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Ramírez-Quesada W, Alvarado-Tapias E, Shalaby S, Hernández-Gea V. Recompensation in Cirrhosis: Biomarkers and Strategies. Semin Liver Dis 2025. [PMID: 40179966 DOI: 10.1055/a-2542-9930] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/05/2025]
Abstract
The onset of decompensation in advanced chronic liver disease (ACLD) is a hallmark in natural history, with a poor prognosis and a significantly increased liver-related mortality. Etiological treatments for viral hepatitis or abstinence in cirrhosis due to alcohol abuse have demonstrated that some patients experience partial to complete clinical and analytical improvement, a stage termed "recompensation." Although recompensation is primarily defined clinically based on treatable etiologies, it is still evolving for conditions like metabolic dysfunction-associated steatotic liver disease (MASLD). Despite the need for specific biomarkers in hepatic recompensation, no biomarkers have been thoroughly studied in this context. Biomarkers identified in compensated ACLD (cACLD) following etiological treatment might be explored for recompensation. Although the pathophysiology mechanisms underlying the hepatic recompensation remain unclear, understanding the mechanism involved in cirrhosis decompensation could help identify potential targets for recompensation. This review provides an update on the hepatic recompensation concept, examines the existing data on invasive and non-invasive biomarkers, mainly in cACLD after cure, that could be raised in recompensation, and explores future therapeutic targets for the hepatic recompensation process.
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Affiliation(s)
- Wagner Ramírez-Quesada
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Departament de Medicina i Ciències de la Salut, Fundació de Recerca Clínic Barcelona (FRCB-IDIBAPS), Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-RareLiver), Universitat de Barcelona, Barcelona, Spain
| | - Edilmar Alvarado-Tapias
- Centre for Biomedical Research in Liver and Digestive Diseases Network (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
- Gastroenterology and Hepatology Department, Hospital Santa Creu i Sant Pau, Autonomus University of Barcelona, Barcelona, Spain
| | - Sarah Shalaby
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Departament de Medicina i Ciències de la Salut, Fundació de Recerca Clínic Barcelona (FRCB-IDIBAPS), Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-RareLiver), Universitat de Barcelona, Barcelona, Spain
| | - Virginia Hernández-Gea
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Departament de Medicina i Ciències de la Salut, Fundació de Recerca Clínic Barcelona (FRCB-IDIBAPS), Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-RareLiver), Universitat de Barcelona, Barcelona, Spain
- Centre for Biomedical Research in Liver and Digestive Diseases Network (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
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2
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Premkumar M, Dhiman RK. Reply. Gastroenterology 2025:S0016-5085(25)00327-0. [PMID: 39894285 DOI: 10.1053/j.gastro.2025.01.222] [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: 01/24/2025] [Accepted: 01/27/2025] [Indexed: 02/04/2025]
Affiliation(s)
- Madhumita Premkumar
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Radha K Dhiman
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India; Mukh-Mantri Punjab Hepatitis C Relief Fund (MMPHCRF), Punjab Government, Punjab, India; Technical Resource Group - National Viral Hepatitis Control Program (NVHCP) Government of India, New Delhi, India; SGPGI, Lucknow, India
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3
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Albillos A, Bañares R, Hernández-Gea V. Portal hypertension: recommendations for diagnosis and treatment. Consensus document sponsored by the Spanish Association for the Study of the Liver (AEEH) and the Biomedical Research Network Centre for Liver and Digestive Diseases (CIBERehd). GASTROENTEROLOGIA Y HEPATOLOGIA 2025; 48:502208. [PMID: 39756832 DOI: 10.1016/j.gastrohep.2024.502208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Revised: 04/07/2024] [Accepted: 04/09/2024] [Indexed: 01/07/2025]
Abstract
Portal hypertension is a hemodynamic abnormality that complicates the course of cirrhosis, as well as other diseases that affect the portal venous circulation. The development of portal hypertension compromises prognosis, especially when it rises above a certain threshold known as clinically significant portal hypertension (CSPH). In the consensus conference on Portal Hypertension promoted by the Spanish Association for the Study of the Liver and the Hepatic and Digestive diseases area of the Biomedical Research Networking Center (CIBERehd), different aspects of the diagnosis and treatment of portal hypertension caused by cirrhosis or other diseases were discussed. The outcome of this discussion was a set of recommendations that achieved varying degrees of consensus among panelists and are reflected in this consensus document. The six areas under discussion were: the relevance of CSPH and the non-invasive methods used for its diagnosis and that of cirrhosis, the prevention of the first episode of decompensation and its recurrence, the treatment of acute variceal bleeding and other complications of portal hypertension, the indications for the use of TIPS, and finally, the diagnosis and treatment of liver vascular diseases.
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Affiliation(s)
- Agustín Albillos
- Servicio de Gastroenterología y Hepatología, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Universidad de Alcalá, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España.
| | - Rafael Bañares
- Servicio de Medicina de Aparato Digestivo, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IISGM), Universidad Complutense, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España.
| | - Virginia Hernández-Gea
- Servicio de Hepatología, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universidad de Barcelona, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, España.
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Albillos A, Bañares R, Hernández-Gea V. Portal hypertension: recommendations for diagnosis and treatment. Consensus document sponsored by the Spanish Association for the Study of the Liver (AEEH) and the Biomedical Research Network Center for Liver and Digestive Diseases (CIBERehd). REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2025; 117:14-57. [PMID: 39350672 DOI: 10.17235/reed.2024.10805/2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/30/2025]
Abstract
Portal hypertension is a hemodynamic abnormality that complicates the course of cirrhosis, as well as other diseases that affect the portal venous circulation. The development of portal hypertension compromises prognosis, especially when it rises above a certain threshold known as clinically significant portal hypertension (CSPH). In the consensus conference on Portal Hypertension promoted by the Spanish Association for the Study of the Liver and the Hepatic and Digestive diseases area of the Biomedical Research Networking Center (CIBERehd), different aspects of the diagnosis and treatment of portal hypertension caused by cirrhosis or other diseases were discussed. The outcome of this discussion was a set of recommendations that achieved varying degrees of consensus among panelists and are reflected in this consensus document. The six areas under discussion were: the relevance of clinically significant portal hypertension and the non-invasive methods used for its diagnosis and that of cirrhosis, the prevention of the first episode of decompensation and its recurrence, the treatment of acute variceal bleeding and other complications of portal hypertension, the indications for the use of TIPS, and finally, the diagnosis and treatment of liver vascular diseases.
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Affiliation(s)
- Agustín Albillos
- Servicio de Gastroenterología y Hepatología, Hospital Universitario Ramón y Cajal, España
| | - Rafael Bañares
- Servicio de Medicina de Aparato Digestivo, Hospital General Universitario Gregorio Marañón
| | - Virginia Hernández-Gea
- Servicio de Hepatología, Hospital Clínic. Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
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5
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Singal AK, Panneerselvam D, Arab JP, Im G, Kuo YF. Delisting From Liver Transplant List for Improvement and Recompensation Among Decompensated Patients at One Year. Am J Gastroenterol 2024:00000434-990000000-01494. [PMID: 39714037 DOI: 10.14309/ajg.0000000000003259] [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: 04/05/2024] [Accepted: 10/03/2024] [Indexed: 12/24/2024]
Abstract
INTRODUCTION Data are limited regarding etiology-specific trends for delisting and recompensation for liver disease improvement among liver transplantation (LT)-listed candidates in the United States. METHODS AND RESULTS A retrospective cohort (2002-2022) using United Network of Organ Sharing database examined etiology-specific trends for delisting and recompensation due to liver disease improvement among candidates listed for LT. Of 120,451 listings in adults, 34,444 (2002-2008), 38,296 (2009-2015), 47,711 (2016-2022) were analyzed. A total of 7,196 (6.2%) were delisted for liver disease improvement, with 5.6%, 7.2%, and 5.3% in 3 respective time periods, Armitage trend P < 0.001. Delisting for improvement of liver disease was 8.1%, 5.8%, 4.0%, 3.9%, and 3.1% among listings for alcohol-associated liver disease (ALD n = 41,647), hepatitis C virus infection (HCV n = 38,797), autoimmune (n = 12,131), metabolic-associated steatohepatitis (MASH n = 22,162), hepatitis B virus infection (HBV n = 3,027), and metabolic liver disease (MLD n = 2,687), respectively. One thousand one hundred twenty-two (15.6% or 0.9%) were delisted for improvement at 1 year with cumulative incidence competing for waitlist mortality and receipt of LT of 1.18, 1.17, 0.64, 0.59, 0.50, and 0.34 for ALD, HBV, HCV, MASH, MLD, and autoimmune, respectively. In a fine and gray model, compared with metabolic, subhazard ratio (95% confidence interval) on delisting at 1 year was 3.47 (31.6-3.81) and 3.44 (2.96-3.99), P < 0.001, for ALD and for HBV, respectively. Of 7,196 delisting for improvement, 567 of 5,750 (9.9%) decompensated at listing had recompensation, 19.5% for HBV, 16.6% for MLD and autoimmune, 9.9% ALD, 8.6% for HCV, and 6.9% for MASH. In a logistic regression model among delisted candidates for improved liver disease, HBV vs MASH etiology was associated with recompensation, 2.37 (1.40-4.03), P < 0.001. DISCUSSION ALD and HBV are most frequent etiologies for delisting due to liver disease improvement. About 10% of delisted patients develop recompensation, with HBV etiology most likely to recompensate. Models and biomarkers are needed to identify these candidates for optimal use of deceased donor livers.
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Affiliation(s)
- Ashwani K Singal
- Department of Medicine, University of Louisville Health Sciences Center, Louisville, Kentucky, USA
- Department of Medicine, Trager Transplant Center at Jewish Hospital, Louisville, Kentucky, USA
- Department of Medicine, KRobley Rex VA Medical Center, Louisville, Kentucky, USA
| | - Deepan Panneerselvam
- Department of Medicine, University of South Dakota, Sioux Falls, South Dakota, USA
| | - Juan P Arab
- Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University & London Health Sciences Centre, London, Ontario, Canada
| | - Gene Im
- Department of Medicine, Mount Sinai School of Medicine, New York, New York, USA
| | - Yong-Fang Kuo
- Department of Biostatistics, University of Texas Medical Branch, Galveston, Texas, USA
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6
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Romano A, Zeni N, Caspanello AR, Phillips S, Piano SS, Angeli P. Follow-up post-HCV virological response to DAA in advanced chronic liver disease. Liver Int 2024; 44:3138-3150. [PMID: 39344755 DOI: 10.1111/liv.16113] [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: 05/09/2024] [Revised: 09/05/2024] [Accepted: 09/11/2024] [Indexed: 10/01/2024]
Abstract
Direct-acting antivirals (DAA) achieve high virological response rates with minimal side effects for many patients. Despite their significant impact on the progression and epidemiology of hepatitis C virus (HCV) associated liver disease, the global annual incidence of chronic infections is expected to remain relatively constant, averaging 1.42 million new cases each year until 2030. Furthermore, by 2030, there will be a 14-17% increase in end-stage liver disease outcomes such as liver-related deaths, hepatocellular carcinoma (HCC), and decompensated cirrhosis in adults aged 18 years and over. Although reductions in liver decompensation, HCC occurrence, and mortality have been shown in patients with advanced liver disease who achieved sustained virological response (SVR) with DAA, these benefits may be less significant in those with decompensated liver cirrhosis. This review aims to summarise the impact of the virological response to DAA on liver disease progression and outcomes in patients with advanced chronic liver disease, which appears to be crucial for defining patient-specific follow-up.
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Affiliation(s)
- A Romano
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy
| | - N Zeni
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy
| | - A R Caspanello
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy
- Department of Clinical and Experimental Medicine, Unit of Medicine and Hepatology, University of Messina, Messina, Italy
| | - S Phillips
- Institute of Hepatology Foundation for Liver Research London UK, School of Immunology and Microbial Sciences King's College London, London, UK
| | - S S Piano
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy
| | - P Angeli
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy
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Piano S, Reiberger T, Bosch J. Mechanisms and implications of recompensation in cirrhosis. JHEP Rep 2024; 6:101233. [PMID: 39640222 PMCID: PMC11617229 DOI: 10.1016/j.jhepr.2024.101233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Revised: 09/02/2024] [Accepted: 09/26/2024] [Indexed: 12/07/2024] Open
Abstract
Decompensated cirrhosis has long been considered the irreversible end stage of liver disease, characterised by further decompensating events until death or liver transplantation. However, the observed clinical improvements after effective antiviral treatments for HBV and HCV and after sustained alcohol abstinence have changed this paradigm, leading to the concept of "recompensation" of cirrhosis. Recompensation of cirrhosis was recently defined by Baveno VII as (i) cure of the primary liver disease aetiology; (ii) disappearance of signs of decompensation (ascites, encephalopathy and portal hypertensive bleeding) off therapy; and (iii) stable improvement of liver function tests (bilirubin, international normalised ratio and albumin). Achieving these recompensation criteria is linked to a significant survival benefit. However, apart from aetiological therapies, no interventions/treatments that facilitate recompensation are available, the molecular mechanisms underlying recompensation remain incompletely understood, and early predictors of recompensation are lacking. Moreover, current recompensation criteria are based on expert opinion and may be refined in the future. Herein, we review the available evidence on cirrhosis recompensation, provide guidance on the clinical management of recompensated patients and discuss future challenges related to cirrhosis recompensation.
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Affiliation(s)
- Salvatore Piano
- Unit of Internal Medicine and Hepatology, Department of Medicine – DIMED, University and Hospital of Padova, Italy
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna Austria
| | - Jaime Bosch
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland
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8
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Tonon M, Gagliardi R, Zeni N, Piano S. Recompensation of cirrhosis in candidates of transplant: Tips and tricks for delisting. Liver Transpl 2024; 30:1181-1187. [PMID: 38926937 DOI: 10.1097/lvt.0000000000000409] [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: 12/27/2023] [Accepted: 05/16/2024] [Indexed: 06/28/2024]
Abstract
Liver transplantation (LT) is the most successful treatment for patients with decompensated cirrhosis. The availability of effective and safe etiological treatments has altered the natural history of decompensated cirrhosis. Recently, the concept of recompensation has been defined. Patients who achieve recompensation may be removed from the waiting list for LT. Therefore, achieving an etiological cure is the cornerstone in the treatment of patients with decompensated cirrhosis. However, most patients improve their liver function after an etiologic cure, and only a proportion of patients achieve true recompensation after an etiological cure. Some patients maintain a condition of "MELD purgatory," that is, an improvement in the Model for End-Stage Liver Disease score without relevant clinical improvement that prevents delisting and may be even detrimental because lower Model for End-Stage Liver Disease score delays LT. Herein, we review the available evidence regarding recompensation and the management of recompensated patients on the waiting list for LT.
