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Mujtaba MA, Elsiesy H, Faiz S, Hussain SA, Gamilla‐Crudo AKN, Karim A, Khan MI, Khattak MW, Zafar Z, Kueht M, Jamil K. Defining Renal Recovery in Patients With Hepatorenal Syndrome-Acute Kidney Injury: Experience From North American Studies. JGH Open 2024; 8:e70058. [PMID: 39664961 PMCID: PMC11631707 DOI: 10.1002/jgh3.70058] [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: 12/21/2023] [Revised: 10/02/2024] [Accepted: 11/11/2024] [Indexed: 12/13/2024]
Abstract
Introduction The degree of improvement in serum creatinine (SCr) has previously been suggested as a sensitive indicator of treatment response in patients with hepatorenal syndrome-acute kidney injury (HRS-AKI), while HRS reversal remains the primary endpoint in clinical trials. Methods A total of ≥ 30% SCr improvement was analyzed as an exploratory prespecified endpoint in the CONFIRM trial. In this post hoc analysis, intent-to-treat population data from three Phase 3 studies (OT-0401, REVERSE, and CONFIRM) conducted in North America in patients with HRS-AKI were pooled to assess the incidence of > 30% improvement in SCr and its association with clinical outcomes. Results Significantly more patients treated with terlipressin achieved > 30% improvement in SCr compared with those who received a placebo (42.9% vs. 23.4%; p < 0.001). Compared with patients who did not achieve > 30% improvement in SCr, those who achieved this threshold had a lower incidence of renal replacement therapy (RRT) (55.2% vs. 14%, respectively; p < 0.001) and greater overall survival at Day 90 (41.6% vs. 71.1%, respectively; p < 0.001); a greater proportion achieved durability of HRS reversal (1% [95% confidence interval, 95% CI: 0] vs. 68.9% [95% CI: 0.6, 0.8]) and more patients were alive without RRT (22.7% vs. 61.6%, respectively; p < 0.001) or transplant (11.6% vs. 43.0%, respectively; p < 0.0001). Additionally, the overall survival and RRT-free survival in the group that achieved > 30% improvement in SCr without HRS reversal were comparable to the overall group that achieved HRS reversal. Conclusion A total of > 30% improvement in SCr levels even without HRS reversal may serve as a clinically meaningful endpoint to define renal recovery in patients with HRS-AKI.
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Affiliation(s)
| | | | - Sara Faiz
- University of Texas Medical BranchGalvestonTexasUSA
| | | | | | - Aftab Karim
- Texas Health Presbyterian HospitalDallasTexasUSA
| | | | | | | | | | - Khurram Jamil
- Mallinckrodt PharmaceuticalsBridgewaterNew JerseyUSA
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Olayinka OT, Orelus J, Nisar MR, Kotha R, Saad-Omer SI, Singh S, Yu AK. Comparative Mortality Rates of Vasoconstrictor Agents in the Management of Hepatorenal Syndrome: A Systematic Review and Meta-Analysis. Cureus 2024; 16:e67034. [PMID: 39286706 PMCID: PMC11402629 DOI: 10.7759/cureus.67034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Accepted: 08/14/2024] [Indexed: 09/19/2024] Open
Abstract
Hepatorenal syndrome (HRS) is an acute complication of advanced liver disease, which manifests with a rapidly progressive decline in kidney function. Though pharmacological treatment has been recently advanced, there are still high mortality rates. The study compares the mortality rate in patients using different vasoconstrictor agents in the management of HRS. A complete literature search was done in the following databases: PubMed, Cochrane Library, PubMed Central (PMC), and Multidisciplinary Digital Publishing Institute (MDPI). Studies were included according to previously established criteria, in which all studies reporting on adult patients with HRS treated with vasoconstrictor agents were eligible. The data extracted were analyzed with a random-effects model to express variability between studies, and the principal measure was the risk ratio (RR) for mortality. Of the 8,137 studies identified, 29 met the inclusion criteria. In the meta-analysis, vasoconstrictors, mainly terlipressin, significantly improved renal function and decreased the need for renal replacement therapy (RRT) versus placebo. However, a significant impact on mortality was lacking (0.94 (0.84-1.06), p = 0.31). The subgroup analysis found that mortality rates were not significantly different between vasoconstrictors, whether used in combination with or without albumin (0.97 (0.77-1.23), p = 0.79, and 0.98 (0.79-1.21), p = 0.86). Global heterogeneity was low, indicating consistent results in the studies. Vasoconstrictors are helpful in managing HRS, with improvement in renal function and reduction in RRT requirements. However, the effect on mortality was small and nonsignificant. Such findings support the use of terlipressin in HRS management; concomitantly, they emphasize the need for personalized treatment strategies and future research to find alternative therapies that may be more effective for improved survival results with fewer side effects.
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Affiliation(s)
- Oluwatoba T Olayinka
- Internal Medicine, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA
| | - Jaslin Orelus
- Emergency Medicine, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA
| | - Mah Rukh Nisar
- Neurology and Medicine, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA
| | - Rudrani Kotha
- Internal Medicine, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA
| | - Sabaa I Saad-Omer
- Internal Medicine, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA
| | - Shivani Singh
- Internal Medicine, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA
| | - Ann Kashmer Yu
- Internal Medicine, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA
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Qaqish F, Dimachkie R, Sasso R, Loeffler J, Hasan M, Deghani S, Abou Yassine A, Deeb L. Safety of Nonselective Beta-Blockers in Decompensated Liver Cirrhosis and Their Role in Inducing Hepatorenal Syndrome. Cureus 2024; 16:e58296. [PMID: 38752039 PMCID: PMC11094662 DOI: 10.7759/cureus.58296] [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: 04/11/2024] [Indexed: 05/18/2024] Open
Abstract
Background Nonselective beta-blockers (NSBBs) have been used in the management of portal hypertension and the prevention of initial and recurrent variceal bleeding in patients with liver cirrhosis. However, there is controversy regarding the use of NSBBs in patients with decompensated cirrhosis (DC) due to concerns over potential adverse effects, such as worsening of hepatic function and risk of hepatorenal syndrome (HRS). HRS is a serious complication of DC characterized by acute kidney injury (AKI) and progressive renal failure, and its development can lead to significant morbidity and mortality in this setting. Therefore, using NSBBs in patients with DC remains an area of ongoing research and debate. Our study aims to investigate the potential effect of NSBBs on HRS development. Methodology A retrospective chart review of 404 patients with cirrhosis was performed across all Northwell Health institutions between January 01, 2019, and December 31, 2020. An analysis was done on 516 patient encounters. Inclusion criteria included patients with an established International Classification of Diseases 10th Revision code of cirrhosis and AKI. After adjusting for clinical predictors, the Student's t-test or Mann-Whitney U-test was used to compare variables between the two outcome groups (HRS vs. no HRS) for the continuous variables. Pearson's chi-square test or Fisher's exact test was used for the categorical variables to test if an association existed between the use of NSBBs at home and HRS. A two-sided p-value <0.05 was considered statistically significant. SAS 9.4 (SAS Institute Inc., Cary, NC, USA) was used for statistical analysis. Results The primary outcome was the development of HRS during the hospital stay. With a total of 109 visits with HRS, we had 21 (23.60%) reported HRS in the 89 visits where NSBBs were used at home before the hospitalization, while 88 (20.61%) HRS were observed in the 427 visits with no NSBB use at home. The use of NSBBs at home was not significantly associated with the development of HRS (odds ratio = 1.1, 95% confidence interval = 0.6-1.9, p = 0.7321). We also found that higher serum albumin on admission is associated with lower odds of HRS. In contrast, increased serum creatinine, bilirubin, presence of ascites, and use of pressors were associated with a higher risk of HRS. Conclusions Our study highlights the relevant safety of NSBB use in end-stage liver disease. Their use did not appear to increase the risk of developing HRS during hospitalization with DC. Further randomized controlled trials are warranted to shed more light on the efficacy, dose tolerance limits, and safety of NSBBs in decompensated end-stage liver disease.
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Affiliation(s)
- Faris Qaqish
- Internal Medicine, Staten Island University Hospital, Staten Island, USA
| | - Reem Dimachkie
- Internal Medicine, Staten Island University Hospital, Staten Island, USA
| | - Roula Sasso
- Internal Medicine, Staten Island University Hospital, Staten Island, USA
| | - Jeffrey Loeffler
- Internal Medicine, Staten Island University Hospital, Staten Island, USA
| | - Mohammed Hasan
- Internal Medicine, Staten Island University Hospital, Staten Island, USA
| | - Shabnam Deghani
- Internal Medicine, Staten Island University Hospital, Staten Island, USA
| | - Ahmad Abou Yassine
- Internal Medicine, Staten Island University Hospital, Staten Island, USA
| | - Liliane Deeb
- Gastroenterology, Staten Island University Hospital, Staten Island, USA
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Giammarino A, Kalia H. A hospitalist's approach to managing acute kidney injury (hepatorenal syndrome) in cirrhosis. Clin Liver Dis (Hoboken) 2024; 23:e0159. [PMID: 38681513 PMCID: PMC11049700 DOI: 10.1097/cld.0000000000000159] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Accepted: 02/17/2024] [Indexed: 05/01/2024] Open
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Glal KAM, El-Haggar SM, Abdel-Salam SM, Mostafa TM. Allopurinol Prevents Cirrhosis-Related Complications: A Quadruple Blind Placebo-Controlled Trial. Am J Med 2024; 137:55-64. [PMID: 37832758 DOI: 10.1016/j.amjmed.2023.09.016] [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: 06/17/2023] [Revised: 09/06/2023] [Accepted: 09/19/2023] [Indexed: 10/15/2023]
Abstract
BACKGROUND Complications associated with liver cirrhosis are various and potentially fatal. The treatment options to counteract hepatic decompensation are limited. Therefore, the study aimed to explore the use of allopurinol in preventing the recurrence of liver cirrhosis-related complications. METHODS One hundred patients with hepatic decompensation were randomized into 1:1 ratio to receive either allopurinol 300 mg or placebo tablets once daily for 6 months. The primary endpoint was the incidence of cirrhosis-related complications (overt ascites, spontaneous bacterial peritonitis, variceal bleeding, hepatorenal syndrome, and hepatic encephalopathy). RESULTS Six months following treatment, allopurinol reduced the relative risk (RR) of any first complication experienced after enrollment by 56% (hazard ratio [HR] 0.44; 95% confidence interval [CI], 0.27-0.62); P ˂ .001). Allopurinol decreased the RR of overt ascites by 67% (HR 0.33; 95% CI, 0.0098-0.94); P = .039] and reduced the RR of spontaneous bacterial peritonitis by about 75% (HR 0.25; 95% CI, 0.05-0.76; P = .01). Likewise, allopurinol was linked to an 80% reduction in the RR of developing hepatorenal syndrome (HR 0.2; 95% CI, 0.04-0.87; P = .033). CONCLUSION Allopurinol significantly decreased the recurrence of overall liver cirrhosis-related complications. Therefore, allopurinol may constitute a promising agent for patients with hepatic decompensation. These positive outcomes could be a result of its ability to reduce bacterial translocation and inflammation. CLINICALTRIALS GOV IDENTIFIER NCT005545670.
