. Rela Institute and Medical Centre, Chennai, India
| | - Susan Paulin
- Department of Liver Intensive Care and Anaesthesia, Dr. Rela Institute and Medical Centre, Chennai, India
| | - Amal Francis Sam
- Department of Liver Intensive Care and Anaesthesia, Dr. Rela Institute and Medical Centre, Chennai, India
| | - Dinesh Jothimani
- Department of Hepatology and Liver Transplantation, Dr. Rela Institute and Medical Centre, Chennai, India
| | - Ashwin Rammohan
- Department of HPB Surgery and Liver Transplantation, Dr. Rela Institute and Medical Centre, Chennai, India
| | - Mohamed Rela
- Department of HPB Surgery and Liver Transplantation, Dr. Rela Institute and Medical Centre, Chennai, India
| |
Collapse
|
|
2
|
Nakamura N, Inoue-Hamano A, Inoue S, Hamada Y. The relationship between hyponatremia and mortality in patients receiving nutrition support. Clin Nutr 2025; 46:37-44. [PMID: 39864379 DOI: 10.1016/j.clnu.2025.01.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 01/06/2025] [Accepted: 01/11/2025] [Indexed: 01/28/2025]
Abstract
BACKGROUND & AIMS Hyponatremia is frequently seen in clinical practice, but most cases are mild and asymptomatic and therefore often go unmanaged. In recent years, it has been reported that the onset or improvement of hyponatremia, even in mild cases, has an impact on mortality and that hyponatremia is directly related to increased mortality. In addition, it has been reported that patients with Nutrition Support Team (NST) are more likely to develop hyponatremia than the general hospitalized population. This study aimed to determine the association between the development and amelioration of hyponatremia and mortality in patients with NST. METHODS A total of 1553 patients who underwent initial NST intervention from April 1, 2013 to March 31, 2017 were included. Hyponatremia was defined as hyponatremia <138 mEq/L and normal serum sodium level was defined as 138-145 mEq/L based on the laboratory reference values of our hospital. Hyponatremia was defined as L and normal sodium as N. Based on sodium levels at the start and end of the intervention, the population was classified into four groups, L-L, N-L, L-N, and N-N (sodium level at the start of intervention - sodium level at the end of intervention), and the 5-year survival rate curve and hazard ratio for death for each group were calculated. Multivariate analysis adjusted for age, sex, and body mass index. RESULTS Analysis revealed that the L-L group with persistent hyponatremia (hazard ratio (HR) = 3.47, vs N-N, p < 0.0001) had the highest risk of death, while the L-N group with improved hyponatremia (HR = 2.19, vs N-N, p < 0.0001) had a significantly lower risk than the L-L group. The risk of death was also increased in the L-N and N-L groups (HR = 1.97, vs. N-N, p << 0.0001) after even one episode of hyponatremia compared to the N-N group. CONCLUSION The results of this study indicate that hyponatremia is associated with poor survival in patients undergoing NST. Future randomized controlled trials are needed to determine whether correction of hyponatremia leads to improved survival in patients undergoing NST to clarify the need for prevention and management of hyponatremia.
Collapse
Affiliation(s)
- Nayu Nakamura
- Department of Therapeutic Nutrition, Institute of Biomedical Sciences, Tokushima University Graduate School, Japan
| | - Arisa Inoue-Hamano
- Department of Therapeutic Nutrition, Institute of Biomedical Sciences, Tokushima University Graduate School, Japan
| | - Seiya Inoue
- Department of Thoracic, Endocrine Surgery and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Japan
| | - Yasuhiro Hamada
- Department of Therapeutic Nutrition, Institute of Biomedical Sciences, Tokushima University Graduate School, Japan.
| |
Collapse
|
|
3
|
Varró G, Bozó É, Vukics K, Baska F, Szántó G, Krámos B, Domány-Kovács K, Kordás KS, Vastag M, Magdó I, Bata I. Development of dual V1a/V2 antagonists containing triazolobenzazepine scaffold. Eur J Med Chem 2025; 283:117069. [PMID: 39631099 DOI: 10.1016/j.ejmech.2024.117069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Revised: 11/08/2024] [Accepted: 11/14/2024] [Indexed: 12/07/2024]
Abstract
The development of a dual V1a/V2 antagonist compound is a complex and challenging task. Conivaptan is up to now the only known V1a/V2 antagonist which was approved for the treatment of euvolemic hyponatremia. Previously, we reported RGH-122, a novel selective V1a antagonist compound. Herein, we describe several promising dual antagonist compounds, which are derived from RGH-122 by using modifications in its tail region. These modifications can result in excellent binding affinity on both V1a and V2 receptors.
Collapse
Affiliation(s)
- Gábor Varró
- Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
| | - Éva Bozó
- Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary
| | | | - Ferenc Baska
- Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary
| | - Gábor Szántó
- Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary
| | - Balázs Krámos
- Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary
| | | | | | - Mónika Vastag
- Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary
| | - Ildikó Magdó
- Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary
| | - Imre Bata
- Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary
| |
Collapse
|
|
4
|
Bai Z, Yin Y, Xu W, Cheng G, Qi X. Predictive model of in-hospital mortality in liver cirrhosis patients with hyponatremia: an artificial neural network approach. Sci Rep 2024; 14:28719. [PMID: 39567595 PMCID: PMC11579295 DOI: 10.1038/s41598-024-73256-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Accepted: 09/16/2024] [Indexed: 11/22/2024] Open
Abstract
Hyponatremia can worsen the outcomes of patients with liver cirrhosis. However, it remains unclear about how to predict the risk of death in cirrhotic patients with hyponatremia. Patients with liver cirrhosis and hyponatremia were screened. Eligible patients were randomly divided into the training (n = 472) and validation (n = 471) cohorts. In the training cohort, the independent predictors for in-hospital death were identified by logistic regression analyses. Odds ratios (ORs) were calculated. An artificial neural network (ANN) model was established in the training cohort. Areas under curve (AUCs) of ANN model, Child-Pugh, model for end-stage liver disease (MELD), and MELD-Na scores were calculated by receiver operating characteristic curve analyses. In multivariate logistic regression analyses, ascites (OR = 2.705, P = 0.042), total bilirubin (OR = 1.004, P = 0.003), serum creatinine (OR = 1.004, P = 0.017), and international normalized ratio (OR = 1.457, P = 0.005) were independently associated with in-hospital death. Based on the four variables, an ANN model was established. Its AUC was 0.865 and 0.810 in the training and validation cohorts, respectively, which was significantly larger than those of Child-Pugh (AUC = 0.757), MELD (AUC = 0.765), and MELD-Na (AUC = 0.769) scores. An ANN model has been developed and validated for the prediction of in-hospital death in patients with liver cirrhosis and hyponatremia.
Collapse
Affiliation(s)
- Zhaohui Bai
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command (Teaching Hospital of Shenyang Pharmaceutical University), Shenyang, China
- Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China
| | - Yuhang Yin
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command (Teaching Hospital of Shenyang Pharmaceutical University), Shenyang, China
- Postgraduate College, China Medical University, Shenyang, China
| | - Wentao Xu
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command (Teaching Hospital of Shenyang Pharmaceutical University), Shenyang, China
| | - Gang Cheng
- NMPA Key Laboratory for Research and Evaluation of Drug Regulatory Technology, Shenyang Pharmaceutical University, Shenyang, China.
| | - Xingshun Qi
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command (Teaching Hospital of Shenyang Pharmaceutical University), Shenyang, China.
- NMPA Key Laboratory for Research and Evaluation of Drug Regulatory Technology, Shenyang Pharmaceutical University, Shenyang, China.
- Department of Gastroenterology, General Hospital of Northern Theater Command Shenyang (Teaching Hospital of Shenyang Pharmaceutical University), Shenyang, China.
| |
Collapse
|
|
5
|
Pollmanns MR, Pajaziti Q, Hohlstein P, Adams JK, Abu Jhaisha S, Kabak E, Hamesch K, Nusser SHA, Weiskirchen R, Wirtz TH, Koch A. Serum Adiponectin Is Elevated in Critically Ill Patients with Liver Disease and Associated with Decreased Overall Survival. Biomedicines 2024; 12:2173. [PMID: 39457486 PMCID: PMC11504267 DOI: 10.3390/biomedicines12102173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Revised: 09/20/2024] [Accepted: 09/22/2024] [Indexed: 10/28/2024] Open
Abstract
BACKGROUND Adiponectin, an adipokine with anti-inflammatory properties, has been implicated in various liver diseases. This study aimed to elucidate the prognostic value of serum adiponectin levels in critically ill patients with liver disease. METHODS This observational study included 161 critically ill patients admitted to the medical ICU of RWTH Aachen University Hospital due to acute liver failure or decompensated advanced chronic liver disease. Serum adiponectin levels were measured at ICU admission and after 48 h. Clinical parameters and outcomes, including transplant-free survival, were analyzed. RESULTS Serum adiponectin concentrations were significantly elevated compared to healthy controls (p < 0.001). Levels were particularly high in patients with sepsis compared to those with gastrointestinal bleeding as the precipitating factor of acute decompensation (p = 0.045) and were higher in female patients (p = 0.023). Adiponectin concentrations correlated with the Model of End-Stage Liver Disease (MELD) score and Child-Pugh score. Multivariate analysis confirmed a significant correlation with total bilirubin (r = 0.292, p < 0.001) and serum sodium (r = -0.265, p = 0.028). Higher adiponectin concentrations were associated with a trend towards poorer 30- and 180-day survival. Cox regression analysis identified a significant association between increased adiponectin concentration and reduced transplant-free survival (p = 0.037), supported by a Kaplan-Meier analysis using a cutoff of 119 ng/mL (log-rank 5.145, p = 0.023). CONCLUSIONS Elevated serum adiponectin concentrations are associated with liver dysfunction and poor outcomes in critically ill patients. Higher adiponectin levels at ICU admission may predict poorer transplant-free survival. Further research in larger, multicenter cohorts is warranted to validate these findings and explore the underlying mechanisms.
Collapse
Affiliation(s)
- Maike R. Pollmanns
- Department for Gastroenterology, Metabolic Disorders and Intensive Care Medicine, RWTH-University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany; (M.R.P.); (Q.P.); (P.H.); (J.K.A.); (S.A.J.); (E.K.); (K.H.); (S.H.A.N.); (T.H.W.)
| | - Qendrim Pajaziti
- Department for Gastroenterology, Metabolic Disorders and Intensive Care Medicine, RWTH-University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany; (M.R.P.); (Q.P.); (P.H.); (J.K.A.); (S.A.J.); (E.K.); (K.H.); (S.H.A.N.); (T.H.W.)
| | - Philipp Hohlstein
- Department for Gastroenterology, Metabolic Disorders and Intensive Care Medicine, RWTH-University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany; (M.R.P.); (Q.P.); (P.H.); (J.K.A.); (S.A.J.); (E.K.); (K.H.); (S.H.A.N.); (T.H.W.)
| | - Jule K. Adams
- Department for Gastroenterology, Metabolic Disorders and Intensive Care Medicine, RWTH-University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany; (M.R.P.); (Q.P.); (P.H.); (J.K.A.); (S.A.J.); (E.K.); (K.H.); (S.H.A.N.); (T.H.W.)
| | - Samira Abu Jhaisha
- Department for Gastroenterology, Metabolic Disorders and Intensive Care Medicine, RWTH-University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany; (M.R.P.); (Q.P.); (P.H.); (J.K.A.); (S.A.J.); (E.K.); (K.H.); (S.H.A.N.); (T.H.W.)
| | - Elena Kabak
- Department for Gastroenterology, Metabolic Disorders and Intensive Care Medicine, RWTH-University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany; (M.R.P.); (Q.P.); (P.H.); (J.K.A.); (S.A.J.); (E.K.); (K.H.); (S.H.A.N.); (T.H.W.)
| | - Karim Hamesch
- Department for Gastroenterology, Metabolic Disorders and Intensive Care Medicine, RWTH-University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany; (M.R.P.); (Q.P.); (P.H.); (J.K.A.); (S.A.J.); (E.K.); (K.H.); (S.H.A.N.); (T.H.W.)
| | - Sophie H. A. Nusser
- Department for Gastroenterology, Metabolic Disorders and Intensive Care Medicine, RWTH-University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany; (M.R.P.); (Q.P.); (P.H.); (J.K.A.); (S.A.J.); (E.K.); (K.H.); (S.H.A.N.); (T.H.W.)
| | - Ralf Weiskirchen
- Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), RWTH University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany;
| | - Theresa H. Wirtz
- Department for Gastroenterology, Metabolic Disorders and Intensive Care Medicine, RWTH-University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany; (M.R.P.); (Q.P.); (P.H.); (J.K.A.); (S.A.J.); (E.K.); (K.H.); (S.H.A.N.); (T.H.W.)
