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Liu F, Sun Y, Tai D, Ren Y, Chng ELK, Wee A, Bedossa P, Huang R, Wang J, Wei L, You H, Rao H. AI Digital Pathology Using qFibrosis Shows Heterogeneity of Fibrosis Regression in Patients with Chronic Hepatitis B and C with Viral Response. Diagnostics (Basel) 2024; 14:1837. [PMID: 39202325 PMCID: PMC11353864 DOI: 10.3390/diagnostics14161837] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Revised: 08/16/2024] [Accepted: 08/20/2024] [Indexed: 09/03/2024] Open
Abstract
This study aimed to understand the dynamic changes in fibrosis and its relationship with the evaluation of post-treatment viral hepatitis using qFibrosis. A total of 158 paired pre- and post-treatment liver samples from patients with chronic hepatitis B (CHB; n = 100) and C (CHC; n = 58) were examined. qFibrosis was employed with artificial intelligence (AI) to analyze the fibrosis dynamics in the portal tract (PT), periportal (PP), midzonal, pericentral, and central vein (CV) regions. All patients with CHB achieved a virological response after 78 weeks of treatment, whereas patients with CHC achieved a sustained viral response after 24 weeks. For patients initially staged as F5/6 (Ishak system) at baseline, the post-treatment cases exhibited a significant reduction in the collagen proportionate area (CPA) (25-69%) and number of collagen strings (#string) (9-72%) across all regions. In contrast, those initially staged as F3/4 at baseline showed a similar CPA and #string trend at 24 weeks. For regression patients, 27 parameters (25 in the CV region) in patients staged as F3/4 and 15 parameters (three in the PT and 12 in the PP regions) in those staged as F5/6 showed significant differences between the CHB and CHC groups at baseline. Following successful antiviral treatment, the pre- and post-treatment liver samples provided quantitative evidence of the heterogeneity of fibrotic features. qFibrosis has the potential to provide new insights into the characteristics of fibrosis regression in both patients with CHB and CHC as early as 24 weeks after antiviral therapy.
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Affiliation(s)
- Feng Liu
- Peking University People’s Hospital, Peking University Hepatology Institute, Infectious Disease and Hepatology Center of Peking University People’s Hospital, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis, Beijing 100044, China; (F.L.); (R.H.); (J.W.)
| | - Yameng Sun
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, 95 Yong-an Road, Xi-Cheng District, Beijing 100050, China;
| | - Dean Tai
- HistoIndex Pte. Ltd., Singapore 117674, Singapore; (D.T.); (E.L.K.C.)
| | - Yayun Ren
- HistoIndex Pte. Ltd., Singapore 117674, Singapore; (D.T.); (E.L.K.C.)
| | - Elaine L. K. Chng
- HistoIndex Pte. Ltd., Singapore 117674, Singapore; (D.T.); (E.L.K.C.)
| | - Aileen Wee
- Department of Pathology, National University Hospital, 5 Lower Kent Ridge Road, Singapore 119074, Singapore
| | | | - Rui Huang
- Peking University People’s Hospital, Peking University Hepatology Institute, Infectious Disease and Hepatology Center of Peking University People’s Hospital, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis, Beijing 100044, China; (F.L.); (R.H.); (J.W.)
| | - Jian Wang
- Peking University People’s Hospital, Peking University Hepatology Institute, Infectious Disease and Hepatology Center of Peking University People’s Hospital, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis, Beijing 100044, China; (F.L.); (R.H.); (J.W.)
| | - Lai Wei
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing 102218, China;
| | - Hong You
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, 95 Yong-an Road, Xi-Cheng District, Beijing 100050, China;
| | - Huiying Rao
- Peking University People’s Hospital, Peking University Hepatology Institute, Infectious Disease and Hepatology Center of Peking University People’s Hospital, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis, Beijing 100044, China; (F.L.); (R.H.); (J.W.)
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Zingg SCW, Lemon K. Donor Viral Hepatitis and Liver Transplantation. Surg Clin North Am 2024; 104:67-77. [PMID: 37953041 DOI: 10.1016/j.suc.2023.07.002] [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: 11/14/2023]
Abstract
Despite increasing numbers of organ transplants completed each year, there continues to be an organ shortage in liver transplantation. This has led to the utilization of previously discarded or "marginal" allografts, such as those from donors with hepatitis C virus (HCV) or hepatitis B virus (HBV). The advent of direct acting antivirals and nucleos(t)ide analogs has allowed these allografts to be safely transplanted regardless of the recipients' hepatitis status with comparable graft and patient survival. Recent advances have even allowed usage of actively viremic donors with similar graft and patient outcomes. This article presents an overview of the use of HCV positive and HBV positive allografts.
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Affiliation(s)
- Sara-Catherine Whitney Zingg
- Department of Surgery, University of Cincinnati College of Medicine, 231 Albert Sabin Way, ML 0558, Cincinnati, OH 45267, USA. https://twitter.com/transplant_u
| | - Kristina Lemon
- Department of Surgery, University of Cincinnati College of Medicine, 231 Albert Sabin Way, ML 0558, Cincinnati, OH 45267, USA; Division of Transplantation, University of Cincinnati School of Mediicne, 231 Albert Sabin Way, ML 0558, Cincinnati, OH 45267, USA.
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Cheng HY, Hu RH, Hsiao CY, Ho MC, Wu YM, Lee PH, Ho CM. Hepatitis C treatment and long-term outcome of patients with hepatocellular carcinoma after resection. J Gastroenterol Hepatol 2023; 38:1618-1628. [PMID: 37402607 DOI: 10.1111/jgh.16276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Revised: 05/28/2023] [Accepted: 06/15/2023] [Indexed: 07/06/2023]
Abstract
BACKGROUND AND AIM This study aimed to investigate the survival outcomes of antiviral agents (direct-acting antivirals [DAAs] or interferon [IFN]) in patients with hepatitis C virus who underwent liver resection for primary hepatocellular carcinoma. METHODS This retrospective single-center study included 247 patients, between 2013 and 2020, being treated with DAAs (n = 93), IFN (n = 73), or no treatment (n = 81). Overall survival (OS), recurrence-free survival (RFS), and risk factors were analyzed. RESULTS After a median follow-up time of 50.4 months, the rates of 5-year OS and RFS in the IFN, DAA, and no treatment groups were 91.5% and 55.4%, 87.2% and 39.8%, and 60.9% and 26.7%, respectively. One hundred and twenty-eight (51.6%) patients developed recurrence; recurrence was mostly (86.7%) intrahepatic, and 58 (23.4%) developed early recurrence, most of which received no antiviral treatment. The OS and RFS were similar between patients who received antiviral treatment before (50.0%) and after surgery, but longer survival was observed in patients achieving sustained virologic response. In multivariate analysis, antiviral treatment was protective for OS (hazard ratio [HR] 0.475, 95% confidence interval [CI]: 0.242-0.933) with significance but not RFS, in contrast to microvascular invasion (OS HR 3.389, 95% CI: 1.637-7.017; RFS HR 2.594, 95% CI: 1.520-4.008). In competing risk analysis, DAAs (subdistribution HR 0.086, 95% CI: 0.007-0.991) were protective against hepatic decompensation events but not recurrence events. CONCLUSION In patients with hepatitis C virus, antiviral treatment suggested OS benefit for primary hepatocellular carcinoma after resection, and DAAs might be protective against hepatic decompensation. Following adjustment for oncological factors, IFN and DAA treatment was not significantly advantageous relative to the other.
