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1
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Chen T, Yang W, Dong R, Yao H, Sun M, Wang J, Zhou Q, Xu J. The effect and application of adiponectin in hepatic fibrosis. Gastroenterol Rep (Oxf) 2024; 12:goae108. [PMID: 39737222 PMCID: PMC11683834 DOI: 10.1093/gastro/goae108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 07/04/2024] [Accepted: 09/24/2024] [Indexed: 01/01/2025] Open
Abstract
Hepatic fibrosis, a degenerative liver lesion, significantly contributes to the deterioration and mortality among patients with chronic liver diseases. The condition arises from various factors including toxins, such as alcohol, infections like different types of viral hepatitis, and metabolic diseases. Currently, there are no effective treatments available for liver fibrosis. Recent research has shown that adiponectin (ADPN) exhibits inhibitory effects on hepatic fibrosis. ADPN, an adipocytokine secreted by mature adipocytes, features receptors that are widely distributed across multiple tissues, especially the liver. In the liver, direct effects of ADPN on liver fibrosis include reducing inflammation and regulating hepatic stellate cell proliferation and migration. And its indirect effects include alleviating hepatic endoplasmic reticulum stress and reducing inflammation in hepatic lobules, thereby mitigating hepatic fibrosis. This review aims to elucidate the regulatory role of ADPN in liver fibrosis, explore how ADPN and its receptors alleviate endoplasmic reticulum stress, summarize ADPN detection methods, and discuss its potential as a novel marker and therapeutic agent in combating hepatic fibrosis.
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Affiliation(s)
- Taoran Chen
- Department of Laboratory Medicine, First Hospital of Jilin University, Changchun, Jilin, P. R. China
| | - Wenjing Yang
- Department of Laboratory Medicine, First Hospital of Jilin University, Changchun, Jilin, P. R. China
| | - Rongrong Dong
- Department of Laboratory Medicine, First Hospital of Jilin University, Changchun, Jilin, P. R. China
| | - Han Yao
- Department of Laboratory Medicine, First Hospital of Jilin University, Changchun, Jilin, P. R. China
| | - Miao Sun
- Department of Laboratory Medicine, First Hospital of Jilin University, Changchun, Jilin, P. R. China
| | - Jiaxin Wang
- Department of Laboratory Medicine, First Hospital of Jilin University, Changchun, Jilin, P. R. China
| | - Qi Zhou
- Department of Pediatrics, First Hospital of Jilin University, Changchun, Jilin, P. R. China
| | - Jiancheng Xu
- Department of Laboratory Medicine, First Hospital of Jilin University, Changchun, Jilin, P. R. China
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Duailibe JBB, Viau CM, Saffi J, Fernandes SA, Porawski M. Protective effect of long-chain polyunsaturated fatty acids on hepatorenal syndrome in rats. World J Nephrol 2024; 13:95627. [PMID: 39351184 PMCID: PMC11439093 DOI: 10.5527/wjn.v13.i3.95627] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2024] [Revised: 06/07/2024] [Accepted: 07/25/2024] [Indexed: 09/19/2024] Open
Abstract
BACKGROUND Hepatorenal syndrome (HRS) is the most prevalent form of acute kidney injury in cirrhotic patients. It is characterized by reduced renal blood flow and represents the most severe complication in cirrhotic patients with advanced disease. Previous research has indicated that antioxidants can delay the onset of a hyperdynamic circulatory state in cirrhosis and improve renal function in HRS patients. Regular omega-3 supplementation has significantly reduced the risk of liver disease. This supplementation could represent an additional therapy for individuals with HRS. AIM To evaluated the antioxidant effect of omega-3 polyunsaturated fatty acid supplementation on the kidneys of cirrhotic rats. METHODS Secondary biliary cirrhosis was induced in rats by biliary duct ligation (BDL) for 28 d. We used 24 male Wistar rats divided into the following groups: I (control); II (treated with omega-3, 1 g/kg of body weight); III (BDL treated with omega-3, 1 g/kg of body weight); and IV (BDL without treatment). The animals were killed by overdose of anesthetic; the kidneys were dissected, removed, frozen in liquid nitrogen, and stored in a freezer at -80℃ for later analysis. We evaluated oxidative stress, nitric oxide (NO) metabolites, DNA damage by the comet assay, cell viability test, and apoptosis in the kidneys. Data were analyzed by one-way analysis of variance, and means were compared using the Tukey test, with P ≤ 0.05. RESULTS Omega-3 significantly decreased the production of reactive oxygen species (P < 0.001) and lipoperoxidation in the kidneys of cirrhotic rats treated with omega-3 (P < 0.001). The activity of the antioxidant enzymes superoxide dismutase and catalase increased in the BDL+omega-3 group compared to the BDL group (P < 0.01). NO production, DNA damage, and caspase-9 cleavage decreased significantly in the omega-3-treated BDL group. There was an increase in mitochondrial electrochemical potential (P < 0.001) in BDL treated with omega-3 compared to BDL. No changes in the cell survival index in HRS with omega-3 compared to the control group (P > 0.05) were observed. CONCLUSION The study demonstrates that omega-3 can protect cellular integrity and function by increasing antioxidant enzymes, inhibiting the formation of free radicals, and reducing apoptosis.
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Affiliation(s)
- João Bruno Beretta Duailibe
- Department of Hepatology, Federal University of Health Sciences of Porto Alegre, Porto Alegre 90050-170, Brazil
| | - Cassiana Macagnan Viau
- Department of Basic Health Sciences, Federal University of Health Sciences of Porto Alegre, Porto Alegre 90050-170, Brazil
| | - Jenifer Saffi
- Department of Basic Health Sciences, Federal University of Health Sciences of Porto Alegre, Porto Alegre 90050-170, Brazil
| | - Sabrina Alves Fernandes
- Department of Hepatology, Federal University of Health Sciences of Porto Alegre, Porto Alegre 90050-170, Brazil
| | - Marilene Porawski
- Department of Hepatology and Basic Health Sciences, Federal University of Health Sciences of Porto Alegre, Porto Alegre 90050-170, Brazil
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Pollmanns MR, Pajaziti Q, Hohlstein P, Adams JK, Abu Jhaisha S, Kabak E, Hamesch K, Nusser SHA, Weiskirchen R, Wirtz TH, Koch A. Serum Adiponectin Is Elevated in Critically Ill Patients with Liver Disease and Associated with Decreased Overall Survival. Biomedicines 2024; 12:2173. [PMID: 39457486 PMCID: PMC11504267 DOI: 10.3390/biomedicines12102173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Revised: 09/20/2024] [Accepted: 09/22/2024] [Indexed: 10/28/2024] Open
Abstract
BACKGROUND Adiponectin, an adipokine with anti-inflammatory properties, has been implicated in various liver diseases. This study aimed to elucidate the prognostic value of serum adiponectin levels in critically ill patients with liver disease. METHODS This observational study included 161 critically ill patients admitted to the medical ICU of RWTH Aachen University Hospital due to acute liver failure or decompensated advanced chronic liver disease. Serum adiponectin levels were measured at ICU admission and after 48 h. Clinical parameters and outcomes, including transplant-free survival, were analyzed. RESULTS Serum adiponectin concentrations were significantly elevated compared to healthy controls (p < 0.001). Levels were particularly high in patients with sepsis compared to those with gastrointestinal bleeding as the precipitating factor of acute decompensation (p = 0.045) and were higher in female patients (p = 0.023). Adiponectin concentrations correlated with the Model of End-Stage Liver Disease (MELD) score and Child-Pugh score. Multivariate analysis confirmed a significant correlation with total bilirubin (r = 0.292, p < 0.001) and serum sodium (r = -0.265, p = 0.028). Higher adiponectin concentrations were associated with a trend towards poorer 30- and 180-day survival. Cox regression analysis identified a significant association between increased adiponectin concentration and reduced transplant-free survival (p = 0.037), supported by a Kaplan-Meier analysis using a cutoff of 119 ng/mL (log-rank 5.145, p = 0.023). CONCLUSIONS Elevated serum adiponectin concentrations are associated with liver dysfunction and poor outcomes in critically ill patients. Higher adiponectin levels at ICU admission may predict poorer transplant-free survival. Further research in larger, multicenter cohorts is warranted to validate these findings and explore the underlying mechanisms.