| | - Alexander Koch
- Department for Gastroenterology, Metabolic Disorders and Intensive Care Medicine, RWTH-University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany; (M.R.P.); (Q.P.); (P.H.); (J.K.A.); (S.A.J.); (E.K.); (K.H.); (S.H.A.N.); (T.H.W.)
| |
Collapse
|
|
6
|
Liang S, Sun L, Zhang Y, Zhang Q, Jiang N, Zhu H, Chen S, Pan H. Sodium fluctuation as a parameter in predicting mortality in general hospitalized patients. Front Med (Lausanne) 2024; 11:1399638. [PMID: 39081691 PMCID: PMC11286384 DOI: 10.3389/fmed.2024.1399638] [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: 03/12/2024] [Accepted: 07/02/2024] [Indexed: 08/02/2024] Open
Abstract
Background Dysnatremia is the most common electrolyte disorder in hospitalized patients. Sodium fluctuation level may be a better parameter in dysnatremia management. We aimed to examine the association between sodium fluctuation level during hospitalization and mortality and to evaluate its value in predicting poor prognosis among general hospitalized patients. Methods Data were collected from patients admitted to Peking Union Medical College Hospital. The generalized estimated equation (GEE) was used to examine the relationship between sodium fluctuation level and mortality. Receiver-operating characteristic (ROC) curve analysis was performed to calculate the optimal cutoff value and the area under the ROC curve (AUC). Results Sodium fluctuation level showed a dose-dependent association with increased mortality in general hospitalized patients. After adjusting age, sex, length of hospital stay, and Charlson comorbidity index, the ORs of group G2 to G6 were 5.92 (95% CI 5.16-6.79), 26.45 (95% CI 22.68-30.86), 50.71 (95% CI 41.78-61.55), 104.38 (95% CI 81.57-133.58), and 157.64 (95% CI 112.83-220.24), respectively, p trend <0.001. Both normonatremia and dysnatremia patients on admission had the dose-dependent associations similar to general hospitalized patients. The AUC of sodium fluctuation level was 0.868 (95% CI 0.859-0.877) in general hospitalized patients, with an optimal cutoff point of 7.5 mmol/L, a sensitivity of 76.5% and a specificity of 84.2%. Conclusion We determined that sodium fluctuation level had a dose-dependent association with increased mortality in general hospitalized patients. Sodium fluctuation level could be used to develop a single parameter system in predicting mortality in general hospitalized patients with acceptable accuracy, sensitivity, and specificity.
Collapse
Affiliation(s)
- Siyu Liang
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Lize Sun
- Eight-year Program of Clinical Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Yuelun Zhang
- Central Research Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Qi Zhang
- Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Nan Jiang
- 4+4 Medical Doctor Program, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Huijuan Zhu
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Shi Chen
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Hui Pan
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| |
Collapse
|
|
7
|
Liang S, Chang Q, Zhang Y, Du H, Zhu H, Chen S, Pan H. CARDS, a Novel Prognostic Index for Risk Stratification and In-Hospital Monitoring. J Clin Med 2024; 13:1961. [PMID: 38610725 PMCID: PMC11012846 DOI: 10.3390/jcm13071961] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2024] [Revised: 03/14/2024] [Accepted: 03/19/2024] [Indexed: 04/14/2024] Open
Abstract
Background: Sodium fluctuation is independently associated with clinical deterioration. We developed and validated a prognostic index based on sodium fluctuation for risk stratification and in-hospital monitoring. Methods: This study included 33,323 adult patients hospitalized at a tertiary care hospital in 2014. The first 28,279 hospitalizations were analyzed to develop the model and then the validity of the model was tested using data from 5044 subsequent hospitalizations. We predict in-hospital mortality using age, comorbidity, range of sodium fluctuation, and duration of sodium fluctuation, abbreviated as CARDS. Results: In-hospital mortality was similar in the derivation (0.6%) and validation (0.4%) cohorts. In the derivation cohort, four independent risk factors for mortality were identified using logistic regression: age (66-75, 2 points; >75, 3 points); Charlson comorbidity index (>2, 5 points); range of sodium fluctuation (7-10, 4 points; >10, 10 points); and duration of fluctuation (≤3, 3 points). The AUC was 0.907 (95% CI: 0.885-0.928) in the derivation cohort and 0.932 (95% CI: 0.895-0.970) in the validation cohort. In the derivation cohort, in-hospital mortality was 0.106% in the low-risk group (0-7 points), 1.076% in the intermediate-risk group (8-14 points), and 8.463% in the high-risk group (15-21 points). In the validation cohort, in-hospital mortality was 0.049% in the low-risk group, 1.064% in the intermediate-risk group, and 8.403% in the high-risk group. Conclusions: These results suggest that patients at low, intermediate, and high risk for in-hospital mortality may be identified by CARDS mainly based on sodium fluctuation.
Collapse
Affiliation(s)
- Siyu Liang
- Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Centre, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences (PUMCH, CAMS & PUMC), Beijing 100730, China; (S.L.); (H.D.); (H.Z.)
| | - Qing Chang
- Medical Affairs, PUMCH, CAMS & PUMC, Beijing 100730, China;
| | - Yuelun Zhang
- Central Research Laboratory, PUMCH, CAMS & PUMC, Beijing 100730, China;
| | - Hanze Du
- Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Centre, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences (PUMCH, CAMS & PUMC), Beijing 100730, China; (S.L.); (H.D.); (H.Z.)
| | - Huijuan Zhu
- Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Centre, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences (PUMCH, CAMS & PUMC), Beijing 100730, China; (S.L.); (H.D.); (H.Z.)
| | - Shi Chen
- Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Centre, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences (PUMCH, CAMS & PUMC), Beijing 100730, China; (S.L.); (H.D.); (H.Z.)
| | - Hui Pan
- Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Centre, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences (PUMCH, CAMS & PUMC), Beijing 100730, China; (S.L.); (H.D.); (H.Z.)
| |
Collapse
|
|
8
|
Chongo G, Soldera J. Use of machine learning models for the prognostication of liver transplantation: A systematic review. World J Transplant 2024; 14:88891. [PMID: 38576762 PMCID: PMC10989468 DOI: 10.5500/wjt.v14.i1.88891] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Revised: 11/08/2023] [Accepted: 12/11/2023] [Indexed: 03/15/2024] Open
Abstract
BACKGROUND Liver transplantation (LT) is a life-saving intervention for patients with end-stage liver disease. However, the equitable allocation of scarce donor organs remains a formidable challenge. Prognostic tools are pivotal in identifying the most suitable transplant candidates. Traditionally, scoring systems like the model for end-stage liver disease have been instrumental in this process. Nevertheless, the landscape of prognostication is undergoing a transformation with the integration of machine learning (ML) and artificial intelligence models. AIM To assess the utility of ML models in prognostication for LT, comparing their per formance and reliability to established traditional scoring systems. METHODS Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, we conducted a thorough and standardized literature search using the PubMed/MEDLINE database. Our search imposed no restrictions on publication year, age, or gender. Exclusion criteria encompassed non-English stu dies, review articles, case reports, conference papers, studies with missing data, or those exhibiting evident methodological flaws. RESULTS Our search yielded a total of 64 articles, with 23 meeting the inclusion criteria. Among the selected studies, 60.8% originated from the United States and China combined. Only one pediatric study met the criteria. Notably, 91% of the studies were published within the past five years. ML models consistently demonstrated satisfactory to excellent area under the receiver operating characteristic curve values (ranging from 0.6 to 1) across all studies, surpassing the performance of traditional scoring systems. Random forest exhibited superior predictive capa bilities for 90-d mortality following LT, sepsis, and acute kidney injury (AKI). In contrast, gradient boosting excelled in predicting the risk of graft-versus-host disease, pneumonia, and AKI. CONCLUSION This study underscores the potential of ML models in guiding decisions related to allograft allocation and LT, marking a significant evolution in the field of prognostication.
Collapse
Affiliation(s)
- Gidion Chongo
- Department of Gastroenterology, University of South Wales, Cardiff CF37 1DL, United Kingdom
| | - Jonathan Soldera
- Department of Gastroenterology, University of South Wales, Cardiff CF37 1DL, United Kingdom
| |
Collapse
|
|
9
|
Nakamura A, Yoshimura T, Ichikawa T. Liver Disease-Related Sarcopenia: A Predictor of Poor Prognosis by Accelerating Hepatic Decompensation in Advanced Chronic Liver Disease. Cureus 2023; 15:e49078. [PMID: 38024081 PMCID: PMC10658123 DOI: 10.7759/cureus.49078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/19/2023] [Indexed: 12/01/2023] Open
Abstract
Background Sarcopenia is considered a prognostic factor for advanced chronic liver disease (ACLD) independent of liver function, but the underlying mechanisms are unknown. Here, we investigated whether sarcopenia contributed to hepatic decompensation and worsened prognosis. Methods This was a single-center retrospective study of 708 patients with chronic liver disease who underwent magnetic resonance elastography (MRE). Magnetic resonance imaging (MRI) was used to diagnose sarcopenia and hepatic decompensation (presence of ascites). Results The incidence of sarcopenia (29% overall) and age were significantly correlated to increased liver stiffness (LS) (p < 0.01 each), but age did not differ for LS ≥ 4 kPa. Rates of thrombocytopenia and varices increased at ≥4 kPa, and ascites (n = 52) accounted for 81% of patients with ≥6 kPa LS. Age, alcoholic liver disease, C-reactive protein, sodium level, and controlling nutritional status score were extracted as factors contributing to sarcopenia (all p < 0.05). In ACLD, sarcopenia was an independent predictor of ascites (p < 0.01), and in a follow-up analysis of 163 patients without ascites at baseline, the incidence of ascites in patients with sarcopenia was significantly higher, even after adjusting for LS and liver severity (p < 0.01). The Cox proportional hazards model indicated albumin-bilirubin score and sarcopenia as independent prognostic factors (p < 0.01 each). Conclusions In ACLD, both portal hypertension and liver disease-related sarcopenia were found to occur at ≥4 kPa. Sarcopenia was accompanied by mildly decreased sodium levels and contributed to the early development of ascites and poor prognosis, independent of liver function.
Collapse
|
|
10
|
Iida H, Maehira H, Mori H, Nitta N, Maekawa T, Takebayashi K, Kaida S, Miyake T, Tani M. Effect of early administration of tolvaptan on pleural effusion post-hepatectomy. Langenbecks Arch Surg 2023; 408:406. [PMID: 37845430 DOI: 10.1007/s00423-023-03136-4] [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: 03/13/2023] [Accepted: 10/04/2023] [Indexed: 10/18/2023]
Abstract
PURPOSE This study evaluated the efficacy of tolvaptan administration at the early stage after hepatectomy to control pleural effusion and improve the postoperative course. METHODS Patients were administered tolvaptan (7.5 mg) and spironolactone (25 mg) from postoperative day 1 to postoperative day 5 (tolvaptan group, n = 68) for 13 months. Early administration of tolvaptan was not provided in the control group (n = 68); however, diuretics were appropriately administered according to the patient's condition. The amount of pleural effusion on computed tomography on postoperative day 5 was compared between the two groups. RESULTS The amount of pleural effusion and increase in body weight on postoperative day 5 showed significant differences in both groups (p < 0.001 and p = 0.019, respectively). However, the rate of pleural aspiration and the duration of postoperative hospitalization were comparable between the groups. The amount of intraoperative blood loss and lack of early administration of tolvaptan were identified as independent risk factors contributing to pleural effusion on multivariate analysis. CONCLUSION Early administration of tolvaptan to patients after hepatectomy was found to be capable of controlling postoperative pleural effusion and increase in body weight, but it did not reduce the rate of pleural aspiration or the hospitalization period.
