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1
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Praktiknjo M, Dollinger M, Braden B, Laleman W, Trebicka J. [Endo-Hepatology: New Endoscopic Solutions for Old Hepatological Problems]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2025. [PMID: 40306648 DOI: 10.1055/a-2590-9998] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/02/2025]
Abstract
With the rapid development of endoscopic ultrasound (EUS), diagnostic and therapeutic platforms have emerged that are applicable in hepatology. New tools such as EUS-guided portal pressure measurement (in combination with EUS-guided liver biopsy) or EUS-guided variceal obliteration using coils and glue present attractive procedures that can potentially overcome the limitations of current gold standards. In this review article, we provide an overview of these new 'endo-hepatology' techniques and highlight their current role in the treatment of liver diseases.
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Affiliation(s)
| | - Matthias Dollinger
- Medizinische Klinik I Gastroenterologie, Nephrologie und Diabetologie, Klinikum Landshut gGmbH, Landshut, Germany
- Innere Medizin I, University Hospital Ulm, Ulm, Germany
| | - Barbara Braden
- Medizinische Klinik B, Universitätsklinikum Münster, Munster, Germany
| | - Wim Laleman
- Medizinische Klinik B, Universitätsklinikum Münster, Munster, Germany
- Department of Gastroenterology and Hepatology, Section of Liver and Biliopancreatic Disorders, University Hospitals Leuven, Leuven, Belgium
| | - Jonel Trebicka
- Medizinische Klinik B, Universitätsklinikum Münster, Munster, Germany
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Thiele M, Johansen S, Israelsen M, Trebicka J, Abraldes JG, Gines P, Krag A. Noninvasive assessment of hepatic decompensation. Hepatology 2025; 81:1019-1037. [PMID: 37801593 PMCID: PMC11825506 DOI: 10.1097/hep.0000000000000618] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Accepted: 07/19/2023] [Indexed: 10/08/2023]
Abstract
Noninvasive tests (NITs) are used in all aspects of liver disease management. Their most prominent break-through since the millennium has been in advancing early detection of liver fibrosis, but their use is not limited to this. In contrast to the symptom-driven assessment of decompensation in patients with cirrhosis, NITs provide not only opportunities for earlier diagnoses but also accurate prognostication, targeted treatment decisions, and a means of monitoring disease. NITs can inform disease management and decision-making based on validated cutoffs and standardized interpretations as a valuable supplement to clinical acumen. The Baveno VI and VII consensus meetings resulted in tangible improvements to pathways of care for patients with compensated and decompensated advanced chronic liver disease, including the combination of platelet count and transient elastography to diagnose clinically significant portal hypertension. Furthermore, circulating NITs will play increasingly important roles in assessing the response to interventions against ascites, variceal bleeding, HE, acute kidney injury, and infections. However, due to NITs' wide availability, there is a risk of inaccurate use, leading to a waste of resources and flawed decisions. In this review, we describe the uses and pitfalls of NITs for hepatic decompensation, from risk stratification in primary care to treatment decisions in outpatient clinics, as well as for the in-hospital management of patients with acute-on-chronic liver failure. We summarize which NITs to use when, for what indications, and how to maximize the potential of NITs for improved patient management.
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Affiliation(s)
- Maja Thiele
- Department of Gastroenterology and Hepatology, Fibrosis, Fatty Liver and Steatohepatitis Research Center Odense (FLASH), Odense University Hospital, Odense, Denmark
- Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
| | - Stine Johansen
- Department of Gastroenterology and Hepatology, Fibrosis, Fatty Liver and Steatohepatitis Research Center Odense (FLASH), Odense University Hospital, Odense, Denmark
- Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
| | - Mads Israelsen
- Department of Gastroenterology and Hepatology, Fibrosis, Fatty Liver and Steatohepatitis Research Center Odense (FLASH), Odense University Hospital, Odense, Denmark
- Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
| | - Jonel Trebicka
- Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
- Department of Internal Medicine B, University of Münster, Münster, Germany
- European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain
| | - Juan G. Abraldes
- Division of Gastroenterology, University of Alberta, Edmonton, Canada
| | - Pere Gines
- Liver Unit, Hospital Clínic of Barcelona, Barcelona, Spain
- Faculty of Medicine and Health Sciences, University of Barcelona, Spain
- Institute of Biomedical Investigation August Pi I Sunyer (IDIBAPS), Barcelona, Spain
- Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain
| | - Aleksander Krag
- Department of Gastroenterology and Hepatology, Fibrosis, Fatty Liver and Steatohepatitis Research Center Odense (FLASH), Odense University Hospital, Odense, Denmark
- Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
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Dabas MM, Maqbool M, Bedros AW, Mazhar H, Papuashvili P, Umar M, Bajwa AB, Patel DH, Abushalha NB, Khattak A, Ahmed J, Mehdi A. Comparative Effectiveness of Endoscopic Versus Pharmacological Interventions for Variceal Rebleeding in Cirrhosis: A Systematic Review. Cureus 2024; 16:e72085. [PMID: 39575046 PMCID: PMC11579546 DOI: 10.7759/cureus.72085] [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: 10/21/2024] [Indexed: 11/24/2024] Open
Abstract
Variceal bleeding is a critical complication in cirrhotic patients, significantly increasing morbidity and mortality risks, particularly after an initial bleeding episode. This systematic review evaluates and compares the effectiveness of endoscopic and pharmacological interventions in preventing variceal rebleeding. A comprehensive search of major databases, including PubMed, MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science, was conducted to identify studies published within the past decade. The review focused on randomized controlled trials, clinical trials, and meta-analyses that assessed the efficacy and safety of these treatments in adult cirrhotic patients with a history of variceal bleeding. The findings suggest that endoscopic interventions, such as band ligation and early transjugular intrahepatic portosystemic shunt (TIPS) placement, effectively reduce immediate rebleeding rates and improve short-term survival, particularly in high-risk patients with advanced cirrhosis. In contrast, pharmacological strategies, including beta-blockers and vasoactive agents, provide effective long-term management with fewer adverse events, especially in patients with milder liver disease. The review underscores the importance of a personalized treatment approach that integrates both endoscopic and pharmacological therapies to optimize outcomes and reduce the burden of rebleeding. It also highlights the need for further high-quality research to clarify the long-term benefits, impact on quality of life, and cost-effectiveness of these interventions. These insights form the basis for refining clinical guidelines and improving patient-centered care in the management of variceal rebleeding.
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Affiliation(s)
| | - Muhammad Maqbool
- Internal Medicine, Shaheed Mohtarma Benazir Bhutto Medical College Lyari, Karachi, PAK
| | | | - Hiba Mazhar
- Gastroenterology, Pakistan Kidney and Liver Institute, Lahore, PAK
| | | | - Muhammad Umar
- Internal Medicine, Faisalabad Medical University, Faisalabad, PAK
| | - Aqsa B Bajwa
- Internal Medicine, Shalamar Medical and Dental College, Riyadh, SAU
| | | | | | - Abid Khattak
- Acute Medicine, Sherwood Forest Hospitals NHS Foundation Trust, Sutton-in-Ashfield, GBR
| | - Junaid Ahmed
- Internal Medicine, Chandka Medical College Hospital, Larkana, PAK
| | - Asma Mehdi
- Surgery, Rawalpindi Medical University, Rawalpindi, PAK
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4
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Brujats A, Villanueva C. Examining the therapeutic landscape of beta-blockers in portal hypertension. Clin Mol Hepatol 2024; 30:1055-1059. [PMID: 38447532 PMCID: PMC11540378 DOI: 10.3350/cmh.2024.0144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2024] [Revised: 03/04/2024] [Accepted: 03/04/2024] [Indexed: 03/08/2024] Open
Affiliation(s)
- Anna Brujats
- Hospital Santa Creu and Sant Pau, Autonomous University of Barcelona, Hospital Sant Pau Biomedical Research Institute (IIB Sant Pau), Barcelona, Spain
| | - Càndid Villanueva
- Hospital Santa Creu and Sant Pau, Autonomous University of Barcelona, Hospital Sant Pau Biomedical Research Institute (IIB Sant Pau), Barcelona, Spain
- Centre for Biomedical Research in Liver and Digestive Diseases Network (CIBERehd), Barcelona, Spain
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Yu JA, Yang SW, Wang Y, Li J, Su TH, Chang J, Chen G. The Balloon Catheter Method and the End-hole Catheter Method in the Measurement of Hepatic Venous Pressure Gradient: a Comparative Study. Cardiovasc Intervent Radiol 2024; 47:1356-1362. [PMID: 39060793 DOI: 10.1007/s00270-024-03814-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2024] [Accepted: 07/13/2024] [Indexed: 07/28/2024]
Abstract
OBJECTIVE This study aims to evaluate the differences between The balloon catheter method and End-hole Catheter Method in measuring hepatic venous pressure gradient (HVPG) among cirrhosis patients. METHODS From October 2017 to January 2024, patients who underwent HVPG measurements using both methods were consecutively included. HVPGs obtained from both methods were compared with the portal vein pressure gradient (PPG) obtained via transjugular intrahepatic portosystemic shunt (TIPS) using paired comparisons. Additionally, the consistency and predictive ability for bleeding risk of the two methods, as well as the impact of intrahepatic veno-venous shunt (IHVS), were analyzed. RESULTS The study enrolled 145 patients, each of whom had HVPG measured by both methods. PPG was measured in 61 patients. There was a statistically significant difference between the PPGs and HVPGs measured by both the balloon catheter method and the end-hole catheter method (P < 0.001), with the HVPG mean values obtained by the end-hole catheter method being closer to the PPGs. In the non-IHVS group, no significant statistical difference was found between the two methods (P = 0.071). In contrast, the IHVS group showed a significant difference (P < 0.001), with a mean difference of 2.98 ± 4.03 mmHg. When IHVS was absent, the measurement results from the end-hole catheter method and the balloon catheter method were found to be highly correlated. The end-hole catheter method has a higher screening capability for patients at risk of bleeding compared to the balloon catheter method (75.90% vs. 72.86%). CONCLUSION HVPG measurements using either the balloon catheter method or end-hole catheter method showed significant difference with the PPG. The end-hole catheter method has a higher screening capability for patients at risk of bleeding, and IHVS could lead to lower HVPG measurements with The balloon catheter method.
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Affiliation(s)
- Jian-An Yu
- Department of Interventional Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Si-Wei Yang
- Department of Interventional Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Yu Wang
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Jian Li
- Department of Interventional Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Tian-Hao Su
- Department of Interventional Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Jiang Chang
- Department of Interventional Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Guang Chen
- Department of Interventional Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
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6
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Drolz A. [Bleeding in liver diseases]. Med Klin Intensivmed Notfmed 2024; 119:458-464. [PMID: 39138654 DOI: 10.1007/s00063-024-01167-3] [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: 06/12/2024] [Accepted: 07/08/2024] [Indexed: 08/15/2024]
Abstract
Bleeding events are feared complications in patients with advanced liver diseases and are associated with morbidity and mortality. In this context, gastrointestinal bleeding, particularly upper gastrointestinal bleeding, has a special clinical importance. In addition to endoscopic measures for hemostasis, reducing portal pressure in particular is a key component of treatment. Although the standard coagulation parameters are often altered in patients with liver diseases, optimizing coagulation plays a secondary role. Typically, a bundle of measures are employed in patients with portal hypertensive bleeding, which nowadays in most cases can halt the bleeding and stabilize the situation. The measures include endoscopy, antibiotic treatment, vasopressor treatment and, if necessary, shunt placement (transjugular intrahepatic portosystemic shunt).
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Affiliation(s)
- Andreas Drolz
- I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Deutschland.
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Garcia-Guix M, Ardevol A, Sapena V, Alvarado-Tápias E, Huertas A, Brujats A, Fajardo J, Cuyas B, Poca M, Guarner C, Torras X, Escorsell À, Villanueva C. Influence of further decompensation on survival across clinical stages of decompensated cirrhosis: The role of portal hypertension and HVPG changes. Liver Int 2024; 44:1971-1989. [PMID: 38634685 DOI: 10.1111/liv.15937] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Revised: 03/13/2024] [Accepted: 04/02/2024] [Indexed: 04/19/2024]
Abstract
BACKGROUND AND AIMS Decompensated-cirrhosis encompasses several stages with different prognosis, such as bleeding, ascites and bleeding-plus-ascites. Development of further-decompensation worsens survival, while non-selective β-blockers (NSBBs) can modify the risk. However, how this applies to each stage is uncertain. We aimed to investigate, in each stage of decompensated-cirrhosis, the influence of further-decompensation on mortality and whether changes in portal-pressure (HVPG) under NSBBs influence these outcomes. METHODS Patients with variceal bleeding were consecutively included differentiating those with bleeding-alone from those who also had ascites. Patients with ascites and high-risk varices referred for primary-prophylaxis were also investigated. A baseline haemodynamic study was performed and was repeated after 1-3-months under NSBBs. Outcomes were investigated by competing-risk. RESULTS Totally 103 patients had bleeding-alone, 186 bleeding-plus-ascites and 187 ascites-alone. Mean follow-up was 32-months (IQR, 12-60). Patients with bleeding-plus-ascites had higher HVPG and were more hyperdynamic than patients with ascites-alone and these than those with bleeding-alone. At each stage, the mortality risk was more than twice in patients developing further-decompensation vs. those without (p < .001). In each stage, HVPG-decrease under NSBBs showed better discrimination to predict further-decompensation than the baseline MELD, Child-Pugh or HVPG, by time-dependent ROC-curves (c-statistic >70%). At each stage, patients without HVPG-decreases, either ≥10% or ≥20% from the baseline, had higher risk of further-decompensation (sHR from 2.43 to 6.73, p < .01) and worse survival. CONCLUSIONS In each stage of decompensated cirrhosis, mortality risk significantly and very markedly increase with further-decompensation. HVPG-non-response to NSBBs may adequately stratify the risk of further decompensation and death, in each stage. This suggests potential benefit with pre-emptive therapies in HVPG-non-responders at each-stage.
