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Singh SA, Prakash K, Kajal K, Loganathan S, K N, Subramanian R, Singh A, Choudhary NS, Mukherjee A, Viswanathan Premkumar G, Sindwani G, Ranade S, Malleeswaran SK, Raghu A, Mathiyazhagan R, Venkatachalapathy S, Pant D, Srivastava P, Kumar L, Vohra V, Rajkumar A, Narsimhan G, Goel A, Aggarwal V, Kumar A, Panackel C. LTSI Consensus Guidelines: Preoperative Cardiac Evaluation in Adult Liver Transplant Recipients. J Clin Exp Hepatol 2025; 15:102419. [PMID: 40177699 PMCID: PMC11959373 DOI: 10.1016/j.jceh.2024.102419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Accepted: 09/27/2024] [Indexed: 01/03/2025] Open
Abstract
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality among LT candidates and accounts for up to 40% of the overall mortality within one month. It is influenced by traditional and nontraditional risk factors related to end-stage liver disease. A large proportion of CLD patients have underlying cardiovascular disease (CVD) especially if the etiology is metabolic associated steatohepatitis. Despite the large number of liver transplantations being conducted in India, there is a lack of an evidence-based guidelines for screening of CVD in this patient population. This consensus statement from Liver Transplant Society of India (LTSI) is the first attempt for developing an evidence-based document on preoperative cardiac evaluation from India. A task force consisting of transplant-anesthesiologists, transplant hepatologists, liver transplant surgeon and cardiologists from high volume centres was formed which reviewed the existing evidence and literature and formulated graded recommendations. The document focuses on identification of underlying cardiac pathologies, risk stratification and optimisation of modifiable cardiac diseases. Implementation of best practices and optimal strategies should be encouraged to improve cardiovascular outcomes in these populations.
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Affiliation(s)
- Shweta A. Singh
- Department of Anaesthesia and Critical Care - Center for Liver & Biliary Sciences (CLBS), Max Super Speciality Hospital (MSSH), Saket, New Delhi, India
| | - Kelika Prakash
- Department of Anaesthesiology, Pain Medicine & Critical Care AIIMS, New Delhi, India
| | - Kamal Kajal
- Department of Anaesthesia and Intensive Care, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Sekar Loganathan
- Department of Anesthesiology, All India Institute of Medical Sciences Kalyani, West Bengal, India
| | - Nandakumar K
- GI/Liver/Renal Intensive Care, Liver & Renal Intensive Care, Apollo Main Hospitals, Chennai, India
| | | | - Anil Singh
- Liver Transplant Anaesthesia & Critical Care, Nanavati Max Super Speciality Hospital, Mumbai, India
| | - Narendra S Choudhary
- Institute of Liver Transplantation & Regenerative Medicine, Medanta the Medicity, Gurugram, India
| | | | | | | | - Sharmila Ranade
- Liver Transplant Anaesthesia, Kokilaben Dhirubhai Ambani Hospital & Medical Research Centre, Andheri East Mumbai, India
| | - Selva K. Malleeswaran
- Department of Liver Anesthesia and Critical Care, Gleneagles Hospitals, Chennai, India
| | - Arun Raghu
- Anaesthesia & Transplant Anaesthesia, Gleneagles BGS Hospital, Bengaluru, India
| | | | | | - Deepanjali Pant
- Institute of Anaesthesiology, Pain & Perioperative Medicine, Sir Ganga Ram Hospital New Delhi, India
| | - Piyush Srivastava
- Department of Liver Transplant Anaesthesia & Critical Care, Fortis Hospiital, Noida, India
| | - Lakshmi Kumar
- Department of Anaesthesiology & Critical Care, Amrita Institute of Medical Sciences, Kochi, India
| | - Vijay Vohra
- Liver Transplant, GI Anaesthesia & Intensive Care, Medanta The Medicity, Gurugram, Haryana, India
| | - Akila Rajkumar
- Liver Intensive Care and Anaesthesia, Dr.Rela Institute & Medical Center, Chennai, India
| | | | - Anupam Goel
- Max Super Speciality Hospital (MSSH) Saket, New Delhi, India
| | - Vinayak Aggarwal
- Clinical Cardiology & Advance Cardiac Imaging, Fortis Memorial Research Institute(FMRI), Gurgaon, India
| | - Ashok Kumar
- Intereventional Cardiologist Advance Heart Failure Specialist, Dr.Rela Institute & Medical Center, Chennai, India
| | - Charles Panackel
- Hepatology & Liver Transplsant, Aster Integrated Liver Care, Kochi, India
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Sozzi A, Aiolfi A, Bonitta G, Bona D, Bonavina L, Biondi A, Rausa E, Simić A, Skrobic O, Popa C, Schlanger D. Esophagectomy in patients with liver cirrhosis: systematic review and meta-analysis of short-term outcomes. Updates Surg 2025; 77:143-152. [PMID: 39718689 DOI: 10.1007/s13304-024-02060-6] [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: 10/09/2024] [Accepted: 12/13/2024] [Indexed: 12/25/2024]
Abstract
Patients with esophageal cancer and concomitant liver cirrhosis (LC) pose a surgical challenge because of the increased risk of postoperative complications and mortality. Purpose of this study was to review the existing literature and estimate perioperative short-term outcomes of esophagectomy in this patient population. Systematic review and meta-analysis. PubMed, MEDLINE, Scopus, Web of Science, Cochrane Central Library, and ClinicalTrials.gov were queried. The search was last updated on July 30th, 2024. Primary outcomes were anastomotic leak (AL) and 90 day mortality. Ten observational studies were included for a total of 387 patients with LC. The age of the included patients ranged from 35 to 85 years, 91.2% were males. The main causes of liver cirrhosis were alcoholic (75%) and viral hepatitis (20.4%). Esophageal squamous cell carcinoma was diagnosed in 58.7% of patients. Ivor-Lewis esophagectomy with intrathoracic anastomosis was reported in 69.9% of patients, while McKeown esophagectomy with cervical anastomosis was reported in 30.1% of patients. The estimated pooled prevalence of AL and 90-day mortality were 13% (95% CI = 6-24%; I2 = 72%) and 17% (95% CI = 10-27%; I2 = 72%), respectively. The estimated pooled prevalence of postoperative pulmonary complication, sepsis, and liver failure were 52% (95% CI = 39-65%), 30% (95% CI = 14-52%), and 9% (95% CI = 4-17%), respectively. Esophagectomy can be performed in properly selected patients with LC and concomitant esophageal cancer. Foregut surgeons should be aware of the not negligible postoperative complications rates and mortality. Risk stratification and attentive perioperative care are essential to minimize serious adverse events.
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Affiliation(s)
- Andrea Sozzi
- I.R.C.C.S. Ospedale Galeazzi - Sant'Ambrogio, Division of General Surgery, Department of Biomedical Science for Health, University of Milan, Istitituto Clinico Sant'Ambrogio, Via C. Belgioioso, 173, 20157, Milan, Italy
| | - Alberto Aiolfi
- I.R.C.C.S. Ospedale Galeazzi - Sant'Ambrogio, Division of General Surgery, Department of Biomedical Science for Health, University of Milan, Istitituto Clinico Sant'Ambrogio, Via C. Belgioioso, 173, 20157, Milan, Italy.
| | - Gianluca Bonitta
- I.R.C.C.S. Ospedale Galeazzi - Sant'Ambrogio, Division of General Surgery, Department of Biomedical Science for Health, University of Milan, Istitituto Clinico Sant'Ambrogio, Via C. Belgioioso, 173, 20157, Milan, Italy
| | - Davide Bona
- I.R.C.C.S. Ospedale Galeazzi - Sant'Ambrogio, Division of General Surgery, Department of Biomedical Science for Health, University of Milan, Istitituto Clinico Sant'Ambrogio, Via C. Belgioioso, 173, 20157, Milan, Italy
| | - Luigi Bonavina
- Division of General and Foregut Surgery, Department of Biomedical Sciences for Health, University of Milan, IRCCS Policlinico San Donato, Milan, Italy
| | - Antonio Biondi
- Surgical Division, Department of General Surgery and Medical Surgical Specialties, G. Rodolico Hospital, University of Catania, 95131, Catania, Italy
| | - Emanuele Rausa
- Unit of Hereditary Digestive Tract Tumors, Fondazione IRCCS Istituto Nazionale Dei Tumori, Via Venezian 1, 20133, Milan, Italy
| | - Aleksandar Simić
- Department of Anaesthesiology and Intensive Care, Hospital for Digestive Surgery, University Clinical Center of Serbia, Belgrade, Serbia
| | - Ognjan Skrobic
- Department of Anaesthesiology and Intensive Care, Hospital for Digestive Surgery, University Clinical Center of Serbia, Belgrade, Serbia
| | - Calin Popa
- Surgery Clinic 3, Regional Institute of Gastroenterology and Hepatology "Prof. Dr. Octavian Fodor", "Iuliu Hațieganul" University of Medicine and Pharmacy, 400394, Cluj-Napoca-Napoca, Romania
| | - Diana Schlanger
- Surgery Clinic 3, Regional Institute of Gastroenterology and Hepatology "Prof. Dr. Octavian Fodor", "Iuliu Hațieganul" University of Medicine and Pharmacy, 400394, Cluj-Napoca-Napoca, Romania
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Praharaj DL, Das S, Mohapatra V, Mallick B, Nath P, Chandra Panigrahi S, Giri S, Sahu SK, Anand AC, Acharya SK. Experience of Performing Hepatic Interventional Radiological Procedures in a Tertiary Care Hospital in Odisha: A Case Series. J Clin Exp Hepatol 2024; 14:101436. [PMID: 38882180 PMCID: PMC11170197 DOI: 10.1016/j.jceh.2024.101436] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2023] [Accepted: 04/14/2024] [Indexed: 06/18/2024] Open
Abstract
INTRODUCTION During last few decades, radiological interventions have played crucial role in the management of the patients with chronic liver diseases. Various procedures including transjugualar intrahepatic portosystemic shunt (TIPS), transjugular liver biopsy (TJLB), transarterial chemoembilization (TACE)/transarterial radioembolization (TARE), balloon retrograde transvenous obliteration (BRTO) and plug-assisted retrograde transvenous obliteration (PARTO) are being performed safely and have significantly improved clinical outcomes in these patients. The technical and clinical success depend on appropriate patient selection along with thorough knowledge and experience to perform these procedures. On the other hand, few adverse events may also be associated with these procedures. The intervention radiologist and hepatologists should identify and treat these complications at the earliest so as to improve outcome of the patient. MATERIALS AND METHODS About 25 hepatic intervention radiology procedures were performed in our center from January 2022 to 2023 May. Among these we have selected five patients who underwent TACE/TIPS/DIPS in our institute. We have selected these cases as in each of these cases we encountered some interesting outcomes/complications which were managed successfully. RESULTS The first case describes 33-year-old male with POEM syndrome and Budd Chiari Syndrome (BCS) who underwent TIPS and immediately had blockade of the stent. The second case is of a 43 years old male having BCS, refractory ascites with umbilical and inguinal hernia. The third case is of a 40 years old female with decompensated cirrhosis who underwent TIPS for portal hypertensive gastropathy. The fourth case is of a 51-years' female with decompensated cirrhosis with sarcopenia. Finally, the fifth case describes 24-year-old female with BCS and hepatocellular carcinoma. In this article we discuss the procedure and clinical course of the patients following the procedure. CONCLUSION Hepatic radiological interventions though widely used can be associated with unusual albeit life threatening complications. Appropriate patient selection and thorough knowledge of procedure along with early diagnosis and management of these complications are key to obtain satisfying long term outcomes.
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Affiliation(s)
- Dibya Lochan Praharaj
- Department of Gastroenterology and Hepatology, KIMS and PBM Hospital, Bhubaneswar, Odisha, India
| | - Swati Das
- Department of Radiology, KIMS and PBM Hospital, Bhubaneswar, Odisha, India
| | - Vedavyas Mohapatra
- Department of GI Surgery, KIMS and PBM Hospital, Bhubaneswar, Odisha, India
| | - Bipadabhanjan Mallick
- Department of Gastroenterology and Hepatology, KIMS and PBM Hospital, Bhubaneswar, Odisha, India
| | - Preetam Nath
- Department of Gastroenterology and Hepatology, KIMS and PBM Hospital, Bhubaneswar, Odisha, India
| | - Sarat Chandra Panigrahi
- Department of Gastroenterology and Hepatology, KIMS and PBM Hospital, Bhubaneswar, Odisha, India
| | - Suprabhat Giri
- Department of Gastroenterology and Hepatology, KIMS and PBM Hospital, Bhubaneswar, Odisha, India
| | - Saroj Kanta Sahu
- Department of Gastroenterology and Hepatology, KIMS and PBM Hospital, Bhubaneswar, Odisha, India
| | - Anil Chandra Anand
- Department of Gastroenterology and Hepatology, KIMS and PBM Hospital, Bhubaneswar, Odisha, India
| | - Subrat Kumar Acharya
- Department of Gastroenterology and Hepatology, KIMS and PBM Hospital, Bhubaneswar, Odisha, India
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Xue X, Li Y, Zhang S, Yao Y, Peng C, Li Y. Hydroxysafflor yellow A exerts anti-fibrotic and anti-angiogenic effects through miR-29a-3p/PDGFRB axis in liver fibrosis. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 132:155830. [PMID: 38959553 DOI: 10.1016/j.phymed.2024.155830] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Revised: 06/03/2024] [Accepted: 06/14/2024] [Indexed: 07/05/2024]
Abstract
BACKGROUND Liver fibrosis is a prevalent pathological process in chronic liver diseases characterized by excessive extracellular matrix (ECM) deposition and abnormal angiogenesis. Notably, hepatic stellate cells (HSCs) are the primary source of ECM. Activated HSCs not only secrete numerous pro-fibrotic cytokines but also are endowed with a pro-angiogenic phenotype to promote pathological angiogenesis. Therefore, targeted modulation of HSCs has emerged as a pivotal strategy for addressing liver fibrosis. Hydroxysafflor yellow A (HSYA) is a homology of medicine and food colourant with good pharmacological activity. However, the precise mechanisms of HSYA against liver fibrosis remain unclear. PURPOSE The objective of this study was to elucidate the impact of HSYA on liver fibrosis and pathological angiogenesis, as well as the underlying mechanisms in vitro and in vivo studies. METHODS The efficacy and mechanisms of HSYA on TGF-β1-induced HSCs and VEGFA-induced endothelial cells were investigated by MTT assay, EdU cell proliferation assay, cell scratch assay, Elisa assay, immunofluorescence assay, molecular docking, cell transfection assay, western blot analysis and RT-qPCR analysis. In CCl4-induced liver fibrosis mice model, H&E, Masson, and Sirius red staining were used to observe histopathology. Serum transaminase activity and liver biochemical indexes were tested by biochemical kit. Immunohistochemical, fluorescence in situ hybridization (FISH), western blot analysis and RT-qPCR analysis were implemented to determine the mechanism of HSYA in vivo. RESULTS Herein, our findings confirmed that HSYA inhibited the proliferation, migration and activation of HSCs, as evidenced by a reduction in cell viability, relative migration rate, EdU staining intensity, and pro-fibrotic mRNAs and proteins expression in vitro. Mechanistically, HSYA played an anti-fibrotic and anti-angiogenic role by partially silencing PDGFRB in activated HSCs, thereby disrupting PDGFRB/MEK/ERK signal transduction and inhibiting the expression of HIF-1α, VEGFA and VEGFR2 proteins. Importantly, PDGFRB was a target gene of miR-29a-3p. Treatment with HSYA reversed the down-regulation of miR-29a-3p and antagonized PDGFRB signaling pathway in TGF-β1-induced HSCs transfected with miR-29a-3p inhibitor. Consistent with our in vitro study, HSYA exhibited a good hepatoprotective effect in CCl4-induced liver fibrosis mice by reducing serum ALT and AST levels, decreasing the contents of four fibrosis indicators (HA, PIIIP, ColIV and LN) and hydroxyproline, and inhibiting the TGF-β1/TGFBR signaling pathway. In terms of mechanisms, HSYA alleviated pathological angiogenesis in fibrotic liver by deactivating PDGFRB signaling pathway and impairing the positive expression of CD31. Subsequently, FISH results further corroborated HSYA affected the activation of HSCs and angiogenesis achieved by the concurrent upregulation of miR-29a-3p and downregulation of α-SMA and VEGFA. Additionally, treatment with HSYA also forged a link between HSCs and endothelial cells, as supported by inhibiting the aberrant proliferation of endothelial cells. CONCLUSION Fundamentally, the current study has illustrated that HSYA ameliorates liver fibrosis by repressing HSCs-mediated pro-fibrotic and pro-angiogenic processes, which is contingent upon the regulatory effect of HSYA on the miR-29a-3p/PDGFRB axis. These findings provide compelling evidence bolstering the potential of HSYA as a therapeutic agent in liver fibrosis.