Collapse
Affiliation(s)
- Hiroya Iida
- Department of Surgery, Shiga University of Medical Science, Seta Tsukinowa-Cho, Otsu, Shiga, 520-2192, Japan.
| | - Hiromitsu Maehira
- Department of Surgery, Shiga University of Medical Science, Seta Tsukinowa-Cho, Otsu, Shiga, 520-2192, Japan
| | - Haruki Mori
- Department of Surgery, Shiga University of Medical Science, Seta Tsukinowa-Cho, Otsu, Shiga, 520-2192, Japan
| | - Nobuhito Nitta
- Department of Surgery, Shiga University of Medical Science, Seta Tsukinowa-Cho, Otsu, Shiga, 520-2192, Japan
| | - Takeru Maekawa
- Department of Surgery, Shiga University of Medical Science, Seta Tsukinowa-Cho, Otsu, Shiga, 520-2192, Japan
| | - Katsushi Takebayashi
- Department of Surgery, Shiga University of Medical Science, Seta Tsukinowa-Cho, Otsu, Shiga, 520-2192, Japan
| | - Sachiko Kaida
- Department of Surgery, Shiga University of Medical Science, Seta Tsukinowa-Cho, Otsu, Shiga, 520-2192, Japan
| | - Toru Miyake
- Department of Surgery, Shiga University of Medical Science, Seta Tsukinowa-Cho, Otsu, Shiga, 520-2192, Japan
| | - Masaji Tani
- Department of Surgery, Shiga University of Medical Science, Seta Tsukinowa-Cho, Otsu, Shiga, 520-2192, Japan
| |
Collapse
|
|
11
|
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
|
|
12
|
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
|
|
13
|
Nakamura A, Yoshimura T, Ichikawa T. Mildly Low Serum Sodium Levels in Chronic Liver Disease: At Risk for Sarcopenia and Portal Hypertension. Cureus 2023; 15:e44419. [PMID: 37664343 PMCID: PMC10473259 DOI: 10.7759/cureus.44419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/30/2023] [Indexed: 09/05/2023] Open
Abstract
OBJECTIVE Hyponatremia and sarcopenia in advanced chronic liver disease (ACLD) are both associated with portal hypertension (PHT) and worse prognosis. This study investigated their interrelationship. METHODS This retrospective study analyzed 751 patients with CLD who underwent magnetic resonance elastography (MRE) at Nippon Kokan Hospital (Kawasaki, Japan). Patients were classified and studied in five groups based on serum sodium (Na) levels: <135, 135-136, 137-138, 139-140, and >140 mEq/L. PHT was assessed by thrombocytopenia, varices, and ascites, and magnetic resonance imaging (MRI) data were used to diagnose sarcopenia. RESULTS The proportions of the five groups were 3/4/13/32/48 (%), and the mean liver stiffness (LS) was 6.6/5.7/4.2/3.2/3.2 (kPa), with significant progressive increases at Na < 139 (p< 0.01). The incidence of all PHT events and sarcopenia also increased at <139 (each p < 0.01). By contrast, the LS thresholds for predicting thrombocytopenia, varices, and ascites increased from 3.5 to 4.7 and 5.1, respectively, and were the same at 3.4 for low Na (<139) and sarcopenia (all p < 0.01). Multivariate analysis of factors associated with low Na identified LS and sarcopenia as independent factors (p < 0.05 both). In the Cox proportional hazards model, low Na was a significant prognostic factor in ACLD (hazard ratio (HR) 5.33, p < 0.01); however, the albumin-bilirubin (ALBI) score (HR 2.49) and sarcopenia (HR 4.03) were extracted in the multivariate analysis (p < 0.05 both). CONCLUSIONS Studies using MRE imaging showed that low Na levels in CLD are associated with worse prognosis, not only due to elevated LS (i.e., PHT) but also the strong association with sarcopenia.
Collapse
|
|
14
|
Coxeter-Smith C, Al-Adhami A, Alrubaiy L. The Usefulness of Mayo End-stage Liver Disease (MELD) and MELD-Sodium (MELD-Na) Scores for Predicting Mortality in Cirrhotic Patients With Spontaneous Bacterial Peritonitis. Cureus 2023; 15:e38343. [PMID: 37143642 PMCID: PMC10151207 DOI: 10.7759/cureus.38343] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/30/2023] [Indexed: 05/06/2023] Open
Abstract
BACKGROUND Spontaneous bacterial peritonitis (SBP) is a common infection in patients with cirrhosis and ascites. Currently, the accuracy of the model for end-stage liver disease (MELD) and MELD-sodium (MELD-Na) as prognostic scores in this cohort is unclear. This study aimed to evaluate and compare the accuracy of MELD and MELD-Na for predicting 90-day mortality and determine whether the mortality risk estimates they provide accurately reflect the poor prognosis of patients with SBP Methods: Patients with cirrhosis and SBP were retrospectively identified from ascitic fluid samples sent for microscopy, culture and sensitivity analysis (1/1/18-31/12/20) and a previous audit. MELD and MELD-Na scores at diagnosis were calculated and associations with 90-day mortality were assessed using univariate analysis. Receiver operator characteristic curves were compared, and standardised mortality ratios (SMRs) were calculated by comparing the number of deaths observed to the number predicted by MELD and MELD-Na. RESULTS Of the 567 patients identified, 15 patients with cirrhosis and SBP were included. The 90-day mortality rate was 66.7% (10/15). Only concurrent hyponatremia (<135mmol/L) was associated with mortality (6/10 non-survivors vs 0/5 survivors, p=0.04). The difference in MELD and MELD-Na's C-statistic was not significant: 0.66 (95% Cl:0.35-0.98) vs 0.74 (95% Cl:0.47-1.0) respectively (p=0.72). Patients with a MELD-Na >18.5 had significantly higher 90-day mortality than patients with MELD-Na ≤18.5 (88.9% (8/9) vs. 33.3% (2/6), p=0.05). The SMR (95% Cl) for each MELD decile evaluated was 33.3 (0-79.5), 11.1 (0.2-22.0) and 3.4 (0-7.0) for scores ≤9,10-19 and 20-29 respectively. For each MELD-Na tertile, these were: 25 (0-59.6), 5.2 (0.1-10.3) and 2.7 (0.1-8.1) for scores <17,17-26, ≥27 respectively. CONCLUSION In a small cohort of patients with cirrhosis and SBP, the MELD's accuracy in predicting 90-day mortality was limited. MELD-Na's accuracy was higher but not significantly. Both scores consistently underestimated participants' mortality, therefore future studies could evaluate the accuracy of alternative prognostic scores in this patient group.
Collapse
Affiliation(s)
| | - Ali Al-Adhami
- Gastroenterology and Hepatology, St Mark's Hospital, London, GBR
| | | |
Collapse
|
|
15
|
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
|
|
16
|
Hyponatremia and Cancer: From Bedside to Benchside. Cancers (Basel) 2023; 15:cancers15041197. [PMID: 36831539 PMCID: PMC9953859 DOI: 10.3390/cancers15041197] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Revised: 02/07/2023] [Accepted: 02/08/2023] [Indexed: 02/16/2023] Open
Abstract
Hyponatremia is the most common electrolyte disorder encountered in hospitalized patients. This applies also to cancer patients. Multiple causes can lead to hyponatremia, but most frequently this electrolyte disorder is due to the syndrome of inappropriate antidiuresis. In cancer patients, this syndrome is mostly secondary to ectopic secretion of arginine vasopressin by tumoral cells. In addition, several chemotherapeutic drugs induce the release of arginine vasopressin by the hypothalamus. There is evidence that hyponatremia is associated to a more negative outcome in several pathologies, including cancer. Many studies have demonstrated that in different cancer types, both progression-free survival and overall survival are negatively affected by hyponatremia, whereas the correction of serum [Na+] has a positive effect on patient outcome. In vitro studies have shown that cells grown in low [Na+] have a greater proliferation rate and motility, due to a dysregulation in intracellular signalling pathways. Noteworthy, vasopressin receptors antagonists, which were approved more than a decade ago for the treatment of euvolemic and hypervolemic hyponatremia, have shown unexpected antiproliferative effects. Because of this property, vaptans were also approved for the treatment of polycystic kidney disease. In vitro evidence indicated that this family of drugs effectively counteracts proliferation and invasivity of cancer cells, thus possibly opening a new scenario among the pharmacological strategies to treat cancer.
Collapse
|
|
17
|
A Retrospective Study to Compare the Incidence of Hyponatremia after Administration between Linezolid and Tedizolid. Antibiotics (Basel) 2023; 12:antibiotics12020345. [PMID: 36830256 PMCID: PMC9952512 DOI: 10.3390/antibiotics12020345] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Revised: 01/31/2023] [Accepted: 02/03/2023] [Indexed: 02/11/2023] Open
Abstract
Linezolid (LZD) and Tedizolid (TZD) are oxazolidinone antibiotic for meticillin-resistant Staphylococcus aureus (MRSA). Severe hyponatremia after LZD administration have been reported. Severe hyponatremia cause seizures, unconsciousness, and even death. Therefore, we conducted a study to assess the change of serum sodium level after LZD and TZD therapy. We enrolled 67 patients treated with LZD and 28 treated with TZD. We monitored the serum sodium level from the administration to 14 days after administration of oxazolidinone drug. Hyponatremia was defined a sodiuln level ≤134 mmol/L after the initiation of oxazolidinone drug. The frequency of hyponatremia in the LZD group was significantly higher than that in the TZD group (39.7% vs. 11.1%, p < 0.05). The rate of patients administered by injection was significantly higher than in the LZD group than in the TZD group (52.9% vs. 14.8%, p < 0.01). Multiple logistic regression analyses identified the albumin level before the oxazolidinone drug therapy as the independent variables associated with the development of hyponatremia. We revealed that TZD is safer than LZD in terms of hyponatremia. Therefore, cases that LZD is administered by injection should be used more carefully with hyponatremia in patients with low albumin level.
Collapse
|
|
18
|
Detection of Hyponatremia Development in Hemodialysis Patients by Routine Automated Conductivity-Based Monitoring. ASAIO J 2023; 69:239-246. [PMID: 35438654 DOI: 10.1097/mat.0000000000001737] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023] Open
Abstract
Predialytic hyponatremia is associated with poor outcome in hemodialysis patients. Hypotonic hyponatremia is the most frequently encountered disorder reflecting mixed disorders combining extracellular fluid overload and free water excess, resulting from the interplay of intermittency of dialysis and diet observance, and likely precipitated by an acute or subacute illness. In this context, hyponatremia requires to be detected and worked up to identify and cure the cause. In this clinical case report, we describe preliminary results of using an online biosensor on a dialysis machine that provides automated predialysis plasma sodium concentration derived from dialysate conductivity measurements. Based on this biosensor, within a 5 year time frame, 11 patients out of more than 130 maintenance hemodialysis patients and over 40,000 dialysis sessions were identified with episodes of predialysis hyponatremia (≤135 mmol/l). In all patients, hyponatremic episodes were indicative of a severe underlying illness associated with fluid overload leading to plasma hypotonicity. Automated online predialysis plasma sodium concentration measurement offers an innovative, reliable, and cost-free tool that permits to detect hyponatremia as marker of an underlying illness development in dialysis patients. The value of this tool in supporting clinical decision-making deserves further studies in a large dialysis population.
Collapse
|
|
19
|
Zeng J, Li Q, Wu Q, Li L, Ye X, Liu J, Cao B. A Novel Online Calculator Predicting Acute Kidney Injury After Liver Transplantation: A Retrospective Study. Transpl Int 2023; 36:10887. [PMID: 36744052 PMCID: PMC9892055 DOI: 10.3389/ti.2023.10887] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Accepted: 01/11/2023] [Indexed: 01/20/2023]
Abstract
Acute kidney injury (AKI) after liver transplantation (LT) is a common complication, and its development is thought to be multifactorial. We aimed to investigate potential risk factors and build a model to identify high-risk patients. A total of 199 LT patients were enrolled and each patient data was collected from the electronic medical records. Our primary outcome was postoperative AKI as diagnosed and classified by the KDIGO criteria. A least absolute shrinkage and selection operating algorithm and multivariate logistic regression were utilized to select factors and construct the model. Discrimination and calibration were used to estimate the model performance. Decision curve analysis (DCA) was applied to assess the clinical application value. Five variables were identified as independent predictors for post-LT AKI, including whole blood serum lymphocyte count, RBC count, serum sodium, insulin dosage and anhepatic phase urine volume. The nomogram model showed excellent discrimination with an AUC of 0.817 (95% CI: 0.758-0.876) in the training set. The DCA showed that at a threshold probability between 1% and 70%, using this model clinically may add more benefit. In conclusion, we developed an easy-to-use tool to calculate the risk of post-LT AKI. This model may help clinicians identify high-risk patients.
Collapse
Affiliation(s)
- Jianfeng Zeng
- Department of Anesthesiology, The Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China
| | - Qiaoyun Li
- Department of Physiology, The Zhongshan Medical School of Sun Yat-sen University, Guangzhou, China
| | - Qixing Wu
- Department of Anesthesiology, The First Affiliated Hospital University of Science and Technology of China, Hefei, China
| | - Li Li
- Department of Anesthesiology, The Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xijiu Ye
- Department of Anesthesiology, The Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China
| | - Jing Liu
- Department of Anesthesiology, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, China,*Correspondence: Jing Liu, ; Bingbing Cao,
| | - Bingbing Cao
- Department of Anesthesiology, The Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China,*Correspondence: Jing Liu, ; Bingbing Cao,
| |
Collapse
|
|
20
|
Salt consumption and mortality risk in cirrhotic patients: results from a cohort study. J Nutr Sci 2022; 11:e99. [PMID: 36405096 PMCID: PMC9672831 DOI: 10.1017/jns.2022.69] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Accepted: 07/29/2022] [Indexed: 11/10/2022] Open
Abstract
Since conducting a long-term randomised clinical trial is not logical and feasible to find the optimum dosage of salt intake in patients with cirrhosis, cohort studies are the best design to assess the long-term effects of dietary salt on the survival of cirrhotic patients. This cohort study aimed to evaluate the association between dietary intake of salt and mortality risk in cirrhotic patients. The present study was designed as a cohort in three referral hospitals in Iran in 2018. One hundred and twenty-one patients aged between 20 and 70 years with established cirrhosis were recruited. Dietary intakes, demographic data and disease severity were evaluated at the baseline. Participants were followed up annually. Crude survival was greater in patients with low-to-moderate salt consumption rather than in those with high consumption, and in non-consumers [34⋅26 (95 % CI 33⋅04, 35⋅49) v. 30⋅41 (95 % CI 27⋅13, 33⋅69) v. 32⋅72 (95 % CI 30⋅63, 34⋅80), P = 0⋅028; log-rank test]. Using the Cox proportional hazard model, it was shown that the risk of mortality in the high-salt consumption category was approximately 126 % higher than that of the reference category (non-consumers) [HR value 2⋅26, (95 % CI 0⋅91, 5⋅63)], while this risk for the low-to-moderate consumption group was about 28 % lower than the reference category [HR value 0⋅72, (95 % CI 0⋅26, 1⋅99), P-trend = 0⋅04]. In conclusion, a high daily dietary intake of salt might increase the rate of mortality and moderate salt restriction (instead of elimination of salt) decreases the risk of death.
