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Berg T, Aehling NF, Bruns T, Welker MW, Weismüller T, Trebicka J, Tacke F, Strnad P, Sterneck M, Settmacher U, Seehofer D, Schott E, Schnitzbauer AA, Schmidt HH, Schlitt HJ, Pratschke J, Pascher A, Neumann U, Manekeller S, Lammert F, Klein I, Kirchner G, Guba M, Glanemann M, Engelmann C, Canbay AE, Braun F, Berg CP, Bechstein WO, Becker T, Trautwein C. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1397-1573. [PMID: 39250961 DOI: 10.1055/a-2255-7246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/11/2024]
Affiliation(s)
- Thomas Berg
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Niklas F Aehling
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Tony Bruns
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martin-Walter Welker
- Medizinische Klinik I Gastroent., Hepat., Pneum., Endokrin. Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Tobias Weismüller
- Klinik für Innere Medizin - Gastroenterologie und Hepatologie, Vivantes Humboldt-Klinikum, Berlin, Deutschland
| | - Jonel Trebicka
- Medizinische Klinik B für Gastroenterologie und Hepatologie, Universitätsklinikum Münster, Münster, Deutschland
| | - Frank Tacke
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Pavel Strnad
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martina Sterneck
- Medizinische Klinik und Poliklinik I, Universitätsklinikum Hamburg, Hamburg, Deutschland
| | - Utz Settmacher
- Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Jena, Deutschland
| | - Daniel Seehofer
- Klinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Eckart Schott
- Klinik für Innere Medizin II - Gastroenterologie, Hepatologie und Diabetolgie, Helios Klinikum Emil von Behring, Berlin, Deutschland
| | | | - Hartmut H Schmidt
- Klinik für Gastroenterologie und Hepatologie, Universitätsklinikum Essen, Essen, Deutschland
| | - Hans J Schlitt
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg, Regensburg, Deutschland
| | - Johann Pratschke
- Chirurgische Klinik, Charité Campus Virchow-Klinikum - Universitätsmedizin Berlin, Berlin, Deutschland
| | - Andreas Pascher
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Münster, Münster, Deutschland
| | - Ulf Neumann
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Essen, Essen, Deutschland
| | - Steffen Manekeller
- Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax- und Gefäßchirurgie, Universitätsklinikum Bonn, Bonn, Deutschland
| | - Frank Lammert
- Medizinische Hochschule Hannover (MHH), Hannover, Deutschland
| | - Ingo Klein
- Chirurgische Klinik I, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - Gabriele Kirchner
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg und Innere Medizin I, Caritaskrankenhaus St. Josef Regensburg, Regensburg, Deutschland
| | - Markus Guba
- Klinik für Allgemeine, Viszeral-, Transplantations-, Gefäß- und Thoraxchirurgie, Universitätsklinikum München, München, Deutschland
| | - Matthias Glanemann
- Klinik für Allgemeine, Viszeral-, Gefäß- und Kinderchirurgie, Universitätsklinikum des Saarlandes, Homburg, Deutschland
| | - Cornelius Engelmann
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Ali E Canbay
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Deutschland
| | - Felix Braun
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
| | - Christoph P Berg
- Innere Medizin I Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - Wolf O Bechstein
- Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Thomas Becker
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
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Plümers R, Dreier J, Knabbe C, Steinmann E, Todt D, Vollmer T. Kinetics of Hepatitis E Virus Infections in Asymptomatic Persons. Emerg Infect Dis 2024; 30:934-940. [PMID: 38666600 PMCID: PMC11060471 DOI: 10.3201/eid3005.231764] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/02/2024] Open
Abstract
To determine the kinetics of hepatitis E virus (HEV) in asymptomatic persons and to evaluate viral load doubling time and half-life, we retrospectively tested samples retained from 32 HEV RNA-positive asymptomatic blood donors in Germany. Close-meshed monitoring of viral load and seroconversion in intervals of ≈4 days provided more information about the kinetics of asymptomatic HEV infections. We determined that a typical median infection began with PCR-detectable viremia at 36 days and a maximum viral load of 2.0 × 104 IU/mL. Viremia doubled in 2.4 days and had a half-life of 1.6 days. HEV IgM started to rise on about day 33 and peaked on day 36; IgG started to rise on about day 32 and peaked on day 53. Although HEV IgG titers remained stable, IgM titers became undetectable in 40% of donors. Knowledge of the dynamics of HEV viremia is useful for assessing the risk for transfusion-transmitted hepatitis E.
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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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4
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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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5
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Tsai WC, Chiang HC, Chiu YC, Chien SC, Cheng PN, Chiu HC. Chronic Hepatitis C Virus Infection: An Ongoing Challenge in Screening and Treatment. Life (Basel) 2023; 13:1964. [PMID: 37895346 PMCID: PMC10608250 DOI: 10.3390/life13101964] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 09/22/2023] [Accepted: 09/23/2023] [Indexed: 10/29/2023] Open
Abstract
With the advent of direct-acting antiviral agents (DAA) in the recent few years, hepatitis C virus (HCV) infection has become a curable infectious disease. Successful clearance of HCV could lead to improvement of both hepatic and extrahepatic outcomes, such as complications of cirrhosis, hepatocellular carcinoma, cardiovascular diseases, and incident diabetes. However, challenges persist in reaching the HCV elimination goals of the World Health Organization by 2030. Among these challenges are identifying those already infected or undiagnosed subjects, re-linking to the care of known but untreated HCV-infected subjects, and developing strategies to enhance treatment rates and compliance in specific or high-risk populations. In addition, issues of post-DAA viral clearance, including avoiding or preventing reinfection in high-risk populations and surveillance of hepatocellular carcinoma, are important to consolidate the treatment's short- and long-term efficacies. In the current DAA era, treatment is the most effective prevention strategy not only in its excellent efficacy and safety but also in preventing HCV spread. All of the surveillance or measures should center on DAA treatment in clinical practice.
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Affiliation(s)
| | | | | | | | - Pin-Nan Cheng
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan; (W.-C.T.); (H.-C.C.); (Y.-C.C.); (S.-C.C.)
| | - Hung-Chih Chiu
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan; (W.-C.T.); (H.-C.C.); (Y.-C.C.); (S.-C.C.)
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Martinez-Castillo M, Altamirano-Mendoza I, Zielinski R, Priebe W, Piña-Barba C, Gutierrez-Reyes G. Collagen matrix scaffolds: Future perspectives for the management of chronic liver diseases. World J Clin Cases 2023; 11:1224-1235. [PMID: 36926129 PMCID: PMC10013111 DOI: 10.12998/wjcc.v11.i6.1224] [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: 10/10/2022] [Revised: 11/21/2022] [Accepted: 02/02/2023] [Indexed: 02/23/2023] Open
Abstract
Approximately 1.5 billion chronic liver disease (CLD) cases have been estimated worldwide, encompassing a wide range of liver damage severities. Moreover, liver disease causes approximately 1.75 million deaths per year. CLD is typically characterized by the silent and progressive deterioration of liver parenchyma due to an incessant inflammatory process, cell death, over deposition of extracellular matrix proteins, and dysregulated regeneration. Overall, these processes impair the correct function of this vital organ. Cirrhosis and liver cancer are the main complications of CLD, which accounts for 3.5% of all deaths worldwide. Liver transplantation is the optimal therapeutic option for advanced liver damage. The liver is one of the most common organs transplanted; however, only 10% of liver transplants are successful. In this context, regenerative medicine has made significant progress in the design of biomaterials, such as collagen matrix scaffolds, to address the limitations of organ transplantation (e.g., low donation rates and biocompatibility). Thus, it remains crucial to continue with experimental and clinical studies to validate the use of collagen matrix scaffolds in liver disease.
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Affiliation(s)
- Moises Martinez-Castillo
- Liver, Pancreas and Motility Laboratory, Unit of Experimental Medicine, School of Medicine, Universidad Nacional Autonoma de Mexico, Mexico City 06726, Mexico City, Mexico
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, United States
| | - Itzel Altamirano-Mendoza
- Liver, Pancreas and Motility Laboratory, Unit of Experimental Medicine, School of Medicine, Universidad Nacional Autonoma de Mexico, Mexico City 06726, Mexico City, Mexico
| | - Rafal Zielinski
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, United States
| | - Waldemar Priebe
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, United States
| | - Cristina Piña-Barba
- Materials Research Institute, Universidad Nacional Autónoma de México, Mexico City 06726, Mexico City, Mexico
| | - Gabriela Gutierrez-Reyes
- Liver, Pancreas and Motility Laboratory, Unit of Experimental Medicine, School of Medicine, Universidad Nacional Autonoma de Mexico, Mexico City 06726, Mexico City, Mexico
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Liu H, Yang XL, Dong ZR, Chen ZQ, Hong JG, Wang DX, Li T. Clinical benefits of direct-acting antivirals therapy in hepatitis C virus patients with hepatocellular carcinoma: A systematic review and meta-analysis. J Gastroenterol Hepatol 2022; 37:1654-1665. [PMID: 35722709 DOI: 10.1111/jgh.15915] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Revised: 05/07/2022] [Accepted: 06/14/2022] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND AIM The purpose of the present study was to evaluate the effect of direct-acting antivirals (DAAs) therapy on the clinical outcomes of hepatitis C virus (HCV) patients with hepatocellular carcinoma (HCC). METHODS We searched multiple electronic databases from database inception to June 14, 2021. Meta-analyses were performed separately for HCC recurrence and overall survival (OS). RESULTS A total of 23 studies were identified for the primary analysis. Compared with no intervention, pooled data showed significant benefit from DAAs therapy in reducing recurrence (adjusted HR = 0.55, 95% CI 0.41-0.74, P < 0.001; I2 = 66.6%, P < 0.001) and improving OS (adjusted HR = 0.36, 95% CI 0.16-0.83, P = 0.017; I2 = 90.7%, P < 0.001) of HCV-related HCC patients. Compared with non-responders, patients with sustained virologic response (SVR) had greater benefit from DAAs therapy in reducing recurrence (HR = 0.37, 95% CI 0.16-0.84, P = 0.017; I2 = 58.8%, P = 0.088) and improving OS (HR = 0.17; 95% CI 0.06-0.50; P = 0.001; I2 = 56.4%, P = 0.130). Though DAAs did not show significant advantages over IFN in reducing recurrence (adjusted HR = 0.96, 95% CI 0.72-1.28, P = 0.784; I2 = 0.0%, P = 0.805), there seems to be a trend toward OS benefit from DAAs therapy (adjusted HR = 0.11, 95% CI 0.01-1.19, P = 0.059). CONCLUSION DAAs therapy can prevent recurrence and improve OS of HCV-related HCC patients, especially for patients with SVR. Further prospective randomized controlled trial is warranted to validate these results.
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Affiliation(s)
- Hui Liu
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, China
| | - Xiao-Li Yang
- Department of Nephrology, Jinan Central Hospital, Shandong University, Jinan, China
| | - Zhao-Ru Dong
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, China
| | - Zhi-Qiang Chen
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, China
| | - Jian-Guo Hong
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, China
| | - Dong-Xu Wang
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, China
| | - Tao Li
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, China.,Department of Hepatobiliary Surgery, The Second Hospital of Shandong University, Jinan, China
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8
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Ahmed Z, Shetty A, Victor DW, Kodali S. Viral hepatitis: A narrative review of hepatitis A–E. World J Meta-Anal 2022; 10:99-121. [DOI: 10.13105/wjma.v10.i3.99] [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: 02/16/2022] [Revised: 04/27/2022] [Accepted: 06/24/2022] [Indexed: 02/06/2023] Open
Abstract
Viral hepatitis continues to be a major health concern leading to hepatic decompensation ranging from acute hepatitis to cirrhosis and hepatocellular carcinoma. The hepatic and extrahepatic manifestations are not only debilitating but also associated with a significant economic burden. Over the last two decades, the field of virology has made significant breakthroughs leading to a better understanding of the pathophysiology of viral hepatitis, which in turn has led to new therapeutic options. The advent of direct-acting antiviral agents changed the landscape of hepatitis C virus (HCV) therapy, and new drugs are in the pipeline for chronic hepatitis B virus (HBV) treatment. There has also been a significant emphasis on screening and surveillance programs, widespread availability of vaccines, and linkage of care. Despite these efforts, significant gaps persist in care, and there is a pressing need for increased collaboration and teamwork across the globe to achieve a reduction of disease burden and elimination of HBV and HCV.
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Affiliation(s)
- Zunirah Ahmed
- Division of Gastroenterology and Hepatology, Underwood Center for Digestive Disorders, Houston Methodist Hospital, Houston, TX 77030, United States
| | - Akshay Shetty
- Department of Gastroenterology and Hepatology, University of California, Los Angeles, CA 90095, United States
| | - David W Victor
- Department of Hepatology, J C Walter Jr Transplant Center, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Weill Cornell Medical College, Houston, TX 77030, United States
| | - Sudha Kodali
- Department of Hepatology, J C Walter Jr Transplant Center, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Weill Cornell Medical College, Houston, TX 77030, United States
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9
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Shekhtman L, Navasa M, Sansone N, Crespo G, Subramanya G, Chung TL, Cardozo-Ojeda EF, Pérez-Del-Pulgar S, Perelson AS, Cotler SJ, Forns X, Uprichard SL, Dahari H. Modeling hepatitis C virus kinetics during liver transplantation reveals the role of the liver in virus clearance. eLife 2021; 10:65297. [PMID: 34730511 PMCID: PMC8608386 DOI: 10.7554/elife.65297] [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: 11/29/2020] [Accepted: 11/01/2021] [Indexed: 12/15/2022] Open
Abstract
While the liver, specifically hepatocytes, are widely accepted as the main source of hepatitis C virus (HCV) production, the role of the liver/hepatocytes in clearance of circulating HCV remains unknown. Frequent HCV kinetic data were recorded and mathematically modeled from five liver transplant patients throughout the anhepatic (absence of liver) phase and for 4 hr post-reperfusion. During the anhepatic phase, HCV remained at pre-anhepatic levels (n = 3) or declined (n = 2) with t1/2~1 hr. Immediately post-reperfusion, virus declined in a biphasic manner in four patients consisting of a rapid decline (t1/2 = 5 min) followed by a slower decline (t1/2 = 67 min). Consistent with the majority of patients in the anhepatic phase, when we monitored HCV clearance at 37°C from culture medium in the absence/presence of chronically infected hepatoma cells that were inhibited from secreting HCV, the HCV t1/2 in cell culture was longer in the absence of chronically HCV-infected cells. The results suggest that the liver plays a major role in the clearance of circulating HCV and that hepatocytes may be involved.
