|
1
|
Bixler D, Annambholta P, Abara WE, Collier MG, Jones J, Mixson-Hayden T, Basavaraju SV, Ramachandran S, Kamili S, Moorman A. Hepatitis B and C virus infections transmitted through organ transplantation investigated by CDC, United States, 2014-2017. Am J Transplant 2019; 19:2570-2582. [PMID: 30861300 PMCID: PMC9112229 DOI: 10.1111/ajt.15352] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2018] [Revised: 02/14/2019] [Accepted: 03/03/2019] [Indexed: 01/25/2023]
Abstract
We evaluated clinical outcomes among organ recipients with donor-derived hepatitis B virus (HBV) or hepatitis C virus (HCV) infections investigated by CDC from 2014 to 2017 in the United States. We characterized new HBV infections in organ recipients if donors tested negative for total anti-HBc, HBsAg and HBV DNA, and new recipient HCV infections if donors tested negative for anti-HCV and HCV RNA. Donor risk behaviors were abstracted from next-of-kin interviews and medical records. During 2014-2017, seven new recipient HBV infections associated with seven donors were identified; six (86%) recipients survived. At last follow-up, all survivors had functioning grafts and five (83%) had started antiviral therapy. Twenty new recipient HCV infections associated with nine donors were identified; 19 (95%) recipients survived. At last follow-up, 18 (95%) survivors had functioning grafts and 14 (74%) had started antiviral treatment. Combining donor next-of kin interviews and medical records, 11/16 (69%) donors had evidence of injection drug use and all met Public Health Service increased risk donor (IRD) criteria. IRD designation led to early diagnosis of recipient infection, and prompt implementation of therapy, likely reducing the risk of graft failure, liver disease, and death.
Collapse
Affiliation(s)
- Danae Bixler
- Division of Viral Hepatitis, Centers for Disease Control and Prevention (CDC), Atlanta, GA
| | - Pallavi Annambholta
- Office of Blood, Organ and Other Tissue Safety, Division of Health care Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA
| | - Winston E Abara
- Division of Viral Hepatitis, Centers for Disease Control and Prevention (CDC), Atlanta, GA
| | - Melissa G. Collier
- Division of Viral Hepatitis, Centers for Disease Control and Prevention (CDC), Atlanta, GA
| | - Jefferson Jones
- Office of Blood, Organ and Other Tissue Safety, Division of Health care Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA
| | - Tonya Mixson-Hayden
- Division of Viral Hepatitis, Centers for Disease Control and Prevention (CDC), Atlanta, GA
| | - Sridhar V Basavaraju
- Office of Blood, Organ and Other Tissue Safety, Division of Health care Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA
| | - Sumathi Ramachandran
- Division of Viral Hepatitis, Centers for Disease Control and Prevention (CDC), Atlanta, GA
| | - Saleem Kamili
- Division of Viral Hepatitis, Centers for Disease Control and Prevention (CDC), Atlanta, GA
| | - Anne Moorman
- Division of Viral Hepatitis, Centers for Disease Control and Prevention (CDC), Atlanta, GA
| |
Collapse
|
|
2
|
Treatment strategies for patients with decompensated liver cirrhosis due to hepatitis C virus infection eligible for liver transplantation: real-life data from five German transplant centers. Eur J Gastroenterol Hepatol 2019; 31:1049-1056. [PMID: 30807443 DOI: 10.1097/meg.0000000000001386] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND Even with highly effective direct-acting antivirals (DAAs) treatment of patients with decompensated hepatitis C (HCV) cirrhosis remains challenging. Clinical deterioration and the need for liver transplantation (LT) may arise despite previous antiviral treatment. It is unclear whether in patients with high Model for End-Stage Liver Disease (MELD) antiviral treatment is too risky and should thus be deferred until after LT. Treatment choices that are currently made in the real-world setting are unclear. METHODS We performed a retrospective multicenter data analysis of patients with decompensated HCV cirrhosis (MELD ≥15) that presented to liver transplant centers that are part of the German Center for Infection Research when highly active DAA therapy was available. Choice of treatment strategy (DAA first vs. transplantation first) was analyzed and correlated with baseline and outcome parameters. RESULTS Thirty-five patients fulfilled the inclusion criteria and their mean MELD score was 18.5±3.78 (median: 17, interquartile range=16-19). In the majority of patients (85.7%) DAA therapy was initiated before LT; survival rates and change in MELD were numerically better in this group compared with those where DAA therapy was withheld (82.1 vs. 40%, P=0.078; ΔMELD: -2.68±6.2 vs. 5.8±14.4, P=0.157). However, DAA treatment was more often initiated in patients with better liver function (MELD: 18±3.54 vs. 21.8±3.9, P=0.008). Three patients discontinued DAA treatment because of clinical deterioration; these patients all had a MELD score above 20 at the start of therapy. CONCLUSION At liver transplant centers in Germany DAA before LT is attempted in the majority of cases. It appears to be associated with an improved outcome and seems safe at least in individuals with MELD below or equal to 20.