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Affiliation(s)
- Xinyan Xue
- State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Yanzhi Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Shenglin Zhang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Yuxin Yao
- State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Cheng Peng
- State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
| | - Yunxia Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
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Jose A, Rahman N, Opotowsky AR, Glorioso TJ, Waldo SW, Zeder K, Seto A, Elwing JM, McCormack FX, Maron BA. Association of Cardiopulmonary Hemodynamics and Mortality in Veterans With Liver Cirrhosis: A Retrospective Cohort Study. J Am Heart Assoc 2024; 13:e033847. [PMID: 38567662 PMCID: PMC11262483 DOI: 10.1161/jaha.123.033847] [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: 01/16/2024] [Accepted: 02/23/2024] [Indexed: 04/04/2024]
Abstract
BACKGROUND Portopulmonary hypertension (PoPH), associated with increased mortality, can limit treatment options for liver diseases. Data on the continuum of clinical risk related to cardiopulmonary hemodynamics in PoPH are lacking. METHODS AND RESULTS As part of the United States national Veterans Affairs Clinical Assessment, Reporting, and Tracking database, we performed a retrospective cohort study of adults with cirrhosis undergoing right heart catheterization between October 1, 2017, and September 30, 2022. Pulmonary hypertension (mean pulmonary arterial pressure [mPAP] >20 mm Hg without PoPH) and PoPH (mPAP >20 mm Hg+pulmonary artery wedge pressure ≤15 mm Hg+pulmonary vascular resistance ≥3 WU) were defined by right heart catheterization hemodynamics. Multivariable Cox proportional hazards using natural splines for hemodynamic variables were used to evaluate the association between cardiopulmonary hemodynamics and mortality following right heart catheterization. A total of 4409 patients were included in the final analysis, predominantly men (96.3%), with a mean age of 68.5 years. Pulmonary hypertension and PoPH were observed in 71.6% and 10.2% of the cohort, respectively. Compared with a reference cardiac index of 2.5 L/min per m2, the hazard for mortality increased progressively with decreasing cardiac index, even after adjustment for mPAP and pulmonary vascular resistance. The minority of patients with PoPH (N=65, 14.5%) were prescribed pulmonary vasodilator therapy. CONCLUSIONS These data suggest that pulmonary hypertension and PoPH are prevalent in veterans with chronic liver disease, but low use of targeted PoPH therapy persists. Cardiac function discriminated mortality risk across a wide range of mPAP and pulmonary vascular resistance values and may diagnose and clarify prognosis in this patient population.
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Affiliation(s)
- Arun Jose
- Veterans Affairs Cincinnati Healthcare SystemCincinnatiOH
- University of CincinnatiOH
| | - Natalia Rahman
- Rocky Mountain Regional VA Medical CenterAuroraCO
- Denver Research InstituteAuroraCO
| | - Alexander R. Opotowsky
- Heart Institute, Cincinnati Children’s Hospital Medical Center, University of CincinnatiOH
| | - Thomas J. Glorioso
- CART Program, Office of Quality and Patient Safety, Veterans Health AdministrationWashingtonDC
| | - Stephen W. Waldo
- Rocky Mountain Regional VA Medical CenterAuroraCO
- CART Program, Office of Quality and Patient Safety, Veterans Health AdministrationWashingtonDC
- University of Colorado School of MedicineAuroraCO
| | - Katarina Zeder
- Brigham and Women’s Hospital and Harvard Medical SchoolBostonMA
- Department of MedicineUniversity of Maryland School of MedicineBaltimoreMD
- The University of Maryland‐Institute for Health ComputingBethesdaMD
- Ludwig Boltzmann Institute for Lung Vascular Research, Medical University of GrazAustria
| | - Arnold Seto
- Veteran’s Affairs Long Beach Healthcare SystemLong BeachCA
| | | | - Francis X. McCormack
- Veterans Affairs Cincinnati Healthcare SystemCincinnatiOH
- University of CincinnatiOH
| | - Bradley A. Maron
- Veterans Affairs Boston Healthcare SystemBostonMA
- Brigham and Women’s Hospital and Harvard Medical SchoolBostonMA
- Department of MedicineUniversity of Maryland School of MedicineBaltimoreMD
- The University of Maryland‐Institute for Health ComputingBethesdaMD
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Mitchell J, Alnemer A, Deiparine S, Stein E, Gorelik L. Anesthetic Considerations for Patients With Mitral Stenosis Undergoing Orthotopic Liver Transplant. Cureus 2023; 15:e47751. [PMID: 38021530 PMCID: PMC10676281 DOI: 10.7759/cureus.47751] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/18/2023] [Indexed: 12/01/2023] Open
Abstract
A 70-year-old male presented for an orthotopic liver transplant (OLT) with co-existing moderate-severe mitral valve stenosis. The hemodynamic goals of managing mitral stenosis posed a significant additional challenge to this patient's care. Intraoperative transesophageal echocardiography (TEE) was critical in guiding volume status and resuscitation. In addition, the patient's valvulopathy guided our vasoactive medication selection and arrhythmia prevention. In this article, we describe the multidisciplinary discussions regarding preoperative valvular intervention as well as the intraoperative techniques used to preserve cardiac output while avoiding coagulopathy and arrhythmias. We discuss the pathophysiology of valvular disease in the context of liver failure and the guidelines by which this disease process is classified. In addition, we discuss the benefits and limitations of intraoperative TEE in evaluating this unique physiology.
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Affiliation(s)
- Justin Mitchell
- Anesthesiology, University of California, Los Angeles (UCLA) Medical Center, Los Angeles, USA
| | - Amar Alnemer
- Anesthesiology, The Ohio State University College of Medicine, Columbus, USA
| | | | - Erica Stein
- Anesthesiology, The Ohio State University Wexner Medical Center, Columbus, USA
| | - Leonid Gorelik
- Anesthesiology, The Ohio State University Wexner Medical Center, Columbus, USA
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Lizaola-Mayo B, Vargas HE. Hepatorenal Syndrome-Acute Kidney Injury in Liver Transplantation. Clin Gastroenterol Hepatol 2023; 21:S20-S26. [PMID: 37625863 DOI: 10.1016/j.cgh.2023.06.010] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Revised: 05/18/2023] [Accepted: 06/07/2023] [Indexed: 08/27/2023]
Abstract
Hepatorenal syndrome (HRS) is a serious complication of cirrhosis. HRS nomenclature has recently changed to HRS-AKI (acute kidney injury). HRS is a complex response to chronic vasodilatory changes brought about by portal hypertension and exacerbated by inflammatory responses that portends poor prognosis to patients with cirrhosis. This syndrome is commonly seen in the setting of infections, particularly spontaneous bacterial peritonitis. Because of the frequency of renal injury in the patient with cirrhosis, HRS-AKI has to be considered high in the differential diagnosis of AKI. Discontinuation of potential triggering agents and elimination of pre-renal AKI, intrinsic renal disease, and structural uropathy as causes of injury are imperative on presentation. Volume expansion with albumin and vasoconstrictive drugs to counteract the underlying splanchnic vasodilation constitutes the most effective medical modality to manage this process. Although the most effective therapy is generally considered to be liver transplantation (LT), the logistic barriers of offering this life-saving therapy on time to all needing it is a major limitation. Terlipressin has been shown to reverse HRS-AKI in a significant proportion of those treated and consequently can lead to increased LT patient survival and freedom from renal replacement therapy. We will review the impact of HRS on the management of patients awaiting LT, present strategies to prevent this significant complication, and discuss major implications of recent therapeutic advances in the setting of LT.
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Affiliation(s)
| | - Hugo E Vargas
- Mayo Clinic Arizona, Liver Transplantation Center, Phoenix, Arizona.
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da Cruz Renó L, Tustumi F, Waisberg DR, Rocha-Santos V, Pinheiro RS, Macedo RA, Nacif LS, Ducatti L, De Martino RB, Trevisan AM, Carneiro-D’Albuquerque L, Andraus W. Venous thromboembolism in in-hospital cirrhotic patients: A systematic review. Front Med (Lausanne) 2022; 9:1027882. [PMID: 36419795 PMCID: PMC9676642 DOI: 10.3389/fmed.2022.1027882] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Accepted: 10/14/2022] [Indexed: 08/30/2023] Open
Abstract
INTRODUCTION Patients with liver cirrhosis are at a higher risk of hospitalization. The present review aimed to assess the risk of thromboembolism and its burden on hospitalized cirrhotic patients. MATERIALS AND METHODS A systematic review (PROSPERO: CRD42021256869) was conducted in PubMed, Embase, Cochrane, Lilacs, and a manual search of references. It evaluated studies that compare cirrhotic patients with venous thromboembolism (VTE) with cirrhotic patients without VTE or studies that compare cirrhotic patients with non-cirrhotic patients. No restrictions were set for the date of publication or language. The last search was conducted in June 2021. RESULTS After selection, 17 studies were included from an initial search of 5,323 articles. The chronic liver disease etiologies comprise viral, alcohol, autoimmune, NASH (non-alcoholic steatohepatitis), cryptogenic, hemochromatosis, cholestasis, and drug-related. The included studies were conflicted regarding the outcomes of VTE, pulmonary embolism, or bleeding. Patients with cirrhosis associated with VTE had prolonged length of hospital stay, and patients with cirrhosis were at higher risk of portal thrombosis. CONCLUSION In-hospital cirrhotic patients are a heterogeneous group of patients that may present both thrombosis and bleeding risk. Clinicians should take extra caution to apply both prophylactic and therapeutic anticoagulation strategies. SYSTEMATIC REVIEW REGISTRATION [https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42021256869].
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Affiliation(s)
| | - Francisco Tustumi
- Transplantation Unit, Department of Gastroenterology, Universidade de São Paulo, São Paulo, Brazil
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9
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Königshofer P, Hofer BS, Brusilovskaya K, Simbrunner B, Petrenko O, Wöran K, Herac M, Stift J, Lampichler K, Timelthaler G, Bauer D, Hartl L, Robl B, Sibila M, Podesser BK, Oberhuber G, Schwabl P, Mandorfer M, Trauner M, Reiberger T. Distinct structural and dynamic components of portal hypertension in different animal models and human liver disease etiologies. Hepatology 2022; 75:610-622. [PMID: 34716927 PMCID: PMC9299647 DOI: 10.1002/hep.32220] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Revised: 10/17/2021] [Accepted: 10/28/2021] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND AIMS Liver fibrosis is the static and main (70%-80%) component of portal hypertension (PH). We investigated dynamic components of PH by a three-dimensional analysis based on correlation of hepatic collagen proportionate area (CPA) with portal pressure (PP) in animals or HVPG in patients. APPROACH AND RESULTS Different animal models (bile duct ligation: n = 31, carbon tetrachloride: n = 12, thioacetamide: n = 12, choline-deficient high-fat diet: n = 12) and patients with a confirmed single etiology of cholestatic (primary biliary cholangitis/primary sclerosing cholangitis: n = 16), alcohol-associated (n = 22), and metabolic (NASH: n = 19) liver disease underwent CPA quantification on liver specimens/biopsies. Based on CPA-to-PP/HVPG correlation, potential dynamic components were identified in subgroups of animals/patients with lower-than-expected and higher-than-expected PP/HVPG. Dynamic PH components were validated in a patient cohort (n = 245) using liver stiffness measurement (LSM) instead of CPA. CPA significantly correlated with PP in animal models (Rho = 0.531; p < 0.001) and HVPG in patients (Rho = 0.439; p < 0.001). Correlation of CPA with PP/HVPG varied across different animal models and etiologies in patients. In models, severity of hyperdynamic circulation and specific fibrosis pattern (portal fibrosis: p = 0.02; septa width: p = 0.03) were associated with PH severity. In patients, hyperdynamic circulation (p = 0.04), vascular dysfunction/angiogenesis (VWF-Ag: p = 0.03; soluble vascular endothelial growth factor receptor 1: p = 0.03), and bile acids (p = 0.04) were dynamic modulators of PH. The LSM-HVPG validation cohort confirmed these and also indicated IL-6 (p = 0.008) and hyaluronic acid (HA: p < 0.001) as dynamic PH components. CONCLUSIONS The relative contribution of "static" fibrosis on PH severity varies by type of liver injury. Next to hyperdynamic circulation, increased bile acids, VWF-Ag, IL-6, and HA seem to indicate a pronounced dynamic component of PH in patients.
