|
1
|
El-Garawani I, Hassab El-Nabi S, Gadallah M, Abdelsameea E. Association between IFN-λ 3 Gene Polymorphisms and Outcome of Treatment with Direct Acting Antivirals in Chronic HCV-Infected Egyptian Patients. Immunol Invest 2021; 50:12-22. [PMID: 32024403 DOI: 10.1080/08820139.2020.1722158] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Background: Single nucleotide polymorphisms (SNPs) of the interferon lambda 3 (IFN-λ 3) gene are associated with viral clearance and treatment response in chronic hepatitis C virus (HCV) infection. Aim: to assess whether specific IFN-λ 3 gene SNP, known as rs12979860 (C > T), could predict the outcome of treatment with direct acting antivirals (DAAs) among Egyptian patients with chronic HCV genotype 4 infection. Methods: Tetra-primer (ARMS-PCR) and PCR-RFLP methods were used for SNP genotyping in 100 chronic HCV-infected patients and 50 healthy subjects as control group. Results: The CC (wild type) genotype of rs12979860 was identified in 20 patients, 50% of them achieved sustained virological response (SVR). SNP genotype TT was found in 17 patients and only 2 of them (11.76%) were responders. The frequency of CT genotypes was significantly higher in responders than in non-responders (p= .021). In contrast, the frequency of TT genotypes was significantly higher in non-responders (42.85%, p< .001). On univariate and multivariate logistic regression analyses of the significant predictors of SVR, there were six predictive factors (Age, diabetes mellitus, AST, albumin, type of therapy and IFN-λ 3 genotype). Conclusion: The TT genotype and T allele were significantly associated with failure to achieve SVR. However, CT genotype of IFN-λ 3 (rs12979860) may be considered as a predictor for SVR in patients who received DAAs.
Collapse
Affiliation(s)
- Islam El-Garawani
- Zoology Department, Faculty of Science, Menoufia University , Shibin Al Kawm, Egypt
| | - Sobhy Hassab El-Nabi
- Zoology Department, Faculty of Science, Menoufia University , Shibin Al Kawm, Egypt
| | - Marwa Gadallah
- Zoology Department, Faculty of Science, Menoufia University , Shibin Al Kawm, Egypt
| | - Eman Abdelsameea
- Hepatology and Gastroenterology Department, National Liver Institute, Menoufia University , Shibin Al Kawm, Egypt
| |
Collapse
|
|
2
|
Castellote J, Gea F, Morano LE, Morillas RM, Pineda JA, Vergara M, Buti M. Factors influencing hepatitis C cure in the era of direct-acting antivirals. GASTROENTEROLOGIA Y HEPATOLOGIA 2020; 42 Suppl 1:1-7. [PMID: 32560767 DOI: 10.1016/s0210-5705(20)30181-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Direct-acting antiviral agents are highly potent drugs with a strong genetic barrier. Consequently, the factors influencing hepatitis C cure have been reduced and have progressively lost importance. Host factors, such as the presence of cirrhosis, race, and treatment adherence, influence sustained viral response. Adherence, together with treatment errors and drug interactions, are also important, especially in older patients. Viral factors, such as viral load, genotype, and the presence of baseline resistances affect the response rate but their influence can be minimised by using pan-genotypic regimens. Treatment simplification and the high efficacy of new antiviral treatments will allow treatment universalisation and will hopefully enable elimination of the infection in the next few decades. Supplement information: This article is part of a supplement entitled "The value of simplicity in hepatitis C treatment", which is sponsored by Gilead. © 2019 Elsevier España, S.L.U. All rights reserved.
Collapse
Affiliation(s)
- José Castellote
- Servicio de Aparato Digestivo, Hospital Universitari de Bellvitge, IDIBELL, L'Hospitalet de Llobregat, Barcelona, España.; Universitat de Barcelona, Barcelona, España.
| | - Francisco Gea
- Unidad de Sistema Digestivo, Hospital Universitario Ramón y Cajal, Madrid, España
| | - Luis Enrique Morano
- Unidad de Patologías Infecciosas, Hospital Universitario Álvaro Cunqueiro, Vigo, Pontevedra, España
| | - Rosa M Morillas
- Servicio de Aparato Digestivo, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, España; CIBEREHD, Instituto Carlos III, Madrid, España
| | - Juan Antonio Pineda
- Unidad de Enfermedades Infecciosas y Microbiología, Hospital Nuestra Señora de Valme, Sevilla, España
| | - Mercedes Vergara
- CIBEREHD, Instituto Carlos III, Madrid, España; Unidad de Hepatología, Parc Taulí Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí I3PT, Universitat Autònoma de Barcelona, Sabadell, Barcelona, España
| | - María Buti
- Unidad de Hepatología, Hospital General Universitario Vall d'Hebron, Barcelona, España
| |
Collapse
|
|
3
|
Gorka S, Gulzar GM, Yattoo GN, Sodhi JS, Dar GA, Laway MA, Kaushik S, Dhar N, Mushfiq S, Aziz RA. Genotype 1 and 3 Response to Velpatasvir and Sofosbuvir in Chronic Hepatitis C in the Kashmiri Population: An Observational Study. J Clin Exp Hepatol 2020; 10:155-162. [PMID: 32189931 PMCID: PMC7068023 DOI: 10.1016/j.jceh.2019.07.