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1
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Hashem M, Medhat MA, Abdeltawab D, Makhlouf NA. Expanding the liver donor pool worldwide with hepatitis C infected livers, is it the time? World J Transplant 2024; 14:90382. [PMID: 38947961 PMCID: PMC11212581 DOI: 10.5500/wjt.v14.i2.90382] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Revised: 02/29/2024] [Accepted: 04/12/2024] [Indexed: 06/13/2024] Open
Abstract
Liver transplantation (LT) provides a life-saving option for cirrhotic patients with complications and hepatocellular carcinoma. Despite the increasing number of liver transplants performed each year, the number of LT candidates on the waitlist remains unchanged due to an imbalance between donor organ supply and the demand which increases the waitlist time and mortality. Living donor liver transplant had a great role in increasing the donor pool and shortened waitlist time for LT candidates. Nevertheless, further strategies can be implemented to increase the pool of potential donors in deceased donor LT, such as reducing the rate of organ discards. Utilizing hepatitis C virus (HCV) seropositive liver grafts is one of the expanded donor organ criteria. A yearly increase of hundreds of transplants is anticipated as a result of maximizing the utilization of HCV-positive organs for HCV-negative recipients. Direct-acting antiviral therapy's efficacy has revolutionized the treatment of HCV infection and the use of HCV-seropositive donors in transplantation. The American Society of Transplantation advises against performing transplants from HCV-infected liver donors (D+) into HCV-negative recipient (R-) unless under Institutional Review Board-approved study rules and with full informed consent of the knowledge gaps associated with such transplants. Proper selection of patients to be transplanted with HCV-infected grafts and confirming their access to direct-acting antivirals if needed is important. National and international consensuses are needed to regulate this process to ensure the maximum benefit and the least adverse events.
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Affiliation(s)
- Mai Hashem
- Fellow of Tropical Medicine and Gastroenterology, Assiut University Hospital, Assiut 71515, Egypt
| | - Mohammed A Medhat
- Department of Tropical Medicine and Gastroenterology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
| | - Doaa Abdeltawab
- Department of Tropical Medicine and Gastroenterology, Al-Rajhi Liver Hospital, Assiut University, Assiut 71515, Egypt
| | - Nahed A Makhlouf
- Department of Tropical Medicine and Gastroenterology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
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2
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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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3
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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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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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Alghamdi AS, Alghamdi H, Alserehi HA, Babatin MA, Alswat KA, Alghamdi M, AlQutub A, Abaalkhail F, Altraif I, Alfaleh FZ, Sanai FM. SASLT guidelines: Update in treatment of hepatitis C virus infection, 2024. Saudi J Gastroenterol 2024; 30:S1-S42. [PMID: 38167232 PMCID: PMC10856511 DOI: 10.4103/sjg.sjg_333_23] [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: 09/20/2023] [Revised: 11/27/2023] [Accepted: 12/03/2023] [Indexed: 01/05/2024] Open
Abstract
ABSTRACT Hepatitis C virus (HCV) infection has been a major global health concern, with a significant impact on public health. In recent years, there have been remarkable advancements in our understanding of HCV and the development of novel therapeutic agents. The Saudi Society for the Study of Liver Disease and Transplantation formed a working group to develop HCV practice guidelines in Saudi Arabia. The methodology used to create these guidelines involved a comprehensive review of available evidence, local data, and major international practice guidelines regarding HCV management. This updated guideline encompasses critical aspects of HCV care, including screening and diagnosis, assessing the severity of liver disease, and treatment strategies. The aim of this updated guideline is to assist healthcare providers in the management of HCV in Saudi Arabia. It summarizes the latest local studies on HCV epidemiology, significant changes in virus prevalence, and the importance of universal screening, particularly among high-risk populations. Moreover, it discusses the promising potential for HCV elimination as a public health threat by 2030, driven by effective treatment and comprehensive prevention strategies. This guideline also highlights evolving recommendations for advancing disease management, including the treatment of HCV patients with decompensated cirrhosis, treatment of those who have previously failed treatment with the newer medications, management in the context of liver transplantation and hepatocellular carcinoma, and treatment for special populations.