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Affiliation(s)
- Hou-Ying Cheng
- Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
- Department of Medicine, National Taiwan University Hospital Jin-Shan Branch, New Taipei, Taiwan
| | - Rey-Heng Hu
- Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
| | - Chih-Yang Hsiao
- Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
| | - Ming-Chih Ho
- Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
| | - Yao-Ming Wu
- Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
| | - Po-Huang Lee
- Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
| | - Cheng-Maw Ho
- Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
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Gambato M, Manuli C, Lynch EN, Battistella S, Germani G, Senzolo M, Zanetto A, Ferrarese A, Vitale A, Gringeri E, Cillo U, Burra P, Russo FP. Long-Term Impact of Direct-Acting Antivirals on Liver Fibrosis and Survival in HCV-Infected Liver Transplant Recipients. Viruses 2023; 15:1702. [PMID: 37632044 PMCID: PMC10458217 DOI: 10.3390/v15081702] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2023] [Revised: 07/26/2023] [Accepted: 07/28/2023] [Indexed: 08/27/2023] Open
Abstract
(1) Background: Little is known about the long-term impact of sustained virological response (SVR) on fibrosis progression and patient survival in liver transplantation (LT) recipients treated with direct-acting antivirals (DAAs). We investigated liver fibrosis evolution and patient survival in hepatitis C virus (HCV)-infected patients receiving DAAs after LT. (2) Methods: All consecutive HCV-infected patients treated with DAAs after LT between May 2014 and January 2019 were considered. The clinical and virological features were registered at the baseline and during the follow-up. The liver fibrosis was assessed by liver biopsy and/or transient elastography (TE) at the baseline and at least 1 year after the end of treatment (EoT). (3) Results: A total of 136 patients were included. The SVR12 was 78% after the first treatment and 96% after retreatment. After the SVR12, biochemical tests improved at the EoT and remained stable throughout the 3-year follow-up. Liver fibrosis improved after the SVR12 (p < 0.001); nearly half of the patients with advanced liver fibrosis experienced an improvement of an F ≤ 2. The factors associated with lower survival in SVR12 patients were the baseline platelet count (p = 0.04) and creatinine level (p = 0.04). (4) Conclusions: The long-term follow-up data demonstrated that SVR12 was associated with an improvement in hepatic function, liver fibrosis, and post-LT survival, regardless of the baseline liver fibrosis. The presence of portal hypertension before the DAAs has an impact on patient survival, even after SVR12.
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Affiliation(s)
- Martina Gambato
- Multivisceral Transplant and Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, Azienda Ospedale-Università Padova, Via Giustiniani 2, 35100 Padova, Italy; (C.M.); (E.N.L.); (S.B.); (G.G.); (M.S.); (A.F.); (P.B.)
- Department of Surgery, Oncology and Gastroenterology, University of Padova, 35100 Padova, Italy; (A.V.); (E.G.); (U.C.)
| | - Chiara Manuli
- Multivisceral Transplant and Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, Azienda Ospedale-Università Padova, Via Giustiniani 2, 35100 Padova, Italy; (C.M.); (E.N.L.); (S.B.); (G.G.); (M.S.); (A.F.); (P.B.)
- Department of Surgery, Oncology and Gastroenterology, University of Padova, 35100 Padova, Italy; (A.V.); (E.G.); (U.C.)
| | - Erica N. Lynch
- Multivisceral Transplant and Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, Azienda Ospedale-Università Padova, Via Giustiniani 2, 35100 Padova, Italy; (C.M.); (E.N.L.); (S.B.); (G.G.); (M.S.); (A.F.); (P.B.)
- Department of Surgery, Oncology and Gastroenterology, University of Padova, 35100 Padova, Italy; (A.V.); (E.G.); (U.C.)
| | - Sara Battistella
- Multivisceral Transplant and Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, Azienda Ospedale-Università Padova, Via Giustiniani 2, 35100 Padova, Italy; (C.M.); (E.N.L.); (S.B.); (G.G.); (M.S.); (A.F.); (P.B.)
- Department of Surgery, Oncology and Gastroenterology, University of Padova, 35100 Padova, Italy; (A.V.); (E.G.); (U.C.)
| | - Giacomo Germani
- Multivisceral Transplant and Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, Azienda Ospedale-Università Padova, Via Giustiniani 2, 35100 Padova, Italy; (C.M.); (E.N.L.); (S.B.); (G.G.); (M.S.); (A.F.); (P.B.)
- Department of Surgery, Oncology and Gastroenterology, University of Padova, 35100 Padova, Italy; (A.V.); (E.G.); (U.C.)
| | - Marco Senzolo
- Multivisceral Transplant and Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, Azienda Ospedale-Università Padova, Via Giustiniani 2, 35100 Padova, Italy; (C.M.); (E.N.L.); (S.B.); (G.G.); (M.S.); (A.F.); (P.B.)
- Department of Surgery, Oncology and Gastroenterology, University of Padova, 35100 Padova, Italy; (A.V.); (E.G.); (U.C.)
| | - Alberto Zanetto
- Multivisceral Transplant and Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, Azienda Ospedale-Università Padova, Via Giustiniani 2, 35100 Padova, Italy; (C.M.); (E.N.L.); (S.B.); (G.G.); (M.S.); (A.F.); (P.B.)
- Department of Surgery, Oncology and Gastroenterology, University of Padova, 35100 Padova, Italy; (A.V.); (E.G.); (U.C.)
| | - Alberto Ferrarese
- Multivisceral Transplant and Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, Azienda Ospedale-Università Padova, Via Giustiniani 2, 35100 Padova, Italy; (C.M.); (E.N.L.); (S.B.); (G.G.); (M.S.); (A.F.); (P.B.)
- Department of Surgery, Oncology and Gastroenterology, University of Padova, 35100 Padova, Italy; (A.V.); (E.G.); (U.C.)
| | - Alessandro Vitale
- Department of Surgery, Oncology and Gastroenterology, University of Padova, 35100 Padova, Italy; (A.V.); (E.G.); (U.C.)
- Hepatobiliary Urgery and Liver Transplantation, Department of Surgery, Oncology and Gastroenterology, Azienda Ospedale-Università Padova, 35100 Padova, Italy
| | - Enrico Gringeri
- Department of Surgery, Oncology and Gastroenterology, University of Padova, 35100 Padova, Italy; (A.V.); (E.G.); (U.C.)
- Hepatobiliary Urgery and Liver Transplantation, Department of Surgery, Oncology and Gastroenterology, Azienda Ospedale-Università Padova, 35100 Padova, Italy
| | - Umberto Cillo
- Department of Surgery, Oncology and Gastroenterology, University of Padova, 35100 Padova, Italy; (A.V.); (E.G.); (U.C.)
- Hepatobiliary Urgery and Liver Transplantation, Department of Surgery, Oncology and Gastroenterology, Azienda Ospedale-Università Padova, 35100 Padova, Italy
| | - Patrizia Burra
- Multivisceral Transplant and Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, Azienda Ospedale-Università Padova, Via Giustiniani 2, 35100 Padova, Italy; (C.M.); (E.N.L.); (S.B.); (G.G.); (M.S.); (A.F.); (P.B.)
- Department of Surgery, Oncology and Gastroenterology, University of Padova, 35100 Padova, Italy; (A.V.); (E.G.); (U.C.)
| | - Francesco Paolo Russo
- Multivisceral Transplant and Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, Azienda Ospedale-Università Padova, Via Giustiniani 2, 35100 Padova, Italy; (C.M.); (E.N.L.); (S.B.); (G.G.); (M.S.); (A.F.); (P.B.)
- Department of Surgery, Oncology and Gastroenterology, University of Padova, 35100 Padova, Italy; (A.V.); (E.G.); (U.C.)