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Affiliation(s)
- Louis Shekhtman
- The Program for Experimental & Theoretical Modeling, Division of Hepatology, Department of Medicine, Stritch School of Medicine, Loyola University Medical Center, Maywood, IL, United States.,Network Science Institute, Northeastern University, Boston, MA, United States
| | - Miquel Navasa
- Liver Unit, Hospital Clínic, IDIBAPS and CIBEREHD, University of Barcelona, Barcelona, Spain
| | - Natasha Sansone
- The Program for Experimental & Theoretical Modeling, Division of Hepatology, Department of Medicine, Stritch School of Medicine, Loyola University Medical Center, Maywood, IL, United States.,Department of Microbiology & Immunology, University of Illinois Chicago, Chicago, IL, United States
| | - Gonzalo Crespo
- Liver Unit, Hospital Clínic, IDIBAPS and CIBEREHD, University of Barcelona, Barcelona, Spain
| | - Gitanjali Subramanya
- The Program for Experimental & Theoretical Modeling, Division of Hepatology, Department of Medicine, Stritch School of Medicine, Loyola University Medical Center, Maywood, IL, United States
| | - Tje Lin Chung
- The Program for Experimental & Theoretical Modeling, Division of Hepatology, Department of Medicine, Stritch School of Medicine, Loyola University Medical Center, Maywood, IL, United States.,Institute for Biostatistics and Mathematical Modeling, Department of Medicine, Goethe Universität Frankfurt, Frankfurt, Germany
| | - E Fabian Cardozo-Ojeda
- The Program for Experimental & Theoretical Modeling, Division of Hepatology, Department of Medicine, Stritch School of Medicine, Loyola University Medical Center, Maywood, IL, United States.,Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States
| | - Sofía Pérez-Del-Pulgar
- Liver Unit, Hospital Clínic, IDIBAPS and CIBEREHD, University of Barcelona, Barcelona, Spain
| | - Alan S Perelson
- Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM, United States
| | - Scott J Cotler
- The Program for Experimental & Theoretical Modeling, Division of Hepatology, Department of Medicine, Stritch School of Medicine, Loyola University Medical Center, Maywood, IL, United States
| | - Xavier Forns
- Liver Unit, Hospital Clínic, IDIBAPS and CIBEREHD, University of Barcelona, Barcelona, Spain
| | - Susan L Uprichard
- The Program for Experimental & Theoretical Modeling, Division of Hepatology, Department of Medicine, Stritch School of Medicine, Loyola University Medical Center, Maywood, IL, United States.,The Infectious Disease and Immunology Research Institute, Stritch School of Medicine, Loyola University Medical Center, Maywood, IL, United States
| | - Harel Dahari
- The Program for Experimental & Theoretical Modeling, Division of Hepatology, Department of Medicine, Stritch School of Medicine, Loyola University Medical Center, Maywood, IL, United States
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10
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Llorens-Revull M, Gregori J, Dopazo C, Rodriguez-Frías F, Garcia-Cehic D, Soria ME, Chen Q, Rando A, Perales C, Esteban JI, Quer J, Bilbao I. Study of Quasispecies Complexity and Liver Damage Progression after Liver Transplantation in Hepatitis C Virus Infected Patients. Genes (Basel) 2021; 12:1731. [PMID: 34828337 PMCID: PMC8625210 DOI: 10.3390/genes12111731] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Revised: 10/22/2021] [Accepted: 10/26/2021] [Indexed: 02/07/2023] Open
Abstract
Cirrhosis derived from chronic hepatitis C virus (HCV) infection is still a common indication for liver transplantation (LT). Reinfection of the engrafted liver is universal in patients with detectable viral RNA at the time of transplant and causes fast progression of cirrhosis (within 5 years) in around one-third of these patients. To prevent damage to the liver graft, effective direct-acting antiviral (DAA) therapy is required as soon as possible. However, because of post-LT clinical instability, it is difficult to determine the optimal time to start DAAs with a low risk of complications. Evaluate changes in quasispecies complexity following LT and seek a predictive index of fast liver damage progression to determine the timing of DAA initiation. HCV genomes isolated from pre-LT and 15-day post-LT serum samples of ten patients, who underwent orthotopic LT, were quantified and sequenced using a next-generation sequencing platform. Sequence alignments, phylogenetic trees, quasispecies complexity measures, biostatistics analyses, adjusted R2 values, and analysis of variance (ANOVA) were carried out. Three different patterns of reinfection were observed (viral bottlenecking, conserved pre-LT population, and mixed populations), suggesting that bottlenecking or homogenization of the viral population is not a generalized effect after liver graft reinfection. None of the quasispecies complexity measures predicted the future degree of liver damage. Higher and more uniform viral load (VL) values were observed in all pre-LT samples, but values were more dispersed in post-LT samples. However, VL increased significantly from the pre-LT to 15-day post-LT samples in patients with advanced fibrosis at 1-year post-LT, suggesting that a VL increase on day 15 may be a predictor of fast liver fibrosis progression. HCV kinetics after LT differ between patients and are not fibrosis-dependent. Higher VL at day 15 post-LT versus pre-LT samples may predict fast liver fibrosis progression.
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Affiliation(s)
- Meritxell Llorens-Revull
- Liver Diseases-Viral Hepatitis, Liver Unit, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain; (M.L.-R.); (J.G.); (D.G.-C.); (M.E.S.); (Q.C.); (C.P.); (J.I.E.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Av. Monforte de Lemos, 3-5, 28029 Madrid, Spain; (C.D.); (F.R.-F.); (I.B.)
- Biochemistry, Molecular Biology, Universitat Autònoma de Barcelona (UAB), Campus de la UAB, Plaça Cívica, 08193 Bellaterra, Spain
| | - Josep Gregori
- Liver Diseases-Viral Hepatitis, Liver Unit, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain; (M.L.-R.); (J.G.); (D.G.-C.); (M.E.S.); (Q.C.); (C.P.); (J.I.E.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Av. Monforte de Lemos, 3-5, 28029 Madrid, Spain; (C.D.); (F.R.-F.); (I.B.)
- Roche Diagnostics SL, Avinguda de la Generalitat, 171-173, 08174 Sant Cugat del Vallès, Spain
| | - Cristina Dopazo
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Av. Monforte de Lemos, 3-5, 28029 Madrid, Spain; (C.D.); (F.R.-F.); (I.B.)
- Hepatobiliopancreatic Surgery and Transplant Unit, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain
| | - Francisco Rodriguez-Frías
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Av. Monforte de Lemos, 3-5, 28029 Madrid, Spain; (C.D.); (F.R.-F.); (I.B.)
- Biochemistry, Molecular Biology, Universitat Autònoma de Barcelona (UAB), Campus de la UAB, Plaça Cívica, 08193 Bellaterra, Spain
- Biochemistry and Microbiology Departments, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain;
| | - Damir Garcia-Cehic
- Liver Diseases-Viral Hepatitis, Liver Unit, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain; (M.L.-R.); (J.G.); (D.G.-C.); (M.E.S.); (Q.C.); (C.P.); (J.I.E.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Av. Monforte de Lemos, 3-5, 28029 Madrid, Spain; (C.D.); (F.R.-F.); (I.B.)
| | - Maria Eugenia Soria
- Liver Diseases-Viral Hepatitis, Liver Unit, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain; (M.L.-R.); (J.G.); (D.G.-C.); (M.E.S.); (Q.C.); (C.P.); (J.I.E.)
| | - Qian Chen
- Liver Diseases-Viral Hepatitis, Liver Unit, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain; (M.L.-R.); (J.G.); (D.G.-C.); (M.E.S.); (Q.C.); (C.P.); (J.I.E.)
| | - Ariadna Rando
- Biochemistry and Microbiology Departments, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain;
| | - Celia Perales
- Liver Diseases-Viral Hepatitis, Liver Unit, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain; (M.L.-R.); (J.G.); (D.G.-C.); (M.E.S.); (Q.C.); (C.P.); (J.I.E.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Av. Monforte de Lemos, 3-5, 28029 Madrid, Spain; (C.D.); (F.R.-F.); (I.B.)
| | - Juan Ignacio Esteban
- Liver Diseases-Viral Hepatitis, Liver Unit, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain; (M.L.-R.); (J.G.); (D.G.-C.); (M.E.S.); (Q.C.); (C.P.); (J.I.E.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Av. Monforte de Lemos, 3-5, 28029 Madrid, Spain; (C.D.); (F.R.-F.); (I.B.)
- Medicine, Universitat Autònoma de Barcelona (UAB), Campus de la UAB, Plaça Cívica, 08193 Bellaterra, Spain
| | - Josep Quer
- Liver Diseases-Viral Hepatitis, Liver Unit, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain; (M.L.-R.); (J.G.); (D.G.-C.); (M.E.S.); (Q.C.); (C.P.); (J.I.E.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Av. Monforte de Lemos, 3-5, 28029 Madrid, Spain; (C.D.); (F.R.-F.); (I.B.)
- Biochemistry, Molecular Biology, Universitat Autònoma de Barcelona (UAB), Campus de la UAB, Plaça Cívica, 08193 Bellaterra, Spain
| | - Itxarone Bilbao
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Av. Monforte de Lemos, 3-5, 28029 Madrid, Spain; (C.D.); (F.R.-F.); (I.B.)
- Hepatobiliopancreatic Surgery and Transplant Unit, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain
- Surgery, Universitat Autònoma de Barcelona (UAB), Campus de la UAB, Plaça Cívica, 08193 Bellaterra, Spain
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11
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Liu CH, Chen CY, Su WW, Liu CJ, Lo CC, Huang KJ, Chen JJ, Tseng KC, Chang CY, Peng CY, Shih YL, Huang CS, Kao WY, Yang SS, Tsai MC, Wu JH, Chen PY, Su PY, Hwang JJ, Fang YJ, Lee PL, Tseng CW, Lee FJ, Lai HC, Hsieh TY, Chang CC, Chang CH, Huang YJ, Kao JH. Sofosbuvir/velpatasvir plus ribavirin for Child-Pugh B and Child-Pugh C hepatitis C virus-related cirrhosis. Clin Mol Hepatol 2021; 27:575-588. [PMID: 34255961 PMCID: PMC8524072 DOI: 10.3350/cmh.2021.0155] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2021] [Revised: 06/29/2021] [Accepted: 07/06/2021] [Indexed: 12/09/2022] Open
Abstract
BACKGROUND/AIMS Real-world studies assessing the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) plus ribavirin (RBV) for Child-Pugh B/C hepatitis C virus (HCV)-related cirrhosis are limited. METHODS We included 107 patients with Child-Pugh B/C HCV-related cirrhosis receiving SOF/VEL plus RBV for 12 weeks in Taiwan. The sustained virologic response rates at off-treatment week 12 (SVR12) for the evaluable population (EP), modified EP, and per-protocol population (PP) were assessed. Thesafety profiles were reported. RESULTS The SVR12 rates in the EP, modified EP and PP were 89.7% (95% confidence interval [CI], 82.5-94.2%), 94.1% (95% CI, 87.8-97.3%), and 100% (95% CI, 96.2-100%). Number of patients who failed to achieve SVR12 were attributed to virologic failures. The SVR12 rates were comparable regardless of patient characteristics. One patient discontinued treatment because of adverse events (AEs). Twenty-four patients had serious AEs and six died, but none were related to SOF/VEL or RBV. Among the 96 patients achieving SVR12, 84.4% and 64.6% had improved Child-Pugh and model for endstage liver disease (MELD) scores. Multivariate analysis revealed that a baseline MELD score ≥15 was associated with an improved MELD score of ≥3 (odds ratio, 4.13; 95% CI, 1.16-14.71; P=0.02). Patients with chronic kidney disease (CKD) stage 1 had more significant estimated glomerular filtration rate declines than patients with CKD stage 2 (-0.42 mL/min/1.73 m2/month; P=0.01) or stage 3 (-0.56 mL/min/1.73 m2/month; P<0.001). CONCLUSION SOF/VEL plus RBV for 12 weeks is efficacious and well-tolerated for Child-Pugh B/C HCV-related cirrhosis.
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Affiliation(s)
- Chen-Hua Liu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Yunlin, Taiwan
| | - Chi-Yi Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan
| | - Wei-Wen Su
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Chun-Jen Liu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Ching-Chu Lo
- Department of Internal Medicine, St. Martin De Porres Hospital, Chiayi, Taiwan
| | - Ke-Jhang Huang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Beigang Hospital, Yunlin, Taiwan
| | - Jyh-Jou Chen
- Division of Gastroenterology and Hepatology, Chi-Mei Medical Center, Liouying, Taiwan
| | - Kuo-Chih Tseng
- Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
- School of Medicine, Tzuchi University, Hualien, Taiwan
| | - Chi-Yang Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Fu Jen Catholic University Hospital, Taipei, Taiwan
| | - Cheng-Yuan Peng
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
- School of Medicine, China Medical University, Taichung, Taiwan
| | - Yu-Lueng Shih
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chia-Sheng Huang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Yang Ming Hospital, Chiayi, Taiwan
| | - Wei-Yu Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan
- School of Medicine, Taipei Medical University College of Medicine, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, Taipei Medical University College of Medicine, Taipei, Taiwan
| | - Sheng-Shun Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan
- Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan
| | - Ming-Chang Tsai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Jo-Hsuan Wu
- Hamilton Glaucoma Center, Shiley Eye Institute and Viterbi Family Department of Ophthalmology, University of California, San Diego, CA, USA
| | - Po-Yueh Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan
| | - Pei-Yuan Su
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Jow-Jyh Hwang
- Department of Internal Medicine, St. Martin De Porres Hospital, Chiayi, Taiwan
| | - Yu-Jen Fang
- Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Yunlin, Taiwan
| | - Pei-Lun Lee
- Division of Gastroenterology and Hepatology, Chi-Mei Medical Center, Liouying, Taiwan
| | - Chi-Wei Tseng
- Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
- School of Medicine, Tzuchi University, Hualien, Taiwan
| | - Fu-Jen Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Fu Jen Catholic University Hospital, Taipei, Taiwan
| | - Hsueh-Chou Lai
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
- School of Medicine, China Medical University, Taichung, Taiwan
| | - Tsai-Yuan Hsieh
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chun-Chao Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan
- School of Medicine, Taipei Medical University College of Medicine, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, Taipei Medical University College of Medicine, Taipei, Taiwan
| | - Chung-Hsin Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Yi-Jie Huang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Jia-Horng Kao
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
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12
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Current management & future directions in post-liver transplant recurrence of viral hepatitis. JOURNAL OF LIVER TRANSPLANTATION 2021. [DOI: 10.1016/j.liver.2021.100027] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
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13
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Suda G, Sakamoto N. Recent advances in the treatment of hepatitis C virus infection for special populations and remaining problems. J Gastroenterol Hepatol 2021; 36:1152-1158. [PMID: 32667068 DOI: 10.1111/jgh.15189] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Revised: 07/02/2020] [Accepted: 07/12/2020] [Indexed: 12/16/2022]
Abstract
Hepatitis C virus (HCV) infection is one of the primary causes of liver cirrhosis, hepatocellular carcinoma (HCC), and liver transplantation (LT). The rate of HCV infection is high in patients on hemodialysis and in patients infected with human immunodeficiency virus (HIV). In liver transplant patients with HCV infection, recurrent HCV infection of the transplanted liver is universal and results in rapid liver fibrosis progression. In patients with HCV/HIV coinfection as well, liver fibrosis advances rapidly. Thus, there is an urgent need for prompt HCV infection treatment in these special populations (i.e. HIV/HCV coinfection, HCV infection after LT, and dialysis patients). Interferon (IFN)-based therapy for HCV infection could not achieve a high rate of sustained viral response and could cause severe adverse events in the aforementioned special populations. Direct-acting antivirals (DAAs) have recently been developed, and clinical trials have shown that IFN-free DAA-based therapies are associated with a significantly better safety and therapeutic profile than IFN-based therapies. However, the majority of the initial DAA trials excluded special populations; thus, the efficacy and safety of IFN-free DAA-based therapy in special populations remained to be clearly established. Although recent clinical trials and clinical studies have shown the high efficacy and safety of this therapy even in special populations, several unresolved problems, including emergence of resistance-associated variants after failure to respond to DAAs and HCC occurrence after DAA therapy, still exist. Hence, in this review, we discuss the recent advances in anti-HCV therapy for special populations and the remaining problems regarding this therapy.