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Affiliation(s)
- Abdullah S. Alghamdi
- Department of Medicine, Gastroenterology Unit, King Fahad Hospital, Jeddah, Saudi Arabia
| | - Hamdan Alghamdi
- Hepatology Section, Hepatobiliary Sciences and Organs Transplant Center, King Abdulaziz Medical City, Riyadh, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
- King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
| | - Haleema A. Alserehi
- General Directorate of Communicable Diseases, Ministry of Health, Riyadh, Saudi Arabia
| | - Mohammed A. Babatin
- Department of Medicine, Gastroenterology Unit, King Fahad Hospital, Jeddah, Saudi Arabia
| | - Khalid A. Alswat
- Liver Disease Research Center, and Riyadh, Saudi Arabia
- College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Mohammed Alghamdi
- Department of Medicine, Division of Gastroenterology, King Fahd Military Complex, Dhahran, Saudi Arabia
| | - Adel AlQutub
- Department of Gastroenterology and Hepatology, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Faisal Abaalkhail
- Department of Medicine, Section of Gastroenterology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
- College of Medicine, Al Faisal University, Riyadh, Saudi Arabia
| | - Ibrahim Altraif
- Hepatology Section, Hepatobiliary Sciences and Organs Transplant Center, King Abdulaziz Medical City, Riyadh, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
- King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
| | | | - Faisal M. Sanai
- Liver Disease Research Center, and Riyadh, Saudi Arabia
- Gastroenterology Section, Department of Medicine, King Abdulaziz Medical City, Jeddah, Saudi Arabia
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6
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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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7
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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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8
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Botto GL, Mantovani LG, Cortesi PA, De Ponti R, D'Onofrio A, Biffi M, Capucci A, Casu G, Notarstefano P, Scaglione M, Zanotto G, Boriani G. The value of wearable cardioverter defibrillator in adult patients with recent myocardial infarction: Economic and clinical implications from a health technology assessment perspective. Int J Cardiol 2022; 356:12-18. [PMID: 35395289 DOI: 10.1016/j.ijcard.2022.04.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 03/16/2022] [Accepted: 04/01/2022] [Indexed: 01/19/2023]
Abstract
AIMS Sudden cardiac death (SCD) causes high mortality and substantial societal burdens for healthcare systems (HSs). The risk of SCD is significantly increased in patients with reduced left ventricular ejection fraction after myocardial infarction (MI). Current guidelines recommend re-evaluation of cardioverter-defibrillator implantation 40 days post-MI, earliest. Medical therapy alone does not provide sufficient protection against SCD, especially in the first month post-MI, and needs time. Consequently, there is a gap in care of high-risk patients upon hospital discharge. The wearable cardioverter defibrillator (WCD) is a proven safe, effective therapy, which temporarily protects from SCD. Little information on WCD cost-effectiveness exists. We conducted this research to demonstrate the medical need of the device in the post-MI setting defining WCD cost-effectiveness. METHODS & RESULTS Based on a randomized clinical trials (RCTs) and Italian and international data, we developed a Markov-model comparing costs, patient survival, and quality-of-life, and calculated the Incremental Cost-Effectiveness Ratio (ICER) of a WCD vs. current standard of care in post-MI patients. The rather conservative base case analysis - based on the RCT intention-to-treat results - produced an ICER of €47,709 per Quality Adjusted Life Year (QALY) gained, which is far lower than the accepted threshold of €60,000 in the Italian National HS. The ICER per Life Year (LY) gained was €38,276. CONCLUSION WCD utilization in post-MI patients is clinically beneficial and cost-effective. While improving guideline directed patient care, the WCD can also contribute to a more efficient use of resources in the Italian HS, and potentially other HSs as well.
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Affiliation(s)
- Giovanni Luca Botto
- Cardiology - Electrophysiology Division, Department of Medicine, Ospedale di Circolo Rho, Ospedale Salvini Garbagnate M.se, ASST Rhodense, Milan, Italy.
| | - Lorenzo Giovanni Mantovani
- Research Centre on Public Health (CESP), University of Milano-Bicocca, Monza, Italy; Value-Based Healthcare Unit, IRCCS Multimedica, Sesto San Giovanni, Italy
| | - Paolo Angelo Cortesi
- Research Centre on Public Health (CESP), University of Milano-Bicocca, Monza, Italy
| | - Roberto De Ponti
- Department of Heart and Vessels, Ospedale di Circolo-University of Insubria, Varese, Italy
| | - Antonio D'Onofrio
- Cardiology Division - Electrophysiology Department - AORN dei Colli, Ospedale Monaldi, Napoli, Italy
| | - Mauro Biffi
- Cardiology Division - Electrophysiology Department, Policlinico S.Orsola Malpighi, Bologna, Italy
| | - Alessandro Capucci
- Cardiology and Arrhytmology Clinic, Azienda Ospedaliero Universitaria Ospedali Riuniti, Ancona, Italy
| | - Gavino Casu
- Cardiology and Intensive Care Unit, Ospedale "San Francesco" Nuoro, Italy
| | | | | | | | - Giuseppe Boriani
- Cardiology Division, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Policlinico di Modena, Modena, Italy
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Cortesi PA, Antonazzo IC, Gasperini C, Nica M, Ritrovato D, Mantovani LG. Cost-effectiveness and budget impact analysis of siponimod in the treatment of secondary progressive multiple sclerosis in Italy. PLoS One 2022; 17:e0264123. [PMID: 35259168 PMCID: PMC8903273 DOI: 10.1371/journal.pone.0264123] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Accepted: 02/04/2022] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND Siponimod is an effective treatment for patients with secondary progressive multiple sclerosis (SPMS), with active disease evidenced by relapses or imaging features characteristic of multiple sclerosis inflammatory activity, however there is a need to evaluate its economic value and sustainability compared to other disease modifying-therapies (DMTs). OBJECTIVE To estimate the siponimod cost-effectiveness profile and its relative budget impact compared with other DMTs, by using the Italian National Healthcare System perspective. METHODS We performed: 1) a cost-effectiveness analysis (CEA) vs interferon beta-1b using an analytical Markov model and a life time-horizon, and 2) a budget impact analysis by using 3-years time-horizon. The results were reported as incremental cost-effectiveness ratio (ICER) and net-monetary benefit (NMB) for CEA, using a willingness to pay threshold of €40,000 per QALY gained, and as difference in the overall budget (Euro) between the scenario with and without siponimod for budget impact. RESULTS In the base case scenario siponimod resulted cost-effective compared with interferon beta-1b 28,891€ per QALY. Overall, the market access of siponimod was associated to an increased budget of about 3€ millions (+0.9%) in the next 3 years simulated. CONCLUSION Compared to interferon beta-1b, siponimod seems to be cost-effective in SPMS patients and sustainable, with less than 1% overall budget increased in the next 3 years. Future studies need to confirm our results in the real word setting and in other countries.