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2019] [Accepted: 07/05/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Our data is one of the earliest study from the Indian subcontinent on Velpatasvir/Sofosbuvir (VEL/SOF) combination in chronic hepatitis C (CHC). The primary end point was to evaluate sustained virologic response (SVR) 12 in CHC-infected patients and to determine its effect in patients with hepatitis C virus-related cirrhosis. The secondary end point was to observe any adverse events related to treatment. METHODS All patients with CHC were randomized into two groups: noncirrhotic and cirrhotic. The combination of VEL/SOF was given as recommended. RESULTS One hundred patients with CHC infection treated with the VEL/SOF regimen were evaluated. A total of 79 (79%) of 100 patients were noncirrhotic, and 21 (21%) were cirrhotic. We achieved SVR12 in 99 (99%) of 100 patients. Among cirrhotics, the mean serum bilirubin (mg/dl), albumin (g/dl), and platelet count (×10³/μL) improved from baseline 1.82 ± 0.87, 3.22 ± 0.69, and 80.19 ± 46.03 to 1.74 ± 0.87, 3.48 ± 0.72, and 85.05 ± 42.50, respectively, at SVR12 (P-value > 0.05). Mean serum alanine aminotransferase (ALT) (U/L) improved from baseline 71.28 ± 59.17 to 35.38 ± 17.39 at SVR12 (P-value < 0.024). Baseline mean liver stiffness measurement (LSM) in cirrhotic patients was 28.24 ± 10.87 kPa, which decreased to 24.04 ± 9.33 kPa at SVR12 (P-value, 0.02). The baseline Model for End-Stage Liver Disease (MELD) score was 13.47 ± 3.66, which decreased to 12.33 ± 5.46 at SVR12 (P-value, 0.28). The Child-Turcotte-Pugh score improved by 1 point in 33.33% (7/21) patients and 2 points in 9.52% (2/21) patients, and in the majority, that is, 38.09% (8/21), the score remained as it is. CONCLUSION A single daily dose of the tablet SOF/VEL combination is safe and effective in all types of CHC. There was a significant improvement in the mean transaminase level and LSM at SVR12. And the MELD score improved by 1 point at SVR12 among cirrhotics.
Collapse
Affiliation(s)
- Suresh Gorka
- Address for correspondence: Suresh Gorka, DM Resident, Department of Gastroenterology, SKIMS, Room No 9, Block B, New Married Hostel, Soura, Srinagar, 190011, India.
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
4
|
Zhu X, Wang M, Liu M, Yu X, Huang P. Efficacy and safety of direct-acting antivirals for treatment-naive patients with genotype 1 hepatitis C virus infection. Per Med 2019; 16:421-429. [PMID: 31591934 DOI: 10.2217/pme-2018-0121] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
This systematic review was performed on the basis of Preferred Reporting Items for Systematic Reviews and Meta-analyses and Cochrane recommendations to compare sustained virological response (SVR12) and the serious adverse events in patients treated by directing-acting antivirals. We conducted a literature search in PubMed/Medline, EBSCO, Embase and the Cochrane Library until 2018. A consistency model was used to get the relative effect of odds ratio among regimens and the possibility for the efficacy and safety of 13 regimen, and we divided these regimens into DUAL or TRIO regimens to conduct integrated data analysis. The results demonstrated that dual or triple directing-acting antiviral-combined regimens had higher SVR12 rates, Daclatasvir plus Asunaprevir may be a good choice for genotype 1 patients, and regimens without Ribavirin and interferon are safer.
Collapse
Affiliation(s)
- Xiaobo Zhu
- Department of Pharmacy, People's Hospital of Danyang, Danyang 212300, China
| | - Mingqi Wang
- Department of Epidemiology, Xu Zhou Medical University, Xuzhou 221000, China
| | - Mei Liu
- Department of Epidemiology, Nanjing Medical University, Nanjing 211166, China
| | - Xinghao Yu
- Department of Epidemiology, Xu Zhou Medical University, Xuzhou 221000, China
| | - Peng Huang
- Department of Epidemiology, Nanjing Medical University, Nanjing 211166, China.,Key Laboratory of Infectious Diseases, Nanjing Medical University, Nanjing 211166, China
| |
Collapse
|
|
5
|
Barrail-Tran A, Goldwirt L, Gelé T, Laforest C, Lavenu A, Danjou H, Radenne S, Leroy V, Houssel-Debry P, Duvoux C, Kamar N, De Ledinghen V, Canva V, Conti F, Durand F, D'Alteroche L, Botta-Fridlund D, Moreno C, Cagnot C, Samuel D, Fougerou-Leurent C, Pageaux GP, Duclos-Vallée JC, Taburet AM, Coilly A. Comparison of the effect of direct-acting antiviral with and without ribavirin on cyclosporine and tacrolimus clearance values: results from the ANRS CO23 CUPILT cohort. Eur J Clin Pharmacol 2019; 75:1555-1563. [PMID: 31384986 DOI: 10.1007/s00228-019-02725-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2019] [Accepted: 07/17/2019] [Indexed: 11/28/2022]
Abstract
PURPOSE Direct-acting antiviral agents have demonstrated their efficacy in treating HCV recurrence after liver transplantation and particularly the sofosbuvir/daclatasvir combination. Pharmacokinetic data on both calcineurin inhibitors and direct-acting antiviral exposure in liver transplant recipients remain sparse. METHODS Patients were enrolled from the ANRS CO23 CUPILT cohort. All patients treated with sofosbuvir/daclatasvir with or without ribavirin were included in this study when blood samples were available to estimate the clearance of immunosuppressive therapy before direct-acting antiviral initiation and during follow-up. Apparent tacrolimus and cyclosporine clearances were estimated from trough concentrations measured using validated quality control assays. RESULTS Sixty-seven mainly male patients (79%) were included, with a mean age of 57 years and mean MELD score of 8.2; 50 were on tacrolimus, 17 on cyclosporine. Ribavirin was combined with sofosbuvir/daclatasvir in 52% of patients. Cyclosporine clearance remained unchanged as well as tacrolimus clearance under the ribavirin-free regimen. Tacrolimus clearance increased 4 weeks after direct-acting antivirals and ribavirin initiation versus baseline (geometric mean ratio 1.81; 90% CI 1.30-2.52). Patients under ribavirin had a significantly higher fibrosis stage (> 2) (p = 0.02) and lower haemoglobin during direct-acting antiviral treatment (p = 0.02) which impacted tacrolimus measurements. Direct-acting antiviral exposure was within the expected range. CONCLUSION Our study demonstrated that liver transplant patients with a recurrence of hepatitis C who are initiating ribavirin combined with a sofosbuvir-daclatasvir direct-acting antiviral regimen may be at risk of lower tacrolimus concentrations because of probable ribavirin-induced anaemia and higher fibrosis score, although there are no effects on cyclosporine levels. TRIAL REGISTRATION NCT01944527.