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Affiliation(s)
| | | | - Sherief M Abdel-Salam
- Department of Tropical Medicine and Infectious Diseases, Faculty of Medicine, Tanta University, Tanta, Egypt
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Badura K, Frąk W, Hajdys J, Majchrowicz G, Młynarska E, Rysz J, Franczyk B. Hepatorenal Syndrome-Novel Insights into Diagnostics and Treatment. Int J Mol Sci 2023; 24:17469. [PMID: 38139297 PMCID: PMC10744165 DOI: 10.3390/ijms242417469] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 12/09/2023] [Accepted: 12/11/2023] [Indexed: 12/24/2023] Open
Abstract
Hepatorenal syndrome (HRS) is a disorder associated with cirrhosis and renal impairment, with portal hypertension as its major underlying cause. Moreover, HRS is the third most common cause of acute kidney injury, thus creating a major public health concern. This review summarizes the available information on the pathophysiological implications of HRS. We discuss pathogenesis associated with HRS. Mechanisms such as dysfunction of the circulatory system, bacterial infection, inflammation, impaired renal autoregulation, circulatory, and others, which have been identified as critical pathways for development of HRS, have become easier to diagnose in recent years. Additionally, relatively recently, renal dysfunction biomarkers have been found indicating renal injury, which are involved in the pathophysiology of HRS. This review also summarizes the available information on the management of HRS, focusing on vasoconstrictive drugs, renal replacement therapy, and liver transplant together with currently being investigated novel therapies. Analyzing new discoveries for the underlying causes of this condition assists the general research to improve understanding of the mechanism of pathophysiology and thus prevention of HRS.
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Affiliation(s)
- Krzysztof Badura
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Weronika Frąk
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Joanna Hajdys
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Gabriela Majchrowicz
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Ewelina Młynarska
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Jacek Rysz
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Beata Franczyk
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
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Huang X, Bindra J, Chopra I, Niewoehner J, Wan GJ. Treatment-Related Cost Analysis of Terlipressin for Adults with Hepatorenal Syndrome with Rapid Reduction in Kidney Function. Adv Ther 2023; 40:5432-5446. [PMID: 37812332 PMCID: PMC10611877 DOI: 10.1007/s12325-023-02674-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2023] [Accepted: 08/31/2023] [Indexed: 10/10/2023]
Abstract
INTRODUCTION Hepatorenal syndrome (HRS), a special form of acute kidney failure, is a rare, acute, life-threatening complication of cirrhosis and has a very poor prognosis. Terlipressin (TERLIVAZ®) is the first and only pharmacological treatment approved by Food and Drug Administration (September 2022) to improve kidney function for adults with HRS with rapid reduction in kidney function. We constructed a decision analytic economic model to estimate the cost per complete response/HRS reversal of terlipressin + albumin from a United States hospital perspective. METHODS A decision analytic model was developed to estimate the HRS treatment-related cost per response over an HRS hospitalization (assuming 14 days). Patients can experience either HRS reversal (complete response) or no HRS reversal (partial/no response) upon receipt of treatment. The efficacy, safety, and treatment duration data were from published head-to-head randomized international trials. Total treatment cost comprised drug acquisition and treatment-related costs (intensive care unit [ICU], dialysis [intermittent or continuous], pulse oximetry monitoring for terlipressin, and adverse events) sourced from the published literature. Cost per response, defined as the total treatment cost per HRS reversal was estimated for each treatment. The number needed to treat (NNT), defined as the number of patients treated to achieve HRS reversal in 1 additional patient, was estimated. RESULTS Cost per response of terlipressin + albumin was lower than midodrine and octreotide + albumin (M&O) (US$85,315 vs. $467,794) and norepinephrine + albumin ($81,614 vs. $139,324). NNT for HRS reversal was 2 patients with terlipressin + albumin vs. M&O + albumin and 4 patients with terlipressin + albumin vs. norepinephrine + albumin, respectively. CONCLUSIONS The analysis shows that terlipressin is a cost-effective treatment due to its higher efficacy and administration in the non-ICU setting. Terlipressin is a value-based treatment option for appropriate adults with HRS with rapid reduction in kidney function.
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Affiliation(s)
- Xingyue Huang
- Mallinckrodt Pharmaceuticals, 440 Route 22 East, Bridgewater, NJ, USA.
| | - Jas Bindra
- Falcon Research Group, North Potomac, MD, USA
| | | | - John Niewoehner
- Mallinckrodt Pharmaceuticals, 440 Route 22 East, Bridgewater, NJ, USA
| | - George J Wan
- Mallinckrodt Pharmaceuticals, 440 Route 22 East, Bridgewater, NJ, USA
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Curry MP, Vargas HE, Befeler AS, Pyrsopoulos NT, Patwardhan VR, Jamil K. Early treatment with terlipressin in patients with hepatorenal syndrome yields improved clinical outcomes in North American studies. Hepatol Commun 2023; 7:e1307. [PMID: 36633470 PMCID: PMC9827960 DOI: 10.1097/01.hc9.0000897228.91307.0c] [Citation(s) in RCA: 25] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2022] [Revised: 09/21/2022] [Accepted: 09/22/2022] [Indexed: 01/13/2023] Open
Abstract
Hepatorenal syndrome type 1 (HRS-1) is a serious complication of advanced cirrhosis and a potentially reversible form of acute kidney injury that is associated with rapidly deteriorating kidney function. Liver transplantation remains the only curative treatment for decompensated cirrhosis. However, terlipressin, a vasopressin analog, successfully reverses HRS-1, and may improve patient survival while awaiting liver transplantation. Patients with higher baseline serum creatinine have a reduced response to treatment with terlipressin. These post hoc analyses examined pooled data from 352 patients with HRS-1 treated with terlipressin in 3 North American-centric, Phase III, placebo-controlled clinical studies (i.e. OT-0401, REVERSE, and CONFIRM)-across 3 serum creatinine subgroups (i.e. <3, ≥3-<5, and ≥5 mg/dL)-to further delineate their correlation with HRS reversal, renal replacement therapy-free survival, and overall survival. Serum creatinine was significantly associated with HRS reversal in univariate and multivariate logistic regression analyses (P<0.001). The incidence of HRS reversal inversely correlated with serum creatinine subgroup (<3 mg/dL, 49.2%; ≥3-<5 mg/dL, 28.0%; ≥5 mg/dL, 9.1%). At Day 30 follow-up, renal replacement therapy-free survival was significantly higher for patients with HRS-1 in the lower serum creatinine subgroups than in the higher subgroup (<5 vs. >5 mg/dL; p=0.01). Terlipressin-treated patients with HRS-1, with a lower baseline serum creatinine level, had a higher overall survival (p<0.001) and higher transplant-free survival at Day 90 (p=0.04). Patients with HRS-1 and lower serum creatinine levels who were treated with terlipressin had higher HRS reversal and survival outcomes, highlighting the significant need to identify and treat patients with HRS-1 early when they often have lower serum creatinine levels, and likely a greater response to terlipressin.
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Affiliation(s)
- Michael P. Curry
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
| | | | - Alex S. Befeler
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Saint Louis University, St. Louis, Missouri, USA
| | - Nikolaos T. Pyrsopoulos
- Division of Gastroenterology and Hepatology, Liver Transplantation, Rutgers-New Jersey Medical School University Hospital, Newark, New Jersey, USA
| | - Vilas R. Patwardhan
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
| | - Khurram Jamil
- Mallinckrodt Pharmaceuticals, Clinton, New Jersey, USA
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Trends in Mortality and Health Care Burden of Cirrhotic Decompensation in Hospitalized Patients: A Nationwide Analysis. J Clin Gastroenterol 2022:00004836-990000000-00035. [PMID: 35862058 DOI: 10.1097/mcg.0000000000001734] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Accepted: 06/05/2022] [Indexed: 12/10/2022]
Abstract
INTRODUCTION Mortality caused by cirrhosis is now the 14th most common cause of death worldwide and 12th most common in the United States. We studied trends in inpatient mortality and hospitalization charges associated with cirrhotic decompensation from esophageal variceal bleeding, ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, and hepatorenal syndrome from 2007 to 2017. MATERIALS AND METHODS Using the National Inpatient Sample databases, we first isolated patients 18 years or older with the diagnosis of cirrhosis using International Classification of Diseases, Ninth Revision (ICD-9) or International Classification of Diseases, Tenth Revision (ICD-10) codes. We then identified patients with the admission diagnosis of esophageal variceal bleeding, ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, and hepatorenal syndrome. Time-series regression was used to determine whether a trend occurred over the study period. We also evaluated for patient-related demographic changes over the study period. RESULTS A total of 259,897 cirrhotic patients with the studied decompensations were captured. During the study period, time-series regression confirmed downtrends in mortality rates and length of stay for all types of decompensations. Conversely, we found increases in hospitalization charges for all types of decompensations. Patient age increased over the study period. Patients were also more likely to be White and pay with. CONCLUSION From 2007 to 2017, inpatient mortality rates and lengths of stay decreased for cirrhotic decompensations for all causes of decompensation. Total charges, conversely, increased for all causes.
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Buccheri S, Da BL. Hepatorenal Syndrome: Definitions, Diagnosis, and Management. Clin Liver Dis 2022; 26:181-201. [PMID: 35487604 DOI: 10.1016/j.cld.2022.01.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Hepatorenal syndrome (HRS) is a hemodynamically driven process mediated by renal dysregulation and inflammatory response. Albumin, antibiotics, and β-blockers are among therapies that have been studied in HRS prevention. There are no Food and Drug Administration-approved treatments for HRS although multiple liver societies have recommended terlipressin as first-line pharmacotherapy. Renal replacement therapy is the primary modality used to bridge to definitive therapy with orthotopic liver transplant or simultaneous liver-kidney transplant. Advances in our understanding of HRS pathophysiology and emerging therapeutic modalities are needed to change outcomes for this vulnerable population.