Collapse
|
|
21
|
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
|
|
22
|
Flores-Calderón J, Cisneros-Garza LE, Chávez-Barrera JA, Vázquez-Frias R, Reynoso-Zarzosa FA, Martínez-Bejarano DL, Consuelo-Sánchez A, Reyes-Apodaca M, Zárate-Mondragón FE, Sánchez-Soto MP, Alcántara-García RI, González-Ortiz B, Ledesma-Ramírez S, Espinosa-Saavedra D, Cura-Esquivel IA, Macías-Flores J, Hinojosa-Lezama JM, Hernández-Chávez E, Zárate-Guerrero JR, Gómez-Navarro G, Bilbao-Chávez LP, Sosa-Arce M, Flores-Fong LE, Lona-Reyes JC, Estrada-Arce EV, Aguila-Cano R. Consensus on the management of complications of cirrhosis of the liver in pediatrics. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2022; 87:462-485. [PMID: 35810090 DOI: 10.1016/j.rgmxen.2022.06.011] [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: 11/12/2021] [Accepted: 03/08/2022] [Indexed: 12/07/2022]
Abstract
The Asociación Mexicana de Hepatología A.C. carried out the Consensus on the Management of Complications of Cirrhosis of the Liver in Pediatrics to provide physicians with useful information for treating said complications. A group of pediatric gastroenterologists and experts in nutrition, nephrology, and infectious diseases participated and reviewed the medical literature. The Delphi method was applied to obtain the level of agreement on the statements that were formulated. The statements were sent to the participants to be analyzed and voted upon, after which they were discussed in virtual sessions, and the final versions were produced. The aim of the consensus results was to issue indications for the management of pediatric patients with liver cirrhosis, to prevent or control complications.
Collapse
Affiliation(s)
- J Flores-Calderón
- UMAE Hospital de Pediatría, CMN XXI Dr. Silvestre Frenk Freund IMSS, Cd, México, Mexico.
| | | | - J A Chávez-Barrera
- UMAE Hospital General CMN La Raza, Dr. Gaudencio González Garza IMSS, Cd, México, Mexico
| | | | | | | | | | | | | | - M P Sánchez-Soto
- Hospital de Especialidades del Niño y la mujer de Querétaro Dr. Felipe Núñez Lara, Querétaro, Mexico
| | | | - B González-Ortiz
- UMAE Hospital de Pediatría, CMN XXI Dr. Silvestre Frenk Freund IMSS, Cd, México, Mexico
| | - S Ledesma-Ramírez
- UMAE Hospital de Pediatría, CMN XXI Dr. Silvestre Frenk Freund IMSS, Cd, México, Mexico
| | - D Espinosa-Saavedra
- UMAE Hospital de Pediatría, CMN XXI Dr. Silvestre Frenk Freund IMSS, Cd, México, Mexico
| | | | - J Macías-Flores
- Hospital Infantil de Especialidades de Chihuahua, Chihuahua, Mexico
| | | | - E Hernández-Chávez
- UMAE Hospital de Pediatría Centro Médico de Occidente, IMSS, Guadalajara, Mexico
| | - J R Zárate-Guerrero
- UMAE Hospital de Pediatría Centro Médico de Occidente, IMSS, Guadalajara, Mexico
| | - G Gómez-Navarro
- UMAE Hospital de Pediatría Centro Médico de Occidente, IMSS, Guadalajara, Mexico
| | - L P Bilbao-Chávez
- UMAE Hospital General CMN La Raza, Dr. Gaudencio González Garza IMSS, Cd, México, Mexico
| | - M Sosa-Arce
- UMAE Hospital General CMN La Raza, Dr. Gaudencio González Garza IMSS, Cd, México, Mexico
| | - L E Flores-Fong
- Nuevo Hospital Civil de Guadalajara "Dr. Juan I. Menchaca", Guadalajara, Mexico
| | - J C Lona-Reyes
- Nuevo Hospital Civil de Guadalajara "Dr. Juan I. Menchaca", Guadalajara, Mexico
| | - E V Estrada-Arce
- Nuevo Hospital Civil de Guadalajara "Dr. Juan I. Menchaca", Guadalajara, Mexico
| | - R Aguila-Cano
- Nuevo Hospital Civil de Guadalajara "Dr. Juan I. Menchaca", Guadalajara, Mexico
| |
Collapse
|
|
23
|
Alleviation of liver cirrhosis and associated portal-hypertension by Astragalus species in relation to their UPLC-MS/MS metabolic profiles: a mechanistic study. Sci Rep 2022; 12:11884. [PMID: 35831335 PMCID: PMC9279505 DOI: 10.1038/s41598-022-15958-1] [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: 05/03/2022] [Accepted: 07/01/2022] [Indexed: 11/08/2022] Open
Abstract
Liver cirrhosis is a late-stage liver disease characterized by excessive fibrous deposition triggering portal-hypertension (PH); the prime restrainer for cirrhosis-related complications. Remedies that can dually oppose hepatic fibrosis and lower PH, may prevent progression into decompensated-cirrhosis. Different Astragalus-species members have shown antifibrotic and diuretic actions with possible subsequent PH reduction. However, A.spinosus and A.trigonus were poorly tested for eliciting these actions. Herein, A.spinosus and A.trigonus roots and aerial parts extracts were subjected to comprehensive metabolic-fingerprinting using UHPLC-MS/MS resulting in 56 identified phytoconstituents, followed by chemometric untargeted analysis that revealed variable metabolic profiles exemplified by different species and organ types. Consequently, tested extracts were in-vivo evaluated for potential antifibrotic/anticirrhotic activity by assessing specific markers. The mechanistic prospective to induce diuresis was investigated by analyzing plasma aldosterone and renal-transporters gene-expression. Serum apelin and dimethylarginine-dimethylaminohydrolase-1 were measured to indicate the overall effect on PH. All extracts amended cirrhosis and PH to varying extents and induced diuresis via different mechanisms. Further, An OPLS model was built to generate a comprehensive metabolic-profiling of A.spinosus and A.trigonus secondary-metabolites providing a chemical-based evidence for their efficacious consistency. In conclusion, A.spinosus and A.trigonus organs comprised myriad pharmacologically-active constituents that act synergistically to ameliorate cirrhosis and associated PH.
Collapse
|
|
24
|
Yoshida S, Suda G, Ohara M, Kimura M, Yang Z, Maehara O, Fu Q, Hosoda S, Akinori K, Tokuchi Y, Yamada R, Kitagataya T, Suzuki K, Kawagishi N, Nakai M, Sho T, Natsuizaka M, Morikawa K, Ogawa K, Ohnishi S, Sakamoto N. Overestimated renal function in patients with liver cirrhosis predicts poor prognosis. Hepatol Res 2022; 52:603-613. [PMID: 35352857 DOI: 10.1111/hepr.13765] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Revised: 02/28/2022] [Accepted: 03/12/2022] [Indexed: 01/18/2023]
Abstract
AIM A high prevalence of overestimated renal function in patients with liver cirrhosis (LC) has been reported; nonetheless, its impact on prognosis remains unclear. We aimed to evaluate the impact of overestimated renal function on prognosis in patients with LC. METHODS An overestimated renal function was defined as a >20% increase in the creatinine-based estimated glomerular filtration rate (eGFR), compared with cystatin C-based eGFR. LC patients with conserved serum, who were evaluated for muscle atrophy and had proper clinical information were included, and their prognostic factors were analyzed. RESULTS A total of 215 consecutive patients with LC were included. The prevalence of overestimated renal function was 29.8% (64/215). Kaplan-Meier survival analysis revealed that patients with overestimated renal function had a poorer prognosis than those without overestimated renal function (hazard ratio [HR]: 2.217 95% confidence interval [CI]: 1.290-3.810; p = 0.001). Subgroup analysis showed that overestimated renal function was a significant prognostic factor, irrespective of sex and the presence of hepatocellular carcinoma (HCC). Multivariate Cox regression analyses revealed that overestimated renal function was a significant and independent factor predictive of poor prognosis in the entire cohort (HR: 2.050; 95% CI: 1.041-4.037; p = 0.038) and in subgroups classified by Child-Pugh class A (HR: 2.131; 95% CI: 1.019-4.458; p = 0.044), Model for End-Stage Liver Disease score ≤9 (HR: 2.303; 95% CI: 1.038-5.109; p = 0.04), and presence of HCC (HR: 2.290; 95% CI: 1.128-4.651; p = 0.022). CONCLUSION Overestimated renal function is a significant and independent prognostic factor in patients with LC.
Collapse
Affiliation(s)
- Sonoe Yoshida
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Goki Suda
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Masatsugu Ohara
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Megumi Kimura
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Zijian Yang
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Osamu Maehara
- Department of Pathophysiology and Therapeutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan
| | | | - Shunichi Hosoda
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Kubo Akinori
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Yoshimasa Tokuchi
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Ren Yamada
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Takashi Kitagataya
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Kazuharu Suzuki
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Naoki Kawagishi
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Masato Nakai
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Takuya Sho
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Mitsuteru Natsuizaka
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Kenichi Morikawa
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Koji Ogawa
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Shunsuke Ohnishi
- Department of Pathophysiology and Therapeutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan
| | - Naoya Sakamoto
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| |
Collapse
|
|
25
|
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
|
|
26
|
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
|
|
27
|
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
|
|
28
|
Thuluvath PJ, Alukal JJ, Zhang T. Impact of Hyponatremia on Morbidity, Mortality, and Resource Utilization in Portal Hypertensive Ascites: A Nationwide Analysis. J Clin Exp Hepatol 2022; 12:871-875. [PMID: 35677510 PMCID: PMC9168704 DOI: 10.1016/j.jceh.2021.10.145] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2021] [Accepted: 10/22/2021] [Indexed: 12/12/2022] Open
Abstract
Background and aims Ascites and hyponatremia are important milestones of worsening portal hypertension in those with cirrhosis. The objective of our study was to evaluate the differences in clinical characteristics, resource utilization, and disposition of hospitalized cirrhotic patients with ascites with and without hyponatremia. Methods The National Inpatient Sample (NIS) database was used to identify all adult hospitalized patients with a diagnosis of cirrhosis and ascites with or without hyponatremia from 2016 to 2017 using ICD-10 codes. Results During the study period, 10,187 (7.6%) hospitalized patients with cirrhosis had ascites and hyponatremia and 34,555 (24.3%) had ascites but no hyponatremia. Elixhauser comorbidity score, excluding liver disease, was higher in hyponatremic patients (median 21 vs. 12, P < 0.001). Acute kidney injury (50.3% vs. 32.8%, P < 0.001) and sepsis (16.8% vs. 11.8%, P < 0.001) were more common in hyponatremic patients compared to those without hyponatremia. Similarly, acute respiratory failure, coagulopathy, hepatorenal syndrome, spontaneous bacterial peritonitis, acute (on chronic) liver failure, and liver cancer were more common in hyponatremic patients. Hyponatremia patients had a higher number of inpatient procedures, longer (6 days vs. 4 days, P < 0.001) hospital stay, and had higher hospital charges ($97,327 vs. $72,278, P < 0.01) than those without hyponatremia. Inpatient mortality was 38% higher in hyponatremic patients (9.8% vs. 7.1%, P < 0.001) compared to those without hyponatremia. Additionally, hyponatremic patients were less likely to have routine home discharges with self-care. Conclusion In conclusion, using a large and diverse national cohort of unselected patients, we were able to show that hyponatremia in patients with cirrhosis and ascites is associated with poor clinical outcomes and increased resource utilization.