Collapse
Affiliation(s)
- Aurélie Barrail-Tran
- AP-HP, Hôpital Bicêtre, Department of Clinical Pharmacy, Hôpitaux Universitaires Paris Sud, Kremlinl-Bicêtre, France.
- Department of Clinical Pharmacy, Université Paris Sud, Châtenay Malabry, France.
- INSERM UMR1184, CEA, Université Paris Sud, Immunologie des Maladies Virales et Autoimmunes (IMVA), Kremlin-Bicêtre, France.
| | - Lauriane Goldwirt
- Department of Pharmacology, Assistance Publique Hôpitaux de Paris, Hôpital Saint-Louis, Paris, France
| | - Thibaut Gelé
- AP-HP, Hôpital Bicêtre, Department of Clinical Pharmacy, Hôpitaux Universitaires Paris Sud, Kremlinl-Bicêtre, France
| | - Claire Laforest
- CHU Rennes, Service de Pharmacologie, Rennes, France
- INSERM, CIC 1414, Rennes, France
| | - Audrey Lavenu
- INSERM, CIC 1414, Rennes, France
- University of Rennes 1, Laboratory of Experimental and Clinical Pharmacology, Rennes, France
| | - Hélène Danjou
- CHU Rennes, Service de Pharmacologie, Rennes, France
- INSERM, CIC 1414, Rennes, France
| | - Sylvie Radenne
- Service d'Hépato-Gastroentérologie, HCL Hôpital de la Croix-Rousse, Lyon, France
| | - Vincent Leroy
- Service d'Hépato-Gastroentérologie, CHU Michallon, Grenoble, France
| | | | - Christophe Duvoux
- Service d'Hépato-Gastroentérologie, AP-HP Hôpital Henri-Mondor, Créteil, France
| | - Nassim Kamar
- Service de Néphrologie, HTA, Dialyse, Transplantation, CHU Rangueil, Toulouse, France
| | | | - Valérie Canva
- Service des Maladies de l'Appareil Digestif, CHRU Huriez, Lille, France
| | - Filomena Conti
- Service de Chirurgie Hépatobiliaire et Transplantation Hépatique, AP-HP Hôpital Pitié-Salpêtrière, Paris, France
| | - François Durand
- Service d'Hépatologie, AP-HP Hôpital Beaujon, Clichy, France
| | | | | | - Christophe Moreno
- CUB, Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Carole Cagnot
- Unit for Basic and Clinical Research on Viral Hepatitis ANRS (France REcheche Nord&sud Sida-hiv Hépatites), Paris, France
| | - Didier Samuel
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, France
- Univ Paris-Sud, UMR-S 1193, Université Paris-Saclay, Villejuif, France
- Inserm, Unité 1193, Université Paris-Saclay, Villejuif, France
- Hepatinov, Villejuif, France
| | | | - Georges-Philippe Pageaux
- Department of Hepatogastroenterology, CHU Saint Eloi, Université de Montpellier, Montpellier, France
| | - Jean-Charles Duclos-Vallée
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, France
- Univ Paris-Sud, UMR-S 1193, Université Paris-Saclay, Villejuif, France
- Inserm, Unité 1193, Université Paris-Saclay, Villejuif, France
- Hepatinov, Villejuif, France
| | - Anne-Marie Taburet
- AP-HP, Hôpital Bicêtre, Department of Clinical Pharmacy, Hôpitaux Universitaires Paris Sud, Kremlinl-Bicêtre, France
- INSERM UMR1184, CEA, Université Paris Sud, Immunologie des Maladies Virales et Autoimmunes (IMVA), Kremlin-Bicêtre, France
- Hepatinov, Villejuif, France
| | - Audrey Coilly
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, France
- Univ Paris-Sud, UMR-S 1193, Université Paris-Saclay, Villejuif, France
- Inserm, Unité 1193, Université Paris-Saclay, Villejuif, France
- Hepatinov, Villejuif, France
| |
Collapse
|
|
6
|
Taneja S, Duseja A, De A, Kumar V, Ramachandran R, Sharma A, Dhiman RK, Gupta KL, Chawla Y. Successful treatment of chronic hepatitis C infection with directly acting antivirals in renal transplant recipients. Nephrology (Carlton) 2018; 23:876-882. [PMID: 28703905 DOI: 10.1111/nep.13109] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/30/2017] [Indexed: 12/15/2022]
Abstract
AIMS The data regarding the treatment of chronic hepatitis C (CHC) in renal transplant recipients is lacking from the Asia-Pacific region. The aim of the present study was to assess the safety and efficacy of directly acting antivirals (DAAs) in the treatment of CHC infection in renal transplant recipients. METHODS A total of 47 CHC infected renal transplant recipients were enrolled in this real life observational cohort analysis between March 2015 and September 2016. Presence of hepatic fibrosis/cirrhosis was assessed on transient elastography (Fibroscan). Fourteen patients were treated with Sofosbuvir and Ribavirin for 24 weeks. Twenty-two patients received Sofosbuvir and Ledipasvir and 12 patients received Sofosbuvir and Daclatasvir with (n = 3) or without (n = 31) Ribavirin for 12 or 24 weeks depending on genotype and underlying cirrhosis. Data were analyzed