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Affiliation(s)
- Philipp Königshofer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Experimental Hepatic Hemodynamic Lab (HEPEX)Medical University of ViennaViennaAustria,Christian Doppler Laboratory for Portal Hypertension and Liver FibrosisMedical University of ViennaViennaAustria,Ludwig Boltzmann Institute for Rare and Undiagnosed DiseasesViennaAustria,CeMM Research Center for Molecular Medicine of the Austrian Academy of SciencesViennaAustria
| | - Benedikt Silvester Hofer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Experimental Hepatic Hemodynamic Lab (HEPEX)Medical University of ViennaViennaAustria,Christian Doppler Laboratory for Portal Hypertension and Liver FibrosisMedical University of ViennaViennaAustria,Ludwig Boltzmann Institute for Rare and Undiagnosed DiseasesViennaAustria
| | - Ksenia Brusilovskaya
- Division of Gastroenterology and Hepatology, Department of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Experimental Hepatic Hemodynamic Lab (HEPEX)Medical University of ViennaViennaAustria,Christian Doppler Laboratory for Portal Hypertension and Liver FibrosisMedical University of ViennaViennaAustria,Ludwig Boltzmann Institute for Rare and Undiagnosed DiseasesViennaAustria,CeMM Research Center for Molecular Medicine of the Austrian Academy of SciencesViennaAustria
| | - Benedikt Simbrunner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Experimental Hepatic Hemodynamic Lab (HEPEX)Medical University of ViennaViennaAustria,Christian Doppler Laboratory for Portal Hypertension and Liver FibrosisMedical University of ViennaViennaAustria,Ludwig Boltzmann Institute for Rare and Undiagnosed DiseasesViennaAustria,CeMM Research Center for Molecular Medicine of the Austrian Academy of SciencesViennaAustria,Vienna Hepatic Hemodynamic Laboratoy, Division of Gastroenterology and Hepatology, Department of Medicine IIIMedical University of ViennaViennaAustria
| | - Oleksandr Petrenko
- Division of Gastroenterology and Hepatology, Department of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Experimental Hepatic Hemodynamic Lab (HEPEX)Medical University of ViennaViennaAustria,Christian Doppler Laboratory for Portal Hypertension and Liver FibrosisMedical University of ViennaViennaAustria,Ludwig Boltzmann Institute for Rare and Undiagnosed DiseasesViennaAustria,CeMM Research Center for Molecular Medicine of the Austrian Academy of SciencesViennaAustria
| | - Katharina Wöran
- Department of PathologyMedical University of ViennaViennaAustria
| | - Merima Herac
- Department of PathologyMedical University of ViennaViennaAustria
| | - Judith Stift
- Department of PathologyMedical University of ViennaViennaAustria
| | - Katharina Lampichler
- Department of Radiology and Nuclear MedicineMedical University of ViennaViennaAustria
| | - Gerald Timelthaler
- The Institute of Cancer ResearchDepartment of Medicine IMedical University of ViennaViennaAustria
| | - David Bauer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Experimental Hepatic Hemodynamic Lab (HEPEX)Medical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic Laboratoy, Division of Gastroenterology and Hepatology, Department of Medicine IIIMedical University of ViennaViennaAustria
| | - Lukas Hartl
- Division of Gastroenterology and Hepatology, Department of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Experimental Hepatic Hemodynamic Lab (HEPEX)Medical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic Laboratoy, Division of Gastroenterology and Hepatology, Department of Medicine IIIMedical University of ViennaViennaAustria
| | - Bernhard Robl
- Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer CenterMedical University of ViennaViennaAustria
| | - Maria Sibila
- Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer CenterMedical University of ViennaViennaAustria
| | - Bruno K. Podesser
- Center for Biomedical ResearchMedical University of ViennaViennaAustria
| | - Georg Oberhuber
- INNPATHInstitute of Pathology, University Hospital of InnsbruckInnsbruckAustria
| | - Philipp Schwabl
- Division of Gastroenterology and Hepatology, Department of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Experimental Hepatic Hemodynamic Lab (HEPEX)Medical University of ViennaViennaAustria,Christian Doppler Laboratory for Portal Hypertension and Liver FibrosisMedical University of ViennaViennaAustria,Ludwig Boltzmann Institute for Rare and Undiagnosed DiseasesViennaAustria,CeMM Research Center for Molecular Medicine of the Austrian Academy of SciencesViennaAustria,Vienna Hepatic Hemodynamic Laboratoy, Division of Gastroenterology and Hepatology, Department of Medicine IIIMedical University of ViennaViennaAustria
| | - Mattias Mandorfer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic Laboratoy, Division of Gastroenterology and Hepatology, Department of Medicine IIIMedical University of ViennaViennaAustria
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Experimental Hepatic Hemodynamic Lab (HEPEX)Medical University of ViennaViennaAustria,Christian Doppler Laboratory for Portal Hypertension and Liver FibrosisMedical University of ViennaViennaAustria,Ludwig Boltzmann Institute for Rare and Undiagnosed DiseasesViennaAustria,CeMM Research Center for Molecular Medicine of the Austrian Academy of SciencesViennaAustria,Vienna Hepatic Hemodynamic Laboratoy, Division of Gastroenterology and Hepatology, Department of Medicine IIIMedical University of ViennaViennaAustria
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10
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Yi Z, Zhang M, Ma Z, Tuo B, Liu A, Deng Z, Zhao Y, Li T, Liu X. Role of the posterior mucosal defense barrier in portal hypertensive gastropathy. Biomed Pharmacother 2021; 144:112258. [PMID: 34614465 DOI: 10.1016/j.biopha.2021.112258] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 09/24/2021] [Accepted: 09/26/2021] [Indexed: 12/15/2022] Open
Abstract
Portal hypertensive gastropathy (PHG) is a complication of cirrhotic or noncirrhotic portal hypertension. PHG is very important in the clinic because it can cause acute or even massive blood loss, and its treatment efficacy and prognosis are poor. Currently, the incidence of PHG in patients with cirrhosis is 20-80%, but its pathogenesis is complicated and poorly understood. Studies have shown that portal hypertension can cause changes in gastric mucosal microcirculation hemodynamics, leading to changes in gastric mucosal histology and function and thereby weakening the mucosal defense barrier. However, no specific drug treatment plans are currently available. This article reviews the current literature to further our understanding of the mechanism underlying PHG and the relationship between PHG and the posterior mucosal defense barrier and to explore new therapeutic targets.
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Affiliation(s)
- Zhiqiang Yi
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, China; Department of Gastroenterology, Fuling Central Hospital of Chongqing City, Chongqing, China
| | - Minglin Zhang
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, China
| | - Zhiyuan Ma
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, China; Digestive Disease Institute of Guizhou Province, Zunyi, Guizhou Province, China; Department of Thyroid and Breast Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, China
| | - Biguang Tuo
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, China; Digestive Disease Institute of Guizhou Province, Zunyi, Guizhou Province, China
| | - Aimin Liu
- Department of Gastroenterology, Fuling Central Hospital of Chongqing City, Chongqing, China
| | - Zilin Deng
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, China
| | - Yingying Zhao
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, China
| | - Taolang Li
- Department of Thyroid and Breast Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, China.
| | - Xuemei Liu
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, China; Digestive Disease Institute of Guizhou Province, Zunyi, Guizhou Province, China.
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11
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Ciccarelli M, Dawson D, Falcao-Pires I, Giacca M, Hamdani N, Heymans S, Hooghiemstra A, Leeuwis A, Hermkens D, Tocchetti CG, van der Velden J, Zacchigna S, Thum T. Reciprocal organ interactions during heart failure: a position paper from the ESC Working Group on Myocardial Function. Cardiovasc Res 2021; 117:2416-2433. [PMID: 33483724 PMCID: PMC8562335 DOI: 10.1093/cvr/cvab009] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Revised: 11/20/2021] [Accepted: 01/08/2021] [Indexed: 12/13/2022] Open
Abstract
Heart failure-either with reduced or preserved ejection fraction (HFrEF/HFpEF)-is a clinical syndrome of multifactorial and gender-dependent aetiology, indicating the insufficiency of the heart to pump blood adequately to maintain blood flow to meet the body's needs. Typical symptoms commonly include shortness of breath, excessive fatigue with impaired exercise capacity, and peripheral oedema, thereby alluding to the fact that heart failure is a syndrome that affects multiple organ systems. Patients suffering from progressed heart failure have a very limited life expectancy, lower than that of numerous cancer types. In this position paper, we provide an overview regarding interactions between the heart and other organ systems, the clinical evidence, underlying mechanisms, potential available or yet-to-establish animal models to study such interactions and finally discuss potential new drug interventions to be developed in the future. Our working group suggests that more experimental research is required to understand the individual molecular mechanisms underlying heart failure and reinforces the urgency for tailored therapeutic interventions that target not only the heart but also other related affected organ systems to effectively treat heart failure as a clinical syndrome that affects and involves multiple organs.
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Affiliation(s)
- Michele Ciccarelli
- University of Salerno, Department of Medicine, Surgery and Dentistry, Via S. Allende 1, 84081, Baronissi(Salerno), Italy
| | - Dana Dawson
- School of Medicine and Dentistry, University of Aberdeen, Aberdeen AB25 2DZ, UK
| | - Inês Falcao-Pires
- Department of Surgery and Physiology, Cardiovascular Research and Development Center, Faculty of Medicine of the University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319, Porto, Portugal
| | - Mauro Giacca
- King’s College London, Molecular Medicine Laboratory, 125 Caldharbour Lane, London WC2R2LS, United Kingdom
- International Centre for Genetic Engineering and Biotechnology (ICGEB), Padriciano, 99, 34149 Trieste, Italy
- Department of Medicine, Surgery and Health Sciences, University of Trieste, Strada di Fiume, 447, 34129 Trieste, Italy
| | - Nazha Hamdani
- Department of Clinical Pharmacology and Molecular Cardiology, Institute of Physiology, Ruhr University Bochum, Universitätsstraße 150, D-44801 Bochum, Germany
- Department of Cardiology, St. Josef-Hospital, Ruhr University Bochum, Universitätsstraße 150, D-44801 Bochum, Germany
| | - Stéphane Heymans
- Centre for Molecular and Vascular Biology, KU Leuven, Herestraat 49, Bus 911, 3000 Leuven, Belgium
- Department of Cardiology, Maastricht University, CARIM School for Cardiovascular Diseases, Universiteitssingel 50, 6229 ER Maastricht, the Netherlands
- ICIN-Netherlands Heart Institute, Holland Heart House, Moreelsepark 1, 3511 EP Utrecht, the Netherlands
| | - Astrid Hooghiemstra
- Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, De Boelelaan 1118, 1081HZ, Amsterdam, The Netherlands
- Department of Medical Humanities, Amsterdam Public Health Research Institute, Amsterdam UMC, Location VUmc, De Boelelaan 1089a, 1081HV, Amsterdam, The Netherlands
| | - Annebet Leeuwis
- Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, De Boelelaan 1118, 1081HZ, Amsterdam, The Netherlands
| | - Dorien Hermkens
- Department of Pathology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105AZ, Amsterdam, the Netherlands
| | - Carlo Gabriele Tocchetti
- Department of Translational Medical Sciences and Interdepartmental Center of Clinical and Translational Research (CIRCET), Federico II University, Naples, Italy
| | - Jolanda van der Velden
- Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Physiology, Amsterdam Cardiovascular Sciences, De Boelelaan 1118, 1081HZ Amsterdam, the Netherlands
| | - Serena Zacchigna
- Department of Medicine, Surgery and Health Sciences, University of Trieste, Strada di Fiume, 447, 34129 Trieste, Italy
- Cardiovascular Biology Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB), Padriciano, 99, 34149 Trieste, Italy
| | - Thomas Thum
- Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany
- REBIRTH Center for Translational Regenerative Medicine, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany
- Fraunhofer Institute of Toxicology and Experimental Medicine, Nicolai-Fuchs-Str. 1, D-30625 Hannover, Germany
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12
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Wong F, Blendis L. Historical Aspects of Ascites and the Hepatorenal Syndrome. Clin Liver Dis (Hoboken) 2021; 18:14-27. [PMID: 34745581 PMCID: PMC8555459 DOI: 10.1002/cld.1090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Accepted: 01/03/2021] [Indexed: 02/04/2023] Open
Abstract
Content available: Author Interview and Audio Recording.
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Affiliation(s)
- Florence Wong
- Department of MedicineDivision of GastroenterologyUniversity of TorontoTorontoONCanada
| | - Laurence Blendis
- Department of MedicineDivision of GastroenterologyUniversity of TorontoTorontoONCanada
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13
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Usefulness of diffusion derived vessel density computed from a simplified IVIM imaging protocol: An experimental study with rat biliary duct blockage induced liver fibrosis. Magn Reson Imaging 2021; 84:115-123. [PMID: 34619291 DOI: 10.1016/j.mri.2021.09.013] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Revised: 08/23/2021] [Accepted: 09/30/2021] [Indexed: 01/10/2023]
Abstract
OBJECTIVES Liver vessel density can be evaluated by DDVD (diffusion derived vessel density): DDVD(b0b1) = Sb0/ROIarea0 - Sb1/ROIarea1, where Sb0 and Sb1 refer to the liver signal when b is 0 or 1 s/mm2. Sb1 and ROIarea1 may be replaced by other b-values. With a rat biliary duct ligation (BDL) model, this study assesses the usefulness of liver DDVD computed from a simplified IVIM imaging protocol using b = 25 and b = 50 to replace b = 1 s/mm2, alone and in combination with other IVIM parameters. METHODS Male Sprague-Dawley rats were used. The rat number was 5, 5, 5, and 3 respectively, for the timepoints of 7, 14, 21, 28 days post-BDL surgery. 12 rats had partial biliary duct recanalization performed after the rats had BDL for 7 days and then again followed-up for a mean of 14 days. Liver diffusion MRIs were acquired at 3.0 T with a b-value distribution of 0, 25, 50, 75, 100, 150, 300, 700, 1000 s/mm2. DDVDmean (control rats n = 6) was the mean of DDVD(b0b25) and DDVD(b0b50). IVIM fitting started from b = 0 s/mm2 with segmented fitting and a threshold b of 50 s/mm2 (n = 5 for control rats). Three 3-D spaces were constructed using a combination of the four diffusion parameters. RESULTS The control rats and BDL rats (n = 18) had a liver DDVDmean of 84.0 ± 26.2 and 44.7 ± 14.4 au/pixel (p < 0.001). All 3-D spaces totally separated healthy livers and all fibrotic livers (n = 30, BDL rats and recanalization rats). The mean relative distance between healthy liver cluster and fibrotic liver cluster was 0.331 for PF, Dslow, and Dfast; 0.381 for PF, Dfast, and DDVDmean; and 0.384 for PF, Dslow, and DDVDmean. CONCLUSION A combination of PF, Dslow, and Dfast allows total separation of healthy livers and fibrotic livers and the integration of DDVD improved the separation.
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Sauerbruch T, Hennenberg M, Trebicka J, Beuers U. Bile Acids, Liver Cirrhosis, and Extrahepatic Vascular Dysfunction. Front Physiol 2021; 12:718783. [PMID: 34393832 PMCID: PMC8358446 DOI: 10.3389/fphys.2021.718783] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Accepted: 06/29/2021] [Indexed: 12/12/2022] Open
Abstract
The bile acid pool with its individual bile acids (BA) is modulated in the enterohepatic circulation by the liver as the primary site of synthesis, the motility of the gallbladder and of the intestinal tract, as well as by bacterial enzymes in the intestine. The nuclear receptor farnesoid X receptor (FXR) and Gpbar1 (TGR5) are important set screws in this process. Bile acids have a vasodilatory effect, at least according to in vitro studies. The present review examines the question of the extent to which the increase in bile acids in plasma could be responsible for the hyperdynamic circulatory disturbance of liver cirrhosis and whether modulation of the bile acid pool, for example, via administration of ursodeoxycholic acid (UDCA) or via modulation of the dysbiosis present in liver cirrhosis could influence the hemodynamic disorder of liver cirrhosis. According to our analysis, the evidence for this is limited. Long-term studies on this question are lacking.
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Affiliation(s)
- Tilman Sauerbruch
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
| | - Martin Hennenberg
- Department of Urology I, University Hospital, LMU Munich, Munich, Germany
| | - Jonel Trebicka
- Translational Hepatology, Medical Department, University of Frankfurt, Frankfurt, Germany
| | - Ulrich Beuers
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, location AMC, Amsterdam, Netherlands
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Yu S, Sun L, Wang H, Jiang J, Zhou Q. Autonomic regulation of imbalance-induced myocardial fibrosis and its mechanism in rats with cirrhosis. Exp Ther Med 2021; 22:1040. [PMID: 34373726 PMCID: PMC8343770 DOI: 10.3892/etm.2021.10472] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Accepted: 06/10/2021] [Indexed: 12/13/2022] Open
Abstract
The aim of the present study was to investigate the changes in cardiac function and myocardial damage in rats with cirrhosis. In addition, a secondary aim was to explore any potential changes in the expression levels of β1-adrenergic (β1) and muscarinic acetylcholine (M2) receptors . A cirrhotic cardiomyopathy (CCM) rat model was established by CCL4-oil solution for subcutaneous injection into the neck. Pathological changes in the liver and myocardial tissues were detecting by H&E staining and Masson trichrome staining. Furthermore, changes in the levels of myocardial enzymes lactate dehydrogenase (LDH), creatine kinase isoenzyme (CK-MB) and troponin in serum were measured by ELISA. The myocardial samples were homogenized and centrifuged. Subsequently, the supernatant was collected for detecting the expression of interleukins in myocardial tissue. Changes in the levels of inflammatory factors, IL-1, IL-2 and IL-6 both in the serum and myocardial tissue were determined by ELISA. Changes in echocardiographic measurements were evaluated using high-frequency ultrasound and the expression levels of β1 and M2 receptors in myocardial tissues were determined by western blotting. The normal lobular structure in liver tissues was found to be disappeared 8 weeks after modeling, which was replaced by pseudolobules in the rats in the CCM group. In addition, the myocardial cells were observed to be swollen and disorderly arranged. Compared with those in the control group, the left ventricular end-systolic and end-diastolic dimensions, interventricular septal dimension and LAD in rats in the CCM8 group were found to be significantly increased. The levels of myocardial enzymes LDH, CK-MB and cardiac troponin in the serum were also revealed to be significantly increased in the CCM8 group. Additionally, the levels of IL-1 and IL-6 in both serum and myocardial tissues were significantly increased in rats in the CCM8 group. However, the levels of IL-2 in both serum and myocardial tissues were decreased, which were observed alongside reductions in myocardial β1 and M2 receptor protein expression in the myocardial tissues. Taken together, these results indicate that inflammatory factors may be involved in mediating damage to the myocardium in rats with cirrhosis. During cirrhosis-induced cardiac dysfunction, there may exist a mechanism for downregulation of autonomic nerve system.