Collapse
|
|
3
|
Weiler N, Zeuzem S, Welker MW. Concise review: Interferon-free treatment of hepatitis C virus-associated cirrhosis and liver graft infection. World J Gastroenterol 2016; 22:9044-9056. [PMID: 27895394 PMCID: PMC5107588 DOI: 10.3748/wjg.v22.i41.9044] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2016] [Revised: 08/09/2016] [Accepted: 10/19/2016] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis C is a major reason for development of cirrhosis and hepatocellular carcinoma and a leading cause for liver transplantation. The development of direct-acting antiviral agents lead to (pegylated) interferon-alfa free antiviral therapy regimens with a remarkable increase in sustained virologic response (SVR) rates and opened therapeutic options for patients with advanced cirrhosis and liver graft recipients. This concise review gives an overview about most current prospective trials and cohort analyses for treatment of patients with liver cirrhosis and liver graft recipients. In patients with compensated cirrhosis Child-Pugh-Turcotte (CTP) class A, all approved agents are safe and SVR rates do not significantly differ from patients without cirrhosis in general. In patients with decompensated cirrhosis CTP class B or C, daclastasvir, ledipasvir, velpatasvir, and sofosbuvir are approved, and SVR rates higher than 90% can be achieved. Especially for patients with a model of end stage liver disease score higher than 15 and therefore eligible for liver transplantation, data is scarce. Reported SVR rates in patients with cirrhosis CTP class C are lower compared to patients with a less severe liver disease. In liver transplant recipients with a maximum of CTP class A, SVR rates are comparable to patients without LT. Patients with decompensated graft cirrhosis should be treated on an individual basis.
Collapse
|
|
4
|
Abstract
BACKGROUND Hepatitis B virus (HBV)- and hepatitis C virus (HCV)-associated liver cirrhosis is a major indication for liver transplantation. This concise review gives an overview about current interferon (IFN)-free treatment options before and after liver transplantation in HBV- or HCV-associated liver disease. METHODS A PubMed database search using the terms hepatitis B, hepatitis C, cirrhosis, and liver transplantation was performed to identify significant clinical studies as well as national and international guidelines. RESULTS Studies investigating IFN-free treatment in patients with decompensated HBV as well as in HCV-associated cirrhosis are scarce. Hepatic recompensation during antiviral therapy seems more frequent in patients with HBV than in those with HCV-associated cirrhosis. Graft hepatitis B or C is characterized by an accelerated and unfavorable course. Graft infection prophylaxis is safe and efficacious in HBV-related liver transplantation. Eradication of HCV prior to liver transplantation prevents HCV graft infection, and IFN-free treatment of established HCV graft infection is safe and associated with high sustained virologic response rates. CONCLUSION Patients with HBV-associated cirrhosis should be treated prior to liver transplantation, and receive a continuing graft infection prophylaxis thereafter. Patients with HCV-associated decompensated cirrhosis may be considered as candidates for antiviral therapy prior to liver transplantation or may be treated subsequently.
Collapse
Affiliation(s)
- Martin-Walter Welker
- Medizinische Klinik 1, Universitätsklinikum Frankfurt, Frankfurt am Main, Germany
| | | |
Collapse
|
|
5
|
Welker MW, Luhne S, Lange CM, Vermehren J, Farnik H, Herrmann E, Welzel T, Zeuzem S, Sarrazin C. Lactic acidosis in patients with hepatitis C virus cirrhosis and combined ribavirin/sofosbuvir treatment. J Hepatol 2016; 64:790-9. [PMID: 26658684 DOI: 10.1016/j.jhep.2015.11.034] [Citation(s) in RCA: 56] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2015] [Revised: 11/12/2015] [Accepted: 11/23/2015] [Indexed: 12/19/2022]
Abstract
BACKGROUND & AIMS Sofosbuvir (SOF) based interferon-alfa free antiviral therapy has become the treatment of choice for patients with chronic hepatitis C virus (HCV) infection. Little is known about safety of drug combinations using two nucleos(t)ide polymerase inhibitors in patients with HCV associated advanced cirrhosis. Here, we report frequent occurrence of lactic acidosis associated with acute-on-chronic hepatic decompensation during ribavirin (RBV) plus SOF based antiviral therapy. METHODS Thirty-five patients with chronic hepatitis C and advanced fibrosis, compensated cirrhosis, and decompensated cirrhosis without and after liver transplantation were treated with SOF based antiviral therapy with and without RBV. Adverse events including lactic acidosis (pH <7.35, lactate >20 mg/dl) were recorded 24 weeks before and during (mean ±SD, 18±11 weeks) antiviral therapy. Efficacy was determined by assessment of serum HCV RNA. RESULTS We observed severe adverse events in 15/35 (43%) patients before (24 weeks) and in 12/35 (34%) patients during antiviral therapy, the majority in association with acute-on-chronic hepatic decompensation. Lactic acidosis occurred in 5/35 (14%) patients during therapy, while no event of lactic acidosis was observed prior to therapy. Lactic acidosis was associated with hepatic decompensation including renal failure and infection, and was severe (pH <7.3) in two patients. CONCLUSIONS RBV in combination with SOF based antiviral therapy in patients with HCV associated advanced cirrhosis may be associated with the development of lactic acidosis. Impaired renal function, and higher MELD/Child-Pugh scores were identified as potential risk factors.
