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Trebicka J, Garcia-Tsao G. Controversies regarding albumin therapy in cirrhosis. Hepatology 2025; 81:288-303. [PMID: 37540192 PMCID: PMC11643133 DOI: 10.1097/hep.0000000000000521] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Accepted: 05/26/2023] [Indexed: 08/05/2023]
Abstract
Albumin is the most abundant protein in the human body and is synthetized exclusively by the liver. Therefore, serum albumin levels are reduced in acute and/or chronic liver disease. In cirrhosis, low levels of albumin predict the outcome. In advanced cirrhosis, the quality of albumin is decreased due to high oxidative stress and a proinflammatory state. Therefore, the administration of i.v. albumin would seem to be of pathophysiological relevance and benefit. Yet, the questions that remain are who, when, how much, and how often. While albumin infusion is recommended after large-volume paracentesis, at diagnosis of spontaneous bacterial peritonitis, in acute kidney injury, and in hepatorenal syndrome, the amount and schedule of albumin to be administered require refinement, particularly given complications related to volume overload that have become increasingly apparent. Other indications for albumin such as infections other than spontaneous bacterial peritonitis, hyponatremia, HE, prevention of poor outcomes in hospitalized, and in outpatients with cirrhosis are still debated. The results of studies in these settings are either negative, controversial, or inconclusive. This sheds some doubts regarding the use of albumin as a "one size fits all" strategy. The indication and patient selection are crucial and not always intuitive. The amount and frequency also seem to play a role in the success or failure of albumin. This review will critically discuss the evidence and underline areas where there are indications for albumin use and others where evidence is still insufficient and will have to await the development/results of randomized controlled trials.
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Affiliation(s)
- Jonel Trebicka
- Department of Internal Medicine B, University of Münster, Münster, Germany
- European Foundation for Study of Chronic Liver Failure, EASL-CLIF-Consortium, Barcelona, Spain
- Department of Gastroenterology and Hepatology, University of Southern Denmark, Odense, Denmark
| | - Guadalupe Garcia-Tsao
- Digestive Diseases Section, Department of Medicine, Yale University, New Haven, Connecticut, USA
- Digestive Diseases Section, Department of Medicine, VA-CT Healthcare System, West Haven, Connecticut, USA
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Gao Y, Liu X, Gao Y, Duan M, Hou B, Chen Y. Pharmacological Interventions for Cirrhotic Ascites: From Challenges to Emerging Therapeutic Horizons. Gut Liver 2024; 18:934-948. [PMID: 39205495 PMCID: PMC11565010 DOI: 10.5009/gnl240038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 05/01/2024] [Accepted: 05/02/2024] [Indexed: 09/04/2024] Open
Abstract
Ascites is the most common complication in patients with decompensated cirrhosis. This condition results in a severely impaired quality of life, excessive healthcare use, recurrent hospitalizations and significant morbidity and mortality. While loop diuretics and mineralocorticoid receptor antagonists are commonly employed for symptom relief, our understanding of their impact on survival remains limited. A comprehensive understanding of the underlying pathophysiological mechanism of ascites is crucial for its optimal management. The renin-angiotensin-aldosterone system (RAAS) is increasingly believed to play a pivotal role in the formation of cirrhotic ascites, as RAAS overactivation leads to a reduction in urine sodium excretion then a decrease in the ability of the kidneys to excrete water. In this review, the authors provide an overview of the pathogenesis of cirrhotic ascites, the challenges associated with current pharmacologic treatments, and the previous attempts to modulate the RAAS, followed by a description of some emerging targeted RAAS agents with the potential to be used to treat ascites.
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Affiliation(s)
- Yuan Gao
- Fourth Department of Liver Disease, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Xin Liu
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University, Beijing, China
| | - Yunyi Gao
- School of Basic Medicine, Qingdao University, Qingdao, China
| | - Meili Duan
- Department of Critical Care Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Bing Hou
- Xenorm MedInfo Center, Beijing, China
| | - Yu Chen
- Fourth Department of Liver Disease, Beijing Youan Hospital, Capital Medical University, Beijing, China
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Pose E, Piano S, Juanola A, Ginès P. Hepatorenal Syndrome in Cirrhosis. Gastroenterology 2024; 166:588-604.e1. [PMID: 38246506 DOI: 10.1053/j.gastro.2023.11.306] [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: 06/16/2023] [Revised: 11/10/2023] [Accepted: 11/19/2023] [Indexed: 01/23/2024]
Abstract
Hepatorenal syndrome (HRS) is a form of kidney dysfunction that characteristically occurs in liver cirrhosis. It is characterized by a marked impairment of kidney function in response to circulatory and hemodynamic alterations that occur in advanced stages of liver cirrhosis, aggravated by systemic inflammation and bacterial translocation. The classical definitions of the types of HRS have been recently revisited and 2 forms of HRS have been redefined: the acute form, referred to as acute kidney injury (HRS-AKI), and the chronic form, referred to as chronic kidney disease. HRS-AKI is one of the most severe forms of AKI in patients with cirrhosis and it consists of an abrupt impairment of kidney function, frequently triggered by an infection, appearing in the setting of advanced decompensated cirrhosis. Differential diagnosis with other causes of AKI is crucial because HRS-AKI requires a specific treatment. Differential diagnosis with AKI-acute tubular necrosis may be challenging and kidney biomarkers may be useful in this setting. Treatment of HRS-AKI is based on the administration of vasoconstrictor drugs in combination with volume expansion with albumin. Prognosis of HRS-AKI is poor, and the ideal definitive treatment consists of liver transplantation or simultaneous liver-kidney transplantation. HRS-AKI has a big impact on patients' quality of life. Management of HRS-AKI remains challenging in specific situations such as alcohol-associated hepatitis or metabolic-associated steatotic liver disease cirrhosis. Developing preventive measures for HRS-AKI, improving its early identification, discovering new biomarkers for differential diagnosis, and improving the response to therapy are some of the unmet needs in the field of HRS-AKI.
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Affiliation(s)
- Elisa Pose
- Liver Unit, Hospital Clínic of Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalunya, Spain; Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Salvatore Piano
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine - DIMED, University of Padova, Padova, Italy
| | - Adrià Juanola
- Liver Unit, Hospital Clínic of Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalunya, Spain; Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Pere Ginès
- Liver Unit, Hospital Clínic of Barcelona, Barcelona, Catalunya, Spain; School of Medicine and Health Sciences, University of Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalunya, Spain; Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain.
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Garcia-Tsao G, Abraldes JG, Rich NE, Wong VWS. AGA Clinical Practice Update on the Use of Vasoactive Drugs and Intravenous Albumin in Cirrhosis: Expert Review. Gastroenterology 2024; 166:202-210. [PMID: 37978969 DOI: 10.1053/j.gastro.2023.10.016] [Citation(s) in RCA: 27] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Revised: 10/08/2023] [Accepted: 10/16/2023] [Indexed: 11/19/2023]
Abstract
DESCRIPTION Cirrhosis is a major cause of morbidity and mortality in the United States and worldwide. It consists of compensated, decompensated, and further decompensated stages; median survival is more than 15 years, 2 years, and 9 months for each stage, respectively. With each stage, there is progressive worsening of portal hypertension and the vasodilatory-hyperdynamic circulatory state, resulting in a progressive decrease in effective arterial blood volume and renal perfusion. Vasoconstrictors reduce portal pressure via splanchnic vasoconstriction and are used in the management of variceal hemorrhage. Intravenous (IV) albumin increases effective arterial blood volume and is used in the prevention of acute kidney injury (AKI) and death after large-volume paracentesis and in patients with spontaneous bacterial peritonitis (SBP). The combination of vasoconstrictors and albumin is used in the reversal of hepatorenal syndrome (HRS-AKI), the most lethal complication of cirrhosis. Because a potent vasoconstrictor, terlipressin, was recently approved by the US Food and Drug Administration, and because recent trials have explored use of IV albumin in other settings, it was considered that a best practice update would be relevant regarding the use of vasoactive drugs and IV albumin in the following 3 specific scenarios: variceal hemorrhage, ascites and SBP, and HRS. METHODS This expert review was commissioned and approved by the American Gastroenterological Association (AGA) Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership. It underwent internal peer review through standard procedures of Gastroenterology. These Best Practice Advice statements were drawn from a review of the published literature and from expert opinion. Some of the statements are unchanged from published guidelines because of lack of new evidence in the literature. Because systematic reviews were not performed, these Best Practice Advice statements do not carry formal ratings regarding the quality and evidence or strength of the presented considerations. Best Practice Advice Statements BEST PRACTICE ADVICE 1: Vasoactive drugs should be initiated as soon as the diagnosis of variceal hemorrhage is suspected or confirmed, preferably before diagnostic and/or therapeutic endoscopy. BEST PRACTICE ADVICE 2: After initial endoscopic hemostasis, vasoactive drugs should be continued for 2-5 days to prevent early rebleeding. BEST PRACTICE ADVICE 3: Octreotide is the vasoactive drug of choice in the management of variceal hemorrhage based on its safety profile. BEST PRACTICE ADVICE 4: IV albumin should be administered at the time of large-volume (>5 L) paracentesis. BEST PRACTICE ADVICE 5: IV albumin may be considered in patients with SBP. BEST PRACTICE ADVICE 6: Albumin should not be used in patients (hospitalized or not) with cirrhosis and uncomplicated ascites. BEST PRACTICE ADVICE 7: Vasoconstrictors should not be used in the management of uncomplicated ascites, after large-volume paracentesis or in patients with SBP. BEST PRACTICE ADVICE 8: IV albumin is the volume expander of choice in hospitalized patients with cirrhosis and ascites presenting with AKI. BEST PRACTICE ADVICE 9: Vasoactive drugs (eg, terlipressin, norepinephrine, and combination of octreotide and midodrine) should be used in the treatment of HRS-AKI, but not in other forms of AKI in cirrhosis. BEST PRACTICE ADVICE 10: Terlipressin is the vasoactive drug of choice in the treatment of HRS-AKI and use of concurrent albumin can be considered when accounting for patient's volume status. BEST PRACTICE ADVICE 11: Terlipressin treatment does not require intensive care unit monitoring and can be administered intravenously through a peripheral line. BEST PRACTICE ADVICE 12: Terlipressin use is contraindicated in patients with hypoxemia and in patients with ongoing coronary, peripheral, or mesenteric ischemia, and should be used with caution in patients with acute-on-chronic liver failure grade 3. The benefits may not outweigh the risks in patients with serum creatinine >5 mg/dL and in patients listed for transplantation with a Model for End-stage Liver Disease ≥35.
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Affiliation(s)
- Guadalupe Garcia-Tsao
- Section of Digestive Diseases, Yale University, New Haven, Connecticut; Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut.
| | - Juan G Abraldes
- Liver Unit, Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada
| | - Nicole E Rich
- Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Vincent Wai-Sun Wong
- Medical Data Analytics Centre, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong; State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong.
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Kim J, Jung E, Yang W, Kim CK, Durnaoglu S, Oh IR, Kim CW, Sinskey AJ, Mihm MC, Lee JH. A Novel Multi-Component Formulation Reduces Inflammation In Vitro and Clinically Lessens the Symptoms of Chronic Eczematous Skin. Int J Mol Sci 2023; 24:12979. [PMID: 37629159 PMCID: PMC10454735 DOI: 10.3390/ijms241612979] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Revised: 08/13/2023] [Accepted: 08/17/2023] [Indexed: 08/27/2023] Open
Abstract
Long-term treatments for inflammatory skin diseases like atopic dermatitis or eczema can cause adverse effects. Super Protein Multifunction (SPM) was investigated as a potential treatment for managing skin inflammation by monitoring the expression of pro-inflammatory cytokines induced using LPS and poly(I:C)/TNFα in HaCaT keratinocytes and Hs27 fibroblasts as measured via RT-PCR. SPM solution was also assessed for its effect on cytokine release, measured using ELISA, in a UVB-irradiated 3D human skin model. To evaluate the efficiency of SPM, 20 patients with mild eczematous skin were randomized to receive SPM or vehicle twice a day for three weeks in a double-blind controlled trial. In vitro studies showed SPM inhibited inflammation-induced IL-1β, IL-6, IL-33, IL-1α, TSLP, and TNFα expression or release. In the clinical study, the SPM group showed significant improvements in the IGA, PA, and DLQI scores compared to the vehicle group. Neither group showed significant differences in VAS (pruritus). Histological analysis showed reduced stratum corneum thickness and inflammatory cell infiltration. The results suggest that SPM may reduce inflammation in individuals with chronic eczematous skin.