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Affiliation(s)
- Shanshan Yu
- Department of Ultrasound, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China
| | - Lei Sun
- Department of Ultrasound, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China
| | - Hua Wang
- Department of Ultrasound, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China
| | - Jue Jiang
- Department of Ultrasound, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China
| | - Qi Zhou
- Department of Ultrasound, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China
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Habib S. Portal Hypertensive Gastropathy. VARICEAL BLEEDING IN LIVER CIRRHOSIS 2021:123-140. [DOI: 10.1007/978-981-15-7249-4_8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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The Presence of Ascites Affects the Predictive Value of HVPG on Early Rebleeding in Patients with Cirrhosis. Gastroenterol Res Pract 2020; 2020:1329857. [PMID: 33299405 PMCID: PMC7710417 DOI: 10.1155/2020/1329857] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2020] [Revised: 08/09/2020] [Accepted: 11/12/2020] [Indexed: 12/12/2022] Open
Abstract
Background and Aims Gastroesophageal variceal bleeding is a serious complication of portal hypertension in cirrhotic patients and could be predicted by hepatic venous pressure gradient (HVPG). However, whether the presence of ascites affects the prognostic value of HVPG for patients with acute variceal bleeding is still unknown. This retrospective study is aimed at investigating the influence of ascites on predictive performance of HVPG for early rebleeding in cirrhotic patients with acute variceal bleeding. Methods In this retrospective study, a total of 148 patients with cirrhosis hospitalized for acute variceal bleeding who underwent HVPG measurement and endoscopic variceal ligation (EVL) for the prevention of rebleeding were included. The receiver operating characteristic curve (ROC) and logistical regression method were employed to analyze the predictive performance of HVPG for early rebleeding. The locally weighted scatterplot smoothing approach was adopted to assess the monotonicity between bleeding risk and HVPG. Results A significantly higher HVPG level was observed in patients with early rebleeding compared to patients without rebleeding in the nonascites cohort. When using HVPG to predict early rebleeding, there was a lower area under curve in the ascites cohort compared to the nonascites cohort. HVPG was recognized as a risk factor for early rebleeding by a logistic regression model only in the nonascites cohort. An overall monotonicity in the trend of change in HVPG and risk for early rebleeding was observed in the nonascites cohort solely. Conclusion The predictive value of HVPG for early rebleeding in patients with cirrhosis that developed acute variceal bleeding is hindered by the presence of ascites.
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Xiao BH, Huang H, Wang LF, Qiu SW, Guo SW, Wáng YXJ. Diffusion MRI Derived per Area Vessel Density as a Surrogate Biomarker for Detecting Viral Hepatitis B-Induced Liver Fibrosis: A Proof-of-Concept Study. SLAS Technol 2020; 25:474-483. [PMID: 32292088 DOI: 10.1177/2472630320915838] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Liver vessel density can be evaluated by an imaging biomarker diffusion-derived vessel density (DDVD): DDVD/area(b0b2) = Sb0/ROIarea0 - Sb2/ROIarea2, where Sb0 and Sb2 refer to the liver signal when b is 0 or 2 (s/mm2); ROIarea0 and ROIarea2 refer to the region of interest (ROI) on b = 0 or 2 images; and Sb2 may be replaced by Sb15 (b = 15). This concept was validated in this study. Liver diffusion images were acquired at 1.5 T. For a scan-rescan repeatability study of six subjects, b values of 0 and 2 were used. The validation study was composed of 26 healthy volunteers and 19 consecutive suspected chronic viral hepatitis B patients, and diffusion images with b values of 0, 2, 15, 20, 30, 45, 50, 60, 80, 100, 200, 300, 600, and 800 were acquired. Four patients did not have liver fibrosis, and the rest were four stage 1, three stage 2, four stage 3, and one stage 4 patients, respectively. The intraclass correlation coefficient for repeatability was 0.994 for DDVD/area(Sb0Sb2) and 0.978 for DDVD/area(Sb0Sb15). In the validation study, DDVD/area(Sb0Sb2) and area(Sb0Sb15) were 14.80 ± 3.06 and 26.58 ± 3.97 for healthy volunteers, 10.51 ± 1.51 and 20.15 ± 2.21 for stage 1-2 fibrosis patients, and 9.42 ± 0.87 and 19.42 ± 1.89 for stage 3-4 fibrosis patients. For 16 patients where IVIM analysis was performed, a combination of DDVD/area, PF, and Dfast achieved the best differentiation for nonfibrotic livers and fibrotic livers. DDVD/area were weakly correlated with PF or Dfast. Both DDVD/area(Sb0Sb2) and area(Sb0Sb15) are useful imaging biomarkers to separate fibrotic and nonfibrotic livers, with fibrotic livers having lower measurements.
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Affiliation(s)
- Ben-Heng Xiao
- Department of Biomedical Engineering, School of Material Science and Engineering, South China University of Technology, Guangzhou, Guangdong Province, China.,Department of Imaging and Interventional Radiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR
| | - Hua Huang
- Department of Radiology, The Third People's Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong Province, China
| | - Li-Fei Wang
- Department of Radiology, The Third People's Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong Province, China
| | - Shi-Wen Qiu
- Department of Biomedical Engineering, School of Material Science and Engineering, South China University of Technology, Guangzhou, Guangdong Province, China
| | - Sheng-Wen Guo
- Department of Biomedical Engineering, School of Material Science and Engineering, South China University of Technology, Guangzhou, Guangdong Province, China
| | - Yì Xiáng J Wáng
- Department of Biomedical Engineering, School of Material Science and Engineering, South China University of Technology, Guangzhou, Guangdong Province, China
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Liu C, Liu Y, Shao R, Wang S, Wang G, Wang L, Zhang M, Hou J, Zhang C, Qi X. The predictive value of baseline hepatic venous pressure gradient for variceal rebleeding in cirrhotic patients receiving secondary prevention. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:91. [PMID: 32175384 PMCID: PMC7049047 DOI: 10.21037/atm.2019.12.143] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/01/2019] [Accepted: 12/06/2019] [Indexed: 12/25/2022]
Abstract
BACKGROUND Baseline hepatic venous pressure gradient (HVPG) has been applied for prediction of variceal rebleeding in patients after acute variceal bleeding. However, for patients receiving secondary prevention, there still lacks evidence about the predictive performance of baseline-HVPG for rebleeding. This study aims to investigate the predictive value of baseline-HVPG for variceal rebleeding in cirrhotic patients receiving secondary prevention. METHODS This retrospective study included 122 patients with cirrhosis accepting secondary prevention of variceal rebleeding in a university hospital. All the included patients had HVPG measurements before rebleeding and had at least 1-year follow-up after HVPG measurement unless the rebleeding occurred. The rebleeding rate in patients with different HVPG levels and time-dependent predictive performance of baseline-HVPG were analysed. A Cox regression model and P for trend were used to assess the rebleeding risk. RESULTS Variceal rebleeding occurred in 22 (18.0%) patients during 1-year follow-up. No significant difference was observed in rebleeding rate between patients with HVPG <16 mmHg and HVPG ≥16 mmHg (17.91% vs. 26.41%, P=0.200). A decreasing trend was observed in area under the curve of HVPG for predicting rebleeding by time. The multivariate Cox model showed an overall decreasing trend in hazard ratio of rebleeding (vs. patients with HVPG <12 mmHg) for patients with 12≤ HVPG <16 mmHg, 16≤ HVPG <20 mmHg and HVPG ≥20 mmHg; besides, an increasing P for trend was observed. CONCLUSIONS A single baseline-HVPG measurement was insufficient for predicting rebleeding in patients with cirrhosis who received secondary prevention.
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Affiliation(s)
- Chuan Liu
- Department of Hepatology Unit and Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Yanna Liu
- Department of Hepatology Unit and Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Ruoyang Shao
- Department of Hepatology Unit and Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Sining Wang
- Department of Gastroenterology, Shandong Provincial Hospital, Shandong University, Jinan 250012, China
| | - Guangchuan Wang
- Department of Gastroenterology, Shandong Provincial Hospital, Shandong University, Jinan 250012, China
| | - Lifen Wang
- Department of Gastroenterology, Shandong Provincial Hospital, Shandong University, Jinan 250012, China
| | - Mingyan Zhang
- Department of Gastroenterology, Shandong Provincial Hospital, Shandong University, Jinan 250012, China
| | - Jinlin Hou
- Department of Hepatology Unit and Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Chunqing Zhang
- Department of Gastroenterology, Shandong Provincial Hospital, Shandong University, Jinan 250012, China
| | - Xiaolong Qi
- Department of Hepatology Unit and Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
- CHESS Center, Institute of Portal Hypertension, The First Hospital of Lanzhou University, Lanzhou 730000, China
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20
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Shenoda B, Boselli J. Vascular syndromes in liver cirrhosis. Clin J Gastroenterol 2019; 12:387-397. [PMID: 30980261 DOI: 10.1007/s12328-019-00956-0] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2018] [Accepted: 02/20/2019] [Indexed: 02/08/2023]
Abstract
Liver cirrhosis is associated with multiple vascular syndromes affecting almost all body systems. Many of these syndromes are directly related to impaired liver function and sometimes reversible after liver transplantation while others arise secondary to portal hypertension and ascites. Altered expression of angiogenic and vasoactive compounds (most importantly nitric oxide), endothelial dysfunction, dysregulated neurohormonal control, and systemic inflammatory state play differential roles in mediating homeostatic instability and abnormal vasogenic response. Important vascular features encountered in liver disease include portal hypertension, splanchnic overflow, abnormal angiogenesis and shunts, portopulmonary syndrome, hepatopulmonary syndrome, and systemic hyperdynamic circulation. Redistribution of effective circulatory volume deviating from vital organs and pooling in splanchnic circulation is also encountered in liver patients which may lead to devastating outcomes as hepatorenal syndrome. Etiologically, vascular syndromes are not isolated phenomena and vascular dysfunction in one system may lead to the development of another in a different system. This review focuses on understanding the pathophysiological factors underlying vascular syndromes related to chronic liver disease and the potential links among them. Many of these syndromes are associated with high mortality, thus it is crucial to look for early biomarkers for these syndromes and develop novel preventive and therapeutic strategies.
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Affiliation(s)
- Botros Shenoda
- Department of Medicine, Drexel University College of Medicine, Philadelphia, PA, 19102, USA
| | - Joseph Boselli
- Department of Medicine, Drexel University College of Medicine, Philadelphia, PA, 19102, USA. .,Drexel Internal Medicine, 205 N. Broad Street, Philadelphia, 19107, USA.
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21
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Li T, Che-Nordin N, Wáng YXJ, Rong PF, Qiu SW, Zhang SW, Zhang P, Jiang YF, Chevallier O, Zhao F, Xiao XY, Wang W. Intravoxel incoherent motion derived liver perfusion/diffusion readouts can be reliable biomarker for the detection of viral hepatitis B induced liver fibrosis. Quant Imaging Med Surg 2019; 9:371-385. [PMID: 31032185 PMCID: PMC6462566 DOI: 10.21037/qims.2019.02.11] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2019] [Accepted: 02/25/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Recent two studies reported that intravoxel incoherent motion (IVIM) analysis can separate healthy livers and viral hepatitis B (VHB) induced liver fibrosis. However, in these two studies the starting b value for bi-exponential decay analysis was b =10 and 15 s/mm2 respectively. The current study has two primary aims. The first is to further confirm the diagnostic value of IVIM in detecting liver fibrosis. The second is to test whether by sampling very low b value densely, then b =0 s/mm2 image could be included to improve IVIM's diagnostic performance. METHODS This was a prospective study with data acquired at the Third Xiangya Hospital of Central South University, Changsha, China. Healthy volunteers and patients suspected of VHB induced liver fibrosis with liver biopsy performed, as well as hepatocellular carcinoma patients scheduled for surgery, were recruited. All the hepatocellular carcinoma patients had liver fibrosis. After exclusions based on pre-defined criteria for image data quality, for IVIM analysis this study included 20 healthy volunteers; 4 chronic VHB patients with biopsy showing no liver fibrosis; 11 stage-1 liver fibrosis patients, 10 stage-2 liver fibrosis patients, 2 stage-3 liver fibrosis patients, and 5 stage-4 liver fibrosis patients. In the liver fibrosis patients, 1, 19, and 8 cases had inflammation grade-0, grade-1, and grade-2 respectively. The reference IVIM bi-exponential decay curve fitting analysis was segmented fitting performed with b =2 s/mm2 image as the starting point and a threshold-b of 60 s/mm2. This reference fitting method was compared with threshold-b of 40 s/mm2, full fitting, fitting starting from b =0, 5, and 10 s/mm2 respectively. The potential correlation between IVIM readouts and liver function was assessed for the liver fibrosis patients. RESULTS Based on the smaller coefficient of variation (CoV) for the volunteer group and the smaller patient/volunteer ratios [= (mean measurement for patient groups)/(mean measurement for healthy volunteers)], the comparison of fitting methods favored the reference approach starting from b =2 s/mm2 with a threshold-b of 60 s/mm2. The IVIM measures of four patients without liver fibrosis resembled those of healthy subjects. PF offered the best diagnostic value for separating healthy livers and fibrotic livers, and a threshold of PF =0.1406 separated all fibrotic livers and healthy livers with an exception of one hepatocellular carcinoma patient (fibrosis grade-2/inflammation grade-2). The correlation between fibrosis grading and inflammation grading was weakly positive; while compared with fibrotic livers with inflammation grade-1, fibrotic livers with inflammation grade-2 showed a trend of higher Dfast. A weak correlation is shown with lower PF and lower Dfast associated with lower total protein, lower albumin; higher alanine transaminase, higher aspartate transaminase; higher total bilirubin, and higher direct bilirubin. CONCLUSIONS Segmented-fitting with threshold-b =60 s/mm2 and starting from non-zero very low b value outperforms other methods. IVIM has high sensitivity in detecting liver fibrosis, and PF and Dfast have potential correlation with serum liver function biomarkers. IVIM measures and liver fibrosis grading are not in a linear relationship.
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Affiliation(s)
- Ting Li
- Department of Radiology, The Third Xiangya Hospital, Central South University, Changsha 410013, China
| | - Nazmi Che-Nordin
- Department of Imaging and Interventional Radiology, Faculty of Medicine, The Chinese University of Hong Kong, New Territories, Hong Kong, China
| | - Yì Xiáng J. Wáng
- Department of Imaging and Interventional Radiology, Faculty of Medicine, The Chinese University of Hong Kong, New Territories, Hong Kong, China
| | - Peng-Fei Rong
- Department of Radiology, The Third Xiangya Hospital, Central South University, Changsha 410013, China
| | - Shi-Wen Qiu
- Department of Imaging and Interventional Radiology, Faculty of Medicine, The Chinese University of Hong Kong, New Territories, Hong Kong, China
| | - Sheng-Wang Zhang
- Department of Radiology, The Third Xiangya Hospital, Central South University, Changsha 410013, China
| | - Pan Zhang
- Department of Infectious Diseases, The Third Xiangya Hospital, Central South University, Changsha 410013, China
| | - Yong-Fang Jiang
- Liver Diseases Research Center, The Second Xiangya Hospital, Central South University, Changsha 410013, China
| | - Olivier Chevallier
- Department of Vascular and Interventional Radiology, François-Mitterrand Teaching Hospital, Université de Bourgogne, Dijon, France
| | - Feng Zhao
- Department of Radiation Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310000, China
| | - Xiao-Yi Xiao
- Department of Radiology, The Third Xiangya Hospital, Central South University, Changsha 410013, China
| | - Wei Wang
- Department of Radiology, The Third Xiangya Hospital, Central South University, Changsha 410013, China
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Huang H, Che-Nordin N, Wang LF, Xiao BH, Chevallier O, Yun YX, Guo SW, Wáng YXJ. High performance of intravoxel incoherent motion diffusion MRI in detecting viral hepatitis-b induced liver fibrosis. ANNALS OF TRANSLATIONAL MEDICINE 2019; 7:39. [PMID: 30906743 PMCID: PMC6389585 DOI: 10.21037/atm.2018.12.33] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/05/2018] [Accepted: 12/23/2018] [Indexed: 12/17/2022]
Abstract
BACKGROUND Recently a small cohort study demonstrated that intravoxel incoherent motion (IVIM) diffusion MRI can detect early stage liver fibrosis. Using modified IVIM data acquisition parameters, the current study aims to confirm this finding. METHODS Twenty-six healthy volunteers, three patients of chronic viral hepatitis-b but without fibrosis and one mild liver steatosis subject, and 12 viral hepatitis-b patients with fibrosis (stage 1-2=7, stage 3-4=5) were included in this study. With a 1.5-T MR scanner and respiration-gating, IVIM diffusion imaging was acquired using a single-shot echo-planar sequence with a b-value series of 2, 0, 1, 15, 20, 30, 45, 50, 60, 80, 100, 200, 300, 600, 800 s/mm2. Signal measurement was performed on right liver parenchyma. The first three very low b-values were excluded to improve the curve fitting stability, and bi-exponential segmented fitting was performed using the 12 b-values of 15~800 s/mm2. Both threshold b-values of 60 s/mm2 and 200 s/mm2 were tested. With a 3-dimensional tool, Dslow (D), PF (f) and Dfast (D*) values were placed along the x-axis, y-axis, and z-axis, and a plane was defined to separate healthy volunteers from liver fibrosis patients. RESULTS Threshold b-value of 60 s/mm2 was preferred over 200 s/mm2 for separating healthy volunteers and liver fibrosis patients. The IVIM measures of the four patients without fibrosis resembled those of healthy volunteers. When threshold b-value =60 s/mm2 was applied, PF (PF <6.49%) could differentiate healthy livers and all fibrotic livers with 100% sensitivity and specificity. For the patients' measurement, PF and Dfast were highly correlated with a Pearson correlation coefficient r of 0.865 (P<0.001); while the correlations between slow diffusion compartment (Dslow) and fast diffusion compartment (Dfast or PF) were not statistically significant. CONCLUSIONS This study confirms previous report that IVIM diffusion MRI has high diagnostic performance in detecting viral hepatitis-b induced liver fibrosis.