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Affiliation(s)
- Sebastiano Buccheri
- Department of Internal Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Health, 400 Community Drive, Manhasset, NY 11030, USA
| | - Ben L Da
- Department of Internal Medicine, Division of Hepatology, Sandra Atlas Bass Center for Liver Diseases & Transplantation, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Health, 400 Community Drive, Manhasset, NY 11030, USA.
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Jamil K, Huang X, Hayashida D, Lodaya K. The Hepatorenal Syndrome (HRS) Patient Pathway: Retrospective Analysis of Electronic Health Records. Curr Ther Res Clin Exp 2022; 96:100663. [PMID: 35399809 PMCID: PMC8987804 DOI: 10.1016/j.curtheres.2022.100663] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Accepted: 02/04/2022] [Indexed: 11/16/2022] Open
Abstract
Background Hepatorenal syndrome (HRS) is among the leading causes of hospitalization and mortality in patients with chronic liver disease. Objective To assess the HRS patient journey from preadmission to postdischarge to understand patient characteristics, disease progression, treatment patterns, and outcomes. Methods We conducted a retrospective study using real-world data from a nationwide electronic health record database (Cerner Health Facts, Kansas City, Missouri). We used ICD-9/10 diagnosis codes to identify patients hospitalized with HRS between January 1, 2009, and January 31, 2018. We assessed patient characteristics and history, clinical presentation, treatment, and outcomes. Regression analysis was conducted to assess the association between patient characteristics and survival while adjusting for demographic and clinical covariates. Results The study included 3563 patients (62% men). Precipitants of HRS included gastrointestinal bleeding (18%), diuretics and infections (30%), and paracentesis (26%). Although 21% of patients had liver injury exclusively associated with alcohol use, 20% had hepatitis C, 8% had nonalcoholic steatohepatitis, and the etiology of the remainder (51%) was either some combination of conditions or unknown. A total of 42% of patients received vasopressors, including octreotide and midodrine (10%), other combinations of vasopressors (11%), or another single vasopressor (21%). In-hospital mortality was 34%, and 14% of patients were discharged to hospice. Regression analysis showed patients with acute-on-chronic liver failure had higher mortality in acute-on-chronic liver failure grades 1 (odds ratio = 1.59), 2 (odds ratio = 2.49), and 3 (odds ratio = 4.53) versus no acute-on-chronic liver failure. Among survivor patients, 38% were readmitted within 90 days of discharge; 23% of readmissions were HRS-related. Conclusions The HRS patient journey presented in this study highlights inconsistencies in, and provides insight into, associated hospital-based treatment strategies. A mortality rate of 34% along with a readmission rate of 23% associated with HRS-related complications warrant more disease awareness and effective treatment. Further research is needed to examine the interactions between the etiology of cirrhosis, precipitants, treatment, and outcomes. (Curr Ther Res Clin Exp. 2022; 82:XXX–XXX)
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Affiliation(s)
| | | | | | - Kunal Lodaya
- Boston Strategic Partners Inc, Boston, Massachusetts
- Address correspondence to: Kunal Lodaya, MD, Boston Strategic Partners, Inc, 4 Wellington St, Suite 3, Boston, MA 02118.
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Anikhindi SA, Ranjan P, Kumar M, Mohan R. A Prospective Study of Prevalence and Predictors of Cirrhotic Cardiomyopathy and Its Role in Development of Hepatorenal Syndrome. J Clin Exp Hepatol 2022; 12:853-860. [PMID: 35677509 PMCID: PMC9168708 DOI: 10.1016/j.jceh.2021.11.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Accepted: 11/09/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND AND AIMS Cirrhotic cardiomyopathy (CCM) is a term used to collectively describe abnormal structural and functional changes in heart of patients with cirrhosis. The present study was undertaken to find the prevalence of CCM in patients with liver cirrhosis and its predictors. We also followed these patients to evaluate the role of CCM in the development of hepatorenal syndrome (HRS). MATERIALS & METHODS This was a prospective study carried out in department of Gastroenterology, Sir Ganga Ram hospital, New Delhi. A total of 104 patients with liver cirrhosis were included. Liver cirrhosis was diagnosed on basis of clinical, biochemical, and imaging features. CCM was defined based on echocardiography. Dobutamine stress echocardiography and hepatic venous pressure gradient (HVPG) were performed in patients who gave consent. HRS was defined as per standard criteria. Patients with CCM were followed for development of HRS. RESULTS Fifty (48%) patients were diagnosed with CCM. All patients had diastolic dysfunction, and none had systolic dysfunction. Median age of patients with CCM was significantly higher (59 [31-78 y] vs. 52 [24-70 y], P < 0.05). Severity of liver disease (Child Turcotte Pugh score and model for end-stage liver disease score) and portal pressures (HVPG) did not differ in patients with or without CCM. Patients with CCM did not have increased incidence of HRS at the end of 6-month follow-up study. CONCLUSION The presence of CCM was not related with the severity of liver dysfunction or portal pressures. Age was a significant determinant of CCM. Diastolic cardiac dysfunction does not influence the occurrence of HRS.
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Key Words
- 2D echo, two-dimensional echocardiography
- CCM, cirrhotic cardiomyopathy
- CTP, Child Turcotte Pugh
- DD, diastolic dysfunction
- DSE, dobutamine stress echocardiography
- FHVP, free hepatic venous pressure
- HRS, hepatorenal syndrome
- HVPG, hepatic venous pressure gradient
- LVEF, left ventricular ejection fraction
- MELD, model for end-stage liver disease
- TDI, tissue Doppler imaging
- cardiomyopathy
- cirrhosis
- diastolic cardiac dysfunction
- hepatorenal syndrome
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Affiliation(s)
- Shrihari A. Anikhindi
- Institute of Liver, Gastroenterology and Pancreaticobiliary Sciences, Sir Ganga Ram Hospital, New Delhi, India
| | - Piyush Ranjan
- Institute of Liver, Gastroenterology and Pancreaticobiliary Sciences, Sir Ganga Ram Hospital, New Delhi, India,Address for correspondence: Piyush Ranjan, Institute of Liver, Gastroenterology and Pancreaticobiliary Sciences, Sir Ganga Ram Hospital, Rajinder Nagar, 110 060, New Delhi, India.
| | - Mandhir Kumar
- Institute of Liver, Gastroenterology and Pancreaticobiliary Sciences, Sir Ganga Ram Hospital, New Delhi, India
| | - Rajat Mohan
- Department of Cardiology, Sir Ganga Ram Hospital, New Delhi, India
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13
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Predictors of Development of Hepatorenal Syndrome in Hospitalized Cirrhotic Patients with Acute Kidney Injury. J Clin Med 2021; 10:jcm10235621. [PMID: 34884323 PMCID: PMC8658275 DOI: 10.3390/jcm10235621] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Revised: 11/23/2021] [Accepted: 11/27/2021] [Indexed: 12/15/2022] Open
Abstract
Hepatorenal syndrome (HRS) is a type of acute kidney injury (AKI), occurring in patients with decompensated liver cirrhosis and is associated with high mortality. We aim to describe the predictors associated with the development of HRS in cirrhotic patients with AKI. We retrospectively analyzed 529 cirrhotic patient encounters with AKI across all Northwell Health institutions between 1 January 2015 and 31 December 2018. We performed multivariate analyses to determine independent predictors of development of HRS. Alcoholic cirrhosis was the most common identified etiology of cirrhosis. The mean Model for End-Stage Liver Disease Scorewas18 (±7). Ascites was the most commonly identified clinical feature of portal hypertension. Infection was identified in 38.4% of patients with urinary tract infection/pyelonephritis being the most common. Spontaneous bacterial peritonitis occurred in 5.9% of patients. The most common cause of AKI was pre-renal. Hepatorenal syndrome was identified in 9.8% of patient encounters. Predictors of HRS were history of ascites, serum creatinine >2.5 mg/dL, albumin <3 g/dL, bilirubin >2 mg/dL and spontaneous bacterial peritonitis. We demonstrate strong predictors for the development of HRS which can aid clinicians to attain an early diagnosis of HRS, leading to prompt and targeted management and improving outcomes.
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Chaney A. A Review for the Practicing Clinician: Hepatorenal Syndrome, a Form of Acute Kidney Injury, in Patients with Cirrhosis. Clin Exp Gastroenterol 2021; 14:385-396. [PMID: 34675586 PMCID: PMC8502008 DOI: 10.2147/ceg.s323778] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Accepted: 09/04/2021] [Indexed: 12/15/2022] Open
Abstract
The hepatorenal syndrome type of acute kidney injury (HRS-AKI), formerly known as type 1 hepatorenal syndrome, is a rapidly progressing renal failure that occurs in many patients with advanced cirrhosis and ascites. Accumulating evidence has led to a recent evolution of diagnostic criteria for this serious complication of end-stage liver disease. The aim of this review is to provide an overview of disease-related characteristics and therapeutic management of patients with HRS-AKI. Relevant literature was compiled to support discussion of the pathophysiology, diagnosis, prognosis, associated conditions, prevention, treatment, and management of HRS-AKI. Onset of HRS-AKI is characterized by sudden severe renal vasoconstriction, leading to an acute reduction in glomerular filtration rate and rapid, potentially life-threatening, renal deterioration. Although our understanding of disease pathophysiology continues to evolve, etiology of HRS-AKI likely involves systemic hemodynamic changes caused by liver disease, inflammation, and damage to renal parenchyma. There is currently no gold standard for diagnosis, which typically involves a clinical workup, abdominal imaging, and laboratory assessments. The current consensus definition of HRS-AKI includes proposed diagnostic criteria based on changes in serum creatinine levels tailored for high sensitivity, and rapid detection to accelerate diagnosis and treatment initiation. The only potential cure for HRS-AKI is liver transplantation; however, vasoconstrictive agents and other supportive measures are used as needed to help maintain survival for patients who are awaiting or are ineligible for transplantation. The severity of HRS-AKI, complex pathology, limited treatment options, and range of associated conditions pose significant challenges for both patients and care providers.