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Ismail B, Benrajab KM, Bejarano P, Ruiz P, Sears D, Tzakis A, Zervos XB. Benign course of residual inflammation at end of treatment of liver transplant recipients after sofosbuvir based therapy. World J Hepatol 2022; 14:602-611. [PMID: 35582292 PMCID: PMC9055203 DOI: 10.4254/wjh.v14.i3.602] [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: 10/23/2021] [Revised: 12/16/2021] [Accepted: 02/16/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Persistent inflammation on histology after successful hepatitis C (HCV) treatment has been reported. However, data regarding the long-term impact in liver transplant recipients is limited, particularly after using direct-acting antiviral (DAA) therapies.
AIM To evaluate the impact of successful treatment with DAAs on histological changes and occult HCV and to describe the clinical course of residual inflammation in liver transplant recipients.
METHODS We conducted a case series of 13 chronic HCV infected liver transplant recipients successfully treated with DAAs between December 2013 and May 2014. All patients were treated for 24 wk and had non-detectable serum HCV RNA by the time of biopsy. Only patients with at least one liver biopsy at or after treatment were included. We examined liver biopsies for evidence of residual inflammation and the presence of intrahepatic HCV RNA.
RESULTS Persistent inflammation was seen in 12/13 patients on end of treatment biopsy. Inflammation was still seen in the available five follow-up biopsies (range 38-48 wk after the end of treatment). Intrahepatic HCV RNA was undetectable in all biopsies. All patients had preserved graft function for a mean follow-up of 2.5 years, except one that developed chronic rejection.
CONCLUSION After successful HCV treatment with DAAs, liver transplant recipients may have persistent inflammation on biopsy without evidence of intracellular RNA. The clinical outcome remained favorable in most patients. Further studies with a larger number and longer follow-up are needed to establish the implication of this finding on long-term graft function.
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Affiliation(s)
- Bahaaeldeen Ismail
- Division of Digestive Diseases and Nutrition, University of Kentucky College of Medicine, Lexington, KY 40536, United States
| | - Karim M Benrajab
- Division of Digestive Diseases and Nutrition, University of Kentucky College of Medicine, Lexington, KY 40536, United States
| | - Pablo Bejarano
- Department of Pathology, Cleveland Clinic Florida, Weston, FL 33331, United States
| | - Phillip Ruiz
- Department of Pathology, University of Miami Miller School of Medicine, Miami, FL 33136, United States
| | - Debbie Sears
- Department of Liver Transplant, Cleveland Clinic Florida, Weston, FL 33331, United States
| | - Andreas Tzakis
- Department of Liver Transplant, Cleveland Clinic Florida, Weston, FL 33331, United States
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Saracco GM, Marzano A, Rizzetto M. Therapy of Chronic Viral Hepatitis: The Light at the End of the Tunnel? Biomedicines 2022; 10:534. [PMID: 35327336 PMCID: PMC8945793 DOI: 10.3390/biomedicines10030534] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Revised: 02/08/2022] [Accepted: 02/16/2022] [Indexed: 02/06/2023] Open
Abstract
Chronic viral hepatitis determines significant morbidity and mortality globally and is caused by three main etiological actors (Hepatitis B Virus, Hepatitis C Virus, and Hepatitis D Virus) with different replicative cycles and biological behaviors. Thus, therapies change according to the different characteristics of the viruses. In chronic hepatitis B, long term suppressive treatments with nucleoside/nucleotide analogues have had a dramatic impact on the evolution of liver disease and liver-related complications. However, a conclusive clearance of the virus is difficult to obtain; new strategies that are able to eradicate the infection are currently objects of research. The therapy for Hepatitis D Virus infection is challenging due to the unique virology of the virus, which uses the synthetic machinery of the infected hepatocyte for its own replication and cannot be targeted by conventional antivirals that are active against virus-coded proteins. Recently introduced antivirals, such as bulevertide and lonafarnib, display definite but only partial efficacy in reducing serum HDV-RNA. However, in combination with pegylated interferon, they provide a synergistic therapeutic effect and appear to represent the current best therapy for HDV-positive patients. With the advent of Direct Acting Antiviral Agents (DAAs), a dramatic breakthrough has occurred in the therapeutic scenario of chronic hepatitis C. Cure of HCV infection is achieved in more than 95% of treated patients, irrespective of their baseline liver fibrosis status. Potentially, the goal of global HCV elimination by 2030 as endorsed by the World Health Organization can be obtained if more global subsidised supplies of DAAs are provided.
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Affiliation(s)
- Giorgio Maria Saracco
- Gastro-Hepatoloy Unit, Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (A.M.); (M.R.)
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Caligiuri A, Gentilini A, Pastore M, Gitto S, Marra F. Cellular and Molecular Mechanisms Underlying Liver Fibrosis Regression. Cells 2021; 10:cells10102759. [PMID: 34685739 PMCID: PMC8534788 DOI: 10.3390/cells10102759] [Citation(s) in RCA: 118] [Impact Index Per Article: 29.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Revised: 10/08/2021] [Accepted: 10/09/2021] [Indexed: 12/12/2022] Open
Abstract
Chronic liver injury of different etiologies may result in hepatic fibrosis, a scar formation process consisting in altered deposition of extracellular matrix. Progression of fibrosis can lead to impaired liver architecture and function, resulting in cirrhosis and organ failure. Although fibrosis was previous thought to be an irreversible process, recent evidence convincingly demonstrated resolution of fibrosis in different organs when the cause of injury is removed. In the liver, due to its high regenerative ability, the extent of fibrosis regression and reversion to normal architecture is higher than in other tissues, even in advanced disease. The mechanisms of liver fibrosis resolution can be recapitulated in the following main points: removal of injurious factors causing chronic hepatic damage, elimination, or inactivation of myofibroblasts (through various cell fates, including apoptosis, senescence, and reprogramming), inactivation of inflammatory response and induction of anti-inflammatory/restorative pathways, and degradation of extracellular matrix. In this review, we will discuss the major cellular and molecular mechanisms underlying the regression of fibrosis/cirrhosis and the potential therapeutic approaches aimed at reversing the fibrogenic process.
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Ehsan N, Sweed D, Elsabaawy M. Evaluation of HCV-related liver fibrosis post-successful DAA therapy. EGYPTIAN LIVER JOURNAL 2021. [DOI: 10.1186/s43066-021-00129-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Abstract
Background
The rapidly developing era of direct-acting antiviral regimens (DAAs) for more than one hepatitis C virus (HCV) genotype had certainly alleviated HCV burden all over the world. Liver fibrosis is the major dramatic complication of HCV infection, and its progression leads to cirrhosis, liver failure, and hepatocellular carcinoma. The impact of DAAs on liver fibrosis had been debatably evaluated with undetermined resolution.
Main body
The aim of this review is to accurately revise the effects of DAA regimens on liver fibrosis which can either be regression, progression, or non-significant association. Liver fibrosis regression is a genuine fact assured by many retrospective and prospective clinical studies. Evaluation could be concluded early post-therapy reflecting the dynamic nature of the process.
Conclusions
The ideal application of DAA regimens in treating HCV has to be accomplished with efficient non-invasive markers in differentiating proper fibrosis evaluation from necroinflammation consequences. Liver biopsy is the gold standard that visualizes the dynamic of fibrosis regression.