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Affiliation(s)
- Hua Huang
- Department of Radiology, The Third People's Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen 518000, China
| | - Nazmi Che-Nordin
- Department of Imaging and Interventional Radiology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China
| | - Li-Fei Wang
- Department of Radiology, The Third People's Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen 518000, China
| | - Ben-Heng Xiao
- Department of Biomedical Engineering, South China University of Technology, Guangzhou 510000, China
| | - Olivier Chevallier
- Department of Vascular and Interventional Radiology, François-Mitterrand Teaching Hospital, Université de Bourgogne, Dijon Cedex, France
| | - Yong-Xing Yun
- Department of Radiology, The Third People's Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen 518000, China
| | - Sheng-Wen Guo
- Department of Biomedical Engineering, South China University of Technology, Guangzhou 510000, China
| | - Yì Xiáng J Wáng
- Department of Imaging and Interventional Radiology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China
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23
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Annicchiarico BE, Santonocito C, Siciliano M, Scapaticci M, Guarino D, Di Stasi C, Riccioni ME, Di Stasio E, Capoluongo E, Gasbarrini A. ACE I allele is associated with more severe portal hypertension in patients with liver cirrhosis: A pilot study. Dig Liver Dis 2019; 51:293-296. [PMID: 30236768 DOI: 10.1016/j.dld.2018.08.005] [Citation(s) in RCA: 5] [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] [Received: 01/10/2018] [Revised: 08/03/2018] [Accepted: 08/04/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND In liver cirrhosis, the renin-angiotensin-aldosterone system is involved in the pathogenesis of portal hypertension. Its effector, angiotensin II, is generated by angiotensin-converting enzyme (ACE). Serum ACE levels are affected by I/D polymorphism of its gene, with alleles I and D being associated, respectively, with lesser and greater activity of the enzyme. In cirrhotic patients carrying the ACE I allele, an increased risk for gastro-oesophageal varices was observed. AIM The aim of our study was to evaluate whether ACE I/D polymorphism influenced portal pressure. METHODS Fifty-one consecutive cirrhotic patients were divided based on ACE genotype (DD, ID, and II). Kidney and liver function tests, upper endoscopy, and hepatic venous pressure gradient measurement (HVPG) were performed in all patients. RESULTS The presence of the ACE I allele was associated with a higher HVPG value (18.7±6.4 vs 10.3±6.3mmHg; P<.001), higher frequency of large gastrooesophageal varices (59.3% vs 25.0%; P<.05), and higher frequency of variceal bleeding (63.0% vs 29.2%; P<.05). No significant differences were found between patients with and those without the ACE I allele regarding Child-Pugh score, MELD score, ascites, and hepatic encephalopathy. CONCLUSION ACE I/D polymorphism seems to influence the severity of portal hypertension and the risk of variceal bleeding in liver cirrhosis, regardless of the severity of liver disease.
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Affiliation(s)
- Brigida E Annicchiarico
- Department of Internal Medicine, Fondazione Policlinico Universitario Agostino Gemelli IRCCS Catholic University of the Sacred Heart, Rome, Italy
| | - Concetta Santonocito
- Laboratory of Clinical Molecular Biology, Department of Biochemistry & Clinical Biochemistry, Fondazione Policlinico Universitario Agostino Gemelli IRCCS Catholic University of the Sacred Heart, Rome, Italy.
| | - Massimo Siciliano
- Department of Internal Medicine, Fondazione Policlinico Universitario Agostino Gemelli IRCCS Catholic University of the Sacred Heart, Rome, Italy
| | - Margherita Scapaticci
- Laboratory of Clinical Molecular Biology, Department of Biochemistry & Clinical Biochemistry, Fondazione Policlinico Universitario Agostino Gemelli IRCCS Catholic University of the Sacred Heart, Rome, Italy; Laboratory Medicine Department, San Camillo Hospital, Treviso, Italy
| | - Donatella Guarino
- Laboratory of Clinical Molecular Biology, Department of Biochemistry & Clinical Biochemistry, Fondazione Policlinico Universitario Agostino Gemelli IRCCS Catholic University of the Sacred Heart, Rome, Italy
| | - Carmine Di Stasi
- Department of Bioimaging and Radiological Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS Catholic University of the Sacred Heart, Rome, Italy
| | - Maria E Riccioni
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS Catholic University of the Sacred Heart, Rome, Italy
| | - Enrico Di Stasio
- Laboratory of Clinical Molecular Biology, Department of Biochemistry & Clinical Biochemistry, Fondazione Policlinico Universitario Agostino Gemelli IRCCS Catholic University of the Sacred Heart, Rome, Italy
| | - Ettore Capoluongo
- Laboratory of Clinical Molecular Biology, Department of Biochemistry & Clinical Biochemistry, Fondazione Policlinico Universitario Agostino Gemelli IRCCS Catholic University of the Sacred Heart, Rome, Italy
| | - Antonio Gasbarrini
- Department of Internal Medicine, Fondazione Policlinico Universitario Agostino Gemelli IRCCS Catholic University of the Sacred Heart, Rome, Italy
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Chang CC, Lee WS, Chuang CL, Hsin IF, Hsu SJ, Huang HC, Lee FY, Lee SD. Effect of ivabradine, a funny current inhibitor, on portal hypertensive rats. J Chin Med Assoc 2019; 82:19-24. [PMID: 30839398 DOI: 10.1016/j.jcma.2018.06.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Abstract
BACKGROUND Ivabradine is a funny current inhibitor which is administered to patients with congestive heart failure to reduce their heart rate (HR) and attenuate oxidative stress. Chronic liver diseases are characterized by portal hypertension and hyperdynamic circulation with tachycardia. The present study aimed to investigate the effect of ivabradine on portal hypertension. METHODS Male Sprague-Dawley rats received partial portal vein ligation (PVL) to induce portal hypertension. The PVL rats were randomly allocated to receive either vehicle or ivabradine treatment for 10 days. Then the hemodynamic data were collected. The levels of oxidative stress markers and the mRNA expression of nitric oxide synthase (NOS) were measured in the collateral vessel, the superior mesentery artery and the liver. In addition, the collateral vascular responsiveness to arginine vasopressin (AVP) was examined in the ivabradine-treated and vehicle-treated PVL rats. RESULTS Treatment with ivabradine significantly lowered the HR (174 ± 20 vs. 374 ± 9 beats/min; p < 0.001) and the superior mesentery arterial flow (SMAf) (6.6 ± 0.3 vs. 9.1 ± 0.7 mL/min/100 g BW; p = 0.005) of the PVL rats compared with the control group. The mean arterial pressure, cardiac index, systemic vascular resistance, portal pressure and serum levels of oxidative stress markers were not significantly affected by ivabradine treatment. In addition, the NOS expression and collateral vascular responsiveness to AVP were not significantly influenced by ivabradine treatment, either. CONCLUSION Ivabradine reduced the HR and SMAf in PVL rats, which alleviated the hyperdynamic circulatory state and splanchnic hyperemia of portal hypertension. However, whether these effects would help alleviate portal hypertension-related complications requires further clinical investigations.
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Affiliation(s)
- Ching-Chih Chang
- Divisions of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC
| | - Wen-Shin Lee
- Divisions of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC
| | - Chiao-Lin Chuang
- Divisions of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC
| | - I-Fang Hsin
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC
- Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC
| | - Shao-Jung Hsu
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC
| | - Hui-Chun Huang
- Divisions of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC
| | - Fa-Yauh Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC
| | - Shou-Dong Lee
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC
- Cheng-Hsin General Hospital, Taipei, Taiwan, ROC
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25
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Ning Q. Main Complications of AECHB and Severe Hepatitis B (Liver Failure). ACUTE EXACERBATION OF CHRONIC HEPATITIS B 2019. [PMCID: PMC7498917 DOI: 10.1007/978-94-024-1603-9_2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Qin Ning
- Department of Infectious Disease, Tongji Hospital, Wuhan, China
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26
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Salman MA, Mansour DA, Balamoun HA, Elbarmelgi MY, Hadad KEE, Abo Taleb ME, Salman A. Portal venous pressure as a predictor of mortality in cirrhotic patients undergoing emergency surgery. Asian J Surg 2019; 42:338-342. [PMID: 30316666 DOI: 10.1016/j.asjsur.2018.09.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2018] [Revised: 09/03/2018] [Accepted: 09/17/2018] [Indexed: 02/07/2023] Open
Abstract
OBJECTIVE Emergency surgery is a risk factor for mortality in cirrhotic patients. Portal hypertension is an essential feature of decompensated cirrhosis. This study aimed to assess the value of portal venous pressure (PVP) measurement in prediction of 1-month mortality in cirrhotic patients undergoing emergency laparotomy. METHODS This prospective study included 121 adults with liver cirrhosis subjected to an emergency laparotomy. Child-Turcotte-Pugh (CTP) score and model for end-stage liver disease (MELD) score were used for preoperative patient evaluation. PVP was measured directly at the beginning of surgery. Portal hypertension (PHT) is diagnosed when PVP is greater than 12 mmHg. The primary outcome measure was the risk of mortality within one month after surgery. RESULTS PVP ranged from 5 to 27 mmHg; 82 patients (67.8%) had PHT. Fifty-five patients (45.5%) died within 1 month. Mortality was significantly associated with increasing CTP Class, MELD score and PHT (p < 0.001 for all). PHT predicts mortality with a sensitivity of 83.6% and specificity of 92.8%. PHT was the only independent predictor of mortality (OR: 23.0, 95%CI: 8.9-59.4). CONCLUSION In patients with liver cirrhosis, emergency laparotomy carries a substantial risk of mortality within one month. Portal hypertension is an independent predictor of risk of mortality in these patients.
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Affiliation(s)
| | - Doaa Ahmed Mansour
- General Surgery Department, Kasralainy School of Medicine, Cairo University, Egypt.
| | - Hany Armia Balamoun
- General Surgery Department, Kasralainy School of Medicine, Cairo University, Egypt.
| | | | | | | | - Ahmed Salman
- Internal Medicine Department, Kasralainy School of Medicine, Cairo University, Egypt.
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Yao S, Kaido T, Uozumi R, Yagi S, Miyachi Y, Fukumitsu K, Anazawa T, Kamo N, Taura K, Okajima H, Uemoto S. Is Portal Venous Pressure Modulation Still Indicated for All Recipients in Living Donor Liver Transplantation? Liver Transpl 2018; 24:1578-1588. [PMID: 29710397 DOI: 10.1002/lt.25180] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2018] [Revised: 04/07/2018] [Accepted: 04/07/2018] [Indexed: 12/13/2022]
Abstract
There is a consensus that portal venous pressure (PVP) modulation prevents portal hypertension (PHT) and consequent complications after adult-to-adult living donor liver transplantation (ALDLT). However, PVP-modulation strategies need to be updated based on the most recent findings. We examined our 10-year experience of PVP modulation and reevaluated whether it was necessary for all recipients or for selected recipients in ALDLT. In this retrospective study, 319 patients who underwent ALDLT from 2007 to 2016 were divided into 3 groups according to the necessity and results of PVP modulation: not indicated (n = 189), indicated and succeeded (n = 92), and indicated but failed (n = 38). Graft survival and associations with various clinical factors were investigated. PVP modulation was performed mainly by splenectomy to lower final PVP to ≤15 mm Hg. Successful PVP modulation improved prognosis to be equivalent to that of patients who did not need modulation, whereas failed modulation was associated with increased incidence of small-for-size syndrome (SFSS; P = 0.003) and early graft loss (EGL; P = 0.006). Among patients with failed modulation, donor age ≥ 45 years (hazard ratio [HR], 3.67; P = 0.02) and ABO incompatibility (HR, 3.90; P = 0.01) were independent risk factors for graft loss. Survival analysis showed that PVP > 15 mm Hg was related to poor prognosis in grafts from either ABO-incompatible or older donor age ≥ 45 years (P < 0.001), but it did not negatively affect grafts from ABO-compatible/identical and young donor age < 45 years (P = 0.27). In conclusion, intentional PVP modulation is not necessarily required in all recipients. Although grafts from both ABO-compatible/identical and young donors can tolerate PHT, lowering PVP to ≤15 mm Hg is a key to preventing SFSS and consequent EGL with grafts from either ABO-incompatible or older donors.
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Affiliation(s)
- Siyuan Yao
- Departments of Surgery, Kyoto University, Kyoto, Japan
| | - Toshimi Kaido
- Departments of Surgery, Kyoto University, Kyoto, Japan
| | - Ryuji Uozumi
- Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Shintaro Yagi
- Departments of Surgery, Kyoto University, Kyoto, Japan
| | | | - Ken Fukumitsu
- Departments of Surgery, Kyoto University, Kyoto, Japan
| | | | - Naoko Kamo
- Departments of Surgery, Kyoto University, Kyoto, Japan
| | - Kojiro Taura
- Departments of Surgery, Kyoto University, Kyoto, Japan
| | | | - Shinji Uemoto
- Departments of Surgery, Kyoto University, Kyoto, Japan
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Nascimento M, Piran R, Da Costa RM, Giordani MA, Carneiro FS, Aguiar DH, Dias MC, Sugizaki MM, Luvizotto RA, Nascimento AF, Bomfim GF. Hepatic injury induced by thioacetamide causes aortic endothelial dysfunction by a cyclooxygenase-dependent mechanism. Life Sci 2018; 212:168-175. [PMID: 30292829 DOI: 10.1016/j.lfs.2018.09.051] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2018] [Revised: 09/22/2018] [Accepted: 09/30/2018] [Indexed: 02/07/2023]
Abstract
Liver cirrhosis is associated with a wide range of cardiovascular abnormalities including hyperdynamic circulation and cirrhotic cardiomyopathy. The pathogenic mechanisms of these cardiovascular changes are multifactorial and include vascular dysregulations. AIM The present study tested the hypothesis that the systemic vascular hyporesponsiveness in thioacetamide (TAA)-induced liver injury model is dependent on nitric oxide (NO) and cyclooxygenase (COX) derivatives. MAIN METHODS Wistar rats were treated with TAA for eight weeks to induce liver injury. KEY FINDINGS The maximal contractile response in concentration-effect curves to phenylephrine was decreased in aorta from TAA-treated rats, but no differences were found in aorta without endothelium, suggesting an endothelium-dependent mechanism in decreased contractile response. There was no difference in the contractile response with and without L-NAME (N(ω)-nitro-l-arginine methyl ester) in rats with liver injury, showing that the TAA treatment impairs NO synthesis. Pre-incubation of the aorta with indomethacin, a COX-inhibitor, normalized the reduced contractile response to phenylephrine in arteries from TAA group. Also, COX-2 and iNOS (inducible nitric oxide syntase) protein expression was increased in aorta from TAA group compared to control group. Animals submitted to TAA treatment had a reduction in systolic blood pressure. Our findings demonstrated that liver injury induced by TAA caused a decrease in aortic contractile response by a COX-dependent mechanism but not by NO release. Also, it was demonstrated an inflammatory process in the aorta of TAA-treated rats by increased expression of COX-2 and iNOS. SIGNIFICANCE Therefore, there is an essential contribution of COX-2 activation in extra-hepatic vascular dysfunction and inflammation present in cirrhosis induced by TAA.