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Affiliation(s)
- Marta Garcia-Guix
- Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
| | - Alba Ardevol
- Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Victor Sapena
- Biostatistics Unit, Medical School, Universitat Autònoma de Barcelona, Barcelona, Spain
- Medical Statistics Core Faculty, IDIBAPS, Hospital Clinic, Barcelona, Spain
| | - Edilmar Alvarado-Tápias
- Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
| | - Anna Huertas
- Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Anna Brujats
- Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
| | - Javier Fajardo
- Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Berta Cuyas
- Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
| | - María Poca
- Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
| | - Carlos Guarner
- Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
| | - Xavier Torras
- Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
| | - Àngels Escorsell
- Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
| | - Càndid Villanueva
- Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
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Vashishtha C, Sarin SK. Bleeding Complications of Portal Hypertension. Clin Liver Dis 2024; 28:483-501. [PMID: 38945639 DOI: 10.1016/j.cld.2024.03.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/02/2024]
Abstract
In portal hypertension, acute variceal bleed is the cause of 2/3rd of all upper gastrointestinal bleeding episodes. It is a life-threatening emergency in patients with cirrhosis. Nonselective beta-blockers by decreasing the hepatic venous pressure gradient are the mainstay of medical therapy for the prevention of variceal bleeding and rebleeding. Evaluation of the severity of bleed, hemodynamic resuscitation, prophylactic antibiotic, and intravenous splanchnic vasoconstrictors should precede the endoscopy procedure. Endoscopic band ligation is the recommended endotherapy. Rescue transjugular intrahepatic port-systemic shunt (TIPS) is recommended for variceal bleed refractory to endotherapy. In patients with a high risk of failure of combined pharmacologic and endoscopic therapy, pre-emptive TIPS may improve the outcome. For gastric varices, "Sarin classification" is universally applied as it is simple and has therapeutic implication. For IGV1 and GOV2, injection cyanoacrylate glue is considered the endotherapy of choice. Endoscopic ultrasound is a useful modality in the management of gastric varices.
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Affiliation(s)
- Chitranshu Vashishtha
- Department of Hepatology, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi 110070, India
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi 110070, India.
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Rodrigues SG, Delgado MG, Stirnimann G, Berzigotti A, Bosch J. Hepatic Venous Pressure Gradient: Measurement and Pitfalls. Clin Liver Dis 2024; 28:383-400. [PMID: 38945633 DOI: 10.1016/j.cld.2024.03.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/02/2024]
Abstract
Measurement of hepatic venous pressure gradient (HVPG) effectively mirrors the severity of portal hypertension (PH) and offers valuable insights into prognosis of liver disease, including the risk of decompensation and mortality. Additionally, HVPG offers crucial information about treatment response to nonselective beta-blockers and other medications, with its utility demonstrated in clinical trials in patients with PH. Despite the widespread dissemination and validation of noninvasive tests, HVPG still holds a significant role in hepatology. Physicians treating patients with liver diseases should comprehend the HVPG measurement procedure, its applications, and how to interpret the results and potential pitfalls.
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Affiliation(s)
- Susana G Rodrigues
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, MEM, Murtenstrasse 35 Office F807, Bern 3008, Switzerland
| | - Maria Gabriela Delgado
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, MEM, Murtenstrasse 35 Office F808, Bern 3008, Switzerland
| | - Guido Stirnimann
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Freiburgstrasse, Bern 3010, Switzerland
| | - Annalisa Berzigotti
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, BHH D115, Freiburgstrasse 10, Bern 3010, Switzerland
| | - Jaime Bosch
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, MEM, Murtenstrasse 35 Office F805, Bern 3008, Switzerland; CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas), Barcelona, Spain.
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10
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Alsaeid M, Sung S, Bai W, Tam M, Wong YJ, Cortes J, Cobo E, Gonzalez JA, Abraldes JG. Heterogeneity of treatment response to beta-blockers in the treatment of portal hypertension: A systematic review. Hepatol Commun 2024; 8:e0321. [PMID: 38285880 PMCID: PMC10830085 DOI: 10.1097/hc9.0000000000000321] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Accepted: 09/28/2023] [Indexed: 01/31/2024] Open
Abstract
BACKGROUND It has been suggested that a relevant proportion of patients do not respond to nonselective beta-blockers (NSBB)s, which raises questions regarding the need for individualized therapy. The existence of potential heterogeneity in the treatment response can be assessed using the variability ratio (VR) of the outcome measurement (in this case, HVPG) between the treated and placebo groups. We conducted a systematic review and meta-analysis of randomized controlled trials to assess the potential heterogeneity in the portal pressure response to NSBBs. METHODS After a systematic search, we quantified the heterogeneity of treatment response with the VR between the treatment and control groups, with VR > 1 indicating potential heterogeneity. We used a similar approach to compare carvedilol with propranolol and statins with placebo. RESULTS We identified 18 studies that included 965 patients. A comparison between beta-blockers and placebo showed a pooled VR of 0.99 (95% CI:0.87-1.14), which suggests a homogeneous HVPG response to NSBB at the individual patient level (ie, no evidence to support that some patients responded to beta-blockers and others did not). For the comparison between carvedilol and propranolol, pooled VR was 0.97 (95% CI 0.82-1.14), suggesting that carvedilol achieves a greater average response (rather than an increase in the proportion of responders). There was no evidence of a heterogeneous response to statins. CONCLUSION Our analysis did not support the existence of a heterogeneous patient-by-patient response to NSBBs in cirrhosis. These findings challenge the concept of personalized therapy based on portal pressure response and indicate that routine portal pressure measurement may not be necessary to guide NSBB therapy.
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Affiliation(s)
- Mohammad Alsaeid
- Liver Unit, Division of Gastroenterology, University of Alberta, Alberta, Canada
| | - Shuen Sung
- Liver Unit, Division of Gastroenterology, University of Alberta, Alberta, Canada
| | - Wayne Bai
- Waikato District Health Board, University of Auckland, Auckland, New Zealand
| | - Matthew Tam
- Liver Unit, Division of Gastroenterology, University of Alberta, Alberta, Canada
| | - Yu Jun Wong
- Liver Unit, Division of Gastroenterology, University of Alberta, Alberta, Canada
| | - Jordi Cortes
- Department of Statistics and Operations Research, Universitat Politècnica de Catalunya, Barcelona-Tech (UPC), Barcelona-Tech, Spain
| | - Erik Cobo
- Department of Statistics and Operations Research, Universitat Politècnica de Catalunya, Barcelona-Tech (UPC), Barcelona-Tech, Spain
| | - Jose Antonio Gonzalez
- Department of Statistics and Operations Research, Universitat Politècnica de Catalunya, Barcelona-Tech (UPC), Barcelona-Tech, Spain
| | - Juan G Abraldes
- Liver Unit, Division of Gastroenterology, University of Alberta, Alberta, Canada
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11
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Ferral H, Schepis F, Gaba RC, Garcia-Tsao G, Zanetto A, Perez-Campuzano V, Haskal ZJ, Garcia-Pagan JC. Endovascular Assessment of Liver Hemodynamics in Patients with Cirrhosis Complicated by Portal Hypertension. J Vasc Interv Radiol 2023; 34:327-336. [PMID: 36516940 DOI: 10.1016/j.jvir.2022.12.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 11/02/2022] [Accepted: 12/04/2022] [Indexed: 12/14/2022] Open
Abstract
The hepatic venous pressure gradient (HVPG) is currently considered the gold standard to assess portal hypertension (PH) in patients with cirrhosis. A meticulous technique is important to achieve accurate and reproducible results, and values obtained during measurement are applied in risk stratification of patients with PH, allocating treatment options, monitoring follow-up, and deciding management options in surgical patients. The use of portosystemic pressure gradients in patients undergoing placement of transjugular intrahepatic portosystemic shunts has been studied extensively and has great influence on decisions on shunt diameter. The purpose of this study was to describe the recommended technique to measure HVPG and portosystemic pressure gradient and to review the existing literature describing the importance of these hemodynamic measurements in clinical practice.
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Affiliation(s)
- Hector Ferral
- Section of Interventional Radiology, Department of Radiology, Louisiana State University, New Orleans, Louisiana
| | - Filippo Schepis
- Hepatic Hemodynamic Laboratory, Division of Gastroenterology, AOU of Modena and University of Modena and Reggio Emilia, Modena, Italy
| | - Ron C Gaba
- Division of Interventional Radiology, Department of Radiology, University of Illinois at Chicago, Chicago, Illinois
| | - Guadalupe Garcia-Tsao
- Digestive Disease Section, Internal Medicine, Yale School of Medicine, New Haven, Connecticut; VA-Connecticut Healthcare System, West Haven, Connecticut
| | - Alberto Zanetto
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, Italy
| | - Valeria Perez-Campuzano
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas, Madrid, Spain; Health Care Provider of the European Reference Network on Rare Liver Disorders, Hamburg, Germany
| | - Ziv J Haskal
- Department of Radiology and Medical Imaging/Interventional Radiology, University of Virginia School of Medicine, Charlottesville, Virginia
| | - Juan Carlos Garcia-Pagan
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas, Madrid, Spain; Health Care Provider of the European Reference Network on Rare Liver Disorders, Hamburg, Germany.
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12
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Sauerbruch T, Hennenberg M, Trebicka J, Schierwagen R. Beta-blockers in patients with liver cirrhosis: Pragmatism or perfection? Front Med (Lausanne) 2023; 9:1100966. [PMID: 36743678 PMCID: PMC9891090 DOI: 10.3389/fmed.2022.1100966] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Accepted: 12/12/2022] [Indexed: 01/11/2023] Open
Abstract
With increasing decompensation, hyperdynamic circulatory disturbance occurs in liver cirrhosis despite activation of vasoconstrictors. Here, the concept of a therapy with non-selective beta-blockers was established decades ago. They lower elevated portal pressure, protect against variceal hemorrhage, and may also have pleiotropic immunomodulatory effects. Recently, the beneficial effect of carvedilol, which blocks alpha and beta receptors, has been highlighted. Carvedilol leads to "biased-signaling" via recruitment of beta-arrestin. This effect and its consequences have not been sufficiently investigated in patients with liver cirrhosis. Also, a number of questions remain open regarding the expression of beta-receptors and its intracellular signaling and the respective consequences in the intra- and extrahepatic tissue compartments. Despite the undisputed role of non-selective beta-blockers in the treatment of liver cirrhosis, we still can improve the knowledge as to when and how beta-blockers should be used in which patients.
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Affiliation(s)
- Tilman Sauerbruch
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
| | - Martin Hennenberg
- Department of Urology, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany
| | - Jonel Trebicka
- Department of Internal Medicine B, University of Münster, Münster, Germany
- European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain
| | - Robert Schierwagen
- Department of Internal Medicine B, University of Münster, Münster, Germany
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13
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Wang L, Zhang Y, Wu YF, Yue ZD, Fan ZH, Zhang CY, Liu FQ, Dong J. Computed tomography perfusion in liver and spleen for hepatitis B virus-related portal hypertension: A correlation study with hepatic venous pressure gradient. World J Gastroenterol 2022; 28:6068-6077. [PMID: 36405387 PMCID: PMC9669822 DOI: 10.3748/wjg.v28.i42.6068] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2022] [Revised: 10/14/2022] [Accepted: 10/31/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Hepatic venous pressure gradient (HVPG) is the gold standard for diagnosis of portal hypertension (PH). However, its use can be limited because it is an invasive procedure. Therefore, it is necessary to explore a non-invasive method to assess PH. AIM To investigate the correlation of computed tomography (CT) perfusion of the liver with HVPG and Child-Pugh score in hepatitis B virus (HBV)-related PH. METHODS Twenty-eight patients (4 female, 24 male) with gastroesophageal variceal bleeding induced by HBV-related PH were recruited in our study. All patients received CT perfusion of the liver before transjugular intrahepatic portosystemic stent-shunt (TIPS) therapy. Quantitative parameters of CT perfusion of the liver, including liver blood flow (LBF), liver blood volume (LBV), hepatic artery fraction, splenic blood flow and splenic blood volume were measured. HVPG was recorded during TIPS therapy. Correlation of liver perfusion with Child-Pugh score and HVPG were analyzed, and the receiver operating characteristic curve was analyzed. Based on HVPG (> 12 mmHg vs ≤ 12 mmHg), patients were divided into moderate and severe groups, and all parameters were compared. RESULTS Based on HVPG, 18 patients were classified into the moderate group and 10 patients were classified into the severe group. The Child-Pugh score, HVPG, LBF and LBV were significantly higher in the moderate group compared to the severe group (all P < 0.05). LBF and LBV were negatively associated with HVPG (r = -0.473, P < 0.05 and r = -0.503, P < 0.01, respectively), whereas splenic blood flow was positively associated with hepatic artery fraction (r = 0.434, P < 0.05). LBV was negatively correlated with Child-Pugh score. Child-Pugh score was not related to HVPG. Using a cutoff value of 17.85 mL/min/100 g for LBV, the sensitivity and specificity of HVPG ≥ 12 mmHg for diagnosis were 80% and 89%, respectively. CONCLUSION LBV and LBF were negatively correlated with HVPG and Child-Pugh scores. CT perfusion imaging is a potential non-invasive quantitative predictor for PH in HBV-related liver cirrhosis.
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Affiliation(s)
- Lei Wang
- Department of Intervention Therapy, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
| | - Yu Zhang
- Interventional Radiology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
| | - Yi-Fan Wu
- Interventional Radiology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
| | - Zhen-Dong Yue
- Interventional Radiology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
| | - Zhen-Hua Fan
- Interventional Radiology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
| | - Chun-Yan Zhang
- Department of Radiology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
| | - Fu-Quan Liu
- Interventional Radiology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
| | - Jian Dong
- Department of Radiology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
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14
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Spleen and Liver Stiffness Evaluation by ARFI Imaging: A Reliable Tool for a Short-Term Monitoring of Portal Hypertension? Int J Hepatol 2022; 2022:7384144. [PMID: 36117519 PMCID: PMC9481411 DOI: 10.1155/2022/7384144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Accepted: 08/16/2022] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND Assessment of hepatic venous pressure gradient (HVPG) is the most reliable, though invasive method for evaluation of portal hypertension. Non-invasive, elastography-based techniques are well established in diagnosis, but not in monitoring of portal hypertension. The aim of our prospective study was to determine the value of acoustic radiation force impulse (ARFI) elastography technique of the liver and spleen in diagnosis and monitoring of portal hypertension. METHODS We prospectively assessed portal hypertension by HVPG and corresponding elastography of the liver and spleen in 31 patients with liver cirrhosis and an indication for primary prophylaxis by non-cardio selective beta-blockers. Investigations were performed at baseline and a follow-up visit after 6-8 weeks. To address the known large variability of values for spleen elastography, well-defined corresponding areas in the spleen were used for baseline and follow-up elastography. Sensitivity, specificity, and AUC-ROC values for both spleen and liver elastography monitoring of portal hypertension were calculated. RESULTS Liver but not spleen elastography significantly correlated with HVPG results and was suitable for initial evaluation of portal hypertension. However, changes in HVPG results did not show any correlation with alterations of ARFI values from baseline to follow-up visits both for liver and spleen elastography. Spleen stiffness results were not homogeneous across the whole organ differing significantly between the upper, hilar, and bottom placed investigation areas. CONCLUSIONS In this prospective study ARFI-based assessment of liver elastography showed itself suitable for initial assessment but not for monitoring of portal hypertension. Spleen elastography was not appropriate for both, evaluation and monitoring of portal hypertension. A possible explanation for this new data that are in some contrast to previously published results is the degree of portal hypertension in our study, a comparatively short follow-up period, and well-defined investigation areas for spleen elastography in repetitive ARFI investigations. This trial is registered with NCT03315767.