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Affiliation(s)
- Maike R. Pollmanns
- Department for Gastroenterology, Metabolic Disorders and Intensive Care Medicine, RWTH-University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany; (M.R.P.); (Q.P.); (P.H.); (J.K.A.); (S.A.J.); (E.K.); (K.H.); (S.H.A.N.); (T.H.W.)
| | - Qendrim Pajaziti
- Department for Gastroenterology, Metabolic Disorders and Intensive Care Medicine, RWTH-University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany; (M.R.P.); (Q.P.); (P.H.); (J.K.A.); (S.A.J.); (E.K.); (K.H.); (S.H.A.N.); (T.H.W.)
| | - Philipp Hohlstein
- Department for Gastroenterology, Metabolic Disorders and Intensive Care Medicine, RWTH-University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany; (M.R.P.); (Q.P.); (P.H.); (J.K.A.); (S.A.J.); (E.K.); (K.H.); (S.H.A.N.); (T.H.W.)
| | - Jule K. Adams
- Department for Gastroenterology, Metabolic Disorders and Intensive Care Medicine, RWTH-University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany; (M.R.P.); (Q.P.); (P.H.); (J.K.A.); (S.A.J.); (E.K.); (K.H.); (S.H.A.N.); (T.H.W.)
| | - Samira Abu Jhaisha
- Department for Gastroenterology, Metabolic Disorders and Intensive Care Medicine, RWTH-University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany; (M.R.P.); (Q.P.); (P.H.); (J.K.A.); (S.A.J.); (E.K.); (K.H.); (S.H.A.N.); (T.H.W.)
| | - Elena Kabak
- Department for Gastroenterology, Metabolic Disorders and Intensive Care Medicine, RWTH-University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany; (M.R.P.); (Q.P.); (P.H.); (J.K.A.); (S.A.J.); (E.K.); (K.H.); (S.H.A.N.); (T.H.W.)
| | - Karim Hamesch
- Department for Gastroenterology, Metabolic Disorders and Intensive Care Medicine, RWTH-University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany; (M.R.P.); (Q.P.); (P.H.); (J.K.A.); (S.A.J.); (E.K.); (K.H.); (S.H.A.N.); (T.H.W.)
| | - Sophie H. A. Nusser
- Department for Gastroenterology, Metabolic Disorders and Intensive Care Medicine, RWTH-University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany; (M.R.P.); (Q.P.); (P.H.); (J.K.A.); (S.A.J.); (E.K.); (K.H.); (S.H.A.N.); (T.H.W.)
| | - Ralf Weiskirchen
- Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), RWTH University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany;
| | - Theresa H. Wirtz
- Department for Gastroenterology, Metabolic Disorders and Intensive Care Medicine, RWTH-University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany; (M.R.P.); (Q.P.); (P.H.); (J.K.A.); (S.A.J.); (E.K.); (K.H.); (S.H.A.N.); (T.H.W.)
| | - Alexander Koch
- Department for Gastroenterology, Metabolic Disorders and Intensive Care Medicine, RWTH-University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany; (M.R.P.); (Q.P.); (P.H.); (J.K.A.); (S.A.J.); (E.K.); (K.H.); (S.H.A.N.); (T.H.W.)
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Rad NK, Heydari Z, Tamimi AH, Zahmatkesh E, Shpichka A, Barekat M, Timashev P, Hossein-Khannazer N, Hassan M, Vosough M. Review on Kidney-Liver Crosstalk: Pathophysiology of Their Disorders. CELL JOURNAL 2024; 26:98-111. [PMID: 38459727 PMCID: PMC10924833 DOI: 10.22074/cellj.2023.2007757.1376] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Revised: 12/25/2023] [Accepted: 12/30/2023] [Indexed: 03/10/2024]
Abstract
Kidney-liver crosstalk plays a crucial role in normal and certain pathological conditions. In pathologic states, both renal-induced liver damage and liver-induced kidney diseases may happen through these kidney-liver interactions. This bidirectional crosstalk takes place through the systemic conditions that mutually influence both the liver and kidneys. Ischemia and reperfusion, cytokine release and pro-inflammatory signaling pathways, metabolic acidosis, oxidative stress, and altered enzyme activity and metabolic pathways establish the base of this interaction between the kidneys and liver. In these concomitant kidney-liver diseases, the survival rates strongly correlate with early intervention and treatment of organ dysfunction. Proper care of a nephrologist and hepatologist and the identification of pathological conditions using biomarkers at early stages are necessary to prevent the complications induced by this complex and potentially vicious cycle. Therefore, understanding the characteristics of this crosstalk is essential for better management. In this review, we discussed the available literature concerning the detrimental effects of kidney failure on liver functions and liver-induced kidney diseases.
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Affiliation(s)
- Niloofar Khoshdel Rad
- Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Zahra Heydari
- World-Class Research Center "Digital Biodesign and Personalized Healthcare", Sechenov University, Moscow, Russia
| | - Amir Hossein Tamimi
- Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Ensieh Zahmatkesh
- Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Anastasia Shpichka
- World-Class Research Center "Digital Biodesign and Personalized Healthcare", Sechenov University, Moscow, Russia
- Institute for Regenerative Medicine, Sechenov University, Moscow, Russia
- Chemistry Department, Lomonosov Moscow State University, Moscow, Russia
| | - Maryam Barekat
- Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Peter Timashev
- World-Class Research Center "Digital Biodesign and Personalized Healthcare", Sechenov University, Moscow, Russia
- Institute for Regenerative Medicine, Sechenov University, Moscow, Russia.
- Chemistry Department, Lomonosov Moscow State University, Moscow, Russia
| | - Nikoo Hossein-Khannazer
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Moustapha Hassan
- Experimental Cancer Medicine, Institution for Laboratory Medicine, Karolinska Institute, Stockholm, Sweden
| | - Massoud Vosough
- Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran. ,
- Experimental Cancer Medicine, Institution for Laboratory Medicine, Karolinska Institute, Stockholm, Sweden
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5
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Pezzino S, Luca T, Castorina M, Puleo S, Latteri S, Castorina S. Role of Perturbated Hemostasis in MASLD and Its Correlation with Adipokines. Life (Basel) 2024; 14:93. [PMID: 38255708 PMCID: PMC10820028 DOI: 10.3390/life14010093] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Revised: 01/04/2024] [Accepted: 01/05/2024] [Indexed: 01/24/2024] Open
Abstract
The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) continues to rise, making it one of the most prevalent chronic liver disorders. MASLD encompasses a range of liver pathologies, from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH) with inflammation, hepatocyte damage, and fibrosis. Interestingly, the liver exhibits close intercommunication with fatty tissue. In fact, adipose tissue could contribute to the etiology and advancement of MASLD, acting as an endocrine organ that releases several hormones and cytokines, with the adipokines assuming a pivotal role. The levels of adipokines in the blood are altered in people with MASLD, and recent research has shed light on the crucial role played by adipokines in regulating energy expenditure, inflammation, and fibrosis in MASLD. However, MASLD disease is a multifaceted condition that affects various aspects of health beyond liver function, including its impact on hemostasis. The alterations in coagulation mechanisms and endothelial and platelet functions may play a role in the increased vulnerability and severity of MASLD. Therefore, more attention is being given to imbalanced adipokines as causative agents in causing disturbances in hemostasis in MASLD. Metabolic inflammation and hepatic injury are fundamental components of MASLD, and the interrelation between these biological components and the hemostasis pathway is delineated by reciprocal influences, as well as the induction of alterations. Adipokines have the potential to serve as the shared elements within this complex interrelationship. The objective of this review is to thoroughly examine the existing scientific knowledge on the impairment of hemostasis in MASLD and its connection with adipokines, with the aim of enhancing our comprehension of the disease.
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Affiliation(s)
- Salvatore Pezzino
- Mediterranean Foundation “GB Morgagni”, 95125 Catania, Italy (M.C.); (S.C.)
| | - Tonia Luca
- Mediterranean Foundation “GB Morgagni”, 95125 Catania, Italy (M.C.); (S.C.)
- Department of Medical, Surgical Sciences and Advanced Technologies “G.F. Ingrassia”, University of Catania, 95123 Catania, Italy;
| | | | - Stefano Puleo
- Mediterranean Foundation “GB Morgagni”, 95125 Catania, Italy (M.C.); (S.C.)
| | - Saverio Latteri
- Department of Medical, Surgical Sciences and Advanced Technologies “G.F. Ingrassia”, University of Catania, 95123 Catania, Italy;
| | - Sergio Castorina
- Mediterranean Foundation “GB Morgagni”, 95125 Catania, Italy (M.C.); (S.C.)
- Department of Medical, Surgical Sciences and Advanced Technologies “G.F. Ingrassia”, University of Catania, 95123 Catania, Italy;
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Badura K, Frąk W, Hajdys J, Majchrowicz G, Młynarska E, Rysz J, Franczyk B. Hepatorenal Syndrome-Novel Insights into Diagnostics and Treatment. Int J Mol Sci 2023; 24:17469. [PMID: 38139297 PMCID: PMC10744165 DOI: 10.3390/ijms242417469] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 12/09/2023] [Accepted: 12/11/2023] [Indexed: 12/24/2023] Open
Abstract
Hepatorenal syndrome (HRS) is a disorder associated with cirrhosis and renal impairment, with portal hypertension as its major underlying cause. Moreover, HRS is the third most common cause of acute kidney injury, thus creating a major public health concern. This review summarizes the available information on the pathophysiological implications of HRS. We discuss pathogenesis associated with HRS. Mechanisms such as dysfunction of the circulatory system, bacterial infection, inflammation, impaired renal autoregulation, circulatory, and others, which have been identified as critical pathways for development of HRS, have become easier to diagnose in recent years. Additionally, relatively recently, renal dysfunction biomarkers have been found indicating renal injury, which are involved in the pathophysiology of HRS. This review also summarizes the available information on the management of HRS, focusing on vasoconstrictive drugs, renal replacement therapy, and liver transplant together with currently being investigated novel therapies. Analyzing new discoveries for the underlying causes of this condition assists the general research to improve understanding of the mechanism of pathophysiology and thus prevention of HRS.