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Affiliation(s)
- M Nascimento
- Institute of Health Science, Federal University of Mato Grosso, Sinop, MT, Brazil
| | - R Piran
- Institute of Health Science, Federal University of Mato Grosso, Sinop, MT, Brazil
| | - R M Da Costa
- Department of Physiology, Institute of Health Sciences, Federal University of Goias, Jatai, Brazil
| | - M A Giordani
- Institute of Health Science, Federal University of Mato Grosso, Sinop, MT, Brazil
| | - F S Carneiro
- Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil
| | - D H Aguiar
- Institute of Health Science, Federal University of Mato Grosso, Sinop, MT, Brazil
| | - M C Dias
- Institute of Health Science, Federal University of Mato Grosso, Sinop, MT, Brazil
| | - M M Sugizaki
- Institute of Health Science, Federal University of Mato Grosso, Sinop, MT, Brazil
| | - R A Luvizotto
- Institute of Health Science, Federal University of Mato Grosso, Sinop, MT, Brazil
| | - A F Nascimento
- Institute of Health Science, Federal University of Mato Grosso, Sinop, MT, Brazil
| | - G F Bomfim
- Institute of Health Science, Federal University of Mato Grosso, Sinop, MT, Brazil.
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Closed-Loop Lumped Parameter Modeling of Hemodynamics During Cirrhogenesis in Rats. IEEE Trans Biomed Eng 2018; 65:2311-2322. [DOI: 10.1109/tbme.2018.2793948] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
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Königshofer P, Brusilovskaya K, Schwabl P, Reiberger T. Animal models of portal hypertension. Biochim Biophys Acta Mol Basis Dis 2018; 1865:1019-1030. [PMID: 30055295 DOI: 10.1016/j.bbadis.2018.07.018] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2018] [Revised: 07/14/2018] [Accepted: 07/16/2018] [Indexed: 12/12/2022]
Abstract
Chronic liver diseases ultimately lead to cirrhosis and portal hypertension (PHT). Indeed, PHT is a major cause of severe complications, while medical treatment is limited to non-selective beta blockers. Sophisticated animal models are needed to investigate novel treatment options for different etiologies of liver disease, effective anti-fibrotic agents as well as vasoactive drugs against PHT. In this review, we present some of the most common animal models of liver disease and PHT - including pre-hepatic, intra-hepatic and post-hepatic PHT in rodents. Methodology for induction, considerations for disease etiology, advantages and limitations and practical issues of these animal models are discussed. The appropriate and sensible use of animal models in preclinical research supporting the 3R concept of replacement, reduction and refinement is highlighted.
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Affiliation(s)
- P Königshofer
- Div. of Gastroenterology and Hepatology, Dept. of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
| | - K Brusilovskaya
- Div. of Gastroenterology and Hepatology, Dept. of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
| | - P Schwabl
- Div. of Gastroenterology and Hepatology, Dept. of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
| | - T Reiberger
- Div. of Gastroenterology and Hepatology, Dept. of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria.
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Systemic hemodynamic response to terlipressin predicts development of hepatorenal syndrome and survival in advanced cirrhosis. Eur J Gastroenterol Hepatol 2018; 30:659-667. [PMID: 29432366 DOI: 10.1097/meg.0000000000001088] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND The aim of this study was to predict the occurrence of hepatorenal syndrome (HRS) and death in patients with advanced cirrhosis and ascites. PATIENTS AND METHODS We retrospectively evaluated 2-year data of 78 patients with cirrhosis and ascites (Child-Pugh B/C: 45/43). The mean arterial pressure (MAP) and cardiac output (CO) were measured in all patients just before administration of 2 mg of terlipressin and 30 min later. Systemic vascular resistance (SVR) was calculated as MAP/CO. ΔMAP, and ΔCO, and ΔSVR were defined as the percentage change of MAP, CO, and SVR, respectively, after terlipressin injection. Plasma renin activity (PRA) and plasma aldosterone were evaluated at baseline. Two multivariate models were used: one excluding (model 1) and one including (model 2) the Model of End-stage Liver Disease score. RESULTS Higher ΔSVR, Model of End-stage Liver Disease score, and PRA were related independently to the severity of cirrhosis. Independent predictors of HRS at 12 and 24 months were ΔSVR (models 1/2: P=0.008/0.01 and 0.01/0.02, respectively), ΔCO (models 1/2: P=0.01/0.03 and 0.03/0.04, respectively), and PRA (models 1/2: P=0.04 and model 1: P=0.04, respectively). ΔSVR at 12 and 24 months (models 1/2: P=0.005/0.01 and 0.01/0.03, respectively) and ΔCO at 24 months (models 1/2: P=0.02/0.01, respectively) were related independently to survival. Patient groups with significantly higher probability of HRS and mortality were identified by certain cutoffs of ΔSVR (20.6 and 22.8%, respectively) and ΔCO (-10.6 and -11.8%, respectively). ΔSVR and ΔCO independently predicted survival in patients with the most advanced cirrhosis and infection-related survival. CONCLUSION An increase in SVR by at least 20% and a decrease in CO at least 10% in response to terlipressin could predict HRS and mortality in patients with advanced cirrhosis.
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Park SH, Joo MS, Kim BH, Yoo HN, Kim SE, Kim JB, Jang MK, Kim DJ, Lee MS. Clinical characteristics and prevalence of adrenal insufficiency in hemodynamically stable patients with cirrhosis. Medicine (Baltimore) 2018; 97:e11046. [PMID: 29952944 PMCID: PMC6039635 DOI: 10.1097/md.0000000000011046] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2017] [Accepted: 05/13/2018] [Indexed: 01/15/2023] Open
Abstract
It is well known that adrenal insufficiency is common in septic shock or hemodynamically unstable patients. But, there is as yet no sufficient clinically significant data about the exact prevalence or differences in the cause of cirrhosis with adrenal insufficiency. To investigate adrenal insufficiency prevalence in hemodynamically stable patients with cirrhosis and determine differences based on cirrhosis severity or etiology.From July 2011 to December 2012, 69 hemodynamically stable patients with cirrhosis without infection admitted at Hallym University Medical Center were enrolled. Adrenal insufficiency was defined as a peak cortisol level < 18 μg/dL, 30 or 60 minutes after 250 μg Synacthen injection.The study included 55 male patients (79.7%), and the mean age was 57.9 ± 12.9 years. Cirrhosis etiology was alcohol consumption, HBV, HCV, both viral and alcohol related, and cryptogenic in 49, 15, 7, 11, 9 patients, respectively. Adrenal insufficiency occurred in 24 patients (34.8%). No differences were found in age, sex, mean arterial pressure, heart rate, HDL, cirrhosis etiology, degree of alcohol consumption, encephalopathy, variceal bleeding history, or hepatocellular carcinoma between patients with or without adrenal insufficiency. Serum albumin level was lower (P < .05), and INR was higher (P < .05) in patients with than in those without adrenal insufficiency. However, multivariate analysis revealed no independent adrenal insufficiency predictor. Significant negative correlations were found between Child-Pugh score and peak cortisol levels (γ=-0.365, P = .008).Adrenal insufficiency was frequent even in hemodynamically stable patients with cirrhosis and tended to be associated with only liver disease severity, being unrelated to cirrhosis etiology.
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Borrelli A, Bonelli P, Tuccillo FM, Goldfine ID, Evans JL, Buonaguro FM, Mancini A. Role of gut microbiota and oxidative stress in the progression of non-alcoholic fatty liver disease to hepatocarcinoma: Current and innovative therapeutic approaches. Redox Biol 2018; 15:467-479. [PMID: 29413959 PMCID: PMC5975181 DOI: 10.1016/j.redox.2018.01.009] [Citation(s) in RCA: 196] [Impact Index Per Article: 28.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2017] [Revised: 01/10/2018] [Accepted: 01/17/2018] [Indexed: 02/07/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) represents the most common chronic liver disease in industrialized countries. NAFLD progresses through the inflammatory phase of non-alcoholic steatohepatitis (NASH) to fibrosis and cirrhosis, with some cases developing liver failure or hepatocellular carcinoma (HCC). Liver biopsy remains the gold standard approach to a definitive diagnosis of NAFLD and the distinction between simple steatosis and NASH. The pathogenesis of NASH is still not clear. Several theories have been proposed ranging from the "Two Hit Theory" to the "Multiple Hit Theory". However, the general consensus is that the gut microbiota, oxidative stress, and mitochondrial damage play key roles in the pathogenesis of NASH. The interaction between the gut epithelia and some commensal bacteria induces the rapid generation of reactive oxygen species (ROS). The main goal of any therapy addressing NASH is to reverse or prevent progression to liver fibrosis/cirrhosis. This problem represents the first "Achilles' heel" of the new molecules being evaluated in most ongoing clinical trials. The second is the inability of these molecules to reach the mitochondria, the primary sites of energy production and ROS generation. Recently, a variety of non-pharmacological and pharmacological treatment approaches for NASH have been evaluated including vitamin E, the thiazolidinediones, and novel molecules related to NASH pathogenesis (including obeticholic acid and elafibranor). Recently, a new isoform of human manganese superoxide dismutase (MnSOD) was isolated and obtained in a synthetic recombinant form designated rMnSOD. This protein has been shown to be a powerful antioxidant capable of mediating ROS dismutation, penetrating biological barriers via its uncleaved leader peptide, and reducing portal hypertension and fibrosis in rats affected by liver cirrhosis. Based on these distinctive characteristics, it can be hypothesized that this novel recombinant protein (rMnSOD) potentially represents a new and highly efficient adjuvant therapy to counteract the progression from NASH to HCC.
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Affiliation(s)
- Antonella Borrelli
- Molecular Biology and Viral Oncology Unit, Istituto Nazionale Tumori IRCCS "Fondazione G Pascale", 80131 Napoli, Italy.
| | - Patrizia Bonelli
- Molecular Biology and Viral Oncology Unit, Istituto Nazionale Tumori IRCCS "Fondazione G Pascale", 80131 Napoli, Italy
| | - Franca Maria Tuccillo
- Molecular Biology and Viral Oncology Unit, Istituto Nazionale Tumori IRCCS "Fondazione G Pascale", 80131 Napoli, Italy
| | | | | | - Franco Maria Buonaguro
- Molecular Biology and Viral Oncology Unit, Istituto Nazionale Tumori IRCCS "Fondazione G Pascale", 80131 Napoli, Italy
| | - Aldo Mancini
- Leadhexa Biotechnologies Inc., Belvedere, CA, USA
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Abstract
OBJECTIVES On the basis of studies with hepatorenal syndrome, it is widely regarded that renal function is impacted in chronic liver disease (CLD). Therefore, we investigated renal function in children with CLD. METHODS In a retrospective study of 277 children with CLD, renal function was investigated as glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), measured as clearance of inulin and para-amino hippuric acid or clearance of iohexol. The data were analyzed with regard to different subgroups of liver disease and to the grade of damage. RESULTS Hyperfiltration (>+2 SD of controls) was found in the subgroups of progressive familial intrahepatic cholestasis (44%), glycogenosis (75%), and acute fulminant liver failure (60%). Patients with biliary atresia, most other patients with metabolic disease and intrahepatic cholestasis, and those with vascular anomalies and cryptogenic cirrhosis had normal renal function. Decreased renal function was found in patients with Alagille's syndrome (64% < -2 SD). Increased GFR and ERPF was found in patients with elevated transaminases, low prothrombin level, high bile acid concentration, and high aspartate-aminotransferase-to-platelet ratio. CONCLUSIONS Most children with CLD had surprisingly well preserved renal function and certain groups had even hyperfiltration. The finding that children with decompensated liver disease and ongoing liver failure had stable kidney function suggests that no prognostic markers of threatening hepatorenal syndrome were at hand. Moreover, estimation of GFR based on serum creatinine fails to reveal hyperfiltration.
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Correale M, Tarantino N, Petrucci R, Tricarico L, Laonigro I, Di Biase M, Brunetti ND. Liver disease and heart failure: Back and forth. Eur J Intern Med 2018; 48:25-34. [PMID: 29100896 DOI: 10.1016/j.ejim.2017.10.016] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2017] [Revised: 10/04/2017] [Accepted: 10/23/2017] [Indexed: 12/18/2022]
Abstract
In their clinical practice, physicians can face heart diseases (chronic or acute heart failure) affecting the liver and liver diseases affecting the heart. Systemic diseases can also affect both heart and liver. Therefore, it is crucial in clinical practice to identify complex interactions between heart and liver, in order to provide the best treatment for both. In this review, we sought to summarize principal evidence explaining the mechanisms and supporting the existence of this complicate cross-talk between heart and liver. Hepatic involvement after heart failure, its pathophysiology, clinical presentation (congestive and ischemic hepatopathy), laboratory and echocardiographic prognostic markers are discussed; likewise, hepatic diseases influencing cardiac function (cirrhotic cardiomyopathy). Several clinical conditions (congenital, metabolic and infectious causes) possibly affecting simultaneously liver and heart have been also discussed. Cardiovascular drug therapy may present important side effects on the liver and hepato-biliary drug therapy on heart and vessels; post-transplantation immunosuppressive drugs may show reciprocal cardio-hepatotoxicity. A heart-liver axis is drafted by inflammatory reactants from the heart and the liver, and liver acts a source of energy substrates for the heart.
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Affiliation(s)
| | - Nicola Tarantino
- Department of Medical & Surgical Sciences, University of Foggia, Italy.
| | - Rossella Petrucci
- Department of Medical & Surgical Sciences, University of Foggia, Italy.
| | - Lucia Tricarico
- Department of Medical & Surgical Sciences, University of Foggia, Italy.
| | - Irma Laonigro
- Ospedali Riuniti University Hospital, Foggia, Italy.
| | - Matteo Di Biase
- Department of Medical & Surgical Sciences, University of Foggia, Italy.