Collapse
Affiliation(s)
- Martin-Walter Welker
- Medizinische Klinik 1, Universitätsklinikum Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
| | - Stefan Luhne
- Medizinische Klinik 1, Universitätsklinikum Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany
| | - Christian M Lange
- Medizinische Klinik 1, Universitätsklinikum Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany
| | - Johannes Vermehren
- Medizinische Klinik 1, Universitätsklinikum Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany
| | - Harald Farnik
- Medizinische Klinik 1, Universitätsklinikum Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany
| | - Eva Herrmann
- Institut für Biostatistik und Mathematische Modellierung, Goethe Universität Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany
| | - Tania Welzel
- Medizinische Klinik 1, Universitätsklinikum Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany
| | - Stefan Zeuzem
- Medizinische Klinik 1, Universitätsklinikum Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany
| | - Christoph Sarrazin
- Medizinische Klinik 1, Universitätsklinikum Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany
| |
Collapse
|
|
6
|
Kim H, Lee KW, Yi NJ, Lee HW, Choi Y, Suh SW, Jeong J, Suh KS. Response-Guided Therapy for Hepatitis C Virus Recurrence Based on Early Protocol Biopsy after Liver Transplantation. J Korean Med Sci 2015; 30:1577-83. [PMID: 26539000 PMCID: PMC4630472 DOI: 10.3346/jkms.2015.30.11.1577] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2014] [Accepted: 07/29/2015] [Indexed: 11/20/2022] Open
Abstract
Hepatitis C virus (HCV) recurrence after liver transplantation (LT) is universal and progressive. Here, we report recent results of response-guided therapy for HCV recurrence based on early protocol biopsy after LT. We reviewed patients who underwent LT for HCV related liver disease between 2010 and 2012. Protocol biopsies were performed at 3, 6, and 12 months after LT in HCV recurrence (positive HCV-RNA). For any degree of fibrosis, ≥ moderate inflammation on histology or HCV hepatitis accompanying with abnormal liver function, we treated with pegylated interferon and ribavirin. We adjusted treatment period according to individual response to treatment. Among 41 HCV related recipients, 25 (61.0%) who underwent protocol biopsies more than once were enrolled in this study. The mean follow-up time was 43.1 (range, 23-55) months after LT. Genotype 1 and 2 showed in 56.0% and 36.0% patients, respectively. Of the 25 patients, 20 (80.0%) started HCV treatment after LT. Rapid or early virological response was observed in 20 (100%) patients. Fifteen (75.0%) patients finished the treatment with end-of-treatment response. Sustained virological response (SVR) was in 11 (55.0%) patients, including 5 (41.7%) of 12 genotype 1 and 6 (75.0%) of 8 non-genotype 1 (P = 0.197). Only rapid or complete early virological response was a significant predictor for HCV treatment response after LT (100% in SVR group vs. 55.6% in non-SVR group, P = 0.026). Overall 3-yr survival rate was 100%. In conclusion, response-guided therapy for HCV recurrence based on early protocol biopsy after LT shows encouraging results.
Collapse
Affiliation(s)
- Hyeyoung Kim
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Nam-Joon Yi
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Hae Won Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - YoungRok Choi
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Suk-Won Suh
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Jaehong Jeong
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| |
Collapse
|
|
7
|
Abstract
The efficacy of antiviral treatment depends on which of the seven genotypes (G1-G7) of hepatitis C virus (HCV) has infected the patient. Conventionally, clinicians regarded G2 and G3 infections as 'easy-to-treat': dual therapy with pegylated interferon and ribavirin produces a sustained virologic response in approximately 40-50% of patients with G1 infection, compared with 80% when analyses report combined data for G2 and G3 patients, which is standard practice in many clinical studies. However, sustained virologic response rates appear to be lower in certain subgroups of people infected with G3 compared with those with G2 or the general HCV-infected population. This review examines the growing evidence that factors related to the virus (e.g., baseline viral load and a rapid virologic response) and host characteristics (e.g., steatosis and fibrosis, metabolic syndrome, host polymorphisms and ethnicity) contribute to variations in therapeutic success in G3 HCV.