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Affiliation(s)
- Amanda Chaney
- Department of Transplant, College of Medicine, Mayo Clinic, Jacksonville, FL, USA
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Nassar M, Nso N, Medina L, Ghernautan V, Novikov A, El-Ijla A, Soliman KM, Kim Y, Alfishawy M, Rizzo V, Daoud A. Liver kidney crosstalk: Hepatorenal syndrome. World J Hepatol 2021; 13:1058-1068. [PMID: 34630874 PMCID: PMC8473490 DOI: 10.4254/wjh.v13.i9.1058] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 05/12/2021] [Accepted: 07/30/2021] [Indexed: 02/06/2023] Open
Abstract
The dying liver causes the suffocation of the kidneys, which is a simplified way of describing the pathophysiology of hepatorenal syndrome (HRS). HRS is characterized by reversible functional renal impairment due to reduced blood supply and glomerular filtration rate, secondary to increased vasodilators. Over the years, HRS has gained much attention and focus among hepatologists and nephrologists. HRS is a diagnosis of exclusion, and in some cases, it carries a poor prognosis. Different classifications have emerged to better understand, diagnose, and promptly treat this condition. This targeted review aims to provide substantial insight into the epidemiology, pathophysiology, diagnosis, and management of HRS, shed light on the various milestones of this condition, and add to our current understanding.
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Affiliation(s)
- Mahmoud Nassar
- Department of Medicine, Icahn School of Medicine at Mount Sinai / NYC Health + Hospitals / Queens, New York, NY 11432, United States
| | - Nso Nso
- Department of Medicine, Icahn School of Medicine at Mount Sinai / NYC Health + Hospitals / Queens, New York, NY 11432, United States
| | - Luis Medina
- Department of Medicine, Icahn School of Medicine at Mount Sinai / NYC Health + Hospitals / Queens, New York, NY 11432, United States
| | - Victoria Ghernautan
- Department of Medicine, Icahn School of Medicine at Mount Sinai / NYC Health + Hospitals / Queens, New York, NY 11432, United States
| | - Anastasia Novikov
- Department of Medicine, Icahn School of Medicine at Mount Sinai / NYC Health + Hospitals / Queens, New York, NY 11432, United States
| | - Alli El-Ijla
- Department of Medicine, Icahn School of Medicine at Mount Sinai / NYC Health + Hospitals / Queens, New York, NY 11432, United States
| | - Karim M Soliman
- Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, United States
| | - Yungmin Kim
- Department of Medicine, Icahn School of Medicine at Mount Sinai / NYC Health + Hospitals / Queens, New York, NY 11432, United States
| | - Mostafa Alfishawy
- Department of Infectious Diseases, Infectious Diseases Consultants and Academic Researchers of Egypt IDCARE, Cairo 11562, Egypt
| | - Vincent Rizzo
- Department of Medicine, Icahn School of Medicine at Mount Sinai / NYC Health + Hospitals / Queens, New York, NY 11432, United States
| | - Ahmed Daoud
- Department of Medicine, Kasr Alainy Medical School, Cairo University, Cairo 11211, Egypt
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16
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Liu PMF, de Carvalho ST, Fradico PF, Cazumbá MLB, Campos RGB, Simões E Silva AC. Hepatorenal syndrome in children: a review. Pediatr Nephrol 2021; 36:2203-2215. [PMID: 33001296 PMCID: PMC7527294 DOI: 10.1007/s00467-020-04762-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Revised: 08/01/2020] [Accepted: 09/05/2020] [Indexed: 02/07/2023]
Abstract
Hepatorenal syndrome (HRS) occurs in patients with cirrhosis or fulminant hepatic failure and is a kind of pre-renal failure due to intense reduction of kidney perfusion induced by severe hepatic injury. While other causes of pre-renal acute kidney injury (AKI) respond to fluid infusion, HRS does not. HRS incidence is 5% in children with chronic liver conditions before liver transplantation. Type 1 HRS is an acute and rapidly progressive form that often develops after a precipitating factor, including gastrointestinal bleeding or spontaneous bacterial peritonitis, while type 2 is considered a slowly progressive form of kidney failure that often occurs spontaneously in chronic ascites settings. HRS pathogenesis is multifactorial. Cirrhosis causes portal hypertension; therefore, stasis and release of vasodilator substances occur in the hepatic vascular bed, leading to vasodilatation of splanchnic arteries and systemic hypotension. Many mechanisms seem to work together to cause this imbalance: splanchnic vasodilatation; vasoactive mediators; hyperdynamic circulation states and subsequent cardiac dysfunction; neuro-hormonal mechanisms; changes in sympathetic nervous system, renin-angiotensin system, and vasopressin. In patients with AKI and cirrhosis, fluid expansion therapy needs to be initiated as soon as possible and nephrotoxic drugs discontinued. Once HRS is diagnosed, pharmacological treatment with vasoconstrictors, mainly terlipressin plus albumin, should be initiated. If there is no response, other options can include surgical venous shunts and kidney replacement therapy. In this regard, extracorporeal liver support can be a bridge for liver transplantation, which remains as the ideal treatment. Further studies are necessary to investigate early biomarkers and alternative treatments for HRS.
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Affiliation(s)
- Priscila Menezes Ferri Liu
- Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Federal University of Minas Gerais, UFMG, Avenida Alfredo Balena, 190, 2nd floor, #281 room, Belo Horizonte, Minas Gerais, 30130-100, Brazil
| | - Sarah Tayná de Carvalho
- Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Federal University of Minas Gerais, UFMG, Avenida Alfredo Balena, 190, 2nd floor, #281 room, Belo Horizonte, Minas Gerais, 30130-100, Brazil
| | - Pollyanna Faria Fradico
- Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Federal University of Minas Gerais, UFMG, Avenida Alfredo Balena, 190, 2nd floor, #281 room, Belo Horizonte, Minas Gerais, 30130-100, Brazil
| | - Maria Luiza Barreto Cazumbá
- Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Federal University of Minas Gerais, UFMG, Avenida Alfredo Balena, 190, 2nd floor, #281 room, Belo Horizonte, Minas Gerais, 30130-100, Brazil
| | - Ramon Gustavo Bernardino Campos
- Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Federal University of Minas Gerais, UFMG, Avenida Alfredo Balena, 190, 2nd floor, #281 room, Belo Horizonte, Minas Gerais, 30130-100, Brazil
| | - Ana Cristina Simões E Silva
- Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Federal University of Minas Gerais, UFMG, Avenida Alfredo Balena, 190, 2nd floor, #281 room, Belo Horizonte, Minas Gerais, 30130-100, Brazil.
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17
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Gupta K, Bhurwal A, Law C, Ventre S, Minacapelli CD, Kabaria S, Li Y, Tait C, Catalano C, Rustgi VK. Acute kidney injury and hepatorenal syndrome in cirrhosis. World J Gastroenterol 2021; 27:3984-4003. [PMID: 34326609 PMCID: PMC8311533 DOI: 10.3748/wjg.v27.i26.3984] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 03/19/2021] [Accepted: 06/22/2021] [Indexed: 02/06/2023] Open
Abstract
Acute kidney injury (AKI) in cirrhosis, including hepatorenal syndrome (HRS), is a common and serious complication in cirrhotic patients, leading to significant morbidity and mortality. AKI is separated into two categories, non-HRS AKI and HRS-AKI. The most recent definition and diagnostic criteria of AKI in cirrhosis and HRS have helped diagnose and prognosticate the disease. The pathophysiology behind non-HRS-AKI and HRS is more complicated than once theorized and involves more processes than just splanchnic vasodilation. The common biomarkers clinicians use to assess kidney injury have significant limitations in cirrhosis patients; novel biomarkers being studied have shown promise but require further studies in clinical settings and animal models. The overall management of non-HRS AKI and HRS-AKI requires a systematic approach. Although pharmacological treatments have shown mortality benefit, the ideal HRS treatment option is liver transplantation with or without simultaneous kidney transplantation. Further research is required to optimize pharmacologic and nonpharmacologic approaches to treatment. This article reviews the current guidelines and recommendations of AKI in cirrhosis.
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Affiliation(s)
- Kapil Gupta
- Division of Gastroenterology and Hepatology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, United States
| | - Abhishek Bhurwal
- Division of Gastroenterology and Hepatology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, United States
| | - Cindy Law
- Division of Gastroenterology and Hepatology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, United States
| | - Scott Ventre
- Department of Internal Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, United States
| | - Carlos D Minacapelli
- Division of Gastroenterology and Hepatology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, United States
| | - Savan Kabaria
- Department of Internal Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, United States
| | - You Li
- Division of Gastroenterology and Hepatology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, United States
| | - Christopher Tait
- Division of Gastroenterology and Hepatology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, United States
| | - Carolyn Catalano
- Division of Gastroenterology and Hepatology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, United States
| | - Vinod K Rustgi
- Division of Gastroenterology and Hepatology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, United States
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18
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Weng J, Han X, Zeng F, Zhang Y, Feng L, Cai L, Liang K, Liu S, Li S, Fu G, Zeng M, Gao Y. Fiber scaffold bioartificial liver therapy relieves acute liver failure and extrahepatic organ injury in pigs. Theranostics 2021; 11:7620-7639. [PMID: 34335954 PMCID: PMC8315066 DOI: 10.7150/thno.58515] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Accepted: 04/15/2021] [Indexed: 02/06/2023] Open
Abstract
Rationale: Acute liver failure (ALF) causes severe liver injury and a systemic inflammatory response, leading to multiorgan failure with a high short-term mortality. Bioartificial liver (BAL) therapy is a promising approach that is hampered by the lack of appropriate bioreactors and carriers to retain hepatic cell function and poor understanding of BAL treatment mechanisms in ALF and extrahepatic organ injury. Recently, we used a fiber scaffold bioreactor (FSB) for the high-density, three-dimensional (3D) culture of primary porcine hepatocytes (PPHs) combined with an absorption component to construct a BAL and verified its function in a D-galactosamine (D-gal)-induced ALF porcine model to evaluate its protective effects on the liver and extrahepatic organs. Methods: Male pigs were randomized into standard/supportive therapy (ST), ST+no-cell BAL (ST+Sham BAL) and ST+BAL groups and received treatment 48 h after receiving a D-gal injection. Changes in blood chemistry and clinical symptoms were monitored for 120 h. Tissues and plasma were collected for analysis by pathological examination, immunoblotting, quantitative PCR and immunoassays. Results: PPHs cultured in the FSB obtained sufficient aeration and nutrition for high-density, 3D culture and maintained superior viability and functionality (biosynthesis and detoxification) compared with those cultured in flasks. All the animals developed ALF, acute kidney injury (AKI) and hepatic encephalopathy (HE) 48 h after D-gal infusion and received corresponding therapies. Animals in the BAL group showed markedly improved survival (4/5; 80%) compared with those in the ST+Sham BAL (0/5; p < 0.001) and ST (0/5; p < 0.001) groups. The levels of blood ammonia and biochemical and inflammatory indices were alleviated after BAL treatment. Increased liver regeneration and attenuations in the occurrence and severity of ALF, AKI and HE were observed in the ST+BAL group compared with the ST (p = 0.0009; p = 0.038) and ST+Sham BAL (p = 0.011; p = 0.031) groups. Gut leakage, the plasma endotoxin level, bacterial translocation, and peripheral and neuroinflammation were alleviated in the ST+BAL group compared with those in the other groups. Conclusions: BAL treatment enhanced liver regeneration and alleviated the systemic inflammatory response and extrahepatic organ injury to prolong survival in the ALF model and has potential as a therapeutic approach for ALF patients.