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Kerbert AJC, Verspaget HW, Navarro ÀA, Jalan R, Solà E, Benten D, Durand F, Ginès P, van der Reijden JJ, van Hoek B, Coenraad MJ. Copeptin in acute decompensation of liver cirrhosis: relationship with acute-on-chronic liver failure and short-term survival. CRITICAL CARE : THE OFFICIAL JOURNAL OF THE CRITICAL CARE FORUM 2017; 21:321. [PMID: 29268760 PMCID: PMC5740749 DOI: 10.1186/s13054-017-1894-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/04/2017] [Accepted: 11/20/2017] [Indexed: 12/18/2022]
Abstract
Background Acute-on-chronic liver failure (ACLF) is characterized by the presence of acute decompensation (AD) of cirrhosis, organ failure, and high short-term mortality rates. Hemodynamic dysfunction and activation of endogenous vasoconstrictor systems are thought to contribute to the pathogenesis of ACLF. We explored whether copeptin, a surrogate marker of arginine vasopressin, is a potential marker of outcome in patients admitted for AD or ACLF and whether it might be of additional value to conventional prognostic scoring systems in these patients. Methods All 779 patients hospitalized for AD of cirrhosis from the CANONIC database with at least one serum sample available for copeptin measurement were included. Presence of ACLF was defined according to the CLIF-consortium organ failure (CLIF-C OF) score. Serum copeptin was measured in samples collected at days 0–2, 3–7, 8–14, 15–21, and 22–28 when available. Competing-risk regression analysis was applied to evaluate the impact of serum copeptin and laboratory and clinical data on short-term survival. Results Serum copeptin concentration was found to be significantly higher in patients with ACLF compared with those without ACLF at days 0–2 (33 (14–64) vs. 11 (4–26) pmol/L; p < 0.001). Serum copeptin at admission was shown to be a predictor of mortality independently of MELD and CLIF-C OF scores. Moreover, baseline serum copeptin was found to be predictive of ACLF development within 28 days of follow-up. Conclusions ACLF is associated with significantly higher serum copeptin concentrations at hospital admission compared with those with traditional AD. Copeptin is independently associated with short-term survival and ACLF development in patients admitted for AD or ACLF. Electronic supplementary material The online version of this article (doi:10.1186/s13054-017-1894-8) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Annarein J C Kerbert
- Department of Gastroenterology-Hepatology, Leiden University Medical Center, PO Box 9600, Leiden, The Netherlands.
| | - Hein W Verspaget
- Department of Gastroenterology-Hepatology, Leiden University Medical Center, PO Box 9600, Leiden, The Netherlands
| | - Àlex Amorós Navarro
- Liver Unit/EASL-CLIF Data Center, Hospital Clínic de Barcelona, Barcelona, Spain
| | - Rajiv Jalan
- Liver Failure Group, UCL Institute for Liver and Digestive Health, UCL Medical School, Royal Free Hospital, London, UK
| | - Elsa Solà
- Liver Unit, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain
| | - Daniel Benten
- Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - François Durand
- Hepatology and Liver Intensive Care Unit, Hospital Beaujon, Clichy, France
| | - Pere Ginès
- Liver Unit, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain
| | - Johan J van der Reijden
- Department of Gastroenterology-Hepatology, Leiden University Medical Center, PO Box 9600, Leiden, The Netherlands
| | - Bart van Hoek
- Department of Gastroenterology-Hepatology, Leiden University Medical Center, PO Box 9600, Leiden, The Netherlands
| | - Minneke J Coenraad
- Department of Gastroenterology-Hepatology, Leiden University Medical Center, PO Box 9600, Leiden, The Netherlands
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Wáng YXJ, Deng M, Li YT, Huang H, Leung JCS, Chen W, Lu PX. A Combined Use of Intravoxel Incoherent Motion MRI Parameters Can Differentiate Early-Stage Hepatitis-b Fibrotic Livers from Healthy Livers. SLAS Technol 2017; 23:259-268. [PMID: 28666091 DOI: 10.1177/2472630317717049] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
This study investigated a combined use of intravoxel incoherent motion (IVIM) parameters, Dslow ( D), PF ( f), and Dfast ( D*), for liver fibrosis evaluation. Sixteen healthy volunteers (F0) and 33 hepatitis-b patients (stage F1 = 15, stage F2-4 = 18) were included. With a 1.5 T MR scanner and respiration gating, IVIM diffusion-weighted imaging was acquired using a single-shot echo-planar imaging sequence with 10 b values of 10, 20, 40, 60, 80, 100, 150, 200, 400, and 800 s/mm2. Signal measurement was performed on right liver parenchyma. With a three-dimensional tool, Dslow, PF, and Dfast values were placed along the x axis, y axis, and z axis, and a plane was defined to separate healthy volunteers from patients. The three-dimensional tool demonstrated that healthy volunteers and all patients with liver fibrosis could be separated. Classification and regression tree showed that a combination of PF (PF < 12.55%), Dslow (Dslow < 1.152 × 10-3 mm2/s), and Dfast (Dfast < 13.36 × 10-3 mm2/s) could differentiate healthy subjects and all fibrotic livers (F1-4) with an area under the curve of logistic regression (AUC) of 0.986. The AUC for differentiation of healthy livers versus F2-4 livers was 1. PF offered the best diagnostic value, followed by Dslow; however, all three parameters of PF, Dslow, and Dfast contributed to liver fibrosis detection.
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Affiliation(s)
- Yì Xiáng J Wáng
- 1 Department of Imaging and Interventional Radiology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, New Territories, Hong Kong SAR
| | - Min Deng
- 1 Department of Imaging and Interventional Radiology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, New Territories, Hong Kong SAR
| | - Yáo T Li
- 1 Department of Imaging and Interventional Radiology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, New Territories, Hong Kong SAR
| | - Hua Huang
- 2 Department of Radiology, The Shenzhen No. 3 People's Hospital, Shenzhen, Guangdong Province, China
| | - Jason Chi Shun Leung
- 3 JC Centre for Osteoporosis Care and Control, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, New Territories, Hong Kong SAR
| | - Weitian Chen
- 1 Department of Imaging and Interventional Radiology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, New Territories, Hong Kong SAR
| | - Pu-Xuan Lu
- 4 Shenzhen Center for Chronic Disease Control, Shenzhen, Guangdong Province, China
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Relative Adrenal Insufficiency in Patients with Cirrhosis: A Systematic Review and Meta-Analysis. Dig Dis Sci 2017; 62:1067-1079. [PMID: 28176190 DOI: 10.1007/s10620-017-4471-8] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2016] [Accepted: 01/20/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND Relative adrenal insufficiency (RAI) is frequently observed in patients with cirrhosis. We sought to identify evidence in the literature regarding the impact of RAI on clinical outcomes in cirrhotic patients. METHODS We conducted a systematic review (SR) and meta-analysis (MA) using the Ovid-MEDLINE, EMBASE, and Cochrane Library databases to identify relevant studies in the literature. RESULTS Of the 182 studies identified, 16 were eligible according to our inclusion criteria. The prevalence of RAI was 49.4% (744/1507), and cirrhotic patients with acute critical illnesses such as sepsis were more likely to have RAI compared to those without critical illnesses (P < 0.001). With respect to clinical outcomes, patients with RAI had poorer survival rates and an increased risk of complications such as bleeding and hepatorenal syndrome compared to those without RAI. Corticosteroid therapy had a beneficial effect on critically ill cirrhotic patients in terms of hospital survival rate. CONCLUSIONS Based on this SR and MA, critically ill patients with cirrhosis have a high risk of RAI, and the presence of RAI is related to a poor prognosis and occurrence of cirrhotic complications.
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Nasr P, Hilliges A, Thorelius L, Kechagias S, Ekstedt M. Contrast-enhanced ultrasonography could be a non-invasive method for differentiating none or mild from severe fibrosis in patients with biopsy proven non-alcoholic fatty liver disease. Scand J Gastroenterol 2016; 51:1126-32. [PMID: 27161854 DOI: 10.3109/00365521.2016.1172336] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE The gold standard for diagnosing fibrosis stage in non-alcoholic fatty liver disease (NAFLD) is liver biopsy. The aim of this study was to determine whether contrast-enhanced ultrasonography (CEUS) with transit time measurements could be a non-invasive alternative for differentiating none or mild from severe fibrosis in NAFLD patients. Various serum markers and clinical variables were also evaluated. MATERIALS AND METHODS Fifty-eight patients with NAFLD underwent CEUS prior to liver biopsy. All patients were also evaluated according to the Göteborg University Cirrhosis Index (GUCI), the AST-Platelet Ratio Index (APRI), the NAFLD fibrosis score, and the FIB-4 and BARD score. RESULTS The hepatic vein arrival time (HV) was shorter in patients with severe fibrosis (25.9 ± 4.8 vs 29.5 ± 4.7 s, p = 0.023), and the difference between the hepatic and portal vein (ΔHV-PV) was shorter (2.3 ± 2.8 vs 6.4 ± 2.8 s, p < 0.0001) while the difference in arrival time between the portal vein and hepatic artery (ΔPV-HA) arrival time was significantly longer (6.0 ± 2.2 vs 3.6 ± 1.6 s, p < 0.0001). The area under receiver operating characteristics curve values for HV, ΔHV-PV and ΔPV-HA to separate none or mild from severe fibrosis was 0.71, 0.83 and 0.84, respectively. The corresponding figures for GUCI, APRI, NAFLD fibrosis score, FIB-4 and BARD score were 0.93, 0.92, 0.86, 0.90 and 0.77, respectively. CONCLUSIONS CEUS and non-invasive scoring systems could exclude severe fibrosis in NAFLD patients.
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Affiliation(s)
- Patrik Nasr
- a The Faculty of Medicine and Health Sciences, Department of Medical and Health Sciences (IMH) , Linköping University , Linköping , Sweden
| | - Annette Hilliges
- a The Faculty of Medicine and Health Sciences, Department of Medical and Health Sciences (IMH) , Linköping University , Linköping , Sweden
| | - Lars Thorelius
- a The Faculty of Medicine and Health Sciences, Department of Medical and Health Sciences (IMH) , Linköping University , Linköping , Sweden
| | - Stergios Kechagias
- a The Faculty of Medicine and Health Sciences, Department of Medical and Health Sciences (IMH) , Linköping University , Linköping , Sweden
| | - Mattias Ekstedt
- a The Faculty of Medicine and Health Sciences, Department of Medical and Health Sciences (IMH) , Linköping University , Linköping , Sweden
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Di Stefano C, Milazzo V, Milan A, Veglio F, Maule S. The role of autonomic dysfunction in cirrhotic patients before and after liver transplantation. Review of the literature. Liver Int 2016; 36:1081-9. [PMID: 27003923 DOI: 10.1111/liv.13126] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2016] [Accepted: 03/15/2016] [Indexed: 02/13/2023]
Abstract
In patients affected by hepatic cirrhosis, autonomic dysfunction is a common finding; usually it is asymptomatic but it may correlate with increased mortality and morbidity before, during and after liver transplant, due to hemodynamic instability in the course of stressful events like sepsis, gastrointestinal bleeding and reperfusion after transplantation surgery. Hyperdynamic circulation and hepatic dysfunction seem to play a role in the pathogenesis of autonomic dysfunction, even if pathophysiological mechanisms are not completely known. We present a revision of previous literature about prevalence, pathophysiological mechanisms, clinical features, and mortality and morbidity of autonomic dysfunction secondary to hepatic cirrhosis.
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Affiliation(s)
- Cristina Di Stefano
- Autonomic Unit and Hypertension Unit, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Valeria Milazzo
- Autonomic Unit and Hypertension Unit, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Alberto Milan
- Autonomic Unit and Hypertension Unit, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Franco Veglio
- Autonomic Unit and Hypertension Unit, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Simona Maule
- Autonomic Unit and Hypertension Unit, Department of Medical Sciences, University of Turin, Turin, Italy
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Assessment of response to beta-blockers by expression of βArr2 and RhoA/ROCK2 in antrum mucosa in cirrhotic patients. J Hepatol 2016; 64:1265-73. [PMID: 26827791 DOI: 10.1016/j.jhep.2016.01.022] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2015] [Revised: 12/30/2015] [Accepted: 01/20/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Non-selective beta-blockers (NSBB) are first choice for prevention of variceal bleeding. But possible deleterious effects in refractory ascites and frequent non-response are clinical drawbacks. Since levels of vasoactive proteins in antrum mucosa reflect vascular dysfunction in cirrhosis, these expression levels might also reflect hemodynamic response to NSBB. METHODS Biopsies from the gastric and duodenal mucosa of 25 patients with cirrhosis were collected and the hepatic venous pressure gradient (HVPG) was measured before and after an acute propranolol challenge. Transcription and protein expression of Ras homolog family member A (RhoA), Rho-kinase (ROCK)2, beta-arrestin2 (βArr2), endothelial nitric oxide synthase (eNOS) and the phosphorylation of downstream effectors VASP and moesin were analyzed using PCR and Western blot. Further 21 patients on NSBB were evaluated on their follow up for events of variceal bleeding defined as non-response. RESULTS Ten patients showed HVPG <10mmHg, further seven patients showed significant hemodynamic response to NSBB, whereas eight patients were non-responders. The mucosal transcription of vasoactive proteins was higher in antrum mucosa compared to corpus and duodenum. The transcriptional levels of vasoactive proteins were higher in patients with HVPG >10mmHg and HVPG >16mmHg. Interestingly, mRNA levels of RhoA and ROCK2 were lower in patients with large varices at endoscopy. Moreover, RhoA and ROCK2 transcription correlated with the decrease of HVPG after acute NSBB challenge. Finally, acute and long-term non-responders showed lower expression of βArr2 in antrum mucosa. CONCLUSION This study shows for the first time that the expression of βArr2 in antrum mucosa biopsies might reflect the hemodynamic response to NSBB and their long-term protective effect. This finding might offer an easy approach at upper endoscopy to facilitate the decision to treat with NSBB if varices are present.
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Ascha M, Abuqayyas S, Hanouneh I, Alkukhun L, Sands M, Dweik RA, Tonelli AR. Predictors of mortality after transjugular portosystemic shunt. World J Hepatol 2016; 8:520-529. [PMID: 27099653 PMCID: PMC4832094 DOI: 10.4254/wjh.v8.i11.520] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2015] [Revised: 01/21/2016] [Accepted: 03/16/2016] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate if echocardiographic and hemodynamic determinations obtained at the time of transjugular intrahepatic portosystemic shunt (TIPS) can provide prognostic information that will enhance risk stratification of patients.
METHODS: We reviewed medical records of 467 patients who underwent TIPS between July 2003 and December 2011 at our institution. We recorded information regarding patient demographics, underlying liver disease, indication for TIPS, baseline laboratory values, hemodynamic determinations at the time of TIPS, and echocardiographic measurements both before and after TIPS. We recorded patient comorbidities that may affect hemodynamic and echocardiographic determinations. We also calculated Model for End-stage Liver Disease (MELD) score and Child Turcotte Pugh (CTP) class. The following pre- and post-TIPS echocardiographic determinations were recorded: Left ventricular ejection fraction, right ventricular (RV) systolic pressure, subjective RV dilation, and subjective RV function. We recorded the following hemodynamic measurements: Right atrial (RA) pressure before and after TIPS, inferior vena cava pressure before and after TIPS, free hepatic vein pressure, portal vein pressure before and after TIPS, and hepatic venous pressure gradient (HVPG).
RESULTS: We reviewed 418 patients with portal hypertension undergoing TIPS. RA pressure increased by a mean ± SD of 4.8 ± 3.9 mmHg (P < 0.001), HVPG decreased by 6.8 ± 3.5 mmHg (P < 0.001). In multivariate linear regression analysis, a higher MELD score, lower platelet count, splenectomy and a higher portal vein pressure were independent predictors of higher RA pressure (R = 0.55). Three variables predicted 3-mo mortality after TIPS in a multivariate analysis: Age, MELD score, and CTP grade C. Change in the RA pressure after TIPS predicted long-term mortality (per 1 mmHg change, HR = 1.03, 95%CI: 1.01-1.06, P < 0.012).
CONCLUSION: RA pressure increased immediately after TIPS particularly in patients with worse liver function, portal hypertension, emergent TIPS placement and history of splenectomy. The increase in RA pressure after TIPS was associated with increased mortality. Age, splenectomy, MELD score and CTP grade were independent predictors of long-term mortality after TIPS.
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Gjeorgjievski M, Cappell MS. Portal hypertensive gastropathy: A systematic review of the pathophysiology, clinical presentation, natural history and therapy. World J Hepatol 2016; 8:231-262. [PMID: 26855694 PMCID: PMC4733466 DOI: 10.4254/wjh.v8.i4.231] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2015] [Revised: 11/30/2015] [Accepted: 01/16/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To describe the pathophysiology, clinical presentation, natural history, and therapy of portal hypertensive gastropathy (PHG) based on a systematic literature review. METHODS Computerized search of the literature was performed via PubMed using the following medical subject headings or keywords: "portal" and "gastropathy"; or "portal" and "hypertensive"; or "congestive" and "gastropathy"; or "congestive" and "gastroenteropathy". The following criteria were applied for study inclusion: Publication in peer-reviewed journals, and publication since 1980. Articles were independently evaluated by each author and selected for inclusion by consensus after discussion based on the following criteria: Well-designed, prospective trials; recent studies; large study populations; and study emphasis on PHG. RESULTS PHG is diagnosed by characteristic endoscopic findings of small polygonal areas of variable erythema surrounded by a pale, reticular border in a mosaic pattern in the gastric fundus/body in a patient with cirrhotic or non-cirrhotic portal hypertension. Histologic findings include capillary and venule dilatation, congestion, and tortuosity, without vascular fibrin thrombi or inflammatory cells in gastric submucosa. PHG is differentiated from gastric antral vascular ectasia by a different endoscopic appearance. The etiology of PHG is inadequately understood. Portal hypertension is necessary but insufficient to develop PHG because many patients have portal hypertension without PHG. PHG increases in frequency with more severe portal hypertension, advanced liver disease, longer liver disease duration, presence of esophageal varices, and endoscopic variceal obliteration. PHG pathogenesis is related to a hyperdynamic circulation, induced by portal hypertension, characterized by increased intrahepatic resistance to flow, increased splanchnic flow, increased total gastric flow, and most likely decreased gastric mucosal flow. Gastric mucosa in PHG shows increased susceptibility to gastrotoxic chemicals and poor wound healing. Nitrous oxide, free radicals, tumor necrosis factor-alpha, and glucagon may contribute to PHG development. Acute and chronic gastrointestinal bleeding are the only clinical complications. Bleeding is typically mild-to-moderate. Endoscopic therapy is rarely useful because the bleeding is typically diffuse. Acute bleeding is primarily treated with octreotide, often with concomitant proton pump inhibitor therapy, or secondarily treated with vasopressin or terlipressin. Nonselective β-adrenergic receptor antagonists, particularly propranolol, are used to prevent bleeding after an acute episode or for chronic bleeding. Iron deficiency anemia from chronic bleeding may require iron replacement therapy. Transjugular-intrahepatic-portosystemic-shunt and liver transplantation are highly successful ultimate therapies because they reduce the underlying portal hypertension. CONCLUSION PHG is important to recognize in patients with cirrhotic or non-cirrhotic portal hypertension because it can cause acute or chronic GI bleeding that often requires pharmacologic therapy.