Collapse
Key Words
- AHRQ, Agency for Healthcare Research and Quality
- AKI, Acute kidney injury
- ALF, Acute liver failure
- HCC, Hepatocellular carcinoma
- HCUP, Healthcare cost and Utilization Project
- HE, Hepatic encephalopathy
- HRS, Hepatorenal syndrome
- ICU, Intensive care units
- NIS, National Inpatient Sample
- SBP, Spontaneous bacterial peritonitis
- SD, Standard deviation
- ascites
- cirrhosis
- hyponatremia
- mortality
- resource utilization
Collapse
Affiliation(s)
- Paul J. Thuluvath
- Institute of Digestive Health & Liver Diseases, Mercy Medical Center, Baltimore MD, USA
- Department of Medicine, University of Maryland School of Medicine, Baltimore MD, USA
| | - Joseph J. Alukal
- Institute of Digestive Health & Liver Diseases, Mercy Medical Center, Baltimore MD, USA
| | - Talan Zhang
- Institute of Digestive Health & Liver Diseases, Mercy Medical Center, Baltimore MD, USA
| |
Collapse
|
|
29
|
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
|
|
30
|
Wang S, Xu Y, Zhao Y, Zhang S, Li M, Li X, He J, Zhou H, Ge Z, Li R, Yang B. N-(4-acetamidophenyl)-5-acetylfuran-2-carboxamide as a novel orally available diuretic that targets urea transporters with improved PD and PK properties. Eur J Med Chem 2021; 226:113859. [PMID: 34601246 DOI: 10.1016/j.ejmech.2021.113859] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Revised: 09/17/2021] [Accepted: 09/17/2021] [Indexed: 10/20/2022]
Abstract
Urea transporters (UTs) have been identified as new targets for diuretics. Functional deletion of UTs led to urea-selective urinary concentrating defects with relative salt sparing. In our previous study, a UT inhibitor with a diarylamide scaffold, which is denoted as 11a, was demonstrated as the first orally available UT inhibitor. However, the oral bioavailability of 11a was only 4.38%, which obstructed its clinical application. In this work, by replacing the nitro group of 11a with an acetyl group, 25a was obtained. Compared with 11a, 25a showed a 10 times stronger inhibitory effect on UT-B (0.14 μM vs. 1.41 μM in rats, and 0.48 μM vs. 5.82 μM in mice) and a much higher inhibition rate on UT-A1. Moreover, the metabolic stability both in vitro and in vivo and the drug-like properties (permeability and solubility) of 25a were obviously improved compared with those of 11a. Moreover, the bioavailability of 25a was 15.18%, which was 3 times higher than that of 11a, thereby resulting in significant enhancement of the diuretic activities in rats and mice. 25a showed excellent potential for development as a promising clinical diuretic candidate for targeting UTs to treat diseases that require long-term usage of diuretics, such as hyponatremia.
Collapse
Affiliation(s)
- Shuyuan Wang
- Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China; State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100191, China.
| | - Yue Xu
- Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China
| | - Yan Zhao
- State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100191, China; College of Pharmacy, Inner Mongolia Medical University, 010110, China
| | - Shun Zhang
- Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China
| | - Min Li
- Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China
| | - Xiaowei Li
- Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China
| | - Jinzhao He
- Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China
| | - Hong Zhou
- Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China
| | - Zemei Ge
- State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100191, China
| | - Runtao Li
- State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100191, China.
| | - Baoxue Yang
- Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China; State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100191, China.
| |
Collapse
|
|
31
|
Bartalis E, Gergics M, Tinusz B, Földi M, Kiss S, Németh D, Solymár M, Szakács Z, Hegyi P, Mezösi E, Bajnok L. Prevalence and Prognostic Significance of Hyponatremia in Patients With Lung Cancer: Systematic Review and Meta-Analysis. Front Med (Lausanne) 2021; 8:671951. [PMID: 34950676 PMCID: PMC8688712 DOI: 10.3389/fmed.2021.671951] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Accepted: 10/29/2021] [Indexed: 01/15/2023] Open
Abstract
Background: The prevalence of hyponatremia is highly variable among patients with lung cancer. However, its prevalence and prognostic significance in subgroups of patients with lung cancer have not yet been evaluated in a meta-analysis. Methods: We have registered our meta-analysis and review protocol to the PROSPERO International Prospective Register of Systematic Reviews, with the following registration number: CRD42020167013. A systematic search was done in the following sources: MEDLINE, Embase, CENTRAL, Web of Science, ClinicalTrials.gov, a WHO Global Health Library. Results: We identified a total of 8,962 potentially eligible studies, and we included 31 articles in our evaluation. The prevalence of hyponatremia in patients with lung cancer varied between 3 and 94.8% with an average of 25% without any significant differences between the following subgroups: histotype, gender, age, Eastern Cooperative Oncology Group (ECOG) state, and the extent of disease. The overall survival (OS) was significantly lower in hyponatremic compared to normonatremic patients at 10 months [RR.59 (95% CI.47-0.74), p < 0.001] and at 20 months [RR.44 (95% CI.33-0.59), p < 0.001], with worse survival rates in non-small cell lung cancer (NSCLC) [RR.27 (95% CI.12-0.44), p < 0.001] than in small cell lung cancer (SCLC) [RR.42 (95% CI.27-0.57), p < 0.001]. If hyponatremia was corrected, OS at 10 months was significantly higher than in the uncorrected hyponatremia group [RR 1.83 (95% CI 1.37-2.44), p < 0.001], but, at 20 months, no statistically significant difference could be found between these subgroups [RR 2.65 (95% CI.94-7.50), p = 0.067]. Conclusions: Patients with lung cancer diagnosed with hyponatremia, especially patients with NSCLC, seem to have significantly lower survival rates than normonatremic patients. If hyponatremia remains uncorrected, the mortality rates might be even higher.
Collapse
Affiliation(s)
- Eszter Bartalis
- Medical School, Institute for Translational Medicine, University of Pécs, Pécs, Hungary
- University of Medicine, Pharmacy, Science and Technology of Târgu Mureş, Târgu Mureş, Romania
| | - Marin Gergics
- First Department of Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - Benedek Tinusz
- Medical School, Institute for Translational Medicine, University of Pécs, Pécs, Hungary
- Szentágothai Research Centre, University of Pécs, Pécs, Hungary
| | - Mária Földi
- Medical School, Institute for Translational Medicine, University of Pécs, Pécs, Hungary
- Szentágothai Research Centre, University of Pécs, Pécs, Hungary
- Doctoral School of Clinical Medicine, University of Szeged, Szeged, Hungary
| | - Szabolcs Kiss
- Medical School, Institute for Translational Medicine, University of Pécs, Pécs, Hungary
- Szentágothai Research Centre, University of Pécs, Pécs, Hungary
- Doctoral School of Clinical Medicine, University of Szeged, Szeged, Hungary
| | - Dávid Németh
- Medical School, Institute for Translational Medicine, University of Pécs, Pécs, Hungary
- Szentágothai Research Centre, University of Pécs, Pécs, Hungary
| | - Margit Solymár
- Medical School, Institute for Translational Medicine, University of Pécs, Pécs, Hungary
- Szentágothai Research Centre, University of Pécs, Pécs, Hungary
| | - Zsolt Szakács
- Medical School, Institute for Translational Medicine, University of Pécs, Pécs, Hungary
- Szentágothai Research Centre, University of Pécs, Pécs, Hungary
| | - Péter Hegyi
- Medical School, Institute for Translational Medicine, University of Pécs, Pécs, Hungary
- Szentágothai Research Centre, University of Pécs, Pécs, Hungary
| | - Emese Mezösi
- First Department of Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - László Bajnok
- First Department of Medicine, Medical School, University of Pécs, Pécs, Hungary
| |
Collapse
|
|
32
|
Fibbi B, Marroncini G, Anceschi C, Naldi L, Peri A. Hyponatremia and Oxidative Stress. Antioxidants (Basel) 2021; 10:1768. [PMID: 34829639 PMCID: PMC8614907 DOI: 10.3390/antiox10111768] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 10/26/2021] [Accepted: 11/03/2021] [Indexed: 12/15/2022] Open
Abstract
Hyponatremia, i.e., the presence of a serum sodium concentration ([Na+]) < 136 mEq/L, is the most frequent electrolyte imbalance in the elderly and in hospitalized patients. Symptoms of acute hyponatremia, whose main target is the central nervous system, are explained by the "osmotic theory" and the neuronal swelling secondary to decreased extracellular osmolality, which determines cerebral oedema. Following the description of neurological and systemic manifestations even in mild and chronic hyponatremia, in the last decade reduced extracellular [Na+] was associated with detrimental effects on cellular homeostasis independently of hypoosmolality. Most of these alterations appeared to be elicited by oxidative stress. In this review, we focus on the role of oxidative stress on both osmolality-dependent and -independent impairment of cell and tissue functions observed in hyponatremic conditions. Furthermore, basic and clinical research suggested that oxidative stress appears to be a common denominator of the degenerative processes related to aging, cancer progression, and hyponatremia. Of note, low [Na+] is able to exacerbate multiple manifestations of senescence and to decrease progression-free and overall survival in oncologic patients.
Collapse
Affiliation(s)
- Benedetta Fibbi
- Pituitary Diseases and Sodium Alterations Unit, AOU Careggi, 50139 Florence, Italy; (B.F.); (G.M.)
- Endocrinology, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, AOU Careggi, 50139 Florence, Italy; (C.A.); (L.N.)
| | - Giada Marroncini
- Pituitary Diseases and Sodium Alterations Unit, AOU Careggi, 50139 Florence, Italy; (B.F.); (G.M.)
- Endocrinology, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, AOU Careggi, 50139 Florence, Italy; (C.A.); (L.N.)
| | - Cecilia Anceschi
- Endocrinology, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, AOU Careggi, 50139 Florence, Italy; (C.A.); (L.N.)
| | - Laura Naldi
- Endocrinology, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, AOU Careggi, 50139 Florence, Italy; (C.A.); (L.N.)
| | - Alessandro Peri
- Pituitary Diseases and Sodium Alterations Unit, AOU Careggi, 50139 Florence, Italy; (B.F.); (G.M.)
- Endocrinology, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, AOU Careggi, 50139 Florence, Italy; (C.A.); (L.N.)
| |
Collapse
|
|
33
|
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
|
|
34
|
Ivanics T, Leonard-Murali S, Mouzaihem H, Moonka D, Kitajima T, Yeddula S, Shamaa MT, Rizzari M, Collins K, Yoshida A, Abouljoud M, Nagai S. Extreme hyponatremia as a risk factor for early mortality after liver transplantation in the MELD-sodium era. Transpl Int 2021; 34:2856-2868. [PMID: 34580929 DOI: 10.1111/tri.14123] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Revised: 08/17/2021] [Accepted: 09/20/2021] [Indexed: 01/15/2023]
Abstract
The impact of hyponatremia on waitlist and post-transplant outcomes following the implementation of MELD-Na-based liver allocation remains unclear. We investigated waitlist and postliver transplant (LT) outcomes in patients with hyponatremia before and after implementing MELD-Na-based allocation. Adult patients registered for a primary LT between 2009 and 2021 were identified in the OPTN/UNOS database. Two eras were defined; pre-MELD-Na and post-MELD-Na. Extreme hyponatremia was defined as a serum sodium concentration ≤120 mEq/l. Ninety-day waitlist outcomes and post-LT survival were compared using Fine-Gray proportional hazard and mixed-effects Cox proportional hazard models. A total of 118 487 patients were eligible (n = 64 940: pre-MELD-Na; n = 53 547: post-MELD-Na). In the pre-MELD-Na era, extreme hyponatremia at listing was associated with an increased risk of 90-day waitlist mortality ([ref: 135-145] HR: 3.80; 95% CI: 2.97-4.87; P < 0.001) and higher transplant probability (HR: 1.67; 95% CI: 1.38-2.01; P < 0.001). In the post-MELD-Na era, patients with extreme hyponatremia had a proportionally lower relative risk of waitlist mortality (HR: 2.27; 95% CI 1.60-3.23; P < 0.001) and proportionally higher transplant probability (HR: 2.12; 95% CI 1.76-2.55; P < 0.001) as patients with normal serum sodium levels (135-145). Extreme hyponatremia was associated with a higher risk of 90, 180, and 365-day post-LT survival compared to patients with normal serum sodium levels. With the introduction of MELD-Na-based allocation, waitlist outcomes have improved in patients with extreme hyponatremia but they continue to have worse short-term post-LT survival.