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Rockey DC, Friedman SL. Fibrosis Regression After Eradication of Hepatitis C Virus: From Bench to Bedside. Gastroenterology 2021; 160:1502-1520.e1. [PMID: 33529675 PMCID: PMC8601597 DOI: 10.1053/j.gastro.2020.09.065] [Citation(s) in RCA: 78] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Revised: 09/01/2020] [Accepted: 09/06/2020] [Indexed: 02/06/2023]
Abstract
Hepatitis C virus (HCV) infection and its complications have been the major cause of cirrhosis and its complications for several decades in the Western world. Until recently, treatment for HCV with interferon-based regimens was associated with moderate success but was difficult to tolerate. More recently, however, an arsenal of novel and highly effective direct-acting antiviral (DAA) drugs has transformed the landscape by curing HCV in a broad range of patients, including those with established advanced fibrosis, cirrhosis, comorbidities, and even those with complications of cirrhosis. Fibrosis is a dynamic process comprising both extracellular matrix deposition, as well as its degradation. With almost universal sustained virologic response (SVR) (ie, elimination of HCV), it is timely to explore whether HCV eradication can reverse fibrosis and cirrhosis. Indeed, fibrosis in several types of liver disease is reversible, including HCV. However, we do not know with certainty in whom fibrosis regression can be expected after HCV elimination, how quickly it occurs, and whether antifibrotic therapies will be indicated in those with persistent cirrhosis. This review summarizes the evidence for reversibility of fibrosis and cirrhosis after HCV eradication, its impact on clinical outcomes, and therapeutic prospects for directly promoting fibrosis regression in patients whose fibrosis persists after SVR.
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Affiliation(s)
- Don C Rockey
- The Medical University of South Carolina, Charleston, South Carolina.
| | - Scott L Friedman
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, New York
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Saleh SA, Salama MM, Alhusseini MM, Mohamed GA. M2BPGi for assessing liver fibrosis in patients with hepatitis C treated with direct-acting antivirals. World J Gastroenterol 2020; 26:2864-2876. [PMID: 32550761 PMCID: PMC7284180 DOI: 10.3748/wjg.v26.i21.2864] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2020] [Revised: 03/27/2020] [Accepted: 05/28/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Assessing liver fibrosis is important for predicting the efficacy of direct-acting antivirals (DAAs) and patient prognosis. Non-invasive techniques to assess liver fibrosis are becoming important. Recently, serum Mac-2 binding protein glycosylation isomer (M2BPGi) was identified as a non-invasive marker of liver fibrosis.
AIM To investigate the diagnostic accuracy of M2BPGi in assessing liver fibrosis in patients with chronic hepatitis C (CHC) treated with DAAs.
METHODS From December 2017 to August 2018, 80 treatment-naïve adult patients with CHC who were eligible for DAAs therapy were consecutively enrolled in this observational cohort study. For 12 weeks, 65 patients were treated with sofosbuvir/daclatasvir, and 15 patients were treated with sofosbuvir/daclatasvir and a weight-based dose of ribavirin at knowledge and technology association for hepatitis C management clinic, Cairo, Egypt. We measured serum M2BPGi levels, PAPAS index, fibrosis-4 (FIB-4) score and liver stiffness measurements (LSM) at baseline and 12 weeks after the end of treatment. Serum M2BPGi levels were measured using enzyme-linked immunosorbent assay.
RESULTS All patients achieved sustained virologic response (SVR12) (100%). Serum M2BPGi levels, LSM, FIB-4 score and PAPAS index decreased significantly at SVR12 (P < 0.05). Serum M2BPGi levels correlated positively with LSM at baseline and SVR12 (P < 0.001). At baseline, compared with the FIB-4 score and PAPAS index, M2BPGi was the best marker to distinguish patients with grade F4 fibrosis (AUC = 0.801, P < 0.001), patients with grade F2 from grade F0-1 fibrosis (AUC = 0.713, P = 0.012), patients with grade F3-4 from grade F0-2 fibrosis (AUC = 0.730, P < 0.001), and patients with grade F2-4 from grade F0-1 fibrosis (AUC = 0.763, P < 0.001). At SVR12, M2BPGi had the greatest AUCs for differentiating patients with grade F4 fibrosis (AUC = 0.844, P < 0.001), patients with grade F3 from grade F0-2 fibrosis (AUC = 0.893, P = 0.002), patients with grade F3-4 from grade F0-2 fibrosis (AUC = 0.891, P < 0.001), and patients with grade F2-4 from grade F0-1 fibrosis (AUC = 0.750, P < 0.001).
CONCLUSION M2BPGi is a reliable marker for the non-invasive assessment and prediction of liver fibrosis regression in patients with CHC who achieved an SVR with DAAs therapy.
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Affiliation(s)
- Shereen A Saleh
- Gastroenterology and Hepatology Unit, Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo 11341, Egypt
| | - Mohamed M Salama
- Gastroenterology and Hepatology Unit, Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo 11341, Egypt
| | - Marwan M Alhusseini
- Gastroenterology and Hepatology Unit, Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo 11341, Egypt
| | - Ghada A Mohamed
- Gastroenterology and Hepatology Unit, Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo 11341, Egypt
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11
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Cieciura T, Hryniewiecka E, Perkowska-Ptasińska A, Ciszek M, Pączek L. Shear Wave Elastography Performance in Noninvasive Assessment of Liver Cirrhosis in Liver Transplant Recipients With the Recurrence of Hepatitis C Infection. Transplant Proc 2020; 52:2480-2483. [PMID: 32446694 DOI: 10.1016/j.transproceed.2020.02.097] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2020] [Revised: 02/09/2020] [Accepted: 02/13/2020] [Indexed: 01/02/2023]
Abstract
BACKGROUND The recurrence of hepatitis C (HCV) after liver transplant (LTX) leads to graft fibrosis and cirrhosis. Liver biopsy remains the criterion standard for their diagnosis and monitoring. Our objective was evaluation of shear wave elastography (SWE) in patients with HCV recurrence after LTX and its comparison with histopathologic fibrosis assessment scoring systems. METHODS A total of 101 LTX recipients with HCV recurrence (42 women [41.6%] and 59 men [58.4%]) were evaluated by graft biopsy specimens (Ishak, Scheurer, and meta-analysis of histologic data in viral hepatitis [Metavir] score) and SWE (liver stiffness). Median age of patients was 59.4 years; median time from LTX was 84.9 months. The study protocol conforms with the Declaration of Helsinki. RESULTS Median liver stiffness was 21.3 kPa. To differentiate between liver fibrosis and cirrhosis, patients were divided into 2 subgroups: Ishak score fibrosis (1-4 [85.2%]) and cirrhosis (5-6 [13.9%]); Scheurer score fibrosis (0-3 [85.2%]) and cirrhosis (4 [12.9%]); Metavir score fibrosis (0-3 [85.2%]) and cirrhosis (4 [14.9%]). We have observed statistically significant differences between liver fibrosis and liver cirrhosis groups defined on the basis of Ishak, Scheurer, and Metavir scoring systems: 20.8 kPa vs 29.6 kPa (P = .001), 20.7 kPa vs 30.3 kPa (P = .0005), and 20.7 kPa vs 28.8 kPa (P = .002), respectively. CONCLUSIONS Our results indicate that SWE may be useful in differentiating patients with advanced cirrhosis from those with fibrosis and may be helpful in the noninvasive diagnosis and monitoring of HCV recurrence after LTX.