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Affiliation(s)
- Goki Suda
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Naoya Sakamoto
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
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14
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Nair SP, Marella HK, Maliakkal B, Snyder H, Handley C, Kothadia JP, Ali B, Satapathy SK, Molnar MZ, Clark I, Jain R, Helmick R, Eymard C, Eason JD. Transplantation of liver from hepatitis C-infected donors to hepatitis C RNA-negative recipients: Histological and virologic outcome. Clin Transplant 2021; 35:e14281. [PMID: 33690929 DOI: 10.1111/ctr.14281] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2020] [Revised: 02/20/2021] [Accepted: 02/27/2021] [Indexed: 01/02/2023]
Abstract
BACKGROUND The virologic and histologic outcomes of a hepatitis C virus (HCV)-infected liver graft into an HCV-negative recipient are not well understood. We aimed to evaluate the sustained virologic response (SVR) rate and the liver histology at 1 year post-Orthotopic liver transplantation (OLT) with an HCV-infected graft. METHODS A total of 33 patients received the HCV antibody (Ab)+/nucleic acid amplification test (NAT)+ graft. Of these patients, 23 were HCV-negative recipients and 10 were HCV-positive recipients. The 1-year biopsy data were available for 24 patients: 15 patients in HCV-negative group who received an HCV Ab+/NAT+graft and 9 patients in HCV-positive group who received an HCV Ab+/NAT+ graft. Patients with (+) HCV ribonucleic acid (RNA) were started on direct-acting antiviral (DAA) treatment approximately 107 days after OLT using either a Glecaprevir-Pibrentasvir or Sofosbuvir-Velpatasvir or Sofosbuvir-Ledipasvir. RESULTS All patients (n = 33) were treated with DAA and achieved SVR. The 1-year post-OLT liver biopsies were available in 24 patients: 9 patients had F1 and F2 fibrosis and 17 patients had minimal to moderate inflammation. There was no statistical difference in fibrosis and inflammation between the HCV-negative vs. HCV-positive recipients. All patients who received the NAT+ graft developed viremia and subsequently achieved SVR with treatment. CONCLUSION At 1 year protocol liver biopsy, patients had inflammation consistent with viral hepatitis despite the successful eradication of HCV.
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Affiliation(s)
- Satheesh P Nair
- James D. Eason Transplant Institute, University of Tennessee Health Science Center', Methodist University Hospital, Memphis, TN, USA
- Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Hemnishil K Marella
- James D. Eason Transplant Institute, University of Tennessee Health Science Center', Methodist University Hospital, Memphis, TN, USA
- Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Benedict Maliakkal
- James D. Eason Transplant Institute, University of Tennessee Health Science Center', Methodist University Hospital, Memphis, TN, USA
- Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Heather Snyder
- James D. Eason Transplant Institute, University of Tennessee Health Science Center', Methodist University Hospital, Memphis, TN, USA
| | - Charlotte Handley
- James D. Eason Transplant Institute, University of Tennessee Health Science Center', Methodist University Hospital, Memphis, TN, USA
| | - Jiten P Kothadia
- James D. Eason Transplant Institute, University of Tennessee Health Science Center', Methodist University Hospital, Memphis, TN, USA
- Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Bilal Ali
- James D. Eason Transplant Institute, University of Tennessee Health Science Center', Methodist University Hospital, Memphis, TN, USA
| | - Sanjaya K Satapathy
- Department of Medicine, Zucker School of Medicine at Hofstra, Sandra Atlas Bass Center for Liver Diseases & Transplantation, Northshore University Hospital/Northwell Health, Manhasset, NY, USA
| | - Miklos Z Molnar
- James D. Eason Transplant Institute, University of Tennessee Health Science Center', Methodist University Hospital, Memphis, TN, USA
| | - Ian Clark
- Department of Pathology, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Richa Jain
- Department of Pathology, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Ryan Helmick
- James D. Eason Transplant Institute, University of Tennessee Health Science Center', Methodist University Hospital, Memphis, TN, USA
| | - Corey Eymard
- James D. Eason Transplant Institute, University of Tennessee Health Science Center', Methodist University Hospital, Memphis, TN, USA
| | - James D Eason
- James D. Eason Transplant Institute, University of Tennessee Health Science Center', Methodist University Hospital, Memphis, TN, USA
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15
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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: 748] [Impact Index Per Article: 149.6] [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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16
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Araujo A, Valenzuela-Granados V, Lopes AB, Michalczuk MT, Mantovani A, Alvares-da-Silva MR. Sofosbuvir-based antiviral therapy in patients with recurrent HCV infection after liver transplant: A real-life experience. Ann Hepatol 2020; 18:450-455. [PMID: 31028014 DOI: 10.1016/j.aohep.2018.09.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2017] [Revised: 09/16/2018] [Accepted: 09/28/2018] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND AIM Recurrent HCV infection after liver transplant (LT) has a negative impact on graft and patient survival. The aim of this study is to describe the efficacy and safety of sofosbuvir (SOF-based) regimens in the treatment of recurrent HCV after liver transplant (LT). MATERIALS AND METHODS This retrospective study included 68 adults with recurrent HCV infection after LT, treated with different SOF-based regimens between March 2015 and December 2016. The choice of regimens, their duration and use of ribavirin (RBV) was made by the treating physician. The efficacy of antiviral treatment was assessed based on the sustained viral response obtained 12 weeks after the end of treatment (SVR12), according to an intention-to-treat analysis. RESULTS The most frequent HCV genotypes were 1 and 3 (n=35, 51.4% and n=31, 45.6%, respectively). Only 22 patients were treatment naïve (32.3%) and 7 had cirrhosis (10.2%). SOF+daclatasvir (DCV) was the most commonly used regimen (n=63, 92.6%). Most patients used RBV (n=56, 82.3%) and were treated for 12 weeks (n=66, 97%). Overall SVR12 was 95.5% (65/68 patients). Three patients had virologic failure. Three patients had serious adverse events, however, no one discontinued treatment prematurely. RBV-related anaemia was the most frequent adverse event (n=34, 50%). Four patients had severe cellular graft rejection after HCV elimination, while immunosuppression remained stable. CONCLUSION SOF-based therapy is highly effective and safe to treat HCV recurrence after LT. Cellular graft rejection following the successful treatment of HCV needs further investigation.
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Affiliation(s)
- Alexandre Araujo
- Division of Gastroenterology and Hepatology, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
| | | | - Antonio B Lopes
- Division of Gastroenterology and Hepatology, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
| | - Matheus T Michalczuk
- Division of Gastroenterology and Hepatology, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
| | - Augusto Mantovani
- Division of Gastroenterology and Hepatology, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
| | - Mario R Alvares-da-Silva
- Division of Gastroenterology and Hepatology, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil; World Gastroenterology Organisation Porto Alegre Hepatology Training Center, Porto Alegre, RS, Brazil; Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
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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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Japan Society of Hepatology guidelines for the management of hepatitis C virus infection: 2019 update. Hepatol Res 2020; 50:791-816. [PMID: 32343477 DOI: 10.1111/hepr.13503] [Citation(s) in RCA: 70] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Revised: 03/03/2020] [Accepted: 03/22/2020] [Indexed: 12/12/2022]
Abstract
The Drafting Committee for Hepatitis Management Guidelines established by the Japan Society of Hepatology (JSH) drafted the first version of the clinical practice guidelines for the management of hepatitis C virus (HCV) infection in 2012. Since then, we have been publishing updates as new drugs for hepatitis C become available and new indications for existing drugs are added. The new approval of sofosbuvir/velpatasvir prompted us to publish the seventh version of the guidelines in Japanese in March 2019. We also published the first English-language version of the JSH guidelines in 2013 and English versions of updates made to the Japanese-language guidelines in 2014 and 2016. In 2020, the Committee has decided to publish a new English version, covering general information about treatment for hepatitis C, drugs used, recommended treatments for chronic hepatitis and cirrhosis, and special populations, such as patients who have renal impairment, are on dialysis, or have developed recurrence of hepatitis C after liver transplantation. Furthermore, the Committee has released a separate publication covering the protective effect of antiviral therapy against hepatocarcinogenesis.
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Jothimani D, Venugopal R, Vij M, Rela M. Post liver transplant recurrent and de novo viral infections. Best Pract Res Clin Gastroenterol 2020; 46-47:101689. [PMID: 33158469 PMCID: PMC7519014 DOI: 10.1016/j.bpg.2020.101689] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Accepted: 09/22/2020] [Indexed: 01/31/2023]
Abstract
Survival following liver transplantation has changed dramatically owing to improvement in surgical techniques, peri-operative care and optimal immunosuppressive therapy. Post-Liver transplant (LT) de novo or recurrent viral infection continues to cause major allograft dysfunction, leading to poor graft and patient survival in untreated patients. Availability of highly effective antiviral drugs has significantly improved post-LT survival. Patients transplanted for chronic hepatitis B infection should receive life-long nucleos(t)ide analogues, with or without HBIg for effective viral control. Patients with chronic hepatitis C should be commenced on directly acting antiviral (DAA) drugs prior to transplantation. DAA therapy for post-LT recurrent hepatitis C infection is associated with close to 100% sustained virological response (SVR), irrespective of genotype. De novo chronic Hepatitis E infection is an increasingly recognised cause of allograft dysfunction in LT recipients. Untreated chronic HEV infection of the graft may lead to liver fibrosis and allograft failure. CMV and EBV can reactivate leading to systemic illness following liver transplantation. With COVID-19 pandemic, post-transplant patients are at risk of SARS-Co-V2 infection. Majority of the LT recipients require hospitalization, and the mortality in this population is around 20%. Early recognition of allograft dysfunction and identification of viral aetiology is essential in the management of post-LT de novo or recurrent infections. Optimising immunosuppression is an important step in reducing the severity of allograft damage in the treatment of post-transplant viral infections. Viral clearance or control can be achieved by early initiation of high potency antiviral therapy.
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Affiliation(s)
- Dinesh Jothimani
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India.
| | - Radhika Venugopal
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India
| | - Mukul Vij
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India
| | - Mohamed Rela
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India
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Fu H, Dong J, Sun Z, Zhang X, Yu A, Chen G, Li W. Efficacy and safety of sofosbuvir-containing regimens in patients with chronic hepatitis C virus infection after liver transplantation: a meta-analysis. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:648. [PMID: 32566585 PMCID: PMC7290620 DOI: 10.21037/atm-20-3074] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Background This meta-analysis evaluated the efficacy and safety of a sofosbuvir (SOF)-containing regimen in patients with hepatitis C virus (HCV) infection after liver transplantation (LT). Methods We performed a systematic search for relevant published data on the PubMed, EMBASE, and Cochrane Library databases. Studies that evaluated any regimen in which SOF was used to treat patients with HCV infection after LT and reported the sustained virologic response 12 weeks (SVR12) after therapy were included. Results A total of 12 studies, involving 892 patients, were included in this analysis. The pooled estimate of SVR12 (sustained virologic response 12 weeks) was 88.1%. Subgroup analysis showed that patients who received SOF plus other DAAs had higher SVR12 than those treated with SOF plus ribavirin or peg-IFN. The pooled incidence of any adverse events (AEs) was 73.7%. Conclusions The results of this study showed that the treatment response of SOF-containing regimens in patients with HCV infection after LT was satisfactory. However, more attention needs to be paid to the high rate of AEs associated with such regimens.
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Affiliation(s)
- Hua Fu
- Hospital and Institute of Hepatobiliary Surgery, Chinese PLA General Hospital, Chinese PLA Medical School, Beijing, China.,Department of Hepatobiliary Surgery, Affiliated Hospital of Chengde Medical University, Chengde, China
| | - Jiahong Dong
- Hospital and Institute of Hepatobiliary Surgery, Chinese PLA General Hospital, Chinese PLA Medical School, Beijing, China.,Center of Hepatopancreatobiliary Diseases, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Zhide Sun
- Department of Hepatobiliary Surgery, Affiliated Hospital of Chengde Medical University, Chengde, China
| | - Xuejun Zhang
- Department of Hepatobiliary Surgery, Affiliated Hospital of Chengde Medical University, Chengde, China
| | - Aijun Yu
- Department of Hepatobiliary Surgery, Affiliated Hospital of Chengde Medical University, Chengde, China
| | - Guoli Chen
- Department of Hepatobiliary Surgery, Affiliated Hospital of Chengde Medical University, Chengde, China
| | - Wei Li
- Department of Hepatobiliary Surgery, Affiliated Hospital of Chengde Medical University, Chengde, China
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Mao JX, Guo WY, Guo M, Liu C, Teng F, Ding GS. Acute rejection after liver transplantation is less common, but predicts better prognosis in HBV-related hepatocellular carcinoma patients. Hepatol Int 2020; 14:347-361. [PMID: 32140981 DOI: 10.1007/s12072-020-10022-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2019] [Accepted: 02/04/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND With a novel finding of significantly lower incidence of acute rejection (AR) in patients with hepatocellular carcinoma (HCC) after liver transplantation, compared with those with benign end-stage liver disease (BESLD), in a large national cohort, we analyzed the correlations among the perioperative immuno-inflammation status, postoperative AR, and prognosis in HCC and BESLD patients with same etiology of hepatitis B virus (HBV), who underwent liver transplantation. METHODS Patients who underwent liver transplantation due to HBV-related HCC or BESLD and experienced AR between September 2008 and April 2017 were analyzed retrospectively and followed up until April 2018. HCC patients with AR were matched with those without AR according to tumor stage and immunosuppressant concentration, at a 1:3 ratio. Preoperative immuno-inflammation status and prognosis of patients in both groups were compared. RESULTS The overall incidences of AR in patients with HCC and BESLD were 8.60% and 10.61%, respectively. The postoperative 28-day incidence of AR was significantly lower in HCC compared with BESLD patients (3.23% vs 7.08%, p = 0.031). Compared with BESLD patients, the rejection activity index and perioperative CD4/CD8 ratio were significantly lower (p = 0.047 and p < 0.001, respectively), while platelet/lymphocyte ratio was significantly higher in HCC patients (p = 0.041). Later tumor stage in HCC patients was associated with higher systemic immuno-inflammation index, neutrophil/lymphocyte ratio, monocyte/lymphocyte ratio, platelet/lymphocyte ratio, aspartate aminotransferase/lymphocyte ratio, C-reactive protein/albumin ratio and fibrinogen level, and lower CD4/CD8 ratio before transplantation. In HCC patients with AR, the percentage of regulatory T cells (CD4+/CD25+) and the level of IL-10 significantly decreased (p = 0.0023, < 0.0001, respectively), while Th1/Th2 ratio, levels of IFN-γ and IL-2 markedly increased before transplantation (p = 0.0018, 0.0059, 0.0416, respectively). Preoperative monocyte/lymphocyte ratio was an independent risk factor for overall and recurrence-free survival after liver transplantation in HCC patients (p = 0.025, < 0.001, respectively). The 1-, 3-, and 5-year survival rates were 76%, 71% and 53% in the AR group, and 67%, 37% and 25% in the non-AR group (p = 0.042). CONCLUSION Preoperative tumor-related immunosuppression may persist after liver transplantation in HCC patients, and reduce the incidence of AR. AR after liver transplantation may indicate a better prognosis in HCC patients.