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Affiliation(s)
- Marta Tonon
- Unit of Internal Medicine and Hepatology, Department of Medicine-DIMED, University and Hospital of Padova, Padova, Italy
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9
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Reiberger T, Lens S, Cabibbo G, Nahon P, Zignego AL, Deterding K, Elsharkawy AM, Forns X. EASL position paper on clinical follow-up after HCV cure. J Hepatol 2024; 81:326-344. [PMID: 38845253 DOI: 10.1016/j.jhep.2024.04.007] [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: 04/05/2024] [Accepted: 04/05/2024] [Indexed: 07/26/2024]
Abstract
Following the advent of direct-acting antivirals (DAAs), hepatitis C virus (HCV) infection can be cured in almost all infected patients. This has led to a number of clinical questions regarding the optimal management of the millions of patients cured of HCV. This position statement provides specific guidance on the appropriate follow-up after a sustained virological response in patients without advanced fibrosis, those with compensated advanced chronic liver disease, and those with decompensated cirrhosis. Guidance on hepatocellular carcinoma risk assessment and the management of extrahepatic manifestations of HCV is also provided. Finally, guidance is provided on the monitoring and treatment of reinfection in at-risk patients. The recommendations are based on the best available evidence and are intended to help healthcare professionals involved in the management of patients after treatment for HCV.
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Affiliation(s)
- Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria. CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
| | - Sabela Lens
- Liver Unit, Hospital Clinic Barcelona. IDIBAPS. Liver and Digestive Diseases Networking Biomedical Research Centre (CIBERehd). University of Barcelona. Spain
| | - Giuseppe Cabibbo
- Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties PROMISE, University of Palermo, Italy
| | - Pierre Nahon
- AP-HP, Hôpitaux Universitaires Paris Seine Saint-Denis, Liver Unit, Bobigny; Université Sorbonne Paris Nord, F-93000 Bobigny; Inserm, UMR-1138 "Functional Genomics of Solid Tumors", Centre de Recherche des Cordeliers, Université de Paris, France
| | - Anna Linda Zignego
- Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy
| | - Katja Deterding
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School. Germany
| | - Ahmed M Elsharkawy
- Liver Unit, Queen Elizabeth Hospital Birmingham. NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham, United Kingdom
| | - Xavier Forns
- Liver Unit, Hospital Clinic Barcelona. IDIBAPS. Liver and Digestive Diseases Networking Biomedical Research Centre (CIBERehd). University of Barcelona. Spain.
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Doyle EH, Aloman C, El-Shamy A, Eng FJ, Kim-Schulze S, Rahman A, Schiano T, Heeger P, Branch AD. Imprinted immune abnormalities in liver transplant patients cured of hepatitis C with antiviral drugs. Liver Transpl 2024; 30:728-741. [PMID: 38315053 DOI: 10.1097/lvt.0000000000000342] [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: 08/17/2023] [Accepted: 01/11/2024] [Indexed: 02/07/2024]
Abstract
Chronic HCV infection induces interferon and dysregulates immune responses through inflammation and chronic antigenic stimulation. Antiviral drugs can cure HCV, providing a unique opportunity to examine the immunological restoration that does and does not occur when a chronic viral infection is eradicated. We quantified blood cytokines levels and used mass cytometry to immunophenotype peripheral blood mononuclear cells before and after HCV cure in 2 groups of patients and controls. At baseline, serum interferon α and soluble CD163 (a macrophage product) were elevated in both liver transplant and nonliver transplant patients compared to controls; the frequencies of several peripheral blood mononuclear cell populations differed from controls; and programmed death protein 1-positivity was increased in nearly all T cell subsets. Many abnormalities persisted after HCV cure, including elevated programmed death protein 1 expression on CD4 naïve and central memory T cells, elevated soluble CD163, and expansion of the plasmablast/plasma cell compartment. Several myeloid-lineage subsets, including Ag-presenting dendritic cells, remained dysregulated. In mechanistic studies, interferon α treatment increased programmed death protein 1 on human T cells and increased T cell receptor signaling. The data identify immunological abnormalities that persist after curative HCV treatment. Before cure, high levels of interferon α may stimulate programmed death protein 1 expression on human T cells, causing persistent functional changes.
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MESH Headings
- Humans
- Liver Transplantation/adverse effects
- Male
- Antiviral Agents/therapeutic use
- Middle Aged
- Female
- Antigens, CD/immunology
- Antigens, CD/blood
- Antigens, CD/metabolism
- Antigens, Differentiation, Myelomonocytic/blood
- Antigens, Differentiation, Myelomonocytic/immunology
- Hepatitis C, Chronic/immunology
- Hepatitis C, Chronic/drug therapy
- Hepatitis C, Chronic/blood
- Hepatitis C, Chronic/surgery
- Interferon-alpha/therapeutic use
- Programmed Cell Death 1 Receptor/antagonists & inhibitors
- Programmed Cell Death 1 Receptor/immunology
- Receptors, Cell Surface/blood
- Receptors, Cell Surface/immunology
- Adult
- Case-Control Studies
- Aged
- Hepacivirus/immunology
- Hepacivirus/drug effects
- Leukocytes, Mononuclear/immunology
- Cytokines/blood
- Immunophenotyping
- Treatment Outcome
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Affiliation(s)
- Erin H Doyle
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Costica Aloman
- Department of Surgery, Westchester Medical Center, New York Medical College, Valhalla, New York, USA
| | - Ahmed El-Shamy
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- College of Graduate Studies, Master of Pharmaceutical Sciences Program
| | - Francis J Eng
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Seunghee Kim-Schulze
- Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Adeeb Rahman
- Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Thomas Schiano
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Peter Heeger
- Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Andrea D Branch
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA
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11
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Shetty A, Lee M, Valenzuela J, Saab S. Cost effectiveness of hepatitis C direct acting agents. Expert Rev Pharmacoecon Outcomes Res 2024; 24:589-597. [PMID: 38665122 DOI: 10.1080/14737167.2024.2348053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Accepted: 04/23/2024] [Indexed: 05/04/2024]
Abstract
INTRODUCTION Introduction of direct acting antivirals (DAA) has transformed treatment of chronic hepatitis C (HCV) and made the elimination of HCV an achievable goal set forward by World Health Organization by 2030. Multiple barriers need to be overcome for successful eradication of HCV. Availability of pan-genotypic HCV regimens has decreased the need for genotype testing but maintained high efficacy associated with DAAs. AREAS COVERED In this review, we will assess the cost-effectiveness of DAA treatment in patients with chronic HCV disease, with emphasis on general, cirrhosis, and vulnerable populations. EXPERT OPINION Multiple barriers exist limiting eradication of HCV, including cost to treatment, access, simplified testing, and implementing policy to foster treatment for all groups of HCV patients. Clinically, DAAs have drastically changed the landscape of HCV, but focused targeting of vulnerable groups is needed. Public policy will continue to play a strong role in eliminating HCV. While we will focus on the cost-effectiveness of DAA, several other factors regarding HCV require on going attention, such as increasing public awareness and decreasing social stigma associated with HCV, offering universal screening followed by linkage to treatment and improving preventive interventions to decrease spread of HCV.
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Affiliation(s)
- Akshay Shetty
- Department of Medicine, University of California at Los Angeles, Los Angeles, CA, USA
- Department of Surgery, University of California at Los Angeles, Los Angeles, CA, USA
| | - Michelle Lee
- Department of Surgery, University of California at Los Angeles, Los Angeles, CA, USA
| | - Julia Valenzuela
- Department of Surgery, University of California at Los Angeles, Los Angeles, CA, USA
| | - Sammy Saab
- Department of Medicine, University of California at Los Angeles, Los Angeles, CA, USA
- Department of Surgery, University of California at Los Angeles, Los Angeles, CA, USA
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12
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Pearlman BL. Direct-Acting Antiviral Therapy for Patients with Chronic Hepatitis C Infection and Decompensated Cirrhosis. Dig Dis Sci 2024; 69:1551-1561. [PMID: 38580885 DOI: 10.1007/s10620-024-08393-x] [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] [Accepted: 03/16/2024] [Indexed: 04/07/2024]
Abstract
Patients with chronic hepatitis C virus (HCV) infection and decompensated cirrhosis are an important population for antiviral therapy yet under-represented in clinical trials. HCV direct-acting antiviral (DAA) therapies, unlike interferon-containing regimens, can be safely utilized in decompensated patients. Per guidelines from the American Association for the Study of Liver Diseases (AASLD), therapy of choice in HCV and decompensated cirrhosis is sofosbuvir, an HCV polymerase inhibitor, combined with a replication complex inhibitor (NS5A inhibitor) with or without ribavirin. Combination therapy with a HCV protease inhibitor and an NS5A inhibitor is effective in this population but is specifically not recommended in AASLD guidelines due to safety concerns. Important risk factors for further decompensation during DAA therapy are serum albumin < 3.5 g/dL, MELD (Model for End-Stage Liver Disease) score > 14, or HCV genotype 3 infection. Although sustained virologic response (SVR) is achieved less often in patients with decompensated vs compensated cirrhosis, in clinical studies response rates are > 80%. Both Child-Turcotte-Pugh Class at baseline and viral genotype can affect these response rates. Achieving SVR lowers risk of mortality, but to a lesser extent than in individuals with compensated cirrhosis. Likewise, treating patients for HCV infection along with successful treatment for hepatocellular carcinoma improves risks of both liver-related and overall mortality. In fewer than one third of cases, treating transplant-eligible, HCV-infected patients pre-transplant enables their delisting from transplant wait lists.
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Affiliation(s)
- Brian L Pearlman
- Center for Hepatitis C, Wellstar Atlanta Medical Center, 285 Boulevard NE, Suite 525, Atlanta, GA, 30312, USA.
- Medical College of Georgia, Augusta, GA, USA.
- Emory School of Medicine, Atlanta, GA, USA.
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13
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Kim DS, Yoon YI, Kim BK, Choudhury A, Kulkarni A, Park JY, Kim J, Sinn DH, Joo DJ, Choi Y, Lee JH, Choi HJ, Yoon KT, Yim SY, Park CS, Kim DG, Lee HW, Choi WM, Chon YE, Kang WH, Rhu J, Lee JG, Cho Y, Sung PS, Lee HA, Kim JH, Bae SH, Yang JM, Suh KS, Al Mahtab M, Tan SS, Abbas Z, Shresta A, Alam S, Arora A, Kumar A, Rathi P, Bhavani R, Panackel C, Lee KC, Li J, Yu ML, George J, Tanwandee T, Hsieh SY, Yong CC, Rela M, Lin HC, Omata M, Sarin SK. Asian Pacific Association for the Study of the Liver clinical practice guidelines on liver transplantation. Hepatol Int 2024; 18:299-383. [PMID: 38416312 DOI: 10.1007/s12072-023-10629-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Accepted: 12/18/2023] [Indexed: 02/29/2024]
Abstract
Liver transplantation is a highly complex and challenging field of clinical practice. Although it was originally developed in western countries, it has been further advanced in Asian countries through the use of living donor liver transplantation. This method of transplantation is the only available option in many countries in the Asia-Pacific region due to the lack of deceased organ donation. As a result of this clinical situation, there is a growing need for guidelines that are specific to the Asia-Pacific region. These guidelines provide comprehensive recommendations for evidence-based management throughout the entire process of liver transplantation, covering both deceased and living donor liver transplantation. In addition, the development of these guidelines has been a collaborative effort between medical professionals from various countries in the region. This has allowed for the inclusion of diverse perspectives and experiences, leading to a more comprehensive and effective set of guidelines.
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Affiliation(s)
- Dong-Sik Kim
- Department of Surgery, Korea University College of Medicine, Seoul, Republic of Korea
| | - Young-In Yoon
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | | | | | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jongman Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dong Jin Joo
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - YoungRok Choi
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jeong-Hoon Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Ho Joong Choi
- Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Ki Tae Yoon
- Department of Internal Medicine, Pusan National University College of Medicine, Yangsan, Republic of Korea
| | - Sun Young Yim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Cheon-Soo Park
- Department of Surgery, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Deok-Gie Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hae Won Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Won-Mook Choi
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Young Eun Chon
- Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea
| | - Woo-Hyoung Kang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jinsoo Rhu
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jae Geun Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Yuri Cho
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Ilsan, Republic of Korea
| | - Pil Soo Sung
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Han Ah Lee
- Department of Internal Medicine, Ewha Womans University, Seoul, Republic of Korea
| | - Ji Hoon Kim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Si Hyun Bae
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jin Mo Yang
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
| | - Mamun Al Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Soek Siam Tan
- Department of Medicine, Hospital Selayang, Batu Caves, Selangor, Malaysia
| | - Zaigham Abbas
- Sindh Institute of Urology and Transplantation, Karachi, Pakistan
| | - Ananta Shresta
- Department of Hepatology, Alka Hospital, Lalitpur, Nepal
| | - Shahinul Alam
- Crescent Gastroliver and General Hospital, Dhaka, Bangladesh
| | - Anil Arora
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital New Delhi, New Delhi, India
| | - Ashish Kumar
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital New Delhi, New Delhi, India
| | - Pravin Rathi
- TN Medical College and BYL Nair Hospital, Mumbai, India
| | - Ruveena Bhavani
- University of Malaya Medical Centre, Petaling Jaya, Selangor, Malaysia
| | | | - Kuei Chuan Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Jun Li
- College of Medicine, Zhejiang University, Hangzhou, China
| | - Ming-Lung Yu
- Department of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | | | | | | | | | | | - H C Lin
- Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Masao Omata
- Department of Gastroenterology, Yamanashi Central Hospital, Yamanashi, Japan
- University of Tokyo, Bunkyo City, Japan
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14
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Kumar N, Choudhary NS. Managing HBV and HCV Infection Pre- and Post-liver Transplant. J Clin Exp Hepatol 2024; 14:101287. [PMID: 38076445 PMCID: PMC10709521 DOI: 10.1016/j.jceh.2023.09.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2022] [Accepted: 09/19/2023] [Indexed: 03/03/2025] Open
Abstract
Hepatitis B and C are common causes of end-stage liver disease and etiologies of liver transplantation. It is important to prevent recurrence in cases of hepatitis B. Nucleos(t)ide analogs are the mainstay of HBV treatment before (in patients with decompensated cirrhosis) and after liver transplantation. After the introduction of direct-acting antivirals, the treatment of HCV has become considerably easy. In patients with advanced HCV-related cirrhosis, it is better to do transplantation first and treat them after liver transplantation. The sustained virological response rates have improved from 8 to 50% in the interferon era to 90% in the direct-acting antivirals era. In the current review, we discuss the treatment of HBV and HCV before and after liver transplantation.