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Affiliation(s)
- Krzysztof Badura
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Weronika Frąk
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Joanna Hajdys
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Gabriela Majchrowicz
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Ewelina Młynarska
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Jacek Rysz
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Beata Franczyk
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
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Roy P, Minhaz N, Shah-Riar P, Simona SY, Tasha T, Binte Hasan T, Abbasi FK, Alam F, Nila SA, Akter J, Akter S, Biswas S, Sultana N. A Comprehensive Systematic Review of the Latest Management Strategies for Hepatorenal Syndrome: A Complicated Syndrome to Tackle. Cureus 2023; 15:e43073. [PMID: 37680416 PMCID: PMC10481992 DOI: 10.7759/cureus.43073] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/06/2023] [Indexed: 09/09/2023] Open
Abstract
Hepatorenal syndrome (HRS), defined by the extreme manifestation of renal impairment in patients with cirrhosis, is characterized by reduced renal blood flow and glomerular filtration rate. It is diagnosed with reduced kidney function confirming the absence of intrinsic kidney disease, such as hematuria or proteinuria. HRS is potentially reversible with liver transplantation or vasoconstrictor drugs. The condition carries a poor prognosis with high mortality rates, particularly in patients with advanced cirrhosis. The latest management for HRS involves a combination of pharmacological and non-pharmacological interventions, aiming to improve renal function and reduce the risk of mortality. Pharmacological treatments include vasoconstrictors, such as terlipressin and midodrine, and albumin infusion, which have been shown to improve renal function and reduce mortality in HRS patients. Non-pharmacological interventions, including invasive procedures such as transjugular intrahepatic portosystemic shunt (TIPS), plasma exchange, liver transplantation, and renal replacement therapy, may also be considered. Though TIPS has been shown to be effective in improving renal function in HRS patients, liver transplantation remains at the top of the consideration for the treatment of end-stage liver disease and HRS. Recent studies have placed importance on early recognition and prompt intervention in HRS patients, as delaying treatment can result in poorer outcomes. Although there are numerous reviews that summarize various aspects of HRS, the recent advancements in the management and pathophysiology of HRS are still insufficient. Therefore, in this review, we summarized a brief pathophysiology and highlighted recent advancements in the management of HRS with a quick review of the latest articles.
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Affiliation(s)
- Pooja Roy
- Internal Medicine, Harlem Hospital Center, New York, USA
| | - Naofel Minhaz
- Internal Medicine, Dhaka Medical College, Dhaka, BGD
| | | | | | - Tasniem Tasha
- Internal Medicine, Rajshahi Medical College, Rajshahi, BGD
| | | | | | - Farhana Alam
- Internal Medicine, Chittagong Medical College, Chittagong, BGD
| | - Shamima A Nila
- Internal Medicine, Cumilla Medical College and Hospital, Cumilla, BGD
| | - Janifa Akter
- Internal Medicine, Gonoshasthaya Samaj Vittik Medical College, Dhaka, BGD
- Internal Medicine, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, BGD
| | - Sharmin Akter
- Internal Medicine, Shaheed Ziaur Rahman Medical College, Bogura, BGD
| | - Shammo Biswas
- Internal Medicine, Sir Salimullah Medical College Mitford Hospital, Dhaka, BGD
| | - Nigar Sultana
- Internal Medicine, Sir Salimullah Medical College Mitford Hospital, Dhaka, BGD
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8
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Wu HHL, Athwal VS, Kalra PA, Chinnadurai R. COVID-19 and hepatorenal syndrome. World J Gastroenterol 2022; 28:5666-5678. [PMID: 36338894 PMCID: PMC9627428 DOI: 10.3748/wjg.v28.i39.5666] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Revised: 09/21/2022] [Accepted: 10/02/2022] [Indexed: 02/06/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) is a highly infectious disease which emerged into a global pandemic. Although it primarily causes respiratory symptoms for affected patients, COVID-19 was shown to have multi-organ manifestations. Elevated liver enzymes appear to be commonly observed during the course of COVID-19, and there have been numerous reports of liver injury secondary to COVID-19 infection. It has been established that patients with pre-existing chronic liver disease (CLD) are more likely to have poorer outcomes following COVID-19 infection compared to those without CLD. Co-morbidities such as diabetes, hypertension, obesity, cardiovascular and chronic kidney disease frequently co-exist in individuals living with CLD, and a substantial population may also live with some degree of frailty. The mechanisms of how COVID-19 induces liver injury have been postulated. Hepatorenal syndrome (HRS) is the occurrence of kidney dysfunction in patients with severe CLD/fulminant liver failure in the absence of another identifiable cause, and is usually a marker of severe decompensated liver disease. Select reports of HRS following acute COVID-19 infection have been presented, although the risk factors and pathophysiological mechanisms leading to HRS in COVID-19 infection or following COVID-19 treatment remain largely unestablished due to the relative lack and novelty of published data. Evidence discussing the management of HRS in high-dependency care and intensive care contexts is only emerging. In this article, we provide an overview on the speculative pathophysiological mechanisms of COVID-19 induced HRS and propose strategies for clinical diagnosis and management to optimize outcomes in this scenario.
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Affiliation(s)
- Henry H L Wu
- Renal Research, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney 2065, New South Wales, Australia
| | - Varinder S Athwal
- Faculty of Biology, Medicine & Health (Division of Diabetes, Metabolism & Gastroenterology), The University of Manchester, Manchester M13 9PL, United Kingdom
| | - Philip A Kalra
- Department of Renal Medicine, Northern Care Alliance NHS Foundation Trust, Salford M6 8HD, United Kingdom
| | - Rajkumar Chinnadurai
- Department of Renal Medicine, Northern Care Alliance NHS Foundation Trust, Salford M6 8HD, United Kingdom
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Abraham AJM, Bobby Z, Chaturvedula L, Vinayagam V, Jacob SE, Habeebullah S. Maternal Adverse Outcomes in Hypertensive Disorders of Pregnancy and Their Association with Serum Adiponectin and Redox Markers. Fetal Pediatr Pathol 2022; 41:1-17. [PMID: 32275184 DOI: 10.1080/15513815.2020.1745973] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
Background: Premature termination of pregnancy because of unmanageable maternal complications in hypertensive disorders of pregnancy (HDP) results in adverse neonatal outcome. Identification of biochemical derangements associated with maternal complications may help in the better medical management of the mother resulting in better neonatal outcomes. Method: Healthy pregnant women (C); pregnant women with gestational hypertension (GH), and preeclampsia (late [LP] and early [EP] onset) were studied. Maternal serum redox markers and adipokines were evaluated for their association with maternal complications. Results: Adiponectin levels were significantly raised in preeclampsia groups when compared with control and GH groups. Univariate and multivariate analysis confirmed that malondialdehyde (MDA) and total antioxidant status (TAS) were associated with eclampsia; adiponectin and TAS with HELLP syndrome; adiponectin, MDA and TAS with severe preeclampsia; and adiponectin with impaired renal function. Conclusion: We identified that increased serum adiponectin, MDA, and TAS were associated with adverse maternal outcomes.