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Affiliation(s)
- Jia-Xi Mao
- Department of Liver Surgery and Organ Transplantation, Changzheng Hospital, Navy Medical University, Shanghai, China
| | - Wen-Yuan Guo
- Department of Liver Surgery and Organ Transplantation, Changzheng Hospital, Navy Medical University, Shanghai, China
| | - Meng Guo
- Department of Liver Surgery and Organ Transplantation, Changzheng Hospital, Navy Medical University, Shanghai, China.,National Key Laboratory of Medical Immunology & Institute of Immunology, Navy Medical University, Shanghai, China
| | - Cong Liu
- Department of Liver Surgery and Organ Transplantation, Changzheng Hospital, Navy Medical University, Shanghai, China
| | - Fei Teng
- Department of Liver Surgery and Organ Transplantation, Changzheng Hospital, Navy Medical University, Shanghai, China.
| | - Guo-Shan Ding
- Department of Liver Surgery and Organ Transplantation, Changzheng Hospital, Navy Medical University, Shanghai, China.
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Wu SH, Loong CC, Chu CJ, Su CW, Lin CC, Hsia CY, Liu C, Lee SD, Wang YJ, Lee FY, Linb NC, Chen CY, Huang YH, Hou MC. Highly effective treatment response and well tolerability by all oral direct acting antivirals for chronic hepatitis C patients post organ transplantation. J Chin Med Assoc 2020; 83:18-24. [PMID: 31714442 DOI: 10.1097/jcma.0000000000000222] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Immunosuppressant-related acceleration of fibrosis has been documented in chronic hepatitis C (CHC) patients who receive organ transplantation (Tx), and sustained virological response (SVR) rates for these patients by pegylated interferon (IFN)-based therapy are generally poor and associated with unfavorable safety profiles. In addition, IFN treatment varies by patient and poses a high risk of post-renal Tx graft rejection. This study was aimed to investigate the efficacy and safety of all oral direct acting antivirals (DAAs) for CHC patients following organ Tx. METHODS A total of 32 organ Tx (liver: 17, kidney: 13, kidney then liver: 1, and heart: 1) patients with CHC on an oral DAA (paritaprevir/ritonavir, ombitasvir, and dasabuvir: 11, daclatasvir and asunaprevir: 4, sofosbuvir-based: 17) were enrolled in the study. DAAs regimen was based by genotype/subtype, patient characteristics, drug interaction profiles, and health insurance coverage. RESULTS Mean patient age was 61.4 ± 9.5 years, 50.0% male, and 15.6% with cirrhosis. Fourteen (43.7%) patients experienced unsuccessful IFN treatment. Genotype distribution was as follows: 1a: 6, 1b: 17, 2: 7, 3: 1, and 6: 1. Mean time between Tx and DAAs therapy was 77.3 ± 11.0 months. Baseline HCV RNA before DAAs was 6.20 ± 0.19 log10 IU/mL. After DAAs, the distribution of week 2 HCV RNA was as follows: <15 IU/mL (53.1%), 15 to 50 IU/mL (15.6%), 50 to 100 IU/mL (6.3%), and >100 IU/mL (25.0%), respectively. The rates of undetectable HCV RNA (<15 IU/mL) at week 4 and end-of-treatment were 93.8% and 100%, respectively. Subjective adverse events during therapy were generally mild, with no treatment terminations. After posttreatment follow-up, all 32 patients (100%) achieved SVR12. CONCLUSION Highly responsive treatment and favorable tolerability were achieved by all oral DAAs in this difficult-to-treat patient population.
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Affiliation(s)
- Sih-Hsien Wu
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Che-Chuan Loong
- Division of Transplantation Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Surgery, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Chi-Jen Chu
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Chien-Wei Su
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Chung-Chi Lin
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
- Healthcare and Services Center, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Cheng-Yuan Hsia
- Division of Transplantation Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Surgery, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Chinsu Liu
- Division of Transplantation Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Surgery, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
- Division of Pediatric Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Shou-Dong Lee
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
- Division of Gastroenterology, Department of Medicine, Cheng Hsin General Hospital, Taipei, Taiwan, ROC
| | - Yuan-Jen Wang
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
- Healthcare and Services Center, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Fa-Yauh Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Niang-Cheng Linb
- Faculty of Surgery, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Cheng-Yen Chen
- Division of Transplantation Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Surgery, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Ming-Chih Hou
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
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Barik S. Molecular Interactions between Pathogens and the Circadian Clock. Int J Mol Sci 2019; 20:ijms20235824. [PMID: 31756974 PMCID: PMC6928883 DOI: 10.3390/ijms20235824] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2019] [Revised: 11/17/2019] [Accepted: 11/17/2019] [Indexed: 12/12/2022] Open
Abstract
The daily periodicity of the Earth's rotation around the Sun, referred to as circadian (Latin "circa" = about, and "diem" = day), is also mirrored in the behavior and metabolism of living beings. The discovery that dedicated cellular genes control various aspects of this periodicity has led to studies of the molecular mechanism of the circadian response at the cellular level. It is now established that the circadian genes impact on a large network of hormonal, metabolic, and immunological pathways, affecting multiple aspects of biology. Recent studies have extended the role of the circadian system to the regulation of infection, host-pathogen interaction, and the resultant disease outcome. This critical review summarizes our current knowledge of circadian-pathogen interaction at both systemic and cellular levels, but with emphasis on the molecular aspects of the regulation. Wherever applicable, the potential of a direct interaction between circadian factors and pathogenic macromolecules is also explored. Finally, this review offers new directions and guidelines for future research in this area, which should facilitate progress.
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Llovet LP, Sciarrone S, Rodríguez-Tajes S, Montironi C, Mescoli C, Rugge M, Crespo G, Burra P, Forns X, Diaz A, Londoño MC. Ductular reaction and hepatocyte ballooning identify patients with fibrosing cholestatic hepatitits after liver transplantation. GASTROENTEROLOGIA Y HEPATOLOGIA 2019; 43:14-21. [PMID: 31495536 DOI: 10.1016/j.gastrohep.2019.07.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/09/2019] [Revised: 06/18/2019] [Accepted: 07/04/2019] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Diagnosis of severe hepatitis C recurrence is based on analytical and histological criteria but there is little information about their correlation. AIM To assess the accuracy of laboratory criteria for the diagnosis of fibrosing cholestatic hepatitis (FCH). PATIENTS AND METHODS Retrospective analysis of prospectively collected data form HCV positive patients who underwent liver transplantation (LT) between 2000 and 2014 in two European university hospitals. Patients were classified according to laboratory criteria such as FCH, cholestatic hepatitis (CH) and non-cholestatic acute hepatitis (NCAH). Histological characteristics were also evaluated. RESULTS Seventy patients with acute HCV recurrence within the first year after LT with an available liver biopsy were included in the study. Most patients were male (70%) with a median age of 58 years (50-64) and infected with genotype 1b (71.4%). Median time from LT to diagnosis of recurrence was 2.96 months (2.1-5.3). Thirty-nine patients were classified as FCH, 21 as CH and 10 as NCAH. Marked hepatocyte ballooning and ductular reaction were associated with the presence of FCH with an OR of 4.66 (p=0.047) and 20.58 (p=0.025), respectively. Considering liver biopsy as the gold standard, the sensitivity, specificity, positive and negative predictive values of the analytical criteria were 0.8, 0.5, 0.3 and 0.9, respectively. However, correlation between histological and analytical criteria was poor (k=0.033). DISCUSSION Analytical criteria may be used to rule out the presence of FCH, but a biopsy is mandatory to confirm the diagnosis. Ductular reaction and hepatocyte ballooning were independent predictors of FCH.
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Affiliation(s)
| | - Salvatore Sciarrone
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | | | - Carla Montironi
- Pathology Department, Hospital Clínic Barcelona, Barcelona, Spain
| | - Claudia Mescoli
- Surgical Pathology & Cytopathology Unit, Department of Medicine (DIMED), Padua University Hospital, Padua, Italy
| | - Massimo Rugge
- Surgical Pathology & Cytopathology Unit, Department of Medicine (DIMED), Padua University Hospital, Padua, Italy
| | - Gonzalo Crespo
- Liver Unit, Hospital Clínic Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain
| | - Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Xavier Forns
- Liver Unit, Hospital Clínic Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain
| | - Alba Diaz
- Pathology Department, Hospital Clínic Barcelona, Barcelona, Spain
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Te H, Doucette K. Viral hepatitis: Guidelines by the American Society of Transplantation Infectious Disease Community of Practice. Clin Transplant 2019; 33:e13514. [DOI: 10.1111/ctr.13514] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2019] [Accepted: 02/12/2019] [Indexed: 12/13/2022]
Affiliation(s)
- Helen Te
- Center for Liver Diseases, Section of Gastroenterology, Hepatology and Nutrition University of Chicago Medicine Chicago Illinois
| | - Karen Doucette
- Division of Infectious Diseases University of Alberta Edmonton Alberta Canada
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Belli LS, Perricone G, Adam R, Cortesi PA, Strazzabosco M, Facchetti R, Karam V, Salizzoni M, Andujar RL, Fondevila C, De Simone P, Morelli C, Fabregat-Prous J, Samuel D, Agarwaal K, Moreno Gonzales E, Charco R, Zieniewicz K, De Carlis L, Duvoux C. Impact of DAAs on liver transplantation: Major effects on the evolution of indications and results. An ELITA study based on the ELTR registry. J Hepatol 2018; 69:810-817. [PMID: 29940268 DOI: 10.1016/j.jhep.2018.06.010] [Citation(s) in RCA: 174] [Impact Index Per Article: 24.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2018] [Revised: 06/05/2018] [Accepted: 06/14/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Direct-acting antivirals (DAAs) have dramatically improved the outcome of patients with hepatitis C virus (HCV) infection including those with decompensated cirrhosis (DC). We analyzed the evolution of indications and results of liver transplantation (LT) in the past 10 years in Europe, focusing on the changes induced by the advent of DAAs. METHODS This is a cohort study based on data from the European Liver Transplant Registry (ELTR). Data of adult LTs performed between January 2007 to June 2017 for HCV, hepatitis B virus (HBV), alcohol (EtOH) and non-alcoholic steatohepatitis (NASH) were analyzed. The period was divided into different eras: interferon (IFN/RBV; 2007-2010), protease inhibitor (PI; 2011-2013) and second generation DAA (DAA; 2014-June 2017). RESULTS Out of a total number of 60,527 LTs, 36,382 were performed in patients with HCV, HBV, EtOH and NASH. The percentage of LTs due to HCV-related liver disease varied significantly over time (p <0.0001), decreasing from 22.8% in the IFN/RBV era to 17.4% in the DAA era, while those performed for NASH increased significantly (p <0.0001). In the DAA era, the percentage of LTs for HCV decreased significantly (p <0.0001) from 21.1% (first semester 2014) to 10.6% (first semester 2017). This decline was more evident in patients with DC (HCV-DC, -58.0%) than in those with hepatocellular carcinoma (HCC) associated with HCV (HCV-HCC, -41.2%). Conversely, three-year survival of LT recipients with HCV-related liver disease improved from 65.1% in the IFN/RBV era to 76.9% in the DAA era, and is now comparable to the survival of recipients with HBV infection (p = 0.3807). CONCLUSIONS In Europe, the number of LTs due to HCV infection is rapidly declining for both HCV-DC and HCV-HCC indications and post-LT survival has dramatically improved over the last three years. This is the first comprehensive study of the overall impact of DAA treatment for HCV on liver transplantation in Europe. LAY SUMMARY After the advent of direct-acting antivirals in 2014, a dramatic decline was observed in the number of liver transplants performed both in patients with decompensated cirrhosis due to hepatitis C virus (HCV), minus 60%, and in those with hepatocellular carcinoma associated with HCV, minus 41%. Furthermore, this is the first large-scale study demonstrating that the survival of liver transplant recipients with HCV-related liver disease has dramatically improved over the last three years and is now comparable to the survival of recipients with hepatitis B virus infection. The reduction in HCV-related indications for LT means that there is a greater availability of livers, at least 600 every year, which can be allocated to patients with indications other than HCV.