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Affiliation(s)
- Naveen Kumar
- Hepatology and Gastroenterology, Narayana Hospital Delhi, India
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15
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Sonderup MW, Kamath PS, Awuku YA, Desalegn H, Gogela N, Katsidzira L, Tzeuton C, Bobat B, Kassianides C, Spearman CW. Managing cirrhosis with limited resources: perspectives from sub-Saharan Africa. Lancet Gastroenterol Hepatol 2024; 9:170-184. [PMID: 38215781 DOI: 10.1016/s2468-1253(23)00279-0] [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: 05/18/2023] [Revised: 08/05/2023] [Accepted: 08/14/2023] [Indexed: 01/14/2024]
Abstract
Cirrhosis represents the end stage of chronic liver disease. Sub-Saharan Africa, a resource-constrained region, has a high burden of chronic liver disease, with causes including chronic viral hepatitis, excessive alcohol use, and metabolic dysfunction-associated steatotic liver disease (MASLD), the risk of which is burgeoning. The development of liver cirrhosis predicts for morbidity and mortality, driven by both liver dysfunction and the consequences of portal hypertension. Compensated cirrhosis portends a better prognosis than decompensated cirrhosis, highlighting the need for the early diagnosis of cirrhosis and its causes. With resource challenges, the diagnosis and management of cirrhosis is demanding, but less costly and less invasive interventions with substantial benefits, ranging from simple blood tests to transient elastography, are feasible in such settings. Simple interventions are also available to manage the complex manifestations of decompensation, such as β blockers in variceal bleeding prophylaxis, salt restriction and appropriate diuretic use in ascites, and lactulose and generic rifaximin in hepatic encephalopathy. Ultimately, managing the underlying causative factors of liver disease is key in improving prognosis. Management demands expanded policy interventions to increase screening and treatment for hepatitis B and C and reduce alcohol use and the metabolic factors driving MASLD. Furthermore, the skills needed for more specialised interventions, such as transjugular intrahepatic portosystemic shunt procedures and even liver transplantation, warrant planning, increased capacity, and support for regional centres of excellence. Such centres are already being developed in sub-Saharan Africa, demonstrating what can be achieved with dedicated initiatives and individuals.
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Affiliation(s)
- Mark W Sonderup
- Division of Hepatology, Department of Medicine, Faculty of Health Sciences, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa.
| | | | - Yaw A Awuku
- Department of Medicine, School of Medicine, University of Health and Allied Sciences, Ho, Ghana
| | - Hailemichael Desalegn
- Department of Internal Medicine, St Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia
| | - Neliswa Gogela
- Division of Hepatology, Department of Medicine, Faculty of Health Sciences, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa
| | - Leolin Katsidzira
- Internal Medicine Unit, Faculty of Medicine and Health Sciences, University of Zimbabwe, Harare, Zimbabwe
| | - Christian Tzeuton
- Faculty of Medicine and Pharmaceutical Sciences of Douala, University of Douala, Douala, Cameroon
| | - Bilal Bobat
- Charlotte Maxeke Johannesburg Academic Hospital, University of the Witwatersrand and Wits Donald Gordon Medical Centre, Johannesburg, South Africa
| | - Chris Kassianides
- Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
| | - C Wendy Spearman
- Division of Hepatology, Department of Medicine, Faculty of Health Sciences, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa
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16
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Sharma M, Alla M, Kulkarni A, Nagaraja Rao P, Nageshwar Reddy D. Managing a Prospective Liver Transplant Recipient on the Waiting List. J Clin Exp Hepatol 2024; 14:101203. [PMID: 38076359 PMCID: PMC10701136 DOI: 10.1016/j.jceh.2023.06.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Accepted: 06/09/2023] [Indexed: 01/05/2025] Open
Abstract
The management of a patient in the peri-transplantation period is highly challenging, and it is even more difficult while the patient is on the transplantation waitlist. Keeping the patient alive during this period involves managing the complications of liver disease and preventing the disease's progression. Based on the pre-transplantation etiology and type of liver failure, there is a difference in the management protocol. The current review is divided into different sections, which include: the management of underlying cirrhosis and complications of portal hypertension, treatment and identification of infections, portal vein thrombosis management, and particular emphasis on the management of patients of hepatocellular carcinoma and acute liver failure in the transplantation waitlist. The review highlights special concerns in the management of patients in the Asian subcontinent also. The review also addresses the issue of delisting from the transplant waitlist to see that futility does not overtake the utility of organs. The treatment modalities are primarily expressed in tabular format for quick reference. The following review integrates the vast issues in this period concisely so that the management during this crucial period is taken care of in the best possible way.
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Affiliation(s)
- Mithun Sharma
- Department of Hepatology and Liver Transplantation, Asian Institute of Gastroenterology Hospitals, Hyderabad, India
| | - Manasa Alla
- Department of Hepatology and Liver Transplantation, Asian Institute of Gastroenterology Hospitals, Hyderabad, India
| | - Anand Kulkarni
- Department of Hepatology and Liver Transplantation, Asian Institute of Gastroenterology Hospitals, Hyderabad, India
| | - Padaki Nagaraja Rao
- Department of Hepatology and Liver Transplantation, Asian Institute of Gastroenterology Hospitals, Hyderabad, India
| | - Duvvur Nageshwar Reddy
- Department of Gastroenterology, Asian Institute of Gastroenterology Hospitals, Hyderabad, India
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17
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Samuel S, Abulawi A, Malik R. Hepatitis C and Nonalcoholic Steatohepatitis in the 21st Century: Impact on Liver Disease and Liver Transplantation. GASTROENTEROLOGY INSIGHTS 2023; 14:249-270. [DOI: 10.3390/gastroent14030018] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
Hepatitis C infection is a leading etiology of hepatic dysfunction and a major indication for liver transplantation due to the development of fibrosis, cirrhosis, and hepatocellular carcinoma. Nonalcoholic fatty liver disease (NAFLD) and, specifically, its subtype nonalcoholic steatohepatitis (NASH) is a rising cause of liver disease. It is predicted to surpass hepatitis C as a leading indication for transplant. The introduction of direct-acting antivirals (DAAs) decreased the prevalence of chronic hepatitis C infections, but the obesity epidemic and metabolic syndrome have increased the prevalence of NASH. Weight loss and dietary modifications are recommended NASH therapies, but unlike for hepatitis C, federally approved agents are lacking and currently under investigation. Clinical trials face many barriers in NASH treatment because of the difficulty of diagnosis and a lack of standardized and accurate clinical and histologic responses. Mortality and morbidity in NASH are heightened because of the presence of multiple comorbidities including cardiovascular disease, diabetes, and renal dysfunction. A liver transplant may be indicated, but a thorough screening of candidates, including a comprehensive cardiovascular assessment, is essential to ensuring successful outcomes pre- and post-transplant. Therapeutic agents for NASH are warranted before it becomes a significant and leading cause of morbidity and mortality worldwide.
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Affiliation(s)
- Sonia Samuel
- Division of Gastroenterology & Hepatology, Albany Medical Center, 47 New Scotland Ave, Albany, NY 12208, USA
| | - Ahmad Abulawi
- Division of Gastroenterology & Hepatology, Albany Medical Center, 47 New Scotland Ave, Albany, NY 12208, USA
| | - Raza Malik
- Division of Gastroenterology & Hepatology, Albany Medical Center, 47 New Scotland Ave, Albany, NY 12208, USA
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18
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Ivashkin VT, Chulanov VP, Mamonova NA, Maevskaya MV, Zharkova MS, Tikhonov IN, Bogomolov PO, Volchkova EV, Dmitriev AS, Znojko OO, Klimova EA, Kozlov KV, Kravchenko IE, Malinnikova EY, Maslennikov RV, Mikhailov MI, Novak KE, Nikitin IG, Syutkin VE, Esaulenko EV, Sheptulin AA, Shirokova EN, Yushchuk ND. Clinical Practice Guidelines of the Russian Society for the Study of the Liver, the Russian Gastroenterological Association, the National Scientific Society of Infectious Disease Specialists for the Diagnosis and Treatment of Chronic Hepatitis C. RUSSIAN JOURNAL OF GASTROENTEROLOGY, HEPATOLOGY, COLOPROCTOLOGY 2023; 33:84-124. [DOI: 10.22416/1382-4376-2023-33-1-84-124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/26/2024]
Abstract
Аim:diagnosis and treatment algorithms in the clinical recommendations intended for general practitioners, gastroenterologists, infectious disease specialists, hepatologists on the of chronic hepatitis C are presented.Summary.Chronic viral hepatitis C is a socially significant infection, the incidence of which in the Russian Federation remains significantly high. Over the past 10 years, great progress has been made in the treatment of hepatitis C — direct acting antiviral drugs have appeared. The spectrum of their effectiveness allows to achieve a sustained virological response in more than 90 % of cases, even in groups that were not previously considered even as candidates for therapy or were difficult to treat — patients receiving renal replacement therapy, after liver transplantation (or other organs), at the stage of decompensated liver cirrhosis, HIV co-infected, etc. Interferons are excluded from the recommendations due to their low effectiveness and a wide range of adverse events. The indications for the treatment have been expanded, namely, the fact of confirmation of viral replication. The terms of dispensary observation of patients without cirrhosis of the liver have been reduced (up to 12 weeks after the end of therapy). Also, these recommendations present approaches to active screening of hepatitis in risk groups, preventive and rehabilitation measures after the end of treatment.Conclusion.Great success has been achieved in the treatment of chronic hepatitis C. In most cases, eradication of viral HCV infection is a real task even in patients at the stage of cirrhosis of the liver, with impaired renal function, HIV co-infection, after solid organs transplantation.
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Affiliation(s)
- V. T. Ivashkin
- Sechenov First Moscow State Medical University (Sechenov University)
| | - V. P. Chulanov
- Center for Epidemiologically Significant Infectious Diseases, National Medical Research Center for Phthisiopulmonology and Infectious Diseases
| | - N. A. Mamonova
- Center for Epidemiologically Significant Infectious Diseases, National Medical Research Center for Phthisiopulmonology and Infectious Diseases
| | - M. V. Maevskaya
- Sechenov First Moscow State Medical University (Sechenov University)
| | - M. S. Zharkova
- Sechenov First Moscow State Medical University (Sechenov University)
| | - I. N. Tikhonov
- Sechenov First Moscow State Medical University (Sechenov University)
| | - P. O. Bogomolov
- M.F. Vladimirsky Moscow Regional Research Clinical Institute
| | - E. V. Volchkova
- Sechenov First Moscow State Medical University (Sechenov University)
| | - A. S. Dmitriev
- Sechenov First Moscow State Medical University (Sechenov University)
| | - O. O. Znojko
- Moscow State University of Medicine and Dentistry
| | | | | | | | - E. Yu. Malinnikova
- Department of Virology, Russian Medical Academy of Continuing Professional Education
| | - R. V. Maslennikov
- Sechenov First Moscow State Medical University (Sechenov University)
| | - M. I. Mikhailov
- North-Western State Medical University named after I.I. Mechnikov
| | | | | | - V. E. Syutkin
- Sklifosovsky Clinical and Research Institute for Emergency Medicine; Russian State Research Center — Burnazyan Federal Medical Biophysical Center
| | | | - A. A. Sheptulin
- Sechenov First Moscow State Medical University (Sechenov University)
| | - E. N. Shirokova
- Sechenov First Moscow State Medical University (Sechenov University)
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19
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Sharma S, Roy A. Recompensation in Cirrhosis: Current Evidence and Future Directions. J Clin Exp Hepatol 2023; 13:329-334. [PMID: 36950490 PMCID: PMC10025679 DOI: 10.1016/j.jceh.2022.08.002] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Accepted: 08/07/2022] [Indexed: 02/17/2023] Open
Abstract
The natural history of cirrhosis has usually been conceptualized in the context of progression from compensated cirrhosis to subsequent stages of decompensation. While this unidirectional concept is the most common pathophysiological trajectory, there has been an emerging understanding of a subgroup of patients which undergo recompensation. While literature mostly based on transplant waitlist registries have indicated towards such a population who experience disease regression, the overall literature about this entity remains inexplicit. An effort to generate consensus on defining recompensation has been attempted which comes with its own nuances and limitations. We summarize the available literature on this emerging yet controversial concept of recompensation in cirrhosis and delve into future implications and impact on real-life practice.