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Affiliation(s)
- Jun Weng
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou 510515, China
- State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou 510515, China
| | - Xu Han
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou 510515, China
- State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou 510515, China
| | - Fanhong Zeng
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou 510515, China
- State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou 510515, China
| | - Yue Zhang
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou 510515, China
- State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou 510515, China
| | - Lei Feng
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou 510515, China
- State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou 510515, China
| | - Lei Cai
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou 510515, China
- State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou 510515, China
| | - Kangyan Liang
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou 510515, China
- State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou 510515, China
| | - Shusong Liu
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou 510515, China
- State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou 510515, China
| | - Shao Li
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou 510515, China
- State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou 510515, China
| | - Gongbo Fu
- Department of Medical Oncology, Jinling Hospital, First School of Clinical Medicine, Southern Medical University, Nanjing 210000, China
| | - Min Zeng
- Guangdong Qianhui Biotechnology Co., Ltd., Guangzhou 510285, China
| | - Yi Gao
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou 510515, China
- State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou 510515, China
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Yang Y, Ge B, Liu Y, Feng J. The efficacy of biomarkers in the diagnosis of acute kidney injury secondary to liver cirrhosis. Medicine (Baltimore) 2021; 100:e25411. [PMID: 33832138 PMCID: PMC8036071 DOI: 10.1097/md.0000000000025411] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Revised: 01/19/2021] [Accepted: 02/08/2021] [Indexed: 01/05/2023] Open
Abstract
ABSTRACT This study is to investigate the role of neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (CysC) and creatinine in the diagnosis of acute kidney injury (AKI) secondary to liver cirrhosis.A total of 825 patients (including 540 liver cirrhosis patients and 285 healthy controls) were enrolled. Liver cirrhosis patients were further subdivided into AKI secondary to liver cirrhosis group (AKI group, 210 patients) and simple liver cirrhosis group (LC group, 330 patients). Serum NGAL/urine NGAL (sNGAL/uNGAL), and serum creatinine (sCr) levels as well as estimated glomerular filtration rates were measured. The diagnostic performances of these indicators in AKI secondary to liver cirrhosis were evaluated.The levels of sNGAL, uNGAL, CysC and sCr in the AKI group were significantly higher than those of LC and healthy control groups. However, the eGFR and c-aGFR of AKI group were significantly lower. With the progression of AKI (AKI-S1→AKI-S2→AKI-S3), the levels of sNGAL, uNGAL, CysC and sCr increased gradually, while the levels of c-aGFR and eGFR decreased gradually. The sNGAL, uNGAL and CysC were positively correlated with sCr (r = 0.638, 0.635, and 0.650), but negatively correlated with c-aGFR (r = -0.617, -0.606 and -0.655). However, eGFR had a negative correlation with sCr (r = -0.711), but a positive correlation with c-aGFR (r = 0.736). ROC curve analysis showed that the area under the curve for uNGAL was the largest (0.976), followed by sNGAL (0.967). The diagnostic efficacy of uNGAL and sNGAL in AKI group were 0.907 and 0.870, and the risk degrees were OR = 54.524 and 5.115, respectively.NGAL might perform better than sCr and CysC in the diagnosis of AKI secondary to liver cirrhosis, while uNGAL might be a better indicator than sNGAL in AKI diagnosis.
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Affiliation(s)
- Yuwei Yang
- Department of Laboratory Medicine, Mianyang Central Hospital, Affiliated to Southwest Medical University, Mianyang
| | - Bin Ge
- Department of Laboratory Medicine, Pidu District People's Hospital, Chengdu, Sichuan, China
| | - Yan Liu
- Department of Laboratory Medicine, Pidu District People's Hospital, Chengdu, Sichuan, China
| | - Jiafu Feng
- Department of Laboratory Medicine, Mianyang Central Hospital, Affiliated to Southwest Medical University, Mianyang
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20
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Casler K, Chaney A. Cirrhosis: An evidence-based approach. Nursing 2021; 51:24-34. [PMID: 33953095 DOI: 10.1097/01.nurse.0000731828.24893.bb] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
ABSTRACT The role of nurses in managing patients with cirrhosis is increasing due to the growing prevalence of the disease. This article reviews the pathophysiology, diagnosis, complications, and management of patients with cirrhosis, with an emphasis on interdisciplinary collaboration and evidence-based practice.
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Affiliation(s)
- Kelly Casler
- Kelly Casler is an assistant professor of clinical nursing at The Ohio State University College of Nursing in Columbus, Ohio, and an FNP at The Healthcare Connection in Lincoln Heights. Amanda Chaney is chair of the advanced practice provider subcommittee and a senior NP at the department of transplant at the Mayo Clinic, Jacksonville, Fla
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21
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Standardized approach of albumin, midodrine and octreotide on hepatorenal syndrome treatment response rate. Eur J Gastroenterol Hepatol 2021; 33:102-106. [PMID: 32243349 DOI: 10.1097/meg.0000000000001700] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Hepatorenal syndrome (HRS) remains a serious complication of cirrhosis with a high mortality rate. There is little information on the effect of standardizing albumin, midodrine and octreotide combination on treatment response in patients with HRS. OBJECTIVE The aim of the study was to determine the impact of a standardized HRS treatment regimen on renal function recovery. The primary outcome was full response rate. Secondary outcomes included partial and no response rates, 30-day all-cause mortality, ICU length of stay (LOS), hospital LOS, liver transplantation and total dose of albumin. METHODS This retrospective study evaluated the impact of using a standardized approach with albumin, midodrine and octreotide on treatment response rates compared to a historical group. RESULTS Of the patients with HRS, 28 received a standardized approach with albumin, midodrine and octreotide while 60 received a nonstandardized approach. Ten percent of patients achieved full response in the prestandardization group compared with 25% in the poststandardization group (P = 0.07). Renal replacement therapy was significantly more prevalent in the prestandardization group vs. poststandardization group (45% vs. 21.4%, P = 0.03). Liver transplantation was performed significantly more often in the prestandardization group compared the poststandardization group (23% vs. 3.6%, P = 0.02). Amount of albumin used was statistically lower in the poststandardization group (425 vs. 332 g, P = 0.05). No significant differences in days of HRS treatment, mortality rate, hospital and ICU LOS were observed. CONCLUSION A trend towards improved treatment response rate was observed after standardizing the HRS treatment regimen. Standardized therapy led to significantly lower rates of renal replacement therapy and liver transplantation, suggesting patients in poststandardization were effectively managed medically without requiring further intervention.
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22
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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.
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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
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23
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Abstract
The NP's role in managing cirrhosis is increasing due to the growing prevalence of the disease. The purpose of this article is to review the pathophysiology, diagnosis, and management of patients with cirrhosis with an emphasis on interdisciplinary collaboration and evidence-based practice. Cirrhosis complications are also discussed.
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Moore K, Jamil K, Verleger K, Luo L, Kebede N, Heisen M, Corman S, Leonardi R, Bakker R, Maï C, Shamseddine N, Huang X, Allegretti AS. Real-world treatment patterns and outcomes using terlipressin in 203 patients with the hepatorenal syndrome. Aliment Pharmacol Ther 2020; 52:351-358. [PMID: 32495956 PMCID: PMC7383732 DOI: 10.1111/apt.15836] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Revised: 03/29/2020] [Accepted: 05/13/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND Hepatorenal syndrome and acute kidney injury are common complications of decompensated cirrhosis, and terlipressin is recommended as first-line vasoconstrictor therapy. However, data on its use outside of clinical trials are lacking. AIMS To assess practice patterns and outcomes around vasoconstrictor use for hepatorenal syndrome in UK hospitals. METHODS This was a multicentre chart review study. Data were extracted from medical records of patients diagnosed with hepatorenal syndrome and treated by vasoconstrictor drugs between January 2013 and December 2017 at 26 hospitals in the United Kingdom. The primary outcome was improvement of kidney function, defined as complete response (serum creatinine improved to ≤1.5 mg/dL), partial response (serum creatinine reduction of ≥20% but >1.5 mg/dL) and overall response (complete or partial response). Other outcomes included need for dialysis, mortality, liver transplantation and adverse events. RESULTS Of the 225 patients included in the analysis, 203 (90%) were treated with terlipressin (median duration, 6 days; range: 2-24 days). Mean (±standard deviation) serum creatinine at vasopressor initiation was 3.25 ± 1.64 mg/dL. Terlipressin overall response rate was 73%. Overall response was higher in patients with mild acute kidney injury (baseline serum creatinine <2.25 mg/dL), compared to those with moderate (serum creatinine ≥2.25 mg/dL and <3.5 mg/dL) or severe (serum creatinine ≥3.5 mg/dL). Ninety-day survival was 86% for all patients (93% for overall responders vs 66% for treatment nonresponders, P < 0.0001). CONCLUSION Terlipressin is the most commonly prescribed vasoconstrictor for patients with hepatorenal syndrome in the United Kingdom. Treatment with terlipressin in patients with less severe acute kidney injury (serum creatinine <2.25 mg/dL) was associated with higher treatment responses, and 90-day survival.