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Affiliation(s)
- Jihee Kim
- Department of Dermatology & Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul 03722, Republic of Korea;
- Scar Laser and Plastic Surgery Center, Yonsei Cancer Hospital, Seoul 03722, Republic of Korea
| | - Eunjoong Jung
- Biocoz Global Korea, R & D Center, Seoul 03181, Republic of Korea; (E.J.); (W.Y.); (C.-K.K.); (S.D.); (I.-R.O.); (C.-W.K.)
| | - Wonmi Yang
- Biocoz Global Korea, R & D Center, Seoul 03181, Republic of Korea; (E.J.); (W.Y.); (C.-K.K.); (S.D.); (I.-R.O.); (C.-W.K.)
| | - Chun-Kang Kim
- Biocoz Global Korea, R & D Center, Seoul 03181, Republic of Korea; (E.J.); (W.Y.); (C.-K.K.); (S.D.); (I.-R.O.); (C.-W.K.)
| | - Serpen Durnaoglu
- Biocoz Global Korea, R & D Center, Seoul 03181, Republic of Korea; (E.J.); (W.Y.); (C.-K.K.); (S.D.); (I.-R.O.); (C.-W.K.)
| | - In-Rok Oh
- Biocoz Global Korea, R & D Center, Seoul 03181, Republic of Korea; (E.J.); (W.Y.); (C.-K.K.); (S.D.); (I.-R.O.); (C.-W.K.)
| | - Chan-Wha Kim
- Biocoz Global Korea, R & D Center, Seoul 03181, Republic of Korea; (E.J.); (W.Y.); (C.-K.K.); (S.D.); (I.-R.O.); (C.-W.K.)
| | - Anthony J. Sinskey
- Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
| | - Martin C. Mihm
- Department of Dermatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA;
| | - Ju Hee Lee
- Department of Dermatology & Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul 03722, Republic of Korea;
- Scar Laser and Plastic Surgery Center, Yonsei Cancer Hospital, Seoul 03722, Republic of Korea
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Bai Z, Wang L, Wang R, Zou M, Méndez-Sánchez N, Romeiro FG, Cheng G, Qi X. Use of human albumin infusion in cirrhotic patients: a systematic review and meta-analysis of randomized controlled trials. Hepatol Int 2022; 16:1468-1483. [PMID: 36048318 DOI: 10.1007/s12072-022-10374-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 06/04/2022] [Indexed: 11/04/2022]
Abstract
BACKGROUND Human albumin infusion is effective for controlling systemic inflammation, thereby probably managing some liver cirrhosis-related complications, such as spontaneous bacterial peritonitis (SBP), hepatic encephalopathy (HE), and hepatorenal syndrome. However, its clinical benefits remain controversial. METHODS EMBASE, PubMed, and Cochrane Library databases were searched. Randomized controlled trials (RCTs) regarding use of human albumin infusion in cirrhotic patients were eligible. Mortality and incidence of liver cirrhosis-related complications were pooled. Effect of human albumin infusion on mortality was also evaluated by subgroup analyses primarily according to target population and duration of human albumin infusion treatment. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. RESULTS Forty-two RCTs were finally included. Meta-analysis showed that human albumin infusion could significantly decrease the mortality of cirrhotic patients (OR = 0.81, 95% CI = 0.67-0.98, p = 0.03). Subgroup analyses showed that human albumin infusion could significantly decrease the mortality of cirrhotic patients with SBP (OR = 0.36, 95% CI = 0.20-0.64, p = 0.0005) and HE (OR = 0.43, 95% CI = 0.22-0.85, p = 0.02), but not those with ascites or non-SBP infections or undergoing large-volume paracentesis. Short-term human albumin infusion treatment could significantly decrease short-term mortality (OR = 0.67, 95% CI = 0.50-0.89, p = 0.005), but not long-term mortality. Long-term human albumin infusion treatment could not significantly decrease long-term mortality (OR = 0.72, 95% CI = 0.48-1.08, p = 0.11). In addition, human albumin infusion could significantly decrease the incidence of renal impairment (OR = 0.63, 95% CI = 0.45-0.88, p = 0.007) and ascites (OR = 0.45, 95% CI = 0.25-0.81, p = 0.007), but not infections or gastrointestinal bleeding. CONCLUSIONS Human albumin infusion may improve the outcomes of cirrhotic patients. However, its indications for different complications and infusion strategy in liver cirrhosis should be further explored.
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Affiliation(s)
- Zhaohui Bai
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, Liaoning, China
- NMPA Key Laboratory for Research and Evaluation of Drug Regulatory Technology, Shenyang Pharmaceutical University, Shenyang, Liaoning, China
| | - Le Wang
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, Liaoning, China
- Postgraduate College, China Medical University, Shenyang, Liaoning, China
| | - Ran Wang
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, Liaoning, China
| | - Meijuan Zou
- NMPA Key Laboratory for Research and Evaluation of Drug Regulatory Technology, Shenyang Pharmaceutical University, Shenyang, Liaoning, China
| | - Nahum Méndez-Sánchez
- Medica Sur Clinic and Foundation and Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico
| | | | - Gang Cheng
- NMPA Key Laboratory for Research and Evaluation of Drug Regulatory Technology, Shenyang Pharmaceutical University, Shenyang, Liaoning, China
| | - Xingshun Qi
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, Liaoning, China.
- NMPA Key Laboratory for Research and Evaluation of Drug Regulatory Technology, Shenyang Pharmaceutical University, Shenyang, Liaoning, China.
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Castro-Narro G, Moctezuma-Velázquez C, Male-Velázquez R, Trejo-Estrada R, Bosques FJ, Moreno-Alcántar R, Rodríguez-Hernández H, Bautista-Santos A, Córtez-Hernández C, Cerda-Reyes E, Pérez-Escobar J, Aldana-Ledesma JM, Aguirre-Valadez J, Ruiz-Velasco JAV, Contreras-Omaña R, Miranda-Zazueta G, Reyes-Bastidas MDR, Meza-Cardona JM, Chávez-Tapia N, Fernández-Pérez NJ, García-Jiménez ES, Torre A. Position statement on the use of albumin in liver cirrhosis. Ann Hepatol 2022; 27:100708. [PMID: 35550187 DOI: 10.1016/j.aohep.2022.100708] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Accepted: 02/15/2022] [Indexed: 02/04/2023]
Abstract
Cirrhosis is characterised by a prolonged asymptomatic period in which the inflammation persists, increasing as the disease progresses. Characteristic of this is the increase in pro-inflammatory cytokines and pro-oxidant molecules which are determining factors in the development of multiple organ dysfunction. In the early development of cirrhosis, splanchnic arterial vasodilation, activation of vasoconstrictor systems (renin-angiotensin-aldosterone) and the sympathetic nervous system (noradrenaline) bring about bacterial translocation and systemic dissemination via portal circulation of bacterial products, and molecular patterns associated with damage, which exacerbate the systemic inflammation present in the patient with cirrhosis. Albumin is a molecule that undergoes structural and functional changes as liver damage progresses, affecting its antioxidant, immunomodulatory, oncotic and endothelial stabilising properties. Our knowledge of the properties of albumin reveals a molecule with multiple treatment options in patients with cirrhosis, from the compensated then decompensated phases to multiple organ dysfunction. Its recognised uses in spontaneous bacterial peritonitis, post-paracentesis circulatory dysfunction, acute kidney injury and hepatorenal syndrome are fully validated, and a treatment option has opened up in decompensated cirrhosis and in acute-on-chronic liver disease.
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Affiliation(s)
- Graciela Castro-Narro
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán" ["Salvador Zubirán" National Institute of Medical Sciences and Nutrition], Mexico City, Mexico; Gastroenterology Unit, Hospital Médica Sur, Mexico City, Mexico
| | - Carlos Moctezuma-Velázquez
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán" ["Salvador Zubirán" National Institute of Medical Sciences and Nutrition], Mexico City, Mexico
| | - Rene Male-Velázquez
- Instituto de la Salud Digestiva y Hepática [Institute of Gastrointestinal and Liver Health], Guadalajara, Jalisco, Mexico
| | | | | | - Rosalba Moreno-Alcántar
- Centro Médico de Alta Especialidad Siglo XXI [21st Century High Speciality Medical Centre], Mexico City, Mexico
| | | | - Aleida Bautista-Santos
- Gastroenterology Department, Centro Médico Nacional 20 de Noviembre ["20 November" National Medical Centre], Mexico City, Mexico
| | | | - Eira Cerda-Reyes
- Hospital Central Militar, Mexico City, Mexico; Escuela Militar de Graduados de Sanidad, Mexico City, Mexico
| | - Juanita Pérez-Escobar
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán" ["Salvador Zubirán" National Institute of Medical Sciences and Nutrition], Mexico City, Mexico
| | | | | | | | - Raúl Contreras-Omaña
- Centro de Estudio e Investigación en Enfermedades Hepáticas y Toxicológicas (CEIHET) [Centre for Study and Research in Hepatic and Toxicological Diseases], Pachuca de Soto, Hidalgo, Mexico
| | - Godolfino Miranda-Zazueta
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán" ["Salvador Zubirán" National Institute of Medical Sciences and Nutrition], Mexico City, Mexico
| | | | | | | | | | | | - Aldo Torre
- Metabolic Unit, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán" ["Salvador Zubirán" National Institute of Medical Sciences and Nutrition], Mexico City, Mexico.
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Heda R, Kovalic AJ, Satapathy SK. Peritransplant Renal Dysfunction in Liver Transplant Candidates. Clin Liver Dis 2022; 26:255-268. [PMID: 35487609 DOI: 10.1016/j.cld.2022.01.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Renal function is intricately tied to Model for End-Stage Liver Disease score and overall prognosis among patients with cirrhosis. The estimation of glomerular filtration rate (GFR) and etiology of renal impairment are even more magnified among cirrhotic patients in the period surrounding liver transplantation. Novel biomarkers including cystatin C and urinary neutrophil gelatinase-associated lipocalin have been demonstrated to more accurately assess renal dysfunction and aid in the diagnosis of competing etiologies. Accurately identifying the severity and chronicity of renal dysfunction among transplant candidates is an imperative component with respect to stratifying patients toward simultaneous liver-kidney transplantation versus liver transplantation alone.
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Affiliation(s)
- Rajiv Heda
- Department of Internal Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA
| | - Alexander J Kovalic
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health, Manhasset, NY 11030, USA
| | - Sanjaya K Satapathy
- Department of Medicine, Division of Hepatology, Sandra Atlas Bass Center for Liver Diseases and Transplantation, Manhasset, NY 11030, USA; Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Health, 400 Community Drive, Manhasset, NY 11030, USA.
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China L, Becares N, Rhead C, Tittanegro T, Freemantle N, O'Brien A. Targeted Albumin Infusions Do Not Improve Systemic Inflammation or Cardiovascular Function in Decompensated Cirrhosis. Clin Transl Gastroenterol 2022; 13:e00476. [PMID: 35333783 PMCID: PMC9132514 DOI: 10.14309/ctg.0000000000000476] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Accepted: 02/09/2022] [Indexed: 11/17/2022] Open
Abstract
INTRODUCTION Albumin is recommended in decompensated cirrhosis, and studies have shown potential immunomodulatory effects. However, 2 large trials of repeated albumin infusions demonstrated contrasting results between outpatients and hospitalized patients. We investigated markers of systemic inflammation, immune function, albumin binding, and cardiovascular function using samples from Albumin To prevenT Infection in chronic liveR failurE (ATTIRE) taken at baseline, day 5, and day 10 of the trial to identify why targeted albumin infusions had no effect in hospitalized patients. METHODS Plasma samples were analyzed from 143 patients (n = 71 targeted albumin; n = 72 standard care at baseline) for cytokines, cardiovascular markers, prostaglandin E2, the effect of plasma on macrophage function, and albumin radioligand binding and oxidation status. The sample size was based on our feasibility study, and samples were selected by a trial statistician stratified by the serum albumin level and the presence of infection at randomization and analyses performed blinded to the study arm. Data were linked to 3-month mortality and treatment groups compared. RESULTS Increased baseline model for end-stage liver disease score, white cell count, calprotectin, CD163, tumor necrosis factor, renin, atrial natriuretic peptide, and syndecan-1 were associated with 3-month mortality. Despite infusing substantially differing volumes of albumin, there were no significant differences in inflammatory markers, albumin-prostaglandin E2 binding, or cardiovascular markers between treatment arms. DISCUSSION Contrary to many preclinical studies, targeted intravenous albumin therapy in hospitalized decompensated cirrhosis had no effect across a broad range of systemic inflammation, albumin function, and cardiovascular mediators and biomarkers compared with standard care, consistent with the null clinical findings.
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Affiliation(s)
- Louise China
- UCL Institute for Liver and Digestive Health, London, UK
| | | | - Camilla Rhead
- UCL Institute for Liver and Digestive Health, London, UK
| | | | - Nick Freemantle
- Comprehensive Clinical Trials Unit, University College London, London, UK
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10
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Simonetti RG, Perricone G, Gluud C. Albumin for people with liver cirrhosis and bacterial infections. Hippokratia 2021. [DOI: 10.1002/14651858.cd014636] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Affiliation(s)
- Rosa G Simonetti
- Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research; Capital Region, Rigshospitalet, Copenhagen University Hospital; Copenhagen Denmark
| | | | - Christian Gluud
- Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research; Capital Region, Rigshospitalet, Copenhagen University Hospital; Copenhagen Denmark
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11
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Liu S, Meng Q, Xu Y, Zhou J. Hepatorenal syndrome in acute-on-chronic liver failure with acute kidney injury: more questions requiring discussion. Gastroenterol Rep (Oxf) 2021; 9:505-520. [PMID: 34925848 PMCID: PMC8677535 DOI: 10.1093/gastro/goab040] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Revised: 07/04/2021] [Accepted: 07/29/2021] [Indexed: 12/13/2022] Open
Abstract
In cirrhosis with ascites, hepatorenal syndrome (HRS) is a specific prerenal dysfunction unresponsive to fluid volume expansion. Acute-on-chronic liver failure (ACLF) comprises a group of clinical syndromes with multiple organ failure and early high mortality. There are differences in the characterization of ACLF between the Eastern and Western medical communities. Patients with ACLF and acute kidney injury (AKI) have more structural injuries, contributing to confusion in diagnosing HRS-AKI. In this review, we discuss progress in the pathogenesis, diagnosis, and management of HRS-AKI, especially in patients with ACLF. Controversy regarding HRS-AKI in ACLF and acute liver failure, hepatic carcinoma, shock, sepsis, and chronic kidney disease is also discussed. Research on the treatment of HRS-AKI with ACLF needs to be more actively pursued to improve disease prognosis.