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Key Words
- ALD, Alcoholic liver disease
- ALF, Acute liver failure
- APASL, Asia Pacific Association for the Study of Liver
- CAID, Cirrhosis associated immune dysfunction
- CSPH, Clinically significant portal hypertension
- CTP, Child-Turcotte-Pugh
- DC, Decompensated cirrhosis
- FAP, Familial amyloid polyneuropathy
- HBV, Hepatitis B Virus
- HCC, Hepatocellular carcinoma
- HCV, Hepatitis C Virus
- HE, Hepatic encephalopathy
- HVPG, Hepatic venous portal gradient
- INR, International normalized ratio
- LT, Liver transplantation
- MELD, Model for end-stage liver disease
- TIPSS, Transjugular intrahepatic porto-systemic shunt
- cACLD, Compensated advanced chronic liver disease
- liver disease
- portal hypertension
- recompensation
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Affiliation(s)
- Sanchit Sharma
- Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, OX39DU, United Kingdom
| | - Akash Roy
- Institute of Gastrosciences and Liver Transplantation, Apollo Multispeciality Hospitals, Kolkata, 700054, India
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20
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Rossotti R, Merli M, Mazzarelli C, De Carlis RM, Travi G, Vecchi M, Viganò R, Lauterio A, Raimondi A, Belli LS, De Carlis LG, Puoti M. Similar survival but higher and delayed hepatocellular carcinoma recurrence in HIV-positive compared to negative cirrhotics undergoing liver transplantation. Dig Liver Dis 2023; 55:268-275. [PMID: 35644890 DOI: 10.1016/j.dld.2022.05.001] [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: 11/13/2021] [Revised: 05/04/2022] [Accepted: 05/05/2022] [Indexed: 02/01/2023]
Abstract
BACKGROUND Liver transplantation (LT) represents the best therapeutic option for hepatocellular carcinoma (HCC) and end-stage liver disease (ESLD). Although HIV infection does not seem to lower survival rates, HCV and HCC recurrence appear more harmful. AIMS To compare the overall survival after LT; evaluate the impact of anti-HCV direct-acting agents (DAA); assess the rate of HCC recurrence in HIV-positive and negative patients. METHODS Subjects with HCV/HBV infection who underwent LT for HCC or ESLD from 2012 to 2019 were retrospectively evaluated. RESULTS Study population included 299 individuals, 31 (10.4%) were HIV-positive. Overall mortality was similar (16.1% versus 19.0%, p = 0.695). HCC recurrence was observed in 6 HIV-positive (19.4%) and in 17 negative subjects (6.3%, p = 0.022). Time to relapse was 831 days in HIV-positive and 315 days in negative patients (p = 0.046). Cox model found a significant role for HIV in univariate analysis but, after adjusting for variables, extra-hepatic tumor was the only factor associated to recurrence (aHR 56.379, p < 0.001). CONCLUSIONS Post-LT survival improved after DAA availability and HIV has no impact on mortality. A higher and delayed rate of HCC recurrence was observed in co-infected individuals: surveillance protocols should be strengthened along time in this population.
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Affiliation(s)
- Roberto Rossotti
- Department of Infectious Diseases, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy.
| | - Marco Merli
- Department of Infectious Diseases, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Chiara Mazzarelli
- Hepatology and Gastroenterology Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Riccardo Maria De Carlis
- Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Giovanna Travi
- Department of Infectious Diseases, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Marta Vecchi
- Department of Infectious Diseases, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Raffaella Viganò
- Hepatology and Gastroenterology Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Andrea Lauterio
- Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Alessandro Raimondi
- Department of Infectious Diseases, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Luca Saverio Belli
- Hepatology and Gastroenterology Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Luciano Gregorio De Carlis
- Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy; School of Medicine, University of Milan-Bicocca, Milan, Italy
| | - Massimo Puoti
- Department of Infectious Diseases, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy; Hepatology and Gastroenterology Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy; Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy; School of Medicine, University of Milan-Bicocca, Milan, Italy
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21
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The Baveno VII concept of cirrhosis recompensation. Dig Liver Dis 2023; 55:431-441. [PMID: 36646527 DOI: 10.1016/j.dld.2022.12.014] [Citation(s) in RCA: 25] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 12/02/2022] [Accepted: 12/18/2022] [Indexed: 01/18/2023]
Abstract
Traditionally, the progression from compensated to decompensated cirrhosis has been regarded as a point of no return in the natural history of the disease. However, this point of view is increasingly being challenged by new evidence on disease regression and hepatic recompensation upon suppression/cure of the underlying aetiology. In order to create a uniform definition of recompensated cirrhosis, standardised criteria have been set out by the Baveno VII consensus, which include the removal of the primary aetiological factor, the resolution of any decompensating events and a sustained improvement in hepatic function. Initial insights into the concept of hepatic recompensation come from previous studies, which have demonstrated that a cure/suppression of the underlying aetiology in patients with prior decompensation leads to significant clinical improvements and favourable outcomes and can even enable the delisting of transplant candidates. Nevertheless, future studies are required to shed light on the natural history of hepatic recompensation, assess modifying factors and potential non-invasive biomarkers of recompensation and explore the molecular mechanisms of disease regression.
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22
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Meunier L, Belkacemi M, Pageaux GP, Radenne S, Vallet-Pichard A, Houssel-Debry P, Duvoux C, Botta-Fridlund D, de Ledinghen V, Conti F, Anty R, Di Martino V, Debette-Gratien M, Leroy V, Gerster T, Lebray P, Alric L, Abergel A, Dumortier J, Besch C, Montialoux H, Samuel D, Duclos-Vallée JC, Coilly A. Patients Treated for HCV Infection and Listed for Liver Transplantation in a French Multicenter Study: What Happens at Five Years? Viruses 2022; 15:137. [PMID: 36680177 PMCID: PMC9865729 DOI: 10.3390/v15010137] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Accepted: 12/26/2022] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND Direct-acting antiviral (DAA) agents for the treatment of hepatitis C virus (HCV) infection have been proven safe and effective in cirrhotic patients awaiting liver transplantation (LT). However, in the long term, data remain minimal regarding the clinical impact of viral eradication on patients listed for decompensated cirrhosis or hepatocellular carcinoma (HCC). We aimed to elucidate the clinical outcomes of patients regarding delisting and the evolution of HCC during the long-term follow-up. METHODS An observational, multicenter, retrospective analysis was carried out on prospectively collected data from HCV-positive patients treated with an interferon-free regimen while awaiting LT in 18 French hospitals. RESULTS A total of 179 patients were included in the study. The indication for LT was HCC in 104 (58.1%) patients and cirrhosis in 75 (41.9%) patients. The sustained virological response was 84.4% and the treatment was well tolerated. At five years, among 75 patients with cirrhosis treated for HCV, 19 (25.3%) were delisted following improvement after treatment. Predictive factors for delisting highlighted an absence of ascites, MELD score ≤ 15, and Child-Pugh score ≤ 7. No patients with refractory ascites were delisted. Among patients with HCC, 82 (78.9%) were transplanted. The drop-out rate was low (6.7%) and few recurrences of HCC after LT were observed. CONCLUSIONS DAAs are safe and effective in patients awaiting LT for cirrhosis or HCC. A quarter of patients with cirrhosis can be delisted because of clinical improvement. Predictive factors for delisting, as a result of improvement, may assist prescribers, before initiating HCV infection therapy in the long-term perspective.
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Affiliation(s)
- Lucy Meunier
- Montpellier Saint Eloi University Hospital, 80 Avenue Augustin Fliche, 34090 Montpellier, France
| | | | - George Philippe Pageaux
- Montpellier Saint Eloi University Hospital, 80 Avenue Augustin Fliche, 34090 Montpellier, France
| | - Sylvie Radenne
- Croix-Rousse Hospital, Lyon University Hospital, 103 Grande Rue de la Croix-Rousse, 69004 Lyon, France
| | - Anaïs Vallet-Pichard
- Cochin Hospital, Public Hospitals of Paris, 27 Rue du Faubourg Saint-Jacques, 75014 Paris, France
| | | | - Christophe Duvoux
- Henri-Mondor University Hospital, Public Hospitals of Paris, 51 Avenue du Maréchal de Lattre de Tassigny, 94010 Créteil, France
| | - Danielle Botta-Fridlund
- Marseille Public Hospital, Timone University Hospital, 264 Rue Saint Pierre, 13005 Marseille, France
| | - Victor de Ledinghen
- Hepatology and Liver Transplantation Unit, Haut-Lévêque Hospital, Bordeaux University Hospital, 33600 Pessac, France
| | - Filomena Conti
- Pitié-Salpêtrière University Hospital, Public Hospitals of Paris, 47-83 Boulevard de l’Hôpital, 75013 Paris, France
| | - Rodolphe Anty
- Archet 2 Hospital, Nice University Hospital, 151 Route de Saint-Antoine, 06200 Nice, France
| | - Vincent Di Martino
- Besançon Regional University Hospital, 3 Boulevard Alexandre Fleming, 25000 Besançon, France
| | | | - Vincent Leroy
- Service d’Hépato-Gastroentérologie, Pôle Digidune, CHU Grenoble Alpes, 38700 La Tronche, France
| | - Theophile Gerster
- Service d’Hépato-Gastroentérologie, Pôle Digidune, CHU Grenoble Alpes, 38700 La Tronche, France
| | - Pascal Lebray
- Pitié-Salpêtrière University Hospital, Public Hospitals of Paris, 47-83 Boulevard de l’Hôpital, 75013 Paris, France
| | - Laurent Alric
- Rangueil Hospital, Toulouse 3 University Hospital, 31000 Toulouse, France
| | - Armand Abergel
- Gabriel-Montpied Hospital, Clermont-Ferrand University Hospital, 58 Rue Montalembert, 63000 Clermont-Ferrand, France
| | - Jérôme Dumortier
- Edouard Herriot Hospital, Lyon University Hospital, 5 Place d’Arsonval, 69003 Lyon, France
| | - Camille Besch
- Hautepierre Hospital, Strasbourg University Hospital, 1 Avenue Molière, 67200 Strasbourg, France
| | - Helene Montialoux
- Rouen University Hospital, 37 Boulevard Gambetta, 76000 Rouen, France
| | - Didier Samuel
- Paul-Brousse Hospital, Public Hospsitals of Paris, 12 Avenue Paul Vaillant Couturier, FHU Hépatinov, 94800 Villejuif, France
| | - Jean-Charles Duclos-Vallée
- Paul-Brousse Hospital, Public Hospsitals of Paris, 12 Avenue Paul Vaillant Couturier, FHU Hépatinov, 94800 Villejuif, France
| | - Audrey Coilly
- Paul-Brousse Hospital, Public Hospsitals of Paris, 12 Avenue Paul Vaillant Couturier, FHU Hépatinov, 94800 Villejuif, France
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Li J, Wu V, Pan CQ. Direct antiviral therapy for hepatitis C cirrhotic patients in liver transplantation settings: a systematic review. Hepatol Int 2022; 16:1020-1031. [PMID: 36085539 DOI: 10.1007/s12072-022-10380-1] [Citation(s) in RCA: 4] [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: 04/11/2022] [Accepted: 06/14/2022] [Indexed: 11/25/2022]
Abstract
BACKGROUND Hepatitis C (HCV)-induced decompensated cirrhosis warrants liver transplantation (LT) as the only ultimate solution. These patients experience liver deterioration, while on the transplant waitlist. However, debate remains over the optimal timing for treating HCV relative to before or after LT. METHODS We performed a literature search between 1/2011 and 1/2022 on PubMed and OVID Medline. Data were extracted from direct antiviral agent (DAA) studies in English. The outcomes of interest included sustained virological response (SVR) rates from various cohorts as well as long- and short-term outcomes in the LT settings. RESULTS After screening, 54 studies were eligible and included into the review. In aligning with the EASL and AASLD guidelines and suggestions, many studies supported DAA therapy before LT in patients with Model for End-stage Liver Disease (MELD) scores < 18 and DAA therapy post-LT in MELD scores > 20 through SVR rates, long-term survival factors, liver deterioration, and incidences of severe adverse events. However, uncertainty still lies in the guideline recommendations and unsettled issues remain for various patient cohorts that may benefit from opposing the guideline cutoffs. Based on the recent studies on predictors of treatment outcomes in decompensated patients and the impact of DAA on the waiting list for LT, we proposed an algorithm to manage patients with MELD scores between 18 and 20. CONCLUSION DAA therapy for decompensated patients must be personalized with consideration of different factors, particularly among those with MELD scores between the two cutoff-values proposed by the current associational guidelines.
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Affiliation(s)
| | - Vivian Wu
- Columbia University, New York, NY, USA
| | - Calvin Q Pan
- Center of Liver Diseases, Beijing Ditan Hospital, Capital Medical University, No. 8, Jingshun East Street, Chaoyang District, Beijing, 100015, China.
- Division of Gastroenterology and Hepatology, Department of Medicine, NYU Langone Health, New York University Grossman School of Medicine, New York, NY, USA.
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El Kassas M, Eltabbakh M, Elbadry M, Tawheed A, Elbaz T. Establishing a research production line in real-life settings: the case of Hepatitis C management in a viral hepatitis specialized Egyptian center. Curr Med Res Opin 2022; 38:553-563. [PMID: 35118916 DOI: 10.1080/03007995.2022.2038489] [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] [Indexed: 11/03/2022]
Abstract
Efforts toward eradicating the Hepatitis C virus (HCV) have advanced rapidly, due to the development of direct-acting antivirals (DAAs), especially with the appearance of pan-genotypic combinations. Real-world studies, in particular, have verified the efficacy and safety of DAA combinations documented in registration trials. This review documents the results of using DAA combinations in real-life settings in everyday clinical practice in Egypt, the country with the highest prevalence of HCV. The significant number of treated patients in Egypt, which exceeded four million allowed tremendous data about the results of HCV management in real-life settings for different treatment regimens and disease conditions. DAA combinations have resulted in high sustained virologic response rates (SVR12) and few adverse reactions in real-life settings. SVR12 rates ranged from 90% to 100%, depending on the combination of drugs used, the HCV genotype, and the stage of liver disease. Most adverse reactions reported in real-world settings were mild and resulted in treatment discontinuation in only a minority of cases. Data from real-life studies covered most aspects of HCV management that were lacking after initial approval studies. More research is needed to tailor treatment and produce generic HCV combinations to overcome the residual limitations of the currently available DAAs.