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Affiliation(s)
- Luca Saverio Belli
- Gastroenterology and Hepatology, Liver Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy.
| | - Giovanni Perricone
- Gastroenterology and Hepatology, Liver Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Rene Adam
- Centre Hépatobiliaire, Université Paris-Sud, Hôpital Paul Brousse, F-94804 Villejuif, France
| | - Paolo A Cortesi
- Research Centre on Public Health (CESP), University of Milan-Bicocca, Monza, Italy
| | | | - Rita Facchetti
- Research Centre on Public Health (CESP), University of Milan-Bicocca, Monza, Italy
| | - Vincent Karam
- Centre Hépatobiliaire, Université Paris-Sud, Hôpital Paul Brousse, F-94804 Villejuif, France
| | - Mauro Salizzoni
- Centro trapianti di fegato, AO San Giovanni Battista, Torino, Italy
| | - Rafael Lopez Andujar
- Hospital Universitario y Politecnico La Fe, Unidad de Chirurgia HPB y TX, Valencia, Spain
| | - Costantino Fondevila
- Hospital Clinic de Barcelona, Dep. of Surgery, University of Barcelona Villaroel, Barcelona, Spain
| | - Paolo De Simone
- Hepatobiliary Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Italy
| | - Cristina Morelli
- Liver and Multiorgan Transplantation, Policlinico Sant'Orsola-Malpighi, Bologna, Italy
| | - Joan Fabregat-Prous
- Hospital Universitari de Bellvitge, Unidad de Transplante Hepatico, Barcelona, Spain
| | - Didier Samuel
- Centre Hépatobiliaire, Université Paris-Sud, Hôpital Paul Brousse, F-94804 Villejuif, France
| | - Kosh Agarwaal
- Institute of Liver Diseases, King's College Hospital, Liver Unit, London, UK
| | | | - Ramon Charco
- Hospital Universitario Vall D Hebron HBP, Surgery & Transplant Department, Barcelona, Spain
| | - Krzysztof Zieniewicz
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Poland
| | - Luciano De Carlis
- Chirurgia generale 2 e Trapianti, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy
| | - Christophe Duvoux
- Department of Hepatology and Liver Transplant Unit, Henri Mondor Hospital, AssistancePublique-Hôpitaux de Paris, Paris-Est University, Creteil, France
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Manzardo C, Londoño MC, Castells LL, Testillano M, Luis Montero J, Peñafiel J, Subirana M, Moreno A, Aguilera V, Luisa González-Diéguez M, Calvo-Pulido J, Xiol X, Salcedo M, Cuervas-Mons V, Manuel Sousa J, Suarez F, Serrano T, Ignacio Herrero J, Jiménez M, Fernandez JR, Giménez C, Del Campo S, Esteban-Mur JI, Crespo G, Moreno A, de la Rosa G, Rimola A, Miro JM. Direct-acting antivirals are effective and safe in HCV/HIV-coinfected liver transplant recipients who experience recurrence of hepatitis C: A prospective nationwide cohort study. Am J Transplant 2018; 18:2513-2522. [PMID: 29963780 DOI: 10.1111/ajt.14996] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2017] [Revised: 06/04/2018] [Accepted: 06/22/2018] [Indexed: 01/25/2023]
Abstract
Direct-acting antivirals have proved to be highly efficacious and safe in monoinfected liver transplant (LT) recipients who experience recurrence of hepatitis C virus (HCV) infection. However, there is a lack of data on effectiveness and tolerability of these regimens in HCV/HIV-coinfected patients who experience recurrence of HCV infection after LT. In this prospective, multicenter cohort study, the outcomes of 47 HCV/HIV-coinfected LT patients who received DAA therapy (with or without ribavirin [RBV]) were compared with those of a matched cohort of 148 HCV-monoinfected LT recipients who received similar treatment. Baseline characteristics were similar in both groups. HCV/HIV-coinfected patients had a median (IQR) CD4 T-cell count of 366 (256-467) cells/µL. HIV-RNA was <50 copies/mL in 96% of patients. The DAA regimens administered were SOF + LDV ± RBV (34%), SOF + SMV ± RBV (31%), SOF + DCV ± RBV (27%), SMV + DCV ± RBV (5%), and 3D (3%), with no differences between the groups. Treatment was well tolerated in both groups. Rates of SVR (negative serum HCV-RNA at 12 weeks after the end of treatment) were high and similar for coinfected and monoinfected patients (95% and 94%, respectively; P = .239). Albeit not significant, a trend toward lower SVR rates among patients with advanced fibrosis (P = .093) and genotype 4 (P = .088) was observed. In conclusion, interferon-free regimens with DAAs for post-LT recurrence of HCV infection in HIV-infected individuals were highly effective and well tolerated, with results comparable to those of HCV-monoinfected patients.
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Affiliation(s)
| | - Maria C Londoño
- Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain
| | - LLuís Castells
- CIBEREHD, Barcelona, Spain.,Liver Unit, Internal Medicine Department, Hospital Vall d'Hebrón, Universitat Autónoma de Barcelona, Barcelona, Spain
| | | | - José Luis Montero
- CIBEREHD, Barcelona, Spain.,Hospital Universitario Reina Sofía-IMIBIC Córdoba, Cordoba, Spain
| | - Judit Peñafiel
- Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Marta Subirana
- Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Ana Moreno
- Hospital Universitario Ramón y Cajal-IRYCIS, Madrid, Spain
| | | | | | | | - Xavier Xiol
- Hospital de Bellvitge-IDIBELL, University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain
| | | | | | | | | | - Trinidad Serrano
- CIBEREHD, Barcelona, Spain.,Hospital Universitario Lozano Blesa, ISS Aragón, Zaragoza, Spain
| | - Jose Ignacio Herrero
- CIBEREHD, Barcelona, Spain.,Clínica Universidad de Navarra, IdiSNA, Pamplona, Spain
| | | | - José R Fernandez
- Servicio de Digestivo, Hospital Universitario Cruces, Barakaldo, Barakaldo
| | | | | | - Juan I Esteban-Mur
- CIBEREHD, Barcelona, Spain.,Liver Unit, Internal Medicine Department, Hospital Vall d'Hebrón, Universitat Autónoma de Barcelona, Barcelona, Spain
| | - Gonzalo Crespo
- Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain.,CIBEREHD, Barcelona, Spain
| | - Asunción Moreno
- Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain
| | | | - Antoni Rimola
- Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain.,CIBEREHD, Barcelona, Spain
| | - Jose M Miro
- Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain
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28
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Berenguer M, Agarwal K, Burra P, Manns M, Samuel D. The road map toward an hepatitis C virus-free transplant population. Am J Transplant 2018; 18:2409-2416. [PMID: 29935050 DOI: 10.1111/ajt.14976] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2017] [Revised: 05/14/2018] [Accepted: 06/15/2018] [Indexed: 01/25/2023]
Abstract
Antiviral therapy to eradicate hepatitis C virus (HCV) infection improves outcomes in patients undergoing liver transplantation (LT) for advanced chronic HCV with or without hepatocellular carcinoma. Traditionally, antiviral therapy focused on the use of interferon (IFN)-based regimens, with antiviral treatment initiated in the posttransplant period once recurrent HCV disease with fibrosis in the allograft was identified. The use of IFN-based therapy was limited in pretransplant patients with advanced liver disease. Earlier intervention, either before transplantation or early after LT, is now feasible with the advent of second-generation direct-acting antiviral agents (DAAs) with superior tolerability and efficacy to IFN-based therapy. These agents have the potential to reduce the number of patients developing HCV-related complications requiring LT and retransplantation, as well as reducing the demand for donor organs. We discuss the pros and cons of pretransplant, peritransplant, and posttransplant therapy with current DAAs, citing available data from clinical trials and real-world experience.
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Affiliation(s)
- M Berenguer
- Liver Transplantation & Hepatology Unit, Hospital Universitario La Fe, University of Valencia-CIBEReHD, Valencia, Spain
| | - K Agarwal
- Institute of Liver Studies, King's College Hospital, London, UK
| | - P Burra
- Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, Padova, Italy
| | - M Manns
- Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany
| | - D Samuel
- Inserm-Paris Sud Unit 1193, Centre Hepatobiliaire, Hopital Paul Brousse, Villejuif, France
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29
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Reau N, Kwo PY, Rhee S, Brown RS, Agarwal K, Angus P, Gane E, Kao J, Mantry PS, Mutimer D, Reddy KR, Tran TT, Hu YB, Gulati A, Krishnan P, Dumas EO, Porcalla A, Shulman NS, Liu W, Samanta S, Trinh R, Forns X. Glecaprevir/Pibrentasvir Treatment in Liver or Kidney Transplant Patients With Hepatitis C Virus Infection. Hepatology 2018; 68:1298-1307. [PMID: 29672891 PMCID: PMC6220874 DOI: 10.1002/hep.30046] [Citation(s) in RCA: 130] [Impact Index Per Article: 18.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2018] [Revised: 04/04/2018] [Accepted: 04/13/2018] [Indexed: 12/15/2022]
Abstract
Well-tolerated, ribavirin-free, pangenotypic hepatitis C virus (HCV) treatments for transplant recipients remain a high priority. Once-daily glecaprevir/pibrentasvir demonstrates high rates of sustained virologic response at 12 weeks posttreatment (SVR12) across all major HCV genotypes (GTs). This trial evaluated the safety and efficacy of glecaprevir/pibrentasvir for patients with chronic HCV GT1-6 infection who had received a liver or kidney transplant. MAGELLAN-2 was a phase 3, open-label trial conducted in patients who were ≥3 months posttransplant. Patients without cirrhosis who were HCV treatment-naive (GT1-6) or treatment-experienced (GT1, 2, 4-6; with interferon-based therapy with or without sofosbuvir, or sofosbuvir plus ribavirin) received glecaprevir/pibrentasvir (300/120 mg) once daily for 12 weeks. The primary endpoint compared the percentage of patients receiving glecaprevir/pibrentasvir with SVR12 to a historic SVR12 rate based on the standard of care. Safety of glecaprevir/pibrentasvir was assessed. In total, 80 liver transplant and 20 kidney transplant patients participated in the trial. Most patients had no or minimal fibrosis (80% had fibrosis scores F0-F1) and were infected with HCV GT1 (57%) or GT3 (24%). The overall SVR12 was 98% (n/N = 98/100; 95% confidence interval, 95.3%-100%), which exceeded the prespecified historic standard-of-care SVR12 threshold of 94%. One patient experienced virologic failure. One patient discontinued because of an adverse event considered to be unrelated to treatment; this patient achieved SVR12. Adverse events were mostly mild in severity, and laboratory abnormalities were infrequent. CONCLUSION Once-daily glecaprevir/pibrentasvir for 12 weeks is a well-tolerated and efficacious, ribavirin-free treatment for patients with chronic HCV GT1-6 infection who have received a liver or kidney transplant. (ClinicalTrials.gov NCT02692703.) (Hepatology 2018; 00:000-000).
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Affiliation(s)
| | - Paul Y. Kwo
- Stanford University School of MedicinePalo AltoCA
| | | | - Robert S. Brown
- Center for Liver Disease and TransplantationWeill Cornell Medical CollegeNew YorkNY
| | - Kosh Agarwal
- Institute of Liver StudiesKing's College Hospital NHS Foundation TrustLondonUK
| | | | - Edward Gane
- New Zealand Liver Transplant UnitAuckland City HospitalAucklandNew Zealand
| | | | | | - David Mutimer
- Queen Elizabeth Hospital and NIHR Liver Biomedical Research UnitBirminghamUK
| | | | | | | | | | | | | | | | | | | | | | | | - Xavier Forns
- Liver Unit, Hospital Clinic, CIBEREHD, IDIBAPSUniversity of BarcelonaBarcelonaSpain
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30
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Zhuang X, Lai AG, McKeating JA, Rowe I, Balfe P. Daytime variation in hepatitis C virus replication kinetics following liver transplant. Wellcome Open Res 2018; 3:96. [PMID: 30175249 PMCID: PMC6107978 DOI: 10.12688/wellcomeopenres.14696.2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/04/2018] [Indexed: 12/26/2022] Open
Abstract
Background: There is a growing interest in the role of circadian regulated pathways in disease pathogenesis. Methods: In a cohort of hepatitis C virus (HCV) infected patients undergoing liver transplantation, we observed differences in early viral infection kinetics of the allograft that associated with the time of liver transplant. Results: A higher frequency of subjects transplanted in the morning showed a rebound in viral RNA levels (n=4/6) during the first week post-surgery. In contrast, no viral rebound was observed in seven subjects transplanted in the afternoon. None of the other parameters previously reported to influence viral replication in the post-transplant setting, such as donor age, cold-ischemia time and length of surgery associated with viral rebound. Conclusions: These observation highlights a role for circadian processes to regulate HCV infection of the liver and warrants further investigation.
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Affiliation(s)
- Xiaodong Zhuang
- Nuffield Department of Medicine, University of Oxford, Oxford, Oxfordshire, OX3 7AZ, UK
| | - Alvina G. Lai
- Nuffield Department of Medicine, University of Oxford, Oxford, Oxfordshire, OX3 7AZ, UK
| | - Jane A. McKeating
- Nuffield Department of Medicine, University of Oxford, Oxford, Oxfordshire, OX3 7AZ, UK
| | - Ian Rowe
- Institute for Data Analytics, University of Leeds, Leeds, Yorkshire, UK
| | - Peter Balfe
- Institute for Immunology and Immunotherapy, University of Birmingham, Birmingham, West Midlands, B15 2TT, UK
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31
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2017 KASL clinical practice guidelines management of hepatitis C: Treatment of chronic hepatitis C. Clin Mol Hepatol 2018; 24:169-229. [PMID: 30092624 PMCID: PMC6166104 DOI: 10.3350/cmh.2018.1004] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2018] [Accepted: 03/06/2018] [Indexed: 12/11/2022] Open
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32
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Zhuang X, Lai AG, McKeating JA, Rowe I, Balfe P. Daytime variation in hepatitis C virus replication kinetics following liver transplant. Wellcome Open Res 2018; 3:96. [PMID: 30175249 PMCID: PMC6107978 DOI: 10.12688/wellcomeopenres.14696.1] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/13/2018] [Indexed: 09/29/2023] Open
Abstract
Background: There is a growing interest in the role of circadian regulated pathways in disease pathogenesis. Methods: In a cohort of hepatitis C virus (HCV) infected patients undergoing liver transplantation, we observed differences in early viral infection kinetics of the allograft that associated with the time of liver transplant. Results: A higher frequency of subjects transplanted in the morning showed a rebound in viral RNA levels (n=4/6) during the first week post-surgery. In contrast, no viral rebound was observed in seven subjects transplanted in the afternoon. None of the other parameters previously reported to influence viral replication in the post-transplant setting, such as donor age, cold-ischemia time and length of surgery associated with viral rebound. Conclusions: These observation highlights a role for circadian processes to regulate HCV infection of the liver and warrants further investigation.
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Affiliation(s)
- Xiaodong Zhuang
- Nuffield Department of Medicine, University of Oxford, Oxford, Oxfordshire, OX3 7AZ, UK
| | - Alvina G. Lai
- Nuffield Department of Medicine, University of Oxford, Oxford, Oxfordshire, OX3 7AZ, UK
| | - Jane A. McKeating
- Nuffield Department of Medicine, University of Oxford, Oxford, Oxfordshire, OX3 7AZ, UK
| | - Ian Rowe
- Institute for Data Analytics, University of Leeds, Leeds, Yorkshire, UK
| | - Peter Balfe
- Institute for Immunology and Immunotherapy, University of Birmingham, Birmingham, West Midlands, B15 2TT, UK
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33
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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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34
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The Mexican consensus on the treatment of hepatitis C. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2018. [DOI: 10.1016/j.rgmxen.2017.11.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022] Open
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35
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Aiza-Haddad I, Ballesteros-Amozurrutia A, Borjas-Almaguer OD, Castillo-Barradas M, Castro-Narro G, Chávez-Tapia N, Chirino-Sprung RA, Cisneros-Garza L, Dehesa-Violante M, Flores-Calderón J, Flores-Gaxiola A, García-Juárez I, González-Huezo MS, González-Moreno EI, Higuera-de la Tijera F, Kershenobich-Stalnikowitz D, López-Méndez E, Malé-Velázquez R, Marín-López E, Mata-Marín JA, Méndez-Sánchez N, Monreal-Robles R, Moreno-Alcántar R, Muñoz-Espinosa L, Navarro-Alvarez S, Pavia-Ruz N, Pérez-Ríos AM, Poo-Ramírez JL, Rizo-Robles MT, Sánchez-Ávila JF, Sandoval-Salas R, Torre A, Torres-Ibarra R, Trejo-Estrada R, Velarde-Ruiz Velasco JA, Wolpert-Barraza E, Bosques-Padilla F. The Mexican consensus on the treatment of hepatitis C. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2018; 83:275-324. [PMID: 29803325 DOI: 10.1016/j.rgmx.2017.11.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/08/2017] [Revised: 10/17/2017] [Accepted: 11/02/2017] [Indexed: 12/12/2022]
Abstract
The aim of the Mexican Consensus on the Treatment of HepatitisC was to develop clinical practice guidelines applicable to Mexico. The expert opinion of specialists in the following areas was taken into account: gastroenterology, infectious diseases, and hepatology. A search of the medical literature was carried out on the MEDLINE, EMBASE, and CENTRAL databases through keywords related to hepatitisC treatment. The quality of evidence was subsequently evaluated using the GRADE system and the consensus statements were formulated. The statements were then voted upon, using the modified Delphi system, and reviewed and corrected by a panel of 34 voting participants. Finally, the level of agreement was classified for each statement. The present guidelines provide recommendations with an emphasis on the new direct-acting antivirals, to facilitate their use in clinical practice. Each case must be individualized according to the comorbidities involved and patient management must always be multidisciplinary.