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Affiliation(s)
- Songtao Liu
- Department of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, P. R. China
- Department of Severe Liver Disease, Beijing You’an Hospital, Capital Medical University, Beijing, P. R. China
| | - Qinghua Meng
- Department of Severe Liver Disease, Beijing You’an Hospital, Capital Medical University, Beijing, P. R. China
| | - Yuan Xu
- Department of Critical Care Medicine, Beijing Tsinghua Chang Gung Hospital, Beijing, P. R. China
| | - Jianxin Zhou
- Department of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, P. R. China
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12
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Engelmann C, Clària J, Szabo G, Bosch J, Bernardi M. Pathophysiology of decompensated cirrhosis: Portal hypertension, circulatory dysfunction, inflammation, metabolism and mitochondrial dysfunction. J Hepatol 2021; 75 Suppl 1:S49-S66. [PMID: 34039492 PMCID: PMC9272511 DOI: 10.1016/j.jhep.2021.01.002] [Citation(s) in RCA: 203] [Impact Index Per Article: 50.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Revised: 12/31/2020] [Accepted: 01/04/2021] [Indexed: 02/07/2023]
Abstract
Patients with acutely decompensated cirrhosis have a dismal prognosis and frequently progress to acute-on-chronic liver failure, which is characterised by hepatic and extrahepatic organ failure(s). The pathomechanisms involved in decompensation and disease progression are still not well understood, and as specific disease-modifying treatments do not exist, research to identify novel therapeutic targets is of the utmost importance. This review amalgamates the latest knowledge on disease mechanisms that lead to tissue injury and extrahepatic organ failure - such as systemic inflammation, mitochondrial dysfunction, oxidative stress and metabolic changes - and marries these with the classical paradigms of acute decompensation to form a single paradigm. With this detailed breakdown of pathomechanisms, we identify areas for future research. Novel disease-modifying strategies that break the vicious cycle are urgently required to improve patient outcomes.
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Affiliation(s)
- Cornelius Engelmann
- Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Berlin, Germany; Institute for Liver and Digestive Health, University College London, London, United Kingdom; Section Hepatology, Clinic for Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig, Germany; Berlin Institute of Health (BIH), Berlin, Germany.
| | - Joan Clària
- European Foundation for the Study of Chronic Liver Failure (EF-Clif) and Grifols Chair, Barcelona, Spain,Biochemistry and Molecular Genetics Service, Hospital ClínicIDIBAPS and CIBERehd, Spain,Department of Biomedical Sciences, University of Barcelona, Barcelona, Spain
| | - Gyongyi Szabo
- Department of Medicine, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA
| | - Jaume Bosch
- IDIBAPS and CIBERehd, University of Barcelona, Barcelona, Spain,Department for Biomedical Research (DBMR), Bern University, Bern, Switzerland
| | - Mauro Bernardi
- Department of Medical and Surgical Sciences; Alma Mater Studiorum – University of Bologna; Italy
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13
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Albumin administration in patients with decompensated liver cirrhosis: a meta-analytic update. Eur J Gastroenterol Hepatol 2021; 33:479-486. [PMID: 32976190 DOI: 10.1097/meg.0000000000001932] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
End-stage liver disease and its related complications exert a huge disease burden and reduce the survival rates of many patients. Albumin administration for patients with decompensated liver cirrhosis has been a controversial topic of discussion. The aim of this study is to investigate whether albumin reduces the mortality and complications of liver cirrhosis compared to standard medical therapy (SMT) alone. Clinical trials in which albumin administration was compared to SMT in patients with liver cirrhosis were included in this meta-analysis. The primary outcome of this study was to evaluate the effect on reducing all-cause mortality. Ascites control, renal failure and hepatic encephalopathy were evaluated as secondary outcomes. Nine clinical trials with 1231 patients were recruited and analyzed using the quality effect model. Mortality rate was significantly reduced in the albumin group [relative risk (RR) 0.73, 95% confidence interval (CI) 0.56-0.96]. Heterogeneity was mild across all studies (I2 23.3%). Studies reporting long-term albumin (LTA) administration were found to have a significant decrease in mortality (RR 0.57, 95% CI 0.44-0.73). However, studies reporting short-term albumin administration were found to have no effect on mortality (RR 0.90, 95% CI 0.56-1.45). Furthermore, there was a significant decrease in the incidence of all secondary outcomes. This meta-analysis provides evidence that LTA administration is significantly effective in reducing the mortality of liver cirrhosis compared to SMT. Albumin administration was also shown to reduce the occurrence of ascites, renal failure and hepatic encephalopathy as complications of liver cirrhosis.
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14
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Ebied AM, Rattanasuwan T, Chen Y, Khoury AP. Albumin Utilization in Spontaneous Bacterial Peritonitis. J Pharm Pract 2021; 35:546-550. [PMID: 33648374 DOI: 10.1177/0897190021997002] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND Albumin has been shown to decrease the incidence of mortality and acute kidney injury (AKI) in patients with spontaneous bacterial peritonitis (SBP). Albumin administration in SBP is recommended within 6 hours of diagnosis and for reserved use in high-risk patients with the following baseline laboratory tests: serum creatinine >1 mg/dL, blood urea nitrogen >30 mg/dL or total bilirubin >4 mg/dL. OBJECTIVE We aimed to assess the impact of an albumin order set restricted to high-risk SBP. METHODS A retrospective cohort study was conducted between Jan 1, 2013 to Feb 28, 2018. The albumin order set was implemented on Sep 20, 2016. Patients were included if they were diagnosed with SBP and had an ascitic fluid polymorphonuclear count ≥ 250 cells/mm3. RESULTS Out of a total of 137 patients reviewed, 88 met the inclusion criteria. The incidence of AKI in the pre-order set and post-order set were 63.93% and 33.33% (p = 0.01), respectively. The incidence of mortality in the pre-order set and post-order set were 36.07% and 7.41% (p = 0.005), respectively. The percentage of patients administered albumin within 6 hours were 24.59% to 40.74% (p = 0.14) in the pre-order set and post-order set, respectively. The percentage of patients who received the recommended albumin dosing regimen ordered was 42.62% vs 96.30% (p < 0.001), in the pre-order set and post-order set, respectively. CONCLUSION The albumin order set restricted to high-risk SBP patients significantly reduced the incidence of AKI and mortality, and improved the appropriateness of albumin regimen ordered.
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Affiliation(s)
- Alex M Ebied
- Department of Clinical Sciences, High Point University Fred Wilson School of Pharmacy, High Point, NC, USA
| | - Thakul Rattanasuwan
- Department of Pharmacotherapy and Translational Research, University of Florida College of Pharmacy, Gainesville, FL, USA
| | - Yiqing Chen
- Department of Pharmacotherapy and Translational Research, University of Florida College of Pharmacy, Gainesville, FL, USA
| | - Adonice P Khoury
- Department of Pharmacotherapy and Translational Research, University of Florida College of Pharmacy, Gainesville, FL, USA
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15
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Abstract
Development of acute kidney injury in patients with chronic liver disease is common and portends a poor prognosis. Diagnosis remains challenging, as traditional markers, such as serum creatinine, are not reliable. Recent development of novel biomarkers may assist with this. Pathophysiology of this condition is multifactorial, relating to physiologic changes associated with portal hypertension, kidney factors, and systemic inflammatory response. Mainstay of treatment remains use of vasoconstrictors along with albumin. Recent guidelines streamline the selection of patients that will require simultaneous liver and kidney transplantation. Posttransplant kidney injury is common relating to multiple factors.
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Affiliation(s)
- Saro Khemichian
- Division of Gastroenterology/Liver, Keck School of Medicine, University of Southern California, 1510 San Pablo Street, Los Angeles, CA 90033, USA
| | - Claire Francoz
- Hepatology and Liver Intensive Care, Hospital Beaujon, 100 Boulevard Du General Leclerc, Clichy 92110, France
| | - Francois Durand
- Hepatology and Liver Intensive Care, Hospital Beaujon, University of Paris, 100 Boulevard Du General Leclerc, Clichy 92110, France
| | - Constantine J Karvellas
- Division of Gastroenterology (Liver Unit), Department of Critical Care Medicine, University of Alberta, 1-40 Zeidler Ledcor Building, Edmonton, Alberta T6G 2X8, Canada
| | - Mitra K Nadim
- Division of Nephrology and Hypertension, Keck School of Medicine, University of Southern California, 1520 San Pablo Street, Suite 4300, Los Angeles, CA 90033, USA.
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16
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Adachi T, Takaki A, Sato S, Tobita H, Kobashi H, Kinomura M, Nakatsuka A, Oyama A, Wada N, Sakata M, Takeuchi Y, Yasunaka T, Onishi H, Shiraha H, Okada H. High expression of a vascular stricture-related marker is predictive of an early response to tolvaptan, and a low fractional excretion of sodium is predictive of a poor long-term survival after tolvaptan administration for liver cirrhosis. Hepatol Res 2020; 50:1347-1354. [PMID: 32939957 DOI: 10.1111/hepr.13573] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Revised: 08/17/2020] [Accepted: 08/28/2020] [Indexed: 12/14/2022]
Abstract
AIM Tolvaptan is a newly available diuretic that has a specific function in water reabsorption inhibition. Given that spironolactone or furosemide induces the aggravation of cirrhotic hyponatremia and dehydration, tolvaptan affects the management strategy of liver cirrhosis. Representative predictive markers of its response include renal function-related markers such as urea nitrogen or creatinine. However, vascular function-related markers have not been well investigated. We investigated the effect of the vascular function-related marker asymmetric dimethylarginine (ADMA) and the effective arterial blood volume (EABV) marker, fractional excretion of sodium (FENa), on the early tolvaptan response and survival in liver cirrhosis. METHODS We prospectively recruited 49 patients who required add-on tolvaptan for refractory ascites or edema. Laboratory data were obtained immediately before and 1 day after tolvaptan administration. Patients exhibiting >1.5 kg weight loss after 1 week were categorized as early responders to tolvaptan. Patients were followed for a median of 200 days and were assessed for survival. RESULTS Early responders showed lower creatinine levels (<1.0 mg/dL), and higher ADMA levels (≥0.61 nmol/mL) than others in a multivariate analysis. Patients with a shorter survival were positive for hepatocellular carcinoma and had a low FENa (<0.35%). CONCLUSION Early responders showed higher ADMA levels reflecting vascular stricture, suggesting that higher vascular tonus is required for a tolvaptan early response. Patients with a shorter survival showed a lower FENa, reflecting a lower EABV and suggesting that adequate EABV is required for the prolonged survival after tolvaptan administration.
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Affiliation(s)
- Takuya Adachi
- Departments of Gastroenterology and Hepatology, and Medical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Kita-ku, Okayama, Japan
| | - Akinobu Takaki
- Departments of Gastroenterology and Hepatology, and Medical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Kita-ku, Okayama, Japan
| | - Shuichi Sato
- Department of Gastroenterology and Hepatology2, Shimane University Faculty of Medicine, Izumo, Shimane, Japan.,Department of Internal Medicine, Izumo City General Medical Center, Nadabun-cho, Izumo Shimane, Japan
| | - Hiroshi Tobita
- Department of Gastroenterology and Hepatology2, Shimane University Faculty of Medicine, Izumo, Shimane, Japan
| | - Haruhiko Kobashi
- Department of Hepatology, Japanese Red Cross Okayama Hospital, Kita-Ku, Okayama, Japan
| | - Masaru Kinomura
- Departments of Gastroenterology and Hepatology, and Medical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Kita-ku, Okayama, Japan.,Department of Internal Medicine, Izumo City General Medical Center, Nadabun-cho, Izumo Shimane, Japan
| | - Atsuko Nakatsuka
- Department of Internal Medicine, Izumo City General Medical Center, Nadabun-cho, Izumo Shimane, Japan
| | - Atsushi Oyama
- Departments of Gastroenterology and Hepatology, and Medical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Kita-ku, Okayama, Japan
| | - Nozomu Wada
- Departments of Gastroenterology and Hepatology, and Medical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Kita-ku, Okayama, Japan
| | - Masahiro Sakata
- Departments of Gastroenterology and Hepatology, and Medical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Kita-ku, Okayama, Japan
| | - Yasuto Takeuchi
- Departments of Gastroenterology and Hepatology, and Medical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Kita-ku, Okayama, Japan
| | - Tetsuya Yasunaka
- Departments of Gastroenterology and Hepatology, and Medical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Kita-ku, Okayama, Japan
| | - Hideki Onishi
- Departments of Gastroenterology and Hepatology, and Medical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Kita-ku, Okayama, Japan
| | - Hidenori Shiraha
- Departments of Gastroenterology and Hepatology, and Medical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Kita-ku, Okayama, Japan
| | - Hiroyuki Okada
- Departments of Gastroenterology and Hepatology, and Medical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Kita-ku, Okayama, Japan
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17
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Wong YJ, Qiu TY, Tam YC, Mohan BP, Gallegos-Orozco JF, Adler DG. Efficacy and Safety of IV albumin for non-spontaneous bacterial peritonitis infection among patients with cirrhosis: A systematic review and meta-analysis. Dig Liver Dis 2020; 52:1137-1142. [PMID: 32586766 DOI: 10.1016/j.dld.2020.05.047] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Revised: 05/27/2020] [Accepted: 05/28/2020] [Indexed: 02/06/2023]
Abstract
UNLABELLED Efficacy and Safety of intravenous albumin for non-spontaneous bacterial peritonitis infection among patients with cirrhosis: A systematic review and meta-analysis of randomized controlled trials INTRODUCTION: Bacterial infection is a common cause of acute-on-chronic liver failure (ACLF) and death among cirrhosis. The benefit of intravenous (IV) albumin among cirrhosis with non-SBP infection remains unclear as individual studies are underpowered to detect the survival benefit of IV albumin. AIM We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of intravenous albumin for non-SBP infection among cirrhosis patients. METHODS We performed a systematic search of electronic databases (Pubmed, MEDLINE and Clinicalkey) up to 1st December 2019. Studies evaluating IV albumin for non-SBP infection were selected. Using random effect model, the pooled odds ratio (OR), 95% confidence interval (95%CI) and heterogeneity were assessed. RESULTS A total of 3 RCTs (406 subjects) fulfilling the inclusion criteria among 218 citations were identified. There was no significant heterogeneity across included studies. In this meta-analysis, we found that the pooled risk of renal impairment (RI) (OR=0.58, 95%CI: 0.28-1.23, I2=0%), mortality at 30 days (OR=1.61, 95%CI: 0.87-3.00, I2=0%) as well as mortality at 90 days (OR=1.30, 95%CI: 0.81-2.07, I2=0%) were similar between albumin and control group. Pooled event of pulmonary edema occurred more commonly in albumin group (OR 5.17, 95%CI 1.62-16.47, I2=0%). More subjects achieved resolution of ACLF in IV albumin group as compared to control group (OR=0.11, 95%CI: 0.02-0.69, p=0.02). CONCLUSION Albumin did not reduce the risk of RI and mortality, yet increases the risk of pulmonary edema. Albumin may promote recovery of ACLF, however, more data is required to validate this benefit.