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15
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Laleman W, Vanderschueren E, Van der Merwe S, Chang KJ. The use of endoscopic ultrasound in the diagnosis and management of portal hypertension. Best Pract Res Clin Gastroenterol 2022; 60-61:101811. [PMID: 36577537 DOI: 10.1016/j.bpg.2022.101811] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2022] [Accepted: 11/10/2022] [Indexed: 11/17/2022]
Abstract
The role of endoscopic ultrasound in the diagnosis and management of chronic liver disease is rapidly increasing. It forms one of the major backbones of endo-hepatology and brings us a step closer to personalized medicine. This review will focus on the particular use of EUS in the diagnosis and management of cirrhotic portal hypertension and potential complications hereof, such as ascites and gastrooesophageal varices. More specifically, EUS-guided Porto-systemic Pressure Gradient (EUS-PPG) measurement, EUS-guided coil and glue embolization of gastric varices, EUS-guided paracentesis and EUS-guided intrahepatic portosystemic shunt creation (IPSS) will be discussed in-depth with regard to clinical status, available data and technical considerations.
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Affiliation(s)
- Wim Laleman
- Department of Gastroenterology and Hepatology, Section of Liver and Biliopancreatic Disorders, University Hospitals Leuven, KU LEUVEN, Leuven, Belgium; Medizinische Klinik B, Universitätsklinikum Münster, Münster University, Münster, Germany.
| | - Emma Vanderschueren
- Department of Gastroenterology and Hepatology, Section of Liver and Biliopancreatic Disorders, University Hospitals Leuven, KU LEUVEN, Leuven, Belgium
| | - Schalk Van der Merwe
- Department of Gastroenterology and Hepatology, Section of Liver and Biliopancreatic Disorders, University Hospitals Leuven, KU LEUVEN, Leuven, Belgium
| | - Kenneth J Chang
- Digestive Health Institute, University of California, Irvine, CA, 92868, USA
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16
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Hofer BS, Simbrunner B, Bauer DJM, Paternostro R, Schwabl P, Scheiner B, Semmler G, Hartl L, Jachs M, Datterl B, Staettermayer AF, Trauner M, Mandorfer M, Reiberger T. Acute hemodynamic response to propranolol predicts bleeding and nonbleeding decompensation in patients with cirrhosis. Hepatol Commun 2022; 6:2569-2580. [PMID: 35808889 PMCID: PMC9426394 DOI: 10.1002/hep4.2021] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Revised: 04/17/2022] [Accepted: 05/29/2022] [Indexed: 11/29/2022] Open
Abstract
Nonselective beta‐blockers are used as prophylaxis for variceal bleeding in patients with advanced chronic liver disease (ACLD). The acute hemodynamic response to intravenous propranolol (i.e., ≥10% reduction in hepatic venous pressure gradient [HVPG]) is linked to a decreased risk of variceal bleeding. In this study, we aimed to investigate the overall prognostic value of an acute response in compensated and decompensated ACLD. We analyzed the long‐term outcome of prospectively recruited patients with ACLD following a baseline HVPG measurement with an intraprocedural assessment of the acute hemodynamic response to propranolol. Overall, we included 98 patients with ACLD (mean ± SD age, 56.4 ± 11.5 years; 72.4% decompensated; 88.8% varices; mean ± SD HVPG, 19.9 ± 4.4 mm Hg) who were followed for a median of 9.6 (interquartile range, 6.5–18.2) months. Fifty‐seven patients (58.2%) demonstrated an acute hemodynamic response to propranolol that was associated with a decreased risk of variceal bleeding (at 12 months, 3.6% vs. 15% in nonresponder; log‐rank, p = 0.038) and hepatic decompensation (at 12 months, 23% vs. 33% in nonresponder; log‐rank, p = 0.096). On multivariate analysis, the acute response was an independent predictor of first/further hepatic decompensation (adjusted hazards ratio, 0.31; 95% confidence interval [CI], 0.13–0.70; p = 0.005). Importantly, there was a tendency toward a prolonged transplant‐free survival in acute responders compared to nonresponders (34.2; 95% CI, 29.2–39.2 vs. 25.2; 95% CI, 19.8–30.6 months; log‐rank, p = 0.191). Conclusions: Patients with ACLD who achieve an acute hemodynamic response to intravenous propranolol experience a lower risk of variceal bleeding and nonbleeding hepatic decompensation events compared to nonresponders. An assessment of the acute hemodynamic response to intravenous propranolol provides important prognostic information in ACLD.
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Affiliation(s)
- Benedikt S Hofer
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria.,Vienna Hepatic Hemodynamic Laboratory, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria.,Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
| | - Benedikt Simbrunner
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria.,Vienna Hepatic Hemodynamic Laboratory, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria.,Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
| | - David J M Bauer
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria.,Vienna Hepatic Hemodynamic Laboratory, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Rafael Paternostro
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria.,Vienna Hepatic Hemodynamic Laboratory, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Philipp Schwabl
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria.,Vienna Hepatic Hemodynamic Laboratory, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria.,Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
| | - Bernhard Scheiner
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria.,Vienna Hepatic Hemodynamic Laboratory, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Georg Semmler
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria.,Vienna Hepatic Hemodynamic Laboratory, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Lukas Hartl
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria.,Vienna Hepatic Hemodynamic Laboratory, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Mathias Jachs
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria.,Vienna Hepatic Hemodynamic Laboratory, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Barbara Datterl
- Pharmacy Department, Vienna General Hospital, Vienna, Austria
| | - Albert F Staettermayer
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Mattias Mandorfer
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria.,Vienna Hepatic Hemodynamic Laboratory, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria.,Vienna Hepatic Hemodynamic Laboratory, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria.,Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
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17
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A Liver Stiffness Measurement-Based Nomogram Predicts Variceal Rebleeding in Hepatitis B-Related Cirrhosis. DISEASE MARKERS 2022; 2022:4107877. [PMID: 35692881 PMCID: PMC9184154 DOI: 10.1155/2022/4107877] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Revised: 04/03/2022] [Accepted: 04/11/2022] [Indexed: 11/17/2022]
Abstract
Background Cirrhosis esophageal variceal rebleeding is a major complication of chronic cirrhosis. The hepatic venous pressure gradient (HVPG) can predict the risk of rebleeding in patients with cirrhosis and has a good correlation with liver stiffness measurement (LSM). However, there are currently few studies based on liver stiffness to predict the risk of rebleeding in patients with liver cirrhosis. This study is aimed at exploring whether liver stiffness can predict rebleeding in patients with hepatitis B virus-related cirrhosis and developing an easy-to-use nomogram for predicting the risk of rebleeding in patients with liver cirrhosis undergoing secondary prevention. Methods A prospective analysis of 289 cirrhosis patients was performed. Univariate and multivariate analyses were used to identify independent prognostic factors to create a nomogram. The performance of the nomogram was evaluated by using a bootstrapped-concordance index and calibration plots. Results Use of a nonselective beta-blocker (NSBB) drug, LSM, hemoglobin, and platelet count were identified as factors that could predict rebleeding. We created a nomogram for rebleeding in cirrhosis by using these risk factors. The predictive ability of the nomogram was assessed by the C-index (0.772, 95% CI 0.732–0.822). The results of the calibration plots showed that the actual observation and prediction values obtained by the nomogram had good consistency. Conclusions LSM can predict the risk of rebleeding in patients with cirrhosis, while the nomogram is a conventional tool for doctors to facilitate a personalized prognostic evaluation.
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18
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Asesio N, Pollo-Flores P, Caliez O, Munteanu M, Ngo A, Ngo Y, Poynard T, Thabut D, Rudler M. Baveno VI criteria as a prognostic factor for clinical complications in patients with compensated cirrhosis. Dig Liver Dis 2022; 54:645-653. [PMID: 34583904 DOI: 10.1016/j.dld.2021.09.004] [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: 05/13/2021] [Revised: 08/16/2021] [Accepted: 09/06/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Combination of liver stiffness measurement and platelets count is a tool to safely rule out varices needing treatment (VNT) in patients with compensated advanced chronic liver disease (cACLD). AIMS to evaluate 4-year liver-related complications and survival in low-risk patients according to Baveno VI criteria. METHODS we conducted a monocentric retrospective analysis of prospectively collected data of all consecutive patients, with cirrhosis (LSM≥12.5 kPa) and without previous complication, evaluated between 2012 and 2015. Liver-related complications and survival were compared between 2 groups of patients: favourable (LSM< 20 kPa and platelet count>150.000/mm3) and unfavourable Baveno VI status patients (LSM ≥ 20 kPa or platelet count ≤150.000/mm3). RESULTS 455 patients with cACLD were analysed. Two hundred patients had favourable Baveno VI criteria, 3.6% with VNT. The 4-year probability of being free of acute decompensation was higher in low-risk patients (94.4 ± 1.8% vs. 85.7%±2.6%, p = 0.018). Unfavourable Baveno status was independently associated with acute decompensation. The probability of being free of HCC was significantly higher in low-risk patients (94.2 ± 1.8% vs. 87.6 ± 2.4%, p = 0.048). Liver-related mortality was not different between the 2 groups (p = 0.56). CONCLUSION The Baveno VI criteria could predict clinical outcome in cACLD.
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Affiliation(s)
- Nicolas Asesio
- Hepatology Department, La Pitié-Salpêtrière Hospital, 47-83 boulevard de l'Hôpital 75013 Paris, France
| | - Priscila Pollo-Flores
- Hepatology Department, La Pitié-Salpêtrière Hospital, 47-83 boulevard de l'Hôpital 75013 Paris, France; CAPES (coordenação de aperfeiçoamento de pessoal de nível superior), Fluminense's Federal University (UFF), Rio de Janeiro, Brasil
| | - Olivier Caliez
- Hepatology Department, La Pitié-Salpêtrière Hospital, 47-83 boulevard de l'Hôpital 75013 Paris, France
| | | | - An Ngo
- BioPredictive, Paris, France
| | - Yen Ngo
- BioPredictive, Paris, France
| | - Thierry Poynard
- Hepatology Department, La Pitié-Salpêtrière Hospital, 47-83 boulevard de l'Hôpital 75013 Paris, France; BioPredictive, Paris, France; Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | - Dominique Thabut
- Hepatology Department, La Pitié-Salpêtrière Hospital, 47-83 boulevard de l'Hôpital 75013 Paris, France; Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | - Marika Rudler
- Hepatology Department, La Pitié-Salpêtrière Hospital, 47-83 boulevard de l'Hôpital 75013 Paris, France; Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Paris, France.
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19
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Tranah TH, Kronsten VT, Shawcross DL. Implications and Management of Cirrhosis-Associated Immune Dysfunction Before and After Liver Transplantation. Liver Transpl 2022; 28:700-716. [PMID: 34738724 DOI: 10.1002/lt.26353] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 10/18/2021] [Accepted: 10/27/2021] [Indexed: 12/28/2022]
Abstract
Cirrhosis-associated immune dysfunction (CAID) describes a panacea of innate and adaptive deficits that result from the sequelae of cirrhotic portal hypertension that is similar in its manifestations regardless of etiology of chronic liver injury. CAID is associated with synchronous observations of dysregulated priming of innate immune effector cells that demonstrate a proinflammatory phenotype but are functionally impaired and unable to adequately prevent invading pathogens. CAID is mainly driven by gut-barrier dysfunction and is associated with deficits of microbial compartmentalization and homeostasis that lead to tonic activation, systemic inflammation, and exhaustion of innate-immune cells. CAID leads to a high frequency of bacterial and fungal infections in patients with cirrhosis that are often associated with acute decompensation of chronic liver disease and acute-on-chronic liver failure and carry a high mortality rate. Understanding the deficits of mucosal and systemic immunity in the context of chronic liver disease is essential to improving care for patients with cirrhosis, preventing precipitants of acute decompensation of cirrhosis, and improving morbidity and survival. In this review, we summarize the detailed dynamic immunological perturbations associated with advanced chronic liver disease and highlight the importance of recognizing immune dysregulation as a sequela of cirrhosis. Furthermore, we address the role of screening, prevention, and early treatment of infections in cirrhosis in improving patient outcomes in transplant and nontransplant settings.