for safety and treatment efficacy [sustained virological response at 12 weeks (SVR12)]. RESULTS The median baseline HCV RNA concentration in the whole group was 7.38 × 106 IU/mL (1.23 × 104 -6.36 × 107 ). The SVR12 rates were 100% in all groups except in the Sofosbuvir and Ribavirin group (86%). Transient Elastography revealed minimal or no fibrosis (F0-F1) in 31 (65.96%) patients, moderate fibrosis (F2) in 11 (23.4%) patients and cirrhosis in five (10.64%) patients. The only serious adverse effect was anaemia observed in eight (57%) patients in the Sofosbuvir and Ribavirin group. CONCLUSION DAAs including Sofosbuvir, Daclatasvir and Ledipasvir with or without ribavirin are safe and effective for the treatment of chronic hepatitis C in renal transplant recipients.
Collapse
Affiliation(s)
- Sunil Taneja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Ajay Duseja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Arka De
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Vivek Kumar
- Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Raja Ramachandran
- Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Ashish Sharma
- Department of Transplant Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Radha K Dhiman
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Krishan L Gupta
- Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Yogesh Chawla
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| |
Collapse
|
|
7
|
Krol E, Pastuch-Gawolek G, Chaubey B, Brzuska G, Erfurt K, Szewczyk B. Novel Uridine Glycoconjugates, Derivatives of 4-Aminophenyl 1-Thioglycosides, as Potential Antiviral Compounds. Molecules 2018; 23:molecules23061435. [PMID: 29899276 PMCID: PMC6100568 DOI: 10.3390/molecules23061435] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2018] [Revised: 06/02/2018] [Accepted: 06/10/2018] [Indexed: 01/19/2023] Open
Abstract
A novel series of uridine glycoconjugates, derivatives of 4-aminophenyl 1-thioglycosides, was designed and synthesized. All compounds were evaluated in vitro for their antiviral activity against hepatitis C virus (HCV) and classical swine fever virus (CSFV), two important human and animal viral pathogens for which new or improved therapeutic options are needed. The antiviral activity of all synthesized compounds was confirmed using pseudo-plaque reduction assays in which a significant arrest of CSFV and HCV growth was observed in the presence of these compounds. Two of the synthesized compounds, 9 and 12, displayed a significant inhibitory effect on HCV and CSFV propagation with IC50 values of 4.9 and 13.5 µM for HCV and 4.2 and 4 µM for CSFV, respectively, with low cytotoxicity. Using various infection and replication models, we have shown that both compounds were able to significantly reduce viral genome replication by up to 90% with IC50 values in the low micromolar range. A structure activity analysis of the synthesized compounds showed that the high antiviral activity was attributed to the hydrophobicity of glycoconjugates and the introduction of elements capable to coordinate metal ions into the spacer connecting the sugar and uridine moiety, which can be useful in the development of new antiviral compounds in the future.
Collapse
Affiliation(s)
- Ewelina Krol
- Department of Recombinant Vaccines, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Abrahama 58, 80-307 Gdansk, Poland.
| | - Gabriela Pastuch-Gawolek
- Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Faculty of Chemistry, Silesian University of Technology, Krzywoustego 4, 44-100 Gliwice, Poland.
- Biotechnology Center, Silesian University of Technology, Krzywoustego 8, 44-100 Gliwice, Poland.
| | - Binay Chaubey
- Department of Recombinant Vaccines, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Abrahama 58, 80-307 Gdansk, Poland.
- Functional Genomics Lab., Centre for Advanced Study, Department of Botany, University of Calcutta, 35, Ballygunge Circular Road, 700019 Kolkata, India.
| | - Gabriela Brzuska
- Department of Recombinant Vaccines, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Abrahama 58, 80-307 Gdansk, Poland.
| | - Karol Erfurt
- Department of Chemical Organic Technology and Petrochemistry, Faculty of Chemistry, Silesian University of Technology, Krzywoustego 4, 44-100 Gliwice, Poland.
| | - Boguslaw Szewczyk
- Department of Recombinant Vaccines, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Abrahama 58, 80-307 Gdansk, Poland.