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Affiliation(s)
- Yu-Jun Wong
- Department of Gastroenterology and Hepatology, Changi General Hospital
| | - Tian-Yu Qiu
- Department of Gastroenterology and Hepatology, Changi General Hospital
| | - Yew-Chong Tam
- Education Resource Centre, Singapore General Hospital, Department of Medicine
| | - Babu P Mohan
- University of Arizona, Tucson, USA; Gastroenterology and Hepatology, University of Utah School of Medicine, Salt Lake City, Utah, USA
| | - Juan-F Gallegos-Orozco
- Gastroenterology and Hepatology, University of Utah School of Medicine, Salt Lake City, Utah, USA
| | - Douglas G Adler
- Gastroenterology and Hepatology, University of Utah School of Medicine, Salt Lake City, Utah, USA.
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18
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Abstract
PURPOSE OF REVIEW Acute kidney injury (AKI) in cirrhosis consists of varying phenotypes, with hepatorenal syndrome (HRS) representing a single entity. Prompt recognition and diagnosis of AKI cause identifies appropriate therapeutic measures. This review provides an overview of AKI definitions, highlights challenges in quantifying renal impairment in cirrhosis, lists novel diagnostic AKI biomarkers, and summarizes transplantation implications. RECENT FINDINGS Biomarkers (neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, interleukin-18, and liver-type fatty acid-binding protein) may assist in the identification of underlying acute tubular necrosis. Of these, neutrophil gelatinase-associated lipocalin is the most promising; however, significant overlap occurs among AKI phenotypes, with diagnostic values yet to be defined. Mainstay treatment of HRS consists of albumin and vasopressors. Acute-on-chronic liver failure grade independently predicts response to terlipressin treatment. Many end-stage liver disease patients with AKI have underlying chronic kidney disease with important implications on pre and postliver transplantation mortality. Simultaneous liver-kidney transplant candidacy is based on low likelihood of renal recovery. SUMMARY Novel biomarkers may assist in identification of acute tubular necrosis and persistent/severe AKI. Norepinephrine has been suggested to be inferior to terlipressin, with additional research required. Increasing acute-on-chronic liver failure grade correlates with lower likelihood of vasopressor response in HRS. Severe preliver transplantation AKI confers significantly worse postliver transplantation renal outcomes.
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19
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MacDonald AJ, Karvellas CJ. Acute kidney injury: A critical care perspective for orthotopic liver transplantation. Best Pract Res Clin Anaesthesiol 2019; 34:69-78. [PMID: 32334788 DOI: 10.1016/j.bpa.2019.12.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Accepted: 12/11/2019] [Indexed: 02/06/2023]
Abstract
Acute kidney injury (AKI) is associated with high perioperative mortality in patients undergoing liver transplantation (LT). In the era of Model of End-stage Liver Disease score-based allocation, more patients with impaired renal function are receiving LT. The majority of preoperative AKI is secondary to azotemia, including hepatorenal syndrome - a progressive form of renal impairment unique to liver failure. Prompt recognition and initiation of cause-directed therapies are central to improving post-transplant survival. Given that, the healthcare providers must develop an expertise in liver failure-related renal complications, specifically their management and perioperative implications. Notably, AKI may complicate intraoperative course, exacerbating hemodynamic instability, metabolic acidosis, and electrolyte and coagulation abnormalities. Adjunctive intraoperative continuous renal replacement therapy has been employed; however, prospective studies remain necessary to validate potential benefits.
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Affiliation(s)
| | - Constantine J Karvellas
- Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Canada; Department of Critical Care Medicine, University of Alberta, Edmonton, Canada.
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20
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Leão GS, John Neto G, Jotz RDF, Mattos AAD, Mattos ÂZD. Albumin for cirrhotic patients with extraperitoneal infections: A meta-analysis. J Gastroenterol Hepatol 2019; 34:2071-2076. [PMID: 31353630 DOI: 10.1111/jgh.14791] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2019] [Accepted: 07/18/2019] [Indexed: 01/29/2023]
Abstract
BACKGROUND AND AIM Bacterial infections are among the main causes of death in patients with cirrhosis. While there are unquestionable benefits of using albumin in patients with spontaneous bacterial peritonitis, the benefits of albumin are controversial for those with extraperitoneal infections. The aim was to compare the use of albumin associated to antibiotics and antibiotics alone in cirrhotic patients with extraperitoneal infections. METHODS A systematic review was performed using MEDLINE and Embase databases. Randomized controlled trials comparing albumin associated to antibiotics and antibiotics alone in cirrhotic patients with extraperitoneal infections were considered eligible, as long as at least one of the following outcomes was evaluated: mortality and renal dysfunction. Meta-analysis was performed using the random effects model, through the Mantel-Haenszel method. The study protocol was registered at PROSPERO platform (CRD42018107191). RESULTS The literature search yielded 812 references. Three randomized controlled trials fulfilled the selection criteria and were included in this meta-analysis. There was no evidence of significant difference between the groups regarding mortality in 30 days (risk ratio [RR] = 1.62, 95% confidence interval [CI]: 0.92-2.84, P = 0.09, I2 = 0%) or in 90 days (RR = 1.27, 95% CI: 0.89-1.83, P = 0.19, I2 = 0%). Regarding renal dysfunction, there was also no evidence of significant difference between the groups (RR = 0.55, 95% CI: 0.25-1.19, P = 0.13, I2 = 0%). CONCLUSION There is no evidence of significant benefits of using albumin for cirrhotic patients with extraperitoneal infections regarding mortality or renal dysfunction.
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Affiliation(s)
- Gabriel Stefani Leão
- Graduate Program in Medicine: Hepatology, Federal University of Health Sciences of Porto Alegre, Porto Alegre, Brazil
| | - Guilherme John Neto
- Gastroenterology and Hepatology Unit, Federal University of Health Sciences of Porto Alegre, Porto Alegre, Brazil
- Gastroenterology and Hepatology Unit, Irmandade Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, Brazil
| | - Raquel de Freitas Jotz
- Gastroenterology and Hepatology Unit, Federal University of Health Sciences of Porto Alegre, Porto Alegre, Brazil
- Gastroenterology and Hepatology Unit, Irmandade Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, Brazil
| | - Angelo Alves de Mattos
- Graduate Program in Medicine: Hepatology, Federal University of Health Sciences of Porto Alegre, Porto Alegre, Brazil
- Gastroenterology and Hepatology Unit, Irmandade Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, Brazil
| | - Ângelo Zambam de Mattos
- Graduate Program in Medicine: Hepatology, Federal University of Health Sciences of Porto Alegre, Porto Alegre, Brazil
- Gastroenterology and Hepatology Unit, Irmandade Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, Brazil
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21
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Fernández J, Clària J, Amorós A, Aguilar F, Castro M, Casulleras M, Acevedo J, Duran-Güell M, Nuñez L, Costa M, Torres M, Horrillo R, Ruiz-Del-Árbol L, Villanueva C, Prado V, Arteaga M, Trebicka J, Angeli P, Merli M, Alessandria C, Aagaard NK, Soriano G, Durand F, Gerbes A, Gustot T, Welzel TM, Salerno F, Bañares R, Vargas V, Albillos A, Silva A, Morales-Ruiz M, Carlos García-Pagán J, Pavesi M, Jalan R, Bernardi M, Moreau R, Páez A, Arroyo V. Effects of Albumin Treatment on Systemic and Portal Hemodynamics and Systemic Inflammation in Patients With Decompensated Cirrhosis. Gastroenterology 2019; 157:149-162. [PMID: 30905652 DOI: 10.1053/j.gastro.2019.03.021] [Citation(s) in RCA: 184] [Impact Index Per Article: 30.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2018] [Revised: 02/25/2019] [Accepted: 03/14/2019] [Indexed: 01/29/2023]
Abstract
BACKGROUND & AIMS We investigated the effect of albumin treatment (20% solution) on hypoalbuminemia, cardiocirculatory dysfunction, portal hypertension, and systemic inflammation in patients with decompensated cirrhosis with and without bacterial infections. METHODS We performed a prospective study to assess the effects of long-term (12 weeks) treatment with low doses (1 g/kg body weight every 2 weeks) and high doses (1.5 g/kg every week) of albumin on serum albumin, plasma renin, cardiocirculatory function, portal pressure, and plasma levels of cytokines, collecting data from 18 patients without bacterial infections (the Pilot-PRECIOSA study). We also assessed the effect of short-term (1 week) treatment with antibiotics alone vs the combination of albumin plus antibiotics (1.5 g/kg on day 1 and 1 g/kg on day 3) on plasma levels of cytokines in biobanked samples from 78 patients with bacterial infections included in a randomized controlled trial (INFECIR-2 study). RESULTS Circulatory dysfunction and systemic inflammation were extremely unstable in many patients included in the Pilot-PRECIOSA study; these patients had intense and reversible peaks in plasma levels of renin and interleukin 6. Long-term high-dose albumin, but not low-dose albumin, was associated with normalization of serum level of albumin, improved stability of the circulation and left ventricular function, and reduced plasma levels of cytokines (interleukin 6, granulocyte colony-stimulating factor, interleukin 1 receptor antagonist, and vascular endothelial growth factor) without significant changes in portal pressure. The immune-modulatory effects of albumin observed in the Pilot-PRECIOSA study were confirmed in the INFECIR-2 study. In this study, patients given albumin had significant reductions in plasma levels of cytokines. CONCLUSIONS In an analysis of data from 2 trials (Pilot-PRECIOSA study and INFECIR-2 study), we found that albumin treatment reduced systemic inflammation and cardiocirculatory dysfunction in patients with decompensated cirrhosis. These effects might be responsible for the beneficial effects of albumin therapy on outcomes of patients with decompensated cirrhosis. ClinicalTrials.gov, Numbers: NCT00968695 and NCT03451292.