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Affiliation(s)
- Angelin Jeba Malar Abraham
- Department of Biochemistry, Jawaharlal Institute of Post Graduate Medical Education and Research, Pondicherry, India
| | - Zachariah Bobby
- Department of Biochemistry, Jawaharlal Institute of Post Graduate Medical Education and Research, Pondicherry, India
| | - Latha Chaturvedula
- Department of Obstetrics and Gynecology, Jawaharlal Institute of Post Graduate Medical Education and Research, Pondicherry, India
| | - Vickneshwaran Vinayagam
- Department of Biochemistry, Jawaharlal Institute of Post Graduate Medical Education and Research, Pondicherry, India
| | - Sajini Elizabeth Jacob
- Department of Pathology, Jawaharlal Institute of Post Graduate Medical Education and Research, Pondicherry, India
| | - Syed Habeebullah
- Department of Obstetrics and Gynecology, Jawaharlal Institute of Post Graduate Medical Education and Research, Pondicherry, India
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10
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Čustović N, Rašić S. RELATIONSHIP OF SERUM ADIPONECTIN AND RESISTIN LEVELS WITH THE SEVERITY OF LIVER FIBROSIS IN PATIENTS WITH CHRONIC HEPATITIS B. J Med Biochem 2021; 41:176-183. [PMID: 35510200 PMCID: PMC9010048 DOI: 10.5937/jomb0-33793] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Accepted: 10/17/2021] [Indexed: 12/04/2022] Open
Abstract
Background Recent research has closely linked adipocytokines to liver inflammation and fibrosis progression in patients with non-alcoholic liver disease. This study aimed to determine the relationship of serum adiponectin and resistin levels with the severity of liver fibrosis in patients with chronic hepatitis B (CHB), depending on the duration of antiviral therapy. Methods The cross-sectional study included 75 patients with CHB divided into two groups: the T1 group (undergoing antiviral therapy for up to 2 years) and the T2 group (undergoing antiviral therapy over 2 years). The control group consisted of 40 healthy people. Serum concentrations of adiponectin and resistin were estimated with the ELISA method, while the degree of liver fibrosis was determined using FIB-4 and APRI score. Results There were no statistically significant differences in the mean serum adiponectin levels in relation to the duration of antiviral therapy. Higher values of serum resistin concentration were confirmed in patients of the T1 group compared to healthy controls (p=0.001) and to the T2 group (p=0.031). The mean level of serum resistin concentration was significantly higher in the group of patients with a higher FIB-4 score (9.12±3.39 vs 5.58±3.36 ng/mL, p=0.001) and higher APRI score (17.45±3.96 ng/mL vs 4.82±1.11 ng/mL, p=0.001). A positive correlation was found between serum resistin levels and the degree of liver fibrosis (p<0.001). There was no significant difference between mean serum adiponectin levels according to the values of FIB-4 and APRI scores. Conclusions Progression of liver fibrosis estimated by FIB4 and APRI scores as well as the length of antiviral treatment had a significant effect on serum resistin values in CHB patients on antiviral therapy.
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Affiliation(s)
- Nerma Čustović
- University of Sarajevo, Clinical Center, Clinic for Gastroenterohepatology, Sarajevo, Bosnia and Herzegovina
| | - Senija Rašić
- University of Sarajevo, Faculty of Medicine, Department of Internal Medicine, Sarajevo, Bosnia and Herzegovina
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11
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Chaney A. A Review for the Practicing Clinician: Hepatorenal Syndrome, a Form of Acute Kidney Injury, in Patients with Cirrhosis. Clin Exp Gastroenterol 2021; 14:385-396. [PMID: 34675586 PMCID: PMC8502008 DOI: 10.2147/ceg.s323778] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Accepted: 09/04/2021] [Indexed: 12/15/2022] Open
Abstract
The hepatorenal syndrome type of acute kidney injury (HRS-AKI), formerly known as type 1 hepatorenal syndrome, is a rapidly progressing renal failure that occurs in many patients with advanced cirrhosis and ascites. Accumulating evidence has led to a recent evolution of diagnostic criteria for this serious complication of end-stage liver disease. The aim of this review is to provide an overview of disease-related characteristics and therapeutic management of patients with HRS-AKI. Relevant literature was compiled to support discussion of the pathophysiology, diagnosis, prognosis, associated conditions, prevention, treatment, and management of HRS-AKI. Onset of HRS-AKI is characterized by sudden severe renal vasoconstriction, leading to an acute reduction in glomerular filtration rate and rapid, potentially life-threatening, renal deterioration. Although our understanding of disease pathophysiology continues to evolve, etiology of HRS-AKI likely involves systemic hemodynamic changes caused by liver disease, inflammation, and damage to renal parenchyma. There is currently no gold standard for diagnosis, which typically involves a clinical workup, abdominal imaging, and laboratory assessments. The current consensus definition of HRS-AKI includes proposed diagnostic criteria based on changes in serum creatinine levels tailored for high sensitivity, and rapid detection to accelerate diagnosis and treatment initiation. The only potential cure for HRS-AKI is liver transplantation; however, vasoconstrictive agents and other supportive measures are used as needed to help maintain survival for patients who are awaiting or are ineligible for transplantation. The severity of HRS-AKI, complex pathology, limited treatment options, and range of associated conditions pose significant challenges for both patients and care providers.
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Affiliation(s)
- Amanda Chaney
- Department of Transplant, College of Medicine, Mayo Clinic, Jacksonville, FL, USA
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12
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Nassar M, Nso N, Medina L, Ghernautan V, Novikov A, El-Ijla A, Soliman KM, Kim Y, Alfishawy M, Rizzo V, Daoud A. Liver Kidney Crosstalk: Hepatorenal Syndrome. World J Hepatol 2021; 13:1058-1068. [PMID: 34630874 PMCID: PMC8473490 DOI: 10.4254/wjh.v13.i9.1058] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 05/12/2021] [Accepted: 07/30/2021] [Indexed: 02/06/2023] Open
Abstract
The dying liver causes the suffocation of the kidneys, which is a simplified way of describing the pathophysiology of hepatorenal syndrome (HRS). HRS is characterized by reversible functional renal impairment due to reduced blood supply and glomerular filtration rate, secondary to increased vasodilators. Over the years, HRS has gained much attention and focus among hepatologists and nephrologists. HRS is a diagnosis of exclusion, and in some cases, it carries a poor prognosis. Different classifications have emerged to better understand, diagnose, and promptly treat this condition. This targeted review aims to provide substantial insight into the epidemiology, pathophysiology, diagnosis, and management of HRS, shed light on the various milestones of this condition, and add to our current understanding.
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Affiliation(s)
- Mahmoud Nassar
- Department of Medicine, Icahn School of Medicine at Mount Sinai / NYC Health + Hospitals / Queens, New York, NY 11432, United States
| | - Nso Nso
- Department of Medicine, Icahn School of Medicine at Mount Sinai / NYC Health + Hospitals / Queens, New York, NY 11432, United States
| | - Luis Medina
- Department of Medicine, Icahn School of Medicine at Mount Sinai / NYC Health + Hospitals / Queens, New York, NY 11432, United States
| | - Victoria Ghernautan
- Department of Medicine, Icahn School of Medicine at Mount Sinai / NYC Health + Hospitals / Queens, New York, NY 11432, United States
| | - Anastasia Novikov
- Department of Medicine, Icahn School of Medicine at Mount Sinai / NYC Health + Hospitals / Queens, New York, NY 11432, United States
| | - Alli El-Ijla
- Department of Medicine, Icahn School of Medicine at Mount Sinai / NYC Health + Hospitals / Queens, New York, NY 11432, United States
| | - Karim M Soliman
- Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, United States
| | - Yungmin Kim
- Department of Medicine, Icahn School of Medicine at Mount Sinai / NYC Health + Hospitals / Queens, New York, NY 11432, United States
| | - Mostafa Alfishawy
- Department of Infectious Diseases, Infectious Diseases Consultants and Academic Researchers of Egypt IDCARE, Cairo 11562, Egypt
| | - Vincent Rizzo
- Department of Medicine, Icahn School of Medicine at Mount Sinai / NYC Health + Hospitals / Queens, New York, NY 11432, United States
| | - Ahmed Daoud
- Department of Medicine, Kasr Alainy Medical School, Cairo University, Cairo 11211, Egypt.
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13
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Berzigotti A, Tsochatzis E, Boursier J, Castera L, Cazzagon N, Friedrich-Rust M, Petta S, Thiele M. EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis - 2021 update. J Hepatol 2021; 75:659-689. [PMID: 34166721 DOI: 10.1016/j.jhep.2021.05.025] [Citation(s) in RCA: 1009] [Impact Index Per Article: 252.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Accepted: 05/28/2021] [Indexed: 02/07/2023]
Abstract
Non-invasive tests are increasingly being used to improve the diagnosis and prognostication of chronic liver diseases across aetiologies. Herein, we provide the latest update to the EASL Clinical Practice Guidelines on the use of non-invasive tests for the evaluation of liver disease severity and prognosis, focusing on the topics for which relevant evidence has been published in the last 5 years.
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14
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Roy B, Palaniyandi SS. Tissue-specific role and associated downstream signaling pathways of adiponectin. Cell Biosci 2021; 11:77. [PMID: 33902691 PMCID: PMC8073961 DOI: 10.1186/s13578-021-00587-4] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Accepted: 04/07/2021] [Indexed: 12/12/2022] Open
Abstract
According to the World Health Organization, metabolic syndrome (MetS) can be defined as a pathological condition characterized by abdominal obesity, insulin resistance, hypertension, and hyperlipidemia. The incidence of MetS keeps rising, as at least 35% of the USA population suffers from MetS. One of the worst comorbidities of metabolic syndrome are cardiovascular diseases that significantly amplifies the mortality associated with this syndrome. There is an urgent need to understand the pathophysiology of MetS to find novel diagnosis, treatment and management to mitigate the MetS and associated complications. Altered circulatory adiponectin levels have been implicated in MetS. Adiponectin has numerous biologic functions including antioxidative, anti-nitrative, anti-inflammatory, and cardioprotective effects. Being a pleiotropic hormone of multiple tissues, tissue-specific key signaling pathways of adiponectin will help finding specific target/s to blunt the pathophysiology of metabolic syndrome and associated disorders. The purpose of this review is to elucidate tissue-specific signaling pathways of adiponectin and possibly identify potential therapeutic targets for MetS as well as to evaluate the potential of adiponectin as a biomarker/therapeutic option in MetS.