Collapse
Affiliation(s)
- Tommy Ivanics
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Detroit, MI, USA
| | | | - Hassan Mouzaihem
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Detroit, MI, USA
| | - Dilip Moonka
- Division of Gastroenterology and Hepatology, Henry Ford Hospital, Detroit, MI, USA
| | - Toshihiro Kitajima
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Detroit, MI, USA
| | - Sirisha Yeddula
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Detroit, MI, USA
| | - Mhd Tayseer Shamaa
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Detroit, MI, USA
| | - Michael Rizzari
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Detroit, MI, USA
| | - Kelly Collins
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Detroit, MI, USA
| | - Atsushi Yoshida
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Detroit, MI, USA
| | - Marwan Abouljoud
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Detroit, MI, USA
| | - Shunji Nagai
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Detroit, MI, USA
| |
Collapse
|
|
35
|
Mahiliavets EV, Bozhko YN, Mahiliavets ON. Use of laparocentesis in the treatment of ascites in patients with liver cirrhosis. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF BELARUS, MEDICAL SERIES 2021; 18:362-374. [DOI: 10.29235/1814-6023-2021-18-3-362-374] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Ascites occurs in about 60 % of patients with cirrhosis within 10 years of diagnosis. Laparocentesis is the preferred first-line therapy in patients with cirrhosis and massive tense ascites, allowing more than 5–6 liters of ascitic fluid to be removed at one time. The search for informative prognostic factors and the development of a method for predicting unfavorable outcomes of repeated laparocenteses in patients with ascites are relevant to timely refer this contingent of patients to perform TIPS.The purpose of the study was to develop and evaluate the diagnostic significance of a model for determining the probability of unfavorable outcomes of laparocentesis in patients with ascites on the background of liver cirrhosis.The results of treatment of 99 patients with the ascitic syndrome associated with intrahepatic portal hypertension were studied. The multiple regression analysis using the binary response logit model was carried out to calculate the prediction models. The analysis of the treatment results of patients with liver cirrhosis and ascites by the laparocentesis method revealed a number of factors that influence the onset of an unfavorable outcome. 2 models with the inclusion of initial variables are the most promising for forecasting. Model A includes: patient weight, serum-ascites total protein gradient, hyponatremia; model B: MELD-Na score, serum-ascitic total protein gradient, patient weight. The developed prediction method is highly informative, effective, easily applicable, and can be widely used in clinical practice.The ability to predict an unfavorable outcome in patients with portal hypertension and ascites after laparocentesis allows for a personalized approach in the process of timely selection of more effective, but also more expensive treatment methods, such as TIPS, which will help us to increase the therapy effectiveness and the survival of this cohort of patients.
Collapse
|
|
36
|
Yoshiji H, Nagoshi S, Akahane T, Asaoka Y, Ueno Y, Ogawa K, Kawaguchi T, Kurosaki M, Sakaida I, Shimizu M, Taniai M, Terai S, Nishikawa H, Hiasa Y, Hidaka H, Miwa H, Chayama K, Enomoto N, Shimosegawa T, Takehara T, Koike K. Evidence-based clinical practice guidelines for Liver Cirrhosis 2020. J Gastroenterol 2021; 56:593-619. [PMID: 34231046 PMCID: PMC8280040 DOI: 10.1007/s00535-021-01788-x] [Citation(s) in RCA: 189] [Impact Index Per Article: 47.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Accepted: 02/25/2021] [Indexed: 02/07/2023]
Abstract
The first edition of the clinical practice guidelines for liver cirrhosis was published in 2010, and the second edition was published in 2015 by the Japanese Society of Gastroenterology (JSGE). The revised third edition was recently published in 2020. This version has become a joint guideline by the JSGE and the Japan Society of Hepatology (JSH). In addition to the clinical questions (CQs), background questions (BQs) are new items for basic clinical knowledge, and future research questions (FRQs) are newly added clinically important items. Concerning the clinical treatment of liver cirrhosis, new findings have been reported over the past 5 years since the second edition. In this revision, we decided to match the international standards as much as possible by referring to the latest international guidelines. Newly developed agents for various complications have also made great progress. In comparison with the latest global guidelines, such as the European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases (AASLD), we are introducing data based on the evidence for clinical practice in Japan. The flowchart for nutrition therapy was reviewed to be useful for daily medical care by referring to overseas guidelines. We also explain several clinically important items that have recently received focus and were not mentioned in the last editions. This digest version describes the issues related to the management of liver cirrhosis and several complications in clinical practice. The content begins with a diagnostic algorithm, the revised flowchart for nutritional therapy, and refracted ascites, which are of great importance to patients with cirrhosis. In addition to the updated antiviral therapy for hepatitis B and C liver cirrhosis, the latest treatments for non-viral cirrhosis, such as alcoholic steatohepatitis/non-alcoholic steatohepatitis (ASH/NASH) and autoimmune-related cirrhosis, are also described. It also covers the latest evidence regarding the diagnosis and treatment of liver cirrhosis complications, namely gastrointestinal bleeding, ascites, hepatorenal syndrome and acute kidney injury, hepatic encephalopathy, portal thrombus, sarcopenia, muscle cramp, thrombocytopenia, pruritus, hepatopulmonary syndrome, portopulmonary hypertension, and vitamin D deficiency, including BQ, CQ and FRQ. Finally, this guideline covers prognosis prediction and liver transplantation, especially focusing on several new findings since the last version. Since this revision is a joint guideline by both societies, the same content is published simultaneously in the official English journal of JSGE and JSH.
Collapse
Affiliation(s)
- Hitoshi Yoshiji
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan.
- Department of Gastroenterology, Nara Medical University, Shijo-cho 840, Kashihara, Nara, 634-8522, Japan.
| | - Sumiko Nagoshi
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Takemi Akahane
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Yoshinari Asaoka
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Yoshiyuki Ueno
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Koji Ogawa
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Takumi Kawaguchi
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Masayuki Kurosaki
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Isao Sakaida
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Masahito Shimizu
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Makiko Taniai
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Shuji Terai
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Hiroki Nishikawa
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Yoichi Hiasa
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Hisashi Hidaka
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Hiroto Miwa
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Kazuaki Chayama
- The Japan Society of Hepatology, Kashiwaya 2 Building 5F, 3-28-10 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan
| | - Nobuyuki Enomoto
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Tooru Shimosegawa
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Tetsuo Takehara
- The Japan Society of Hepatology, Kashiwaya 2 Building 5F, 3-28-10 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan
| | - Kazuhiko Koike
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| |
Collapse
|
|
37
|
Yoshiji H, Nagoshi S, Akahane T, Asaoka Y, Ueno Y, Ogawa K, Kawaguchi T, Kurosaki M, Sakaida I, Shimizu M, Taniai M, Terai S, Nishikawa H, Hiasa Y, Hidaka H, Miwa H, Chayama K, Enomoto N, Shimosegawa T, Takehara T, Koike K. Evidence-based clinical practice guidelines for liver cirrhosis 2020. Hepatol Res 2021; 51:725-749. [PMID: 34231046 DOI: 10.1111/hepr.13678] [Citation(s) in RCA: 100] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Accepted: 05/26/2021] [Indexed: 12/14/2022]
Abstract
The first edition of the clinical practice guidelines for liver cirrhosis was published in 2010, and the second edition was published in 2015 by the Japanese Society of Gastroenterology (JSGE). The revised third edition was recently published in 2020. This version has become a joint guideline by the JSGE and the Japanese Society of Hepatology (JSH). In addition to the clinical questions (CQs), background questions (BQs) are new items for basic clinical knowledge, and future research questions (FRQs) are newly added clinically important items. Concerning the clinical treatment of liver cirrhosis, new findings have been reported over the past 5 years since the second edition. In this revision, we decided to match the international standards as much as possible by referring to the latest international guidelines. Newly developed agents for various complications have also made great progress. In comparison with the latest global guidelines, such as the European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases (AASLD), we are introducing data based on the evidence for clinical practice in Japan. The flowchart for nutrition therapy was reviewed to be useful for daily medical care by referring to overseas guidelines. We also explain several clinically important items that have recently received focus and were not mentioned in the last editions. This digest version describes the issues related to the management of liver cirrhosis and several complications in clinical practice. The content begins with a diagnostic algorithm, the revised flowchart for nutritional therapy, and refracted ascites, which are of great importance to patients with cirrhosis. In addition to the updated antiviral therapy for hepatitis B and C liver cirrhosis, the latest treatments for non-viral cirrhosis, such as alcoholic steatohepatitis/non-alcoholic steatohepatitis (ASH/NASH) and autoimmune-related cirrhosis, are also described. It also covers the latest evidence regarding the diagnosis and treatment of liver cirrhosis complications, namely gastrointestinal bleeding, ascites, hepatorenal syndrome and acute kidney injury, hepatic encephalopathy, portal thrombus, sarcopenia, muscle cramp, thrombocytopenia, pruritus, hepatopulmonary syndrome, portopulmonary hypertension, and vitamin D deficiency, including BQ, CQ and FRQ. Finally, this guideline covers prognosis prediction and liver transplantation, especially focusing on several new findings since the last version. Since this revision is a joint guideline by both societies, the same content is published simultaneously in the official English journal of JSGE and JSH.
Collapse
Affiliation(s)
- Hitoshi Yoshiji
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan.,Department of Gastroenterology, Nara Medical University, Nara, Japan
| | - Sumiko Nagoshi
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Takemi Akahane
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Yoshinari Asaoka
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Yoshiyuki Ueno
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Koji Ogawa
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Takumi Kawaguchi
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Masayuki Kurosaki
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Isao Sakaida
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Masahito Shimizu
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Makiko Taniai
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Shuji Terai
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Hiroki Nishikawa
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Yoichi Hiasa
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Hisashi Hidaka
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Hiroto Miwa
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | | | - Nobuyuki Enomoto
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Tooru Shimosegawa
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | | | - Kazuhiko Koike
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| |
Collapse
|
|
38
|
Zhou Y, Yang W, Liu G, Gao W. Risks of vaptans in hypernatremia and serum sodium overcorrection: A systematic review and meta-analysis of randomised controlled trials. Int J Clin Pract 2021; 75:e13939. [PMID: 33336480 DOI: 10.1111/ijcp.13939] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2020] [Accepted: 12/14/2020] [Indexed: 12/25/2022] Open
Abstract
OBJECTIVE Serum sodium overcorrection and hypernatremia are significant health risks. We conducted a systematic review and meta-analysis to evaluate the risks of vaptans in hypernatremia and serum sodium overcorrection. METHODS We searched PubMed, Embase, and CENTRAL for randomised controlled trials. We included studies comparing vaptans and placebo with data on hypernatremia and serum sodium overcorrection. The study quality was assessed using the Cochrane Collaboration's risk-of-bias assessment tool. Fixed-effect model meta-analysis was used to pool the data. Different analyses were performed to ensure the accuracy of the results. RESULTS Twenty-eight studies were included in the meta-analysis of hypernatremia incidence. Treatment with vaptans resulted in a higher risk of hypernatremia than placebo (3.8% vs 1.0%, odds ratio [OR] 2.69; 95% confidence interval [CI] 1.97-3.68). The subgroup with baseline hyponatremia had a lower risk of hypernatremia incidence; however, the use of loop diuretics increased the risk. Fourteen studies were included in the analysis of the incidence of serum sodium overcorrection. A higher risk of serum sodium overcorrection was found in using vaptans vs placebo (4.4% vs 1.4%; OR 2.26; 95% CI 1.32-3.86). CONCLUSION Vaptans showed higher risks in the incidence of hypernatremia and serum sodium overcorrection than placebo. In addition, combination with loop diuretics increased the risk of hypernatremia. The risk of serum sodium overcorrection should be concerned in patients with hyponatremia and normal serum sodium equally. Using a low dose of vaptans can reduce both risks.
Collapse
Affiliation(s)
- Ya Zhou
- Department of Health Care and Endocrinology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Shandong, China
| | - Wenru Yang
- Department of Health Care, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Shandong, China
| | - Guotao Liu
- Department of Health Care, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Shandong, China
| | - Weiyi Gao
- Department of Health Care, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Shandong, China
| |
Collapse
|
|
39
|
Management of Cirrhotic Ascites under the Add-on Administration of Tolvaptan. Int J Mol Sci 2021; 22:ijms22115582. [PMID: 34070416 PMCID: PMC8197450 DOI: 10.3390/ijms22115582] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 05/21/2021] [Accepted: 05/22/2021] [Indexed: 12/15/2022] Open
Abstract
Tolvaptan is a recently available diuretic that blocks arginine vasopressin receptor 2 in the renal collecting duct. Its diuretic mechanism involves selective water reabsorption by affecting the water reabsorption receptor aquaporin 2. Given that liver cirrhosis patients exhibit hyponatremia due to their pseudo-aldosteronism and usage of natriuretic agents, a sodium maintaining agent, such as tolvaptan, is physiologically preferable. However, large scale studies indicating the patients for whom this would be effective and describing management under its use have been insufficient. The appropriate management of cirrhosis patients treated with tolvaptan should be investigated. In the present review, we collected articles investigating the effectiveness of tolvaptan and factors associated with survival and summarized their management reports. Earlier administration of tolvaptan before increasing the doses of natriuretic agents is recommended because this may preserve effective arterial blood volume.