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Affiliation(s)
- Paolo Angelo Cortesi
- Research Centre on Public Health (CESP), University of Milano-Bicocca, Monza, Italy
- Value-Based Healthcare Unit, IRCCS MultiMedica, Sesto San Giovanni, Italy
| | | | - Claudio Gasperini
- Department of Neurology, Multiple Sclerosis Centre, San Camillo-Forlanini Hospital, Rome, Italy
| | | | | | - Lorenzo Giovanni Mantovani
- Research Centre on Public Health (CESP), University of Milano-Bicocca, Monza, Italy
- Value-Based Healthcare Unit, IRCCS MultiMedica, Sesto San Giovanni, Italy
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10
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Saracco GM, Marzano A, Rizzetto M. Therapy of Chronic Viral Hepatitis: The Light at the End of the Tunnel? Biomedicines 2022; 10:534. [PMID: 35327336 PMCID: PMC8945793 DOI: 10.3390/biomedicines10030534] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Revised: 02/08/2022] [Accepted: 02/16/2022] [Indexed: 02/06/2023] Open
Abstract
Chronic viral hepatitis determines significant morbidity and mortality globally and is caused by three main etiological actors (Hepatitis B Virus, Hepatitis C Virus, and Hepatitis D Virus) with different replicative cycles and biological behaviors. Thus, therapies change according to the different characteristics of the viruses. In chronic hepatitis B, long term suppressive treatments with nucleoside/nucleotide analogues have had a dramatic impact on the evolution of liver disease and liver-related complications. However, a conclusive clearance of the virus is difficult to obtain; new strategies that are able to eradicate the infection are currently objects of research. The therapy for Hepatitis D Virus infection is challenging due to the unique virology of the virus, which uses the synthetic machinery of the infected hepatocyte for its own replication and cannot be targeted by conventional antivirals that are active against virus-coded proteins. Recently introduced antivirals, such as bulevertide and lonafarnib, display definite but only partial efficacy in reducing serum HDV-RNA. However, in combination with pegylated interferon, they provide a synergistic therapeutic effect and appear to represent the current best therapy for HDV-positive patients. With the advent of Direct Acting Antiviral Agents (DAAs), a dramatic breakthrough has occurred in the therapeutic scenario of chronic hepatitis C. Cure of HCV infection is achieved in more than 95% of treated patients, irrespective of their baseline liver fibrosis status. Potentially, the goal of global HCV elimination by 2030 as endorsed by the World Health Organization can be obtained if more global subsidised supplies of DAAs are provided.
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Affiliation(s)
- Giorgio Maria Saracco
- Gastro-Hepatoloy Unit, Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (A.M.); (M.R.)
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Sintusek P, Thanapirom K, Komolmit P, Poovorawan Y. Eliminating viral hepatitis in children after liver transplants: How to reach the goal by 2030. World J Gastroenterol 2022; 28:290-309. [PMID: 35110951 PMCID: PMC8771616 DOI: 10.3748/wjg.v28.i3.290] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 08/12/2021] [Accepted: 01/06/2022] [Indexed: 02/06/2023] Open
Abstract
Viral hepatitis infections are a great burden in children who have received liver transplant. Hepatotropic viruses can cause liver inflammation that can develop into liver graft fibrosis and cirrhosis over the long term. Immunological reactions due to viral hepatitis infections are associated with or can mimic graft rejection, rendering the condition difficult to manage. Prevention strategies using vaccinations are agreeable to patients, safe, cost-effective and practical. Hence, strategies to eliminate viral hepatitis A and B focus mainly on immunization programmes for children who have received a liver transplant. Although a vaccine has been developed to prevent hepatitis C and E viruses, its use is not licensed worldwide. Consequently, eliminating hepatitis C and E viruses mainly involves early detection in children with suspected cases and effective treatment with antiviral therapy. Good hygiene and sanitation are also important to prevent hepatitis A and E infections. Donor blood products and liver grafts should be screened for hepatitis B, C and E in children who are undergoing liver transplantation. Future research on early detection of viral hepatitis infections should include molecular techniques for detecting hepatitis B and E. Moreover, novel antiviral drugs for eradicating viral hepatitis that are highly effective and safe are needed for children who have undergone liver transplantation.