Collapse
Affiliation(s)
- Maria Buti
- Liver Unit, Hospital Universitario Valle Hebron and Ciberehd del Instituto, Carlos III Paseo Valle Hebron 119, Barcelona 08035, Spain
| | | |
Collapse
|
|
8
|
Murakami K, Kawagishi N, Ishida K, Sekiguchi S, Fujishima F, Sasano H, Ohuchi N. Fibrosing cholestatic hepatitis developing within one month after living donor liver transplantation for chronic hepatitis C-related cirrhosis: a case report. Transplant Proc 2015; 46:995-8. [PMID: 24767401 DOI: 10.1016/j.transproceed.2013.09.047] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2013] [Accepted: 09/26/2013] [Indexed: 01/01/2023]
Abstract
Fibrosing cholestatic hepatitis (FCH) is a life-threatening consequence of hepatitis C virus (HCV) infection occurring in a small minority of liver transplantation (LT) recipients. We herein report a case of early-onset FCH after living donor LT in a 47-year-old woman with HCV-related cirrhosis. The patient underwent balloon-occluded retrograde transvenous obliteration of a splenorenal shunt to treat an impaired portal flow on the sixth postoperative day (POD 6) and a bypass operation for hepatic artery thrombosis on POD 12. Thereafter, the serum bilirubin levels increased gradually; however, computed tomography revealed no evidence of biliary stricture. The serum HCV-RNA level on POD 27 was >7.8 log IU/mL. Histopathology of a needle graft biopsy performed on POD 28 revealed FCH with extensive portal fibrosis accompanied by mild inflammation, hepatocyte ballooning, and ductular proliferation with cholestasis. The patient received combination therapy with pegylated interferon, ribavirin, and double-filtration plasmapheresis for the treatment of early-onset FCH. Both the recipient and the donor carried the major genotype single nucleotide polymorphism (TT) at rs8099917 near the interleukin-28B gene. Furthermore, the HCV genotype was treatment-sensitive 2a. Nonetheless, the recipient died of hepatic failure on POD 211. Thus far, few cases of FCH occurring within 1 month after LT have been reported. In addition, the early onset of FCH may be an adverse prognostic factor.
Collapse
Affiliation(s)
- K Murakami
- Division of Transplantation, Reconstruction and Endoscopic Surgery, Tohoku University Hospital, Sendai, Japan.
| | - N Kawagishi
- Division of Transplantation, Reconstruction and Endoscopic Surgery, Tohoku University Hospital, Sendai, Japan
| | - K Ishida
- Department of Diagnostic Pathology, Iwate Medical School of Medicine, Morioka, Japan
| | - S Sekiguchi
- Division of Transplantation, Reconstruction and Endoscopic Surgery, Tohoku University Hospital, Sendai, Japan
| | - F Fujishima
- Department of Pathology, Tohoku University Hospital, Sendai, Japan
| | - H Sasano
- Department of Pathology, Tohoku University Hospital, Sendai, Japan
| | - N Ohuchi
- Division of Surgical Oncology, Tohoku University Hospital, Sendai, Japan
| |
Collapse
|
|
9
|
Vercauteren K, Mesalam AA, Leroux-Roels G, Meuleman P. Impact of lipids and lipoproteins on hepatitis C virus infection and virus neutralization. World J Gastroenterol 2014; 20:15975-91. [PMID: 25473151 PMCID: PMC4239485 DOI: 10.3748/wjg.v20.i43.15975] [Citation(s) in RCA: 15] [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: 05/28/2014] [Revised: 07/09/2014] [Accepted: 09/05/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) infections represent a major global health problem. End-stage liver disease caused by chronic HCV infection is a major indication for liver transplantation. However, after transplantation the engrafted liver inevitably becomes infected by the circulating virus. Direct acting antivirals are not yet approved for use in liver transplant patients, and limited efficacy and severe side effects hamper the use of pegylated interferon combined with ribavirin in a post-transplant setting. Therefore, alternative therapeutic options need to be explored. Viral entry represents an attractive target for such therapeutic intervention. Understanding the mechanisms of viral entry is essential to define the viral and cellular factors involved. The HCV life cycle is dependent of and associated with lipoprotein physiology and the presence of lipoproteins has been correlated with altered antiviral efficacy of entry inhibitors. In this review, we summarise the current knowledge on how lipoprotein physiology influences the HCV life cycle. We focus especially on the influence of lipoproteins on antibodies that target HCV envelope proteins or antibodies that target the cellular receptors of the virus. This information can be particularly relevant for the prevention of HCV re-infection after liver transplantation.
Collapse
|
|
10
|
Vercauteren K, Van Den Eede N, Mesalam AA, Belouzard S, Catanese MT, Bankwitz D, Wong-Staal F, Cortese R, Dubuisson J, Rice CM, Pietschmann T, Leroux-Roels G, Nicosia A, Meuleman P. Successful anti-scavenger receptor class B type I (SR-BI) monoclonal antibody therapy in humanized mice after challenge with HCV variants with in vitro resistance to SR-BI-targeting agents. Hepatology 2014; 60:1508-18. [PMID: 24797654 PMCID: PMC4211977 DOI: 10.1002/hep.27196] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2014] [Accepted: 04/29/2014] [Indexed: 02/06/2023]
Abstract
UNLABELLED Hepatitis C virus (HCV)-induced endstage liver disease is currently a major indication for liver transplantation. After transplantation the donor liver inevitably becomes infected with the circulating virus. Monoclonal antibodies (mAbs) against the HCV coreceptor scavenger receptor class B type I (SR-BI) inhibit HCV infection of different genotypes, both in cell culture and in humanized mice. Anti-SR-BI mAb therapy is successful even when initiated several days after HCV exposure, supporting its potential applicability to prevent HCV reinfection of liver allografts. However, HCV variants with reduced SR-BI dependency have been described in the literature, which could potentially limit the use of SR-BI targeting therapy. In this study we show, both in a preventative and postexposure setting, that humanized mice infected with HCV variants exhibiting increased in vitro resistance to SR-BI-targeting molecules remain responsive to anti-SR-BI mAb therapy in vivo. A 2-week antibody therapy readily cleared HCV RNA from the circulation of infected humanized mice. We found no evidence supporting increased SR-BI-receptor dependency of viral particles isolated from humanized mice compared to cell culture-produced virus. However, we observed that, unlike wild-type virus, the in vitro infectivity of the resistant variants was inhibited by both human high density lipoprotein (HDL) and very low density lipoprotein (VLDL). The combination of mAb1671 with these lipoproteins further increased the antiviral effect. CONCLUSION HCV variants that are less dependent on SR-BI in vitro can still be efficiently blocked by an anti-SR-BI mAb in humanized mice. Since these variants are also more susceptible to neutralization by anti-HCV envelope antibodies, their chance of emerging during anti-SR-BI therapy is severely reduced. Our data indicate that anti-SR-BI receptor therapy could be an effective way to prevent HCV infection in a liver transplant setting.