Collapse
|
|
40
|
Hartl L, Jachs M, Desbalmes C, Schaufler D, Simbrunner B, Paternostro R, Schwabl P, Bauer DJM, Semmler G, Scheiner B, Bucsics T, Eigenbauer E, Marculescu R, Szekeres T, Peck-Radosavljevic M, Kastl S, Trauner M, Mandorfer M, Reiberger T. The differential activation of cardiovascular hormones across distinct stages of portal hypertension predicts clinical outcomes. Hepatol Int 2021; 15:1160-1173. [PMID: 34021479 PMCID: PMC8514393 DOI: 10.1007/s12072-021-10203-9] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Accepted: 04/30/2021] [Indexed: 02/07/2023]
Abstract
Background and aims The cardiovascular hormones renin/angiotensin/aldosterone (RAA), brain-type natriuretic peptide (BNP)and arginine-vasopressin (AVP) are key regulators of systemic circulatory homeostasis in portal hypertension (PH). We assessed (i) the activation of renin, BNP and AVP across distinct stages of PH and (ii) whether activation of these hormones correlates with clinical outcomes. Methods Plasma levels of renin, proBNP and copeptin (AVP biomarker) were determined in 663 patients with advanced chronic liver disease (ACLD) undergoing hepatic venous pressure gradient (HVPG) measurement at the Vienna General Hospital between 11/2011 and 02/2019. We stratified for Child stage (A–C), HVPG (6–9 mmHg, 10–15 mmHg, ≥ 16 mmHg) and compensated vs. decompensated ACLD. Results With increasing PH, hyperdynamic state was indicated by higher heart rates (6–9 mmHg: median 71.0 [IQR 18.0] bpm, 10–15 mmHg: 76.0 [19.0] bpm, ≥ 16 mmHg: 80.0 [22.0] bpm; p < 0.001), lower mean arterial pressure (6–9 mmHg: 103.0 [13.5] mmHg, 10–15 mmHg: 101.0 [19.5] mmHg, ≥ 16 mmHg: 99.0 [21.0] mmHg; p = 0.032) and lower serum sodium (6–9 mmHg: 139.0 [3.0] mmol/L, 10–15 mmHg: 138.0 [4.0] mmol/L, ≥ 16 mmHg: 138.0 [5.0] mmol/L; p < 0.001). Across HVPG strata (6–9 mmHg vs. 10–15 mmHg vs ≥ 16 mmHg), median plasma levels of renin (21.0 [50.5] vs. 25.1 [70.9] vs. 65.4 [219.6] µIU/mL; p < 0.001), proBNP (86.1 [134.0] vs. 63.6 [118.0], vs. 132.2 [208.9] pg/mL; p = 0.002) and copeptin (7.8 [7.7] vs. 5.6 [8.0] vs. 10.7 [18.6] pmol/L; p = 0.024) increased with severity of PH. Elevated renin levels independently predicted first hepatic decompensation (adjusted hazard ratio [aHR]: 1.69; 95% confidence interval [95% CI] 1.07–2.68; p = 0.025) and mortality in compensated patients (aHR: 3.15; 95% CI 1.70–5.84; p < 0.001) and the overall cohort aHR: 1.42; 95% CI 1.01–2.01; p = 0.046). Elevated copeptin levels predicted mortality in decompensated patients (aHR: 5.77; 95% CI 1.27–26.33; p = 0.024) and in the overall cohort (aHR: 3.29; 95% CI 1.36–7.95; p = 0.008). ProBNP levels did not predict clinical outcomes. Conclusions The cardiovascular hormones renin, proBNP and AVP are activated with progression of ACLD and PH. Renin activation is a risk factor for hepatic decompensation and mortality, especially in compensated patients. Increased plasma copeptin is a risk factor for mortality, in particular in decompensated patients. Supplementary Information The online version contains supplementary material available at 10.1007/s12072-021-10203-9.
Collapse
Affiliation(s)
- Lukas Hartl
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.,Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
| | - Mathias Jachs
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.,Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
| | - Christopher Desbalmes
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.,Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
| | - Dunja Schaufler
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.,Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
| | - Benedikt Simbrunner
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.,Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria.,Christian Doppler Lab for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
| | - Rafael Paternostro
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.,Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
| | - Philipp Schwabl
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.,Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria.,Christian Doppler Lab for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
| | - David Josef Maria Bauer
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.,Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
| | - Georg Semmler
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.,Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
| | - Bernhard Scheiner
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.,Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
| | - Theresa Bucsics
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.,Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
| | - Ernst Eigenbauer
- IT-Systems and Communications, Medical University of Vienna, Vienna, Austria
| | - Rodrig Marculescu
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | - Thomas Szekeres
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | - Markus Peck-Radosavljevic
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.,Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria.,Department of Internal Medicine and Gastroenterology (IMuG), Hepatology, Endocrinology, Rheumatology and Nephrology, Central Emergency Medicine (ZAE), Klinikum Klagenfurt am Wörthersee, Klagenfurt, Austria
| | - Stefan Kastl
- Division of Cardiology, Department of Medicine II, Medical University of Vienna, Vienna, Austria
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Mattias Mandorfer
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.,Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria. .,Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria. .,Christian Doppler Lab for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria.
| |
Collapse
|
|
41
|
Hong SK, Lee KW, Hong SY, Suh S, Hong K, Han ES, Lee JM, Choi Y, Yi NJ, Suh KS. Efficacy of Liver Resection for Single Large Hepatocellular Carcinoma in Child-Pugh A Cirrhosis: Analysis of a Nationwide Cancer Registry Database. Front Oncol 2021; 11:674603. [PMID: 33996606 PMCID: PMC8121000 DOI: 10.3389/fonc.2021.674603] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Accepted: 04/12/2021] [Indexed: 01/27/2023] Open
Abstract
Background Therapeutic strategies and good prognostic factors are important for patients with single large hepatocellular carcinoma (HCC). This retrospective study aimed to identify the prognostic factors in patients with single large HCC with good performance status and Child-Pugh A cirrhosis using a large national cancer registry database and to recommend therapeutic strategies. Methods Among 12139 HCC patients registered at the Korean Primary Liver Cancer Registry between 2008 and 2015, single large (≥ 5 cm) HCC patients with Eastern Cooperative Oncology Group (ECOG) performance status 0 and Child-Pugh score A were selected. Results Overall, 466 patients were analyzed. The 1-,2-,3-, and 5-year survival rates after initial treatment were 84.9%, 71.0%, 60.1%, and 51.6%, respectively, and progression-free survival rates were 43.6%, 33.0%, 29.0%, and 26.8%, respectively. Platelet count < 100 × 109/L (P < 0.001), sodium level < 135 mmol/L (P = 0.002), maximum tumor diameter ≥ 10 cm (P = 0.001), and treatment other than resection (transarterial therapy vs. resection: P < 0.001, others vs. resection: P = 0.002) were significantly associated with poorer overall survival; sodium < 135 mmol/L (P = 0.015), maximum tumor diameter ≥ 10 cm (P < 0.001), and treatment other than resection (transarterial therapy vs. resection: P < 0.001, others vs. resection: P = 0.001) were independently associated with poorer progression-free survival. Conclusion Resection as an initial treatment should be considered when possible, even in patients with single large HCC with good performance status and mild cirrhosis. Caution should be exercised in patients with low platelet level (< 100 × 109/L), low serum sodium level (< 135 mmol/L), and maximum tumor diameter ≥ 10 cm.
Collapse
Affiliation(s)
- Suk Kyun Hong
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - Su Young Hong
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - Sanggyun Suh
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - Kwangpyo Hong
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - Eui Soo Han
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - Jeong-Moo Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - YoungRok Choi
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - Nam-Joon Yi
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| |
Collapse
|
|
42
|
Zaprudnova RA. Level of natremia as an index of the condition of the organism of animals under stress. REGULATORY MECHANISMS IN BIOSYSTEMS 2021. [DOI: 10.15421/022116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
In the diagnosis of stressful conditions in humans and other animals, ionic indicators remain practically unused. In this work, we studied the changes in the concentrations of sodium ions in the blood plasma of freshwater fish under stress caused by stressors of different quality and quantity. Most of the experiments were carried out on adult bream (Abramis brama L) from the Rybinsk Reservoir. Separate experiments were duplicated on adult individuals of roach (Rutilus rutilus L.), pike (Esox lucius L.), and blue bream (Abramis ballerus L.). The concentration of cations in the blood plasma was determined using a Flapho-4 flame photometer. Under the action of mild and short-term stressors of different qualities, the sodium concentration in the internal environment altered toward an increase in concentration gradients on the cell membrane (eustress or physiological stress). Hypernatremia was approximately 10%. Under the action of strong and/or prolonged stressors of different strength, the sodium concentration in the internal environment changed toward a decrease in concentration gradients on the cell membrane (distress or pathological stress). Hyponatremia was 50% in the conditions of acute lethal stress, 20% in subacute lethal stress, 10% or more in chronic lethal stress. During strong acute reversible stress, hyponatremia could reach 30%. Analysis of the material on mammals allowed us to conclude that the adaptation mechanisms in fish and higher vertebrates are similar. In this work, for the first time, the state of the system of electrolyte balance of animals under stress was analyzed from the standpoint of the leading role of ionic concentration gradients on the cell membrane (mainly sodium) in the energetics (level of disequilibrium) of the organism. We propose a concept that in normal and extreme conditions fish use two different defense reactions (or adaptation strategies): active and passive, consisting, respectively, in increasing or decreasing the level of disequilibrium (energy) in the organism. The hyponatremia recorded by numerous authors, which accompanies diseases in humans, is evidently a nonspecific reaction of the organism and serves as an indicator of reduced energy of the organism. It is suggested that the sodium level in the internal environment of the organism be used for diagnosing the stress state of animals.
Collapse
|
|
43
|
Thalji L, Thalji NM, Heimbach JK, Ibrahim SH, Kamath PS, Hanson A, Schulte PJ, Haile DT, Kor DJ. Renal Function Parameters and Serum Sodium Enhance Prediction of Wait-List Outcomes in Pediatric Liver Transplantation. Hepatology 2021; 73:1117-1131. [PMID: 32485002 DOI: 10.1002/hep.31397] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Revised: 04/03/2020] [Accepted: 05/03/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS Reliance on exception points to prioritize children for liver transplantation (LT) stems from concerns that the Pediatric End-Stage Liver Disease (PELD) score underestimates mortality. Renal dysfunction and serum sodium disturbances are negative prognosticators in adult LT candidates and various pediatric populations, but are not accounted for in PELD. We retrospectively evaluated the effect of these parameters in predicting 90-day wait-list death/deterioration among pediatric patients (<12 years) listed for isolated LT in the United States between February 2002 and June 2018. APPROACH AND RESULTS Among 4,765 patients, 2,303 (49.3%) were transplanted, and 231 (4.8%) died or deteriorated beyond transplantability within 90 days of listing. Estimated glomerular filtration rate (eGFR) (hazard ratio [HR] 1.09 per 5-unit decrease, 95% confidence interval [CI] 1.06-1.10) and dialysis (HR 7.24, 95% CI 3.57-14.66) were univariate predictors of 90-day death/deterioration (P < 0.001). The long-term benefit of LT persisted in patients with renal dysfunction, with LT as a time-dependent covariate conferring a 2.4-fold and 17-fold improvement in late survival among those with mild and moderate-to-severe dysfunction, respectively. Adjusting for PELD, sodium was a significant nonlinear predictor of outcome, with 90-day death/deterioration risk increased at both extremes of sodium (HR 1.20 per 1-unit decrease below 137 mmol/L, 95% CI 1.16-1.23; HR per 1-unit increase above 137 mmol/L 1.13, 95% CI 1.10-1.17, P < 0.001). A multivariable model incorporating PELD, eGFR, dialysis, and sodium demonstrated improved performance and superior calibration in predicting wait-list outcomes relative to the PELD score. CONCLUSIONS Listing eGFR, dialysis, and serum sodium are potent, independent predictors of 90-day death/deterioration in pediatric LT candidates, capturing risk not accounted for by PELD. Incorporation of these variables into organ allocation systems may highlight patient subsets with previously underappreciated risk, augment ability of PELD to prioritize patients for transplantation, and ultimately mitigate reliance on nonstandard exceptions.
Collapse
Affiliation(s)
- Leanne Thalji
- Department of Anesthesiology and Perioperative MedicineMayo ClinicRochesterMN
| | | | | | - Samar H Ibrahim
- Department of PediatricsDivision of Gastroenterology and HepatologyMayo ClinicRochesterMN
| | - Patrick S Kamath
- Department of MedicineDivision of Gastroenterology and HepatologyMayo ClinicRochesterMN
| | - Andrew Hanson
- Division of Biomedical StatisticsMayo ClinicRochesterMN
| | | | - Dawit T Haile
- Department of Anesthesiology and Perioperative MedicineMayo ClinicRochesterMN
| | - Daryl J Kor
- Department of Anesthesiology and Perioperative MedicineMayo ClinicRochesterMN
| |
Collapse
|
|
44
|
Ala M, Mohammad Jafari R, Hajiabbasi A, Dehpour AR. Aquaporins and diseases pathogenesis: From trivial to undeniable involvements, a disease-based point of view. J Cell Physiol 2021; 236:6115-6135. [PMID: 33559160 DOI: 10.1002/jcp.30318] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Revised: 01/11/2021] [Accepted: 01/12/2021] [Indexed: 01/01/2023]
Abstract
Aquaporins (AQPs), as transmembrane proteins, were primarily identified as water channels with the ability of regulating the transmission of water, glycerol, urea, and other small-sized molecules. The classic view of AQPs involvement in therapeutic plan restricted them and their regulators into managing only a narrow spectrum of the diseases such as diabetes insipidus and the syndrome of inappropriate ADH secretion. However, further investigations performed, especially in the third millennium, has found that their cooperation in water transmission control can be manipulated to handle other burden-imposing diseases such as cirrhosis, heart failure, Meniere's disease, cancer, bullous pemphigoid, eczema, and Sjögren's syndrome.