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Affiliation(s)
| | | | - O D Borjas-Almaguer
- Hospital Universitario «Dr. José Eleuterio González», Monterrey, Nuevo León, México
| | | | - G Castro-Narro
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | | | | | - L Cisneros-Garza
- Centro de Enfermedades Hepáticas del Hospital San José, Monterrey, Nuevo León, México
| | | | - J Flores-Calderón
- Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Ciudad de México, México
| | | | - I García-Juárez
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | | | - E I González-Moreno
- Hospital Universitario «Dr. José Eleuterio González», Monterrey, Nuevo León, México
| | | | | | - E López-Méndez
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - R Malé-Velázquez
- Instituto de Salud Digestiva y Hepática, Guadalajara, Jalisco, México
| | | | - J A Mata-Marín
- Hospital de Infectología del Centro Médico Nacional «La Raza», Ciudad de México, México
| | | | - R Monreal-Robles
- Hospital Universitario «Dr. José Eleuterio González», Monterrey, Nuevo León, México
| | | | - L Muñoz-Espinosa
- Hospital Universitario «Dr. José Eleuterio González», Monterrey, Nuevo León, México
| | | | - N Pavia-Ruz
- Hospital Infantil de México «Federico Gómez», Ciudad de México, México
| | - A M Pérez-Ríos
- Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Jalisco, México
| | - J L Poo-Ramírez
- Clínica San Jerónimo de Salud Hepática y Digestiva, Ciudad de México, México
| | | | - J F Sánchez-Ávila
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | | | - A Torre
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
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36
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Suda G, Ogawa K, Morikawa K, Sakamoto N. Treatment of hepatitis C in special populations. J Gastroenterol 2018; 53:591-605. [PMID: 29299684 PMCID: PMC5910474 DOI: 10.1007/s00535-017-1427-x] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2017] [Accepted: 12/19/2017] [Indexed: 02/08/2023]
Abstract
Hepatitis C virus (HCV) infection is one of the primary causes of liver cirrhosis and hepatocellular carcinoma. In hemodialysis patients, the rate of HCV infection is high and is moreover associated with a poor prognosis. In liver transplantation patients with HCV infection, recurrent HCV infection is universal, and re-infected HCV causes rapid progression of liver fibrosis and graft loss. Additionally, in patients with HCV and human immunodeficiency virus (HIV) co-infection, liver fibrosis progresses rapidly. Thus, there is an acute need for prompt treatment of HCV infection in these special populations (i.e., hemodialysis, liver transplantation, HIV co-infection). However, until recently, the standard anti-HCV treatment involved the use of interferon-based therapy. In these special populations, interferon-based therapies could not achieve a high rate of sustained viral response and moreover were associated with a higher rate of adverse events. With the development of novel direct-acting antivirals (DAAs), the landscape of anti-HCV therapy for special populations has changed dramatically. Indeed, in special populations treated with interferon-free DAAs, the sustained viral response rate was above 90%, with a lower incidence and severity of adverse events.
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Affiliation(s)
- Goki Suda
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
| | - Koji Ogawa
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Kenichi Morikawa
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Naoya Sakamoto
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
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Puchades Renau L, Berenguer M. Introduction to hepatitis C virus infection: Overview and history of hepatitis C virus therapies. Hemodial Int 2018; 22 Suppl 1:S8-S21. [DOI: 10.1111/hdi.12647] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Lorena Puchades Renau
- Department of Gastroenterology, Hepatology Unit & Instituto de Investigación La Fe; Hospital Universitari i Politècnic La Fe; Valencia Spain
| | - Marina Berenguer
- Department of Gastroenterology, Hepatology Unit & Instituto de Investigación La Fe; Hospital Universitari i Politècnic La Fe; Valencia Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd); Valencia Spain
- School of Medicine; University of Valencia; Valencia Spain
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Tronina O, Ślubowska K, Mikołajczyk-Korniak N, Komuda-Leszek E, Wieczorek-Godlewska R, Łągiewska B, Pacholczyk M, Lisik W, Kosieradzki M, Durlik M. Fibrosing Cholestatic Hepatitis C After Liver Transplantation: Therapeutic Options Before and After Introduction of Direct-Acting Antivirals: Our Experience and Literature Review. Transplant Proc 2018; 49:1409-1418. [PMID: 28736015 DOI: 10.1016/j.transproceed.2017.01.077] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2016] [Accepted: 01/24/2017] [Indexed: 12/26/2022]
Abstract
BACKGROUND Cirrhosis caused by hepatitis C is the most common indication for liver transplantation. The most aggressive form of hepatitis C virus (HCV) relapse after liver transplantation is fibrosing cholestatic hepatitis C, which can be observed in 2% to 15% of recipients. METHODS Double therapy with peg-interferon and ribavirin was characterized by low antiviral response, rapid fibrosis, and frequent graft failure within 1 year after surgery. RESULTS Introduction of direct-acting antivirals for HCV treatment allows for more efficient therapy with less adverse reactions, including patients with fibrosing cholestatic hepatitis C. CONCLUSIONS We present 4 (2.5%) cases of cholestatic viral hepatitis C recurrence in patients undergoing transplantation between 2006 and 2015 at the Transplantation Institute of Warsaw; during this period, 158 liver transplants were performed in patients with cirrhosis caused by HCV infection.
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Affiliation(s)
- O Tronina
- Department of Transplantation Medicine, Nephrology, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland.
| | - K Ślubowska
- Department of Transplantation Medicine, Nephrology, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland
| | - N Mikołajczyk-Korniak
- Department of Transplantation Medicine, Nephrology, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland
| | - E Komuda-Leszek
- Department of Transplantation Medicine, Nephrology, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland
| | - R Wieczorek-Godlewska
- Department of Transplantation Medicine, Nephrology, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland
| | - B Łągiewska
- Department of General and Transplantation Surgery, Medical University of Warsaw, Warsaw, Poland
| | - M Pacholczyk
- Department of General and Transplantation Surgery, Medical University of Warsaw, Warsaw, Poland
| | - W Lisik
- Department of General and Transplantation Surgery, Medical University of Warsaw, Warsaw, Poland
| | - M Kosieradzki
- Department of General and Transplantation Surgery, Medical University of Warsaw, Warsaw, Poland
| | - M Durlik
- Department of Transplantation Medicine, Nephrology, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland
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Bodro M, Sanclemente G, Crespo G, Linares L, Marcos MA, Marco F, Miquel R, Forns X, Navasa M, Moreno A. Severe Hepatitis C Recurrence as a Risk Factor for Opportunistic Infections in Liver Transplant Recipients. Transplant Proc 2018; 50:1437-1443. [PMID: 29880367 DOI: 10.1016/j.transproceed.2018.02.081] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2017] [Revised: 12/13/2017] [Accepted: 02/17/2018] [Indexed: 02/07/2023]
Abstract
OBJECTIVE The aim of the study was to determine the clinical characteristics, frequency of opportunistic infections (OI), and the outcomes for liver transplant recipients with severe hepatitis C virus (HCV) recurrence. In addition, the objective was to evaluate HCV recurrence as a risk factor for developing an OI. METHODS We conducted a retrospective observational study recording all liver transplant recipients from July 1, 2003, to December 31, 2012. Patients with liver disease due to HCV were selected. Active surveillance of infections was conducted periodically, and patients were classified according to presence of severe HCV recurrence. RESULTS Three hundred seventy patients underwent liver transplantation because of chronic HCV. One hundred forty-seven patients presented severe recurrence (SR) (49%) and 50 (17%) of them had post-liver transplant cholestatic hepatitis C. Patients with SR presented OI, especially cytomegalovirus (CMV) infections and invasive fungal infections, more frequently than patients without SR (33% vs 13%; P < .001). From the diagnosis of SR to the presentation of OI, the median number of days was 169 (6-2083). Acute allograft rejection (OR 1.8 95% confidence interval [CI] 1.1-3.3) donor age ≥60 years (OR 2.9 95% CI 1.3-6.8), and SR (OR 2.8, 95% CI 1.6-5.1) were independently associated with the development of OI in liver transplant recipients. CONCLUSION A high index of suspicion of opportunistic infections must be maintained when faced with severe HCV recurrence in liver transplant recipients. Moreover, active surveillance against CMV infection and other prophylactic strategies against opportunistic infections should be considered.
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Affiliation(s)
- M Bodro
- Infectious Diseases Department, Hospital Clínic-IDIBAPS-CIBERHED, University of Barcelona, Barcelona, Spain.
| | - G Sanclemente
- Infectious Diseases Department, Hospital Clínic-IDIBAPS-CIBERHED, University of Barcelona, Barcelona, Spain
| | - G Crespo
- Liver Transplant Unit, Hospital Clínic-IDIBAPS-CIBERHED, University of Barcelona, Barcelona, Spain
| | - L Linares
- Infectious Diseases Department, Hospital Clínic-IDIBAPS-CIBERHED, University of Barcelona, Barcelona, Spain
| | - M A Marcos
- Microbiology Department, Hospital Clínic-IDIBAPS-CIBERHED, University of Barcelona, Barcelona, Spain
| | - F Marco
- Microbiology Department, Hospital Clínic-IDIBAPS-CIBERHED, University of Barcelona, Barcelona, Spain
| | - R Miquel
- Pathology Unit, Hospital Clínic-IDIBAPS-CIBERHED, University of Barcelona, Barcelona, Spain
| | - X Forns
- Liver Transplant Unit, Hospital Clínic-IDIBAPS-CIBERHED, University of Barcelona, Barcelona, Spain
| | - M Navasa
- Liver Transplant Unit, Hospital Clínic-IDIBAPS-CIBERHED, University of Barcelona, Barcelona, Spain
| | - A Moreno
- Infectious Diseases Department, Hospital Clínic-IDIBAPS-CIBERHED, University of Barcelona, Barcelona, Spain
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40
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Abaalkhail F, Elsiesy H, Elbeshbeshy H, Shawkat M, Yousif S, Ullah W, Alabbad S, Al-Jedai A, Ajlan A, Broering D, Saab S, Al Sebayel M, Al-Hamoudi W. Treatment of Patients With Hepatitis C Virus Infection With Ledipasvir-Sofosbuvir in the Liver Transplant Setting. Transplantation 2017; 101:2739-2745. [PMID: 28795982 DOI: 10.1097/tp.0000000000001907] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Hepatitis C virus (HCV) infection is a major cause of liver cirrhosis and hepatocellular carcinoma and the leading indication for liver transplantation. In the Middle East, genotype 4 HCV infection is the most common genotype. However, limited data exists on the treatment of genotype-4 in the liver transplant setting. We evaluated the safety and efficacy of ledipasvir (LDV)-sofosbuvir (SOF) in treating HCV genotype-4 infected patients with cirrhosis or postliver transplantation. METHODS This prospective, single-arm, observational study includes cohort of patients with cirrhosis before liver transplantation (cohort A) and a cohort of postliver transplantation patients (cohort B). Patients received LDV/SOF (90-400 mg) once daily for 12 to 24 weeks with or without ribavirin (RBV). Patients with creatinine clearance below 30 were excluded. RESULTS A total of 111 patients (61 cirrhotic; 50 postliver transplants) with HCV genotype 4 were treated in King Faisal Specialist Hospital and Research Center; 55% cohort A and 44% cohort B received RBV. Sustained virological response sustain virological response (SVR)12 was 91.8% and 86% of cohorts A and B, respectively. There were no treatment-related mortality or serious adverse effects. RBV dose reduction occurred in 25% without any treatment discontinuation. SVR12 rates in cohort A were significantly higher in patients with a viral load below 800 000 (100% vs 83.9%, P value = 0.022). Viral load did not impact SVR rates in cohort B. The use of RBV did not increase SVR12 and was associated with anemia. CONCLUSIONS LDV/SOF without RBV is an effective and safe treatment option for patients with HCV genotype 4 infection in preliver and postliver transplant settings.
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Affiliation(s)
- Faisal Abaalkhail
- 1 Department of Liver Transplantation & Hepatobiliary-Pancreatic Surgery, Division of Organ Transplant Center, King Faisal Specialist Hospital & Research Center-Riyadh, Riyadh, Saudi Arabia. 2 College of Medicine, Alfaisal University, Riyadh, Saudi Arabia. 3 Department of Internal Medicine, Minia University, Minia, Egypt. 4 Department of Medicine, University of California, Los Angeles, Los Angeles, CA. 5 Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia
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Cheung A, Levitsky J. Follow-up of the Post-Liver Transplantation Patient: A Primer for the Practicing Gastroenterologist. Clin Liver Dis 2017; 21:793-813. [PMID: 28987263 DOI: 10.1016/j.cld.2017.06.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
The focus in liver transplantation in the next 10 years will likely change from preventing viral disease recurrence to minimizing the toll of rejection and fatty liver disease, minimizing the complications from immunosuppression with withdrawal strategies, and more optimal management of long-term risks, such as malignancy, cardiovascular disease, and renal failure. In addition, now that short-term results (<1 year) have improved significantly, there will be a shift toward improving long-term patient and graft survival, as well as a focus on primary care preventive strategies.
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Affiliation(s)
- Amanda Cheung
- Division of Gastroenterology and Hepatology, Northwestern University, 676 North Saint Clair, Suite 1400, Chicago, IL 60611, USA
| | - Josh Levitsky
- Division of Gastroenterology and Hepatology, Northwestern University, 676 North Saint Clair, Suite 1400, Chicago, IL 60611, USA.