| |
Collapse
|
|
8
|
Association between alanine aminotransferase elevation and UGT1A1*6 polymorphisms in daclatasvir and asunaprevir combination therapy for chronic hepatitis C. J Gastroenterol 2018; 53:780-786. [PMID: 29094205 DOI: 10.1007/s00535-017-1405-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2017] [Accepted: 10/20/2017] [Indexed: 02/04/2023]
Abstract
BACKGROUND Liver damage presented as alanine aminotransferase (ALT) elevation and high ALT-caused treatment discontinuation occurs with high frequency in Japanese patients receiving daclatasvir plus asunaprevir (DCV/ASV) therapy for hepatitis C virus (HCV) infection, and its mechanism is unknown. METHODS A total of 247 Japanese patients consisting of two independent cohorts with genotype-1b HCV infection receiving DCV/ASV therapy were included. The association of ALT levels during therapy and single nucleotide polymorphisms (SNP) of five drug-metabolizing enzyme loci selected for their possible influence on NS3/4A and NS5A inhibitors was investigated. RESULTS Among five SNPs, we found a significant correlation between the presence of the UGT1A1 rs4148323 A allele and ALT elevation (Grade 3 elevation in AA 57%, AG 18%, and GG 4%, P = 8.4E - 06) and drug discontinuation (AA 22%, AG 11%, and GG 2.5%, P = 8.7E - 04), while no association was observed with ALT values at baseline (Grade 3 elevation AA 0%, AG 4%, and GG 2%, P = 0.5). In contrast, patients with risk A allele for drug-induced ALT elevation had a tendency to respond more favorably to treatment (AA 100%, AG 93%, and GG 90%, P = 0.29). CONCLUSIONS Through the analysis we suggest that the A allele in UGT1A1 rs4148323 (UGT1A1*6), which is highly prevalent in the Japanese population, should be considered a risk for the development of DCV/ASV therapy-induced ALT elevation. Pretreatment SNP testing of UGT1A1*6 might be beneficial for the prediction of liver damage induced by DCV/ASV or even by DCV/ASV plus beclabuvir.
Collapse
|
|
9
|
Shafii AE, Harris DD, Baz M. Clearance of Hepatitis C Virus Prior to Lung Transplantation: A Case Report. Transplant Proc 2018; 49:1682-1684. [PMID: 28838464 DOI: 10.1016/j.transproceed.2017.06.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2017] [Accepted: 06/16/2017] [Indexed: 02/07/2023]
Abstract
Hepatitis C virus (HCV) continues to be considered a relative contraindication to lung transplantation due to concerns of progression of liver disease with the introduction of immunosuppression. Since the recent introduction of effective antiviral therapy for HCV, new approaches in the management of the HCV-positive recipient are being utilized in liver transplantation to clear HCV pre- and post-transplant. Herein, we report use of ledipasvir/sofosbuvir for HCV clearance prior to lung transplantation in a patient with usual interstitial pneumonia. Listing for transplant was delayed until completion of HCV treatment, and he subsequently required extracorporeal membrane oxygenation as a bridge to transplantation due to progressive hypoxia. With antiviral cure rates exceeding 90%, HCV should no longer be considered a relative contraindication to lung transplant, and timing of antiviral treatment should consider the progressive nature of the recipient's lung disease.
Collapse
Affiliation(s)
- A E Shafii
- Department of Surgery, Division of Cardiothoracic Surgery, University of Kentucky, Lexington, Kentucky, USA.
| | - D D Harris
- University of Kentucky College of Medicine, Lexington, Kentucky, USA
| | - M Baz
- Department of Surgery, Division of Cardiothoracic Surgery, University of Kentucky, Lexington, Kentucky, USA
| |
Collapse
|
|
10
|
Successful Treatment of Fibrosing Cholestatic Hepatitis With Daclatasvir and Asunaprevir After Liver Transplantation: A Case Report. Transplant Proc 2018; 50:2877-2881. [PMID: 30401415 DOI: 10.1016/j.transproceed.2018.03.057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2018] [Accepted: 03/02/2018] [Indexed: 11/22/2022]
Abstract
BACKGROUND Fibrosing cholestatic hepatitis (FCH) is an aggressive form of hepatitis C virus (HCV) recurrence after liver transplantation (LT). Most FCH cases are fatal, occurring as a secondary disease following rapidly progressive liver dysfunction and graft failure. We report a case of early-onset FCH after LT that was successfully treated using daclatasvir and asunaprevir. CASE REPORT A 59-year-old woman underwent living donor LT for HCV-related liver cirrhosis. However, liver function was not improved after LT and gradually worsened. A liver biopsy was performed at 30 and 47 days after the living donor LT to identify the cause of the liver dysfunction. The first biopsy result showed no specific finding. However, combined treatment with pegylated interferon and ribavirin was started because of a high HCV viral load (> 8.0 log IU/mL). Nevertheless, liver function and HCV viral load deteriorated, and the second biopsy performed on postoperative day 47 revealed FCH. We converted the antiviral agents into daclatasvir and asunaprevir and performed plasmapheresis twice. Since then, the liver dysfunction and HCV viral load gradually improved, and HCV RNA clearance occurred at week 11 after treatment. The patient achieved a sustained virologic response at week 24 after completion of the treatment. CONCLUSION Daclatasvir combined with asunaprevir can be a useful treatment option in potentially fatal FCH after LT.