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Affiliation(s)
- Bipradas Roy
- Division of Hypertension and Vascular Research, Department of Internal Medicine, Henry Ford Health System, Integrative Biosciences Center (IBio), Room #3402, 6135 Woodward, Detroit, MI 48202 USA
- Department of Physiology, Wayne State University, Detroit, MI 48202 USA
| | - Suresh Selvaraj Palaniyandi
- Division of Hypertension and Vascular Research, Department of Internal Medicine, Henry Ford Health System, Integrative Biosciences Center (IBio), Room #3402, 6135 Woodward, Detroit, MI 48202 USA
- Department of Physiology, Wayne State University, Detroit, MI 48202 USA
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15
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Nishikawa H, Enomoto H, Nishiguchi S, Iijima H. Sarcopenic Obesity in Liver Cirrhosis: Possible Mechanism and Clinical Impact. Int J Mol Sci 2021; 22:1917. [PMID: 33671926 PMCID: PMC7919019 DOI: 10.3390/ijms22041917] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Revised: 02/08/2021] [Accepted: 02/11/2021] [Indexed: 02/07/2023] Open
Abstract
The picture of chronic liver diseases (CLDs) has changed considerably in recent years. One of them is the increase of non-alcoholic fatty liver disease. More and more CLD patients, even those with liver cirrhosis (LC), tend to be presenting with obesity these days. The annual rate of muscle loss increases with worsening liver reserve, and thus LC patients are more likely to complicate with sarcopenia. LC is also characterized by protein-energy malnutrition (PEM). Since the PEM in LC can be invariable, the patients probably present with sarcopenic obesity (Sa-O), which involves both sarcopenia and obesity. Currently, there is no mention of Sa-O in the guidelines; however, the rapidly increasing prevalence and poorer clinical consequences of Sa-O are recognized as an important public health problem, and the diagnostic value of Sa-O is expected to increase in the future. Sa-O involves a complex interplay of physiological mechanisms, including increased inflammatory cytokines, oxidative stress, insulin resistance, hormonal disorders, and decline of physical activity. The pathogenesis of Sa-O in LC is diverse, with a lot of perturbations in the muscle-liver-adipose tissue axis. Here, we overview the current knowledge of Sa-O, especially focusing on LC.
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Affiliation(s)
- Hiroki Nishikawa
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan; (H.E.); (H.I.)
- Center for Clinical Research and Education, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
| | - Hirayuki Enomoto
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan; (H.E.); (H.I.)
| | - Shuhei Nishiguchi
- Department of Internal Medicine, Kano General Hospital, Osaka 531-0041, Japan;
| | - Hiroko Iijima
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan; (H.E.); (H.I.)
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16
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Kucukoglu O, Sowa JP, Mazzolini GD, Syn WK, Canbay A. Hepatokines and adipokines in NASH-related hepatocellular carcinoma. J Hepatol 2021; 74:442-457. [PMID: 33161047 DOI: 10.1016/j.jhep.2020.10.030] [Citation(s) in RCA: 81] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Revised: 10/26/2020] [Accepted: 10/28/2020] [Indexed: 12/12/2022]
Abstract
The incidence of hepatocellular carcinoma (HCC) is increasing in industrialised societies; this is likely secondary to the increasing burden of non-alcoholic fatty liver disease (NAFLD), its progressive form non-alcoholic steatohepatitis (NASH), and the metabolic syndrome. Cumulative studies suggest that NAFLD-related HCC may also develop in non-cirrhotic livers. However, prognosis and survival do not differ between NAFLD- or virus-associated HCC. Thus, research has increasingly focused on NAFLD-related risk factors to better understand the biology of hepatocarcinogenesis and to develop new diagnostic, preventive, and therapeutic strategies. One important aspect thereof is the role of hepatokines and adipokines in NAFLD/NASH-related HCC. In this review, we compile current data supporting the use of hepatokines and adipokines as potential markers of disease progression in NAFLD or as early markers of NAFLD-related HCC. While much work must be done to elucidate the mechanisms and interactions underlying alterations to hepatokines and adipokines, current data support the possible utility of these factors - in particular, angiopoietin-like proteins, fibroblast growth factors, and apelin - for detection or even as therapeutic targets in NAFLD-related HCC.
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Affiliation(s)
- Ozlem Kucukoglu
- Department of Gastroenterology, Hepatology, and Infectious Diseases, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany
| | - Jan-Peter Sowa
- Department of Medicine, Ruhr University Bochum, University Hospital Knappschaftskrankenhaus Bochum, 44892 Bochum, Germany
| | - Guillermo Daniel Mazzolini
- Laboratory of Gene Therapy, Instituto de Investigaciones en Medicina Traslacional, CONICET-Universidad Austral, Buenos Aires 999071, Argentina; Liver Unit, Hospital Universitario Austral, Universidad Austral, Argentina
| | - Wing-Kin Syn
- Section of Gastroenterology, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC, USA; Division of Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, SC, USA; Department of Physiology, Faculty of Medicine and Nursing, University of Basque Country UPV/EHU, 48940 Leioa, Vizcaya, Spain
| | - Ali Canbay
- Department of Gastroenterology, Hepatology, and Infectious Diseases, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany; Department of Medicine, Ruhr University Bochum, University Hospital Knappschaftskrankenhaus Bochum, 44892 Bochum, Germany.
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17
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Chou YT, Liu TT, Yang UC, Huang CC, Liu CW, Huang SF, Li TH, Liu HM, Lin MW, Yang YY, Lee TY, Huang YH, Hou MC, Lin HC. Intestinal SIRT1 Deficiency-Related Intestinal Inflammation and Dysbiosis Aggravate TNFα-Mediated Renal Dysfunction in Cirrhotic Ascitic Mice. Int J Mol Sci 2021; 22:ijms22031233. [PMID: 33513830 PMCID: PMC7865325 DOI: 10.3390/ijms22031233] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Revised: 01/21/2021] [Accepted: 01/22/2021] [Indexed: 12/14/2022] Open
Abstract
In advanced cirrhosis, the TNFα-mediated intestinal inflammation and bacteria dysbiosis are involved in the development of inflammation and vasoconstriction-related renal dysfunction. In colitis and acute kidney injury models, activation of SIRT1 attenuates the TNFα-mediated intestinal and renal abnormalities. This study explores the impacts of intestinal SIRT1 deficiency and TNFα-mediated intestinal abnormalities on the development of cirrhosis-related renal dysfunction. Systemic and renal hemodynamics, intestinal dysbiosis [cirrhosis dysbiosis ratio (CDR) as marker of dysbiosis], and direct renal vasoconstrictive response (renal vascular resistance (RVR) and glomerular filtration rate (GFR)) to cumulative doses of TNFα were measured in bile duct ligated (BDL)-cirrhotic ascitic mice. In SIRT1IEC-KO-BDL-ascitic mice, the worsening of intestinal dysbiosis exacerbates intestinal inflammation/barrier dysfunction, the upregulation of the expressions of intestinal/renal TNFα-related pathogenic signals, higher TNFα-induced increase in RVR, and decrease in GFR in perfused kidney. In intestinal SIRT1 knockout groups, the positive correlations were identified between intestinal SIRT1 activity and CDR. Particularly, the negative correlations were identified between CDR and RVR, with the positive correlation between CDR and GFR. In mice with advanced cirrhosis, the expression of intestinal SIRT1 is involved in the linkage between intestinal dysbiosis and vasoconstriction/hypoperfusion-related renal dysfunction through the crosstalk between intestinal/renal TNFα-related pathogenic inflammatory signals.
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Affiliation(s)
- Yu-Te Chou
- Department of Medicine, Taipei Veterans General Hospital, Taipei 11267, Taiwan; (Y.-T.C.); (C.-W.L.); (Y.-H.H.); (M.-C.H.)
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11267, Taiwan; (T.-T.L.); (U.-C.Y.); (C.-C.H.); (S.-F.H.); (T.-H.L.); (M.-W.L.)
| | - Tze-Tze Liu
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11267, Taiwan; (T.-T.L.); (U.-C.Y.); (C.-C.H.); (S.-F.H.); (T.-H.L.); (M.-W.L.)
- Genomic Research Center, National Yang Ming Chiao Tung University, Taipei 11267, Taiwan
| | - Ueng-Cheng Yang
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11267, Taiwan; (T.-T.L.); (U.-C.Y.); (C.-C.H.); (S.-F.H.); (T.-H.L.); (M.-W.L.)
- Institute of Biomedical Informatics, Taipei 11267, Taiwan
| | - Chia-Chang Huang
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11267, Taiwan; (T.-T.L.); (U.-C.Y.); (C.-C.H.); (S.-F.H.); (T.-H.L.); (M.-W.L.)