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Affiliation(s)
- Javier Fernández
- EF Clif, EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain; Hospital Clínic, IDIBAPS and CIBERehd, Barcelona, Spain.
| | - Joan Clària
- EF Clif, EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain; Hospital Clínic, IDIBAPS and CIBERehd, Barcelona, Spain
| | - Alex Amorós
- EF Clif, EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain
| | - Ferrán Aguilar
- EF Clif, EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain
| | - Miriam Castro
- Hospital Clínic, IDIBAPS and CIBERehd, Barcelona, Spain
| | | | - Juan Acevedo
- South West Liver Unit, Derriford Hospital, Plymouth, United Kingdom
| | | | - Laura Nuñez
- Bioscience Research Group, Grifols, Barcelona, Spain
| | | | - Mireia Torres
- Bioscience Research Group, Grifols, Barcelona, Spain
| | | | - Luis Ruiz-Del-Árbol
- Department of Gastroenterology, Hospital Ramón y Cajal and CIBERehd, Madrid, Spain
| | - Cándido Villanueva
- Department of Gastroenterology, Hospital de Sant Pau and CIBERehd, Barcelona, Spain
| | | | | | - Jonel Trebicka
- EF Clif, EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain; Department of Internal Medicine, University Hospital of Bonn, Bonn, Germany
| | - Paolo Angeli
- EF Clif, EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain; Unit of Internal Medicine and Hepatology, Department of Medicine, DIMED, University of Padova, Padova, Italy
| | - Manuela Merli
- Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy
| | - Carlo Alessandria
- Division of Gastroenterology and Hepatology, San Giovanni Battista Hospital, Torino, Italy
| | - Niels Kristian Aagaard
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - German Soriano
- Department of Gastroenterology and Hepatology, Hospital of Santa Creu i Sant Pau and CIBERehd, Barcelona, Spain
| | - François Durand
- Service d'Hépatologie, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France
| | - Alexander Gerbes
- Department of Medicine II, Liver Centre Munich, University Hospital, LMU Munich, Munich, Germany
| | - Thierry Gustot
- Liver Transplant Unit, Erasme Hospital (ULB), Brussels, Belgium
| | - Tania M Welzel
- Medical Department I, Goethe University, Frankfurt, Germany
| | - Francesco Salerno
- Department of Internal Medicine, Policlinico IRCCS San Donato, Milano, Italy
| | - Rafael Bañares
- Department of Gastroenterology, Hospital Gregorio Marañon, and CIBERehd, Madrid, Spain
| | - Victor Vargas
- Department of Internal Medicine, Hospital Vall d'Hebron and CIBERehd, Barcelona, Spain
| | - Agustin Albillos
- Department of Gastroenterology, Hospital Ramón y Cajal and CIBERehd, Madrid, Spain
| | - Aníbal Silva
- Hospital Clínic, IDIBAPS and CIBERehd, Barcelona, Spain
| | | | | | - Marco Pavesi
- EF Clif, EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain
| | - Rajiv Jalan
- Liver Failure Group, Institute for Liver Disease Health, University College London, Royal Free Hospital, London, United Kingdom
| | - Mauro Bernardi
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Richard Moreau
- EF Clif, EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain; Service d'Hépatologie, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France; Inserm, Université Paris Diderot-Paris 7, Centre de Recherche sur l'Inflammation, Paris, France
| | - Antonio Páez
- Bioscience Research Group, Grifols, Barcelona, Spain
| | - Vicente Arroyo
- EF Clif, EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain
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22
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Paine CH, Biggins SW, Pichler RH. Albumin in Cirrhosis: More Than a Colloid. ACTA ACUST UNITED AC 2019; 17:231-243. [DOI: 10.1007/s11938-019-00227-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
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23
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Paine CH, Pichler RH. Treatment of Hyponatremia in End-Stage Liver Disease: New Tools in the Shed. Am J Gastroenterol 2018; 113:1728-1729. [PMID: 30323267 DOI: 10.1038/s41395-018-0269-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Cary H Paine
- Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington, USA
| | - Raimund H Pichler
- Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington, USA
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24
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China L, Skene SS, Bennett K, Shabir Z, Hamilton R, Bevan S, Chandler T, Maini AA, Becares N, Gilroy D, Forrest EH, O’Brien A. ATTIRE: Albumin To prevenT Infection in chronic liveR failurE: study protocol for an interventional randomised controlled trial. BMJ Open 2018; 8:e023754. [PMID: 30344180 PMCID: PMC6196858 DOI: 10.1136/bmjopen-2018-023754] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION Circulating prostaglandin E2 levels are elevated in acutely decompensated cirrhosis and have been shown to contribute to immune suppression. Albumin binds to and inactivates this immune-suppressive lipid mediator. Human albumin solution (HAS) could thus be repurposed as an immune-restorative drug in these patients.This is a phase III randomised controlled trial (RCT) to verify whether targeting a serum albumin level of ≥35 g/L in hospitalised patients with decompensated cirrhosis using repeated intravenous infusions of 20% HAS will reduce incidence of infection, renal dysfunction and mortality for the treatment period (maximum 14 days or discharge if <14 days) compared with standard medical care. METHODS AND ANALYSIS Albumin To prevenT Infection in chronic liveR failurE stage 2 is a multicentre, open-label, interventional RCT. Patients with decompensated cirrhosis admitted to the hospital with a serum albumin of <30 g/L are eligible, subject to exclusion criteria. Patients randomised to intravenous HAS will have this administered, according to serum albumin levels, for up to 14 days or discharge. The infusion protocol aims to increase serum albumin to near-normal levels.The composite primary endpoint is: new infection, renal dysfunction or mortality within the trial treatment period. Secondary endpoints include mortality at up to 6 months, incidence of other organ failures, cost-effectiveness and quality of life outcomes and time to liver transplant. The trial will recruit 866 patients at more than 30 sites across the UK. ETHICSANDDISSEMINATION Research ethics approval was given by the London-Brent research ethics committee (ref: 15/LO/0104). The clinical trials authorisation was issued by the medicines and healthcare products regulatory agency (ref: 20363/0350/001-0001). The trial is registered with the European Medicines Agency (EudraCT 2014-002300-24) and has been adopted by the National Institute for Health Research (ISRCTN 14174793). This manuscript refers to version 6.0 of the protocol. Results will be disseminated through peer-reviewed journals and international conferences. Recruitment of the first participant occurred on 25 January 2016.
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Affiliation(s)
- Louise China
- Division of Medicine, University College London, London, UK
| | - Simon S Skene
- School of Biosciences and Medicine, University of Surrey, Guildford, UK
| | - Kate Bennett
- Comprehensive Clinical Trials Unit, UCL, London, UK
| | | | | | - Scott Bevan
- Comprehensive Clinical Trials Unit, UCL, London, UK
| | | | | | | | - Derek Gilroy
- Division of Medicine, University College London, London, UK
| | - Ewan H Forrest
- Department of Gastroenterology, Glasgow Royal Infirmary, NHS Greater Glasgow and Clyde, Glasgow, UK
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25
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Katsounas A, Canbay A. Intensive Care Therapy for Patients with Advanced Liver Diseases. Visc Med 2018; 34:283-289. [PMID: 30345286 DOI: 10.1159/000492088] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Decompensated cirrhosis is characterized by high hospitalization rates and costs, frequent readmissions, and poor short-term survival. Patients admitted to the hospital with acute variceal bleeding and/or hepatic encephalopathy and/or renal dysfunction are at serious risk for developing infection and/or sepsis; in turn, this renders them highly susceptible to the development of multi-system organ failure. The lack of standardized intensive care unit management protocols in patients with cirrhosis along with only few data reports from longitudinal clinical trials makes it difficult for hepatologists and critical care specialists to provide uniform evidence for clinical practice that could safely consolidate favorable outcomes such as lower hospitalization rates and/or mortality. Based on a rigorous online search of the scientific literature as well as a longtime clinical experience of the authors in the field of hepatology and critical care medicine, this work represents a focused effort to elucidate the specific bio-morbidity of advanced liver diseases in relation to the aforementioned challenges in clinical management. Further meta-analyses and/or systematic reviews are needed to enable clinicians to develop more effective strategies to bridge patients with decompensated liver disease to recompensation or liver transplantation.
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Affiliation(s)
- Antonios Katsounas
- Department for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Magdeburg, Magdeburg, Germany
| | - Ali Canbay
- Department for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Magdeburg, Magdeburg, Germany
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26
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Shizuma T. Spontaneous bacterial and fungal peritonitis in patients with liver cirrhosis: A literature review. World J Hepatol 2018; 10:254-266. [PMID: 29527261 PMCID: PMC5838444 DOI: 10.4254/wjh.v10.i2.254] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2017] [Revised: 12/31/2017] [Accepted: 01/24/2018] [Indexed: 02/06/2023] Open
Abstract
Spontaneous bacterial (SBP) and spontaneous fungal peritonitis (SFP) can be a life-threatening infection in patients with liver cirrhosis (LC) and ascites. One of the possible mechanisms of developing SBP is bacterial translocation. Although the number of polymorphonuclear cells in the culture of ascitic fluid is diagnostic for SBP, secondary bacterial peritonitis is necessary to exclude. The severity of underlying liver dysfunction is predictive of developing SBP; moreover, renal impairment and infections caused by multidrug-resistant (MDR) organism are associated with a fatal prognosis of SBP. SBP is treated by antimicrobials, but initial empirical treatment may not succeed because of the presence of MDR organisms, particularly in nosocomial infections. Antibiotic prophylaxis is recommended for patients with LC at a high risk of developing SBP, gastrointestinal bleeding, or a previous episode of SBP, but the increase in the risk of developing an infection caused by MDR organisms is a serious concern globally. Less is known about SFP in patients with LC, but the severity of underlying liver dysfunction may increase the hospital mortality. SFP mortality has been reported to be higher than that of SBP partially because the difficulty of early differentiation between SFP and SBP induces delayed antifungal therapy for SFP.
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Affiliation(s)
- Toru Shizuma
- Department of Physiology, Tokai University School of Medicine, Isehara 2591193, Japan
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27
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He GL, Feng L, Cai L, Zhou CJ, Cheng Y, Jiang ZS, Pan MX, Gao Y. Artificial liver support in pigs with acetaminophen-induced acute liver failure. World J Gastroenterol 2017; 23:3262-3268. [PMID: 28566885 PMCID: PMC5434431 DOI: 10.3748/wjg.v23.i18.3262] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2016] [Revised: 01/24/2017] [Accepted: 03/20/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To establish a reversible porcine model of acute liver failure (ALF) and treat it with an artificial liver system.
METHODS Sixteen pigs weighing 30-35 kg were chosen and administered with acetaminophen (APAP) to induce ALF. ALF pigs were then randomly assigned to either an experimental group (n = 11), in which a treatment procedure was performed, or a control group (n = 5). Treatment was started 20 h after APAP administration and continued for 8 h. Clinical manifestations of all animals, including liver and kidney functions, serum biochemical parameters and survival times were analyzed.
RESULTS Twenty hours after APAP administration, the levels of serum aspartate aminotransferase, total bilirubin, creatinine and ammonia were significantly increased, while albumin levels were decreased (P < 0.05). Prothrombin time was found to be extended with progression of ALF. After continuous treatment for 8 h (at 28 h), aspartate aminotransferase, total bilirubin, creatinine, and ammonia showed a decrease in comparison with the control group (P < 0.05). A cross-section of livers revealed signs of vacuolar degeneration, nuclear fragmentation and dissolution. Concerning survival, porcine models in the treatment group survived for longer times with artificial liver system treatment (P < 0.05).
CONCLUSION This model is reproducible and allows for quantitative evaluation of new liver systems, such as a bioartificial liver. The artificial liver system (ZHJ-3) is safe and effective for the APAP-induced porcine ALF model.
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28
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Walayat S, Martin D, Patel J, Ahmed U, N Asghar M, Pai AU, Dhillon S. Role of albumin in cirrhosis: from a hospitalist's perspective. J Community Hosp Intern Med Perspect 2017. [PMID: 28634518 PMCID: PMC5463675 DOI: 10.1080/20009666.2017.1302704] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Albumin, a negatively charged globular protein encoded on chromosome 4, is one of the most abundant proteins in the plasma and accounts for approximately 75% of plasma oncotic pressure. The role of albumin in the management of various disease states has shown to be beneficial historically. Low serum albumin is a predictor of mortality and poor outcomes. In cirrhotics undergoing paracentesis, albumin infusion prevents rapid re-accumulation of ascitic fluid while simultaneously decreasing the risk of post-paracentesis related circulatory dysfunction. Additionally, albumin is utilized in patients with hepatorenal syndrome (HRS) and spontaneous bacterial peritonitis (SBP). Overall, albumin appears to be an effective pharmacological agent in the management of cirrhosis and its complications.
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Affiliation(s)
- Saqib Walayat
- Department of Internal Medicine, University of Illinois Peoria Campus, OSF Saint Francis Medical Center, Peoria, IL, USA
| | - Daniel Martin
- Department of Gastroenterology and Hepatology, University of Illinois Peoria Campus, OSF Saint Francis Medical Center, Peoria, IL, USA
| | - Jaymon Patel
- Department of Internal Medicine, University of Illinois Peoria Campus, OSF Saint Francis Medical Center, Peoria, IL, USA
| | - Umair Ahmed
- Department of Internal Medicine, University of Illinois Peoria Campus, OSF Saint Francis Medical Center, Peoria, IL, USA
| | - Muhammad N Asghar
- Department of Internal Medicine, University of Illinois Peoria Campus, OSF Saint Francis Medical Center, Peoria, IL, USA.,Department of Medicine, CMH Lahore Medical College, Lahore, Pakistan
| | - Aparna U Pai
- Department of Internal Medicine, Palos Community Hospital, Palos Heights, IL, USA
| | - Sonu Dhillon
- Department of Gastroenterology and Hepatology, University of Illinois Peoria Campus, OSF Saint Francis Medical Center, Peoria, IL, USA
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29
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Mas-Font S, Ros-Martinez J, Pérez-Calvo C, Villa-Díaz P, Aldunate-Calvo S, Moreno-Clari E. Prevention of acute kidney injury in Intensive Care Units. Med Intensiva 2017; 41:116-126. [PMID: 28190602 DOI: 10.1016/j.medin.2016.12.004] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2016] [Revised: 11/29/2016] [Accepted: 12/01/2016] [Indexed: 12/13/2022]
Abstract
Acute kidney injury (AKI) is a growing concern in Intensive Care Units. The advanced age of our patients, with the increase in associated morbidity and the complexity of the treatments provided favor the development of AKI. Since no effective treatment for AKI is available, all efforts are aimed at prevention and early detection of the disorder in order to establish secondary preventive measures to impede AKI progression. In critical patients, the most frequent causes are sepsis and situations that result in renal hypoperfusion; preventive measures are therefore directed at securing hydration and correct hemodynamics through fluid perfusion and the use of inotropic or vasoactive drugs, according to the underlying disease condition. Apart from these circumstances, a number of situations could lead to AKI, related to the administration of nephrotoxic drugs, intra-tubular deposits, the administration of iodinated contrast media, liver failure and major surgery (mainly heart surgery). In these cases, in addition to hydration, there are other specific preventive measures adapted to each condition.