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Affiliation(s)
- Palittiya Sintusek
- The Thai Pediatric Gastroenterology, Hepatology and Immunology (TPGHAI) Research Unit, Chulalongkorn University, Bangkok 10330, Thailand
- Division of Gastroenterology, Department of Pediatrics, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok 10330, Thailand
| | - Kessarin Thanapirom
- Division of Gastroenterology, Department of Medicine, Liver Fibrosis and Cirrhosis Research Unit, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
- Center of Excellence in Liver Diseases, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok 10330, Thailand
| | - Piyawat Komolmit
- Division of Gastroenterology, Department of Medicine, Liver Fibrosis and Cirrhosis Research Unit, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
- Center of Excellence in Liver Diseases, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok 10330, Thailand
| | - Yong Poovorawan
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
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12
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Stanciu C, Muzica CM, Girleanu I, Cojocariu C, Sfarti C, Singeap AM, Huiban L, Chiriac S, Cuciureanu T, Trifan A. An update on direct antiviral agents for the treatment of hepatitis C. Expert Opin Pharmacother 2021; 22:1729-1741. [PMID: 33896315 DOI: 10.1080/14656566.2021.1921737] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Accepted: 04/21/2021] [Indexed: 02/06/2023]
Abstract
Introduction: The development of direct-acting antiviral (DAA) agents for the treatment of hepatitis C virus (HCV) infection has completely transformed the management of this disease. The advantages of using DAA therapies include high efficacy (sustained virological response (SVR) rate >95%) with minimal side effects, good tolerability, easy drug administration (once daily oral dosing), and short duration of treatment (8-12 weeks). This transformative nature of DAA therapy underpins the goal of the World Health Organization to eliminate HCV infection as a public health threat by 2030.Areas covered: This review seeks to address the current status of DAA therapies, including recent developments, current limitations, and future challenges.Expert opinion: The current DAA regimens, with their high effectiveness and safety profiles, have changed patient perception of HCV infection from a disease that requires complex evaluation and long-term monitoring to a disease that can be cured after one visit to the general practitioner. Despite the remarkably high success rate of DAAs, few patients (4-5%) fail to obtain SVR even after treatment. Five years ahead, the landscape of HCV treatment will undoubtedly continue to evolve, and more pan-genotypic treatment options will be available to all patients.
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Affiliation(s)
- Carol Stanciu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, ST. SpiridonEmergency Hospital, Iasi, Romania
| | - Cristina Maria Muzica
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, ST. SpiridonEmergency Hospital, Iasi, Romania
| | - Irina Girleanu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, ST. SpiridonEmergency Hospital, Iasi, Romania
| | - Camelia Cojocariu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, ST. SpiridonEmergency Hospital, Iasi, Romania
| | - Catalin Sfarti
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, ST. SpiridonEmergency Hospital, Iasi, Romania
| | - Ana-Maria Singeap
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, ST. SpiridonEmergency Hospital, Iasi, Romania
| | - Laura Huiban
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, ST. SpiridonEmergency Hospital, Iasi, Romania
| | - Stefan Chiriac
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, ST. SpiridonEmergency Hospital, Iasi, Romania
| | - Tudor Cuciureanu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, ST. SpiridonEmergency Hospital, Iasi, Romania
| | - Anca Trifan
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, ST. SpiridonEmergency Hospital, Iasi, Romania
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Boriani G, Mantovani LG, Cortesi PA, De Ponti R, D'Onofrio A, Arena G, Curnis A, Forleo G, Guerra F, Porcu M, Sgarito G, Botto GL. Cost-minimization analysis of a wearable cardioverter defibrillator in adult patients undergoing ICD explant procedures: Clinical and economic implications. Clin Cardiol 2021; 44:1497-1505. [PMID: 34427926 PMCID: PMC8571546 DOI: 10.1002/clc.23709] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 07/26/2021] [Accepted: 07/30/2021] [Indexed: 12/12/2022] Open
Abstract
Aims Patients with permanently increased risk of sudden cardiac death (SCD) can be protected by implantable cardioverter defibrillators (ICD). If an ICD must be removed due to infection, for example, immediate reimplantation might not be possible or indicated. The wearable cardioverter defibrillator (WCD) is an established, safe and effective solution to protect patients from SCD during this high‐risk bridging period. Very few economic evaluations on WCD use are currently available. Methods We conducted a systematic review to evaluate the available evidence of WCD in patients undergoing ICD explant/lead extraction. Additionally, a decision model was developed to compare use and costs of the WCD with standard therapy (in‐hospital stay). For this purpose, a cost‐minimization analysis was conducted, and complemented by a one‐way sensitivity analysis. Results In the base case scenario, the WCD was less expensive compared to standard therapy. The cost‐minimization analysis showed a cost reduction of €1782 per patient using the WCD. If costs of standard care were changed, cost savings associated with the WCD varied from €3500 to €0, assuming costs for standard care of €6800 to €3600. Conclusion After ICD explantation, patients can be safely and effectively protected from SCD after hospital discharge through WCD utilization. Furthermore, the use of a WCD for this patient group is cost saving when compared to standard therapy.