Collapse
Affiliation(s)
- Koen Vercauteren
- Department of Clinical Chemistry, Microbiology and Immunology, CEVAC, Gent, Belgium
| | - Naomi Van Den Eede
- Department of Clinical Chemistry, Microbiology and Immunology, CEVAC, Gent, Belgium
| | - Ahmed Atef Mesalam
- Department of Clinical Chemistry, Microbiology and Immunology, CEVAC, Gent, Belgium
| | - Sandrine Belouzard
- Institut Pasteur de Lille, Center for Infection & Immunity of Lille, Inserm U1019, CNRS UMR8204, Université Lille Nord de France
| | - Maria Teresa Catanese
- Center for the Study of Hepatitis C, Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, USA,Department of Infectious Diseases, King’s College London School of Medicine, Guy’s Hospital, London SE1 9RT, United Kingdom
| | - Dorothea Bankwitz
- Institute of Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research; a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany
| | | | | | - Jean Dubuisson
- Institut Pasteur de Lille, Center for Infection & Immunity of Lille, Inserm U1019, CNRS UMR8204, Université Lille Nord de France
| | - Charles M. Rice
- Center for the Study of Hepatitis C, Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, USA
| | - Thomas Pietschmann
- Institute of Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research; a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany
| | - Geert Leroux-Roels
- Department of Clinical Chemistry, Microbiology and Immunology, CEVAC, Gent, Belgium
| | - Alfredo Nicosia
- CEINGE, via Gaetano Salvatore 486, 80145, Naples, Italy,Department of Molecular Medicine and Medical Biotechnology, University of Naples Frederico II, Naples, Italy
| | - Philip Meuleman
- Department of Clinical Chemistry, Microbiology and Immunology, CEVAC, Gent, Belgium,Corresponding author: Prof. Dr. Philip Meuleman, Center for Vaccinology – Ghent University, UZ Gent, Building A, 1st floor, De Pintelaan 185, B-9000 Gent, Belgium., Phone: +32 9 332 02 05, Fax: +32 9 332 63 11,
| |
Collapse
|
|
11
|
Baseline MELD score predicts hepatic decompensation during antiviral therapy in patients with chronic hepatitis C and advanced cirrhosis. PLoS One 2013; 8:e71262. [PMID: 23936497 PMCID: PMC3731309 DOI: 10.1371/journal.pone.0071262] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2013] [Accepted: 06/27/2013] [Indexed: 02/07/2023] Open
Abstract
Background and Aims In patients with advanced liver cirrhosis due to chronic hepatitis C virus (HCV) infection antiviral therapy with peginterferon and ribavirin is feasible in selected cases only due to potentially life-threatening side effects. However, predictive factors associated with hepatic decompensation during antiviral therapy are poorly defined. Methods In a retrospective cohort study, 68 patients with HCV-associated liver cirrhosis (mean MELD score 9.18±2.72) were treated with peginterferon and ribavirin. Clinical events indicating hepatic decompensation (onset of ascites, hepatic encephalopathy, upper gastrointestinal bleeding, hospitalization) as well as laboratory data were recorded at baseline and during a follow up period of 72 weeks after initiation of antiviral therapy. To monitor long term sequelae of end stage liver disease an extended follow up for HCC development, transplantation and death was applied (240weeks, ±SD 136weeks). Results Eighteen patients (26.5%) achieved a sustained virologic response. During the observational period a hepatic decompensation was observed in 36.8%. Patients with hepatic decompensation had higher MELD scores (10.84 vs. 8.23, p<0.001) and higher mean bilirubin levels (26.74 vs. 14.63 µmol/l, p<0.001), as well as lower serum albumin levels (38.2 vs. 41.1 g/l, p = 0.015), mean platelets (102.64 vs. 138.95/nl, p = 0.014) and mean leukocytes (4.02 vs. 5.68/nl, p = 0.002) at baseline as compared to those without decompensation. In the multivariate analysis the MELD score remained independently associated with hepatic decompensation (OR 1.56, 1.18–2.07; p = 0.002). When the patients were grouped according to their baseline MELD scores, hepatic decompensation occurred in 22%, 59%, and 83% of patients with MELD scores of 6–9, 10–13, and >14, respectively. Baseline MELD score was significantly associated with the risk for transplantation/death (p<0.001). Conclusions Our data suggest that the baseline MELD score predicts the risk of hepatic decompensation during antiviral therapy and thus contributes to decision making when antiviral therapy is discussed in HCV patients with advanced liver cirrhosis.