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Affiliation(s)
- Tomasz Cieciura
- Department of Immunology, Transplant Medicine, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland
| | - Ewa Hryniewiecka
- Department of Immunology, Transplant Medicine, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland
| | | | - Michał Ciszek
- Department of Immunology, Transplant Medicine, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland.
| | - Leszek Pączek
- Department of Immunology, Transplant Medicine, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland
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12
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Shiha G, Soliman R, Mikhail N, Ibrahim A, Serwah A, Khattab M. Changes in hepatic fibrosis stages after achieving SVR following direct‐acting anti‐viral treatment: a prospective study. ACTA ACUST UNITED AC 2020. [DOI: 10.1002/ygh2.384] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Gamal Shiha
- Egyptian Liver Research Institute and Hospital (ELRIAH) Sherbin, El‐Mansoura Egypt
- Hepatology and Gastroenterology Unit Internal Medicine Department Faculty of Medicine Mansoura University Mansoura Egypt
| | - Reham Soliman
- Egyptian Liver Research Institute and Hospital (ELRIAH) Sherbin, El‐Mansoura Egypt
- 2-Tropical Medicine Department Faculty of Medicine Port Said University Port Said Egypt
| | - Nabiel Mikhail
- Egyptian Liver Research Institute and Hospital (ELRIAH) Sherbin, El‐Mansoura Egypt
- Department of Biostatistics and Cancer Epidemiology South Egypt Cancer InstituteAssiut University Assiut Egypt
| | - Alaa Ibrahim
- Internal Medicine Department Faculty of Medicine Banha University Banha Egypt
| | - Abdel‐Hamid Serwah
- Internal Medicine Department Faculty of Medicine Suez Canal University Egypt
| | - Mahmoud Khattab
- Internal Medicine Department Faculty of Medicine Minya University Minya Egypt
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13
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Liver stiffness in chronic hepatitis C virus infection. ACTA ACUST UNITED AC 2020; 57:85-98. [PMID: 30447147 DOI: 10.2478/rjim-2018-0034] [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: 07/18/2018] [Indexed: 11/20/2022]
Abstract
INTRODUCTION The severity of liver fibrosis can be assessed noninvasively today by liver stiffness measurements. Vibration-controlled transient elastography, shear wave elastography or magnetic resonance elastography are techniques increasingly used for this purpose. METHODS This article presents the recent advances in the use of new techniques for liver fibrosis assessment in chronic hepatitis C: the correlation between liver stiffness values and liver fibrosis estimated by liver biopsies, the prognosis role of liver stiffness values, their usefulness in monitoring the treatment response, in assessing the severity of portal hypertension and in estimating the presence of esophageal varices. Scientific articles from January 2017 to January 2018 were searched in PubMed and PubMed Central databases, using the terms "liver stiffness" and "hepatitis C". RESULTS The median liver stiffness values measured with different techniques are not identical, so that FibroScan thresholds cannot be used on any other elastographic machine. The higher the liver's stiffness measurement, the higher the liver-related events in patients with chronic hepatitis C. A liver stiffness measurement over 17 kPa could be an independent predictor for the presence of esophageal varices as well as a spleen with a longitudinal span ≥ 15 cm for patients with a value of liver stiffness < 17 kPa. A progressive and persistent decrease in liver stiffness is dependent on sustained virological response achievement. The lack of liver stiffness decrease has been associated with relapsers and a low value of liver stiffness at baseline. CONCLUSION Liver stiffness provides clues about the severity and evolution of liver disease.
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14
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Verna EC, Tsapepas D, Emond JC, Brown RS, Mohan S. Utilization of Hepatitis C Virus (HCV)-Viremic Organs for HCV Negative Recipients: Is Practice Speeding Past the Evidence? Hepatology 2020; 71:4-7. [PMID: 31505047 DOI: 10.1002/hep.30933] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2019] [Accepted: 08/20/2019] [Indexed: 01/26/2023]
Affiliation(s)
- Elizabeth C Verna
- Department of Medicine, Center for Liver Disease and Transplantation, Columbia University Irving Medical Center, New York, NY
| | - Demetra Tsapepas
- Department of Transplantation, New York-Presbyterian Hospital, Columbia University Irving Medical Center, New York, NY.,Department of Surgery, Center for Liver Disease and Transplantation, Columbia University Irving Medical Center, New York, NY
| | - Jean C Emond
- Department of Surgery, Center for Liver Disease and Transplantation, Columbia University Irving Medical Center, New York, NY
| | - Robert S Brown
- Department of Medicine, Center for Liver Disease and Transplantation, Columbia University Irving Medical Center, New York, NY.,Department of Medicine, Center for Liver Disease and Transplantation, Weill Cornell Medicine, New York, NY
| | - Sumit Mohan
- Department of Medicine, Division of Nephrology, Columbia University Irving Medical Center, New York, NY.,Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY
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15
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Abstract
PURPOSE OF REVIEW Hepatitis C virus (HCV) infection has been the leading cause of cirrhosis in the United States now for the last several decades. With the introduction of highly effective direct acting antiviral (DAA) drugs, cure rates are now almost 100%. With this explosion of effective therapy, it is possible that many patients with HCV may have reversion in fibrosis. The purpose of this review is, therefore, to report on recent findings in this field. RECENT FINDINGS Older data that examined the effect of interferon-based HCV therapy indicate that fibrosis reverses after HCV eradication. More recent work in the DAA era similarly indicates that fibrosis is reversible. A caveat is that DAA therapy causes rapid viral clearance, and appears to lead to rapid reductions in inflammation. Some tools (such as transient elastography), which may also reflect the inflammatory response, and thus may 'overestimate' of fibrosis reversal. However, emerging data suggesting improved outcomes in patients with cirrhosis after HCV clearance support the concept that even cirrhosis reverses in some patients. SUMMARY Fibrosis (and cirrhosis) reversion, to some extent, occurs after HCV clearance. This topic is vitally important and information continues to emerge; more data on this subject are expected and needed.
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16
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The safety and efficacy of ledipasvir/sofosbuvir with or without ribavirin in the treatment of orthotopic liver transplant recipients with recurrent hepatitis C: real-world data. Eur J Gastroenterol Hepatol 2018; 30:761-765. [PMID: 29481384 DOI: 10.1097/meg.0000000000001101] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
BACKGROUND Recurrent hepatitis C (RHC) in orthotopic liver transplantation (OLT) population is associated with accelerated rates of fibrosis, low efficacy and decreased tolerability with traditional therapies. AIM The aim of this study was to evaluate the safety and efficacy of ledipasvir/sofosbuvir (LED/SOF) with or without ribavirin (RBV) in OLT patients with RHC. PATIENTS AND METHODS Patients at least 3 months post-OLT and with documented RHC were treated with LED/SOF with or without RBV for either 12 or 24 weeks. End-of-treatment and sustained virological response 12 weeks after the completion of treatment were documented. Patients were closely monitored for treatment-related adverse effects and the potential need for adjustment in their immunosuppression. RESULTS Seventy-one patients were included in the study. Median age was 62 years. Median time from OLT was 55 months. Twenty-six (36.6%) patients were treatment-naive and 45 (63.4%) had previously failed interferon-based therapies. The majority of patients (57.7%) had stage F0-F2 fibrosis. Sixty-seven (94.3%) patients completed 12 weeks of LED/SOF with RBV, three patients completed 12 or 24 weeks of LED/SOF without RBV, and one patient completed only 8 weeks of LED/SOF without RBV owing to severe allograft dysfunction. Sustained virological response was near universal in our cohort (98.5%) regardless of genotype, fibrosis stage, and regimen or treatment duration. Most commonly reported side effects were malaise and gastrointestinal upset. No patient required adjustment in immunosuppression and no episodes of rejection were documented during treatment. CONCLUSION The combination of LED/SOF with RBV for 12 weeks or LED/SOF for 24 weeks is very effective and safe in treating OLT recipients with RHC.