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42
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Sajjad EA, Radkowski M, Perkowska-Ptasińska A, Pacholczyk M, Durlik M, Fedorowicz M, Pietrzak R, Ziarkiewicz-Wróblewska B, Włodarski P, Malejczyk J. Negative Correlation Between Hepatitis C Virus (HCV) and Let-7 MicroRNA Family in Transplanted Livers: The Role of rs868 Single-Nucleotide Polymorphism. Ann Transplant 2017; 22:638-645. [PMID: 29061957 PMCID: PMC6248281 DOI: 10.12659/aot.905540] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Background Genetic alterations of TGF-β pathway members, including its transmembrane receptor, TGFBR1, may influence the course of HCV infection. Rs868 is a single-nucleotide polymorphism of the 3′UTR region of TGFBR1, located in a binding site for the conserved let-7/miR98 microRNA family. Previously, we demonstrated a favorable course of hepatitis C recurrence after liver transplantation in rs868 AG genotype of the transplanted liver when compared to rs868 AA. The aim of the present study was to confirm the biological effect of rs868. Material/Methods HepG2 cell line was transfected with luciferase vectors cloned with 3′UTR of TGFBR1 gene encompassing different rs868 alleles. Post-transplant liver biopsies from 61 patients with HCV-related end-stage liver disease were evaluated histopathologically and analyzed for the expression of TGFBR1 mRNA, let-7/miR98 microRNAs, HCV RNA load, and rs868 genotype. Results Luciferase expression was significantly lower in the A allele-containing vector. TGFBR1 mRNA and HCV RNA load were correlated negatively with let-7/miR98 microRNAs and this correlation was significantly stronger for rs868 AG compared to AA genotype. A strong positive correlation was demonstrated between TGFBR1 and HCV in both genotypes. In AG heterozygotes, let-7/miR98 microRNAs showed a strong negative correlation with periportal or periseptal interface hepatitis (Ishak A score). Conclusions There is a negative correlation between let-7/miR98 microRNAs and HCV viral load and TGFBR1 mRNA after liver transplantation. In the rs868 AG heterozygotes, this correlation was stronger and there was a negative correlation between let-7/miR98 and Ishak A score, which is in concordance with the previously demonstrated protective role of this genotype in post-transplant hepatitis C recurrence.
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Affiliation(s)
- Emir Ahmed Sajjad
- Department of Histology and Embryology, Centre for Biostructure Research, Medical University of Warsaw, Warsaw, Poland
| | - Marek Radkowski
- Department of Immunopathology of Infectious and Parasitic Diseases, Medical University of Warsaw, Warsaw, Poland
| | - Agnieszka Perkowska-Ptasińska
- Department of Transplantology, Nephrology and Internal Medicine, Medical University of Warsaw, Transplantation Institute, Warsaw, Poland
| | - Marek Pacholczyk
- Department of General Surgery and Transplantology, Medical University of Warsaw, Transplantation Institute, Warsaw, Poland
| | - Magdalena Durlik
- Department of Transplantology, Nephrology and Internal Medicine, Medical University of Warsaw, Transplantation Institute, Warsaw, Poland
| | - Mikołaj Fedorowicz
- Department of Histology and Embryology, Centre for Biostructure Research, Medical University of Warsaw, Warsaw, Poland
| | - Renata Pietrzak
- Department of Histology and Embryology, Centre for Biostructure Research, Medical University of Warsaw, Warsaw, Poland
| | | | - Paweł Włodarski
- Department of Histology and Embryology, Centre for Biostructure Research, Medical University of Warsaw, Warsaw, Poland
| | - Jacek Malejczyk
- Department of Histology and Embryology, Centre for Biostructure Research, Medical University of Warsaw, Warsaw, Poland
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Abstract
BACKGROUND Current national hepatitis C virus (HCV) guidelines do not recommend the use of elbasvir (EBR)/grazoprevir (GZR) in postliver transplantation (LT) patients due to drug-drug interactions with immunosuppression agents. However, recommendations do not address the treatment of HCV in renally impaired post-LT patients. Treatment regimens that are recommended for post-LT patients are not safe in patients with severe renal impairment and patients on dialysis. EBR/GZR is approved for use in patients with renal impairment and patients on dialysis, but not in the post-LT setting. METHODS Authors reviewed the electronic medical records of 3 treatment-naive HCV genotype 1a male post-LT patients on hemodialysis who were treated with EBR/GZR with or without ribavirin for 12 or 16 weeks. RESULTS No patients had serious adverse drug events during treatment and no patients stopped treatment early or died. Providers monitored immunosuppression levels; both patients who were taking tacrolimus required immunosuppression dose adjustments during HCV treatment. No patients experienced organ rejection. All patients achieved sustained virologic response. CONCLUSIONS Current HCV guidelines do not address the treatment options for post-LT patients with severe renal impairment or who are on dialysis, nor do published accounts of use of EBR/GZR in this patient population exist. Clinicians may benefit from exposure to real-world cases of HCV treatment in this historically difficult-to-cure patient population. Providers must address drug-drug interactions with EBR/GZR and monitor for changes in immunosuppression levels to ensure safety with its use in post-LT patients.
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44
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Guo X, Wang S, Qiu ZG, Dou YL, Liu WL, Yang D, Shen ZQ, Chen ZL, Wang JF, Zhang B, Wang XW, Guo XF, Zhang XL, Jin M, Li JW. Efficient replication of blood-borne hepatitis C virus in human fetal liver stem cells. Hepatology 2017; 66:1045-1057. [PMID: 28407288 DOI: 10.1002/hep.29211] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2017] [Accepted: 04/05/2017] [Indexed: 02/06/2023]
Abstract
UNLABELLED The development of pathogenic mechanisms, specific antiviral treatments and preventive vaccines for hepatitis C virus (HCV) infection has been limited due to lack of cell culture models that can naturally imitate the entire HCV life cycle. Here, we established an HCV cell culture model based on human fetal liver stem cells (hFLSCs) that supports the entire blood-borne hepatitis C virus (bbHCV) life cycle. More than 90% of cells remained infected by various genotypes. bbHCV was efficiently propagated, and progeny virus were infectious to hFLSCs. The virus could be passed efficiently between cells. The viral infectivity was partially blocked by specific antibodies or small interfering RNA against HCV entry factors, whereas HCV replication was inhibited by antiviral drugs. We observed viral particles of approximately 55 nm in diameter in both cell culture media and infected cells after bbHCV infection. CONCLUSION Our data show that the entire bbHCV life cycle could be naturally imitated in hFLSCs. This model is expected to provide a powerful tool for exploring the process and the mechanism of bbHCV infection at the cellular level and for evaluating the treatment and preventive strategies of bbHCV infection. (Hepatology 2017;66:1045-1057).
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Affiliation(s)
- Xuan Guo
- Department of Environment and Health, Tianjin Institute of Health and Environmental Medicine, Key Laboratory of Risk Assessment and Control for Environment & Food Safety, Tianjin, China
| | - Shu Wang
- Department of Environment and Health, Tianjin Institute of Health and Environmental Medicine, Key Laboratory of Risk Assessment and Control for Environment & Food Safety, Tianjin, China
| | - Zhi-Gang Qiu
- Department of Environment and Health, Tianjin Institute of Health and Environmental Medicine, Key Laboratory of Risk Assessment and Control for Environment & Food Safety, Tianjin, China
| | - Ya-Ling Dou
- Peking Union Medical College Hospital, Chinese Medical Academy, Beijing, China
| | - Wei-Li Liu
- Department of Environment and Health, Tianjin Institute of Health and Environmental Medicine, Key Laboratory of Risk Assessment and Control for Environment & Food Safety, Tianjin, China
| | - Dong Yang
- Department of Environment and Health, Tianjin Institute of Health and Environmental Medicine, Key Laboratory of Risk Assessment and Control for Environment & Food Safety, Tianjin, China
| | - Zhi-Qiang Shen
- Department of Environment and Health, Tianjin Institute of Health and Environmental Medicine, Key Laboratory of Risk Assessment and Control for Environment & Food Safety, Tianjin, China
| | - Zhao-Li Chen
- Department of Environment and Health, Tianjin Institute of Health and Environmental Medicine, Key Laboratory of Risk Assessment and Control for Environment & Food Safety, Tianjin, China
| | - Jing-Feng Wang
- Department of Environment and Health, Tianjin Institute of Health and Environmental Medicine, Key Laboratory of Risk Assessment and Control for Environment & Food Safety, Tianjin, China
| | - Bin Zhang
- Department of Environment and Health, Tianjin Institute of Health and Environmental Medicine, Key Laboratory of Risk Assessment and Control for Environment & Food Safety, Tianjin, China
| | - Xin-Wei Wang
- Department of Environment and Health, Tianjin Institute of Health and Environmental Medicine, Key Laboratory of Risk Assessment and Control for Environment & Food Safety, Tianjin, China
| | - Xiang-Fei Guo
- Department of Environment and Health, Tianjin Institute of Health and Environmental Medicine, Key Laboratory of Risk Assessment and Control for Environment & Food Safety, Tianjin, China
| | - Xue-Lian Zhang
- Department of Environment and Health, Tianjin Institute of Health and Environmental Medicine, Key Laboratory of Risk Assessment and Control for Environment & Food Safety, Tianjin, China
| | - Min Jin
- Department of Environment and Health, Tianjin Institute of Health and Environmental Medicine, Key Laboratory of Risk Assessment and Control for Environment & Food Safety, Tianjin, China
| | - Jun-Wen Li
- Department of Environment and Health, Tianjin Institute of Health and Environmental Medicine, Key Laboratory of Risk Assessment and Control for Environment & Food Safety, Tianjin, China
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Vukotic R, Conti F, Fagiuoli S, Morelli MC, Pasulo L, Colpani M, Foschi FG, Berardi S, Pianta P, Mangano M, Donato MF, Malinverno F, Monico S, Tamè M, Mazzella G, Belli LS, Viganò R, Carrai P, Burra P, Russo FP, Lenci I, Toniutto P, Merli M, Loiacono L, Iemmolo R, Degli Antoni AM, Romano A, Picciotto A, Rendina M, Andreone P. Long-term outcomes of direct acting antivirals in post-transplant advanced hepatitis C virus recurrence and fibrosing cholestatic hepatitis. J Viral Hepat 2017; 24:858-864. [PMID: 28370880 DOI: 10.1111/jvh.12712] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2016] [Accepted: 02/22/2017] [Indexed: 12/14/2022]
Abstract
Long-term functional outcomes of sofosbuvir-based antiviral treatment were evaluated in a cohort study involving 16 Italian centres within the international compassionate use programme for post-transplant hepatitis C virus (HCV) recurrence. Seventy-three patients with cirrhosis (n=52) or fibrosing cholestatic hepatitis (FCH, n=21) received 24-week sofosbuvir with ribavirin±pegylated interferon or interferon-free sofosbuvir-based regimen with daclatasvir/simeprevir+ribavirin. The patients were observed for a median time of 103 (82-112) weeks. Twelve of 73 (16.4%) died (10 non-FCH, 2 FCH) and two underwent re-LT. Sustained virological response was achieved in 46 of 66 (69.7%): 31 of 47 (66%) non-FCH and 15 of 19 (79%) FCH patients. All relapsers were successfully retreated. Comparing the data of baseline with last follow-up, MELD and Child-Turcotte-Pugh scores improved both in non-FCH (15.3±6.5 vs 10.5±3.8, P<.0001 and 8.4±2.1 vs 5.7±1.3, P<.0001, respectively) and FCH (17.3±5.9 vs 10.1±2.8, P=.001 and 8.2±1.6 vs 5.5±1, P=.001, respectively). Short-treatment mortality was higher in patients with baseline MELD≥25 than in those with MELD<25 (42.9% vs 4.8%, P=.011). Long-term mortality was 53.3% among patients with baseline MELD≥20 and 7.5% among those with MELD<20 (P<.0001). Among deceased patients 75% were Child-Turcotte-Pugh class C at baseline, while among survivors 83.9% were class A or B (P<.0001). Direct acting antivirals-based treatments for severe post-transplant hepatitis C recurrence, comprising fibrosing cholestatic hepatitis, significantly improve liver function, even without viral clearance and permit an excellent long-term survival. The setting of severe HCV recurrence may require the identification of "too-sick-to-treat patients" to avoid futile treatments.
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Affiliation(s)
- R Vukotic
- Centro di Ricerca per lo Studio delle Epatiti, Dipartimento di Scienze Mediche e Chirurgiche, Università degli Studi di Bologna, Bologna, Italy
| | - F Conti
- Centro di Ricerca per lo Studio delle Epatiti, Dipartimento di Scienze Mediche e Chirurgiche, Università degli Studi di Bologna, Bologna, Italy
| | - S Fagiuoli
- Dipartimento di Medicina Specialistica e dei Trapianti, U.S.C. Gastroenterologia Epatologia e Trapiantologia, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy
| | - M C Morelli
- Centro di Ricerca per lo Studio delle Epatiti, Dipartimento di Scienze Mediche e Chirurgiche, Università degli Studi di Bologna, Bologna, Italy
| | - L Pasulo
- Dipartimento di Medicina Specialistica e dei Trapianti, U.S.C. Gastroenterologia Epatologia e Trapiantologia, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy
| | - M Colpani
- Dipartimento di Medicina Specialistica e dei Trapianti, U.S.C. Gastroenterologia Epatologia e Trapiantologia, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy
| | - F G Foschi
- AUSL della Romagna, Presidio Ospedaliero di Faenza, Faenza, Italy
| | - S Berardi
- Centro di Ricerca per lo Studio delle Epatiti, Dipartimento di Scienze Mediche e Chirurgiche, Università degli Studi di Bologna, Bologna, Italy
| | - P Pianta
- Centro di Ricerca per lo Studio delle Epatiti, Dipartimento di Scienze Mediche e Chirurgiche, Università degli Studi di Bologna, Bologna, Italy
| | - M Mangano
- Centro di Ricerca per lo Studio delle Epatiti, Dipartimento di Scienze Mediche e Chirurgiche, Università degli Studi di Bologna, Bologna, Italy
| | - M F Donato
- Gastroenterologia ed Epatologia, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico ed Univerisità di Milano, Milan, Italy
| | - F Malinverno
- Gastroenterologia ed Epatologia, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico ed Univerisità di Milano, Milan, Italy
| | - S Monico
- Gastroenterologia ed Epatologia, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico ed Univerisità di Milano, Milan, Italy
| | - M Tamè
- Centro di Ricerca per lo Studio delle Epatiti, Dipartimento di Scienze Mediche e Chirurgiche, Università degli Studi di Bologna, Bologna, Italy
| | - G Mazzella
- Centro di Ricerca per lo Studio delle Epatiti, Dipartimento di Scienze Mediche e Chirurgiche, Università degli Studi di Bologna, Bologna, Italy
| | - L S Belli
- Dipartimento di Epatologia e Gastroenterologia, Ospedale Niguarda, Milan, Italy
| | - R Viganò
- Dipartimento di Epatologia e Gastroenterologia, Ospedale Niguarda, Milan, Italy
| | - P Carrai
- Chirurgia biliopancreatica e Trapianto di Fegato, Università di Pisa, Pisa, Italy
| | - P Burra
- Dipartimento di Chirurgia, Oncologia e Gastroenterologia, Unità di Trapianto Multiviscerale, Ospedale Universitario Padova, Padua, Italy
| | - F P Russo
- Dipartimento di Chirurgia, Oncologia e Gastroenterologia, Unità di Trapianto Multiviscerale, Ospedale Universitario Padova, Padua, Italy
| | - I Lenci
- Unità di Epatologia, Università Tor Vergata, Rome, Italy
| | - P Toniutto
- Medicina Interna Sezione di Trapianto di Fegato, Università di Udine, Udine, Italy
| | - M Merli
- Dipartimento di Medicina Clinica La Sapienza, Gastroenterologia, Università di Roma, Rome, Italy
| | | | - R Iemmolo
- Chirurgia Oncologica Epato-bilio-pancreatica e Chirurgia dei Trapianti di fegato, AOU di Modena, Modena, Italy
| | - A M Degli Antoni
- Unità di Malattie Infettive ed Epatologia, AOU di Parma, Parma, Italy
| | - A Romano
- Dipartimento di Medicina, Unità delle Emergenze epatologiche e dei Trapianti di fegato, Università di Padova, Padua, Italy
| | - A Picciotto
- Dipartimento di Medicina Interna, Università degli Studi di Genova, Genova, Italy
| | - M Rendina
- Unità Operativa Gastroenterologia ed Endoscopia Digestiva, Policlinico Universitario di Bari, Bari, Italy
| | - P Andreone
- Centro di Ricerca per lo Studio delle Epatiti, Dipartimento di Scienze Mediche e Chirurgiche, Università degli Studi di Bologna, Bologna, Italy
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Cano A, Mariño Z, Millet O, Martínez-Arranz I, Navasa M, Falcón-Pérez JM, Pérez-Cormenzana M, Caballería J, Embade N, Forns X, Bosch J, Castro A, Mato JM. A Metabolomics Signature Linked To Liver Fibrosis In The Serum Of Transplanted Hepatitis C Patients. Sci Rep 2017; 7:10497. [PMID: 28874799 PMCID: PMC5585246 DOI: 10.1038/s41598-017-10807-y] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2017] [Accepted: 08/11/2017] [Indexed: 12/17/2022] Open
Abstract
Liver fibrosis must be evaluated in patients with hepatitis C virus (HCV) after liver transplantation because its severity affects their prognosis and the recurrence of HCV. Since invasive biopsy is still the gold standard to identify patients at risk of graft loss from rapid fibrosis progression, it becomes crucial the development of new accurate, non-invasive methods that allow repetitive examination of the patients. Therefore, we have developed a non-invasive, accurate model to distinguish those patients with different liver fibrosis stages. Two hundred and three patients with HCV were histologically classified (METAVIR) into five categories of fibrosis one year after liver transplantation. In this cross-sectional study, patients at fibrosis stages F0-F1 (n = 134) were categorised as “slow fibrosers” and F2-F4 (n = 69) as “rapid fibrosers”. Chloroform/methanol serum extracts were analysed by reverse ultra-high performance liquid chromatography coupled to mass spectrometry. A diagnostic model was built through linear discriminant analyses. An algorithm consisting of two sphingomyelins and two phosphatidylcholines accurately classifies rapid and slow fibrosers after transplantation. The proposed model yielded an AUROC of 0.92, 71% sensitivity, 85% specificity, and 84% accuracy. Moreover, specific bile acids and sphingomyelins increased notably along with liver fibrosis severity, differentiating between rapid and slow fibrosers.