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Affiliation(s)
- Mohamed El Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Mohamed Eltabbakh
- Tropical Medicine department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohamed Elbadry
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Ahmed Tawheed
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Tamer Elbaz
- Endemic Medicine and Hepatogastroenterology, Department, Faculty of Medicine, Helwan University, Cairo, Egypt
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25
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D'Ambrosio R, Degasperi E, Anolli MP, Fanetti I, Borghi M, Soffredini R, Iavarone M, Tosetti G, Perbellini R, Sangiovanni A, Sypsa V, Lampertico P. Incidence of liver- and non-liver-related outcomes in patients with HCV-cirrhosis after SVR. J Hepatol 2022; 76:302-310. [PMID: 34592366 DOI: 10.1016/j.jhep.2021.09.013] [Citation(s) in RCA: 60] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 09/03/2021] [Accepted: 09/10/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS As the long-term benefits of a sustained virological response (SVR) in HCV-related cirrhosis following direct-acting antiviral (DAA) treatment remain undefined, we assessed the incidence and predictors of liver-related events (LREs), non-liver-related events (NLREs) and mortality in DAA-treated patients with cirrhosis. METHODS Consecutive patients with cirrhosis and SVR were enrolled in a longitudinal, single-center study, and divided into 3 cohorts: Cohort A (Child-Pugh A without a previous LRE), Cohort B (Child-Pugh B or Child-Pugh A with prior non-hepatocellular carcinoma [HCC] LREs), Cohort C (previous HCC). RESULTS A total of 636 patients with cirrhosis (median 65 years-old, 58% males, 89% Child-Pugh A) were followed for 51 (8-68) months (Cohort A n = 480, Cohort B n = 89, Cohort C n = 67). The 5-year estimated cumulative incidences of LREs were 10.4% in Cohort A vs. 32.0% in Cohort B (HCC 7.7% vs. 19.7%; ascites 1.4% vs. 8.6%; variceal bleeding 1.3% vs. 7.8%; encephalopathy 0 vs. 2.5%) vs. 71% in Cohort C (HCC only) (p <0.0001). The corresponding figures for NLREs were 11.7% in Cohort A vs. 17.9% in Cohort B vs. 17.5% in Cohort C (p = 0.32). The 5-year estimated probabilities of liver-related vs. non-liver-related deaths were 0.5% vs. 4.5% in Cohort A, 16.2% vs. 8.8% in Cohort B and 12.1% vs. 7.7% in Cohort C. The all-cause mortality rate in Cohort A was similar to the rate expected for the general population stratified by age, sex and calendar year according to the Human Mortality Database, while it was significantly higher in Cohort B. CONCLUSIONS Patients with cirrhosis and an SVR on DAAs face risks of liver-related and non-liver-related events and mortality; however, their incidence is strongly influenced by pre-DAA patient history. LAY SUMMARY In this large single-center study enrolling patients with hepatitis C virus (HCV)-related cirrhosis cured by direct-acting antivirals, pre-treatment liver disease history strongly influenced long-term outcomes. In patients with HCV-related cirrhosis, hepatocellular carcinoma was the most frequent liver-related complication after viral cure. Due to improved long-term outcomes, patients with cirrhosis after HCV cure are exposed to a significant proportion of non-liver-related events.
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Affiliation(s)
- Roberta D'Ambrosio
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy.
| | - Elisabetta Degasperi
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy
| | - Maria Paola Anolli
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy
| | - Ilaria Fanetti
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy
| | - Marta Borghi
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy
| | - Roberta Soffredini
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy
| | - Massimo Iavarone
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy
| | - Giulia Tosetti
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy
| | - Riccardo Perbellini
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy
| | - Angelo Sangiovanni
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy
| | - Vana Sypsa
- Department of Hygiene, Epidemiology and Medical Statistics, Medical School National and Kapodistrian University of Athens, Athens, Greece
| | - Pietro Lampertico
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy; CRC "A. M. and A. Migliavacca" Center for Liver Disease, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
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26
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Kouroumalis E, Voumvouraki A. Hepatitis C virus: A critical approach to who really needs treatment. World J Hepatol 2022; 14:1-44. [PMID: 35126838 PMCID: PMC8790391 DOI: 10.4254/wjh.v14.i1.1] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 04/14/2021] [Accepted: 12/31/2021] [Indexed: 02/06/2023] Open
Abstract
Introduction of effective drugs in the treatment of hepatitis C virus (HCV) infection has prompted the World Health Organization to declare a global eradication target by 2030. Propositions have been made to screen the general population and treat all HCV carriers irrespective of the disease status. A year ago the new severe acute respiratory syndrome coronavirus 2 virus appeared causing a worldwide pandemic of coronavirus disease 2019 disease. Huge financial resources were redirected, and the pandemic became the first priority in every country. In this review, we examined the feasibility of the World Health Organization elimination program and the actual natural course of HCV infection. We also identified and analyzed certain comorbidity factors that may aggravate the progress of HCV and some marginalized subpopulations with characteristics favoring HCV dissemination. Alcohol consumption, HIV coinfection and the presence of components of metabolic syndrome including obesity, hyperuricemia and overt diabetes were comorbidities mostly responsible for increased liver-related morbidity and mortality of HCV. We also examined the significance of special subpopulations like people who inject drugs and males having sex with males. Finally, we proposed a different micro-elimination screening and treatment program that can be implemented in all countries irrespective of income. We suggest that screening and treatment of HCV carriers should be limited only in these particular groups.
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Affiliation(s)
- Elias Kouroumalis
- Department of Gastroenterology, University of Crete Medical School, Heraklion 71500, Crete, Greece
| | - Argyro Voumvouraki
- First Department of Internal Medicine, AHEPA University Hospital, Thessaloniki 54621, Greece
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Cuesta-Sancho S, Márquez-Coello M, Illanes-Álvarez F, Márquez-Ruiz D, Arizcorreta A, Galán-Sánchez F, Montiel N, Rodriguez-Iglesias M, Girón-González JA. Hepatitis C: Problems to extinction and residual hepatic and extrahepatic lesions after sustained virological response. World J Hepatol 2022; 14:62-79. [PMID: 35126840 PMCID: PMC8790402 DOI: 10.4254/wjh.v14.i1.62] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2021] [Revised: 08/02/2021] [Accepted: 12/10/2021] [Indexed: 02/06/2023] Open
Abstract
Loss of follow-up or reinfections hinder the expectations of hepatitis C eradication despite the existence of highly effective treatments. Moreover, the elimination of the infection does not imply the reversion of those chronic alterations derived from the previous infection by hepatitis C virus (HCV). This review analyzes the risk factors associated with loss to follow-up in diagnosis or treatment, and the possibility of reinfection. Likewise, it assesses the residual alterations induced by chronic HCV infection considering the liver alterations (inflammation, fibrosis, risk of decompensation, hepatocellular carcinoma, liver transplantation) and, on the other hand, the comorbidities and extrahepatic manifestations (cryoglobulinemia, non-Hodgkin lymphoma, peripheral insulin resistance, and lipid, bone and cognitive alterations). Peculiarities present in subjects coinfected with human immunodeficiency virus are analyzed in each section.
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Affiliation(s)
- Sara Cuesta-Sancho
- Medicina Interna, Hospital Universitario Puerta del Mar, Facultad de Medicina, Universidad de Cádiz, Instituto para la Investigación e Innovación en Ciencias Biomédicas de Cádiz (INiBICA), Cádiz 11009, Spain
| | - Mercedes Márquez-Coello
- Medicina Interna, Hospital Universitario Puerta del Mar, Facultad de Medicina, Universidad de Cádiz, Instituto para la Investigación e Innovación en Ciencias Biomédicas de Cádiz (INiBICA), Cádiz 11009, Spain
| | - Francisco Illanes-Álvarez
- Medicina Interna, Hospital Universitario Puerta del Mar, Facultad de Medicina, Universidad de Cádiz, Instituto para la Investigación e Innovación en Ciencias Biomédicas de Cádiz (INiBICA), Cádiz 11009, Spain
| | - Denisse Márquez-Ruiz
- Medicina Interna, Hospital Universitario Puerta del Mar, Facultad de Medicina, Universidad de Cádiz, Instituto para la Investigación e Innovación en Ciencias Biomédicas de Cádiz (INiBICA), Cádiz 11009, Spain
| | - Ana Arizcorreta
- Medicina Interna, Hospital Universitario Puerta del Mar, Facultad de Medicina, Universidad de Cádiz, Instituto para la Investigación e Innovación en Ciencias Biomédicas de Cádiz (INiBICA), Cádiz 11009, Spain
| | - Fátima Galán-Sánchez
- Microbiología, Hospital Universitario Puerta del Mar, Facultad de Medicina, Universidad de Cádiz, Instituto para la Investigación e Innovación en Ciencias Biomédicas de Cádiz (INiBICA), Cádiz 11009, Spain
| | - Natalia Montiel
- Microbiología, Hospital Universitario Puerta del Mar, Facultad de Medicina, Universidad de Cádiz, Instituto para la Investigación e Innovación en Ciencias Biomédicas de Cádiz (INiBICA), Cádiz 11009, Spain
| | - Manuel Rodriguez-Iglesias
- Microbiología, Hospital Universitario Puerta del Mar, Facultad de Medicina, Universidad de Cádiz, Instituto para la Investigación e Innovación en Ciencias Biomédicas de Cádiz (INiBICA), Cádiz 11009, Spain
| | - José-Antonio Girón-González
- Medicina Interna, Hospital Universitario Puerta del Mar, Facultad de Medicina, Universidad de Cádiz, Instituto para la Investigación e Innovación en Ciencias Biomédicas de Cádiz (INiBICA), Cádiz 11009, Spain
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Magro B, Pinelli D, De Giorgio M, Lucà MG, Ghirardi A, Carrobio A, Baronio G, Del Prete L, Nounamo F, Gianatti A, Colledan M, Fagiuoli S. Pre-Transplant Alpha-Fetoprotein > 25.5 and Its Dynamic on Waitlist Are Predictors of HCC Recurrence after Liver Transplantation for Patients Meeting Milan Criteria. Cancers (Basel) 2021; 13:5976. [PMID: 34885087 PMCID: PMC8656660 DOI: 10.3390/cancers13235976] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2021] [Revised: 11/22/2021] [Accepted: 11/25/2021] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND AND AIM Hepatocellular carcinoma (HCC) recurrence rates after liver transplantation (LT) range between 8 and 20%. Alpha-fetoprotein (AFP) levels at transplant can predict HCC recurrence, however a defined cut-off value is needed to better stratify patients. The aim of this study was to evaluate the rate of HCC recurrence at our centre and to identify predictors, focusing on AFP. METHODS We retrospectively analysed 236 consecutive patients that were waitlisted for HCC who all met the Milan criteria from January 2001 to December 2017 at our liver transplant centre. A total of twenty-nine patients dropped out while they were waitlisted, and 207 patients were included in the final analysis. All survival analyses included the competing-risk model. RESULTS The mean age was 56.8 ± 6.8 years. A total of 14% were female (n = 29/207). The median MELD (model for end-stage liver disease) at LT was 12 (9-16). The median time on the waitlist was 92 (41-170) days. The HCC recurrence rate was 16.4% (n = 34/208). The mean time to recurrence was 3.3 ± 2.8 years. The median AFP levels at transplant were higher in patients with HCC recurrence (p < 0.001). At multivariate analysis, the AFP value at transplant that was greater than 25.5 ng/mL (AUC 0.69) was a strong predictor of HCC recurrence after LT [sHR 3.3 (1.6-6.81); p = 0.001]. The HCC cumulative incidence function (CIF) of recurrence at 10 years from LT was significantly higher in patients with AFP > 25.5 ng/mL [34.3% vs. 11.5% (p = 0.001)]. Moreover, an increase in AFP > 20.8%, was significantly associated with HCC recurrence (p = 0.034). CONCLUSIONS In conclusion, in our retrospective study, the AFP level at transplant > 25.5 ng/mL and its increase greater than 20.8% on the waitlist were strong predictors of HCC recurrence after LT in a cohort of patients that were waitlisted within the Milan criteria. However further studies are needed to validate these data.
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Affiliation(s)
- Bianca Magro
- Gastroenterology, Hepatology and Liver Transplantation, Department of Medicine-Papa Giovanni, XXIII Hospital, 24122 Bergamo, Italy; (M.D.G.); (M.G.L.); (S.F.)
| | - Domenico Pinelli
- Unit of Hepato-Biliary Surgery and Liver Transplantation, ASST Papa Giovanni XXIII, 24122 Bergamo, Italy; (D.P.); (G.B.); (L.D.P.); (F.N.); (M.C.)
| | - Massimo De Giorgio
- Gastroenterology, Hepatology and Liver Transplantation, Department of Medicine-Papa Giovanni, XXIII Hospital, 24122 Bergamo, Italy; (M.D.G.); (M.G.L.); (S.F.)
| | - Maria Grazia Lucà
- Gastroenterology, Hepatology and Liver Transplantation, Department of Medicine-Papa Giovanni, XXIII Hospital, 24122 Bergamo, Italy; (M.D.G.); (M.G.L.); (S.F.)
| | - Arianna Ghirardi
- FROM Research Foundation, Papa Giovanni XXIII Hospital, 24122 Bergamo, Italy; (A.G.); (A.C.)
| | - Alessandra Carrobio
- FROM Research Foundation, Papa Giovanni XXIII Hospital, 24122 Bergamo, Italy; (A.G.); (A.C.)
| | - Giuseppe Baronio
- Unit of Hepato-Biliary Surgery and Liver Transplantation, ASST Papa Giovanni XXIII, 24122 Bergamo, Italy; (D.P.); (G.B.); (L.D.P.); (F.N.); (M.C.)
| | - Luca Del Prete
- Unit of Hepato-Biliary Surgery and Liver Transplantation, ASST Papa Giovanni XXIII, 24122 Bergamo, Italy; (D.P.); (G.B.); (L.D.P.); (F.N.); (M.C.)
| | - Franck Nounamo
- Unit of Hepato-Biliary Surgery and Liver Transplantation, ASST Papa Giovanni XXIII, 24122 Bergamo, Italy; (D.P.); (G.B.); (L.D.P.); (F.N.); (M.C.)
| | - Andrea Gianatti
- Pathology Unit, ASST Papa Giovanni XXIII, 24122 Bergamo, Italy;
| | - Michele Colledan
- Unit of Hepato-Biliary Surgery and Liver Transplantation, ASST Papa Giovanni XXIII, 24122 Bergamo, Italy; (D.P.); (G.B.); (L.D.P.); (F.N.); (M.C.)
| | - Stefano Fagiuoli
- Gastroenterology, Hepatology and Liver Transplantation, Department of Medicine-Papa Giovanni, XXIII Hospital, 24122 Bergamo, Italy; (M.D.G.); (M.G.L.); (S.F.)