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Affiliation(s)
- Thomas H Tranah
- Institute of Liver Studies, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK.,Institute of Liver Studies, King's College Hospital National Health Service Foundation Trust, London, UK
| | - Victoria T Kronsten
- Institute of Liver Studies, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK.,Institute of Liver Studies, King's College Hospital National Health Service Foundation Trust, London, UK
| | - Debbie L Shawcross
- Institute of Liver Studies, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK.,Institute of Liver Studies, King's College Hospital National Health Service Foundation Trust, London, UK
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20
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Jachs M, Reiberger T. Non-selective Beta Blockers in Liver Cirrhosis. PHARMACOTHERAPY FOR LIVER CIRRHOSIS AND ITS COMPLICATIONS 2022:127-140. [DOI: 10.1007/978-981-19-2615-0_8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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21
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Warnes TW, Roberts SA, Smith A, Cope VM, Vales P, Haboubi NY, McMahon RF. Portal hypertension in primary biliary cholangitis: prevalence, natural history and histological correlates. Eur J Gastroenterol Hepatol 2021; 33:1595-1602. [PMID: 33323761 DOI: 10.1097/meg.0000000000002033] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVES The histopathological mechanisms underlying portal hypertension in primary biliary cholangitis (PBC) are poorly understood, as is its natural history. We have therefore determined the prevalence, severity and progression of portal hypertension in PBC and investigated whether its presence is related to specific histological lesions. METHODS Hepatic venous pressure gradient (HVPG) was measured in 86 patients, with 186 assessments over up to 7 years of follow-up and the results correlated with a semiquantitative grading of 8 histological features and nodular regenerative hyperplasia (NRH). RESULTS Portal hypertension (HVPG >5 mmHg) was present in 88% of all assessments (86% at baseline), and in 45% of patients at baseline was >12 mmHg (high-risk portal hypertension). The rise in portal pressure occurs early in the disease, since 45% of patients with normal serum bilirubin had a raised HVPG, as did 72% of patients with early (Ludwig stages 1 and 2) disease. After baseline, there was a small increase in HVPG over the next 5 years in most patients. In patients with precirrhotic PBC, 82% had portal hypertension and in 34% this was >12 mmHg. Portal pressure correlated significantly with a semiquantitative grading of cholestasis, interface hepatitis and portal tract and sinusoidal fibrosis. NRH was present in only 20% of wedge biopsies. CONCLUSIONS Portal hypertension commences in the early stages of PBC, long preceding both rises in serum bilirubin and the development of cirrhosis. Around 34% of precirrhotic PBC patients have 'high-risk' portal hypertension, which is associated with lesions in the portal tracts and sinusoids rather than with NRH.
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Affiliation(s)
- Thomas W Warnes
- Liver Unit, Department of Gastroenterology, Manchester Royal Infirmary
| | - Stephen A Roberts
- Centre of Biostatistics, School of Health Sciences, Manchester Academic Health Science Centre, University of Manchester
| | - Alexander Smith
- Liver Unit, Department of Gastroenterology, Manchester Royal Infirmary
| | | | - Patricia Vales
- Department of Medical Physics, Manchester Royal Infirmary
| | | | - Raymond F McMahon
- Department of Histopathology, Manchester Royal Infirmary, Manchester University NHS Foundation Trust, Manchester, UK
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22
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Bai W, Al-Karaghouli M, Stach J, Sung S, Matheson GJ, Abraldes JG. Test-Retest Reliability and Consistency of HVPG and Impact on Trial Design: A Study in 289 Patients from 20 Randomized Controlled Trials. Hepatology 2021; 74:3301-3315. [PMID: 34181770 DOI: 10.1002/hep.32033] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Revised: 06/10/2021] [Accepted: 06/24/2021] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIMS Portal hypertension (PH) is a major driver for cirrhosis complications. Portal pressure is estimated in practice by the HVPG. The assessment of HVPG changes has been used for drug development in PH. This study aimed at quantifying the test-retest reliability and consistency of HVPG in the specific context of randomized controlled trials (RCTs) for the treatment of PH in cirrhosis and its impact on power calculations for trial design. APPROACH AND RESULTS We conducted a search of published RCTs in patients with cirrhosis reporting individual patient-level data of HVPG at baseline and after an intervention, which included a placebo or an untreated control arm. Baseline and follow-up HVPGs in the control groups were extracted after digitizing the plots. We assessed reliability and consistency and the potential impact of study characteristics. We retrieved a total of 289 before and after HVPG measurements in the placebo/untreated groups from 20 RCTs. The time span between the two HVPG measurements ranged between 20 minutes and 730 days. Pre-/post-HVPG variability was lower in studies including only compensated patients; therefore, modeled sample size calculations for trials in compensated cirrhosis were lower than for decompensated cirrhosis. A higher proportion of alcohol-associated cirrhosis and unicentric trials was associated with lower differences between baseline and follow-up measurements. The smallest detectable difference in an individual was 26% and 30% in compensated and decompensated patients, respectively. CONCLUSIONS The test-retest reliability of HVPG is overall excellent. Within-individual variance was higher in studies including higher proportions of decompensated patients. These findings should be taken into account when performing power analysis for trials based on the effects on HVPG or when considering HVPG as a tool to guide therapy of PH.
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Affiliation(s)
- Wayne Bai
- Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, AB, Canada
| | - Mustafa Al-Karaghouli
- Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, AB, Canada
| | - Jesse Stach
- Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, AB, Canada.,Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB, Canada
| | - Shuen Sung
- Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, AB, Canada
| | - Granville J Matheson
- Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY.,Department of Clinical Neuroscience, Center for Psychiatry Research, Karolinska Institutet and Stockholm County Council, Stockholm, Sweden
| | - Juan G Abraldes
- Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, AB, Canada
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23
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Guo H, Zhang F, Yin X, Zhang M, Xiao J, Wang Y, Zhang B, Zhang W, Zou X, Zhuge Y. Endoscopic therapy + β-blocker vs. covered transjugular intrahepatic portosystemic shunt for prevention of variceal rebleeding in cirrhotic patients with hepatic venous pressure gradient ≥16 mmHg. Eur J Gastroenterol Hepatol 2021; 33:1427-1435. [PMID: 32868650 DOI: 10.1097/meg.0000000000001872] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND OBJECTIVE Currently, monitoring hepatic venous pressure gradient (HVPG) have been proved to be the best predictor for the risk of variceal bleeding. We performed the study to evaluate the effect of endoscopic therapy + β-blocker vs. covered transjugular intrahepatic portosystemic shunt (TIPS) for the prevention of variceal rebleeding in cirrhotic patients with HVPG ≥16 mmHg. METHODS Consecutive cirrhotic patients with HVPG ≥16 mmHg treated with endoscopic therapy + β-blocker or covered TIPS for variceal bleeding were retrospectively gathered between April 2013 and December 2018. The variceal rebleeding rate, survival, and incidence of overt hepatic encephalopathy (OHE) were compared. RESULTS A total of 83 patients were analyzed, of which 46 received endoscopic therapy + β-blocker and 37 covered TIPS. During a median follow-up of 12.0 months, the rebleeding rate (32.6 vs. 10.8%, P = 0.017) and rate of OHE (2.2 vs. 27.0%, P = 0.001) showed significant differences between the two groups, while liver transplantation-free survival (93.5 vs. 94.6%, P = 0.801) was similar. Preoperative and postoperative Child-Turcotte-Pugh scores were similar in either group. In addition, no significant differences of rebleeding rate (25.0 vs. 21.3%, P = 0.484) and survival (97.2 vs. 91.5%, P = 0.282) were observed between patients with 16 mmHg ≤ HVPG < 20 mmHg and HVPG ≥ 20 mmHg. CONCLUSION Covered TIPS was more effective than endoscopic therapy + β-blocker in preventing rebleeding in patients with HVPG ≥16 mmHg but did not improve survival. TIPS also induce more OHE.
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Affiliation(s)
- Huiwen Guo
- Department of Gastroenterology, Nanjing Medical University Drum Tower Clinical Medical School
| | - Feng Zhang
- Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Xiaochun Yin
- Department of Gastroenterology, Nanjing Medical University Drum Tower Clinical Medical School
| | - Ming Zhang
- Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Jiangqiang Xiao
- Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Yi Wang
- Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Bin Zhang
- Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Wei Zhang
- Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Xiaoping Zou
- Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Yuzheng Zhuge
- Department of Gastroenterology, Nanjing Medical University Drum Tower Clinical Medical School
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24
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Yao Q, Chen W, Yan C, Yu J, Jiang T, Cao H. Efficacy and Safety of Treatments for Patients With Portal Hypertension and Cirrhosis: A Systematic Review and Bayesian Network Meta-Analysis. Front Med (Lausanne) 2021; 8:712918. [PMID: 34540867 PMCID: PMC8446274 DOI: 10.3389/fmed.2021.712918] [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: 05/21/2021] [Accepted: 08/12/2021] [Indexed: 12/19/2022] Open
Abstract
Background and Aims: Viral hepatitis are one of the main causes of liver cirrhosis. The treatment of portal hypertension caused by liver cirrhosis is difficult and diverse, and the therapeutic effect is unknown. Bayesian network meta-analysis was performed to compare the efficacy and safety of treatments for patients with portal hypertension and cirrhosis, including a transjugular intrahepatic portosystemic shunt (TIPS), endoscopic therapy, surgical therapy and medications. Methods: Eligible articles were searched for in PubMed, Embase, Cochrane Library and Web of Science databases from their inception until June 2020. Using the "gemtc-0.8.4" package in R v.3.6.3 software and the Just Another Gibbs Sampler v.4.2.0 program, network meta-analysis was performed using a random effects model within a Bayesian framework. The odds ratios for all-cause rebleeding, bleeding-related mortality, overall survival (OS), treatment failure and hepatic encephalopathy were determined within the Bayesian framework. Results: Forty randomized controlled trials were identified, including 4,006 adult patients and nine treatment strategies. Our results showed that distal splenorenal shunt and TIPS provided the best control of hemorrhage. Endoscopic variceal ligation with medication resulted in the highest OS rate. Medication alone resulted in poor OS and treatment failure. Conclusions: We performed a systematic comparison of diverse treatments for cirrhotic patients with portal hypertension. Our meta-analysis indicated that a TIPS and distal splenorenal shunt resulted in lower rates of rebleeding than did other therapies. Furthermore, drugs are more suitable for combination therapy than monotherapy.
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Affiliation(s)
- Qigu Yao
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- National Clinical Research Center for Infectious Diseases, Hangzhou, China
| | - Wenyi Chen
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- National Clinical Research Center for Infectious Diseases, Hangzhou, China
| | - Cuilin Yan
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jiong Yu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- National Clinical Research Center for Infectious Diseases, Hangzhou, China
| | - Tian'an Jiang
- National Clinical Research Center for Infectious Diseases, Hangzhou, China
- Department of Ultrasound, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Hongcui Cao
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- National Clinical Research Center for Infectious Diseases, Hangzhou, China
- Zhejiang Provincial Key Laboratory for Diagnosis and Treatment of Aging and Physic-Chemical Injury Diseases, Hangzhou, China
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25
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Bruno R, Cammà C, Caraceni P, D'Amico G, Grattagliano I, La Mura V, Riggio O, Schepis F, Senzolo M, Angeli P, de Franchis R. Portal Hypertension and Ascites: Patient-and Population-centered Clinical Practice Guidelines by the Italian Association for the Study of the Liver (AISF). Dig Liver Dis 2021; 53:1089-1104. [PMID: 34321192 DOI: 10.1016/j.dld.2021.06.021] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Revised: 05/30/2021] [Accepted: 06/20/2021] [Indexed: 02/06/2023]
Abstract
Portal hypertension and ascites are two crucial events in the natural history of liver cirrhosis, whose appearance marks a downward shift in the prognosis of the disease. Over the years, several international and national societies have issued clinical practice guidelines for the diagnosis and management of portal hypertension and ascites. The present document addresses the needs of an updated guidance on the clinical management of these conditions. Accordingly, the AISF Governing Board appointed a multi-disciplinary committee of experts for drafting an update of the most recent EASL Clinical Practice Guidelines. The aim of this work was to adapt the EASL recommendations to national regulations and resources, local circumstances and settings, infrastructure, and cost/benefit strategies to avoid duplication of efforts and optimize resource utilization. The committee defined the objectives, the key issues and retrieved the relevant evidence by performing a systematic review of the literature. Finally, the committee members (chosen on the basis of their specific expertise) identified the guidelines' key questions and developed them following the PICO format (Population, Intervention, Comparison, Outcomes). For each of the PICO questions, the systematic review of the literature was made on the most important scientific databases (Pubmed, Scopus, Embase).
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26
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[Clinical presentation of bleeding in critically ill patients in the intensive care unit : Organ systems and clinical implications]. Med Klin Intensivmed Notfmed 2021; 116:482-490. [PMID: 34427697 DOI: 10.1007/s00063-021-00845-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Accepted: 07/09/2021] [Indexed: 10/20/2022]
Abstract
Bleedings are frequent and clinically important complications in critically ill patients in the intensive care unit, and-depending on location and intensity-are associated with high morbidity and mortality. The clinical impact of different bleeding entities is affected by the location (e.g. intracerebral bleedings), the severity (e.g. fulminant variceal bleeding) and the incidence (e.g. gastrointestinal bleeding) of the respective bleeding type. Therapy varies among bleeding entities, but consists of stabilization of the patient, control of the bleeding, and prevention of complications. This review describes relevant therapeutic aspects of selected bleeding complications in critically ill patients.
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27
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Zanetto A, Shalaby S, Feltracco P, Gambato M, Germani G, Russo FP, Burra P, Senzolo M. Recent Advances in the Management of Acute Variceal Hemorrhage. J Clin Med 2021; 10:3818. [PMID: 34501265 PMCID: PMC8432221 DOI: 10.3390/jcm10173818] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 08/21/2021] [Accepted: 08/24/2021] [Indexed: 12/12/2022] Open
Abstract
Gastrointestinal bleeding is one of the most relevant causes of death in patients with cirrhosis and clinically significant portal hypertension, with gastroesophageal varices being the most frequent source of hemorrhage. Despite survival has improved thanks to the standardization on medical treatment aiming to decrease portal hypertension and prevent infections, mortality remains significant. In this review, our goal is to discuss the most recent advances in the management of esophageal variceal hemorrhage in cirrhosis with specific attention to the treatment algorithms involving the use of indirect measurement of portal pressure (HVPG) and transjugular intrahepatic portosystemic shunt (TIPS), which aim to further reduce mortality in high-risk patients after acute variceal hemorrhage and in the setting of secondary prophylaxis.
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Affiliation(s)
- Alberto Zanetto
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, Via Giustiniani 2, 35128 Padova, Italy; (A.Z.); (S.S.); (M.G.); (G.G.); (F.P.R.); (P.B.)
| | - Sarah Shalaby
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, Via Giustiniani 2, 35128 Padova, Italy; (A.Z.); (S.S.); (M.G.); (G.G.); (F.P.R.); (P.B.)
| | - Paolo Feltracco
- Anesthesiology and Intensive Care Unit, Department of Medicine, Padova University Hospital, 35128 Padova, Italy;
| | - Martina Gambato
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, Via Giustiniani 2, 35128 Padova, Italy; (A.Z.); (S.S.); (M.G.); (G.G.); (F.P.R.); (P.B.)
| | - Giacomo Germani
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, Via Giustiniani 2, 35128 Padova, Italy; (A.Z.); (S.S.); (M.G.); (G.G.); (F.P.R.); (P.B.)
| | - Francesco Paolo Russo
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, Via Giustiniani 2, 35128 Padova, Italy; (A.Z.); (S.S.); (M.G.); (G.G.); (F.P.R.); (P.B.)
| | - Patrizia Burra
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, Via Giustiniani 2, 35128 Padova, Italy; (A.Z.); (S.S.); (M.G.); (G.G.); (F.P.R.); (P.B.)
| | - Marco Senzolo
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, Via Giustiniani 2, 35128 Padova, Italy; (A.Z.); (S.S.); (M.G.); (G.G.); (F.P.R.); (P.B.)