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Affiliation(s)
- Ainara Cano
- OWL, Parque Tecnológico de Bizkaia, Derio, 48160, Bizkaia, Spain.
| | - Zoe Mariño
- Liver Unit, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd); Institut d'Investigacions Biomediques August Pi Sunyer (IDIBAPS), Barcelona, Spain
| | - Oscar Millet
- Metabolomic Unit, CIC bioGUNE, CIBERehd, Parque Tecnológico de Bizkaia, Derio, 48160, Spain.,Ikerbasque, Basque Foundation for Science, Bilbao, Bizkaia, Spain
| | | | - Miquel Navasa
- Liver Unit, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd); Institut d'Investigacions Biomediques August Pi Sunyer (IDIBAPS), Barcelona, Spain
| | - Juan Manuel Falcón-Pérez
- Metabolomic Unit, CIC bioGUNE, CIBERehd, Parque Tecnológico de Bizkaia, Derio, 48160, Spain.,Ikerbasque, Basque Foundation for Science, Bilbao, Bizkaia, Spain
| | | | - Joan Caballería
- Liver Unit, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd); Institut d'Investigacions Biomediques August Pi Sunyer (IDIBAPS), Barcelona, Spain
| | - Nieves Embade
- Metabolomic Unit, CIC bioGUNE, CIBERehd, Parque Tecnológico de Bizkaia, Derio, 48160, Spain
| | - Xavier Forns
- Liver Unit, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd); Institut d'Investigacions Biomediques August Pi Sunyer (IDIBAPS), Barcelona, Spain
| | - Jaume Bosch
- Liver Unit, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd); Institut d'Investigacions Biomediques August Pi Sunyer (IDIBAPS), Barcelona, Spain
| | - Azucena Castro
- OWL, Parque Tecnológico de Bizkaia, Derio, 48160, Bizkaia, Spain
| | - José María Mato
- Metabolomic Unit, CIC bioGUNE, CIBERehd, Parque Tecnológico de Bizkaia, Derio, 48160, Spain
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Anand AC, Agarwal SK, Garg HK, Khanna S, Gupta S. Sofosbuvir and Ribavirin for 24 Weeks Is An Effective Treatment Option for Recurrent Hepatitis C Infection After Living Donor Liver Transplantation. J Clin Exp Hepatol 2017; 7:165-171. [PMID: 28970701 PMCID: PMC5620355 DOI: 10.1016/j.jceh.2017.06.007] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2017] [Accepted: 06/19/2017] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Recurrent hepatitis C virus (HCV) has been a serious problem after liver transplantation (LT). We report our experience of 24-week therapy with sofosbuvir (SOF) and ribavirin (RBV) in post-LT recurrent HCV in living donor liver transplantation (LDLT) setting in South Asia. METHODS Data from all patients treated for post-transplantation HCV recurrence in a single center were analyzed. Treatment regimen was 24 weeks of SOF 400 mg daily and RBV (starting at 800 mg daily, increased as tolerated). Sustained virological response (SVR) was assessed 12 weeks and 24 weeks after completion of treatment. RESULTS 63 patients (median age 52 [range 30-69] years; 80% males) were treated. Most (76.2%) were treatment experienced and predominant HCV genotype was 3 (77.7%) followed by 1 (20.6%). Median transient elastography (Fibroscan) score was 7 (range 3-11) kPa and none of the patients had cirrhosis. SVR12 was achieved in 60 of 63 patients (95.2%) while SVR24 was noted in 59 (93.7%). SVR12 rates were as good in genotype-3 as in genotype-1. Older age, longer period after transplantation, higher Fibroscan value and higher need for erythropoietin were likely to be associated with relapse. Adverse effects were noted in 34 patients and weakness and fatigue were the commonest side effects. Significant drop in hemoglobin (<8 g/dL) was seen in 6 patients. CONCLUSIONS SOF + RBV combination therapy for 24 weeks was safe and effective in treatment of for post-LT recurrent HCV in a single LT center and remains relevant due to its low cost and lack of drug interactions.
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Key Words
- CBC, complete blood counts
- DAA, directly acting antivirals
- HCC, hepatocellular carcinoma
- HCV, hepatitis C virus
- Hb%, hemoglobin
- KFT, kidney function tests
- LDLT, living donor liver transplantation
- LFT, liver function tests
- LT, liver transplantation
- RBV, ribavirin
- SOF, sofosbuvir
- SVR, sustained virological response
- g/dL, grams per decilitre
- genotype-1
- genotype-3
- kPA, kilo pascals
- living donor liver transplantation
- recurrent hepatitis C
- sustained viral response
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Affiliation(s)
- Anil C. Anand
- Department of Hepatology & Gastroenterology, Indraprastha Apollo Hospital, Sarita Vihar, Mathura Road, New Delhi 110076, India
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48
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Fernández Carrillo C, Crespo G, de la Revilla J, Castells L, Buti M, Montero JL, Fábrega E, Fernández I, Serrano-Millán C, Hernández V, Calleja JL, Londoño MC. Successful Continuation of HCV Treatment After Liver Transplantation. Transplantation 2017; 101:1009-1012. [PMID: 27906834 DOI: 10.1097/tp.0000000000001596] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Guidelines recommend that patients with hepatitis C virus (HCV)-related liver disease be treated for HCV before liver transplant (LT) to eliminate the virus before surgery. However, the unpredictability of donor organ availability may limit treatment duration. Interruption of HCV treatment with resumption post-LT is 1 potential solution which has not been investigated widely. METHODS Patients from 5 clinical centers included in the large, national, noninterventional Hepa-C registry who started treatment with direct-acting antiviral agents while awaiting LT were identified retrospectively and followed up prospectively. Fifteen patients who had treatment interruptions around LT were identified. RESULTS The majority of patients (12/15) received interferon-free regimens, most commonly sofosbuvir + daclatasvir (8/12), for a total of 24 weeks (13/15). Treatment was discontinued temporarily for a median of 5 (range, 2-33) days. Fourteen patients completing 12 weeks of follow-up achieved a sustained virological response. One patient who died before week 12 posttreatment achieved a response at posttreatment week 4. Treatment was generally well tolerated. Serious adverse events were recorded in 2 of 15 patients (anaemia in 1 patient; pneumonia in 1 patient); all arose after LT. CONCLUSIONS Resumption of direct-acting antiviral agent therapy after a temporary interruption around LT was highly effective, achieving sustained virological response in all patients who completed 12 weeks of posttreatment follow-up. Treatment was generally well tolerated pretransplantation and posttransplantation, with a low rate of serious adverse events. Such a strategy may offer an important new approach to the treatment of patients awaiting LT which may be assessed in future studies.
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Affiliation(s)
- Carlos Fernández Carrillo
- 1 Liver Unit, Hospital Universitario Puerta de Hierro-Majadahonda, IDIPHIM, CIBERehd, Majadahonda, Madrid, Spain. 2 Liver Unit, Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain. 3 Liver Unit, Internal Medicine Department, Hospital Universitario Vall d'Hebron, CIBERehd, Barcelona, Spain. 4 Hepatology and Liver Transplant Unit, Hospital Universitario Reina Sofía, IMIBIC, CIBERehd, Córdoba, Spain. 5 Gastroenterology and Hepatology Unit, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain. 6 Digestive Service, Hospital Universitario 12 de Octubre, Madrid, Spain. 7 Liver Unit, Hospital Universitario Puerta de Hierro, Universidad Autónoma de Madrid and CIBERehd, Madrid, Spain
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49
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Lenci I, Bosa A, Milana M, Baiocchi L, Antonucci FP, Aragri M, Ceccherini-Silberstein F, Perno CF, Tisone G, Angelico M. Evidence of Spontaneous Post-transplant HCV Eradication in Two Failed DAA Treatments Awaiting Liver Transplantation. Dig Dis Sci 2017; 62:2193-2195. [PMID: 28500586 DOI: 10.1007/s10620-017-4594-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2017] [Accepted: 04/25/2017] [Indexed: 12/09/2022]
Affiliation(s)
- Ilaria Lenci
- Hepatology Unit, Department of Experimental Medicine and Surgery, Policlinico Tor Vergata, Rome, Italy.
| | - Alessandra Bosa
- Hepatology Unit, Department of Experimental Medicine and Surgery, Policlinico Tor Vergata, Rome, Italy
| | - Martina Milana
- Hepatology Unit, Department of Experimental Medicine and Surgery, Policlinico Tor Vergata, Rome, Italy
| | - Leonardo Baiocchi
- Hepatology Unit, Department of Experimental Medicine and Surgery, Policlinico Tor Vergata, Rome, Italy
| | - Francesco Paolo Antonucci
- Virology Unit, Department of Experimental Medicine and Surgery, Policlinico Tor Vergata, Rome, Italy
| | - Marianna Aragri
- Virology Unit, Department of Experimental Medicine and Surgery, Policlinico Tor Vergata, Rome, Italy
| | | | - Carlo Federico Perno
- Virology Unit, Department of Experimental Medicine and Surgery, Policlinico Tor Vergata, Rome, Italy
| | - Giuseppe Tisone
- Liver Transplant Center, Department of Experimental Medicine and Surgery, Policlinico Tor Vergata, Rome, Italy
| | - Mario Angelico
- Hepatology Unit, Department of Experimental Medicine and Surgery, Policlinico Tor Vergata, Rome, Italy
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50
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Hughes MG, Tucker WW, Reddy S, Brier ME, Koch D, McClain CJ, Jonsson CB, Matoba N, Chung D. Rate of hepatitis C viral clearance by human livers in human patients: Liver transplantation modeling primary infection and implications for studying entry inhibition. PLoS One 2017; 12:e0180719. [PMID: 28732019 PMCID: PMC5521768 DOI: 10.1371/journal.pone.0180719] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2016] [Accepted: 06/20/2017] [Indexed: 02/06/2023] Open
Abstract
To better understand the dynamics of early hepatitis C virus (HCV) infection, we determined how rapidly non-cirrhotic HCV-uninfected liver allografts clear HCV from the circulation of cirrhotic HCV-infected patients at the time of transplantation but before administration of immunosuppression. Specifically, we characterized serum HCV kinetics during the first 90 min of reperfusion for 19 chronically HCV-infected patients transplanted with an HCV-uninfected liver by measuring serum viral load immediately prior to reperfusion (t = 0) and then every 15 min for a total of 90 min (t = 90). Immunosuppression was withheld until all samples were taken to better model primary infection. During this period, rates of viral clearance varied more than 20-fold with a median rate constant of 0.0357 1/min, range 0.0089-0.2169; half-life (minutes) median 19.4, range 3.2-77.8. The majority of viral clearance occurred within the first 60 min. The amount of blood transfused during this 90-min period (a potential confounding variable of this human liver transplant model of primary infection) accounted for 53% and 59% of k (r = 0.53, p = 0.05) and half-life (r = 0.59, p = 0.03) variability, respectively. No other clinical variables tested (age, allograft weight, and degree of reperfusion injury as assessed by peak postoperative ALT or AST) accounted for the remaining variability (p>0.05). CONCLUSION In a human liver transplant model of primary infection, HCV rapidly clears the bloodstream. With approximately 90% of clearance occurring in the first 90 minutes of reperfusion, studies of HCV entry inhibition could utilize rate of clearance during this early period as an outcome measure.
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Affiliation(s)
- Michael G. Hughes
- Department of Surgery, University of Louisville, Louisville, Kentucky, United States of America
- * E-mail:
| | - William W. Tucker
- Department of Surgery, University of Louisville, Louisville, Kentucky, United States of America
| | - Sreelatha Reddy
- Department of Surgery, University of Louisville, Louisville, Kentucky, United States of America
| | - Michael E. Brier
- Department of Medicine, University of Louisville, Louisville, Kentucky, United States of America
| | - David Koch
- Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, United States of America
| | - Craig J. McClain
- Department of Medicine, University of Louisville, Louisville, Kentucky, United States of America
- Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, United States of America
- Robley Rex Louisville Veteran Affairs Medical Center, Louisville, Kentucky, United States of America
| | - Colleen B. Jonsson
- Department of Microbiology, University of Tennessee, Knoxville, Tennessee, United States of America
| | - Nobuyuki Matoba
- Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, United States of America
| | - Donghoon Chung
- Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky, United States of America
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