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Affiliation(s)
- S Mas-Font
- Intensive Care Medicine, Hospital General Universitario de Castellón, Spain.
| | - J Ros-Martinez
- Intensive Care Medicine, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain
| | - C Pérez-Calvo
- Intensive Care Medicine, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain
| | - P Villa-Díaz
- Intensive Care Medicine, Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Madrid, Spain
| | - S Aldunate-Calvo
- Intensive Care Medicine, Complejo Hospitalario de Navarra, Pamplona, Spain
| | - E Moreno-Clari
- Intensive Care Medicine, Hospital General Universitario de Castellón, Spain
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30
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Angeli P, Piano S, Arroyo V. Brexit from current guideline recommendations? Gut 2016; 65:1919. [PMID: 27464709 DOI: 10.1136/gutjnl-2016-312422] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2016] [Revised: 07/05/2016] [Accepted: 07/07/2016] [Indexed: 12/08/2022]
Affiliation(s)
- Paolo Angeli
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy
| | - Salvatore Piano
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy
| | - Vicente Arroyo
- European Foundation for the Study of Chronic Liver Failure (EF-CLIF), Barcelona, Spain.,European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) Consortium, Barcelona, Spain
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31
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Bittencourt PL, Terra C, Parise ER, Farias AQ, Arroyo V, Fernandez J, Pereira G, Maubouisson LM, Andrade GM, Costa FGDB, Codes L, Andrade AR, Mattos AAD, Torres A, Couto F, Zyngier I. Intensive care management of patients with liver disease: proceedings of a single-topic conference sponsored by the Brazilian Society of Hepatology. ARQUIVOS DE GASTROENTEROLOGIA 2016; 52 Suppl 1:55-72. [PMID: 26959806 DOI: 10.1590/s0004-28032015000500004] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Survival rates of critically ill patients with liver disease has sharply increased in recent years due to several improvements in the management of decompensated cirrhosis and acute liver failure. This is ascribed to the incorporation of evidence-based strategies from clinical trials aiming to reduce mortality. In order to discuss the cutting-edge evidence regarding critical care of patients with liver disease, a joint single topic conference was recently sponsored by the Brazilian Society of Hepatology in cooperation with the Brazilian Society of Intensive Care Medicine and the Brazilian Association for Organ Transplantation. This paper summarizes the proceedings of the aforementioned meeting and it is intended to guide intensive care physicians, gastroenterologists and hepatologists in the care management of patients with liver disease.
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Affiliation(s)
- Paulo Lisboa Bittencourt
- Hospital Português, Salvador, Brazil.,Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, BA, Brasil
| | - Carlos Terra
- Hospital Universitário Pedro Ernesto, Universidade do Estado do Rio de Janeiro, RJ, Brazil
| | | | - Alberto Queiroz Farias
- Departamento de Gastroenterologia, Faculdade de Medicina, Universidade de São Paulo, SP, Brazil
| | | | | | - Gustavo Pereira
- Departamento de Gastroenterologia, Hospital Federal do Bonsucesso, Rio de Janeiro, RJ, Brasil
| | | | | | | | - Liana Codes
- Hospital Português, Salvador, Brazil.,Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, BA, Brasil
| | - Antônio Ricardo Andrade
- Hospital Português, Salvador, Brazil.,Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, BA, Brasil
| | | | - André Torres
- Hospital Universitário Pedro Ernesto, Universidade do Estado do Rio de Janeiro, RJ, Brazil
| | - Fernanda Couto
- Departamento de Gastroenterologia, Hospital Federal do Bonsucesso, Rio de Janeiro, RJ, Brasil
| | - Ivan Zyngier
- Departamento de Gastroenterologia, Hospital Federal do Bonsucesso, Rio de Janeiro, RJ, Brasil
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Effect of different therapeutic modalities on systemic, renal, and hepatic hemodynamics and short-term outcomes in cirrhotic patients with spontaneous bacterial peritonitis. Eur J Gastroenterol Hepatol 2016; 28:777-85. [PMID: 27097354 DOI: 10.1097/meg.0000000000000635] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Spontaneous bacterial peritonitis (SBP) is a major risk factor for hepatorenal syndrome. Albumin infusion has been shown to prevent renal impairment and reduce mortality in SBP. The study aimed to compare the effect of different therapeutic modalities on hemodynamics and short clinical outcomes in high-risk patients with SBP. METHODS Two hundred cirrhotic patients with SBP and bilirubin greater than 4 mg[Fraction Slash]dl or creatinine more than 1 mg[Fraction Slash]dl were enrolled. Patients were randomized to receive albumin, terlipressin, low-dose albumin plus terlipressin, or midodrine. Systemic, renal, and hepatic hemodynamics were estimated at baseline, 3, and 10 days of treatment. Renal impairment was diagnosed when the blood urea nitrogen or serum creatinine levels increased by more than 50% of the pretreatment value. RESULTS SBP resolved in most of patients in all groups (P>0.05). Cardiac output and portal flow decreased, whereas systemic vascular resistance increased significantly in terlipressin and albumin plus terlipressin groups compared with the albumin group after 3 and 10 days. After 10 days, plasma renin activity, renal, and hepatic arteries resistive index were significantly higher in the midodrine group compared with the albumin group. The midodrine group did not show any significant changes in the heart rate, mean arterial pressure, cardiac output, and portal blood flow compared with the albumin group after 3 or 10 days. There was no significant difference in renal impairment or mortality between any of the groups. CONCLUSION Terlipressin and low-dose albumin plus terlipressin could be used as a therapeutic alternative to standard-dose albumin in high-risk SBP patients.
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33
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Population Based Trends in the Incidence of Hospital Admission for the Diagnosis of Hepatorenal Syndrome: 1998-2011. Int J Nephrol 2016; 2016:8419719. [PMID: 27144022 PMCID: PMC4837259 DOI: 10.1155/2016/8419719] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2015] [Accepted: 03/21/2016] [Indexed: 02/08/2023] Open
Abstract
Background and Objectives. Hepatorenal syndrome carries a high risk of mortality. Understanding the incidence and mortality trends in hepatorenal syndrome will help inform future studies regarding the safety and efficacy of potential therapeutic interventions. Design and Methods. We conducted a retrospective cohort study using the Nationwide Inpatient Sample. We identified hospitalizations from January 1998–June 2011 with a primary diagnosis of hepatorenal syndrome. To characterize the incidence trends in monthly hepatorenal syndrome hospitalizations, we fit a piecewise linear model with a change point at January 2008. We examined hospital and patient characteristics before and after the change point. Results. Hospital admissions with a diagnosis of hepatorenal syndrome increased markedly between September of 2007 and March of 2008. Comparing patients who were admitted with a diagnosis of hepatorenal syndrome prior to 2008 with those after 2008, we found that length of stay increased while the mortality of patients admitted for hepatorenal syndrome decreased. Conclusion. The revision of the diagnostic criteria for hepatorenal syndrome may have contributed to the increase in the incidence of admissions for hepatorenal syndrome. However, the changes in the principles of hepatorenal syndrome management may have also contributed to the increase in incidence and lower mortality.
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34
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China L, Muirhead N, Skene SS, Shabir Z, PH De Maeyer R, Maini AAN, W Gilroy D, J O'Brien A. ATTIRE: Albumin To prevenT Infection in chronic liveR failurE: study protocol for a single-arm feasibility trial. BMJ Open 2016; 6:e010132. [PMID: 26810999 PMCID: PMC4735307 DOI: 10.1136/bmjopen-2015-010132] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
INTRODUCTION Circulating prostaglandin E2 levels are elevated in acutely decompensated cirrhosis and have been shown to contribute to immune suppression. Albumin binds and inactivates this hormone. Human albumin solution could thus be repurposed as an immune restorative drug in these patients.This feasibility study aims to determine whether it is possible and safe to restore serum albumin to >30 g/L and maintain it at this level in patients admitted with acute decompensated cirrhosis using repeated 20% human albumin infusions according to daily serum albumin levels. METHODS AND ANALYSIS Albumin To prevenT Infection in chronic liveR failurE (ATTIRE) stage 1 is a multicentre, open label dose feasibility trial. Patients with acutely decompensated cirrhosis admitted to hospital with a serum albumin of <30 g/L are eligible, subject to exclusion criteria. Daily intravenous human albumin solution will be infused, according to serum albumin levels, for up to 14 days or discharge in all patients. The primary end point is daily serum albumin levels for the duration of the treatment period and the secondary end point is plasma-induced macrophage dysfunction. The trial will recruit 80 patients. Outcomes will be used to assist with study design for an 866 patient randomised controlled trial at more than 30 sites across the UK. ETHICS AND DISSEMINATION Research ethics approval was given by the London-Brent research ethics committee (ref: 15/LO/0104). The clinical trials authorisation was issued by the medicines and healthcare products regulatory agency (ref: 20363/0350/001-0001). RESULTS Will be disseminated through peer reviewed journals and international conferences. Recruitment of the first participant occurred on 26/05/2015. TRIAL REGISTRATION NUMBER The trial is registered with the European Medicines Agency (EudraCT 2014-002300-24) and has been adopted by the NIHR (ISRCTN 14174793). This manuscript refers to V.4.0 of the protocol; Pre-results.
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Affiliation(s)
- Louise China
- Division of Medicine, University College London (UCL), London, UK
| | - Nicola Muirhead
- Comprehensive Clinical Trials Unit, University College London (UCL), London, UK
| | - Simon S Skene
- Comprehensive Clinical Trials Unit, University College London (UCL), London, UK
| | - Zainib Shabir
- Comprehensive Clinical Trials Unit, University College London (UCL), London, UK
| | | | | | - Derek W Gilroy
- Division of Medicine, University College London (UCL), London, UK
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35
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Role of albumin in diseases associated with severe systemic inflammation: Pathophysiologic and clinical evidence in sepsis and in decompensated cirrhosis. J Crit Care 2015; 33:62-70. [PMID: 26831575 DOI: 10.1016/j.jcrc.2015.12.019] [Citation(s) in RCA: 127] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2015] [Revised: 10/21/2015] [Accepted: 12/18/2015] [Indexed: 02/06/2023]
Abstract
The metabolism of albumin in inflammatory states such as sepsis or major surgery is complex and still not well characterized. Nevertheless, in inflammatory states, albumin synthesis has been observed to increase. By contrast, in decompensated cirrhosis, a disease characterized by systemic inflammation, albumin synthesis by the liver may decrease to 30% to 50% of normal values. Furthermore, in these conditions, there are high capillary leakage and altered albumin kinetics. The discussion regarding the effect of exogenous albumin administration on intravascular volume in inflammatory states should therefore address albumin turnover. To add complexity to our understanding of the effects of albumin, there are many data indicating that the therapeutic action of albumin is mediated not only through the impact on plasma volume expansion but also through a modulatory effect on inflammation and oxidative stress. All these characteristics are relevant to diseases associated with systemic inflammation including sepsis and decompensated cirrhosis.
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36
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37
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Spinella R, Sawhney R, Jalan R. Albumin in chronic liver disease: structure, functions and therapeutic implications. Hepatol Int 2015; 10:124-32. [PMID: 26420218 DOI: 10.1007/s12072-015-9665-6] [Citation(s) in RCA: 136] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2015] [Accepted: 08/19/2015] [Indexed: 02/08/2023]
Abstract
Human serum albumin is a critical plasma protein produced by the liver with a number of accepted clinical indications in chronic liver disease including management of circulatory and renal dysfunction in patients with ascites. Advanced cirrhosis is characterised by reduced albumin concentration as well as impaired albumin function as a result of specific structural changes and oxidative damage. Traditionally, the biologic and therapeutic role of albumin in liver disease was attributed to its oncotic effects but it is now understood that albumin has a wide range of other important physiologic functions such as immunomodulation, endothelial stabilisation, antioxidant effects and binding multiple drugs, toxins and other molecules. This review discusses the multifunctional properties of albumin and, in particular, the biologic and clinical implications of structural and functional changes of albumin that are associated with cirrhosis. Based on these insights, we explore the current and potential future therapeutic uses of albumin in liver disease.
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Affiliation(s)
- Rosaria Spinella
- Liver Failure Group, Institute for Liver and Digestive Health, University College London, Royal Free Hospital, London, NW3 2PF, UK.
| | - Rohit Sawhney
- Liver Failure Group, Institute for Liver and Digestive Health, University College London, Royal Free Hospital, London, NW3 2PF, UK
| | - Rajiv Jalan
- Liver Failure Group, Institute for Liver and Digestive Health, University College London, Royal Free Hospital, London, NW3 2PF, UK.