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Affiliation(s)
- Mihajlo Gjeorgjievski
- Mihajlo Gjeorgjievski, Mitchell S Cappell, Division of Gastroenterology and Hepatology, William Beaumont Hospital, Royal Oak, MI 48073, United States
| | - Mitchell S Cappell
- Mihajlo Gjeorgjievski, Mitchell S Cappell, Division of Gastroenterology and Hepatology, William Beaumont Hospital, Royal Oak, MI 48073, United States
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Elwir S, Hal H, Veith J, Schreibman I, Kadry Z, Riley T. Radiographical findings in patients with liver cirrhosis and hepatic encephalopathy. Gastroenterol Rep (Oxf) 2015; 4:221-5. [PMID: 26463277 PMCID: PMC4976681 DOI: 10.1093/gastro/gov049] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2015] [Accepted: 08/23/2015] [Indexed: 01/28/2023] Open
Abstract
Background and aims: Hepatic encephalopathy is a common complication encountered in patients with liver cirrhosis. Hepatic encephalopathy is not reflected in the current liver transplant allocation system. Correlation was sought between hepatic encephalopathy with findings detected on radiographic imaging studies and the patient’s clinical profile. Methods: A retrospective analysis was conducted of patients with cirrhosis, who presented for liver transplant evaluation in 2009 and 2010. Patients with hepatocellular carcinoma, ejection fraction less than 60% and who had a TIPS (transjugular intrahepatic portosystemic shunting) procedure or who did not complete the evaluation were excluded. Statistical analysis was performed and variables found to be significant on univariate analysis (P < 0.05) were analysed by a multivariate logistic regression model. Results: A total of 117 patients met the inclusion criteria and were divided into a hepatic encephalopathy group (n = 58) and a control group (n = 59). Univariate analysis found that a smaller portal vein diameter, smaller liver antero-posterior diameter, liver nodularity and use of diuretics or centrally acting medications showed significant correlation with hepatic encephalopathy. This association was confirmed for smaller portal vein, use of diuretics and centrally acting medications in the multivariate analysis. Conclusion: A decrease in portal vein diameter was associated with increased risk of encephalopathy. Identifying patients with smaller portal vein diameter may warrant screening for encephalopathy by more advanced psychometric testing, and more aggressive control of constipation and other factors that may precipitate encephalopathy.
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Affiliation(s)
- Saleh Elwir
- Department of Internal Medicine, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania (PA), USA
| | - Hassan Hal
- Department of Radiology, Penn State Milton S. Hershey Medical Center, Hershey, PA, USA
| | - Joshua Veith
- Penn State Milton S. Hershey Medical Center and School of Medicine, Hershey, PA, USA
| | - Ian Schreibman
- Division of Gastroenterology and Hepatology, Penn State Milton S. Hershey Medical Center, Hershey, PA, USA
| | - Zakiyah Kadry
- Division of Transplant Surgery, Penn State Milton S. Hershey Medical Center, Hershey PA, USA
| | - Thomas Riley
- Division of Gastroenterology and Hepatology, Penn State Milton S. Hershey Medical Center, Hershey, PA, USA
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Trebicka J, Wix C, von Heydebrand M, Hittatiya K, Reiberger T, Klein S, Schierwagen R, Kristiansen G, Peck-Radosavljevic M, Fischer HP, Møller S, Bendtsen F, Krag A, Sauerbruch T. Expression of vasoactive proteins in gastric antral mucosa reflects vascular dysfunction in patients with cirrhosis and portal hypertension. Liver Int 2015; 35:1393-402. [PMID: 24912856 DOI: 10.1111/liv.12613] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2014] [Accepted: 05/24/2014] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Patients with cirrhosis display hypocontractility of splanchnic vessels because of dysregulation of vasoactive proteins, such as decreased effect of RhoA/ROCK and increased activity of β-Arrestin-2 and eNOS. However, it is unknown whether the dysregulation of vasoactive proteins is displayed in other vessels. We investigated whether expression of vasoactive proteins can be evaluated in gastric mucosa vessels. METHODS Biopsies from the gastric mucosa of 111 patients with cirrhosis were collected at three different centres and from 13 controls. Forty-nine patients had received TIPS. Portal pressure gradient was measured in 49 patients with TIPS and in 16 patients without TIPS. Biopsies from the antrum were conserved in formaldehyde for immunohistochemistry or shock-frozen for PCR and Western blot. RESULTS The mucosal transcription of vascular markers (αSMA, CD31) was higher in cirrhotic patients than controls, which was confirmed by immunohistochemistry. On average, relative mucosal levels of RhoA and ROCK were lower, while β-Arrestin-2 levels were higher in cirrhotic patients compared to controls. Transcriptional levels of eNOS increased with presence of ascites and grade of oesophageal varices. Patients with TIPS showed less pronounced markers of vascular dysfunction in gastric mucosa. CONCLUSION This is the first evidence that the expression of vasoactive proteins in mucosa from the gastric antrum of patients with cirrhosis reflects their vascular dysfunction and possibly changes after therapeutic interventions.
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Affiliation(s)
- Jonel Trebicka
- Department of Internal Medicine I, University of Bonn, Bonn, Germany; Gastrounit, Medical Division, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark
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Anastasiadis SN, Giouleme OI, Germanidis GS, Vasiliadis TG. Relative adrenal insufficiency in cirrhotic patients. CLINICAL MEDICINE INSIGHTS. GASTROENTEROLOGY 2015; 8:13-7. [PMID: 25780347 PMCID: PMC4348066 DOI: 10.4137/cgast.s18127] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/29/2014] [Revised: 09/19/2014] [Accepted: 10/12/2014] [Indexed: 12/19/2022]
Abstract
Relative adrenal insufficiency (RAI) was demonstrated in patients with cirrhosis and liver failure. A relationship appears to exist between the severity of the liver disease and the presence of RAI. Neither the mechanism nor the exact prevalence of RAI is fully understood. There is though a hypothesis that low high-density lipoprotein (HDL) levels in this group of patients may be responsible for the insufficiency of cortisol. Several questions also arise about the way and the kind of cortisol (total cortisol, free cortisol, or even salivary cortisol) that should be measured. The presence of RAI in patients with cirrhosis is unquestionable, but still several studies should come up in order to properly define it and fully understand it.
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Affiliation(s)
- Sotirios N Anastasiadis
- 3rd Department of Internal Medicine, Papageorgiou Hospital, Aristotle University of Thessaloniki, Greece
| | - Olga I Giouleme
- 2nd Prop. Clinic of Internal Medicine, Hippokration Hospital, Aristotle University of Thessaloniki, Greece
| | - Georgios S Germanidis
- 1st Department of Internal Medicine, AHEPA Hospital, Aristotle University of Thessaloniki, Greece
| | - Themistoklis G Vasiliadis
- 3rd Department of Internal Medicine, Papageorgiou Hospital, Aristotle University of Thessaloniki, Greece
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GUO SHIBIN, LI QING, DUAN ZHIJUN, WANG QIUMING, ZHOU QIN, SUN XIAOYU. Octreotide attenuates liver fibrosis by inhibiting hepatic heme oxygenase-1 expression. Mol Med Rep 2015; 11:83-90. [PMID: 25338529 PMCID: PMC4237075 DOI: 10.3892/mmr.2014.2735] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2013] [Accepted: 07/21/2014] [Indexed: 01/05/2023] Open
Abstract
The aim of the present study was to investigate the effects of octreotide treatment on hepatic heme oxygenase-1 (HO-1) expression, together with the influence of altered hepatic HO-1 expression levels on hepatic function and fibrosis in bile duct-ligated rats. The rats were divided randomly into sham, cirrhotic, cobalt protoporphyrin and octreotide treatment groups. The expression levels of hepatic HO-1 mRNA were measured by reverse-transcription polymerase chain reaction, while the protein expression was determined by western blotting and immunohistochemical analysis. Hematoxylin and eosin, and Van Gieson's staining, along with determination of the hydroxyproline content in the liver, were performed to determine the degree of liver fibrosis. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL) and carboxyhemoglobin (COHb) in arterial blood, and the mean arterial pressure and portal vein pressure were also measured. As compared with the sham group, hepatic HO-1 mRNA and protein expression levels, serum levels of ALT, AST and TBIL, COHb in arterial blood, hydroxyproline and collagen type I content were all significantly increased in the cirrhotic group. As compared with the cirrhotic group, the octreotide-treated group exhibited significantly reduced hepatic HO-1 expression levels, serum levels of ALT, AST and TBIL, COHb in arterial blood and the extent of hepatic fibrosis, whereas the cobalt protoporphyrin group exhibited significantly increased hepatic HO-1 expression levels, as well as aggravated hepatic function and fibrosis (P<0.05). In conclusion, octreotide inhibited hepatic HO-1 overexpression in cirrhotic rats, reduced hepatic HO-1 expression levels to relieve liver injury and attenuated liver fibrosis.
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Affiliation(s)
- SHI-BIN GUO
- Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 0086-116011, P.R. China
| | - QING LI
- Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 0086-116011, P.R. China
- Department of Gastroenterology, Dalian Friendship Hospital, Dalian, Liaoning 0086-116011, P.R. China
| | - ZHI-JUN DUAN
- Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 0086-116011, P.R. China
| | - QIU-MING WANG
- Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 0086-116011, P.R. China
| | - QIN ZHOU
- Department of Pharmacology, Dalian Medical University, Dalian, Liaoning 0086-116011, P.R. China
| | - XIAO-YU SUN
- Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 0086-116011, P.R. China
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Adebayo D, Morabito V, Davenport A, Jalan R. Renal dysfunction in cirrhosis is not just a vasomotor nephropathy. Kidney Int 2014; 87:509-15. [PMID: 25296092 PMCID: PMC4346614 DOI: 10.1038/ki.2014.338] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2013] [Revised: 04/17/2014] [Accepted: 04/17/2014] [Indexed: 12/13/2022]
Abstract
The short-term mortality of cirrhotic patients who develop renal dysfunction remains unacceptably high, and as such the treatment of this condition is an unmet need. Although features of kidney injury are well recognized in these patients, the pathophysiology is complex and not completely understood. Improved understanding of the pathophysiological mechanisms involved in renal dysfunction occurring on a background of cirrhosis is key to developing effective treatment strategies to improve survival. Renal dysfunction due to hepatorenal syndrome (HRS) is characteristic of cirrhosis. Our current understanding is that HRS is functional in nature and occurs as a consequence of hemodynamic changes associated with portal hypertension. However, there is evidence in the literature suggesting that, histologically, the kidneys are not always normal in the vast majority of patients who present with renal dysfunction on the background of cirrhosis. Furthermore, there is emerging data implicating nonvasomotor mechanisms in the pathophysiology of renal dysfunction in cirrhosis. This mini-review aims to present the evidence suggesting that factors other than hemodynamic dysregulation have an important role in the development of this major complication for patients with progressive cirrhosis.
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Affiliation(s)
- Danielle Adebayo
- Liver Failure Group, UCL Institute for Liver and Digestive Health, UCL Medical School, Royal Free Hospital, London, UK
| | - Vincenzo Morabito
- Liver Failure Group, UCL Institute for Liver and Digestive Health, UCL Medical School, Royal Free Hospital, London, UK
| | - Andrew Davenport
- UCL Centre for Nephrology, Royal Free London NHS Foundation Trust, London, UK
| | - Rajiv Jalan
- Liver Failure Group, UCL Institute for Liver and Digestive Health, UCL Medical School, Royal Free Hospital, London, UK
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Sauerbruch T, Trebicka J. Future therapy of portal hypertension in liver cirrhosis - a guess. F1000PRIME REPORTS 2014; 6:95. [PMID: 25374673 PMCID: PMC4191223 DOI: 10.12703/p6-95] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
In patients with chronic liver disease, portal hypertension is driven by progressive fibrosis and intrahepatic vasoconstriction. Interruption of the initiating and perpetuating etiology—mostly leading to necroinflammation—is possible for several underlying causes, such as autoimmune hepatitis, hepatitis B virus (HBV) infection, and most recently hepatitis C virus (HCV) infection. Thus, in the long run, lifestyle-related liver damage due to chronic alcoholism or morbid obesity will remain the main factor leading to portal hypertension. Both causes are probably more easily countered by socioeconomic measures than by individual approaches. If chronic liver injury supporting fibrogenesis and portal hypertension cannot be interrupted, a wide variety of tools are available to modulate and reduce intrahepatic resistance and therewith portal hypertension. Many of these have been evaluated in animal models. Also, some well-established drugs, which are used in humans for other indications (for example, statins), are promising if applied early and concomitantly to standard therapy. In the future, more individually tailored strategies must also be considered in line with the spectrum of portal hypertensive complications and risk factors defined by high-throughput analysis of the patient’s genome, transcriptome, metabolome, or microbiome.
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Singhal A, Mukerji AN, Thomaides A, Karachristos A, Maloo M, Sanchez B, Keresztury M, Santora TA, Jain A. Chronotropic incompetence on dobutamine stress echocardiography in candidates for a liver transplant. EXP CLIN TRANSPLANT 2014; 11:546-53. [PMID: 24344945 DOI: 10.6002/ect.2012.0295] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
OBJECTIVES We evaluated dobutamine stress echocardiography as an initial screening test for a cardiac evaluation before a liver transplant. MATERIALS AND METHODS We retrospectively examined 111 liver transplant candidates who had undergone previous cardiac evaluation; 30 of whom had undergone a liver transplant. RESULTS Eighty patients (72.1%) completed a dobutamine stress echocardiography (41 chronotropically competent, 39 incompetent), while 31 patients (27.9%) required us to terminate early. Overall, 68 patients (61%) were on β-blockers (21 required early dobutamine stress echocardiography termination, 30 chronotropically incompetent, and 17 competent). Patient results were normal. Thirty patients underwent a liver transplant. Among candidates requiring termination of early dobutamine stress echocardiography, posttransplant cardiac events included 1 fatal acute myocardial infarction, 1 nonfatal acute myocardial infarction, and 1 idiopathic cardiomyopathy. Among chronotropically incompetent patients, 2 patients had transient bradycardia, and among those who were chronotropically competent, 1 had refractory atrial fibrillation, and 1 had transient bradycardia. CONCLUSIONS Nearly 50% of patients with end-stage liver disease may not reach the target heart rate. Early termination of dobutamine stress echocardiography because of cardiac symptoms or significant echocardiographic changes have more effect in predicting postoperative cardiac events, but further evaluation is required even if their target heart rate is close to that desired. Lower target heart rate may be acceptable in chronotropically incompetent individuals provided they are asymptomatic, have no echocardiographic changes, or cardiovascular risk factors, especially if they are on β-blockers.
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Affiliation(s)
- Ashish Singhal
- Division of Abdominal Organ Transplantation, Department of Surgery, Temple University Hospital, Philadelphia, PA 19140 USA
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