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28
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Garcia-Pagan JC, Francoz C, Montagnese S, Senzolo M, Mookerjee RP. Management of the major complications of cirrhosis: Beyond guidelines. J Hepatol 2021; 75 Suppl 1:S135-S146. [PMID: 34039484 DOI: 10.1016/j.jhep.2021.01.027] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Revised: 01/17/2021] [Accepted: 01/20/2021] [Indexed: 02/07/2023]
Abstract
Along with a growing understanding of the pathophysiology of cirrhosis and its complications, new therapies and management strategies have emerged in recent years. Many of these advances have helped inform the current EASL clinical practice guidelines1 on the management of some of the key complications of cirrhosis, such as ascites, variceal bleeding and infection. However, there are still some aspects of management where the evidence base is less clear, and/or where opinions amongst practitioners remain divided. Some of these more controversial areas are explored in this section, wherein we present evidence culminating in a suggested management approach based on expert opinion and extending beyond the current guidelines.
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Affiliation(s)
- Juan Carlos Garcia-Pagan
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Universitat de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain; Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Spain
| | - Claire Francoz
- Hepatology and Liver Intensive Care Unit, Hôpital Beaujon, INSERM. Clichy; France
| | | | - Marco Senzolo
- Gastroenterology, Multi-visceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padua, Italy
| | - Rajeshwar P Mookerjee
- Institute for Liver and Digestive Health, University College London, UK; Department of Hepatology and Gastroenterology, Aarhus University, Denmark.
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29
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Veldhuijzen van Zanten D, Buganza E, Abraldes JG. The Role of Hepatic Venous Pressure Gradient in the Management of Cirrhosis. Clin Liver Dis 2021; 25:327-343. [PMID: 33838853 DOI: 10.1016/j.cld.2021.01.002] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Quantifying the degree of portal hypertension provides useful information to estimate prognosis and to evaluate new therapies for portal hypertension. This quantification is done in clinical practice with the measurement of the hepatic venous pressure gradient. This article addresses the applications of measuring portal pressure in cirrhosis, including the differential diagnosis of portal hypertension; estimation of prognosis in cirrhosis, including preoperative evaluation before hepatic and extrahepatic surgery; assessment of the response to drug therapy (mainly in the context of drug development); and assessing the regression of portal hypertension syndrome.
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Affiliation(s)
- Daniel Veldhuijzen van Zanten
- Department of Medicine, University of Alberta, 13-103 Clinical Sciences Building, 11350-83 Avenue, Edmonton, Alberta T6G 2G3, Canada
| | - Elizabeth Buganza
- Division of Gastroenterology, Zeidler Ledcor Centre, University of Alberta, 8540 112 St NW, Edmonton, Alberta T6G 2X8, Canada
| | - Juan G Abraldes
- Division of Gastroenterology, University of Alberta, 8540 112 St NW, 1-38 Zeidler Ledcor Centre, Edmonton, Alberta T6G 2X8, Canada.
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30
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Jachs M, Reiberger T. Prevention of Variceal Bleeding and Rebleeding by Nonselective Beta-Blockers: A Tailored Approach. Clin Liver Dis 2021; 25:311-326. [PMID: 33838852 DOI: 10.1016/j.cld.2021.01.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Indexed: 01/31/2023]
Abstract
Nonselective beta-blockers represent the mainstay of medical therapy in the prophylaxis of variceal bleeding and rebleeding in patients with portal hypertension. Their efficacy has been demonstrated by numerous trials; however, there exist safety concerns in advanced disease, such as in patients with refractory ascites. Importantly, nonselective beta-blockers also exert nonhemodynamic beneficial effects that may contribute to a prolonged decompensation-free survival, as recently shown in the PREDESCI trial. This review summarizes the current evidence on nonselective beta-blocker therapy and proposes a tailored, patient-centered approach for the use of nonselective beta-blockers in patients with portal hypertension.
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Affiliation(s)
- Mathias Jachs
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, Vienna A-1090, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria; Christian Doppler Lab for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, Vienna A-1090, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria; Christian Doppler Lab for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria.
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31
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Plaz Torres MC, Best LM, Freeman SC, Roberts D, Cooper NJ, Sutton AJ, Roccarina D, Benmassaoud A, Iogna Prat L, Williams NR, Csenar M, Fritche D, Begum T, Arunan S, Tapp M, Milne EJ, Pavlov CS, Davidson BR, Tsochatzis E, Gurusamy KS. Secondary prevention of variceal bleeding in adults with previous oesophageal variceal bleeding due to decompensated liver cirrhosis: a network meta-analysis. Cochrane Database Syst Rev 2021; 3:CD013122. [PMID: 33784794 PMCID: PMC8094621 DOI: 10.1002/14651858.cd013122.pub2] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
BACKGROUND Approximately 40% to 95% of people with cirrhosis have oesophageal varices. About 15% to 20% of oesophageal varices bleed in about one to three years of diagnosis. Several different treatments are available, which include endoscopic sclerotherapy, variceal band ligation, beta-blockers, transjugular intrahepatic portosystemic shunt (TIPS), and surgical portocaval shunts, among others. However, there is uncertainty surrounding their individual and relative benefits and harms. OBJECTIVES To compare the benefits and harms of different initial treatments for secondary prevention of variceal bleeding in adults with previous oesophageal variceal bleeding due to decompensated liver cirrhosis through a network meta-analysis and to generate rankings of the different treatments for secondary prevention according to their safety and efficacy. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and trials registers until December 2019 to identify randomised clinical trials in people with cirrhosis and a previous history of bleeding from oesophageal varices. SELECTION CRITERIA We included only randomised clinical trials (irrespective of language, blinding, or status) in adults with cirrhosis and previous history of bleeding from oesophageal varices. We excluded randomised clinical trials in which participants had no previous history of bleeding from oesophageal varices, previous history of bleeding only from gastric varices, those who failed previous treatment (refractory bleeding), those who had acute bleeding at the time of treatment, and those who had previously undergone liver transplantation. DATA COLLECTION AND ANALYSIS We performed a network meta-analysis with OpenBUGS using Bayesian methods and calculated the differences in treatments using hazard ratios (HR), odds ratios (OR) and rate ratios with 95% credible intervals (CrI) based on an available-case analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance. MAIN RESULTS We included a total of 48 randomised clinical trials (3526 participants) in the review. Forty-six trials (3442 participants) were included in one or more comparisons. The trials that provided the information included people with cirrhosis due to varied aetiologies. The follow-up ranged from two months to 61 months. All the trials were at high risk of bias. A total of 12 interventions were compared in these trials (sclerotherapy, beta-blockers, variceal band ligation, beta-blockers plus sclerotherapy, no active intervention, TIPS (transjugular intrahepatic portosystemic shunt), beta-blockers plus nitrates, portocaval shunt, sclerotherapy plus variceal band ligation, beta-blockers plus nitrates plus variceal band ligation, beta-blockers plus variceal band ligation, sclerotherapy plus nitrates). Overall, 22.5% of the trial participants who received the reference treatment (chosen because this was the commonest treatment compared in the trials) of sclerotherapy died during the follow-up period ranging from two months to 61 months. There was considerable uncertainty in the effects of interventions on mortality. Accordingly, none of the interventions showed superiority over another. None of the trials reported health-related quality of life. Based on low-certainty evidence, variceal band ligation may result in fewer serious adverse events (number of people) than sclerotherapy (OR 0.19; 95% CrI 0.06 to 0.54; 1 trial; 100 participants). Based on low or very low-certainty evidence, the adverse events (number of participants) and adverse events (number of events) may be different across many comparisons; however, these differences are due to very small trials at high risk of bias showing large differences in some comparisons leading to many differences despite absence of direct evidence. Based on low-certainty evidence, TIPS may result in large decrease in symptomatic rebleed than variceal band ligation (HR 0.12; 95% CrI 0.03 to 0.41; 1 trial; 58 participants). Based on moderate-certainty evidence, any variceal rebleed was probably lower in sclerotherapy than in no active intervention (HR 0.62; 95% CrI 0.35 to 0.99, direct comparison HR 0.66; 95% CrI 0.11 to 3.13; 3 trials; 296 participants), beta-blockers plus sclerotherapy than sclerotherapy alone (HR 0.60; 95% CrI 0.37 to 0.95; direct comparison HR 0.50; 95% CrI 0.07 to 2.96; 4 trials; 231 participants); TIPS than sclerotherapy (HR 0.18; 95% CrI 0.08 to 0.38; direct comparison HR 0.22; 95% CrI 0.01 to 7.51; 2 trials; 109 participants), and in portocaval shunt than sclerotherapy (HR 0.21; 95% CrI 0.05 to 0.77; no direct comparison) groups. Based on low-certainty evidence, beta-blockers alone and TIPS might result in more, other compensation, events than sclerotherapy (rate ratio 2.37; 95% CrI 1.35 to 4.67; 1 trial; 65 participants and rate ratio 2.30; 95% CrI 1.20 to 4.65; 2 trials; 109 participants; low-certainty evidence). The evidence indicates considerable uncertainty about the effect of the interventions including those related to beta-blockers plus variceal band ligation in the remaining comparisons. AUTHORS' CONCLUSIONS The evidence indicates considerable uncertainty about the effect of the interventions on mortality. Variceal band ligation might result in fewer serious adverse events than sclerotherapy. TIPS might result in a large decrease in symptomatic rebleed than variceal band ligation. Sclerotherapy probably results in fewer 'any' variceal rebleeding than no active intervention. Beta-blockers plus sclerotherapy and TIPS probably result in fewer 'any' variceal rebleeding than sclerotherapy. Beta-blockers alone and TIPS might result in more other compensation events than sclerotherapy. The evidence indicates considerable uncertainty about the effect of the interventions in the remaining comparisons. Accordingly, high-quality randomised comparative clinical trials are needed.
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Affiliation(s)
| | - Lawrence Mj Best
- Division of Surgery and Interventional Science, University College London, London, UK
- Department of Therapy, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation
| | - Suzanne C Freeman
- Department of Health Sciences, University of Leicester, Leicester, UK
| | - Danielle Roberts
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Nicola J Cooper
- Department of Health Sciences, University of Leicester, Leicester, UK
| | - Alex J Sutton
- Department of Health Sciences, University of Leicester, Leicester, UK
| | - Davide Roccarina
- Sheila Sherlock Liver Centre, Royal Free Hospital and the UCL Institute of Liver and Digestive Health, London, UK
| | - Amine Benmassaoud
- Sheila Sherlock Liver Centre, Royal Free Hospital and the UCL Institute of Liver and Digestive Health, London, UK
| | - Laura Iogna Prat
- Sheila Sherlock Liver Centre, Royal Free Hospital and the UCL Institute of Liver and Digestive Health, London, UK
| | - Norman R Williams
- Surgical & Interventional Trials Unit (SITU), UCL Division of Surgery & Interventional Science, London, UK
| | - Mario Csenar
- Division of Surgery and Interventional Science, University College London, London, UK
| | | | | | - Sivapatham Arunan
- General and Colorectal Surgery, Ealing Hospital and Imperial College, London, Northwood, UK
| | | | | | - Chavdar S Pavlov
- Department of Therapy, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation
| | - Brian R Davidson
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Emmanuel Tsochatzis
- Sheila Sherlock Liver Centre, Royal Free Hospital and the UCL Institute of Liver and Digestive Health, London, UK
| | - Kurinchi Selvan Gurusamy
- Division of Surgery and Interventional Science, University College London, London, UK
- Department of Therapy, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation
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Agarwal S, Sharma S, Anand A, Gunjan D, Saraya A. Liver stiffness assessment as an alternative to hepatic venous pressure gradient for predicting rebleed after acute variceal bleed: A proof-of-concept study. JGH OPEN 2021; 5:73-80. [PMID: 33490616 PMCID: PMC7812463 DOI: 10.1002/jgh3.12449] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Revised: 10/08/2020] [Accepted: 10/27/2020] [Indexed: 12/25/2022]
Abstract
Background and Aim Hepatic venous pressure gradient (HVPG), although an important determinant in predicting rebleeding after an episode of acute variceal bleed (AVB), is seldom utilized in clinical practice. We aimed to study the role of liver stiffness measurement (LSM) after variceal bleeding as a potential noninvasive predictor of rebleed. Methods This was a post hoc analysis of clinical trial of patients undergoing HVPG (postbleed HVPG) and LSM (postbleed LSM) assessment within 3–5 days of index AVB. HVPG response was assessed after 4 weeks of pharmacotherapy. Comparative assessment of long‐term rebleeding rates stratified using postbleed LSM, postbleed HVPG, and HVPG response was performed. Decision curve analysis (DCA) was conducted to identify the most appropriate tool for routine use. Results Long‐term clinical and HVPG response data were available for 48 patients post‐AVB, of whom 45 patients had valid postbleed LSM. Rebleeding occurred in 13 (28%) patients over a median follow‐up of 4 years with no early rebleeds. Postbleed LSM >30 kPa and baseline HVPG >15 mm Hg were optimal cutoffs for identifying patients at high risk of rebleeding. Time‐dependent receiver operating characteristic curves and competing risk analysis accounting for death showed similar discriminative values for all three stratification tools. At usual risk thresholds, HVPG response had maximum benefit on DCA followed by postbleed LSM. On DCA, 50–60 additional HVPGs were required to detect one additional patient at high risk of rebleed. Conclusion Liver stiffness measurement during AVB can potentially be used as an alternative to portal pressure indices in decompensated cirrhosis to identify those at high risk of late‐onset rebleed.