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Karagiannakis DS, Papatheodoridis G, Vlachogiannakos J. Recent advances in cirrhotic cardiomyopathy. Dig Dis Sci 2015; 60:1141-1151. [PMID: 25404411 DOI: 10.1007/s10620-014-3432-8] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2014] [Accepted: 11/08/2014] [Indexed: 12/15/2022]
Abstract
Cirrhotic cardiomyopathy, a cardiac dysfunction presented in patients with cirrhosis, represents a recently recognized clinical entity. It is characterized by altered diastolic relaxation, impaired contractility, and electrophysiological abnormalities, in particular prolongation of the QT interval. Several mechanisms seem to be involved in the pathogenesis of cirrhotic cardiomyopathy, including impaired function of beta-receptors, altered transmembrane currents, and overproduction of cardiodepressant factors, like nitric oxide, tumor necrosis factor α, and endogenous cannabinoids. Diastolic dysfunction is the first manifestation of cirrhotic cardiomyopathy and reflects the increased stiffness of the cardiac mass, which leads to delayed left ventricular filling. On the other hand, systolic incompetence is presented later, is usually unmasked during pharmacological or physical stress, and predisposes to the development of hepatorenal syndrome. The prolongation of QT is found in about 50 % of cirrhotic patients, but rarely leads to fatal arrhythmias. Cirrhotics with blunted cardiac function seem to have poorer survival rates compared to those without, and the risk is particularly increased during the insertion of transjugular intrahepatic portosystemic shunt or liver transplantation. Till now, there is no specific treatment for the management of cirrhotic cardiomyopathy. New agents, targeting to its pathogenetical mechanisms, may play some role as future therapeutic options.
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Affiliation(s)
- Dimitrios S Karagiannakis
- Department of Gastroenterology, Medical School of Athens University, Laiko General Hospital, 17 Agiou Thoma Street, 11527, Athens, Greece,
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Thévenot T, Bureau C, Oberti F, Anty R, Louvet A, Plessier A, Rudler M, Heurgué-Berlot A, Rosa I, Talbodec N, Dao T, Ozenne V, Carbonell N, Causse X, Goria O, Minello A, De Ledinghen V, Amathieu R, Barraud H, Nguyen-Khac E, Becker C, Paupard T, Botta-Fridlung D, Abdelli N, Guillemot F, Monnet E, Di Martino V. Effect of albumin in cirrhotic patients with infection other than spontaneous bacterial peritonitis. A randomized trial. J Hepatol 2015; 62:822-830. [PMID: 25463545 DOI: 10.1016/j.jhep.2014.11.017] [Citation(s) in RCA: 142] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2014] [Revised: 11/05/2014] [Accepted: 11/06/2014] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Albumin infusion improves renal function and survival in cirrhotic patients with spontaneous bacterial peritonitis (SBP) but its efficacy in other types of infections remains unknown. We investigated this issue through a multicenter randomized controlled trial. METHODS A total of 193 cirrhotic patients with a Child-Pugh score greater than 8 and sepsis unrelated to SBP were randomly assigned to receive antibiotics plus albumin (1.5 g/kg on day 1 and 1g/kg on day 3; albumin group [ALB]: n=96) or antibiotics alone (control group [CG]: n=97). The primary endpoint was the 3-month renal failure rate (increase in creatinine ⩾50% to reach a final value ⩾133 μmol/L). The secondary endpoint was 3-month survival rate. RESULTS Forty-seven (24.6%) patients died (ALB: n=27 vs. CG: n=20; 3-month survival: 70.2% vs. 78.3%; p=0.16). Albumin infusion delayed the occurrence of renal failure (mean time to onset, ALB: 29.0 ± 21.8 vs. 11.7 ± 9.1 days, p=0.018) but the 3-month renal failure rate was similar (ALB: 14.3% vs. CG: 13.5%; p=0.88). By multivariate analysis, MELD score (p<0.0001), pneumonia (p=0.0041), hyponatremia (p=0.031) and occurrence of renal failure (p<0.0001) were predictors of death. Of note, pulmonary edema developed in 8/96 (8.3%) patients in the albumin group of whom two died, one on the day and the other on day 33 following albumin infusion. CONCLUSIONS In cirrhotic patients with infections other than SBP, albumin infusion delayed onset of renal failure but did not improve renal function or survival at 3 months. Infusion of large amounts of albumin should be cautiously administered in the sickest cirrhotic patients.
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Affiliation(s)
- Thierry Thévenot
- Service d'Hépatologie, hôpital Jean Minjoz, 25000 Besançon, France.
| | - Christophe Bureau
- Service d'Hépato-Gastroentérologie, hôpital Purpan, clinique Dieulafoy, 31059 Toulouse, France
| | - Frédéric Oberti
- Service d' d'Hépato-Gastroentérologie, hôpital d'Angers, 4 rue Larrey, 49100 Angers, France
| | - Rodolphe Anty
- Service d'Hépato-Gastroentérologie, hôpital Archet, rue St Antoine Ginestier, 06200 Nice, France
| | - Alexandre Louvet
- Service des Maladies de l'Appareil Digestif, CHRU de Lille, rue M. Polonovs.ki, 59037 Lille cedex, France
| | - Aurélie Plessier
- Inserm U-773, Service d'Hépatologie, hôpital Beaujon, 100 boulevard du Général Leclerc, 92118 Clichy cédex, France
| | - Marika Rudler
- Service d'Hépato-Gastroentérologie, hôpital Pitié-Salpétrière, 47-83 boulevard de l'Hôpital, 75651 Paris cedex 13, France
| | | | - Isabelle Rosa
- Service d'Hépato-Gastroentérologie, CHIC de Créteil, 40 avenue de Verdun, 94010 Créteil cedex, France
| | - Nathalie Talbodec
- Service d'Hépato-Gastroentérologie, centre hospitalier, 135 rue du Président Coty, 59 200 Tourcoing, France
| | - Thong Dao
- Inserm U-1075, Service d'Hépato-Gastroentérologie, hôpital de Caen, avenue de la Côte de Nacre, 14000 Caen, France
| | - Violaine Ozenne
- Service d'Hépato-Gastroentérologie, hôpital Lariboisière, 2 rue Ambroise-Paré, 75010 Paris, France
| | - Nicolas Carbonell
- Service d'Hépato-Gastroentérologie, hôpital Saint-Antoine, 184 rue du Fbg St Antoine, 75571 Paris cedex 12, France
| | - Xavier Causse
- Service d'Hépato-Gastroentérologie, hôpital de la Source, BP 6709, 45067 Orléans cedex 12, France
| | - Odile Goria
- Service d'Hépato-Gastroentérologie, hôpital de Rouen, 1 Rue Germont, 76000 Rouen, France
| | - Anne Minello
- Service d'Hépato-Gastroentérologie, hôpital du Bocage, BP 1542, 21034 Dijon cedex, France
| | - Victor De Ledinghen
- Service d'Hépato-Gastroentérologie, hôpital du haut Levêque, 33604 Pessac cedex, France
| | - Roland Amathieu
- Service d'Hépato-Gastroentérologie, hôpital Jean Verdier, av. du 14 juillet, 93143 Bondy cedex, France
| | - Hélène Barraud
- Service d'Hépato-Gastroentérologie, hôpital de Brabois, rue du Morvan, 54511 Vandoeuvre-les-Nancy cedex, France
| | - Eric Nguyen-Khac
- Service d'Hépato-Gastroentérologie, hôpital d'Amiens, 2 Place Victor Pauchet, 80080 Amiens, France
| | - Claire Becker
- Service d'Hépato-Gastroentérologie, hôpital de Lens, 99 route de la Bassée, SP-8, 62307 Lens cedex, France
| | - Thierry Paupard
- Service d'Hépato-Gastroentérologie, hôpital de Dunkerque, 130 avenue Louis Herbeaux, 59385 Dunkerque cedex 1, France
| | - Danielle Botta-Fridlung
- Service d'Hépato-Gastroentérologie, hôpital de la Conception, 147 Bd Baille, 13005 Marseille, France
| | - Naceur Abdelli
- Service d'Hépato-Gastroentérologie, hôpital de Chalons-en-Champagne, 51 rue du commandant Derrien, 51005 Chalons-en-Champagne cedex, France
| | - François Guillemot
- Service d'Hépato-Gastroentérologie, hôpital de Roubaix, 11-17 Boulevard Lacordaire, 59100 Roubaix, France
| | - Elisabeth Monnet
- Service d'Hépatologie, hôpital Jean Minjoz, 25000 Besançon, France
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Garcia-Martinez R, Noiret L, Sen S, Mookerjee R, Jalan R. Albumin infusion improves renal blood flow autoregulation in patients with acute decompensation of cirrhosis and acute kidney injury. Liver Int 2015; 35:335-43. [PMID: 24620819 DOI: 10.1111/liv.12528] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2013] [Accepted: 03/09/2014] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS In cirrhotic patients with renal failure, renal blood flow autoregulation curve is shifted to the right, which is consequent upon sympathetic nervous system activation and endothelial dysfunction. Albumin infusion improves renal function in cirrhosis by mechanisms that are incompletely understood. We aimed to determine the effect of albumin infusion on systemic haemodynamics, renal blood flow, renal function and endothelial function in patients with acute decompensation of cirrhosis and acute kidney injury. METHODS Twelve patients with refractory ascites and 10 patients with acute decompensation of cirrhosis and acute kidney injury were studied. Both groups were treated with intravenous albumin infusion, 40-60 g/days over 3-4 days. Cardiac and renal haemodynamics were measured. Endothelial activation/dysfunction was assessed using von Willebrand factor and serum nitrite levels. F2α Isoprostanes, resting neutrophil burst and noradrenaline levels were quantified as markers of oxidative stress, endotoxemia and sympathetic activation respectively. RESULTS Albumin infusion leads to a shift in the renal blood flow autoregulation curve towards normalization, which resulted in a significant increase in renal blood flow. Accordingly, improvement of renal function was observed. In parallel, a significant decrease in sympathetic activation, inflammation/oxidative stress and endothelial activation/dysfunction was documented. Improvement of renal blood flow correlated with improvement in endothelial activation (r = 0.741, P < 0.001). CONCLUSIONS The data suggest that albumin infusion improves renal function in acutely decompensated cirrhotic patients with acute kidney injury by impacting on renal blood flow autoregulation. This is possibly achieved through endothelial stabilization and a reduction in the sympathetic tone, endotoxemia and oxidative stress.
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Affiliation(s)
- Rita Garcia-Martinez
- Liver Failure Group, UCL Institute for Liver and Digestive Health, The Royal Free Hospital, Pond Street, London, NW3 2PF, UK
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Affiliation(s)
- Nadia K Bozanich
- Medicine, Indiana University School of Medicine, 975 West Walnut, IB 327, Indianapolis, IN 46202, USA
| | - Paul Y Kwo
- Medicine, Indiana University School of Medicine, 975 West Walnut, IB 327, Indianapolis, IN 46202, USA.
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Pipili C, Cholongitas E. Renal dysfunction in patients with cirrhosis: Where do we stand? World J Gastrointest Pharmacol Ther 2014; 5:156-168. [PMID: 25133044 PMCID: PMC4133441 DOI: 10.4292/wjgpt.v5.i3.156] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2013] [Revised: 02/08/2014] [Accepted: 05/08/2014] [Indexed: 02/06/2023] Open
Abstract
Patients with cirrhosis and renal failure are high-risk patients who can hardly be grouped to form precise instructions for diagnosis and treatment. When it comes to evaluate renal function in patients with cirrhosis, determination of acute kidney injury (AKI), chronic kidney disease (CKD) or AKI on CKD should be made. First it should be excluded the prerenal causes of AKI. All cirrhotic patients should undergo renal ultrasound for measurement of renal resistive index in every stage of liver dysfunction and urine microscopy for differentiation of all causes of AKI. If there is history of dehydration on the ground of normal renal ultrasound and urine microscopy the diuretics should be withdrawn and plasma volume expansion should be tried with albumin. If the patient does not respond, the correct diagnosis is HRS. In case there is recent use of nephrotoxic agents or contrast media and examination shows shock, granular cast in urinary sediment and proteinuria above 0.5 g daily, acute tubular necrosis is the prominent diagnosis. Renal biopsy should be performed when glomerular filtration rate is between 30-60 mL/min and there are signs of parenchymal renal disease. The acute renal function is preferable to be assessed with modified AKIN. Patients with AKIN stage 1 and serum creatinine ≥ 1.5 mg/dL should be at close surveillance. Management options include hemodynamic monitoring and management of fluid balance and infections, potentially driving to HRS. Terlipressin is the treatment of choice in case of established HRS, administered until there are signs of improvement, but not more than two weeks. Midodrine is the alternative for therapy continuation or when terlipressin is unavailable. Norepinephrine has shown similar effect with terlipressin in patients being in Intensive Care Unit, but with much lower cost than that of terlipressin. If the patient meets the requirements for transplantation, dialysis and transjugular intrahepatic portosystemic shunt are the bridging therapies to keep the transplant candidate in the best clinical status. The present review clarifies the latest therapeutic modalities and the proposed recommendations and algorithms in order to be applied in clinical practice.