- Division of Clinical Skills Training Center, Department of Medical Education, Taipei Veterans General Hospital, Taipei 112, Taiwan
- Institute of Clinical Medicine, National Yang-Ming University, Taipei 11267, Taiwan
| | - Chih-Wei Liu
- Department of Medicine, Taipei Veterans General Hospital, Taipei 11267, Taiwan; (Y.-T.C.); (C.-W.L.); (Y.-H.H.); (M.-C.H.)
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11267, Taiwan; (T.-T.L.); (U.-C.Y.); (C.-C.H.); (S.-F.H.); (T.-H.L.); (M.-W.L.)
- Institute of Clinical Medicine, National Yang-Ming University, Taipei 11267, Taiwan
| | - Shiang-Fen Huang
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11267, Taiwan; (T.-T.L.); (U.-C.Y.); (C.-C.H.); (S.-F.H.); (T.-H.L.); (M.-W.L.)
- Division of Infection, Taipei Veterans General Hospital, Taipei 11267, Taiwan
| | - Tzu-Hao Li
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11267, Taiwan; (T.-T.L.); (U.-C.Y.); (C.-C.H.); (S.-F.H.); (T.-H.L.); (M.-W.L.)
- Institute of Clinical Medicine, National Yang-Ming University, Taipei 11267, Taiwan
- Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 11267, Taiwan
| | - Hsuan-Miao Liu
- Graduate Institute of Traditional Chinese Medicine, Chang Guang Memorial Hospital, Linkou 33371, Taiwan; (H.-M.L.); (T.-Y.L.)
| | - Ming-Wei Lin
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11267, Taiwan; (T.-T.L.); (U.-C.Y.); (C.-C.H.); (S.-F.H.); (T.-H.L.); (M.-W.L.)
- Institute of Public Health, National Yang-Ming University, Taipei 11267, Taiwan
| | - Ying-Ying Yang
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11267, Taiwan; (T.-T.L.); (U.-C.Y.); (C.-C.H.); (S.-F.H.); (T.-H.L.); (M.-W.L.)
- Division of Clinical Skills Training Center, Department of Medical Education, Taipei Veterans General Hospital, Taipei 112, Taiwan
- Institute of Clinical Medicine, National Yang-Ming University, Taipei 11267, Taiwan
- Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei 11267, Taiwan
- Correspondence: (Y.-Y.Y.); (H.-C.L.); Tel.: +886-2-2875-7725 (Y.-Y.Y.); +886-2-2875-2249 (H.-C.L.); Fax: +886-2-2875-7726 (Y.-Y.Y.); +886-2-2875-7809 (H.-C.L.)
| | - Tzung-Yan Lee
- Graduate Institute of Traditional Chinese Medicine, Chang Guang Memorial Hospital, Linkou 33371, Taiwan; (H.-M.L.); (T.-Y.L.)
| | - Yi-Hsiang Huang
- Department of Medicine, Taipei Veterans General Hospital, Taipei 11267, Taiwan; (Y.-T.C.); (C.-W.L.); (Y.-H.H.); (M.-C.H.)
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11267, Taiwan; (T.-T.L.); (U.-C.Y.); (C.-C.H.); (S.-F.H.); (T.-H.L.); (M.-W.L.)
- Institute of Public Health, National Yang-Ming University, Taipei 11267, Taiwan
- Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei 11267, Taiwan
| | - Ming-Chih Hou
- Department of Medicine, Taipei Veterans General Hospital, Taipei 11267, Taiwan; (Y.-T.C.); (C.-W.L.); (Y.-H.H.); (M.-C.H.)
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11267, Taiwan; (T.-T.L.); (U.-C.Y.); (C.-C.H.); (S.-F.H.); (T.-H.L.); (M.-W.L.)
| | - Han-Chieh Lin
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11267, Taiwan; (T.-T.L.); (U.-C.Y.); (C.-C.H.); (S.-F.H.); (T.-H.L.); (M.-W.L.)
- Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei 11267, Taiwan
- Correspondence: (Y.-Y.Y.); (H.-C.L.); Tel.: +886-2-2875-7725 (Y.-Y.Y.); +886-2-2875-2249 (H.-C.L.); Fax: +886-2-2875-7726 (Y.-Y.Y.); +886-2-2875-7809 (H.-C.L.)
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18
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Chang ML, Yang Z, Yang SS. Roles of Adipokines in Digestive Diseases: Markers of Inflammation, Metabolic Alteration and Disease Progression. Int J Mol Sci 2020; 21:E8308. [PMID: 33167521 PMCID: PMC7663948 DOI: 10.3390/ijms21218308] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 10/30/2020] [Accepted: 11/01/2020] [Indexed: 12/13/2022] Open
Abstract
Adipose tissue is a highly dynamic endocrine tissue and constitutes a central node in the interorgan crosstalk network through adipokines, which cause pleiotropic effects, including the modulation of angiogenesis, metabolism, and inflammation. Specifically, digestive cancers grow anatomically near adipose tissue. During their interaction with cancer cells, adipocytes are reprogrammed into cancer-associated adipocytes and secrete adipokines to affect tumor cells. Moreover, the liver is the central metabolic hub. Adipose tissue and the liver cooperatively regulate whole-body energy homeostasis via adipokines. Obesity, the excessive accumulation of adipose tissue due to hyperplasia and hypertrophy, is currently considered a global epidemic and is related to low-grade systemic inflammation characterized by altered adipokine regulation. Obesity-related digestive diseases, including gastroesophageal reflux disease, Barrett's esophagus, esophageal cancer, colon polyps and cancer, non-alcoholic fatty liver disease, viral hepatitis-related diseases, cholelithiasis, gallbladder cancer, cholangiocarcinoma, pancreatic cancer, and diabetes, might cause specific alterations in adipokine profiles. These patterns and associated bases potentially contribute to the identification of prognostic biomarkers and therapeutic approaches for the associated digestive diseases. This review highlights important findings about altered adipokine profiles relevant to digestive diseases, including hepatic, pancreatic, gastrointestinal, and biliary tract diseases, with a perspective on clinical implications and mechanistic explorations.
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Affiliation(s)
- Ming-Ling Chang
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan 33305, Taiwan
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan
| | - Zinger Yang
- Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA;
| | - Sien-Sing Yang
- Liver Center, Cathay General Hospital Medical Center, Taipei 10630, Taiwan;
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19
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Zhang P, Konja D, Wang Y. Adipose tissue secretory profile and cardiometabolic risk in obesity. ENDOCRINE AND METABOLIC SCIENCE 2020. [DOI: 10.1016/j.endmts.2020.100061] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
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20
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Heydari M, Cornide-Petronio ME, Jiménez-Castro MB, Peralta C. Data on Adiponectin from 2010 to 2020: Therapeutic Target and Prognostic Factor for Liver Diseases? Int J Mol Sci 2020; 21:5242. [PMID: 32718097 PMCID: PMC7432057 DOI: 10.3390/ijms21155242] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Revised: 07/15/2020] [Accepted: 07/22/2020] [Indexed: 12/13/2022] Open
Abstract
The review describes the role of adiponectin in liver diseases in the presence and absence of surgery reported in the literature in the last ten years. The most updated therapeutic strategies based on the regulation of adiponectin including pharmacological and surgical interventions and adiponectin knockout rodents, as well as some of the scientific controversies in this field, are described. Whether adiponectin could be a potential therapeutic target for the treatment of liver diseases and patients submitted to hepatic resection or liver transplantation are discussed. Furthermore, preclinical and clinical data on the mechanism of action of adiponectin in different liver diseases (nonalcoholic fatty disease, alcoholic liver disease, nonalcoholic steatohepatitis, liver cirrhosis and hepatocellular carcinoma) in the absence or presence of surgery are evaluated in order to establish potential targets that might be useful for the treatment of liver disease as well as in the practice of liver surgery associated with the hepatic resections of tumors and liver transplantation.