Collapse
Affiliation(s)
- Moein Ala
- Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.,Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Razieh Mohammad Jafari
- Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Asghar Hajiabbasi
- Guilan Rheumatology Research Center, Razi Hospital, Guilan University of Medical Sciences, Rasht, Iran
| | - Ahmad Reza Dehpour
- Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.,Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.,Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
| |
Collapse
|
|
45
|
Goudsmit BFJ, Putter H, Tushuizen ME, de Boer J, Vogelaar S, Alwayn I, van Hoek B, Braat AE. Validation of the Model for End-stage Liver Disease sodium (MELD-Na) score in the Eurotransplant region. Am J Transplant 2021; 21:229-240. [PMID: 32529758 PMCID: PMC7818465 DOI: 10.1111/ajt.16142] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Revised: 05/12/2020] [Accepted: 06/08/2020] [Indexed: 01/25/2023]
Abstract
The MELD score is used in the Eurotransplant (ET) region to allocate liver grafts. Hyponatremia in cirrhotic patients is an important predictor of death but is not incorporated in MELD. This study investigated the performance of the MELD-Na score for the ET region. All adult patients with chronic liver disease on the ET liver transplantation waiting list (WL) allocated through lab MELD scores were included. The MELD-corrected effect of serum sodium (Na) concentration at listing on the 90-day WL mortality was calculated using Cox regression. The MELD-Na performance was assessed with c-indices, calibration per decile and Brier scores. The reclassification from MELD to MELD-Na score was calculated to estimate the impact of MELD-Na-based allocation in the ET region. For the 5223 included patients, the risk of 90-day WL death was 2.9 times higher for hyponatremic patients. The MELD-Na had a significantly higher c-index of 0.847 (SE 0.007) and more accurate 90-day mortality prediction compared to MELD (Brier score of 0.059 vs 0.061). It was estimated that using MELD-Na would reduce WL mortality by 4.9%. The MELD-Na score yielded improved prediction of 90-day WL mortality in the ET region and using MELD-Na for liver allocation will very likely reduce WL mortality.
Collapse
Affiliation(s)
- Ben F. J. Goudsmit
- Division of TransplantationDepartment of Surgery, Leiden University Medical CentreLeidenThe Netherlands,Eurotransplant International FoundationLeidenThe Netherlands,Division of TransplantationDepartment of Gastroenterology and Hepatology, Leiden University Medical CentreLeidenThe Netherlands
| | - Hein Putter
- Department of Biomedical Data SciencesLeidenThe Netherlands
| | - Maarten E. Tushuizen
- Division of TransplantationDepartment of Gastroenterology and Hepatology, Leiden University Medical CentreLeidenThe Netherlands
| | - Jan de Boer
- Eurotransplant International FoundationLeidenThe Netherlands
| | - Serge Vogelaar
- Eurotransplant International FoundationLeidenThe Netherlands
| | - I.P.J. Alwayn
- Division of TransplantationDepartment of Surgery, Leiden University Medical CentreLeidenThe Netherlands
| | - Bart van Hoek
- Division of TransplantationDepartment of Gastroenterology and Hepatology, Leiden University Medical CentreLeidenThe Netherlands
| | - Andries E. Braat
- Division of TransplantationDepartment of Surgery, Leiden University Medical CentreLeidenThe Netherlands
| |
Collapse
|
|
46
|
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
|
|
47
|
Hyponatremia Is Associated With Increased Mortality in Children on the Waiting List for Liver Transplantation. Transplant Direct 2020; 6:e604. [PMID: 33134484 PMCID: PMC7591120 DOI: 10.1097/txd.0000000000001050] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Revised: 07/13/2020] [Accepted: 07/14/2020] [Indexed: 12/21/2022] Open
Abstract
Our aim was to determine whether hyponatremia is associated with waiting list or posttransplantation mortality in children having liver transplantation (LT).
Collapse
|
|
48
|
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
|
|
49
|
Gupta S, Tio MC, Gutowski ED, Stecker MS, Verma A, Motwani SS, Mount DB, McMahon GM, Waikar SS. Incidence of Hyponatremia in Patients With Indwelling Peritoneal Catheters for Drainage of Malignant Ascites. JAMA Netw Open 2020; 3:e2017859. [PMID: 33104204 PMCID: PMC7588930 DOI: 10.1001/jamanetworkopen.2020.17859] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
IMPORTANCE Indwelling peritoneal catheters (IPCs) are frequently used to drain tense, symptomatic, malignant ascites. Large-volume drainage may lead to hyponatremia owing to massive salt depletion. To date, no studies have examined the epidemiology of hyponatremia after placement of an IPC. OBJECTIVE To evaluate the incidence of hyponatremia after IPC placement, the risk factors associated with its development, and how it is managed. DESIGN, SETTING, AND PARTICIPANTS This cohort study retrospectively reviewed the medical records of 461 patients who had IPCs placed during the period between 2006 and 2016 at a tertiary care hospital in Boston, Massachusetts, of whom 309 patients met the inclusion criteria. Data analysis was performed from June to November 2019. MAIN OUTCOMES AND MEASURES Main outcomes were the incidence of hyponatremia (with a serum sodium level <135 mEq/L) after IPC placement, the risk factors for its development, and how it was managed. We also examined the clinical course of a subset of 21 patients with hypovolemic hyponatremia. RESULTS Of the 309 eligible patients with laboratory results both before IPC placement and 2 days or more after IPC placement, 189 (72.1%) were female, and the mean (SD) age was 59 (12) years. The overall incidence of hyponatremia after IPC placement was 84.8% (n = 262), of whom 21 patients (8.0%) had severe hyponatremia. The mean (SD) decrease in serum sodium level before vs after IPC placement was 5 (5.1) mEq/L and decreased by 10 mEq/L or more among 52 patients (16.8%). Patients with hyponatremia prior to IPC placement had an 8-fold higher adjusted odds of having persistent hyponatremia after IPC placement (odds ratio, 7.9; 95% CI, 2.9-21.7). Patients with hepatopancreatobiliary malignant neoplasms were more likely to develop hyponatremia (78 of 262 patients with hyponatremia [29.8%] vs 7 of 47 patients without hyponatremia [14.9%]). Hyponatremia was either unrecognized or untreated in 189 patients (72.1%). CONCLUSIONS AND RELEVANCE Although the placement of an IPC is often a palliative measure, hyponatremia is common and is often untreated or unrecognized. Patients at highest risk, such as those with hyponatremia at baseline and those with hepatopancreatobiliary malignant neoplams, should be evaluated carefully prior to IPC placement and may warrant closer monitoring after placement. In all cases, hyponatremia should be evaluated and managed within the context of a patient's overall goals of care.
Collapse
Affiliation(s)
- Shruti Gupta
- Division of Renal Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
- Harvard Medical School, Boston, Massachusetts
| | - Maria Clarissa Tio
- Division of Renal Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
- Harvard Medical School, Boston, Massachusetts
| | | | - Michael S. Stecker
- Harvard Medical School, Boston, Massachusetts
- Division of Angiography and Interventional Radiology, Department of Radiology, Brigham and Women’s Hospital, Boston, Massachusetts
| | - Ashish Verma
- Division of Renal Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
- Harvard Medical School, Boston, Massachusetts
| | - Shveta S. Motwani
- Division of Renal Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
- Harvard Medical School, Boston, Massachusetts
- Dana-Farber Cancer Institute, Boston, Massachusetts
| | - David B. Mount
- Division of Renal Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
- Harvard Medical School, Boston, Massachusetts
| | - Gearoid M. McMahon
- Division of Renal Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
- Harvard Medical School, Boston, Massachusetts
| | - Sushrut S. Waikar
- Division of Renal Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
- Section of Nephrology, Department of Medicine, Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts
| |
Collapse
|
|
50
|
Vaz NF, da Cunha VNR, Cunha-Silva M, Sevá-Pereira T, de Souza Almeida JR, Mazo DF. Evolution of diagnostic criteria for acute kidney injury in patients with decompensated cirrhosis: A prospective study in a tertiary university hospital. Clin Res Hepatol Gastroenterol 2020; 44:551-563. [PMID: 31427198 DOI: 10.1016/j.clinre.2019.07.004] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2019] [Revised: 06/22/2019] [Accepted: 07/19/2019] [Indexed: 02/04/2023]
Abstract
BACKGROUND Recently, changes in acute kidney injury (AKI) diagnostic criteria have been proposed (ICA-AKI criteria). However, in Brazil there is a paucity of data and analyses that evaluate AKI in patients with cirrhosis and determine the impact of the implemented AKI criteria changes. Therefore, this study sought to evaluate the incidence of AKI in patients with cirrhosis; to evaluate the agreement between traditional and ICA-AKI criteria; and to assess its clinical and laboratory characteristics, etiologies, risk factors and outcomes. METHODS This is a prospective cohort study in hospitalized patients with cirrhosis and acute decompensation. The total number of hospitalizations was evaluated using the PWP statistical model for recurring events; P values<0.05 were considered significant. RESULTS A total of 154 admissions of 75 patients were included in the study. Among the hospitalizations, 89 (57.79%) met the ICA-AKI criteria. There was substantial agreement between both AKI classifications (Kappa 0.7293). The main etiology of AKI was pre-renal (59.55%), followed by renal (26.96%) and hepatorenal syndrome (10.11%). A multivariate analysis uncovered risk factors for ICA-AKI, including the MELD score (P=0.0162, RR:1.055, 95% CI:1.010-1.101) and the use of furosemide (P=0.001,RR:2.360, 95% CI:1.417-3.931). A univariate analysis found an association between in-hospital mortality and serum creatinine (sCr)≥1.5mg/dL(P=0.0373), MELD (P=0.0296), bilirubin (P=0.0064), and infection (P=0.0045), while in the multivariate analysis, the bilirubin levels (P=0.0030, RR:1.077, 95% CI: 1.025-1.130) and the presence of shock (P=0.0002, RR:8.511, 95% CI: 2.746-26.377) were associated with in-hospital mortality. Among the hospitalizations with AKI, death was significantly associated with non-response to treatment and dialysis. Initial stage 1A-AKI had lower in-hospital mortality than stage 1B-AKI. CONCLUSIONS AKI incidence was high in this cohort of patients with decompensated cirrhosis, and substantial agreement between AKI definitions was observed. In-hospital mortality was associated with worse liver function, AKI, infection and the presence of shock. Also, sCr>1,5mg/dL remained an important prognostic factor.
Collapse
Affiliation(s)
- Nayana Fonseca Vaz
- Division of Gastroenterology (Gastrocentro), School of Medical Sciences, University of Campinas (UNICAMP), Rua Carlos Chagas n°420, 13083-878 Campinas, Brazil
| | - Vanessa Nogueira Rodrigues da Cunha
- Division of Gastroenterology (Gastrocentro), School of Medical Sciences, University of Campinas (UNICAMP), Rua Carlos Chagas n°420, 13083-878 Campinas, Brazil
| | - Marlone Cunha-Silva
- Division of Gastroenterology (Gastrocentro), School of Medical Sciences, University of Campinas (UNICAMP), Rua Carlos Chagas n°420, 13083-878 Campinas, Brazil
| | - Tiago Sevá-Pereira
- Division of Gastroenterology (Gastrocentro), School of Medical Sciences, University of Campinas (UNICAMP), Rua Carlos Chagas n°420, 13083-878 Campinas, Brazil
| | - Jazon Romilson de Souza Almeida
- Division of Gastroenterology (Gastrocentro), School of Medical Sciences, University of Campinas (UNICAMP), Rua Carlos Chagas n°420, 13083-878 Campinas, Brazil
| | - Daniel F Mazo
- Division of Gastroenterology (Gastrocentro), School of Medical Sciences, University of Campinas (UNICAMP), Rua Carlos Chagas n°420, 13083-878 Campinas, Brazil; Division of Clinical Gastroenterology and Hepatology, Department of Gastroenterology, University of São Paulo School of Medicine, Avenida Dr. Enéas de Carvalho Aguiar n°255, Instituto Central, 9159 Sao Paulo, Brazil.
| |
Collapse
|