Collapse
|
|
12
|
Abstract
The first human liver transplant operation was performed by Thomas Starzl in 1963. The next two decades were marked by difficulties with donor organ quality, recipient selection, operative and perioperative management, immunosuppression and infectious complications. Advances in each of these areas transformed liver transplantation from an experimental procedure to a standard treatment for end-stage liver disease and certain cancers. From the handful of pioneering programmes, liver transplantation has expanded to hundreds of programmes in >80 countries. 1-year patient survival rates have exceeded 80% and outcomes continue to improve. This success has created obstacles. Ongoing challenges of liver transplantation include those concerning donor organ shortages, recipients with more advanced disease at transplant, growing need for retransplantation, toxicities and adverse effects associated with long-term immunosuppression, obesity and NASH epidemics, HCV recurrence and the still inscrutable biology of hepatocellular carcinoma. This Perspectives summarizes this transformation over time and details some of the challenges ahead.
Collapse
Affiliation(s)
- Ali Zarrinpar
- Ronald Reagan UCLA Medical Center, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, 757 Westwood Plaza, Los Angeles, CA 90095-7054, USA
| | | |
Collapse
|
|
13
|
Ciria R, Pleguezuelo M, Khorsandi SE, Davila D, Suddle A, Vilca-Melendez H, Rufian S, de la Mata M, Briceño J, Cillero PL, Heaton N. Strategies to reduce hepatitis C virus recurrence after liver transplantation. World J Hepatol 2013; 5:237-50. [PMID: 23717735 PMCID: PMC3664282 DOI: 10.4254/wjh.v5.i5.237] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2012] [Revised: 11/16/2012] [Accepted: 12/01/2012] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) is a major health problem that leads to chronic hepatitis, cirrhosis and hepatocellular carcinoma, being the most frequent indication for liver transplantation in several countries. Unfortunately, HCV re-infects the liver graft almost invariably following reperfusion, with an accelerated history of recurrence, leading to 10%-30% of patients progressing to cirrhosis within 5 years of transplantation. In this sense, some groups have even advocated for not re-transplanting this patients, as lower patient and graft outcomes have been reported. However, the management of HCV recurrence is being optimized and several strategies to reduce post-transplant recurrence could improve outcomes, decrease the rate of re-transplantation and optimize the use of available grafts. Three moments may be the focus of potential actions in order to decrease the impact of viral recurrence: the pre-transplant moment, the transplant environment and the post-transplant management. In the pre-transplant setting, it is not well established if reducing the pre transplant viral load affects the risk for HCV progression after transplant. Obviously, antiviral treatment can render the patient HCV RNA negative post transplant but the long-term benefit has not yet been fully established to justify the cost and clinical risk. In the transplant moment, factors as donor age, cold ischemia time, graft steatosis and ischemia/reperfusion injury may lead to a higher and more aggressive viral recurrence. After the transplant, discussion about immunosuppression and the moment to start the treatment (prophylactic, pre-emptive or once-confirmed) together with new antiviral drugs are of interest. This review aims to help clinicians have a global overview of post-transplant HCV recurrence and strategies to reduce its impact on our patients.
Collapse
Affiliation(s)
- Ruben Ciria
- Ruben Ciria, Shirin Elizabeth Khorsandi, Diego Davila, Abid Suddle, Hector Vilca-Melendez, Nigel Heaton, Institute of Liver Studies, King's College Hospital, London SE5 9RS, United Kingdom
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
14
|
Chávez-Tapia NC, Ridruejo E, Alves de Mattos A, Bessone F, Daruich J, Sánchez-Ávila JF, Cheinquer H, Zapata R, Uribe M, Bosques-Padilla F, Gadano A, Sosa A, Dávalos-Moscol M, Marroni C, Muñoz-Espinoza L, Castro-Narro G, Paraná R, Méndez-Sánchez N. An update on the management of hepatitis C: guidelines for protease inhibitor-based triple therapy from the Latin American Association for the Study of the Liver. Ann Hepatol 2013; 12 Suppl 2:s3-s35. [PMID: 23559487 DOI: 10.1016/s1665-2681(19)31404-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2025]
Abstract
Hepatitis C is a common cause of end-stage liver disease, and the main indication for liver transplantation in Latin America. Treatment of hepatitis C infected patients improves important long-term outcomes as mortality. Sustained viral response is reached in near 50% of patients with the previous management based in pegylated interferon and ribavirin. Recently new drugs were available increasing sustained viral response significantly, changing the standard of care to triple therapy. This guidelines provides a framework for practitioner in Latin America, to the management of patients with hepatitis C chronic infection.