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In the Era of Direct-Acting Antivirals, Liver Transplant Delisting Due to Clinical Improvement for Hepatitis C Remains Infrequent. Clin Gastroenterol Hepatol 2021; 19:2389-2397.e2. [PMID: 32971230 DOI: 10.1016/j.cgh.2020.09.033] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Revised: 08/28/2020] [Accepted: 09/16/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND / AIMS Studies have suggested marked increases in transplant delisting due to clinical improvement for patients with hepatitis C virus (HCV) associated cirrhosis in the era of direct acting antivirals (DAAs). This study provides a 'real world' assessment of waitlist dynamics for HCV transplant candidates in the current era. METHODS This was a retrospective cohort study of adults waitlisted for liver transplant (LT) alone between 1/1/2005-12/31/2018 using national US data. The post-DAA era included all listings occurring after 1/1/2013. Temporal trends in waitlisting, patient characteristics and outcomes with decompensated cirrhosis were evaluated. Adjusted competing risks models assessed the interaction of DAA-era and HCV history on (i) waitlist mortality, and (ii) delisting due to clinical improvement. RESULTS Overall listing rates for HCV patients have decreased in the DAA era and particularly with Model for End-stage Liver Disease score ≥15 and ≥30. Rates of refractory ascites and severe encephalopathy at listing have increased. Delisting due to clinical improvement remains low (6.1% for 2013-2017 versus 5.2% for 2009-2012 versus 4% for 2005-2008; p < .001) and, for many, ascites (46.5%) and encephalopathy (30.5%) persist at delisting. Waitlist recovery is more frequent for HCV patients post-DAA (adjusted SHR 1.78 vs pre-DAA, 95% CI: 1.58-2.02; p < .001), while improvements in waitlist mortality by era are similar to non-HCV candidates (adjusted SHR 0.74 [95% CI: 0.7-0.78; p < .001] and 0.77 [95% CI: 0.74-0.8; p < .001], respectively). CONCLUSION Listing rates for decompensated HCV cirrhosis have decreased in the DAA era. Delisting of HCV patients for clinical improvement has increased, but remains infrequent and many continue to experience considerable morbidity.
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Nabatchikova EA, Abdurakhmanov DT, Rozina TP, Nikulkina EN, Tanaschuk EL, Moiseev SV. Delisting and clinical outcomes of liver transplant candidates after hepatitis C virus eradication: A long-term single-center experience. Clin Res Hepatol Gastroenterol 2021; 45:101714. [PMID: 33930587 DOI: 10.1016/j.clinre.2021.101714] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 04/05/2021] [Accepted: 04/10/2021] [Indexed: 02/04/2023]
Abstract
BACKGROUND Previous short-term studies have reported on liver function improvements and delisting among liver transplantation (LT) candidates with hepatitis C virus (HCV) and decompensated liver cirrhosis after successful antiviral therapy. This study aimed to evaluate the long-term impact of HCV eradication on liver function, portal hypertension, probability of delisting, and clinical outcomes in patients awaiting LT. METHODS Forty-five LT candidates with decompensated HCV cirrhosis were prospectively observed after HCV eradication by direct-acting antiviral therapy. The median follow-up (FU) time was 24 months. RESULTS Twenty-six (57.8%) patients were delisted due to clinical improvement. Multivariate analysis revealed male gender (hazard ratio (HR) 3.28; p = 0.022), baseline Child - Turcotte - Pugh class C (HR 4.81; p = 0.003), and delta prothrombin index <2% between baseline and the time of sustained virological response (HR 3.82; p = 0.01) as independent risk factors for non-delisting. During a median FU of 21 months after delisting, hepatocellular carcinoma (HCC) developed in 2 (7.7%) patients. Among non-delisted patients, HCC developed in 6 (31.6%) cases, variceal bleeding developed in 3 (15.8%) patients, and spontaneous bacterial peritonitis developed in 2 (10.5%) patients. CONCLUSION HCV eradication lead to the delisting of more than 50% of patients, but did not eliminate the HCC risk, and close monitoring of patients should continue after the end of treatment.
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Affiliation(s)
- Ekaterina A Nabatchikova
- The Department of Internal, Occupational Diseases and Rheumatology, Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya st., Moscow, 119991, Russia.
| | - Dzhamal T Abdurakhmanov
- The Department of Internal, Occupational Diseases and Rheumatology, Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya st., Moscow, 119991, Russia
| | - Teona P Rozina
- The Department of Internal, Occupational Diseases and Rheumatology, Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya st., Moscow, 119991, Russia; The Department of Internal Diseases, Faculty of Fundamental Medicine, M.V. Lomonosov Moscow State University, 27-1 Lomonosov prospect, Moscow, 119192, Russia
| | - Elena N Nikulkina
- The Department of Internal, Occupational Diseases and Rheumatology, Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya st., Moscow, 119991, Russia
| | - Elena L Tanaschuk
- The Department of Internal, Occupational Diseases and Rheumatology, Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya st., Moscow, 119991, Russia
| | - Sergey V Moiseev
- The Department of Internal, Occupational Diseases and Rheumatology, Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya st., Moscow, 119991, Russia; The Department of Internal Diseases, Faculty of Fundamental Medicine, M.V. Lomonosov Moscow State University, 27-1 Lomonosov prospect, Moscow, 119192, Russia
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Khoo T, Lam D, Olynyk JK. Impact of modern antiviral therapy of chronic hepatitis B and C on clinical outcomes of liver disease. World J Gastroenterol 2021; 27:4831-4845. [PMID: 34447229 PMCID: PMC8371504 DOI: 10.3748/wjg.v27.i29.4831] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 05/14/2021] [Accepted: 07/21/2021] [Indexed: 02/06/2023] Open
Abstract
Chronic infections with the hepatitis B and C viruses have significant worldwide health and economic impacts. Previous treatments for hepatitis C such as interferon and ribavirin therapy were ineffective and poorly tolerated by patients. The introduction of directly acting curative antiviral therapy for hepatitis C and the wider use of nucleos(t)ide analogues for suppression of chronic Hepatitis B infection have resulted in many positive developments. Decreasing the prevalence of hepatitis B and C have concurrently reduced transmission rates and hence, the number of new infections. Antiviral treatments have decreased the rates of liver decompensation and as a result, lowered hospitalisation and mortality rates for both chronic hepatitis B and C infection. The quality of life of chronically infected patients has also been improved significantly by modern treatment. Antiviral therapy has stopped the progression of liver disease to cirrhosis in certain patient cohorts and prevented ongoing hepatocellular damage in patients with existing cirrhosis. Longer term benefits of antiviral therapy include a reduced risk of developing hepatocellular carcinoma and decreased number of patients requiring liver transplantation. This review article assesses the literature and summarises the impact of modern antiviral therapy of chronic hepatitis B and C on clinical outcomes from liver disease.
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Affiliation(s)
- Tiffany Khoo
- Department of Gastroenterology and Hepatology, Fiona Stanley Hospital, Murdoch 6150, Australia
- School of Medical and Health Sciences, Edith Cowan University, Joondalup 6027, Australia
| | - Danielle Lam
- Department of Gastroenterology and Hepatology, Fiona Stanley Hospital, Murdoch 6150, Australia
- School of Medical and Health Sciences, Edith Cowan University, Joondalup 6027, Australia
| | - John K Olynyk
- Department of Gastroenterology and Hepatology, Fiona Stanley Hospital, Murdoch 6150, Australia
- School of Medical and Health Sciences, Edith Cowan University, Joondalup 6027, Australia
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Villard C, Westman J, Frank J, Jynge O, Sparrelid E, Jorns C. The potential use of extended criteria donors and eligible recipients in liver transplantation for unresectable colorectal liver metastases in Central Sweden. Hepatobiliary Surg Nutr 2021; 10:476-485. [PMID: 34430526 PMCID: PMC8350992 DOI: 10.21037/hbsn.2020.03.10] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2019] [Accepted: 03/03/2020] [Indexed: 02/05/2023]
Abstract
BACKGROUND Unresectable colorectal liver metastases (CRLM) is a condition with poor prognosis. A recent treatment alternative improving survival in patients with unresectable CRLM, has emerged with the introduction of liver transplantation (LT), yet not uncontroversial with the current organ shortage. This study aimed to retrospectively investigate the potential of declined donors with acceptable risk as liver graft donors and patients with unresectable CRLM as potential recipients. METHODS All declined donors in central Sweden and all patients with CRLM discussed at multidisciplinary team conference at Karolinska University Hospital, January 2013-October 2018, were identified. Donors were classified according to the European Committee Guide to the quality and safety of organs for transplantation and potential recipients were evaluated by selection criteria, based on studies on the Norwegian Secondary Cancer study database. RESULTS Out of 1,462 evaluated potential donors, 62 (2.7 pmp) donors were identified, corresponding to 6-18% of the utilized donor pool. Out of 1,008 included patients with CRLM, 25 (2.1 pmp) potential recipients were recognized. Eligibility for LT and left-sided colon cancer were favorable prognostic factors. CONCLUSIONS Today's donor pool could increase with the use of extended criteria donors, which is sufficient and display an acceptable risk-benefit ratio for patients with unresectable CRLM. With current selection criteria a small subset of patients with unresectable CRLM are eligible recipients. This subset of patients has a better survival compared to patients ineligible for LT.
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Affiliation(s)
- Christina Villard
- Department of Cancer, Division of Upper GI, Karolinska University Hospital, Stockholm, Sweden
| | | | | | - Oystein Jynge
- Department of Transplantation Surgery, Karolinska University Hospital, Stockholm, Sweden
| | - Ernesto Sparrelid
- Department of Cancer, Division of Upper GI, Karolinska University Hospital, Stockholm, Sweden;,Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Carl Jorns
- Department of Transplantation Surgery, Karolinska University Hospital, Stockholm, Sweden;,Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
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Pose E, Torrents A, Reverter E, Perez-Campuzano V, Campos-Varela I, Avitabile E, Gratacós-Ginès J, Castellote J, Castells L, Colmenero J, Tort J, Ginès P, Crespo G. A notable proportion of liver transplant candidates with alcohol-related cirrhosis can be delisted because of clinical improvement. J Hepatol 2021; 75:275-283. [PMID: 33746085 DOI: 10.1016/j.jhep.2021.02.033] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Revised: 02/03/2021] [Accepted: 02/24/2021] [Indexed: 01/05/2023]
Abstract
BACKGROUND & AIMS To what extent patients with alcohol-related decompensated cirrhosis can improve until recovery from decompensation remains unclear. We aimed to investigate the probability of recovery and delisting due to improvement in patients with alcohol-related decompensated cirrhosis on the waiting list (WL) for liver transplantation (LT). METHODS We conducted a registry-based, multicenter, retrospective study including all patients admitted to the LT WL in Catalonia (Spain) with the indication of alcohol-, HCV-, cholestasis- or non-alcoholic steatohepatitis-related decompensated cirrhosis between January 2007 and December 2018. Competing-risk analysis was used to investigate variables associated with delisting due to improvement in patients with alcohol-related decompensated cirrhosis. Criteria for delisting after improvement were not predefined. Outcomes of patients after delisting were also studied. RESULTS One-thousand and one patients were included, 420 (37%) with alcohol-related decompensated cirrhosis. Thirty-six (8.6%) patients with alcohol-related decompensated cirrhosis were delisted after improvement at a median time of 29 months after WL admission. Lower model for end-stage liver disease (MELD) score, higher platelets and either female sex or lower height were independently associated with delisting due to improvement, while time of abstinence did not reach statistical significance in multivariate analysis (p = 0.055). Five years after delisting, the cumulative probability of remaining free from liver-related death or LT was 76%, similar to patients with HCV-related decompensated cirrhosis delisted after improvement. CONCLUSIONS A significant proportion of LT candidates with alcohol-related cirrhosis can be delisted due to improvement, which is predicted by low MELD score and higher platelet count at WL admission. Women also have a higher probability of being delisted after improvement, partially due to reduced early access to LT for height discrepancies. Early identification of patients with potential for improvement may avoid unnecessary transplants. LAY SUMMARY Patients with alcohol-related cirrhosis can improve until being delisted in approximately 9% of cases. Low model for end-stage liver disease score and high platelet levels at admission predict delisting after improvement, and women have higher probabilities of being delisted due to improvement. Long-term outcomes after delisting are generally favorable.
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Affiliation(s)
- Elisa Pose
- Liver Unit, Hospital Clínic, Faculty of Medicine, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
| | - Abiguei Torrents
- Organització Catalana de Trasplantaments (OCATT), Servei Català de la Salut, Catalonia, Spain
| | - Enric Reverter
- Liver Unit, Hospital Clínic, Faculty of Medicine, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Valeria Perez-Campuzano
- Liver Transplant Unit, Liver Unit, Hospital Universitari de Bellvitge, IDIBELL, Universitat de Barcelona, Spain
| | - Isabel Campos-Varela
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain; Liver Unit, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Campus, Universitat Autònoma de Barcelona, Spain
| | - Emma Avitabile
- Liver Unit, Hospital Clínic, Faculty of Medicine, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Jordi Gratacós-Ginès
- Liver Unit, Hospital Clínic, Faculty of Medicine, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Jose Castellote
- Liver Transplant Unit, Liver Unit, Hospital Universitari de Bellvitge, IDIBELL, Universitat de Barcelona, Spain
| | - Lluis Castells
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain; Liver Unit, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Campus, Universitat Autònoma de Barcelona, Spain
| | - Jordi Colmenero
- Liver Unit, Hospital Clínic, Faculty of Medicine, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Jaume Tort
- Organització Catalana de Trasplantaments (OCATT), Servei Català de la Salut, Catalonia, Spain
| | - Pere Ginès
- Liver Unit, Hospital Clínic, Faculty of Medicine, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Gonzalo Crespo
- Liver Unit, Hospital Clínic, Faculty of Medicine, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
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Compagnoni S, Bruno EM, Madonia G, Cannizzaro M, Madonia S. Direct antiviral agents in hepatitis C virus related liver disease: Don't count the chickens before they're hatched. World J Gastroenterol 2021; 27:2771-2783. [PMID: 34135553 PMCID: PMC8173378 DOI: 10.3748/wjg.v27.i21.2771] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 03/26/2021] [Accepted: 04/28/2021] [Indexed: 02/06/2023] Open
Abstract
Since molecules with direct-acting antiviral (DAA) became available, the landscape of the treatment of hepatitis C virus (HCV) infection has completely changed. The new drugs are extremely effective in eradicating infection, and treatment is very well tolerated with a duration of 8-12 wk. This review aims to report the outstanding clinical benefits of DAA and to highlight their critical disadvantages, identifying some clinically relevant hot topics. First, do the rates of virological response remain as high when patients with more advanced cirrhosis are considered? Large studies have shown slightly lower but still satisfactory rates of response in these patients. Nevertheless, modified schedules with an extended treatment duration and use of ribavirin may be necessary. Second, does the treatment of HCV infection affect the risk of occurrence and recurrence of liver cancer? Incidence is reduced after viral eradication but remains high enough to warrant periodic surveillance for an early diagnosis. In contrast, the risk of recurrence seems to be unaffected by viral clearance; however, DAA treatment improves survival because of the reduced risk of progression of liver disease. Third, can HCV treatment also have favorable effects on major comorbidities? HCV eradication is associated with a reduced incidence of diabetes, an improvement in glycemic control and a decreased risk of cardiovascular events; nevertheless, a risk of hypoglycemia during DAA treatment has been reported. Finally, is it safe to treat patients with HCV/ hepatitis B virus (HBV) coinfection? In this setting, HCV is usually the main driver of viral activity, while HBV replication is suppressed. Because various studies have described HBV reactivation after HCV clearance, a baseline evaluation for HBV coinfection and a specific follow-up is mandatory.