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Arroyo V, García-Martinez R, Salvatella X. Human serum albumin, systemic inflammation, and cirrhosis. J Hepatol 2014; 61:396-407. [PMID: 24751830 DOI: 10.1016/j.jhep.2014.04.012] [Citation(s) in RCA: 407] [Impact Index Per Article: 37.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2014] [Revised: 04/04/2014] [Accepted: 04/06/2014] [Indexed: 12/16/2022]
Abstract
Human serum albumin (HSA) is one of the most frequent treatments in patients with decompensated cirrhosis. Prevention of paracentesis-induced circulatory dysfunction, prevention of type-1 HRS associated with bacterial infections, and treatment of type-1 hepatorenal syndrome are the main indications. In these indications treatment with HSA is associated with improvement in survival. Albumin is a stable and very flexible molecule with a heart shape, 585 residues, and three domains of similar size, each one containing two sub-domains. Many of the physiological functions of HSA rely on its ability to bind an extremely wide range of endogenous and exogenous ligands, to increase their solubility in plasma, to transport them to specific tissues and organs, or to dispose of them when they are toxic. The chemical structure of albumin can be altered by some specific processes (oxidation, glycation) leading to rapid clearance and catabolism. An outstanding feature of HSA is its capacity to bind lipopolysaccharide and other bacterial products (lipoteichoic acid and peptidoglycan), reactive oxygen species, nitric oxide and other nitrogen reactive species, and prostaglandins. Binding to NO and prostaglandins are reversible, so they can be transferred to other molecules at different sites from their synthesis. Through these functions, HSA modulates the inflammatory reaction. Decompensated cirrhosis is a disease associated systemic inflammation, which plays an important role in the pathogenesis of organ or system dysfunction/failure. Although, the beneficial effects of HAS have been traditionally attributed to plasma volume expansion, they could also relate to its effects modulating systemic and organ inflammation.
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Affiliation(s)
- Vicente Arroyo
- Liver Unit, Hospital Clinic, Centre Esther Koplowitz, IDIBAPS, University of Barcelona, Barcelona, Spain; EASL-Cronic Liver Failure Consortium, Fundació Clinic, Barcelona, Spain.
| | | | - Xavier Salvatella
- ICREA and BSC-CRG-IRB Research Programme in Computational Biology, IRB Barcelona (IRB), Barcelona, Spain
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Leithead JA, Hayes PC, Ferguson JW. Review article: advances in the management of patients with cirrhosis and portal hypertension-related renal dysfunction. Aliment Pharmacol Ther 2014; 39:699-711. [PMID: 24528130 DOI: 10.1111/apt.12653] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2013] [Revised: 10/12/2013] [Accepted: 01/19/2014] [Indexed: 12/15/2022]
Abstract
BACKGROUND In cirrhosis, portal hypertension is associated with a spectrum of renal dysfunction that has significant implications for morbidity and mortality. AIM To discuss recent progress in the patho-physiological mechanisms and therapeutic options for portal hypertension-related renal dysfunction. METHODS A literature search using Pubmed was performed. RESULTS Portal hypertension-related renal dysfunction occurs in the setting of marked neuro-humoral and circulatory derangement. A systemic inflammatory response is a pathogenetic factor in advanced disease. Such physiological changes render the individual vulnerable to further deterioration of renal function. Patients are primed to develop acute kidney injury when exposed to additional 'hits', such as sepsis. Recent progress has been made regarding our understanding of the aetiopathogenesis. However, treatment options once hepatorenal syndrome develops are limited, and prognosis remains poor. Various strategies to prevent acute kidney injury are suggested. CONCLUSION Prevention of acute kidney injury in high risk patients with cirrhosis and portal hypertension-related renal dysfunction should be a clinical priority.
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Affiliation(s)
- J A Leithead
- Liver Unit, Queen Elizabeth Hospital, Birmingham, UK; NIHR Biomedical Research Unit and Centre for Liver Research, University of Birmingham, Birmingham, UK
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45
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Garcia-Martinez R, Caraceni P, Bernardi M, Gines P, Arroyo V, Jalan R. Albumin: pathophysiologic basis of its role in the treatment of cirrhosis and its complications. Hepatology 2013; 58:1836-46. [PMID: 23423799 DOI: 10.1002/hep.26338] [Citation(s) in RCA: 305] [Impact Index Per Article: 25.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2012] [Accepted: 02/11/2013] [Indexed: 12/11/2022]
Abstract
Since the introduction of human serum albumin as a plasma expander in the 1940s, considerable research has allowed a better understanding of its biochemical properties and potential clinical benefits. Albumin has a complex structure, which is responsible for a variety of biological functions. In disease, the albumin molecule is susceptible to modifications that may alter its biological activity. During the last decades, different methods to measure albumin function have been developed. Recent studies have shown that not only albumin concentration but also albumin function is reduced in liver failure. This observation led to the concept of effective albumin concentration, which represents the fact that plasma albumin concentration does not reflect its function. Indeed, in liver disease albumin function is several times less than its concentration. In patients with cirrhosis, albumin infusion reduces mortality in patients with spontaneous bacterial peritonitis and improves outcome following large volume paracentesis. In combination with vasoconstrictors, albumin is useful in the management of patients with hepatorenal syndrome. Its role is being investigated in a large number of indications, which rely on its volume and nonvolume expansion functions such as stroke, severe sepsis, Alzheimer's disease, malaria, burns, and ovarian hyperstimulation syndrome. This review explores the above concepts, reviews the available evidence for the use of albumin in liver diseases, defines therapeutic limitations, and explores the challenges that should be addressed in future research.
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Affiliation(s)
- Rita Garcia-Martinez
- Liver Failure Group, UCL Institute for Liver and Digestive Health, Royal Free Hospital, University College London, London, UK
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Kwok CS, Krupa L, Mahtani A, Kaye D, Rushbrook SM, Phillips MG, Gelson W. Albumin reduces paracentesis-induced circulatory dysfunction and reduces death and renal impairment among patients with cirrhosis and infection: a systematic review and meta-analysis. BIOMED RESEARCH INTERNATIONAL 2013; 2013:295153. [PMID: 24222902 PMCID: PMC3816020 DOI: 10.1155/2013/295153] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/30/2013] [Revised: 07/31/2013] [Accepted: 08/05/2013] [Indexed: 01/07/2023]
Abstract
BACKGROUND Studies have suggested that albumin has a value in cirrhotic patients undergoing paracentesis but its value in infection and sepsis is less clear. We planned to perform a meta-analysis of the risk of adverse outcomes in cirrhotic patients with and without albumin use. METHODS We searched MEDLINE and EMBASE in January 2013 for randomized studies of cirrhotic patients that reported the risk of adverse events and mortality with albumin and no albumin exposure. We performed random effects meta-analysis and assessed heterogeneity using the I² statistic. RESULTS Our review included 16 studies covering 1,518 patients. The use of albumin in paracentesis was associated with significantly reduced risk of paracentesis-induced circulatory dysfunction (OR 0.26 95%, CI 0.08-0.93) and there was a nonsignificant difference in death, encephalopathy, hyponatraemia, readmission, and renal impairment. Compared to the other volume expanders, albumin use showed no difference in clinical outcomes. In cirrhotic patients with any infection, there was a significant reduction in mortality (OR 0.46 95%, CI 0.25-0.86) and renal impairment (OR 0.34 95%, CI 0.15-0.75) when albumin was used. CONCLUSION The use of albumin in cirrhotic patients is valuable in patients with any infection and it reduces the risk of circulatory dysfunction among patients undergoing paracentesis.
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Affiliation(s)
- Chun Shing Kwok
- Norfolk and Norwich University Hospital, Colney Lane, Norwich NR4 7UY, UK
| | - Lukasz Krupa
- Norfolk and Norwich University Hospital, Colney Lane, Norwich NR4 7UY, UK
| | - Ash Mahtani
- Norwich Medical School, University of East Anglia, Norwich NR4 7TJ, UK
| | - Duncan Kaye
- Norwich Medical School, University of East Anglia, Norwich NR4 7TJ, UK
| | - Simon M. Rushbrook
- Norfolk and Norwich University Hospital, Colney Lane, Norwich NR4 7UY, UK
| | - Martin G. Phillips
- Norfolk and Norwich University Hospital, Colney Lane, Norwich NR4 7UY, UK
| | - William Gelson
- Norfolk and Norwich University Hospital, Colney Lane, Norwich NR4 7UY, UK
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Lee KCL, Palacios Jimenez C, Alibhai H, Chang YM, Leckie PJ, Baker LA, Stanzani G, L Priestnall S, Mookerjee RP, Jalan R, Davies NA. A reproducible, clinically relevant, intensively managed, pig model of acute liver failure for testing of therapies aimed to prolong survival. Liver Int 2013; 33:544-51. [PMID: 23331547 DOI: 10.1111/liv.12042] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2012] [Accepted: 11/01/2012] [Indexed: 12/14/2022]
Abstract
BACKGROUND A clinically relevant, translational large animal model of acute liver failure (ALF) is required for testing of novel therapies to prolong survival in acute liver failure, to permit spontaneous liver recovery or to act as a bridge to transplantation. AIMS The aim was to establish a pig model of acetaminophen-induced ALF that mimics the human clinical syndrome, is managed as in a human intensive care unit and has a predictable survival time. METHODS Nine female pigs were anaesthetised and instrumented for continuous intensive care monitoring and management using: target-driven protocols for treatment of cardiovascular collapse, metabolic acidosis and electrolyte abnormalities; intermittent positive pressure ventilation; and continuous renal replacement therapy. Six animals were induced to ALF with acetaminophen (paracetamol). Three animals acted as controls. RESULTS Irreversible acute liver failure, defined as rise in prothrombin time >3 times normal, occurred 19.3 ± 1.8 h after the onset of acetaminophen administration. Death occurred predictably 12.6 ± 2.7 h thereafter, with acute hepatocellular necrosis in all animals. Clinical progression of liver failure mimicked the human condition including development of coagulopathy, intracranial hypertension, hyperammonaemia, cardiovascular collapse, elevation in creatinine, metabolic acidosis and hyperlactataemia. In addition, cardiovascular monitoring clearly demonstrated progressive cardiac dysfunction in ALF. CONCLUSIONS A reproducible, clinically relevant, intensively managed, large animal model of acute liver failure, with death as a result of multi-organ failure, has been successfully validated for translational studies of disease progression and therapies designed to prolong survival in man.
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Affiliation(s)
- Karla C L Lee
- Department of Veterinary Clinical Sciences, Royal Veterinary College, University of London, UK.
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Thevenot T, Monnet E, Di Martino V. Effect of albumin on survival in septic cirrhotic patients other than spontaneous bacterial peritonitis. The question remains open. J Hepatol 2013; 58:638-9. [PMID: 23220370 DOI: 10.1016/j.jhep.2012.10.034] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2012] [Revised: 10/10/2012] [Accepted: 10/11/2012] [Indexed: 12/04/2022]
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Guevara M, Arroyo V, Ginès P. Reply to: "Effect of albumin on survival in septic cirrhotic patients other than spontaneous bacterial peritonitis. The question remains open". J Hepatol 2013; 58:640. [PMID: 23220371 DOI: 10.1016/j.jhep.2012.11.047] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2012] [Accepted: 11/30/2012] [Indexed: 12/04/2022]
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Bortoluzzi A, Ceolotto G, Gola E, Sticca A, Bova S, Morando F, Piano S, Fasolato S, Rosi S, Gatta A, Angeli P. Positive cardiac inotropic effect of albumin infusion in rodents with cirrhosis and ascites: molecular mechanisms. Hepatology 2013; 57:266-76. [PMID: 22911662 DOI: 10.1002/hep.26021] [Citation(s) in RCA: 97] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2011] [Accepted: 08/01/2012] [Indexed: 12/14/2022]
Abstract
UNLABELLED The aim of this study was to evaluate the effect and molecular mechanism of albumin infusion on cardiac contractility in experimental cirrhosis with ascites. Cardiac contractility was recorded ex vivo in rats with cirrhosis and ascites and in control rats after the injection in the caudal vein of albumin, saline, or hydroxyethyl starch (HES). Gene and protein expression of β-receptors and pathways involved in their intracellular signaling such as Gα(i2) protein (Gα(i2)), adenylate cyclase 3 (Adcy3), protein expression of tumor necrosis factor alpha (TNF-α) and inducible nitric oxide synthase (iNOS), were evaluated in cardiac tissue in both groups. Phosphorylation and membrane-translocation of the cytosolic components of nicotinamide adenine dinucleotide phosphate (NAD(P)H)-oxidase and translocation of nuclear factor kappa B (NF-κB) were also evaluated. After saline intravenous injection, cardiac contractility was significantly reduced in rats with cirrhosis as compared to control rats (P < 0.01). This was associated with: (1) increased expression of protein Gα(i2) (P < 0.05), TNF-α (P < 0.05), iNOS (P < 0.05); (2) increased NAD(P)H-oxidase activity (P < 0.05); (3) increased nuclear translocation of NF-κB (P < 0.05); and (4) lower expression of Adcy 3 (P < 0.05) in cardiac tissue of rats with cirrhosis. After albumin injection cardiac contractility (P < 0.01), protein expression of TNF-α, iNOS, Gα(i2), and Adcy3, NAD(P)H-oxidase activity and nuclear translocation of NF-κB in cardiac tissue of rats with cirrhosis were reversed to control levels (P < 0.05). HES injection did not modify cardiac contractility and nuclear translocation of NF-κB in cardiac tissue of rats with cirrhosis. CONCLUSION Albumin exerts a positive cardiac inotropic effect in rats with cirrhosis and ascites counteracting the negative effects of oxidative stress- and TNF-α-induced activation of NF-κB-iNOS pathway and oxidative stress-induced alteration of β-receptor signaling.
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Affiliation(s)
- Alessia Bortoluzzi
- Department of Medicine DIMED, University of Padova Medical School, Italy
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