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Affiliation(s)
- Giuseppe Boriani
- Cardiology Division, Department of Biomedical, Metabolic and Neural SciencesUniversity of Modena and Reggio EmiliaPoliclinico di ModenaItaly
| | - Lorenzo Giovanni Mantovani
- Research Centre on Public Health (CESP)University of Milano‐BicoccaMonzaItaly
- Value‐Based Healthcare UnitIRCCS MultimedicaSesto San GiovanniItaly
| | | | - Roberto De Ponti
- Department of Heart and VesselsOspedale di Circolo‐University of InsubriaVareseItaly
| | - Antonio D'Onofrio
- Cardiology Division – Electrophysiology Department – AORN dei Colli – Ospedale MonaldiNapoliItaly
| | - Giuseppe Arena
- Cardiology DepartmentAzienda Usl Toscana Nord OvestMassa CarraraItaly
| | - Antonio Curnis
- Cardiology DepartmentPresidio Ospedaliero di Brescia, ASST Spedali CiviliBresciaItaly
| | - Giovanni Forleo
- Cardiology Department, Electrophysiology and Arrhtymology DivisionOspedale Luigi Sacco ‐ Polo UniversitarioMilanItaly
| | - Federico Guerra
- Cardiology and Arrhytmology ClinicAzienda Ospedaliero Universitaria Ospedali RiunitiAnconaItaly
| | - Maurizio Porcu
- Cardiology DepartmentAzienda Ospedaliera “G. Brotzu”CagliariItaly
| | - Giuseppe Sgarito
- Cardiology Department, Electrophysiology and Arrhtymology DivisionA.R.N.A.S. Ospedali CivicoPalermoItaly
| | - Giovanni Luca Botto
- Cardiology – Electrophysiology Division, Department of MedicineOspedale di Circolo Rho, Ospedale Salvini Garbagnate M.se, ASST RhodenseMilanItaly
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Cost-Effectiveness Analysis of Rivaroxaban Plus Aspirin Compared with Aspirin Alone in Patients with Coronary and Peripheral Artery Diseases in Italy. Clin Drug Investig 2021; 41:459-468. [PMID: 33725323 PMCID: PMC8149345 DOI: 10.1007/s40261-021-01023-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/06/2021] [Indexed: 10/28/2022]
Abstract
BACKGROUND Rivaroxaban is a selective inhibitor of coagulation factor Xa and its combination with aspirin showed better outcomes in the prevention of recurrent cardiovascular disease than aspirin alone. OBJECTIVE This analysis aimed to economically compare the cost effectiveness of rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily) with aspirin alone in patients with coronary artery disease (CAD) or peripheral artery disease (PAD) and related subgroups. METHODS The analysis simulates the perspective of the Italian National Healthcare Service and used a state-transition decision Markov model. Clinical efficacy data and health events risks were gathered from the COMPASS trial. Health outcomes and costs (in Euros) were evaluated over a lifetime horizon and were discounted at 3.5% per annum. Direct healthcare costs entered the analysis. Results were expressed in terms of incremental cost-effectiveness ratio (ICER), defined as cost per quality-adjusted life-year (QALY) gained. One-way deterministic and probabilistic sensitivity analyses were performed. RESULTS For the CAD or PAD population, rivaroxaban plus aspirin was more effective and costly compared with aspirin alone. Incremental costs and efficacy produced an ICER of €16,522 per QALY gained. Analyses found similar trends for the PAD and CAD groups, with respective ICERs of €8003 and €18,599, while ICERs for the other groups were lower than €13,000 per QALY. Sensitivity analyses confirmed these findings. CONCLUSION Compared with aspirin alone, rivaroxaban plus aspirin is cost effective in preventing recurrent cardiovascular events in all patients with CAD or PAD, from the Italian perspective. These results could help clinicians and decision makers to develop improved strategies for cardiovascular disease prevention.