Collapse
|
|
11
|
Early outcomes using hepatitis C-positive donors for cardiac transplantation in the era of effective direct-acting anti-viral therapies. J Heart Lung Transplant 2018. [PMID: 29530322 DOI: 10.1016/j.healun.2018.01.1293] [Citation(s) in RCA: 141] [Impact Index Per Article: 20.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Given the shortage of suitable donor hearts for cardiac transplantation, and the favorable safety and efficacy of current agents used to treat hepatitis C virus (HCV), our institution recently piloted transplantation of select patients using HCV-positive donors. METHODS Between September 2016 and March 2017, 12 HCV-naive patients and 1 patient with a history of treated HCV underwent heart transplantation (HT) using hearts from HCV-positive donors after informed consent. Patients who acquired HCV were referred to hepatology and treated with direct-acting anti-viral therapies (DAAs). Data collection and analysis were performed with institutional review board approval. RESULTS At the time of HT, mean age of recipients was 53 ± 10 years, and 8 patients (61.5%) were on left ventricular assist device support. After consent to consider an HCV-positive heart, mean time to HT was 11 ± 12 days. Nine of 13 patients (69%) developed HCV viremia after transplant, including 8 who completed DAA treatment and demonstrated cure, as defined by a sustained virologic response 12 weeks after treatment. One patient died during Week 7 of his treatment due to pulmonary embolism. DAAs were well tolerated in all treated patients. CONCLUSIONS In the era of highly effective DAAs, the use of HCV-positive donors represents a potential approach to safely expand the donor pool. Additional follow-up is needed to elucidate long-term outcomes.
Collapse
|
|
12
|
Omichi K, Akamatsu N, Mori K, Togashi J, Arita J, Kaneko J, Hasegawa K, Sakamoto Y, Kokudo N. Asunaprevir/daclatasvir and sofosbuvir/ledipasvir for recurrent hepatitis C following living donor liver transplantation. Hepatol Res 2017; 47:1093-1101. [PMID: 27875005 DOI: 10.1111/hepr.12845] [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] [Received: 10/09/2016] [Revised: 11/03/2016] [Accepted: 11/18/2016] [Indexed: 02/08/2023]
Abstract
AIM This study aimed to clarify the efficacy and safety of interferon-free therapy using asunaprevir and daclatasvir, or sofosbuvir and ledipasvir for post living donor liver transplantation (LDLT) recipients with hepatitis C virus (HCV). METHODS A retrospective cohort study of LDLT recipients with HCV genotype 1b treated with asunaprevir (100 mg twice daily) and daclatasvir (60 mg once daily), or sofosbuvir (400 mg/day) and ledipasvir (90 mg/day) was carried out. RESULTS Ten patients without mutations in the area of L31 and Y93 completed the treatment with asunaprevir and daclatasvir. Five of them had end-stage chronic kidney disease, including three hemodialysis patients. Of the 10 patients, nine completed the protocol of 24 weeks; one stopped the treatment due to the development of aortic valve stenosis. All nine patients who completed the 24-week treatment protocol achieved end of treatment response. Nineteen patients received treatment with sofosbuvir and ledipasvir. Of the 19 patients, 18 completed the protocol of 12 weeks; one stopped treatment due to severe interstitial pneumonia. All 18 patients who completed the 12-week treatment protocol achieved end of treatment response. All patients in both treatment groups who completed the regimen and reached 3 months after the end of treatment achieved sustained virological response at 12 weeks after treatment. Liver functions were significantly improved at the end of treatment, and no adverse events were observed. CONCLUSIONS Interferon-free therapy using asunaprevir and daclatasvir, or sofosbuvir and ledipasvir, is highly effective for post-LDLT recipients with HCV genotype 1b.
Collapse
Affiliation(s)
- Kiyohiko Omichi
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Nobuhisa Akamatsu
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kazuhiro Mori
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Junichi Togashi
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Junichi Arita
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Junichi Kaneko
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kiyoshi Hasegawa
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yoshihiro Sakamoto
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Norihiro Kokudo
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| |
Collapse
|
|
13
|
Forns X, Berenguer M, Herzer K, Sterneck M, Donato MF, Andreone P, Fagiuoli S, Cieciura T, Durlik M, Calleja JL, Mariño Z, Shukla U, Verbinnen T, Lenz O, Ouwerkerk-Mahadevan S, Peeters M, Janssen K, Kalmeijer R, Jessner W. Efficacy, safety, and pharmacokinetics of simeprevir, daclatasvir, and ribavirin in patients with recurrent hepatitis C virus genotype 1b infection after orthotopic liver transplantation: The Phase II SATURN study. Transpl Infect Dis 2017; 19. [PMID: 28295849 DOI: 10.1111/tid.12696] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2016] [Revised: 12/13/2016] [Accepted: 12/30/2016] [Indexed: 01/02/2023]
Abstract
BACKGROUND Recurrent hepatitis C virus (HCV) infection following liver transplantation is associated with accelerated progression to graft failure and reduced patient survival. METHODS The Phase II, open-label SATURN study (NCT01938625) investigated the combination of simeprevir (SMV), daclatasvir (DCV), and ribavirin (RBV) administered for 24 weeks in 35 patients with recurrent HCV genotype (GT) 1b infection after orthotopic liver transplantation (OLT). RESULTS High rates of both on-treatment and sustained virologic response 12 weeks after end of treatment (SVR12) were achieved in patients who were either treatment-naïve or had failed post-OLT treatment with peginterferon and RBV. Overall, 91% of patients (32/35) achieved SVR12. The combination was generally well tolerated, with an adverse event profile consistent with that observed in previous clinical trials of SMV or DCV separately. Co-administration of SMV with cyclosporine resulted in significantly increased SMV plasma exposures, which was not the case with the co-administration of SMV with tacrolimus. Therefore, the concomitant use of SMV with cyclosporine is not recommended. CONCLUSION The interferon-free combination of SMV, DCV, and RBV administered for 24 weeks was shown to be effective and well tolerated in the treatment of post-OLT HCV GT1b-infected patients.