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17
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Alem SA, Said M, Anwar I, Abdellatif Z, Elbaz T, Eletreby R, AbouElKhair M, El-Serafy M, Mogawer S, El-Amir M, El-Shazly M, Hosny A, Yosry A. Improvement of liver stiffness measurement, acoustic radiation force impulse measurements, and noninvasive fibrosis markers after direct-acting antivirals for hepatitis C virus G4 recurrence post living donor liver transplantation: Egyptian cohort. J Med Virol 2018; 90:1508-1515. [PMID: 29718546 DOI: 10.1002/jmv.25210] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2017] [Accepted: 04/13/2018] [Indexed: 12/12/2022]
Abstract
Progression of recurrent hepatitis C is accelerated in liver transplant (LT) recipients. Direct-acting antivirals (DAAs) have recently emerged as a promising therapeutic regimen for the treatment of hepatitis C virus infection. Rates of sustained virological response (SVR) have drastically improved since the introduction of DAAs. The aim is to elucidate the changes in liver stiffness measurement (LSM) by transient elastography (TE) as well as acoustic radiation force impulse (ARFI) elastography and fibrosis scores after DAA treatment in LT recipients with hepatitis C virus recurrence. A single-center, prospective study including 58 LT recipients with hepatitis C recurrence who received different sofosbuvir-based treatment regimens. Transient elastography and ARFI elastography values were recorded as well as fibrosis 4 score (FIB-4) and aspartate aminotransferase-to-platelet ratio index were calculated at baseline and SVR at week 24 (SVR24). The outcome was improvement in LSM and at least a 20% decrease in LSM at SVR24 compared with baseline. The sustained virological response was 98.1%. There was improvement of platelet counts, alanine aminotransferase, and aspartate aminotransferase, which in turn caused improvement in fibrosis scores at SVR24. LSM by TE and ARFI elastography decreased from the baseline median value of 6.3 kPa (interquartile range [IQR]; 4.6 to 8.8 kPa) and 1.28 m/s (IQR; 1.07 to 1.53 m/s) to an SVR24 median value of 6.2 kPa (IQR; 4.85 to 8.9 kPa) and 1.12 (IQR; 0.97 to 1.30 m/s), respectively. Logistic regression analysis showed that baseline viral load was the only significant predictor of improvement in LS after DAA therapy at SVR24. Sofosbuvir-based treatment resulted in an early improvement in parameters of liver fibrosis in post-LT patients with hepatitis C recurrence.
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Affiliation(s)
- Shereen Abdel Alem
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed Said
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ismail Anwar
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Zeinab Abdellatif
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Tamer Elbaz
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Rasha Eletreby
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mahmoud AbouElKhair
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Magdy El-Serafy
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Sherif Mogawer
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mona El-Amir
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mostafa El-Shazly
- General Surgery & Liver Transplantation Unit, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Adel Hosny
- General Surgery & Liver Transplantation Unit, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ayman Yosry
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
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18
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Mauro E, Crespo G, Montironi C, Londoño MC, Hernández-Gea V, Ruiz P, Sastre L, Lombardo J, Mariño Z, Díaz A, Colmenero J, Rimola A, Garcia-Pagán JC, Brunet M, Forns X, Navasa M. Portal pressure and liver stiffness measurements in the prediction of fibrosis regression after sustained virological response in recurrent hepatitis C. Hepatology 2018; 67:1683-1694. [PMID: 28960366 DOI: 10.1002/hep.29557] [Citation(s) in RCA: 109] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2017] [Revised: 08/21/2017] [Accepted: 09/25/2017] [Indexed: 12/11/2022]
Abstract
UNLABELLED Sustained virological response (SVR) improves survival in post-liver transplant (LT) recurrent hepatitis C. However, the impact of SVR on fibrosis regression is not well defined. In addition, the performance of noninvasive methods to evaluate the presence of fibrosis and portal hypertension (PH) post-SVR has been scarcely evaluated. We aimed to investigate the degree of fibrosis regression (decrease ≥1 METAVIR stage) after-SVR and its associated factors in recurrent hepatitis C, as well as the diagnostic capacity of noninvasive methods in the assessment of liver fibrosis and PH after viral clearance. We evaluated 112 hepatitis C virus-infected LT recipients who achieved SVR between 2001 and 2015. A liver biopsy was performed before treatment and 12 months post-SVR. Hepatic venous pressure gradient (HVPG), liver stiffness measurement (LSM), and Enhanced Liver Fibrosis (ELF) score were also determined at the same time points. Sixty-seven percent of the cohort presented fibrosis regression: 43% in recipients with cirrhosis and 72%-85% in the remaining stages (P = 0.002). HVPG, LSM, and ELF significantly decreased post-SVR. Liver function significantly improved, and survival was significantly better in patients achieving fibrosis regression. Baseline HVPG and LSM as well as decompensations before therapy were independent predictors of fibrosis regression. One year post-SVR, LSM had a high diagnostic accuracy to discard the presence of advanced fibrosis (AF) and clinically significant PH (AUROC, 0.902 and 0.888). CONCLUSION In conclusion, SVR post-LT induces fibrosis regression in most patients, leading to significant clinical benefits. Pretreatment HVPG and LSM are significant determinants of the likelihood of fibrosis regression. Finally, LSM accurately predicts the presence of AF and PH 1 year after SVR and thus can be used to determine monitoring strategies. (Hepatology 2018;67:1683-1694).
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Affiliation(s)
- Ezequiel Mauro
- Liver Transplant Unit, Liver Unit, IDIBAPS, CIBERehd, Hospital Clínic, Barcelona, Spain.,Liver Unit, Hospital Italiano, Buenos Aires, Argentina
| | - Gonzalo Crespo
- Liver Transplant Unit, Liver Unit, IDIBAPS, CIBERehd, Hospital Clínic, Barcelona, Spain
| | | | | | - Virginia Hernández-Gea
- Barcelona Hemodynamics Laboratory, Liver Unit, IDIBAPS, CIBERehd, Hospital Clínic, Barcelona, Spain
| | - Pablo Ruiz
- Liver Transplant Unit, Liver Unit, IDIBAPS, CIBERehd, Hospital Clínic, Barcelona, Spain
| | - Lydia Sastre
- Liver Transplant Unit, Liver Unit, IDIBAPS, CIBERehd, Hospital Clínic, Barcelona, Spain
| | - Julissa Lombardo
- Liver Transplant Unit, Liver Unit, IDIBAPS, CIBERehd, Hospital Clínic, Barcelona, Spain
| | - Zoe Mariño
- Liver Unit, IDIBAPS, CIBERehd, Hospital Clínic, Barcelona, Spain
| | - Alba Díaz
- Pathology Department, Hospital Clínic, Barcelona, Spain
| | - Jordi Colmenero
- Liver Transplant Unit, Liver Unit, IDIBAPS, CIBERehd, Hospital Clínic, Barcelona, Spain
| | - Antoni Rimola
- Liver Transplant Unit, Liver Unit, IDIBAPS, CIBERehd, Hospital Clínic, Barcelona, Spain
| | - Juan Carlos Garcia-Pagán
- Barcelona Hemodynamics Laboratory, Liver Unit, IDIBAPS, CIBERehd, Hospital Clínic, Barcelona, Spain
| | - Mercé Brunet
- Pharmacology and Toxicology, IDIBAPS, CIBERehd, Hospital Clínic, University of Barcelona, Barcelona, Spain
| | - Xavier Forns
- Liver Unit, IDIBAPS, CIBERehd, Hospital Clínic, Barcelona, Spain
| | - Miquel Navasa
- Liver Transplant Unit, Liver Unit, IDIBAPS, CIBERehd, Hospital Clínic, Barcelona, Spain
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19
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Unger LW, Berlakovich GA, Trauner M, Reiberger T. Management of portal hypertension before and after liver transplantation. Liver Transpl 2018; 24:112-121. [PMID: 28752925 DOI: 10.1002/lt.24830] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2017] [Revised: 07/23/2017] [Accepted: 07/25/2017] [Indexed: 12/19/2022]
Abstract
Orthotopic liver transplantation (OLT) represents a curative treatment option for end-stage liver disease (ESLD). Although epidemiology of ESLD has recently changed due to the rising prevalence of nonalcoholic fatty liver disease and the decreased burden of hepatitis C virus infections due to highly effective antiviral regimens, the management of portal hypertension (PHT) remains a clinical challenge in the pre- and post-OLT setting. The measurement of the hepatic venous pressure gradient represents the most reliable but invasive tool for assessment of the severity of PHT. Although novel liver ultrasound and magnetic resonance-based elastography methods have been developed, their value to screen for liver fibrosis and PHT in transplanted patients remains to be established. Nonselective beta-blockers represent the cornerstone of medical treatment of PHT, but more studies on their effects on clinical endpoints after OLT are needed. Statins are widely used to treat hyperlipidemia, which is a common condition after OLT. Although a growing body of evidence suggests that statins decrease portal pressure and PHT-related complications in ESLD, studies on potential benefits of statins after OLT are lacking. Finally, transjugular intrahepatic portosystemic shunts (TIPS) are effective in decreasing PHT and seem to decrease mortality on the OLT waiting list. Moreover, TIPS does not have an impact on liver function nor complicate the transplant surgical procedures. TIPS may also be used after OLT, but the evidence is limited. In conclusion, whereas the management of PHT in patients with ESLD is based on strong evidence, further data on the value of noninvasive monitoring tools as well as on medical and invasive treatment options in the post-OLT setting are needed to improve management strategies in patients with recurrent PHT after liver transplantation. Liver Transplantation 24 112-121 2018 AASLD.