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Affiliation(s)
- Misaq Heydari
- Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), 08036 Barcelona, Spain; (M.H.); (M.E.C.-P.)
| | | | - Mónica B. Jiménez-Castro
- Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), 08036 Barcelona, Spain; (M.H.); (M.E.C.-P.)
| | - Carmen Peralta
- Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), 08036 Barcelona, Spain; (M.H.); (M.E.C.-P.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 08036 Barcelona, Spain
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Matiollo C, Rateke ECDM, de Oliveira KG, Turnes BL, da Silva TE, Maccali C, Latini AS, Narciso-Schiavon JL, Schiavon LL. Elevated neopterin levels are associated with acute-on-chronic liver failure and mortality in patients with liver cirrhosis. Dig Liver Dis 2020; 52:753-760. [PMID: 32434738 DOI: 10.1016/j.dld.2020.03.024] [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: 12/03/2019] [Revised: 03/09/2020] [Accepted: 03/26/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Macrophage activation plays a central role in hepatic and systemic inflammation and is involved in the pathogenesis of acute-on-chronic liver failure (ACLF). AIMS This study aimed to investigate neopterin levels in patients admitted for acute decompensation (AD) of cirrhosis, evaluating its relationship with ACLF and prognosis. METHODS This prospective cohort study included 205 adult subjects hospitalized for AD of cirrhosis. Twenty-one healthy subjects and 89 patients with stable cirrhosis were evaluated as controls. RESULTS Circulating neopterin was higher in AD as compared to stable cirrhosis and healthy controls (p<0.001). ACLF was independently associated with higher neopterin levels (OR 1.015, 95% CI 1.002-1.028, p = 0.025). In the multivariate Cox regression analysis, neopterin levels (HR = 1.002, IC 95% 1.000-1.004, p = 0.041), Child-Pugh class C, and ACLF were predictors of 30-day survival. Among patients with ACLF, the Kaplan-Meier survival probability was 71.4% in those with neopterin levels < 25 nmol/L and 31.0% if neopterin ≥ 25 nmol/L (p<0.001). CONCLUSIONS Higher circulating neopterin was associated with ACLF in patients hospitalized for AD of cirrhosis. Neopterin levels were also independently predictors of high short-term mortality, especially among patients with ACLF, and could represent a useful biomarker of macrophage activation in clinical practice.
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Affiliation(s)
- Camila Matiollo
- Laboratório de Análises Clínicas, Hospital Universitário, Universidade Federal de Santa Catarina, Brazil
| | | | - Karina Ghisoni de Oliveira
- Laboratório de Bioenergética e Estresse Oxidativo - LABOX, Universidade Federal de Santa Catarina, Brazil
| | - Bruna Lenfers Turnes
- Laboratório de Bioenergética e Estresse Oxidativo - LABOX, Universidade Federal de Santa Catarina, Brazil
| | - Telma Erotides da Silva
- Serviço de Gastroenterologia, Hospital Universitário, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
| | - Claudia Maccali
- Serviço de Gastroenterologia, Hospital Universitário, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
| | - Alexandra Susana Latini
- Laboratório de Bioenergética e Estresse Oxidativo - LABOX, Universidade Federal de Santa Catarina, Brazil
| | - Janaína Luz Narciso-Schiavon
- Serviço de Gastroenterologia, Hospital Universitário, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
| | - L L Schiavon
- Serviço de Gastroenterologia, Hospital Universitário, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
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22
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Thomson MJ, Taylor A, Sharma P, Lok AS, Tapper EB. Limited Progress in Hepatorenal Syndrome (HRS) Reversal and Survival 2002-2018: A Systematic Review and Meta-Analysis. Dig Dis Sci 2020; 65:1539-1548. [PMID: 31571102 PMCID: PMC7103565 DOI: 10.1007/s10620-019-05858-2] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2019] [Accepted: 09/19/2019] [Indexed: 01/08/2023]
Abstract
INTRODUCTION Type 1 hepatorenal syndrome (HRS) is a fatal complication of cirrhosis. Treatments trend toward HRS reversal, but few show clear mortality benefit. We sought to quantify the progress-or lack thereof-in improving outcomes of type 1 HRS over time. METHODS We performed a systematic review and meta-analysis for randomized controlled trials (RCTs) comparing type 1 HRS outcomes including (a) overall survival (liver transplant-free survival if reported) and (b) HRS reversal. Each study arm was analyzed separately to look at changes in outcomes over time. RCTs published comparing medical treatments for type 1 HRS were searched using several databases through July 31, 2019. RESULTS Fourteen RCTs (28 arms) involving 778 participants enrolled between 2002 and 2018 were included. Twelve RCTs measured HRS reversal. In conjunction with albumin (or plasma expander), the most common medications used were terlipressin (13 arms), antibiotics (7), norepinephrine (6), dopamine (4), and midodrine/octreotide (3). Pooled survival rate was 34.6% (95% CI 26.4-43.8), and pooled HRS reversal rate was 42.8% (95% CI 34.2-51.9). Regression analyzing the incremental effect of the year the RCT was initiated showed that more recent studies were not associated with improved survival (OR 1.02, 95% CI 0.94-1.11, p = 0.66) or HRS reversal rates (OR 1.03, 95% CI 0.96-1.11, p = 0.41). There was no survival improvement when RCTs with endpoints assessed ≤ or > 1 month were analyzed separately with respective OR of 1.07 (95% CI 0.95-1.20, p = 0.26) and 0.97 (95% CI 0.85-1.12, p = 0.70). CONCLUSION Outcomes have not improved for patients with type 1 HRS since 2002. There is a need to improve prevention and treatment of type 1 HRS.
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Affiliation(s)
- Mary J Thomson
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, 3912 Taubman Center, 1500 E. Medical Center Drive, Ann Arbor, MI, 48109, USA.
- Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor, MI, USA.
| | - Arthur Taylor
- Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Pratima Sharma
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, 3912 Taubman Center, 1500 E. Medical Center Drive, Ann Arbor, MI, 48109, USA
| | - Anna S Lok
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, 3912 Taubman Center, 1500 E. Medical Center Drive, Ann Arbor, MI, 48109, USA
- Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor, MI, USA
| | - Elliot B Tapper
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, 3912 Taubman Center, 1500 E. Medical Center Drive, Ann Arbor, MI, 48109, USA
- Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor, MI, USA
- Veterans Affairs Hospital, Ann Arbor, MI, USA
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23
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Fluid Biomarkers for Predicting the Prognosis of Liver Cirrhosis. BIOMED RESEARCH INTERNATIONAL 2020; 2020:7170457. [PMID: 32280697 PMCID: PMC7114768 DOI: 10.1155/2020/7170457] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/06/2019] [Revised: 01/12/2020] [Accepted: 02/04/2020] [Indexed: 12/15/2022]
Abstract
Liver cirrhosis is the terminal stage of most chronic liver conditions, with a high risk of mortality. Careful evaluation of the prognosis of cirrhotic patients and providing precise management are crucial to reduce the risk of mortality. Although the liver biopsy and hepatic venous pressure gradient (HVPG) can efficiently evaluate the prognosis of cirrhotic patients, their application is limited due to the invasion procedures. Child-Pugh score and the model for end-stage liver disease (MELD) score had been widely used in the assessment of cirrhotic prognosis, but the defects of subjective variable application in Child-Pugh score and unsuitability to all phases of liver cirrhosis in MELD score limit their prognostic values. In recent years, continuous efforts have been made to investigate the prognostic value of body fluid biomarkers for cirrhotic patients, and promising results have been reported. Since the collection of fluid specimens is easy, noninvasive, and repeatable, fluid biomarkers can be ideal indicators to predict the prognosis of cirrhosis. Here, we reviewed noninvasive fluid biomarkers in different prognostic functions, including the prediction of survival and complication development.
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Ibrahim DM, Shaaban ESE, Fouad TA. Circulating Resistin Is Associated with Plasma Glucagon-Like Peptide-1 in Cirrhotic Patients with Hepatitis C Virus Genotype-4 Infection. Endocr Res 2020; 45:17-23. [PMID: 31177870 DOI: 10.1080/07435800.2019.1627551] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Purpose: Limited and contradictory data on the circulating levels of glucagon-like peptide (GLP-1) and resistin in hepatitis C virus genotype-4 (HCV-4) cirrhotic patients are present. Thus, this study aimed to evaluate their concentrations and to investigate the association between total GLP-1, resistin, and insulin resistance in those patients.Materials and Methods: Non-diabetic HCV-4 cirrhotic patients (n = 80; 40 with Child-Pugh A, 20 with Child-Pugh B, and 20 with Child-Pugh C), and 25 healthy subjects were enrolled in this study. The basal circulating levels of total GLP-1 and resistin along with serum insulin, glucose, total cholesterol, and triglycerides were measured.Results: Plasma GLP-1 and serum resistin levels were significantly higher in cirrhotic patients than controls (P < . 001). Moreover, circulating GLP-1 and resistin levels increased in a stepwise fashion in line with increasing grade of liver damage. According to Spearman's rank correlation, both GLP-1 and resisitin correlated positively with each other, insulin, homeostatic model assessment of insulin resistance, alanine aminotransferase (ALT), total bilirubin, and international normalized ratio while they correlated negatively with albumin (P < .001). Multiple stepwise regression analysis showed that ALT, serum resistin and Child-Pugh score independently influenced the GLP-1 levels in cirrhotic patients.Conclusions: Circulating levels of GLP-1 and resistin were elevated in cirrhotic patients with HCV-4. Further, the severity of liver cirrhosis and serum resistin were the determinant factors explaining the variability of GLP-1 levels by about 84%. In addition, a positive relation was found between insulin resistance and both GLP-1 and resistin levels.