Collapse
Affiliation(s)
- Xavier Forns
- Liver Unit, Hospital Clinic, IDIBAPS and CIBEREHD, University of Barcelona, Barcelona, Spain
| | - Marina Berenguer
- Department of Digestive Diseases, Hepatology and Liver Transplantation Unit, La Fe University Hospital and CIBEREHD, Valencia, Spain
| | - Kerstin Herzer
- Department of General, Visceral and Transplantation Surgery and Department of Gastroenterology and Hepatology, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Martina Sterneck
- Department of Hepatobiliary and Transplant Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | | | - Pietro Andreone
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Stefano Fagiuoli
- Gastroenterology and Transplant Hepatology, Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - Tomasz Cieciura
- Department of Immunology, Transplant Medicine and Internal Diseases, Transplantation Institute, Medical University of Warsaw, Warsaw, Poland
| | - Magdalena Durlik
- Department of Transplantation Medicine and Nephrology, Transplantation Institute, Medical University of Warsaw, Warsaw, Poland
| | - Jose Luis Calleja
- Liver Unit, Hospital Universitario Puerta de Hierro, CIBEREHD and IDIPHIM, Madrid, Spain
| | - Zoe Mariño
- Liver Unit, Hospital Clinic, IDIBAPS and CIBEREHD, University of Barcelona, Barcelona, Spain
| | - Umesh Shukla
- Janssen Research & Development, LLC, Titusville, NJ, USA
| | | | | | | | | | | | | | | |
Collapse
|
|
14
|
Sanchez Antolin G, Testillano M, Pascasio JM, Narvaez Rodriguez I, Prieto M, Otero A, Herrero JI, Londoño M, Fernandez Vazquez I, Castells L. Efficacy and Safety of Therapy With Simeprevir and Sofosbuvir in Liver Transplant Recipients Infected by Hepatitis C Virus Genotype 4: Cohort Spanish Society of Liver Transplantation Cohort. Transplant Proc 2017; 48:3013-3016. [PMID: 27932134 DOI: 10.1016/j.transproceed.2016.08.034] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2016] [Accepted: 08/22/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND Patients with hepatitis C virus (HCV) genotype 4 infection are poorly represented in clinical trials of 2nd-generation direct-acting antivirals (DAAs), and more data are needed to help guide treatment decisions. We still have even fewer data concerning liver transplant patients. Simeprevir (SIM) and sofosbuvir (SOF) combination is useful to treat this genotype. The aim of this study was to know the efficacy and safety of the combination SIM + SOF ± ribavirin (RBV) in a group of liver transplant patients with HCV genotype 4 infection in Spain in real life. METHODS This was a multicenter retrospective study, including 28 HCV genotype 4 patients from 11 liver transplant centers who were treated with SIM + SOF ± RBV. We included in the analysis demographic, clinical, and virologic data and details of serious adverse events (SAEs), including mortality rate 6 months after treatment. RESULTS All patients were male, mean age 52 ± 9.43 years, and 50% were IL28B CT and 37.5% TT; 46.42% of them were pretreated and 76.9 were null responders. Fibrosis stage 4 was found in 38.7% of patients; in 67.8% of those cases the diagnosis of fibrosis was made with the use of Fibroscan, in 21.4% by liver biopsy. The average Fibroscan was 13.86 KPa. The average Model for End-Stage Liver Disease (MELD) score of cirrhotic patients was 10.9 and the Child-Pugh score was A in 70%, B in 20%, and C in 10%. We included RBV in 75% of patients, and treatment duration was 12 weeks in all patients. The sustained virologic response at week 12 (SVR12) was 95.23%. There were no discontinuations due to SAEs, but the mortality rate at 6 months after treatment was 7.14%. All deceased patients were cirrhotic, Child C, and with an average MELD score of 20. CONCLUSIONS The combination SIM + SOF ± RBV to treat HCV genotype 4 in liver transplant patients is an option with high rates of SVR12 and very safe, similarly to genotype 1. There was no treatment-related mortality, but when it is administered in advanced stages of fibrosis it may not be enough to prevent mortality associated with cirrhotic hepatitis C recurrence after transplantation.
Collapse
Affiliation(s)
- G Sanchez Antolin
- Hepatology Unit, Liver Transplant Unit, Hospital Universitario Rio Hortega, Valladolid, Spain.