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Affiliation(s)
- Stella Compagnoni
- Department of Internal Medicine, V. Cervello Hospital, University of Palermo, Palermo 90146, Italy
| | - Erica Maria Bruno
- Department of Internal Medicine, V. Cervello Hospital, University of Palermo, Palermo 90146, Italy
| | - Giorgio Madonia
- Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo 90127, Italy
| | - Marco Cannizzaro
- Department of Emergency Medicine, A. Ajello Hospital, Trapani 91026, Italy
| | - Salvatore Madonia
- Department of Internal Medicine, V. Cervello Hospital, Palermo 90146, Italy
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Negro F. Residual risk of liver disease after hepatitis C virus eradication. J Hepatol 2021; 74:952-963. [PMID: 33276027 DOI: 10.1016/j.jhep.2020.11.040] [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: 06/04/2020] [Revised: 11/20/2020] [Accepted: 11/26/2020] [Indexed: 12/11/2022]
Abstract
Treatment of hepatitis C with direct-acting antivirals is safe and highly efficacious, resulting in viral clearance (sustained virological response [SVR]) in the vast majority of patients. Although SVR is mostly permanent and associated with a significant reduction of liver morbidity and mortality, some patients may still suffer from a major risk of progressive liver damage, potentially leading to severe complications - including liver decompensation, hepatocellular carcinoma and death. This concise review discusses some of the most important features of residual liver disease in patients with chronic hepatitis C who have achieved SVR after antiviral therapy.
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Affiliation(s)
- Francesco Negro
- Divisions of Gastroenterology and hepatology, Geneva University Hospitals, Geneva, Switzerland; Divisions of Clinical pathology, Geneva University Hospitals, Geneva, Switzerland.
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Weinfurtner K, Reddy KR. Hepatitis C viraemic organs in solid organ transplantation. J Hepatol 2021; 74:716-733. [PMID: 33212088 DOI: 10.1016/j.jhep.2020.11.014] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Revised: 11/04/2020] [Accepted: 11/06/2020] [Indexed: 02/07/2023]
Abstract
Although rates of organ donation and solid organ transplantation have been increasing over the last few decades, demand for organs still greatly exceeds supply. Several strategies have been utilised to increase organ supply, including utilisation of high-risk (e.g. HCV antibody-positive) donors. In this context, organs from HCV antibody-positive donors have been used in recipients with chronic HCV since the early 1990s. Recently, transplantation of HCV-viraemic organs into HCV-naïve recipients has garnered significant interest, owing to the development of safe and highly effective direct-acting antivirals and increased experience of treating HCV in the post-transplant setting. Preliminary studies based largely in the US have shown excellent outcomes in kidney, liver, heart, and lung transplantation. This practice has the potential to significantly increase transplantation rates and decrease waitlist mortality; however, intentionally transmitting an infectious disease to recipients has important practical and ethical implications. Further, the generalisability of the US experience to other countries is limited by significant differences in HCV-viraemic donor populations. This review summarises the current data on this practice, discusses barriers to implementation, and highlights areas that warrant further study.
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Affiliation(s)
- Kelley Weinfurtner
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - K Rajender Reddy
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania.
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Pawlotsky JM, Negro F, Aghemo A, Berenguer M, Dalgard O, Dusheiko G, Marra F, Puoti M, Wedemeyer H. EASL recommendations on treatment of hepatitis C: Final update of the series ☆. J Hepatol 2020; 73:1170-1218. [PMID: 32956768 DOI: 10.1016/j.jhep.2020.08.018] [Citation(s) in RCA: 732] [Impact Index Per Article: 146.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Accepted: 08/18/2020] [Indexed: 02/08/2023]
Abstract
Hepatitis C virus (HCV) infection is a major cause of chronic liver disease, with approximately 71 million chronically infected individuals worldwide. Clinical care for patients with HCV-related liver disease has advanced considerably thanks to an enhanced understanding of the pathophysiology of the disease, as well as developments in diagnostic procedures and improvements in therapy and prevention. These therapies make it possible to eliminate hepatitis C as a major public health threat, as per the World Health Organization target, although the timeline and feasibility vary from region to region. These European Association for the Study of the Liver recommendations on treatment of hepatitis C describe the optimal management of patients with recently acquired and chronic HCV infections in 2020 and onwards.
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Domínguez Domínguez L, Matarranz M, Lagarde M, Bisbal O, Hernando A, Lumbreras C, Rubio R, Pulido F. HCV eradication with all-oral therapy in cirrhotic HIV-coinfected patients: an observational study of early changes in liver function and fibrosis tests. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2020; 111:626-632. [PMID: 31240941 DOI: 10.17235/reed.2019.6086/2018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
INTRODUCTION liver laboratory tests improve in hepatitis C virus (HCV)-monoinfected and cirrhotic patients who achieve HCV cure after interferon-free treatment. OBJECTIVE AND METHODS this study evaluates the changes in those tests in human immunodeficiency virus (HIV)-positive subjects with an eradicated HCV-coinfection using direct-acting antivirals and with a pre-therapy liver stiffness ≥ 14.6 kPa or clinical data of cirrhosis. Serum albumin, bilirubin, creatinine, platelet count and international normalized ratio (INR) values were collected at baseline, week 4, at the end of treatment and 24 weeks after the end-of-treatment. Fibrosis-4 score (FIB4) and Model for End-stage Liver Disease (MELD) score values were calculated and liver stiffness was estimated by transient elastography at baseline and 24 weeks after the end-of-treatment. The means were compared with the Student's t test or the repeated measures ANOVA test. RESULTS direct-acting antivirals were prescribed to 131 HIV/HCV-coinfected cirrhotic patients. A sustained virological response was confirmed in 120 cases. Albumin, bilirubin and platelet count values improved in the entire population 24 weeks after the end-of-treatment. INR and MELD score values decreased when patients with atazanavir and/or acenocoumarol were excluded and liver fibrosis tests significantly diminished. Nine patients developed liver decompensation and there were three deaths. CONCLUSION in conclusion, HCV eradication was associated with a short-term improvement in biochemical liver function and fibrosis tests in HIV-coinfected patients with cirrhosis, although clinical events still occur.
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Affiliation(s)
| | - Mariano Matarranz
- Unidad VIH, Servicio de Medicina Interna, Hospital Universitario 12 de Octubre
| | - María Lagarde
- Unidad VIH, Servicio de Medicina Interna, Hospital Universitario 12 de Octubre
| | - Otilia Bisbal
- Unidad VIH, Servicio de Medicina Interna, Hospital Universitario 12 de Octubre
| | | | - Carlos Lumbreras
- Unidad VIH, Servicio de Medicina Interna, Hospital Universitario 12 de Octubre
| | - Rafael Rubio
- Unidad VIH, Servicio de Medicina Interna, Hospital Universitario 12 de Octubre
| | - Federico Pulido
- Unidad VIH, Servicio de Medicina Interna, Hospital Universitario 12 de Octubre
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Yu ML, Chen PJ, Dai CY, Hu TH, Huang CF, Huang YH, Hung CH, Lin CY, Liu CH, Liu CJ, Peng CY, Lin HC, Kao JH, Chuang WL. 2020 Taiwan consensus statement on the management of hepatitis C: Part (II) special populations. J Formos Med Assoc 2020; 119:1135-1157. [PMID: 32354689 DOI: 10.1016/j.jfma.2020.04.002] [Citation(s) in RCA: 59] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Accepted: 04/05/2020] [Indexed: 12/13/2022] Open
Abstract
Hepatitis C virus (HCV) infection is a silent killer that leads to rapid progression of liver cirrhosis and hepatocellular carcinoma (HCC). High prevalence of HCV infection has been reported in Taiwan, especially in high-risk populations including people who inject drugs (PWID) and patients requiring dialysis. Besides, certain populations merit special considerations due to suboptimal outcome, potential drug-drug interaction, or possible side effect. Therefore, in the second part of this 2-part consensus, the Taiwan Association for the Study of the Liver (TASL) proposes the treatment recommendations for the special population in order to serve as guidance to optimizing the outcome in the direct-acting antiviral (DAA) era. Special populations include patients with acute or recent HCV infection, previous DAA failure, chronic kidney disease, decompensated cirrhosis, HCC, liver and other solid organ transplantations, receiving an HCV viremic organ, hepatitis B virus (HBV) and HCV dual infection, HCV and human immunodeficiency virus (HIV) coinfection, active tuberculosis infection, PWID, bleeding disorders and hemoglobinopathies, children and adolescents, and pregnancy. Moreover, future perspectives regarding the management of hepatitis C are also discussed and summarized in this consensus statement.
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Affiliation(s)
- Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine and Hepatitis Research Center, College of Medicine, Center for Cancer Research and Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan.
| | - Pei-Jer Chen
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine and Hepatitis Research Center, College of Medicine, Center for Cancer Research and Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Tsung-Hui Hu
- Division of Hepato-Gastroenterology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine and Hepatitis Research Center, College of Medicine, Center for Cancer Research and Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Chao-Hung Hung
- Division of Hepato-Gastroenterology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chun-Yen Lin
- Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; School of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chen-Hua Liu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Jen Liu
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Cheng-Yuan Peng
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Jia-Horng Kao
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine and Hepatitis Research Center, College of Medicine, Center for Cancer Research and Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan
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Hepatitis C: Does Successful Treatment Alter the Natural History and Quality of Life? Gastroenterol Clin North Am 2020; 49:301-314. [PMID: 32389364 DOI: 10.1016/j.gtc.2020.01.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The cure of chronic hepatitis C infection has a major impact on the morbidity and mortality of infected patients. It is now clear that sustained virologic response improves overall survival and significantly reduces the risk of liver failure, fibrosis progression, need of liver transplantation, and incidence of hepatocellular carcinoma. Moreover, hepatitis C eradication improves a broad range of extrahepatic manifestations, such as dermatologic, neoplastic, cardiovascular, and endocrine, and improves quality of life.
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41
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Giannini EG, De Maria C, Crespi M, Demarzo MG, Fazio V, Grasso A, Torre F, Bodini G, Marabotto E, Furnari M. Course of oesophageal varices and performance of noninvasive predictors following Hepatitis C Virus clearance in compensated advanced chronic liver disease. Eur J Clin Invest 2020; 50:e13231. [PMID: 32291753 DOI: 10.1111/eci.13231] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Revised: 02/25/2020] [Accepted: 03/19/2020] [Indexed: 12/26/2022]
Abstract
BACKGROUND In patients with hepatitis C virus (HCV) and compensated advanced chronic liver disease (cACLD), there is evidence that sustained virological response (SVR) to direct-acting antivirals (DAA) may ameliorate portal hypertension, although both the course of oesophageal varices and the performance of their noninvasive predictors following DAA-induced SVR are less defined. In this study, our aim was to assess the variation in oesophageal varices status in HCV patients with cACLD who obtained an SVR to DAAs and to evaluate the diagnostic performance of noninvasive predictors of varices after HCV cure. MATERIAL AND METHODS Sixty-three HCV patients with cACLD and SVR to DAAs were prospectively followed up, and oesophageal varices surveillance was carried out according to the Baveno VI indications. Appearance and disappearance of varices, accuracy performance of their noninvasive predictors (Baveno/expanded Baveno VI criteria, platelet count/spleen diameter ratio) and number of endoscopies spared with their application were calculated. RESULTS Following SVR, varices developed or disappeared in 12.1% and 17.4% of patients, respectively. The negative predictive value for varices of the Baveno VI, expanded Baveno VI criteria and platelet count/spleen diameter ratio following SVR was 88.2% (65.6-96.7), 83.3% (66.3-92.7) and 80.7% (67.1-89.5), respectively. Their application would have saved 30.4%, 42.9% and 55.4% of endoscopies, with no varices needing treatment missed using both Baveno VI criteria. CONCLUSIONS In HCV patients with cACLD, following SVR to DAA, the expanded Baveno VI criteria provide the best balance between utility (diagnostic accuracy and endoscopies avoided) and safety (varices needing treatment missed) for varices surveillance.
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Affiliation(s)
- Edoardo G Giannini
- Gastroenterology Unit, Department of Internal Medicine, IRCCS-Ospedale Policlinico San Martino, University of Genoa, Genoa, Italy
| | - Costanza De Maria
- Gastroenterology Unit, Department of Internal Medicine, IRCCS-Ospedale Policlinico San Martino, University of Genoa, Genoa, Italy
| | - Mattia Crespi
- Gastroenterology Unit, Department of Internal Medicine, IRCCS-Ospedale Policlinico San Martino, University of Genoa, Genoa, Italy
| | - Maria Giulia Demarzo
- Gastroenterology Unit, Department of Internal Medicine, IRCCS-Ospedale Policlinico San Martino, University of Genoa, Genoa, Italy
| | - Valentina Fazio
- Gastroenterology Unit, Department of Internal Medicine, San Paolo Hospital, Savona, Italy
| | - Alessandro Grasso
- Gastroenterology Unit, Department of Internal Medicine, San Paolo Hospital, Savona, Italy
| | - Francesco Torre
- Gastroenterology Unit, Department of Internal Medicine, IRCCS-Ospedale Policlinico San Martino, University of Genoa, Genoa, Italy
| | - Giorgia Bodini
- Gastroenterology Unit, Department of Internal Medicine, IRCCS-Ospedale Policlinico San Martino, University of Genoa, Genoa, Italy
| | - Elisa Marabotto
- Gastroenterology Unit, Department of Internal Medicine, IRCCS-Ospedale Policlinico San Martino, University of Genoa, Genoa, Italy
| | - Manuele Furnari
- Gastroenterology Unit, Department of Internal Medicine, IRCCS-Ospedale Policlinico San Martino, University of Genoa, Genoa, Italy
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Negro F. Natural History of Hepatic and Extrahepatic Hepatitis C Virus Diseases and Impact of Interferon-Free HCV Therapy. Cold Spring Harb Perspect Med 2020; 10:cshperspect.a036921. [PMID: 31636094 DOI: 10.1101/cshperspect.a036921] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The hepatitis C virus (HCV) infects 71.1 million persons and causes 400,000 deaths annually worldwide. HCV mostly infects the liver, causing acute and chronic necroinflammatory damage, which may progress toward cirrhosis and hepatocellular carcinoma. In addition, HCV has been associated with several extrahepatic manifestations. The advent of safe and effective direct-acting antivirals (DAAs) has made the dream of eliminating this public health scourge feasible in the medium term. Prospective studies using DAA-based regimens have shown the benefit of HCV clearance in terms of both liver- and non-liver-related mortality.