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Affiliation(s)
- Samagra Agarwal
- Department of Gastroenterology and Human Nutrition Unit All India Institute of Medical Sciences New Delhi India
| | - Sanchit Sharma
- Department of Gastroenterology and Human Nutrition Unit All India Institute of Medical Sciences New Delhi India
| | - Abhinav Anand
- Department of Gastroenterology and Human Nutrition Unit All India Institute of Medical Sciences New Delhi India
| | - Deepak Gunjan
- Department of Gastroenterology and Human Nutrition Unit All India Institute of Medical Sciences New Delhi India
| | - Anoop Saraya
- Department of Gastroenterology and Human Nutrition Unit All India Institute of Medical Sciences New Delhi India
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Kovalic AJ, Satapathy SK. Secondary Prophylaxis of Variceal Bleeding in Liver Cirrhosis. VARICEAL BLEEDING IN LIVER CIRRHOSIS 2021:77-121. [DOI: 10.1007/978-981-15-7249-4_7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Sharma S, Agarwal S, Gunjan D, Kaushal K, Anand A, Gopi S, Mohta S, Saraya A. Outcomes of Portal Pressure-Guided Therapy in Decompensated Cirrhosis With Index Variceal Bleed in Asian Cohort. J Clin Exp Hepatol 2021; 11:443-452. [PMID: 34276151 PMCID: PMC8267357 DOI: 10.1016/j.jceh.2020.11.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Accepted: 11/06/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND AND AIMS Hemodynamic response to pharmacotherapy improves survival in patients with cirrhosis post variceal bleeding, but long-term outcomes remain unexplored especially in this part of the world. We aimed to study the long-term impact of portal pressure reduction on liver-related outcomes after index variceal bleed. METHODS Patients with hepatic venous pressure gradient (HVPG) more than 12 mm Hg after index variceal bleed were given non-selective beta-blockers in combination with variceal band ligation. HVPG response was assessed after 4 weeks. Patients were followed up for rebleed events, survival, additional decompensation events and safety outcomes. Rebleed and other decompensations were compared using competing risks analysis, taking death as competing event, and survival was compared using Kaplan-Meier analysis. RESULTS Forty-eight patients (29 responders and 19 non-responders) were followed up for a median duration of 45 (24-56) months. Rebleeding rates at 1, 3 and 5 years were 10.3%, 20.7% and 20.7% in responders and 15.8%, 44.7% and 51.1% in non-responders, respectively (Gray's test, P = 0.044). Survival rates at 1, 3 and 5 years were 89.7%, 72.1% and 51.9% in responders and 89.5%, 44% and 37.7% in non-responders, respectively (log-rank test, P = 0.1). Both severity of liver disease (MELD score, multivariate sub-distributional hazards ratio: 1.166 [1.014-1.341], P = 0.030) and HVPG non-response (multivariate sub-distributional hazards ratio: 2.476 [1.87-7.030], P = 0.045) predicted rebleeding risk while survival was dependent only on severity of liver disease (MELD > 12, multivariate hazards ratio: 2.36 [1.04-5.38], P = 0.041). CONCLUSION Baseline severity of liver disease predicted survival and rebleed in these patients. Hemodynamic response, although associated with lower rebleeding rate, had limited impact on survival.
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Key Words
- ACLF, acute on chronic liver failure
- AFP, alpha-fetoprotein
- AVB, acute variceal bleed
- CT, computed tomography
- CTP, Child–Turcotte–Pugh
- EASL-CLIF, European Association of Study of Liver Disease – Chronic Liver Failure Consortium
- EBL, endoscopic band ligation
- EGD, esophagogastroduodenoscopy
- HE, hepatic encephalopathy
- HRS, hepatorenal syndrome
- HVPG, hepatic venous pressure gradient
- MELD, model for end-stage liver disease
- NSBB, non-selective beta-blockers
- SBP, spontaneous bacterial peritonitis
- acute variceal bleed
- hemodynamic response and carvedilol
- hepatic venous pressure gradient
- non-selective beta-blockers
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Affiliation(s)
| | | | | | | | | | | | | | - Anoop Saraya
- Address for correspondence: Anoop Saraya, Professor and Head of Department, Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110029, India.
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Tong H, Gan C, Wei B, Wang ZD, Li XD, Qian SJ, Huan H, Zhang LH, Yang Z, Chen YL, Gu YH, Chen LX, Yang YH, Wu H, Tang CW. Risk factors for overt hepatic encephalopathy after transjugular intrahepatic portosystemic shunt creation in patients with liver cirrhosis. J Dig Dis 2021; 22:31-40. [PMID: 33128287 DOI: 10.1111/1751-2980.12957] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 09/03/2020] [Accepted: 10/28/2020] [Indexed: 02/05/2023]
Abstract
OBJECTIVE This study aimed to determine the risk factors and establish a risk score for post-transjugular intrahepatic portosystemic shunt (TIPS) overt hepatic encephalopathy (OHE). METHODS Altogether 299 and 62 cirrhotic patients receiving TIPS from January 2015 to March 2018 were divided into the derivation and validation cohorts, respectively. The data of the derivation cohort were analyzed for risk factors of post-TIPS OHE. A risk score was established from the derivation cohort and verified by the validation cohort. RESULTS During a median follow-up of 112.6 weeks, 52 (17.4%) patients in the derivation cohort experienced post-TIPS OHE. Logistic regression showed that alcoholic cirrhosis (odds ratio [OR] 3.068, 95% confidence interval [CI] 1.423-6.613, P = 0.004), stent diameter of 10 mm (OR 12.046 [95% CI 2.308-62.862], P = 0.003), portal pressure gradient (PPG) decrement ≥60% (OR 3.548 [95% CI 1.741-7.230], P < 0.001), model for end-stage liver disease (MELD) score ≥10 (OR 2.695 [95% CI 1.203-6.035], P = 0.016), blood ammonia (OR 1.009 [95% CI 1.000-1.018], P = 0.043) and notable hydrothorax (OR 4.393 [95% CI 1.554-12.415], P = 0.005) were associated with an increased risk of post-TIPS OHE. The risk score reached a promising risk evaluation of post-TIPS OHE when verified by the validation cohort (sensitivity 71.4%, specificity 70.7%, accuracy 71.0%). CONCLUSIONS Alcoholic cirrhosis and notable hydrothorax are independent risk factors for post-TIPS OHE in liver cirrhosis, together with the stent diameter of 10 mm, PPG decrement ≥60%, MELD score ≥10 and blood ammonia. The established risk score is reliable to identify high-risk individuals of developing post-TIPS OHE.
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Affiliation(s)
- Huan Tong
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Can Gan
- West China School of Medicine, Sichuan University, Chengdu, Sichuan Province, China
| | - Bo Wei
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Zhi Dong Wang
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Xiao Dan Li
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Shuai Jie Qian
- West China School of Medicine, Sichuan University, Chengdu, Sichuan Province, China
| | - Hui Huan
- West China School of Medicine, Sichuan University, Chengdu, Sichuan Province, China
| | - Lin Hao Zhang
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Zhu Yang
- West China School of Medicine, Sichuan University, Chengdu, Sichuan Province, China
| | - Yi Long Chen
- West China Biomedical Big Data Center, West China School of Medicine, Sichuan University, Chengdu, Sichuan Province, China.,Medical Big Data Center, Sichuan University, Chengdu, Sichuan Province, China
| | - Yong Hong Gu
- West China Biomedical Big Data Center, West China School of Medicine, Sichuan University, Chengdu, Sichuan Province, China.,Medical Big Data Center, Sichuan University, Chengdu, Sichuan Province, China
| | - Liu Xiang Chen
- West China School of Medicine, Sichuan University, Chengdu, Sichuan Province, China
| | - Yu Hang Yang
- West China School of Medicine, Sichuan University, Chengdu, Sichuan Province, China
| | - Hao Wu
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Cheng Wei Tang
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
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Abstract
This editorial comments on the findings from the study by Jindal et al. recently published in The American Journal of Gastroenterology. Weaknesses and strengths of the study are presented, and potential therapeutic strategies for compensated cirrhotic patients with an HVPG ≥20 mm Hg are proposed.
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Chang Y, Suk KT, Jeong SW, Yoo JJ, Kim SG, Kim YS, Lee SH, Kim HS, Kang SH, Baik SK, Kim DJ, Kim MY, Jang JY. Application of Hepatic Venous Pressure Gradient to Predict Prognosis in Cirrhotic Patients with a Low Model for End-Stage Liver Disease Score. Diagnostics (Basel) 2020; 10:805. [PMID: 33050413 PMCID: PMC7599657 DOI: 10.3390/diagnostics10100805] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 09/30/2020] [Accepted: 10/08/2020] [Indexed: 12/23/2022] Open
Abstract
UNLABELLED : Background/aim: We aimed to derive a model representing the dynamic status of cirrhosis and to discriminate patients with poor prognosis even if the Model for End-Stage Liver Disease (MELD) score is low. METHODS This study retrospectively enrolled 700 cirrhotic patients with a MELD score of less than 20 who underwent hepatic venous pressure gradient (HVPG) measurement. A model named H6C score (= HVPG + 6 × CTP score) to predict overall survival was derived and internal and external validations were conducted with the derivation and validation cohorts. RESULTS The H6C score using the HVPG was developed based on a multivariate Cox regression analysis. The H6C score showed a great predictive power for overall survival with a time-dependent AUC of 0.733, which was superior to that of a MELD of 0.602. In patients with viral etiology, the performance of the H6C score was much improved with a time-dependent AUC of 0.850 and was consistently superior to that of the MELD (0.748). Patients with an H6C score below 45 demonstrated an excellent overall survival with a 5-year survival rate of 91.5%. Whereas, patients with an H6C score above 64 showed a dismal prognosis with a 5-year survival rate of 51.1%. The performance of the H6C score was further verified to be excellent in the validation cohort. CONCLUSION This new model using the HVPG provides an excellent predictive power in cirrhotic patients, especially with viral etiology. In patients with H6C above 64, it would be wise to consider early liver transplantation to positively impact long-term survival, even when the MELD score is low.
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Affiliation(s)
- Young Chang
- Department of Internal Medicine, Institute for Digestive Research, Digestive Disease Center, Soonchunhyang University College of Medicine, Seoul 04401, Korea; (Y.C.); (S.W.J.)
| | - Ki Tae Suk
- Department of Internal Medicine, Institute for Liver and Digestive Diseases, Hallym University College of Medicine, Chuncheon 24252, Korea; (K.T.S); (D.J.K.)
| | - Soung Won Jeong
- Department of Internal Medicine, Institute for Digestive Research, Digestive Disease Center, Soonchunhyang University College of Medicine, Seoul 04401, Korea; (Y.C.); (S.W.J.)
| | - Jeong-Ju Yoo
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon 14584, Korea; (J.-J.Y.); (S.G.K.); (Y.S.K.)
| | - Sang Gyune Kim
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon 14584, Korea; (J.-J.Y.); (S.G.K.); (Y.S.K.)
| | - Young Seok Kim
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon 14584, Korea; (J.-J.Y.); (S.G.K.); (Y.S.K.)
| | - Sae Hwan Lee
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan 31151, Korea; (S.H.L.); (H.S.K.)
| | - Hong Soo Kim
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan 31151, Korea; (S.H.L.); (H.S.K.)
| | - Seong Hee Kang
- Department of Internal Medicine, Yonsei University, Wonju College of Medicine, Wonju 26426, Korea; (S.H.K.); (S.K.B.)
| | - Soon Koo Baik
- Department of Internal Medicine, Yonsei University, Wonju College of Medicine, Wonju 26426, Korea; (S.H.K.); (S.K.B.)
| | - Dong Joon Kim
- Department of Internal Medicine, Institute for Liver and Digestive Diseases, Hallym University College of Medicine, Chuncheon 24252, Korea; (K.T.S); (D.J.K.)
| | - Moon Young Kim
- Department of Internal Medicine, Yonsei University, Wonju College of Medicine, Wonju 26426, Korea; (S.H.K.); (S.K.B.)
| | - Jae Young Jang
- Department of Internal Medicine, Institute for Digestive Research, Digestive Disease Center, Soonchunhyang University College of Medicine, Seoul 04401, Korea; (Y.C.); (S.W.J.)
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La Mura V, Garcia-Guix M, Berzigotti A, Abraldes JG, García-Pagán JC, Villanueva C, Bosch J. A Prognostic Strategy Based on Stage of Cirrhosis and HVPG to Improve Risk Stratification After Variceal Bleeding. Hepatology 2020; 72:1353-1365. [PMID: 31960441 DOI: 10.1002/hep.31125] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Accepted: 12/22/2019] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND AIMS A hepatic venous pressure gradient (HVPG) decrease of 20% or more (or ≤12 mm Hg) indicates a good prognosis during propranolol/nadolol treatment but requires two HVPG measurements. We aimed to simplify the risk stratification after variceal bleeding using clinical data and HVPG. METHODS A total of 193 patients with cirrhosis (62% with ascites and/or hepatic encephalopathy [HE]) who were within 7 days of bleeding had their HVPG measured before and at 1-3 months of treatment with propranolol/nadolol plus endoscopic band ligation. The endpoints were rebleeding and rebleeding/transplantation-free survival for 4 years. Another cohort (n = 231) served as the validation set. RESULTS During follow-up, 45 patients had variceal bleeding and 61 died. The HVPG responders (n = 71) had lower rebleeding risk (10% vs. 34%, P = 0.001) and better survival than the 122 nonresponders (61% vs. 39%, P = 0.001). Patients with HE (n = 120) had lower survival than patients without HE (40% vs. 63%, P = 0.005). Among the patients with ascites/HE, those with baseline HVPG ≤ 16 mm Hg (n = 16) had a low rebleeding risk (13%). In contrast, among patients with ascites/HE and baseline HVPG > 16 mm Hg, only the HVPG responders (n = 32) had a good prognosis, with lower rebleeding risk and better survival than the nonresponders (n = 72) (respective proportions: 7% vs. 39%, P = 0.018; 56% vs. 30% P = 0.010). These findings allowed us to develop a strategy for risk stratification in which HVPG response was measured only in patients with ascites and/or HE and baseline HVPG > 16 mm Hg. This method reduced the "gray zone" (i.e., high-risk patients who had not died on follow-up) from 46% to 35% and decreased the HVPG measurements required by 42%. The validation cohort confirmed these results. CONCLUSIONS Restricting HVPG measurements to patients with ascites/HE and measuring HVPG response only if the patient's baseline HVPG is over 16 mm Hg improves detection of high-risk patients while markedly reducing the number of HVPG measurements required.