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Affiliation(s)
- Kevin Moore
- UCL Institute of Liver and Digestive HealthRoyal Free HospitalUniversity College LondonLondonUK
| | | | | | | | | | | | | | - Roberta Leonardi
- UCL Institute of Liver and Digestive HealthRoyal Free HospitalUniversity College LondonLondonUK
| | | | | | | | | | - Andrew S. Allegretti
- Division of NephrologyDepartment of MedicineMassachusetts General HospitalBostonMAUSA
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Lee JH, Yoon EL, Park SE, Park JY, Choi JM, Jeon TJ, Shin WC, Choi WC. Clinical Significance of Urinary Neutrophil Gelatinase-associated Lipocalin Levels in Defining the Various Etiologies of Acute Kidney Injury in Liver Cirrhosis Patients. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2020; 74:212-218. [PMID: 31650797 DOI: 10.4166/kjg.2019.74.4.212] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/11/2019] [Revised: 07/12/2019] [Accepted: 07/24/2019] [Indexed: 01/09/2023]
Abstract
Background/Aims A diagnosis of hepatorenal syndrome (HRS) is based on a differential evaluation of acute kidney injury (AKI), which may aggravate the clinical course. This study assessed the clinical significance of the urinary neutrophil gelatinase- associated lipocalin (u-NGAL) levels in a differential diagnosis of AKI in patients with liver cirrhosis (LC). Methods Patients with LC who developed AKI were enrolled prospectively. Clinically, patients with AKI were classified into prerenal azotemia (PRA), HRS, and acute tubular necrosis (ATN) groups. Results Fifty-five patients (male, 74.5%) with LC who exhibited AKI upon admission were enrolled; 28, 9, and 18 patients were included in the PRA, HRS, and ATN groups, respectively. The baseline model for end-stage liver disease (MELD) scores was similar in the subgroups. The median event creatinine level, measured at the time of the AKI diagnosis, was similar in the HRS and ATN subgroups. On the other hand, the median event u-NGAL level differed significantly between the three subgroups (PRA, HRS, and ATN: 37 vs. 134 vs. 2,625 ng/mL, p=0.003). In particular, the median u-NGAL level of the HRS group was clearly different from those of the PRA (p<0.001) and ATN (p<0.001) groups. Multivariable analysis revealed the natural logarithm of the u-NGAL level (hazard ratio [HR] 1.77, p=0.031) and the MELD score (HR 1.17, p=0.027) to be independent prognostic factors for in-hospital mortality in patients with LC and AKI. Conclusions The median u-NGAL level differentiated HRS from ATN and served as a clinical indicator of in-hospital mortality for patients with LC and AKI.
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Affiliation(s)
- Jong Ho Lee
- Department of Internal Medicine, Hankook General Hospital, Cheongju, Korea
| | - Eileen L Yoon
- Department of Internal Medicine, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Korea
| | - Seong Eun Park
- Department of Internal Medicine, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Korea
| | - Ji Young Park
- Department of Internal Medicine, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Korea
| | - Jeong Min Choi
- Department of Internal Medicine, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Korea
| | - Tae Joo Jeon
- Department of Internal Medicine, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Korea
| | - Won Chang Shin
- Department of Internal Medicine, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Korea
| | - Won-Choong Choi
- Department of Internal Medicine, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Korea
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Kalmykova ZA, Kononenko IV, Mayorov AY. [Diabetes mellitus and chronic liver diseases. Part 1: general mechanisms of etiology and pathogenesis]. TERAPEVT ARKH 2019; 91:106-111. [PMID: 32598639 DOI: 10.26442/00403660.2019.10.000165] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Indexed: 12/12/2022]
Abstract
In recent years there has been an active discussion about the relationship between diabetes mellitus (DM) and chronic liver diseases (CLD). On the one hand, patients with diabetes have an increased risk of developing CLD. On the other hand, patients with CLD very often identify abnormal glucose metabolism which ultimately leads to impaired glucose tolerance and the development of diabetes. This review outlines potential causal relationships between some CLD and DM. Common mechanisms that provoke metabolic and autoimmune disorders in the development of various nosologies of the CKD group, leading to steatosis, insulin resistance, impaired glucose tolerance and the development of diabetes are described. Certain features of the assessment of carbohydrate metabolism compensation in patients with hepatic dysfunction, anemia and protein metabolism disorders are described.
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27
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Best LMJ, Freeman SC, Sutton AJ, Cooper NJ, Tng E, Csenar M, Hawkins N, Pavlov CS, Davidson BR, Thorburn D, Cowlin M, Milne EJ, Tsochatzis E, Gurusamy KS. Treatment for hepatorenal syndrome in people with decompensated liver cirrhosis: a network meta-analysis. Cochrane Database Syst Rev 2019; 9:CD013103. [PMID: 31513287 PMCID: PMC6740336 DOI: 10.1002/14651858.cd013103.pub2] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Hepatorenal syndrome is defined as renal failure in people with cirrhosis in the absence of other causes. In addition to supportive treatment such as albumin to restore fluid balance, the other potential treatments include systemic vasoconstrictor drugs (such as vasopressin analogues or noradrenaline), renal vasodilator drugs (such as dopamine), transjugular intrahepatic portosystemic shunt (TIPS), and liver support with molecular adsorbent recirculating system (MARS). There is uncertainty over the best treatment regimen for hepatorenal syndrome. OBJECTIVES To compare the benefits and harms of different treatments for hepatorenal syndrome in people with decompensated liver cirrhosis. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and trial registers until December 2018 to identify randomised clinical trials on hepatorenal syndrome in people with cirrhosis. SELECTION CRITERIA We included only randomised clinical trials (irrespective of language, blinding, or publication status) in adults with cirrhosis and hepatorenal syndrome. We excluded randomised clinical trials in which participants had previously undergone liver transplantation. DATA COLLECTION AND ANALYSIS Two authors independently identified eligible trials and collected data. The outcomes for this review included mortality, serious adverse events, any adverse events, resolution of hepatorenal syndrome, liver transplantation, and other decompensation events. We performed a network meta-analysis with OpenBUGS using Bayesian methods and calculated the odds ratio (OR), rate ratio, hazard ratio (HR), and mean difference (MD) with 95% credible intervals (CrI) based on an available-case analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance. MAIN RESULTS We included a total of 25 trials (1263 participants; 12 interventions) in the review. Twenty-three trials (1185 participants) were included in one or more outcomes. All the trials were at high risk of bias, and all the evidence was of low or very low certainty. The trials included participants with liver cirrhosis of varied aetiologies as well as a mixture of type I hepatorenal syndrome only, type II hepatorenal syndrome only, or people with both type I and type II hepatorenal syndrome. Participant age ranged from 42 to 60 years, and the proportion of females ranged from 5.8% to 61.5% in the trials that reported this information. The follow-up in the trials ranged from one week to six months. Overall, 59% of participants died during this period and about 35% of participants recovered from hepatorenal syndrome. The most common interventions compared were albumin plus terlipressin, albumin plus noradrenaline, and albumin alone.There was no evidence of a difference in mortality (22 trials; 1153 participants) at maximal follow-up between the different interventions. None of the trials reported health-related quality of life. There was no evidence of differences in the proportion of people with serious adverse events (three trials; 428 participants), number of participants with serious adverse events per participant (two trials; 166 participants), proportion of participants with any adverse events (four trials; 402 participants), the proportion of people who underwent liver transplantation at maximal follow-up (four trials; 342 participants), or other features of decompensation at maximal follow-up (one trial; 466 participants). Five trials (293 participants) reported number of any adverse events, and five trials (219 participants) reported treatment costs. Albumin plus noradrenaline had fewer numbers of adverse events per participant (rate ratio 0.51, 95% CrI 0.28 to 0.87). Eighteen trials (1047 participants) reported recovery from hepatorenal syndrome (as per definition of hepatorenal syndrome). In terms of recovery from hepatorenal syndrome, in the direct comparisons, albumin plus midodrine plus octreotide and albumin plus octreotide had lower recovery from hepatorenal syndrome than albumin plus terlipressin (HR 0.04; 95% CrI 0.00 to 0.25 and HR 0.26, 95% CrI 0.07 to 0.80 respectively). There was no evidence of differences between the groups in any of the other direct comparisons. In the network meta-analysis, albumin and albumin plus midodrine plus octreotide had lower recovery from hepatorenal syndrome compared with albumin plus terlipressin. FUNDING two trials were funded by pharmaceutical companies; five trials were funded by parties who had no vested interest in the results of the trial; and 18 trials did not report the source of funding. AUTHORS' CONCLUSIONS Based on very low-certainty evidence, there is no evidence of benefit or harm of any of the interventions for hepatorenal syndrome with regards to the following outcomes: all-cause mortality, serious adverse events (proportion), number of serious adverse events per participant, any adverse events (proportion), liver transplantation, or other decompensation events. Low-certainty evidence suggests that albumin plus noradrenaline had fewer 'any adverse events per participant' than albumin plus terlipressin. Low- or very low-certainty evidence also found that albumin plus midodrine plus octreotide and albumin alone had lower recovery from hepatorenal syndrome compared with albumin plus terlipressin.Future randomised clinical trials should be adequately powered; employ blinding, avoid post-randomisation dropouts or planned cross-overs (or perform an intention-to-treat analysis); and report clinically important outcomes such as mortality, health-related quality of life, adverse events, and recovery from hepatorenal syndrome. Albumin plus noradrenaline and albumin plus terlipressin appear to be the interventions that should be compared in future trials.