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Affiliation(s)
- Doaa M Ibrahim
- Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt
| | - El Saeid E Shaaban
- Internal Medicine Department, El-Mataria Teaching Hospital, The General Organization for Teaching Hospitals and Institutes, Cairo, Egypt
| | - Tarek A Fouad
- Internal Medicine Department, El-Mataria Teaching Hospital, The General Organization for Teaching Hospitals and Institutes, Cairo, Egypt
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25
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Best LMJ, Freeman SC, Sutton AJ, Cooper NJ, Tng E, Csenar M, Hawkins N, Pavlov CS, Davidson BR, Thorburn D, Cowlin M, Milne EJ, Tsochatzis E, Gurusamy KS, Cochrane Hepato‐Biliary Group. Treatment for hepatorenal syndrome in people with decompensated liver cirrhosis: a network meta-analysis. Cochrane Database Syst Rev 2019; 9:CD013103. [PMID: 31513287 PMCID: PMC6740336 DOI: 10.1002/14651858.cd013103.pub2] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Hepatorenal syndrome is defined as renal failure in people with cirrhosis in the absence of other causes. In addition to supportive treatment such as albumin to restore fluid balance, the other potential treatments include systemic vasoconstrictor drugs (such as vasopressin analogues or noradrenaline), renal vasodilator drugs (such as dopamine), transjugular intrahepatic portosystemic shunt (TIPS), and liver support with molecular adsorbent recirculating system (MARS). There is uncertainty over the best treatment regimen for hepatorenal syndrome. OBJECTIVES To compare the benefits and harms of different treatments for hepatorenal syndrome in people with decompensated liver cirrhosis. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and trial registers until December 2018 to identify randomised clinical trials on hepatorenal syndrome in people with cirrhosis. SELECTION CRITERIA We included only randomised clinical trials (irrespective of language, blinding, or publication status) in adults with cirrhosis and hepatorenal syndrome. We excluded randomised clinical trials in which participants had previously undergone liver transplantation. DATA COLLECTION AND ANALYSIS Two authors independently identified eligible trials and collected data. The outcomes for this review included mortality, serious adverse events, any adverse events, resolution of hepatorenal syndrome, liver transplantation, and other decompensation events. We performed a network meta-analysis with OpenBUGS using Bayesian methods and calculated the odds ratio (OR), rate ratio, hazard ratio (HR), and mean difference (MD) with 95% credible intervals (CrI) based on an available-case analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance. MAIN RESULTS We included a total of 25 trials (1263 participants; 12 interventions) in the review. Twenty-three trials (1185 participants) were included in one or more outcomes. All the trials were at high risk of bias, and all the evidence was of low or very low certainty. The trials included participants with liver cirrhosis of varied aetiologies as well as a mixture of type I hepatorenal syndrome only, type II hepatorenal syndrome only, or people with both type I and type II hepatorenal syndrome. Participant age ranged from 42 to 60 years, and the proportion of females ranged from 5.8% to 61.5% in the trials that reported this information. The follow-up in the trials ranged from one week to six months. Overall, 59% of participants died during this period and about 35% of participants recovered from hepatorenal syndrome. The most common interventions compared were albumin plus terlipressin, albumin plus noradrenaline, and albumin alone.There was no evidence of a difference in mortality (22 trials; 1153 participants) at maximal follow-up between the different interventions. None of the trials reported health-related quality of life. There was no evidence of differences in the proportion of people with serious adverse events (three trials; 428 participants), number of participants with serious adverse events per participant (two trials; 166 participants), proportion of participants with any adverse events (four trials; 402 participants), the proportion of people who underwent liver transplantation at maximal follow-up (four trials; 342 participants), or other features of decompensation at maximal follow-up (one trial; 466 participants). Five trials (293 participants) reported number of any adverse events, and five trials (219 participants) reported treatment costs. Albumin plus noradrenaline had fewer numbers of adverse events per participant (rate ratio 0.51, 95% CrI 0.28 to 0.87). Eighteen trials (1047 participants) reported recovery from hepatorenal syndrome (as per definition of hepatorenal syndrome). In terms of recovery from hepatorenal syndrome, in the direct comparisons, albumin plus midodrine plus octreotide and albumin plus octreotide had lower recovery from hepatorenal syndrome than albumin plus terlipressin (HR 0.04; 95% CrI 0.00 to 0.25 and HR 0.26, 95% CrI 0.07 to 0.80 respectively). There was no evidence of differences between the groups in any of the other direct comparisons. In the network meta-analysis, albumin and albumin plus midodrine plus octreotide had lower recovery from hepatorenal syndrome compared with albumin plus terlipressin. FUNDING two trials were funded by pharmaceutical companies; five trials were funded by parties who had no vested interest in the results of the trial; and 18 trials did not report the source of funding. AUTHORS' CONCLUSIONS Based on very low-certainty evidence, there is no evidence of benefit or harm of any of the interventions for hepatorenal syndrome with regards to the following outcomes: all-cause mortality, serious adverse events (proportion), number of serious adverse events per participant, any adverse events (proportion), liver transplantation, or other decompensation events. Low-certainty evidence suggests that albumin plus noradrenaline had fewer 'any adverse events per participant' than albumin plus terlipressin. Low- or very low-certainty evidence also found that albumin plus midodrine plus octreotide and albumin alone had lower recovery from hepatorenal syndrome compared with albumin plus terlipressin.Future randomised clinical trials should be adequately powered; employ blinding, avoid post-randomisation dropouts or planned cross-overs (or perform an intention-to-treat analysis); and report clinically important outcomes such as mortality, health-related quality of life, adverse events, and recovery from hepatorenal syndrome. Albumin plus noradrenaline and albumin plus terlipressin appear to be the interventions that should be compared in future trials.
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Affiliation(s)
- Lawrence MJ Best
- University College LondonDivision of Surgery and Interventional ScienceRowland Hill StreetLondonUKNW32PF
| | - Suzanne C Freeman
- University of LeicesterDepartment of Health SciencesUniversity RoadLeicesterUKLE1 7RH
| | - Alex J Sutton
- University of LeicesterDepartment of Health SciencesUniversity RoadLeicesterUKLE1 7RH
| | - Nicola J Cooper
- University of LeicesterDepartment of Health SciencesUniversity RoadLeicesterUKLE1 7RH
| | - Eng‐Loon Tng
- Ng Teng Fong General Hospital National University Health SystemDepartment of Medicine1 Jurong East Street 21SingaporeSingapore609606
| | - Mario Csenar
- University College LondonDivision of Surgery and Interventional ScienceRowland Hill StreetLondonUKNW32PF
| | - Neil Hawkins
- University of GlasgowHEHTAUniversity Ave Glasgow G12 8QQGlasgowUK
| | - Chavdar S Pavlov
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University HospitalCochrane Hepato‐Biliary GroupBlegdamsvej 9CopenhagenDenmarkDK‐2100
- 'Sechenov' First Moscow State Medical UniversityCenter for Evidence‐Based MedicinePogodinskja st. 1\1MoscowRussian Federation119881
| | - Brian R Davidson
- University College LondonDivision of Surgery and Interventional ScienceRowland Hill StreetLondonUKNW32PF
| | - Douglas Thorburn
- Royal Free Hospital and the UCL Institute of Liver and Digestive HealthSheila Sherlock Liver CentrePond StreetLondonUKNW3 2QG
| | | | | | - Emmanuel Tsochatzis
- Royal Free Hospital and the UCL Institute of Liver and Digestive HealthSheila Sherlock Liver CentrePond StreetLondonUKNW3 2QG
| | - Kurinchi Selvan Gurusamy
- University College LondonDivision of Surgery and Interventional ScienceRowland Hill StreetLondonUKNW32PF
- 'Sechenov' First Moscow State Medical UniversityCenter for Evidence‐Based MedicinePogodinskja st. 1\1MoscowRussian Federation119881
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Zhang D, Bai J, Ma Z, Ma X, Cao X, Li F. Regulatory roles of adiponectin receptor 1 and 2 in sheep preadipocytes during adipocyte differentiation. ITALIAN JOURNAL OF ANIMAL SCIENCE 2019. [DOI: 10.1080/1828051x.2019.1568838] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Affiliation(s)
- Derong Zhang
- College of Animal Science and Technology, Gansu Agricultural University, Lanzhou, China
- Gansu Engineering Research Center for Animal Cell, Northwest Minzu University, Lanzhou, China
| | - Jialin Bai
- Gansu Engineering Research Center for Animal Cell, Northwest Minzu University, Lanzhou, China
| | - Zhongren Ma
- Gansu Engineering Research Center for Animal Cell, Northwest Minzu University, Lanzhou, China
| | - Xiaoxia Ma
- Gansu Engineering Research Center for Animal Cell, Northwest Minzu University, Lanzhou, China
| | - Xin Cao
- Experiment Center of Northwest Minzu University, Lanzhou, China
| | - Fadi Li
- College of Animal Science and Technology, Gansu Agricultural University, Lanzhou, China
- College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou, China
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Amin AA, Alabsawy EI, Jalan R, Davenport A. Epidemiology, Pathophysiology, and Management of Hepatorenal Syndrome. Semin Nephrol 2019; 39:17-30. [PMID: 30606404 DOI: 10.1016/j.semnephrol.2018.10.002] [Citation(s) in RCA: 48] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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