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Affiliation(s)
- Vincenzo La Mura
- Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Barcelona, Spain
- Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Medicina Generale-Emostasi e Trombosi, Milano, Italy
- CRC "A.M. e A. Migliavacca" per lo Studio e la Cura delle Malattie del Fegato, Milano, Italy
- Dipartimento di Scienze Biomediche per la Salute, Università Degli Studi di Milano, Milano, Italy
| | - Marta Garcia-Guix
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Barcelona, Spain
- Gastrointestinal Bleeding Unit, Department of Gastroenterology, Hospital de Sant Pau, Autonomous University, Barcelona, Spain
| | - Annalisa Berzigotti
- Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Barcelona, Spain
- Swiss Liver, Hepatology, University Clinic for Visceral Medicine and Surgery, Inselspital, University of Bern, Bern, Switzerland
| | - Juan G Abraldes
- Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Barcelona, Spain
- Division of Gastroenterology, University of Alberta, Edmonton, AB, Canada
| | - Juan Carlos García-Pagán
- Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Barcelona, Spain
| | - Candid Villanueva
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Barcelona, Spain
- Gastrointestinal Bleeding Unit, Department of Gastroenterology, Hospital de Sant Pau, Autonomous University, Barcelona, Spain
| | - Jaime Bosch
- Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Barcelona, Spain
- Swiss Liver, Hepatology, University Clinic for Visceral Medicine and Surgery, Inselspital, University of Bern, Bern, Switzerland
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Kumar A, Sharma P, Arora A. Letter to the Editor: A Prognostic Algorithm Based on Stage of Cirrhosis and Hepatic Venous Pressure Gradient to Improve Risk Stratification After Variceal Bleeding. Hepatology 2020; 72:1494. [PMID: 32246493 DOI: 10.1002/hep.31254] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/07/2022]
Affiliation(s)
- Ashish Kumar
- Institute of Liver, Gastroenterology, and Panceatico-Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, 110060, India
| | - Praveen Sharma
- Institute of Liver, Gastroenterology, and Panceatico-Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, 110060, India
| | - Anil Arora
- Institute of Liver, Gastroenterology, and Panceatico-Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, 110060, India
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Ardevol A, Alvarado-Tapias E, Garcia-Guix M, Brujats A, Gonzalez L, Hernández-Gea V, Aracil C, Pavel O, Cuyas B, Graupera I, Colomo A, Poca M, Torras X, Concepción M, Villanueva C. Early rebleeding increases mortality of variecal bleeders on secondary prophylaxis with β-blockers and ligation. Dig Liver Dis 2020; 52:1017-1025. [PMID: 32653417 DOI: 10.1016/j.dld.2020.06.005] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2019] [Revised: 05/14/2020] [Accepted: 06/01/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND/AIMS Despite secondary-prophylaxis with β-blockers and endoscopic-variceal-ligation rebleeding is frequent, particularly within the first-6-weeks. Early-rebleeding may have greater impact on death-risk than late rebleeding, which may affect therapy. We assessed whether the influence of rebleeding on long-term survival of patients on secondary-prophylaxis is greater in patients with early-rebleeding. METHODS 369 patients with cirrhosis were consecutively included once recovered from first variceal-bleeding. The impact of rebleeding on survival was investigated according to whether it occurred within 6-weeks (early-rebleeding) or later (late-rebleeding). RESULTS During 46-months of follow-up (IQR: 14-61), 45 patients (12%) had early-rebleeding, 74(20%) had late-rebleeding and 250(68%) had not rebleeding. Mortality risk was higher in early-rebleeding group vs. late-rebleeding (HR = 0.476, 95%CI = 0.318-0.712, p < 0.001) and was similar in late-rebleeding group vs. no-rebleeding (HR = 0.902, 95%CI = 0.749-1.086, p = 0.271). Adjusting for baseline risk-factors, early-rebleeding was independently associated with mortality-risk (HR = 1.58, 95%CI = 1.02-2.45; p = 0.04). Child-Pugh&MELD scores improved at 3rd-4th-week only in patients without early-rebleeding (p < 0.05). Presence of ascites or encephalopathy, MELD-score>12 and HVPG>20 mmHg identified patients at risk of early-rebleeding. CONCLUSIONS Patients with early-rebleeding have higher risk of death than patients without rebleeding and even than those rebleeding later. Our results suggest that patients at risk of early rebleeding might benefit from preemptive therapies such as early-TIPS.
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Affiliation(s)
- Alba Ardevol
- Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Institut de Recerca, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Edilmar Alvarado-Tapias
- Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Institut de Recerca, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
| | - Marta Garcia-Guix
- Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Institut de Recerca, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Anna Brujats
- Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Institut de Recerca, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Laura Gonzalez
- Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Institut de Recerca, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Virginia Hernández-Gea
- Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Institut de Recerca, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, IDIBAPS, University of Barcelona, Centro de Investigación Biomédica Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Carles Aracil
- Hospital Arnau de Vilanova,(IRBLleida), Lleida, Spain
| | - Oana Pavel
- Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Institut de Recerca, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
| | - Berta Cuyas
- Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Institut de Recerca, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Isabel Graupera
- Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Institut de Recerca, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
| | - Alan Colomo
- Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Institut de Recerca, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
| | - Maria Poca
- Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Institut de Recerca, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
| | - Xavier Torras
- Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Institut de Recerca, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Mar Concepción
- Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Institut de Recerca, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Càndid Villanueva
- Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Institut de Recerca, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Universitat Autònoma de Barcelona, Barcelona, Spain.
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Shao R, Li Z, Wang J, Qi R, Liu Q, Zhang W, Mao X, Song X, Li L, Liu Y, Zhao X, Liu C, Li X, Zuo C, Wang W, Qi X. Hepatic venous pressure gradient-guided laparoscopic splenectomy and pericardial devascularisation versus endoscopic therapy for secondary prophylaxis for variceal rebleeding in portal hypertension (CHESS1803): study protocol of a multicenter randomised controlled trial in China. BMJ Open 2020; 10:e030960. [PMID: 32580978 PMCID: PMC7312451 DOI: 10.1136/bmjopen-2019-030960] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2019] [Revised: 02/15/2020] [Accepted: 04/28/2020] [Indexed: 12/20/2022] Open
Abstract
INTRODUCTION Gastro-oesophageal variceal bleeding is one of the most common and severe complications with high mortality in cirrhotic patients who developed portal hypertension. Hepatic venous pressure gradient (HVPG) is a globally recommended golden standard for the portal pressure assessment and an HVPG ≥16 mm Hg indicates a higher risk of death and rebleeding. This study aims to compare the effectiveness and safety of splenectomy and pericardial devascularisation (laparoscopic therapy) plus propranolol and endoscopic therapy plus propranolol for variceal rebleeding in cirrhotic patients with HVPG between 16 and 20 mm Hg. METHODS AND ANALYSIS This is a multicenter, randomised, controlled clinical trial. Participants will be 1:1 assigned randomly into either laparoscopic or endoscopic groups. Forty participants whose transjugular HVPG lies between 16 and 20 mm Hg with a history of gastro-oesophageal variceal bleeding will be recruited from three sites in China. Participants will receive either endoscopic therapy plus propranolol or laparoscopic therapy plus propranolol. The primary outcome measure will be the occurrence of gastro-oesophageal variceal rebleeding. Secondary outcome measures will include overall survival, occurrence of hepatocellular carcinoma, the occurrence of venous thrombosis, the occurrence of adverse events, quality of life and tolerability of treatment. Outcome measures will be evaluated at baseline, 12 weeks, 24 weeks, 36 weeks, 48 weeks and 60 weeks. Multivariate COX regression model will be introduced for analyses of occurrence data and Kaplan-Meier analysis with the log-rank test for intergroup comparison. ETHICS AND DISSEMINATION Ethical approval was obtained from all three participating sites. Primary and secondary outcome data will be submitted for publication in peer-reviewed journals and widely disseminated. TRIAL REGISTRATION NUMBER NCT03783065; Pre-results. TRIAL STATUS Recruitment for this study started in December 2018 while the first participant was randomised in January 2019. Recruitment is estimated to stop in October 2019.
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Affiliation(s)
- Ruoyang Shao
- CHESS Center, Institute of Portal Hypertension, The First Hospital of Lanzhou University, Lanzhou, China
- Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Zhiwei Li
- Department of Hepatobiliary Surgery, The Third People's Hospital of Shenzhen, Shenzhen, China
| | - Jitao Wang
- Department of Hepatobiliary Surgery, Xingtai Institute of Cancer Control, Xingtai, China
| | - Ruizhao Qi
- Department of General Surgery, The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Qingbo Liu
- Department of Hepatobiliary Surgery, Shunde Hospital, Southern Medical University, Foshan, China
| | - Weijie Zhang
- Department of Hepatobiliary Surgery, Shunde Hospital, Southern Medical University, Foshan, China
| | - Xiaorong Mao
- CHESS Center, Institute of Portal Hypertension, The First Hospital of Lanzhou University, Lanzhou, China
| | - Xiaojing Song
- CHESS Center, Institute of Portal Hypertension, The First Hospital of Lanzhou University, Lanzhou, China
| | - Lei Li
- CHESS Center, Institute of Portal Hypertension, The First Hospital of Lanzhou University, Lanzhou, China
| | - Yanna Liu
- CHESS Center, Institute of Portal Hypertension, The First Hospital of Lanzhou University, Lanzhou, China
| | - Xin Zhao
- Department of Hepatobiliary Surgery, The Third People's Hospital of Shenzhen, Shenzhen, China
| | - Chuan Liu
- CHESS Center, Institute of Portal Hypertension, The First Hospital of Lanzhou University, Lanzhou, China
| | - Xun Li
- CHESS Center, Institute of Portal Hypertension, The First Hospital of Lanzhou University, Lanzhou, China
| | - Changzeng Zuo
- Department of Hepatobiliary Surgery, Xingtai Institute of Cancer Control, Xingtai, China
| | - Weidong Wang
- Department of Hepatobiliary Surgery, Shunde Hospital, Southern Medical University, Foshan, China
| | - Xiaolong Qi
- CHESS Center, Institute of Portal Hypertension, The First Hospital of Lanzhou University, Lanzhou, China
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Magaz M, Baiges A, Hernández-Gea V. Precision medicine in variceal bleeding: Are we there yet? J Hepatol 2020; 72:774-784. [PMID: 31981725 DOI: 10.1016/j.jhep.2020.01.008] [Citation(s) in RCA: 57] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2019] [Revised: 01/13/2020] [Accepted: 01/14/2020] [Indexed: 12/14/2022]
Abstract
Variceal bleeding is one of the most feared complications of portal hypertension in patients with cirrhosis because of its deleterious impact on prognosis. Adequate management of patients at risk of developing variceal bleeding includes the prevention of the first episode of variceal bleeding and rebleeding, and is crucial in modifying prognosis. The presence of clinically significant portal hypertension is the main factor determining the risk of development of varices and other liver-related decompensations; therefore, it should be carefully screened for and monitored. Treating patients with clinically significant portal hypertension based on their individual risk of portal hypertension-related bleeding undoubtedly improves prognosis. The evaluation of liver haemodynamics and liver function can stratify patients according to their risk of bleeding and are no question useful tools to guide therapy in an individualised manner. That said, recent data support the idea that tailoring therapy to patient characteristics may effectively impact on prognosis and increase survival in all clinical scenarios. This review will focus on evaluating the available evidence supporting the use of individual risk characteristics for clinical decision-making and their impact on clinical outcome and survival. In primary prophylaxis, identification and treatment of patients with clinically significant portal hypertension improves decompensation-free survival. In the setting of acute variceal bleeding, the risk of failure and rebleeding can be easily predicted, allowing for early escalation of treatment (i.e. pre-emptive transjugular intrahepatic portosystemic shunt) which can improve survival in appropriate candidates. Stratifying the risk of recurrent variceal bleeding based on liver function and haemodynamic response to non-selective beta-blockers allows for tailored treatment, thereby increasing survival and avoiding adverse events.
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Affiliation(s)
- Marta Magaz
- Unidad de Hemodinámica Hepática, Servicio de Hepatología, Hospital Clínic, Universidad de Barcelona, Instituto de Investigaciones Biomédicas Augusto Pi Suñer (IDIBAPS), Barcelona, Spain
| | - Anna Baiges
- Unidad de Hemodinámica Hepática, Servicio de Hepatología, Hospital Clínic, Universidad de Barcelona, Instituto de Investigaciones Biomédicas Augusto Pi Suñer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Barcelona, Spain
| | - Virginia Hernández-Gea
- Unidad de Hemodinámica Hepática, Servicio de Hepatología, Hospital Clínic, Universidad de Barcelona, Instituto de Investigaciones Biomédicas Augusto Pi Suñer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Barcelona, Spain.
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Zanetto A, Garcia-Tsao G. Gastroesophageal Variceal Bleeding Management. THE CRITICALLY ILL CIRRHOTIC PATIENT 2020:39-66. [DOI: 10.1007/978-3-030-24490-3_4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Reverter E. Liver biopsy? Long life to the transjugular route. Dig Liver Dis 2019; 51:1152-1153. [PMID: 31054963 DOI: 10.1016/j.dld.2019.03.031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2019] [Accepted: 03/26/2019] [Indexed: 12/11/2022]
Affiliation(s)
- Enric Reverter
- Liver and Digestive ICU, Liver Unit, Hospital Clínic of Barcelona, Spain.
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Stift J, Semmler G, Walzel C, Mandorfer M, Schwarzer R, Schwabl P, Paternostro R, Scheiner B, Wöran K, Pinter M, Stättermayer AF, Trauner M, Peck-Radosavljevic M, Ferlitsch A, Reiberger T. Transjugular aspiration liver biopsy performed by hepatologists trained in HVPG measurements is safe and provides important diagnostic information. Dig Liver Dis 2019; 51:1144-1151. [PMID: 30862438 DOI: 10.1016/j.dld.2019.01.020] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2018] [Revised: 01/24/2019] [Accepted: 01/25/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND Transjugular liver biopsy (TJLB) represents an alternative to percutaneous liver biopsy especially in patients with impaired coagulation and ascites. AIMS To describe safety and diagnostic yield of aspiration TJLB performed by hepatologists experienced in hepatic venous pressure gradient (HVPG) measurements. METHODS 445 TJLB of 399 patients between 01/2007-12/2016 were retrospectively assessed. RESULTS Histological diagnosis was obtained in 423 (95.1%) biopsies - including 11 (100%) patients with acute liver failure and 34 (97.1%) patients after liver transplantation. A median number of 5 portal tracts (interquartile range:2-9) was obtained. HVPG negatively correlated with sample length (Spearman ρ = -0.310; p < 0.001) and number of portal tracts (ρ = -0.212; p < 0.001). Among n = 151 patients with unknown etiology of liver disease, etiology was successfully identified on liver histology in 126 patients (83.4%). Complications occurred in 28 biopsies (6.3%) including 25 (5.6%) minor and 3 (0.7%) major complications. No deaths due to TJLB were observed. Neither the presence of ascites (6.6% complications) nor of coagulopathy (platelets<50G/L and/or prothrombin time<50%; 4.8% complications) increased the risk for complications. CONCLUSIONS TJLB performed by hepatologists experienced in HVPG measurements is safe - even in patients with ascites or coagulopathy. TJLB has good diagnostic value for histological evaluation of liver disease and acute liver failure.