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Affiliation(s)
- Lawrence MJ Best
- University College LondonDivision of Surgery and Interventional ScienceRowland Hill StreetLondonUKNW32PF
| | - Suzanne C Freeman
- University of LeicesterDepartment of Health SciencesUniversity RoadLeicesterUKLE1 7RH
| | - Alex J Sutton
- University of LeicesterDepartment of Health SciencesUniversity RoadLeicesterUKLE1 7RH
| | - Nicola J Cooper
- University of LeicesterDepartment of Health SciencesUniversity RoadLeicesterUKLE1 7RH
| | - Eng‐Loon Tng
- Ng Teng Fong General Hospital National University Health SystemDepartment of Medicine1 Jurong East Street 21SingaporeSingapore609606
| | - Mario Csenar
- University College LondonDivision of Surgery and Interventional ScienceRowland Hill StreetLondonUKNW32PF
| | - Neil Hawkins
- University of GlasgowHEHTAUniversity Ave Glasgow G12 8QQGlasgowUK
| | - Chavdar S Pavlov
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University HospitalCochrane Hepato‐Biliary GroupBlegdamsvej 9CopenhagenDenmarkDK‐2100
- 'Sechenov' First Moscow State Medical UniversityCenter for Evidence‐Based MedicinePogodinskja st. 1\1MoscowRussian Federation119881
| | - Brian R Davidson
- University College LondonDivision of Surgery and Interventional ScienceRowland Hill StreetLondonUKNW32PF
| | - Douglas Thorburn
- Royal Free Hospital and the UCL Institute of Liver and Digestive HealthSheila Sherlock Liver CentrePond StreetLondonUKNW3 2QG
| | | | | | - Emmanuel Tsochatzis
- Royal Free Hospital and the UCL Institute of Liver and Digestive HealthSheila Sherlock Liver CentrePond StreetLondonUKNW3 2QG
| | - Kurinchi Selvan Gurusamy
- University College LondonDivision of Surgery and Interventional ScienceRowland Hill StreetLondonUKNW32PF
- 'Sechenov' First Moscow State Medical UniversityCenter for Evidence‐Based MedicinePogodinskja st. 1\1MoscowRussian Federation119881
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Niewinski G, Raszeja-Wyszomirska J, Hrenczuk M, Rozga A, Malkowski P, Rozga J. Intermittent high-flux albumin dialysis with continuous venovenous hemodialysis for acute-on-chronic liver failure and acute kidney injury. Artif Organs 2019; 44:91-99. [PMID: 31267563 DOI: 10.1111/aor.13532] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Revised: 06/13/2019] [Accepted: 06/25/2019] [Indexed: 12/14/2022]
Abstract
Acute-on-chronic liver failure (ACLF) requiring intensive medical care and associated with acute kidney injury (AKI) has a mortality rate as high as 90% due to the lack of effective therapies. In this study, we assessed the effects of intermittent high-flux single-pass albumin dialysis (SPAD) coupled with continuous venovenous hemodialysis (CVVHD) on 28-day and 90-day survival and an array of clinical and laboratory parameters in patients with severe ACLF and renal insufficiency. Sixteen patients were studied. The diagnosis of ACLF and AKI was made in accordance with current EASL Clinical Practice Guidelines, including the recommendations of the International Club of Ascites. All patients received SPAD/CVVHD treatments as the blood purification therapy to support liver, kidneys, and other organs. Five patients were transplanted and 11 were not listed for transplantation because of active alcoholism. Data at the initiation of SPAD/CVVHD were compared with early morning data after the termination of the extracorporeal treatment phase. All patients had ACLF and renal insufficiency with 13/16 additionally fulfilling the AKI criteria. A total of 37 SPAD/CVVHD treatments were performed [2.3 ± 1.4]. The baseline MELD-Na score was 37.6 ± 6.6 and decreased to 33.4 ± 8.7 after SPAD/CVVHD (P < 0.001). In parallel, the CLIF-C ACLF grade and OF score, estimated at 28- and 90-day mortality, AKI stage, hepatic encephalopathy grade, and liver function tests were lowered (P = 0.001-0.032). The 28- and 90-day survivals were 56.2% overall and 53.8% in AKI. Survival in patients not transplanted (n = 11) was 45.4%. In patients with severe ACLF and AKI, the renal replacement therapy coupled with high-performance albumin dialysis improved estimated 28- and 90-day survival and several key clinical and laboratory parameters. It is postulated that these results may be further improved with earlier intervention and more SPAD treatments per patient. High-performance albumin dialysis improves survival and key clinical and laboratory parameters in severe ACLF and AKI.
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Affiliation(s)
- Grzegorz Niewinski
- 2nd Department of Anesthesiology and Intensive Medical Care, Central Independent Public Clinical Hospital, Medical University of Warsaw, Warsaw, Poland
| | - Joanna Raszeja-Wyszomirska
- Liver and Internal Medicine Unit, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Marta Hrenczuk
- Department of Surgical and Transplantation Nursing and Extracorporeal Therapies, Medical University of Warsaw, Warsaw, Poland
| | - Agata Rozga
- School of Interactive Computing, Georgia Institute of Technology, Atlanta, Georgia
| | - Piotr Malkowski
- Department of Surgical and Transplantation Nursing and Extracorporeal Therapies, Medical University of Warsaw, Warsaw, Poland
| | - Jacek Rozga
- Department of Surgical and Transplantation Nursing and Extracorporeal Therapies, Medical University of Warsaw, Warsaw, Poland
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Chiang CW, Lin YJ, Huang YB. Terlipressin-Induced Peripheral Cyanosis in a Patient with Liver Cirrhosis and Hepatorenal Syndrome. AMERICAN JOURNAL OF CASE REPORTS 2019; 20:5-9. [PMID: 30600312 PMCID: PMC6325660 DOI: 10.12659/ajcr.913150] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Hepatorenal syndrome (HRS), which is a type of functional renal impairment, is one of the most serious complications in patients with liver cirrhosis. Terlipressin can induce splanchnic vasoconstriction, which increases the renal blood flow and has beneficial effects on HRS. However, terlipressin administration may cause serious ischemic complications such as skin ischemia, peripheral gangrene, and ischemic bowel necrosis. Here, we report a case of peripheral cyanosis following terlipressin administration in a cirrhotic patient with HRS. CASE REPORT The patient was a 65-year-old male. He was considered to have type-1 HRS, and thus, terlipressin was administered. However, peripheral cyanosis involving the fingers, toes, area around an umbilical hernia, and scrotum was noted. Thus, terlipressin administration was discontinued. Subsequently, his condition rapidly improved. CONCLUSIONS We reported a case of peripheral cyanosis following terlipressin administration, which resolved after discontinuation of terlipressin administration. It is important to recognize the early signs of side effects and discontinue the administration of the suspected drug immediately.
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Affiliation(s)
- Chi-Wen Chiang
- Division of Pharmacy, Pingtung Hospital, Ministry of Health and Welfare, Pingtung, Taiwan.,School of Pharmacy, Master Program in Clinical Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yun-Ju Lin
- Division of Nursing, Pingtung Hospital, Ministry of Health and Welfare, Pingtung, Taiwan
| | - Yaw-Bin Huang
- School of Pharmacy, Master Program in Clinical Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.,Department of Pharmacy, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
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30
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Amin AA, Alabsawy EI, Jalan R, Davenport A. Epidemiology, Pathophysiology, and Management of Hepatorenal Syndrome. Semin Nephrol 2019; 39:17-30. [PMID: 30606404 DOI: 10.1016/j.semnephrol.2018.10.002] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Maraolo AE, Buonomo AR, Zappulo E, Scotto R, Pinchera B, Gentile I. Unsolved Issues in the Treatment of Spontaneous Peritonitis in Patients with Cirrhosis: Nosocomial Versus Community-acquired Infections and the Role of Fungi. Rev Recent Clin Trials 2019; 14:129-135. [PMID: 30514194 DOI: 10.2174/1574887114666181204102516] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2018] [Revised: 11/26/2018] [Accepted: 11/27/2018] [Indexed: 06/09/2023]
Abstract
INTRODUCTION Historically, spontaneous bacterial peritonitis (SBP) has represented one of the most frequent and relevant infectious complications of advanced liver disease, and this is still valid today. Nevertheless, in recent years the role of fungi as causative pathogens of primary peritonitis in patients with cirrhosis has become not negligible. Another issue is linked with the traditional distinction, instrumental in therapeutic choice, between community-acquired and nosocomial forms, according to the onset. Between these two categories, another one has been introduced: the so-called "healthcare-associated infections". OBJECTIVE To discuss the most controversial aspects in the management of SBP nowadays in the light of best available evidence. METHODS A review of recent literature through MEDLINE was performed. RESULTS The difference between community-acquired and nosocomial infections is crucial to guide empiric antibiotic therapy, since the site of acquisition impact on the likelihood of multidrug-resistant bacteria as causative agents. Therefore, third-generation cephalosporins cannot be considered the mainstay of treatment in each episode. Furthermore, the distinction between healthcare-associated and nosocomial form seems very subtle, especially in areas wherein antimicrobial resistance is widespread, warranting broad-spectrum antibiotic regimens for both. Finally, spontaneous fungal peritonitis is a not common but actually underestimated entity, linked to high mortality. Especially in patients with septic shock and/or failure of an aggressive antibiotic regimen, the empiric addition of an antifungal agent might be considered. CONCLUSION Spontaneous bacterial peritonitis is one of the most important complications in patients with cirrhosis. A proper empiric therapy is crucial to have a positive outcome. In this respect, a careful assessment of risk factors for multidrug-resistant pathogens is crucial. Likewise important, mostly in nosocomial cases, is not to overlook the probability of a fungal ascitic infection, namely a spontaneous fungal peritonitis.
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Affiliation(s)
- Alberto Enrico Maraolo
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, 80131, Naples, Italy
| | - Antonio Riccardo Buonomo
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, 80131, Naples, Italy
| | - Emanuela Zappulo
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, 80131, Naples, Italy
| | - Riccardo Scotto
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, 80131, Naples, Italy
| | - Biagio Pinchera
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, 80131, Naples, Italy
| | - Ivan Gentile
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, 80131, Naples, Italy
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Abstract
Inflammation is an adaptive process to the noxious stimuli that the human body is constantly exposed to. From the local inflammatory response to a full-blown systemic inflammation, a wide complex sequence of events occurs. Persistent immunosuppression and catabolism may ensue, until multiple organ failure finally sets in. And since clinically useful and specific biomarkers are lacking, diagnosis may come late. A thorough understanding of these events (how they begin, how they evolve, and how to modulate them) is imperative, but as yet poorly studied. This review aims to consolidate current knowledge of these events so that the management of these patients is not only evidence-based, but also built on an understanding of the inner workings of the human body in health and in disease.
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Affiliation(s)
- Miguel Lourenço Varela
- Internal Medicine 1, Hospital de Faro, Centro Hospitalar Universitário do Algarve, Rua Leão Penedo, Faro, 8000-386, Portugal.
- Intensive Care Medicine 1, Hospital de Faro, Centro Hospitalar Universitário do Algarve, Rua Leão Penedo, Faro, 8000-386, Portugal.
| | - Mihail Mogildea
- Internal Medicine 1, Hospital de Faro, Centro Hospitalar Universitário do Algarve, Rua Leão Penedo, Faro, 8000-386, Portugal
| | - Ignacio Moreno
- Internal Medicine 1, Hospital de Faro, Centro Hospitalar Universitário do Algarve, Rua Leão Penedo, Faro, 8000-386, Portugal
| | - Ana Lopes
- Internal Medicine 1, Hospital de Faro, Centro Hospitalar Universitário do Algarve, Rua Leão Penedo, Faro, 8000-386, Portugal
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Maraolo AE, Gentile I, Buonomo AR, Pinchera B, Borgia G. Current evidence on the management of hepatitis B in pregnancy. World J Hepatol 2018; 10:585-594. [PMID: 30310536 PMCID: PMC6177570 DOI: 10.4254/wjh.v10.i9.585] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Revised: 04/26/2018] [Accepted: 06/09/2018] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) infection is one of the main public health problems across the globe, since almost one third of the world population presents serological markers of contact with the virus. A profound impact on the epidemiology has been exerted by universal vaccination programmes in many countries, nevertheless the infection is still widespread also in its active form. In the areas of high endemicity (prevalence of hepatitis B surface antigen positivity > 7%), mother-to-child transmission represents the main modality of infection spread. That makes the correct management of HBV in pregnancy a matter of utmost importance. Furthermore, the infection in pregnancy needs to be carefully assessed and handled not only with respect to the risk of vertical transmission but also with respect to gravid women health. Each therapeutic or preventive choice deserves to be weighed upon attentively. On many aspects evidence is scarce or controversial. This review will highlight the latest insights into the paramount steps in managing HBV in pregnancy, with particular attention to recommendations from recent guidelines and data from up-do-date research syntheses.