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Affiliation(s)
- Francesco Negro
- Divisions of Clinical Pathology and of Gastroenterology and Hepatology, University Hospital, 1211 Genève 4, Switzerland
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43
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Campello E, Radu CM, Zanetto A, Bulato C, Shalaby S, Spiezia L, Franceschet E, Burra P, Russo FP, Simioni P. Changes in plasma circulating microvesicles in patients with HCV-related cirrhosis after treatment with direct-acting antivirals. Liver Int 2020; 40:913-920. [PMID: 31454463 DOI: 10.1111/liv.14234] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2019] [Revised: 07/29/2019] [Accepted: 08/22/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS The eradication of Hepatitis C (HCV) infection by direct-acting antiviral (DAAs) agents has been linked to an amelioration of liver synthesis and regression of fibrosis. Although changes in number and type of circulating microvesicles (MVs) have been reported in cirrhosis, conclusive data on the effect of DAAs treatment on MVs profile in HCV cirrhotic patients remain scarce. METHODS We measured the levels of endothelial, platelet and hepatocyte MVs, as well as MVs-expressing versican core protein (VCAN+) in patients with HCV-related cirrhosis at baseline, end of treatment (EOT), at 12, 24 and 48 weeks (W) after EOT by new generation flow cytometry. RESULTS Fifty-eight patients were enrolled (86% Child's A). MVs were increased at EOT vs baseline, though only platelet MVs revealed a statistically significant difference (P < .01). MV levels did not change significantly after EOT notwithstanding a steady downward trend towards baseline levels. Conversely, VCAN + MVs dropped significantly at EOT (P < .001) and remained low throughout the follow-up. Hepatocyte MVs significantly correlated with liver stiffness (r = .40, P = .0021). Eight composite outcomes occurred during the 1-year follow-up: three portal vein thromboses (PVTs), two hepatocellular carcinomas (HCCs) and three liver decompensation. Child's B, the presence of F2 oesophageal varices (OR for interaction 19.2 [95% CI 1.45-253.7], P = .023) and platelet MVs (OR 1.026 [95% CI 1.00-1.05, P = .023) correlated significantly with clinical outcomes. CONCLUSIONS VCAN + MVs appear to mirror the profibrotic status of the cirrhotic disease; hepatocyte MVs correlate with liver stiffness and increased platelet MV levels could be associated with a worse clinical outcome.
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Affiliation(s)
- Elena Campello
- Department of Medicine, Thrombotic and Haemorrhagic Diseases Unit, Padova University Hospital, Padova, Italy
| | - Claudia M Radu
- Department of Medicine, Thrombotic and Haemorrhagic Diseases Unit, Padova University Hospital, Padova, Italy
| | - Alberto Zanetto
- Department of Surgery, Oncology and Gastroenterology, Gastroenterology and Multivisceral Transplant Unit, Padova University Hospital, Padova, Italy
| | - Cristiana Bulato
- Department of Medicine, Thrombotic and Haemorrhagic Diseases Unit, Padova University Hospital, Padova, Italy
| | - Sarah Shalaby
- Department of Surgery, Oncology and Gastroenterology, Gastroenterology and Multivisceral Transplant Unit, Padova University Hospital, Padova, Italy
| | - Luca Spiezia
- Department of Medicine, Thrombotic and Haemorrhagic Diseases Unit, Padova University Hospital, Padova, Italy
| | - Enrica Franceschet
- Department of Surgery, Oncology and Gastroenterology, Gastroenterology and Multivisceral Transplant Unit, Padova University Hospital, Padova, Italy
| | - Patrizia Burra
- Department of Surgery, Oncology and Gastroenterology, Gastroenterology and Multivisceral Transplant Unit, Padova University Hospital, Padova, Italy
| | - Francesco P Russo
- Department of Surgery, Oncology and Gastroenterology, Gastroenterology and Multivisceral Transplant Unit, Padova University Hospital, Padova, Italy
| | - Paolo Simioni
- Department of Medicine, Thrombotic and Haemorrhagic Diseases Unit, Padova University Hospital, Padova, Italy
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Indolfi G, Giannini EG. Hepatitis C virus therapy in children: No one should be left behind. Liver Int 2020; 40:283-285. [PMID: 31967401 DOI: 10.1111/liv.14331] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Accepted: 12/12/2019] [Indexed: 02/06/2023]
Affiliation(s)
- Giuseppe Indolfi
- Department of NEUROFARBA, Meyer Children's University Hospital, University of Florence, Florence, Italy
| | - Edoardo G Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS - Ospedale Policlinico San Martino, Genoa, Italy
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Khan AS, Adams N, Vachharajani N, Dageforde L, Wellen J, Shenoy S, Crippin JS, Doyle MB, Chapman WC. Liver transplantation for hepatitis C patients in the era of direct-acting antiviral treatment: A retrospective cohort study. Int J Surg 2020; 75:84-90. [PMID: 32014598 DOI: 10.1016/j.ijsu.2020.01.145] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Revised: 01/10/2020] [Accepted: 01/23/2020] [Indexed: 12/27/2022]
Abstract
INTRODUCTION Direct-acting antivirals (DAA's) have revolutionized hepatitis-C virus (HCV) treatment, however controversy remains regarding timing of treatment in relation to liver-transplant (LT). METHODS Single-center retrospective study assessing outcomes of listed HCV positive patients in the DAA-era (2014-2017). Patients treated with DAA's before LT (DAA pre-LT) were compared to those who were not treated before LT (No DAA pre-LT) RESULTS: 156 HCV positive patients were listed during study-period; 104 (67%) underwent LT while 52 (33%) were de-listed. Of transplanted patients, 48 (46%) received DAA pre-LT while 56 (54%) were treated post-LT. Both groups were comparable in age, gender, MELD, patient and graft survival and cure-rates (98% in DAA pre-LTvs.95% in No DAA pre-LT; p > 0.05). DAA pre-LT group required higher number of treatments-per-patient to clear virus (1.46vs.1.06; p = 0.0006), spent more time on waitlist (331d.vs150d; p = 0.0040) and were less likely to receive livers from HCV positive donors (6%vs.25%; p = 0.0148). Twenty-nine (56%) of the 52 delisted received DAA. They had lower listing-MELD (12vs.18; p = 0.0033), and were more likely to be delisted for "condition improved" (34%vs.4%; p = 0.0143) compared to the 23 (44%) delisted patients who did not receive DAA's. CONCLUSIONS DAA's were equally effective in clearing HCV in listed patients irrespective of timing. DAA pre-LT can disadvantage some patients through increase number of treatments needed and longer waitlist times, but treatment in some listed patients with low-MELD can improve condition and alleviate need for LT.
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Affiliation(s)
- Adeel S Khan
- Section of Transplant Surgery, Washington University St. Louis, One Barnes-Jewish Hospital Plaza, Suite 6107 Queeny Tower, St Louis, MO, 63110, USA.
| | - Nathaniel Adams
- Section of Transplant Surgery, Washington University St. Louis, One Barnes-Jewish Hospital Plaza, Suite 6107 Queeny Tower, St Louis, MO, 63110, USA.
| | - Neeta Vachharajani
- Section of Transplant Surgery, Washington University St. Louis, One Barnes-Jewish Hospital Plaza, Suite 6107 Queeny Tower, St Louis, MO, 63110, USA.
| | - LeighAnne Dageforde
- Section of Transplant Surgery, Washington University St. Louis, One Barnes-Jewish Hospital Plaza, Suite 6107 Queeny Tower, St Louis, MO, 63110, USA.
| | - Jason Wellen
- Section of Transplant Surgery, Washington University St. Louis, One Barnes-Jewish Hospital Plaza, Suite 6107 Queeny Tower, St Louis, MO, 63110, USA.
| | - Surendra Shenoy
- Section of Transplant Surgery, Washington University St. Louis, One Barnes-Jewish Hospital Plaza, Suite 6107 Queeny Tower, St Louis, MO, 63110, USA.
| | - Jeffrey S Crippin
- Department of Medicine, Washington University St. Louis, One Barnes-Jewish Hospital Plaza, Suite 6107 Queeny Tower, St Louis, MO, 63110, USA.
| | - Majella B Doyle
- Section of Transplant Surgery, Washington University St. Louis, One Barnes-Jewish Hospital Plaza, Suite 6107 Queeny Tower, St Louis, MO, 63110, USA.
| | - William C Chapman
- Section of Transplant Surgery, Washington University St. Louis, One Barnes-Jewish Hospital Plaza, Suite 6107 Queeny Tower, St Louis, MO, 63110, USA.
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Lledó G, Benítez-Gutiérrez L, Arias A, Requena S, Cuervas-Mons V, de Mendoza C. Benefits of hepatitis C cure with antivirals: why test and treat? Future Microbiol 2019; 14:425-435. [PMID: 30900911 DOI: 10.2217/fmb-2019-0041] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Chronic hepatitis C virus (HCV) infection is one of the major causes of death worldwide due to infectious agents. The advent of direct-acting antivirals has dramatically improved the chance of HCV elimination, even for patients with decompensated cirrhosis. Along with HCV cure, benefits are recognized in terms of regression of liver fibrosis and risk of hepatocellular carcinoma. Furthermore, beyond hepatic outcomes, several extrahepatic benefits may result from sustained HCV eradication, including improvements in the neurocognitive function and reduced cardiovascular disease risk. Finally, there is no doubt that the individual success of direct-acting antivirals is largely contributing to halt HCV transmission globally, in the absence of an effective HCV prophylactic vaccine.
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Affiliation(s)
- Gema Lledó
- Internal Medicine Department, Hospital Puerta de Hierro-Majadahonda, Madrid, Spain
| | | | - Ana Arias
- Internal Medicine Department, Hospital Puerta de Hierro-Majadahonda, Madrid, Spain
| | - Silvia Requena
- Internal Medicine Department, Hospital Puerta de Hierro-Majadahonda, Madrid, Spain.,Internal Medicine Laboratory, Research Institute Puerta de Hierro-Segovia de Arana, Madrid, Spain
| | - Valentín Cuervas-Mons
- Internal Medicine Department, Hospital Puerta de Hierro-Majadahonda, Madrid, Spain.,Internal Medicine Laboratory, Research Institute Puerta de Hierro-Segovia de Arana, Madrid, Spain.,Universidad Autónoma, Madrid. Spain
| | - Carmen de Mendoza
- Internal Medicine Department, Hospital Puerta de Hierro-Majadahonda, Madrid, Spain.,Internal Medicine Laboratory, Research Institute Puerta de Hierro-Segovia de Arana, Madrid, Spain.,San Pablo-CEU University, Madrid. Spain
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Unger LW, Mandorfer M, Reiberger T. Portal Hypertension after Liver Transplantation—Causes and Management. CURRENT HEPATOLOGY REPORTS 2019; 18:59-66. [DOI: 10.1007/s11901-019-00450-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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The Changing Face of Liver Transplantation in the United States: The Effect of HCV Antiviral Eras on Transplantation Trends and Outcomes. Transplant Direct 2019; 5:e427. [PMID: 30882032 PMCID: PMC6411219 DOI: 10.1097/txd.0000000000000866] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2019] [Accepted: 01/04/2019] [Indexed: 02/07/2023] Open
Abstract
Background Hepatitis C virus (HCV) cirrhosis is the leading indication for liver transplantation in the United States, although nonalcoholic steatohepatitis (NASH) is on the rise. Increasingly effective HCV antivirals are available, but their association with diagnosis-specific liver transplantation rates and early graft survival is not known. Methods The Scientific Registry of Transplant Recipients database records were retrospectively stratified by HCV antiviral era: interferon (2003-2010), protease inhibitors (2011-2013), and direct-acting antivirals (2014 to present). Kaplan-Meier, χ2, and multivariable Cox proportional hazards regression models evaluated the effects of antiviral era and etiology of liver disease on transplantation rates and graft survival over 3 years. Results Liver transplants for HCV decreased (35.3% to 23.6%), whereas those for NASH and alcoholic liver disease increased (5.8% to 16.5% and 15.6% to 24.0%) with each advancing era (all P < 0.05). Early graft survival improved with each advancing era for HCV but not for hepatitis B virus, NASH, or alcoholic liver disease (multivariable model era by diagnosis interaction P < 0.001). Era-specific multivariable models demonstrated that the risk of early graft loss for NASH was 22% lower than for HCV in the interferon era (hazard ratio, 0.78; 95% confidence interval, 0.64-0.96; P = 0.02) but risks associated with these diagnoses did not differ significantly in the protease inhibitor (P = 0.06) or direct-acting antiviral eras (P = 0.08). Conclusions Increasing effectiveness of HCV antivirals corresponds with decreased rates of liver transplantation for HCV and improved early graft survival. As the rates of liver transplant for NASH continue to increase, focus will be needed on the prevention and effective therapies for this disease.
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Terrault NA, Pageaux GP. A changing landscape of liver transplantation: King HCV is dethroned, ALD and NAFLD take over! J Hepatol 2018; 69:767-768. [PMID: 30104027 DOI: 10.1016/j.jhep.2018.07.020] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2018] [Accepted: 07/22/2018] [Indexed: 12/04/2022]
Affiliation(s)
- Norah A Terrault
- Gastroenterology/Hepatology, University of California San Francisco, CA, USA.
| | - Georges-Philippe Pageaux
- Hepatology and Liver Transplantation Unit, CHU Saint Eloi, Montpellier University, 34295 Montpellier, France.
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