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Affiliation(s)
- Judith Stift
- Department of Pathology, Medical University of Vienna, Vienna, Austria.
| | - Georg Semmler
- Division of Gastroenterology & Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria.
| | - Cita Walzel
- Division of Gastroenterology & Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria.
| | - Mattias Mandorfer
- Division of Gastroenterology & Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria.
| | - Remy Schwarzer
- Division of Gastroenterology & Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria.
| | - Philipp Schwabl
- Division of Gastroenterology & Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria.
| | - Rafael Paternostro
- Division of Gastroenterology & Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria.
| | - Bernhard Scheiner
- Division of Gastroenterology & Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria.
| | - Katharina Wöran
- Department of Pathology, Medical University of Vienna, Vienna, Austria.
| | - Matthias Pinter
- Division of Gastroenterology & Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria.
| | - Albert Friedrich Stättermayer
- Division of Gastroenterology & Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
| | - Michael Trauner
- Division of Gastroenterology & Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Markus Peck-Radosavljevic
- Department of Gastroenterology & Hepatology, Endocrinology and Nephrology, Klinikum Klagenfurt, Klagenfurt, Austria; Division of Gastroenterology & Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
| | - Arnulf Ferlitsch
- Department of Internal Medicine I,Hospital of St. John of God, Vienna, Austria; Division of Gastroenterology & Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
| | - Thomas Reiberger
- Division of Gastroenterology & Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria.
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Matsushima H, Fujiki M, Sasaki K, Rotroff DM, Sands M, Bayona Molano MDP, Aucejo F, Diago Uso T, Eghtesad B, Miller C, Quintini C, Hashimoto K. Predictive Value of Hepatic Venous Pressure Gradient for Graft Hemodynamics in Living Donor Liver Transplantation. Liver Transpl 2019; 25:1034-1042. [PMID: 30980599 DOI: 10.1002/lt.25471] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2018] [Accepted: 03/08/2019] [Indexed: 02/07/2023]
Abstract
The hepatic venous pressure gradient (HVPG) measurement is known to correlate with the severity of portal hypertension in patients with liver cirrhosis. This retrospective study investigated the clinical value of preoperative measurement of HVPG in patients who underwent adult-to-adult living donor liver transplantation (LDLT) and its predictive value for hepatic hemodynamics after graft reperfusion. For this study, 75 patients who underwent adult-to-adult LDLT were divided into 2 groups (HVPG <16 mm Hg or HVPG ≥16 mm Hg) to investigate the correlation between preoperative HVPG and characteristics and surgical outcomes of the patients, including portal vein flow (PVF) and hepatic artery flow (HAF) after graft reperfusion. In total, 35 (46.7%) patients had an HVPG ≥16 mm Hg. These patients had significantly higher international normalized ratio values, serum creatinine levels, and Model for End-Stage Liver Disease scores compared with the 40 patients with HVPG <16 mm Hg. They also had higher rates of variceal bleeding, encephalopathy, and intractable ascites as well as lower serum albumin levels and platelet counts compared with those patients with HVPG <16 mm Hg. Portal inflow modulation (PIM) was frequently performed in the patients with HVPG ≥16 mm Hg compared with those with HVPG <16 mm Hg. No significant differences in surgical outcomes after LDLT were found between these 2 groups except for postoperative ascites. Preoperative HVPG showed a positive correlation with PVF and a negative correlation with HAF after graft reperfusion (false discovery rate [FDR] P = 0.08 and FDR P = 0.08, respectively). In linear regression analyses, preoperative HVPG was independently associated with PVF after graft reperfusion. In conclusion, our findings indicate that preoperative HVPG is associated with hepatic hemodynamics after graft implantation in LDLT. HVPG as a routine preoperative evaluation may be helpful for surgical planning of PIM.
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Affiliation(s)
- Hajime Matsushima
- Department of General Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH
| | - Masato Fujiki
- Department of General Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH
| | - Kazunari Sasaki
- Department of General Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH
| | - Daniel M Rotroff
- Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH
| | - Mark Sands
- Department of Radiology, Cleveland Clinic, Cleveland, OH
| | | | - Federico Aucejo
- Department of General Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH
| | - Teresa Diago Uso
- Department of General Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH
| | - Bijan Eghtesad
- Department of General Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH
| | - Charles Miller
- Department of General Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH
| | - Cristiano Quintini
- Department of General Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH
| | - Koji Hashimoto
- Department of General Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH
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Mandorfer M, Hernández-Gea V, Reiberger T, García-Pagán JC. Hepatic Venous Pressure Gradient Response in Non-Selective Beta-Blocker Treatment—Is It Worth Measuring? ACTA ACUST UNITED AC 2019. [DOI: 10.1007/s11901-019-00469-x] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Reverter E, Lozano JJ, Alonso C, Berzigotti A, Seijo S, Turon F, Baiges A, Martínez-Chantar ML, Mato JM, Martínez-Arranz I, La Mura V, Hernández-Gea V, Bosch J, García-Pagán JC. Metabolomics discloses potential biomarkers to predict the acute HVPG response to propranolol in patients with cirrhosis. Liver Int 2019; 39:705-713. [PMID: 30637923 DOI: 10.1111/liv.14042] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2018] [Revised: 12/12/2018] [Accepted: 01/10/2019] [Indexed: 02/13/2023]
Abstract
BACKGROUND In cirrhosis, a decrease in hepatic venous pressure gradient (HVPG) > 10% after acute iv propranolol (HVPG response) is associated with a lower risk of decompensation and death. Only a part of patients are HVPG responders and there are no accurate non-invasive markers to identify them. We aimed at discovering metabolomic biomarkers of HVPG responders to propranolol. METHODS Sixty-six patients with cirrhosis and HVPG ≥ 10 mm Hg in whom the acute HVPG response to propranolol was assessed, were prospectively included. A targeted metabolomic serum analysis using ultrahigh-performance liquid chromatography coupled to mass spectrometry was performed. Different combinations of 2-3 metabolites identifying HVPG responders (HVPG reduction > 10%) were obtained by stepwise logistic regression. The best of these model (AUROC, Akaike criterion) underwent internal cross-validation and cut-offs to classify responders/non-responders was proposed. RESULTS A total of 41/66 (62%) patients were HVPG responders. Three hundred and eighty-nine metabolites were detected and 177 were finally eligible. Eighteen metabolites were associated to the HVPG response at univariate analysis; at multivariable analysis, a model including a phosphatidylcholine (PC(P-16:0/22:6)) and a free fatty acid (20:2(n-6), eicosadienoic acid) performed well for HVPG response, with an AUROC of 0.801 (0.761 at internal validation). The cut-off 0.629 was the most efficient for overall classification (49/66 patients correctly classified). Two cut-off values allowed identifying responders (0.688, PPV 84%) and non-responders (0.384, NPV 82%) with undetermined values for 17/66 patients. Clinical variables did not add to the model. CONCLUSIONS The combination of two metabolites helps at identifying HVPG responders to acute propranolol. It could be a useful non-invasive test to classify the HVPG response to propranolol.
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Affiliation(s)
- Enric Reverter
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Juan J Lozano
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Cristina Alonso
- OWL Metabolomics, Parque Tecnológico de Bizkaia, Bizkaia, Spain
| | - Annalisa Berzigotti
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Susana Seijo
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Fanny Turon
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Anna Baiges
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Mari L Martínez-Chantar
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
- CIC bioGUNE, Parque Tecnológico de Bizkaia, Bizkaia, Spain
| | - José M Mato
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
- CIC bioGUNE, Parque Tecnológico de Bizkaia, Bizkaia, Spain
| | | | - Vincenzo La Mura
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Virginia Hernández-Gea
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Jaume Bosch
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Juan C García-Pagán
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
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Ortiz GA, Garcia-Tsao G. Future Pharmacological Therapies of Portal Hypertension. CURRENT HEPATOLOGY REPORTS 2019; 18:36-48. [PMID: 35722634 PMCID: PMC9205466 DOI: 10.1007/s11901-019-00448-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
PURPOSE OF REVIEW To provide an overview of recent pharmacological treatments for portal hypertension evaluated in early clinical trials, with particular emphasis on the pathophysiological basis of their use. RECENT FINDINGS In patients with compensated cirrhosis, even small decreases in portal pressure (as small as 1 mmHg) are associated with a lower probability of decompensation. In patients with decompensated cirrhosis, portal pressure "response" to non-selective beta-blocker (NSBB) therapy is associated with a lower mortality. When present, significant portal hypertension persists even after elimination of the etiology of cirrhosis and this justifies the continued development of new drugs that target portal hypertension. SUMMARY Over several decades we have gained great depth in the understanding of portal hypertension, its mechanisms and complications. NSBBs, which act by reducing portal venous inflow (an extrahepatic target), are effective in reducing portal pressure and have been the mainstay of therapy for portal hypertension in the last 35 years -being effective in preventing decompensation and variceal hemorrhage. However, because not all patients will have a sufficient response to NSBB and some may be intolerant to NSBB, alternative drugs or drugs that will augment the effect of NSBB on portal pressure are being tested in pre-clinical and early-clinical trials. Many of these drugs target more than one of the intrahepatic or extrahepatic mechanisms implicated in the pathogenesis of portal hypertension in cirrhosis. Out of these proposed therapies, statins have emerged as the most promising new pharmacological therapy for the treatment of portal hypertension.
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Affiliation(s)
- Guillermo A. Ortiz
- Digestive Diseases Section, Department of Medicine, Yale University, New Haven, CT, USA
- Digestive Diseases Section, Department of Internal medicine, VA-CT Healthcare System, West Haven, CT, USA
| | - Guadalupe Garcia-Tsao
- Digestive Diseases Section, Department of Medicine, Yale University, New Haven, CT, USA
- Digestive Diseases Section, Department of Internal medicine, VA-CT Healthcare System, West Haven, CT, USA
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Wei ZG, Wei FX, Shao ZW, Su GH, Qi XP, Zhang YC. Lowering hepatic venous pressure agent carvedilol versus variceal banding ligation for clinical outcomes of cirrhotic portal hypertension. Ther Clin Risk Manag 2018; 15:45-57. [PMID: 30636878 PMCID: PMC6307671 DOI: 10.2147/tcrm.s184863] [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] [Indexed: 11/23/2022] Open
Abstract
OBJECTIVE Carvedilol is nonselective beta-blocker with a mild anti-alpha-1-adrenergic effect. Several studies proposed improved hemodynamic effects of carvedilol compared with propanolol. Our study was to perform a systematic review and meta-analysis of randomized control trials comparing carvedilol with variceal banding ligation (VBL). METHODS Studies were searched on online databases MEDLINE, EMBASE(Ovid), the Cochrane Library, Chinese Wanfang Database, and China National Knowledge Infrastructure between January 2000 and May 2018. Incidence of bleeding and mortality were main outcome measures. Subgroup analysis and sensitivity analysis were conducted to ensure the robustness of pooled estimates. RESULTS Ten randomized control trials including 1,269 cirrhotic patients were chosen. Compared with VBL, carvedilol showed similar preventive efficacy of risk ratios (RRs) in variceal bleeding, and bleeding-related mortality over different follow-up periods from 6 months to 24 months. Also, significant differences between carvedilol and VBL in overall mortality and other causes of mortality were failed to be found. Carvedilol achieved a lower incidence of portal hypertension gastropathy in both 6 months (RR=0.49, 95% CI: 0.38-0.64, P<0.00001) and 12 months (RR=0.35, 95% CI: 0.26-0.47, P<0.00001). Two trials compared combination of carvedilol and VBL with VBL alone; however, the results failed to find an improved preventive efficacy of bleeding (RR=0.71, 95% CI: 0.15-3.30, P=0.67). CONCLUSION Carvedilol is equivalent to invasive VBL for variceal bleeding prevention. It can be well tolerated and may be of benefit to portal hypertension gastropathy. However, available data during 24 months follow-up did not support a potential advantage of carvedilol for prognosis as a lowering hepatic venous pressure agent.
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Affiliation(s)
- Zhen-Gang Wei
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou 730030, China,
- Hepato-Biliary-Pancreatic Institute, Lanzhou University Second Hospital, Lanzhou 730030, China,
- Lanzhou University Second Clinical Medical College, Lanzhou University Second Hospital, Lanzhou University, Lanzhou 730030, China,
| | - Feng-Xian Wei
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou 730030, China,
- Hepato-Biliary-Pancreatic Institute, Lanzhou University Second Hospital, Lanzhou 730030, China,
- Lanzhou University Second Clinical Medical College, Lanzhou University Second Hospital, Lanzhou University, Lanzhou 730030, China,
| | - Zi-Wei Shao
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou 730030, China,
- Hepato-Biliary-Pancreatic Institute, Lanzhou University Second Hospital, Lanzhou 730030, China,
- Lanzhou University Second Clinical Medical College, Lanzhou University Second Hospital, Lanzhou University, Lanzhou 730030, China,
| | - Guo-Hong Su
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou 730030, China,
- Hepato-Biliary-Pancreatic Institute, Lanzhou University Second Hospital, Lanzhou 730030, China,
- Lanzhou University Second Clinical Medical College, Lanzhou University Second Hospital, Lanzhou University, Lanzhou 730030, China,
| | - Xue-Ping Qi
- Lanzhou University Second Clinical Medical College, Lanzhou University Second Hospital, Lanzhou University, Lanzhou 730030, China,
| | - You-Cheng Zhang
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou 730030, China,
- Hepato-Biliary-Pancreatic Institute, Lanzhou University Second Hospital, Lanzhou 730030, China,
- Lanzhou University Second Clinical Medical College, Lanzhou University Second Hospital, Lanzhou University, Lanzhou 730030, China,
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