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Affiliation(s)
- Alberto Enrico Maraolo
- Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples 80131, Italy
| | - Ivan Gentile
- Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples 80131, Italy
| | - Antonio Riccardo Buonomo
- Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples 80131, Italy
| | - Biagio Pinchera
- Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples 80131, Italy
| | - Guglielmo Borgia
- Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples 80131, Italy
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Maraolo AE, Gentile I, Pinchera B, Nappa S, Borgia G. Current and emerging pharmacotherapy for the treatment of bacterial peritonitis. Expert Opin Pharmacother 2018; 19:1317-1325. [PMID: 30071176 DOI: 10.1080/14656566.2018.1505867] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Spontaneous bacterial peritonitis (SBP) is the quintessential model of bacterial infection in cirrhotic patients. In these particularly frail subjects, infections clearly worsen prognosis increasing substantially mortality. Furthermore, treatment of SBP has become more challenging because of the growing impact of multidrug-resistant (MDR) bacteria. AREAS COVERED This review addresses the reasons behind the change in therapeutic recommendations for SBP that have occurred in the past few years, by focusing on the following aspects: the importance of an early appropriate empirical treatment, the difference between nosocomial and non-nosocomial forms and the overall microbiological shift (rise of Gram-positive bacteria and MDR strains) that have affected SBP. EXPERT OPINION Until recently, third-generation cephalosporins have represented the cornerstone of SBP treatment, a safe choice covering the most important causative agents, namely Enterobacteriaceae. Unfortunately, massive exposure to health systems makes cirrhotic patients prone to MDR infections, which poses significant challenges, all the while not forgetting to strike a balance between effective antimicrobial activity and the risk of toxicity in these fragile subjects. Moreover, there is sparse information about new antibiotics in cirrhotic patients and about drugs levels in ascitic fluid. Therefore, further research is needed to optimize the treatment of SBP.
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Affiliation(s)
- Alberto Enrico Maraolo
- a Department of Clinical Medicine and Surgery, Section of Infectious Diseases , University of Naples Federico II , Naples , Italy
| | - Ivan Gentile
- a Department of Clinical Medicine and Surgery, Section of Infectious Diseases , University of Naples Federico II , Naples , Italy
| | - Biagio Pinchera
- a Department of Clinical Medicine and Surgery, Section of Infectious Diseases , University of Naples Federico II , Naples , Italy
| | - Salvatore Nappa
- a Department of Clinical Medicine and Surgery, Section of Infectious Diseases , University of Naples Federico II , Naples , Italy
| | - Guglielmo Borgia
- a Department of Clinical Medicine and Surgery, Section of Infectious Diseases , University of Naples Federico II , Naples , Italy
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Xu XL. Value of cystatin C, β2 macroglobulin, serum creatinine, and blood urea nitrogen in predicting hepatorenal syndrome in patients with acute-on-chronic liver failure. Shijie Huaren Xiaohua Zazhi 2018; 26:700-706. [DOI: 10.11569/wcjd.v26.i12.700] [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] [Indexed: 02/06/2023] Open
Abstract
AIM To assess the predictive value of cystatin C (Cys-C), β2 macroglobulin (β2-MG), serum creatinine (Scr), and blood urea nitrogen (BUN) for hepatorenal syndrome (HRS) in patients with acute-on-chronic liver failure (ACLF) .
METHODS Thirty-six ACLF patients with HRS (HRS group) treated at our hospital from February 2014 to December 2017 were analyzed retrospectively. Thirty-six patients with ACLF without HRS were selected as an ACLF group, and 50 patients with chronic liver disease (CLD) were selected as a CLD group. Cys-C, β2-MG, Scr, and BUN were compared between the three groups. The receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic efficacy of Cys-C, β2-MG, Scr, and BUN, alone or in combination, in predicting HRS in patients with ACLF.
RESULTS The levels of Cys-C, β2-MG, Scr, and BUN in the three groups were statistically different (F = 47.330, 23.693, 41.220, 26.715; P = 0.000 for all). Compared with the CLD and ACLF groups, Cys-C (t = 9.386, 4.807, P = 0.000 for both), β2-MG (t = 30.265, 4.116; P = 0.000 for both), Scr (t = 7.457, 7.415; P = 0.000 for both), and BUN (t = 6.608, 5.014; P = 0.000 for both) were significantly increased in the HRS group. ROC curve analysis showed that Scr had the highest AUC (0.799), followed by Cys-C (AUC = 0.789), β2-MG (AUC = 0.741), and BUN (AUC = 0.910). The combination of Cys-C, β2-MG, and Scr (AUC = 0.910) performed significantly better than any of the four indexes alone. Using the best cutoff point of the ROC curve as the predictive index, the diagnostic accuracy rate of the combination of Cys-C, β2-MG, and Scr for HRS was 80.33% (sensitivity, 91.67%; specificity, 75.58%; positive predictive value, 61.11%; negative predictive value, 95.59%). The sensitivity of combined indexes was significantly higher than any of the four indexes alone (χ2 = 10, 8.692, 7.432, 3.956; P = 0.002, 0.003, 0.006, 0.047).
CONCLUSION The levels of Cys-C, β2-MG, Scr, and BUN in ACLF patients with HRS significantly increase. The combination of Cys-C, β2-MG, and Scr has higher accuracy for predicting HRS in ACLF patients.
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Affiliation(s)
- Xiao-Lin Xu
- Department of Nephrology, Shaoxing Central Hospital, Shaoxing 312000, Zhejiang Province, China
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Roumelioti ME, Glew RH, Khitan ZJ, Rondon-Berrios H, Argyropoulos CP, Malhotra D, Raj DS, Agaba EI, Rohrscheib M, Murata GH, Shapiro JI, Tzamaloukas AH. Fluid balance concepts in medicine: Principles and practice. World J Nephrol 2018; 7:1-28. [PMID: 29359117 PMCID: PMC5760509 DOI: 10.5527/wjn.v7.i1.1] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2017] [Revised: 11/16/2017] [Accepted: 11/27/2017] [Indexed: 02/06/2023] Open
Abstract
The regulation of body fluid balance is a key concern in health and disease and comprises three concepts. The first concept pertains to the relationship between total body water (TBW) and total effective solute and is expressed in terms of the tonicity of the body fluids. Disturbances in tonicity are the main factor responsible for changes in cell volume, which can critically affect brain cell function and survival. Solutes distributed almost exclusively in the extracellular compartment (mainly sodium salts) and in the intracellular compartment (mainly potassium salts) contribute to tonicity, while solutes distributed in TBW have no effect on tonicity. The second body fluid balance concept relates to the regulation and measurement of abnormalities of sodium salt balance and extracellular volume. Estimation of extracellular volume is more complex and error prone than measurement of TBW. A key function of extracellular volume, which is defined as the effective arterial blood volume (EABV), is to ensure adequate perfusion of cells and organs. Other factors, including cardiac output, total and regional capacity of both arteries and veins, Starling forces in the capillaries, and gravity also affect the EABV. Collectively, these factors interact closely with extracellular volume and some of them undergo substantial changes in certain acute and chronic severe illnesses. Their changes result not only in extracellular volume expansion, but in the need for a larger extracellular volume compared with that of healthy individuals. Assessing extracellular volume in severe illness is challenging because the estimates of this volume by commonly used methods are prone to large errors in many illnesses. In addition, the optimal extracellular volume may vary from illness to illness, is only partially based on volume measurements by traditional methods, and has not been determined for each illness. Further research is needed to determine optimal extracellular volume levels in several illnesses. For these reasons, extracellular volume in severe illness merits a separate third concept of body fluid balance.
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Affiliation(s)
- Maria-Eleni Roumelioti
- Division of Nephrology, Department of Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87131, United States
| | - Robert H Glew
- Department of Surgery, University of New Mexico School of Medicine, Albuquerque, NM 87131, United States
| | - Zeid J Khitan
- Division of Nephrology, Department of Medicine, Joan Edwards School of Medicine, Marshall University, Huntington, WV 25701, United States
| | - Helbert Rondon-Berrios
- Division of Renal and Electrolyte, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, United States
| | - Christos P Argyropoulos
- Division of Nephrology, Department of Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87131, United States
| | - Deepak Malhotra
- Division of Nephrology, Department of Medicine, University of Toledo School of Medicine, Toledo, OH 43614-5809, United States
| | - Dominic S Raj
- Division of Renal Disease and Hypertension, Department of Medicine, George Washington University, Washington, DC 20037, United States
| | - Emmanuel I Agaba
- Division of Nephology, Department of Medicine, Jos University Medical Center, Jos, Plateau State 930001, Nigeria
| | - Mark Rohrscheib
- Division of Nephrology, Department of Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87131, United States
| | - Glen H Murata
- Research Service, Raymond G Murphy VA Medical Center and University of New Mexico School of Medicine, Albuquerque, NM 87108, United States
| | | | - Antonios H Tzamaloukas
- Research Service, Raymond G Murphy VA Medical Center and University of New Mexico School of Medicine, Albuquerque, NM 87108, United States
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Testino G. Hepatorenal syndrome: role of the transjugular intrahepatic stent shunt in real life practice. Med Pharm Rep 2017; 90:464-465. [PMID: 29151800 PMCID: PMC5683841 DOI: 10.15386/cjmed-847] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2017] [Revised: 07/27/2017] [Accepted: 08/21/2017] [Indexed: 12/28/2022] Open
Affiliation(s)
- Gianni Testino
- Alcohological Regional Center - Ligurian Region. IRCCS AOU San Martino-IST, Genova, Italy
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