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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: 758] [Impact Index Per Article: 151.6] [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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Meunier L, Pageaux GP, Coilly A. HCV treatment in cirrhotic patients: Should we use a different approach for patients awaiting a liver transplant. J Hepatol 2020; 73:984-985. [PMID: 32653222 DOI: 10.1016/j.jhep.2020.05.026] [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: 04/24/2020] [Revised: 05/13/2020] [Accepted: 05/18/2020] [Indexed: 12/04/2022]
Affiliation(s)
- Lucy Meunier
- Liver and Transplantation Unit, Montpellier University Hospital, Montpellier, France.
| | | | - Audrey Coilly
- Hepatobiliary Center, Paul Brousse Hospital APHP, Villejuif, France
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18
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Charatcharoenwitthaya P, Wongpaitoon V, Komolmit P, Sukeepaisarnjaroen W, Tangkijvanich P, Piratvisuth T, Sanpajit T, Sutthivana C, Bunchorntavakul C, Sobhonslidsuk A, Chonprasertsuk S, Siripipattanamongkol C, Sethasine S, Tanwandee T. Real-world effectiveness and safety of sofosbuvir and nonstructural protein 5A inhibitors for chronic hepatitis C genotype 1, 2, 3, 4, or 6: a multicentre cohort study. BMC Gastroenterol 2020; 20:47. [PMID: 32138687 PMCID: PMC7057522 DOI: 10.1186/s12876-020-01196-0] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Accepted: 02/17/2020] [Indexed: 02/07/2023] Open
Abstract
Background We investigated real-world effectiveness and safety of sofosbuvir and the nonstructural protein 5A inhibitors in the treatment of patients infected with hepatitis C virus (HCV) genotypes 1, 2, 3, 4, or 6. Methods We analyzed data from 1021 patients with HCV infection (506 with genotype 1; 16 with genotype 2; 314 with genotype 3; 13 with genotype 4; 166 with genotype 6) who received 12 to 24 weeks of daclatasvir plus sofosbuvir (n = 767), ledipasvir/sofosbuvir (n = 197), or sofosbuvir/velpatasvir (n = 57), with or without ribavirin in 12 centers across Thailand to estimate sustained virologic response at post-treatment week 12 (SVR12). Results Overall, SVR12 rate was 98.0% (95% confidence interval [CI], 96.7–98.8%) with daclatasvir plus sofosbuvir, 97.9% (95% CI, 94.8–99.2%) with ledipasvir/sofosbuvir, and 96.5% (95% CI, 88.1–99.0%) with sofosbuvir/velpatasvir. SVR12 was achieved by 99.2% (95% CI, 97.9–99.7%) of subjects with genotype 1 infection, 100% (95% CI, 78.5–100%) of those with genotype 2 infection, 96.7% (95% CI, 94.0–98.2%) of those with genotype 3 infection, 90.9% (95% CI, 62.3–98.4%) of those with genotype 4 infection, and 96.7% (95% CI 92.5–98.6%) of those with genotype 6 infection. Patients with advanced liver disease were at risk of treatment failure. Only four patients discontinued treatment before week 4 due to non-hepatic adverse events. Conclusions In this large cohort of patients with various HCV genotypes managed in the real-world practice setting, daclatasvir plus sofosbuvir, ledipasvir/sofosbuvir, and sofosbuvir/velpatasvir achieved high SVR rates with good safety profile, comparable to those observed in clinical trials.
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Affiliation(s)
| | | | - Piyawat Komolmit
- Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | | | | | | | | | | | | | | | | | | | | | - Tawesak Tanwandee
- Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
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Murag S, Dennis BB, Kim D, Ahmed A, Cholankeril G. Recent advances in liver transplantation with HCV seropositive donors. F1000Res 2019; 8:F1000 Faculty Rev-2151. [PMID: 31942236 PMCID: PMC6944251 DOI: 10.12688/f1000research.20387.1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/17/2019] [Indexed: 12/15/2022] Open
Abstract
The paradigm shift from interferon-based to direct-acting antiviral (DAA) therapy for the treatment of hepatitis C virus (HCV) infection has revolutionized the field of liver transplantation. These advances in effective HCV treatment, along with the persistent shortage in available liver grafts, have encouraged investigators to assess the need for adopting more inclusive donor policies. Owing to the poor outcomes following liver transplantation with recurrent HCV infection, liver transplantation using HCV seropositive donors (non-viremic and viremic) had been restricted. However, as a result of the growing supply of HCV seropositive donors from the recent opioid epidemic along with the advent of efficacious DAA therapy to treat HCV recurrence, there has been an increasing trend to use HCV seropositive donors for both HCV seropositive and seronegative recipients. The review aims to discuss recent advances and associated outcomes related to the use of HCV seropositive grafts for liver transplantation.