Collapse
|
|
15
|
Vercauteren K, Leroux-Roels G, Meuleman P. Blocking HCV entry as potential antiviral therapy. Future Virol 2012. [DOI: 10.2217/fvl.12.47] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
|
|
16
|
Sikka S. Treatment of hepatitis C in liver transplant patient. APOLLO MEDICINE 2012. [DOI: 10.1016/s0976-0016(12)60121-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022] Open
|
|
17
|
Doerr HW, Cinatl J. Recent publications in medical microbiology and immunology: a retrospective. Med Microbiol Immunol 2012; 201:1-5. [PMID: 22033658 DOI: 10.1007/s00430-011-0219-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2011] [Indexed: 01/15/2023]
Abstract
A look back is done to some clinical and basic research activities recently published in medical microbiology and immunology. The review covers clinical experiences and in vitro experiments to understand the emergency, pathogenicity, epidemic spread, and vaccine-based prevention of avian and swine-origin flu. Some new developments and concepts in diagnosis, (molecular) epidemiology, and therapy of AIDS, viral hepatitis C, and herpesvirus-associated diseases are outlined. Regulation of immune system has been discussed in a special issue 2010 including some aspects of CNS affections (measles). Mycobacterial infection and its prevention by modern recombinant vaccines have reached new interest, as well as new concepts of vaccination and prophylaxis against several other bacteria. Adaptation to host niches enables immune escape (example brucella) and determines virulence (example N. meningitidis). Chlamydia pneumoniae, previously considered to trigger atherosclerosis, is hypothetically associated to Alzheimer disease, while CMV, another putative trigger of atherosclerosis, gains evidence of oncomodulation in CNS tumor diseases. In terms of globalization, exotic virus infections are increasingly imported from southern countries.
Collapse
Affiliation(s)
- H W Doerr
- Institute of Medical Virology, University Hospital of Frankfurt/M., Frankfurt/Main, Germany.
| | | |
Collapse
|
|
18
|
Wertheim JA, Petrowsky H, Saab S, Kupiec-Weglinski JW, Busuttil RW. Major challenges limiting liver transplantation in the United States. Am J Transplant 2011; 11:1773-84. [PMID: 21672146 PMCID: PMC3166424 DOI: 10.1111/j.1600-6143.2011.03587.x] [Citation(s) in RCA: 130] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Liver transplantation is the gold standard of care in patients with end-stage liver disease and those with tumors of hepatic origin in the setting of liver dysfunction. From 1988 to 2009, liver transplantation in the United States grew 3.7-fold from 1713 to 6320 transplants annually. The expansion of liver transplantation is chiefly driven by scientific breakthroughs that have extended patient and graft survival well beyond those expected 50 years ago. The success of liver transplantation is now its primary obstacle, as the pool of donor livers fails to keep pace with the growing number of patients added to the national liver transplant waiting list. This review focuses on three major challenges facing liver transplantation in the United States and discusses new areas of investigation that address each issue: (1) the need for an expanded number of useable donor organs, (2) the need for improved therapies to treat recurrent hepatitis C after transplantation and (3) the need for improved detection, risk stratification based upon tumor biology and molecular inhibitors to combat hepatocellular carcinoma.
Collapse
Affiliation(s)
- Jason A. Wertheim
- Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Los Angeles, CA
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA
| | - Henrik Petrowsky
- Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Los Angeles, CA
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA
| | - Sammy Saab
- Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Los Angeles, CA
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA
- Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA
| | - Jerzy W. Kupiec-Weglinski
- Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Los Angeles, CA
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA
| | - Ronald W. Busuttil
- Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Los Angeles, CA
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA
| |
Collapse
|
|
19
|
Barritt AS, Darling JM, Hayashi PH. New and Evolving Management Paradigms for Hepatitis C after Liver Transplantation. CURRENT HEPATITIS REPORTS 2011; 10:179-185. [PMID: 22448143 PMCID: PMC3308145 DOI: 10.1007/s11901-011-0103-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/31/2023]
Abstract
Hepatitis-C induced liver failure is the leading indication for liver transplantation in the United States, and the burden of hepatitis C virus (HCV)-induced liver disease is not expected to peak for at least another decade. 2011 will usher in a new era of directly acting antiviral therapies and personalized medicine that will assist patients and clinicians in choosing the best drug regimen. Specific markers to predict sustained virologic response (SVR) in the posttransplant setting are under development, and the role of graft genetic markers like interleukin-28B and interferon-γ inducible protein-10 have yet to be fully defined. Lessons and experiences from treating the pretransplant population will be applied to patients with recurrent posttransplant HCV while studies specific to this population proceed. New paradigms for HCV treatment give promise to reducing the pretransplant burden of disease and improving SVR rates in the posttransplant population.