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Affiliation(s)
| | | | - Michael Trauner
- Vienna Hepatic Hemodynamic Laboratory, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Thomas Reiberger
- Vienna Hepatic Hemodynamic Laboratory, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
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20
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Singh S, Facciorusso A, Loomba R, Falck-Ytter YT. Magnitude and Kinetics of Decrease in Liver Stiffness After Antiviral Therapy in Patients With Chronic Hepatitis C: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2018; 16:27-38.e4. [PMID: 28479504 PMCID: PMC5671365 DOI: 10.1016/j.cgh.2017.04.038] [Citation(s) in RCA: 142] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2017] [Revised: 03/23/2017] [Accepted: 04/27/2017] [Indexed: 12/15/2022]
Abstract
BACKGROUND & AIMS We performed a systematic review and meta-analysis to estimate the decrease in liver stiffness, measured by vibration-controlled transient elastrography (VCTE), in patients with hepatitis C virus infection who achieved a sustained virologic response (SVR). METHODS We searched the literature through October 2016 for observational studies or randomized controlled trials of adults with hepatitis C virus infection who received antiviral therapy (either direct-acting antiviral agents or interferon-based therapies), underwent liver stiffness measurement using VCTE before starting therapy, and had at least 1 follow-up VCTE after completion of therapy; studies also provided data on mean or median liver stiffness measurements for patients who did and did not achieve an SVR. We identified 24 studies, and estimated weighted mean difference (and 95% confidence interval) in liver stiffness in patients with versus without SVR using random-effects meta-analysis. RESULTS In patients who achieved SVR, liver stiffness decreased by 2.4 kPa at the end of therapy (95% CI, -1.7 to -3.0), by 3.1 kPa 1-6 months after therapy (95% CI, -1.6 to -4.7), by 3.2 kPa 6-12 months after therapy (90% CI, -2.6 to -3.9), and 4.1 kPa 12 months or more after therapy (95% CI, -3.3 to -4.9) (median decrease, 28.2%; interquartile range, 21.8-34.8). In contrast, there was no significant change in liver stiffness in patients who did not achieve an SVR (at 6-12 months after therapy, decrease of 0.6 kPa; 95% CI, -1.7 to 0.5). Decreases in liver stiffness were significantly greater in patients treated with direct-acting antiviral agents than with interferon-based therapy (decrease of 4.5 kPa vs decrease of 2.6 kPa; P = .03), cirrhosis at baseline (decrease of 5.1 kPa vs decrease of 2.8 kPa in patients with no cirrhosis; P = .02), or high pretreatment levels of alanine aminotransferase (P < .01). Among patients with baseline liver stiffness >9.5 kPa, 47% (95% CI, 27%-68%) achieved posttreatment liver stiffness of <9.5 kPa. CONCLUSIONS In a systematic review and meta-analysis, we associated eradication of hepatitis C virus infection (SVR) with significant decreases in liver stiffness, particularly in patients with high baseline level of inflammation or patients who received direct-acting antiviral agents. Almost half the patients considered to have advanced fibrosis, based on VCTE, before therapy achieved posttreatment liver stiffness levels <9.5 kPa. Clinical Trial Registration no: CRD42016051034.
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Affiliation(s)
- Siddharth Singh
- Division of Gastroenterology, University of California San Diego, La Jolla, California; Division of Biomedical Informatics, University of California San Diego, La Jolla, California.
| | - Antonio Facciorusso
- Gastroenterology Unit, Department of Medical Sciences, University of
Foggia, Foggia, Italy
| | - Rohit Loomba
- Division of Gastroenterology, University of California San Diego, La
Jolla, California,NAFLD Translational Research Unit, La Jolla, California
| | - Yngve T. Falck-Ytter
- Division of Gastroenterology and Hepatology, Case and VA Medical
Center, Case Western Reserve University, Cleveland, Ohio
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21
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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] [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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Burra P, Zanetto A. Filling the gap between clinical trials and real life in the treatment of severe HCV recurrence after liver transplantation. Transpl Int 2017; 30:239-242. [PMID: 28102906 DOI: 10.1111/tri.12917] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2017] [Accepted: 01/12/2017] [Indexed: 02/06/2023]
Affiliation(s)
- Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Alberto Zanetto
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
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Disease Reversibility in Patients With Post-Hepatitis C Cirrhosis: Is the Point of No Return the Same Before and After Liver Transplantation? A Review. Transplantation 2017; 101:916-923. [PMID: 28060241 DOI: 10.1097/tp.0000000000001633] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Liver fibrosis can regress in patients with chronic hepatitis in whom the underlying cause of liver damage is adequately treated. Studies documenting this benefit have been mostly performed in the setting of viral hepatitis, particularly hepatitis C virus, where sustained viral response has been unequivocally shown to result in histological and clinical improvement. With the advent of the new IFN-free regimens, highly effective and safe even in those historically considered "difficult to treat and cure patients," additional benefits have been documented in patients treated at advanced stages of disease, including improvement in liver function with hepatic "recompensation," reduction of portal hypertension, and eventually avoidance of liver transplantation. Disease reversibility has been also demonstrated in the posttransplant setting and appears to be similar to what is observed in the nontransplant patient.