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Affiliation(s)
- Soumya Murag
- Department of Medicine, Santa Clara Valley Medical Center, Santa Clara, CA, USA
| | - Brittany B. Dennis
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Donghee Kim
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - George Cholankeril
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
- Department of Health Research and Policy, Division of Epidemiology, Stanford University School of Medicine, Stanford, CA, USA
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Ji F, Yeo YH, Wei MT, Ogawa E, Enomoto M, Lee DH, Iio E, Lubel J, Wang W, Wei B, Ide T, Preda CM, Conti F, Minami T, Bielen R, Sezaki H, Barone M, Kolly P, Chu PS, Virlogeux V, Eurich D, Henry L, Bass MB, Kanai T, Dang S, Li Z, Dufour JF, Zoulim F, Andreone P, Cheung RC, Tanaka Y, Furusyo N, Toyoda H, Tamori A, Nguyen MH. Sustained virologic response to direct-acting antiviral therapy in patients with chronic hepatitis C and hepatocellular carcinoma: A systematic review and meta-analysis. J Hepatol 2019; 71:473-485. [PMID: 31096005 DOI: 10.1016/j.jhep.2019.04.017] [Citation(s) in RCA: 54] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2018] [Revised: 03/31/2019] [Accepted: 04/25/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The effect of hepatocellular carcinoma (HCC) on the response to interferon-free direct-acting antiviral (DAA) therapy in patients with chronic hepatitis C (CHC) infection remains unclear. Using a systematic review and meta-analysis approach, we aimed to investigate the effect of DAA therapy on sustained virologic response (SVR) among patients with CHC and either active, inactive or no HCC. METHODS PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from 1/1/2013 to 9/24/2018. The pooled SVR rates were computed using DerSimonian-Laird random-effects models. RESULTS We included 49 studies from 15 countries, comprised of 3,341 patients with HCC and 35,701 without HCC. Overall, the pooled SVR was lower in patients with HCC than in those without HCC (89.6%, 95% CI 86.8-92.1%, I2 = 79.1% vs. 93.3%, 95% CI 91.9-94.7%, I2 = 95.0%, p = 0.0012), translating to a 4.8% (95% CI 0.2-7.4%) SVR reduction by meta-regression analysis. The largest SVR reduction (18.8%) occurred in patients with active/residual HCC vs. inactive/ablated HCC (SVR 73.1% vs. 92.6%, p = 0.002). Meanwhile, patients with HCC who received a prior liver transplant had higher SVR rates than those who did not (p <0.001). Regarding specific DAA regimens, patients with HCC treated with ledipasvir/sofosbuvir had lower SVR rates than patients without HCC (92.6%, n = 884 vs. 97.8%, n = 13,141, p = 0.026), but heterogeneity was high (I2 = 84.7%, p <0.001). The SVR rate was similar in patients with/without HCC who were treated with ombitasvir/paritaprevir/ritonavir ± dasabuvir (n = 101) (97.2% vs. 94.8%, p = 0.79), or daclatasvir/asunaprevir (91.7% vs. 89.8%, p = 0.66). CONCLUSION Overall, SVR rates were lower in patients with HCC, especially with active HCC, compared to those without HCC, though heterogeneity was high. Continued efforts are needed to aggressively screen, diagnose, and treat HCC to ensure higher CHC cure rates. LAY SUMMARY There are now medications (direct-acting antivirals or "DAAs") that can "cure" hepatitis C virus, but patients with hepatitis C and liver cancer may be less likely to achieve cure than those without liver cancer. However, patients with liver cancer are also more likely to have advanced liver disease and risk factors that can decrease cure rates, so better controlled studies are needed to confirm these findings.
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Affiliation(s)
- Fanpu Ji
- Department of Infectious Diseases, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China; Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA; National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China; Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Yee Hui Yeo
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | - Mike Tzuhen Wei
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | - Eiichi Ogawa
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA; Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Masaru Enomoto
- Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Dong Hyun Lee
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA; Division of Gastroenterology, Department of Internal Medicine, Good Gang-An Hospital, Busan, Republic of Korea
| | - Etsuko Iio
- Department of Virology & Liver Unit, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan
| | - John Lubel
- Eastern Health Clinical School, Monash University, Melbourne, Victoria, Australia
| | - Wenjun Wang
- Department of Infectious Diseases, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Bin Wei
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | - Tatsuya Ide
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan
| | - Carmen Monica Preda
- University of Medicine and Pharmacy "Carol Davila", Department of Gastroenterology and Hepatology, Clinical Institute Fundeni, Bucharest, Romania
| | - Fabio Conti
- Research Centre for the Study of Hepatitis, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Tatsuya Minami
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Japan
| | - Rob Bielen
- Faculty of Medicine and Life Sciences, Hasselt University, Belgium
| | - Hitomi Sezaki
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan
| | - Michele Barone
- Gastroenterology Unit, Department of Emergency and Organ Transplantation, Azienda Universitario-Ospedaliera Policlinico, University of Bari, Bari, Italy
| | - Philippe Kolly
- Department of Clinical Research, University of Bern, Bern, Switzerland; University Clinic of Visceral Surgery and Medicine, Inselspital Bern, Bern, Switzerland
| | - Po-Sung Chu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Victor Virlogeux
- Department of Hepatology, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France
| | - Dennis Eurich
- Department of Surgery Campus Charité Mitte / Campus Virchow-Klinikum, Berlin, Germany
| | - Linda Henry
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | - Michelle B Bass
- Lane Medical Library & Knowledge Management Center, Stanford University, Palo Alto, CA, USA
| | - Takanori Kanai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Shuangsuo Dang
- Department of Infectious Diseases, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Zongfang Li
- National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China; Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Jean-François Dufour
- Department of Clinical Research, University of Bern, Bern, Switzerland; University Clinic of Visceral Surgery and Medicine, Inselspital Bern, Bern, Switzerland
| | - Fabien Zoulim
- Department of Hepatology, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France; Cancer Research Center of Lyon (CRCL-INSERM U1052), Lyon University, Lyon, France
| | - Pietro Andreone
- Research Centre for the Study of Hepatitis, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Ramsey C Cheung
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA; Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA
| | - Yasuhito Tanaka
- Department of Virology & Liver Unit, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan
| | - Norihiro Furusyo
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Akihiro Tamori
- Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA.