Collapse
Affiliation(s)
- A. Sidney Barritt
- Division of Gastroenterology and Hepatology, The University of North Carolina at Chapel Hill, 8004 Burnett Womack, CB #7568, Chapel Hill, NC 27599-7568, USA
| | - Jama M. Darling
- Division of Gastroenterology and Hepatology, The University of North Carolina at Chapel Hill, 8014 Burnett Womack, CB #7568, Chapel Hill, NC 27599-7568, USA
| | - Paul H. Hayashi
- Division of Gastroenterology and Hepatology, The University of North Carolina at Chapel Hill, 8011 Burnett Womack, CB #7568, Chapel Hill, NC 27599-7568, USA
| |
Collapse
|
|
20
|
Abstract
The introduction of direct acting antiviral agents (DAAs) will markedly change treatment options for individuals who have a chronic HCV infection. Within the next few months, licensing of two HCV protease inhibitors (boceprevir and telaprevir) for the treatment of patients with chronic hepatitis C as part of a triple therapy with PEG-IFN-α and ribavirin is anticipated in the USA, Europe and many other countries. Final results of pivotal phase III clinical trials in previously untreated and treatment-experienced patients with HCV genotype 1 infection were presented at the Annual Meeting of the American Association for the Study of the Liver 2010 held in Boston, MA, USA, and at the Annual Conference of the Asian Pacific Association for the Study of the Liver 2011, held in Bangkok, Thailand. This article summarizes the results of these phase III trials in consideration of accumulating data on important baseline and on-treatment predictive factors for treatment response, such as the host IL28B genotype and the rapid virologic response; the introduction of these new therapies into clinical practice is also covered. Furthermore, preliminary data on the combination of different classes of DAAs, such as HCV protease inhibitors and HCV polymerase inhibitors, without interferon α are discussed.
Collapse
Affiliation(s)
- Wolf Peter Hofmann
- Medizinische Klinik 1, Klinikum der Johann Wolfgang Goethe-Universität, Theodor Stern-Kai 7, Frankfurt am Main 60590, Germany
| | | |
Collapse
|
|
21
|
Sugawara Y, Tamura S, Kokudo N. Antiviral treatment for hepatitis C virus infection after liver transplantation. HEPATITIS RESEARCH AND TREATMENT 2010; 2010:475746. [PMID: 21151523 PMCID: PMC2989693 DOI: 10.1155/2010/475746] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/21/2010] [Revised: 08/13/2010] [Accepted: 10/06/2010] [Indexed: 12/16/2022]
Abstract
A significant proportion of patients with chronic hepatitis C virus (HCV) infection develop liver cirrhosis and complications of end-stage liver disease over two to three decades and require liver transplantation, however, reinfection is common and leads to further adverse events under immunosuppression. Pretransplant antiviral or preemptive therapy is limited to mildly decompensated patients due to poor tolerance. The mainstay of management represents directed antiviral therapy after evidence of recurrence of chronic hepatitis C. Combined pegylated interferon and ribavirin therapy is the current standard treatment with sustained viral response rates of 25% to 45%. The rate is lower than that in the immunocompetent population, partly due to the high prevalence of intolerability. To date, there is no general consensus regarding the antiviral treatment modality, timing, or dosing for HCV in patients with advanced liver disease and after liver transplantation. New anti-HCV drugs to delay disease progression or to enhance viral clearance are necessary.
Collapse
Affiliation(s)
- Yasuhiko Sugawara
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Sumihito Tamura
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Norihiro Kokudo
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| |
Collapse
|
|
22
|
Aytaman A, Kaufman M, Terrault NA. Management of posttransplant hepatitis C infection. Curr Opin Organ Transplant 2010; 15:301-9. [PMID: 20445452 DOI: 10.1097/mot.0b013e3283398237] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
PURPOSE OF REVIEW Chronic hepatitis C virus (HCV) infection is the leading cause of liver transplantation. Outcome of HCV-associated liver transplantation has been worse than transplantation from other causes. This is mostly related to universal recurrence of HCV in the allograft leading to graft and patient loss or retransplantation. Current antiviral therapies (AVTs) are inadequate and ineffective in the vast majority of the patients with intolerable side effects in most. However, a sustained virologic response (SVR) is associated with improved graft and patient survival. New specifically targeted AVTs for HCV (STAT-C) agents in development will significantly improve the success of AVT. This review focuses on recent data in peritransplant management of HCV with special emphasis on predictors of outcome, diagnosis, prevention and control of reinfection with newer treatments on the horizon. RECENT FINDINGS In the immediate pretransplant setting, AVT should be considered in select patients to eradicate the virus. Careful donor selection, immunosuppression (IMS) modulation with steroid and calcineurin inhibitor (CNI) minimization, avoidance of T-cell-depleting treatments and acute rejection episodes, and control of metabolic syndrome can improve allograft outcomes and improve the response to AVT. AVT prior to significant damage to the allograft is strongly recommended. SUMMARY With modified novel IMS protocols, careful donor selection, and AVT prior to significant damage to the allograft we can improve the outcome of posttransplant hepatitis C infection. Albeit there are no available data on new antiviral agents, STAT-Cs will have a significant impact in this setting in the near future.
Collapse
Affiliation(s)
- Ayse Aytaman
- VA New York Harbor HCS Brooklyn, Brooklyn, New York 11209, USA.
| | | | | |
Collapse
|