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Martini S, Tandoi F, Terzi di Bergamo L, Strona S, Lavezzo B, Sacco M, Maione F, Gonella F, Strignano P, Dell Olio D, Salizzoni M, Saracco GM, Romagnoli R. Negativization of viremia prior to liver transplant reduces early allograft dysfunction in hepatitis C-positive recipients. Liver Transpl 2017; 23:915-924. [PMID: 28422425 DOI: 10.1002/lt.24772] [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: 01/31/2017] [Revised: 03/15/2017] [Accepted: 04/07/2017] [Indexed: 12/13/2022]
Abstract
Although early allograft dysfunction (EAD) negatively impacts survival from the first months following liver transplantation (LT), direct-acting antiviral agents (DAAs) have revolutionized hepatitis C virus (HCV) therapy. We investigated the EAD definition best predicting 90-day graft loss and identified EAD risk factors in HCV-positive recipients. From November 2002 to June 2016, 603 HCV-positive patients (hepatocellular carcinoma, 53.4%) underwent a first LT with HCV-negative donors. The median recipient Model for End-Stage Liver Disease (MELD) score was 15, and the median donor age was 63 years. At LT, 77 (12.8%) patients were HCV RNA negative; negativization was achieved and maintained by pre-LT antiviral therapy (61 patients) or pre-LT plus a pre-emptive post-LT course (16 patients); 60 (77.9%) patients received DAAs and 17 (22.1%) interferon. We compared 3 different EAD definitions: (1) bilirubin ≥ 10 mg/dL or international normalized ratio ≥ 1.6 on day 7 after LT or aspartate aminotransferase or alanine aminotransferase > 2000 IU/L within 7 days of LT; (2) bilirubin > 10 mg/dL on days 2-7 after LT; and (3) MELD ≥ 19 on day 5 after LT. EAD defined by MELD ≥ 19 on day 5 after LT had the lowest negative (0.1) and the highest positive (1.9) likelihood ratio to predict 90-day graft loss. At 90 days after LT, 9.2% of recipients with EAD lost their graft as opposed to 0.7% of those without EAD (P < 0.001). At multivariate analysis, considering variables available at LT, MELD at LT of >25 (OR = 7.4) or 15-25 (OR = 3.2), graft macrovesicular steatosis ≥ 30% (OR = 6.7), HCV RNA positive at LT (OR = 2.7), donor age > 70 years (OR = 2.0), earlier LT era (OR = 1.8), and cold ischemia time ≥ 8 hours (OR = 1.8) were significant risk factors for EAD. In conclusion, in HCV-positive patients, MELD ≥ 19 on day 5 after LT best predicts 90-day graft loss. Preventing graft infection by pre-/peri-LT antiviral therapy reduces EAD incidence and could be most beneficial in high-MELD patients and recipients of suboptimal grafts. Liver Transplantation 23 915-924 2017 AASLD.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Dominic Dell Olio
- Regional Transplant Center, Piedmont, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy
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25
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Rezaee-Zavareh MS, Hesamizadeh K, Sharafi H, Alavian SM. Treatment of Hepatitis C Infection with Direct-Acting Antiviral Agents in Liver-Transplant Patients: A Systematic Review and Meta-Analysis. HEPATITIS MONTHLY 2017; 17. [DOI: 10.5812/hepatmon.12324] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/03/2023]
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Little EC, Berenguer M. The New Era of Hepatitis C: Therapy in Liver Transplant Recipients. Clin Liver Dis 2017; 21:421-434. [PMID: 28364822 DOI: 10.1016/j.cld.2016.12.012] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Hepatitis C virus (HCV) is the leading cause of end-stage liver disease in both Europe and the United States and is the most common reason for liver transplant. In the absence of antiviral therapy, recurrent infection is the norm with subsequent graft hepatitis and impaired survival. Whether it may be better to postpone therapy in patients in whom higher risk of failure and toxicity is coupled with lower chance of liver function improvement likely depends on several factors, including waiting time, center allocation policy, presence of hepatocellular carcinoma and local prevalence of anti-HCV-positive donors.
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Affiliation(s)
- Ester Coelho Little
- Banner Transplant Institute, 1441 North 12th Street, Second floor, Phoenix, AZ 85006, USA; Banner University Medical Center Phoenix, Phoenix, AZ, USA
| | - Marina Berenguer
- Servicio de Medicina Digestivo (Torre F-5), La Fe University Hospital, Ciberehd*, University of Valencia, Avda Fernando Abril Martorell n 106, Valencia 46026, Spain.
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Qu Y, Guo Y, Li T, Ye Q, Sun C, Wang L, Yang B. Efficacy and safety of sofosbuvir-based interferon-free therapies for hepatitis C in liver transplant recipients. J Gastroenterol Hepatol 2017; 32:740-748. [PMID: 27749979 DOI: 10.1111/jgh.13614] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/10/2016] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIM The aim of this study is to assess the efficacy and safety of sofosbuvir-based interferon-free therapies in liver transplantation recipients with hepatitis C virus infection recurrence. METHODS A systematic literature search was conducted in PubMed, EMBASE, Web of Science, and CENTRAL on the Cochrane Library without time or language limitation. The search strategy used was "sofosbuvir AND transplantation." Sustained virologic response at 12 weeks after the end of treatment (SVR12) rate, incidence of serious adverse events (SAEs) and/or adverse events, discontinuation rate with 95% confidence intervals (CI) were pooled with random-effects model. RESULTS Twenty-two studies (1730 patients) were included for our meta-analysis. The pooled SVR12 rate was 90.1% (95% CI 86.4-93.4%, I2 = 81.6%). SVR12 rate was higher in patients with mild fibrosis than in patients with advanced fibrosis and cirrhosis (RR = 1.072, 95% CI 1.031-1.115, I2 = 3.6%). For patients with hepatitis C virus genotype 1, the pooled SVR12 rate was 91.9% (95% CI 89.2-94.2%, I2 = 53.3%). The pooled SAEs incidence was 8.3% (95% CI 5.6-11.5%, I2 = 78.4%). The pooled discontinuation rate because of adverse events or SAEs was 3.3% (95% CI 1.8-5.2%). CONCLUSIONS Sofosbuvir-based interferon-free therapy is an effective and well-tolerated treatment strategy for patients with hepatitis C virus infection recurrence after liver transplantation.
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Affiliation(s)
- Yundong Qu
- Department of Infectious Diseases and Hepatology, The Second Hospital of Shandong University, Jinan, Shandong, China
| | - Ying Guo
- Department of Intensive Care Unit, The Second Hospital of Shandong University, Jinan, Shandong, China
| | - Tao Li
- Department of Infectious Diseases and Hepatology, The Second Hospital of Shandong University, Jinan, Shandong, China
| | - Qian Ye
- Department of Infectious Diseases and Hepatology, The Second Hospital of Shandong University, Jinan, Shandong, China
| | - Chao Sun
- Central Research Laboratory, The Second Hospital of Shandong University, Jinan, Shandong, China
| | - Lei Wang
- Department of Infectious Diseases and Hepatology, The Second Hospital of Shandong University, Jinan, Shandong, China
| | - Baohua Yang
- Department of Infectious Diseases and Hepatology, The Second Hospital of Shandong University, Jinan, Shandong, China
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Abstract
Cirrhosis due to chronic hepatitis C (HCV) is the leading indication for liver transplantation in North America and Europe. HCV re-infection post-transplant is nearly universal and if left untreated negatively affects patient and graft survival. Until recently, treatment options for HCV were limited to interferon (IFN)-based therapies which had low sustained viral response (SVR) rates and were poorly tolerated in the post-transplant setting. In the last 3 years, the promise of the directly acting antivirals (DAAs) for the treatment of HCV has been fulfilled with high sustained viral response (SVR) rates and a low side effect profile demonstrated in both registration trials and real-world studies. This innovation has allowed post-liver transplant patients with HCV recurrence access to interferon-free therapies with extraordinary efficacy, safety, tolerability, and fewer drug-drug interactions.
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