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Treatment strategies for patients with decompensated liver cirrhosis due to hepatitis C virus infection eligible for liver transplantation: real-life data from five German transplant centers. Eur J Gastroenterol Hepatol 2019; 31:1049-1056. [PMID: 30807443 DOI: 10.1097/meg.0000000000001386] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND Even with highly effective direct-acting antivirals (DAAs) treatment of patients with decompensated hepatitis C (HCV) cirrhosis remains challenging. Clinical deterioration and the need for liver transplantation (LT) may arise despite previous antiviral treatment. It is unclear whether in patients with high Model for End-Stage Liver Disease (MELD) antiviral treatment is too risky and should thus be deferred until after LT. Treatment choices that are currently made in the real-world setting are unclear. METHODS We performed a retrospective multicenter data analysis of patients with decompensated HCV cirrhosis (MELD ≥15) that presented to liver transplant centers that are part of the German Center for Infection Research when highly active DAA therapy was available. Choice of treatment strategy (DAA first vs. transplantation first) was analyzed and correlated with baseline and outcome parameters. RESULTS Thirty-five patients fulfilled the inclusion criteria and their mean MELD score was 18.5±3.78 (median: 17, interquartile range=16-19). In the majority of patients (85.7%) DAA therapy was initiated before LT; survival rates and change in MELD were numerically better in this group compared with those where DAA therapy was withheld (82.1 vs. 40%, P=0.078; ΔMELD: -2.68±6.2 vs. 5.8±14.4, P=0.157). However, DAA treatment was more often initiated in patients with better liver function (MELD: 18±3.54 vs. 21.8±3.9, P=0.008). Three patients discontinued DAA treatment because of clinical deterioration; these patients all had a MELD score above 20 at the start of therapy. CONCLUSION At liver transplant centers in Germany DAA before LT is attempted in the majority of cases. It appears to be associated with an improved outcome and seems safe at least in individuals with MELD below or equal to 20.
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Kwong AJ, Kim WR, Flemming JA. De Novo Hepatocellular Carcinoma Among Liver Transplant Registrants in the Direct Acting Antiviral Era. Hepatology 2018; 68:1288-1297. [PMID: 29672886 PMCID: PMC6173633 DOI: 10.1002/hep.30045] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2018] [Accepted: 04/09/2018] [Indexed: 12/11/2022]
Abstract
The risk of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV) receiving direct acting antivirals (DAAs) has been debated. This study aims to describe the incidence of HCC among patients listed for liver transplantation (LT) in the DAA era. Individuals with cirrhosis listed for LT from January 2003 to December 2015 were identified using the Scientific Registry for Transplant Recipients database. Patients with HCC at listing or HCC exception within 180 days were excluded. Patients were divided into three eras based on listing date: eras 1 (2003-2010), 2 (2011-2013), and 3 (2014-2015). Incidence rates of HCC were calculated by era and compared using incident rate ratios (IRRs). The association between HCC and listing era was evaluated using Cox regression and competing risk analyses, the latter considering death and LT as competing events. Of the 48,158 eligible wait-list registrants, 3112 (6.5%) received HCC exceptions after a median of 493 days. In 20,039 individuals with HCV, the incidence of HCC was 49% higher in era 3 versus era 1 (IRR 1.49, 95% confidence interval [CI] 1.24-1.79). In multivariate analysis, those in era 3 had a higher hazard of HCC compared with era 1 (hazard ratio 1.22, 95% CI 1.01-1.48). However, in multivariable competing risks analysis, with death and LT considered as competing events for de novo HCC, era was no longer associated with HCC (subdistribution hazard ratio 0.83, 95% CI 0.69-1.00). CONCLUSION In this large population-based cohort of LT registrants, the incidence of HCC among HCV patients has increased in the DAA era. Competing risks analysis suggests that this may be explained by changes in rates of LT and wait-list mortality in the HCV population during this time. (Hepatology 2018; 00:000-000).
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Affiliation(s)
- Allison J. Kwong
- Division of Gastroenterology and Hepatology, Stanford University, Stanford, United States
| | - W. Ray Kim
- Division of Gastroenterology and Hepatology, Stanford University, Stanford, United States
| | - Jennifer A. Flemming
- Departments of Medicine and Public Health Sciences, Queen's University, Kingston, Ontario, Canada
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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 2018. J Hepatol 2018; 69:461-511. [PMID: 29650333 DOI: 10.1016/j.jhep.2018.03.026] [Citation(s) in RCA: 1205] [Impact Index Per Article: 172.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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