| | - M Testillano
- Hepatology Unit, Liver Transplant Unit, Hospital Universitario Cruces, Bilbao, Spain
| | - J M Pascasio
- Hepatology Unit, Hospital Universitario Virgen del Rocio, CIBERhed, Sevilla, Spain
| | - I Narvaez Rodriguez
- Gastroenterology Service, Liver Transplant Unit Hospital Infanta Cristina, Badajoz, Spain
| | - M Prieto
- Hepatology Unit, Hospital, Liver Transplant Unit Universitario La Fe, Valencia, Spain
| | - A Otero
- Liver Transplant Unit, Hospital Universitario Juan Canalejo, La Coruña, Spain
| | - J I Herrero
- Service of Internal Medicine, Liver Transplant Unit, CUN, Pamplona, Spain
| | - M Londoño
- Hepatology Service, Liver Transplant Unit, Hospital Clinic, CIBERhed, Barcelona, Spain
| | - I Fernandez Vazquez
- Service of Gastroenterology, Hepatology Unit, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - L Castells
- Service of Hepatology, CIBERhed Hospital Universitario, Vall d'Hebrón, Spain
| | | |
Collapse
|
|
15
|
Hori T, Onishi Y, Kamei H, Kurata N, Ishigami M, Ishizu Y, Ogura Y. Fibrosing Cholestatic Hepatitis in a Complicated Case of an Adult Recipient After Liver Transplantation: Diagnostic Findings and Therapeutic Dilemma. AMERICAN JOURNAL OF CASE REPORTS 2016; 17:597-604. [PMID: 27545580 PMCID: PMC4994933 DOI: 10.12659/ajcr.898427] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Patient: Male, 66 Final Diagnosis: Fibrosing cholestatic hepatitis Symptoms: Prolonged jaundice and intractable ascites Medication: Steroid pulse therapy and direct-acting antivirals Clinical Procedure: Liver transplantation Specialty: Transplantology
Collapse
Affiliation(s)
- Tomohide Hori
- Department of Transplant Surgery, Nagoya University Hospital, Nagoya, Japan
| | - Yasuharu Onishi
- Department of Transplant Surgery, Nagoya University Hospital, Nagoya, Japan
| | - Hideya Kamei
- Department of Transplantation Surgery, Nagoya University Hospital, Nagoya, Japan
| | - Nobuhiko Kurata
- Department of Transplant Surgery, Nagoya University Hospital, Nagoya, Japan
| | - Masatoshi Ishigami
- Department of Transplant Surgery, Nagoya University Hospital, Nagoya, Japan
| | - Yoji Ishizu
- Department of Transplant Surgery, Nagoya University Hospital, Nagoya, Japan
| | - Yasuhiro Ogura
- Department of Transplant Surgery, Nagoya University Hospital, Nagoya, Japan
| |
Collapse
|
|
16
|
Bonaventura A, Montecucco F. Sofosbuvir/velpatasvir: A promising combination. World J Hepatol 2016; 8:785-789. [PMID: 27429714 PMCID: PMC4937166 DOI: 10.4254/wjh.v8.i19.785] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2016] [Revised: 05/23/2016] [Accepted: 06/16/2016] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) affects 3% of the world population. It represents the main cause of chronic liver disease and is responsible for extra-hepatic complications, such as type 2 diabetes and cardiovascular diseases. HCV includes 7 genotypes differing in the nucleotide sequence variability, the geographic distribution, the rates of viral clearance, the risk of progression to liver fibrosis and to hepatocellular carcinoma, and the response to therapy. Last years have seen remarkable advances in the field of HCV infection with the approval of direct antiviral agents (DAAs) targeting key viral proteins involved in the HCV replication. Several oral regimens combining DAAs from different families have been developed and these regimens showed increased and sustained virological response rates to above 90% reducing the treatment duration to 12 wk or less. In particular, sofosbuvir, a nucleotide analogue nonstructural (NS)5B polymerase inhibitor, and velpatasvir, a NS5A inhibitor, have been tested in two phase 3 trials, the ASTRAL-2 (against HCV genotype 2) and the ASTRAL-3 (against HCV genotype 3), demonstrating to be effective, safe, and well tolerated in patients who were 18 years of age or older and had at least a 6-mo history of HCV infection with a compensated liver disease.
Collapse
|
|
17
|
Hori T, Onishi Y, Kamei H, Kurata N, Ishigami M, Ishizu Y, Ogura Y. Fibrosing cholestatic hepatitis C in post-transplant adult recipients of liver transplantation. Ann Gastroenterol 2016; 29:454-459. [PMID: 27708510 PMCID: PMC5049551 DOI: 10.20524/aog.2016.0069] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2016] [Accepted: 06/06/2016] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C recurrence continues to present a major challenge in liver transplantation (LT). Approximately 10% of hepatitis C virus (HCV)-positive recipients will develop fibrosing cholestatic hepatitis (FCH) after LT. FCH is clinically characterized as marked jaundice with cholestatic hepatic dysfunction and high titers of viremia. Pathologically, FCH manifests as marked hepatocyte swelling, cholestasis, periportal peritrabecular fibrosis and only mild inflammation. This progressive form usually involves acute liver failure, and rapidly results in graft loss. A real-time and precise diagnosis based on histopathological examination and viral measurement is indispensable for the adequate treatment of FCH. Typical pathological findings of FCH are shown. Currently, carefully selected combinations of direct-acting antivirals (DAAs) offer the potential for highly effective and safe regimens for hepatitis C, both in the pre- and post-transplant settings. Here, we review FCH caused by HCV in LT recipients, and current strategies for sustained virological responses after LT. Only a few cases of successfully treated FCH C after LT by DAAs have been reported. The diagnostic findings and therapeutic dilemma are discussed based on a literature review.
Collapse
Affiliation(s)
- Tomohide Hori
- Department of Transplant Surgery (Tohomide Hori, Yasuharu Onishi, Hideya Kamei, Nobuhiko Kurata, Yasuhiro Ogura), Nagoya University Hospital, Nagoya, Japan
| | - Yasuharu Onishi
- Department of Transplant Surgery (Tohomide Hori, Yasuharu Onishi, Hideya Kamei, Nobuhiko Kurata, Yasuhiro Ogura), Nagoya University Hospital, Nagoya, Japan
| | - Hideya Kamei
- Department of Transplant Surgery (Tohomide Hori, Yasuharu Onishi, Hideya Kamei, Nobuhiko Kurata, Yasuhiro Ogura), Nagoya University Hospital, Nagoya, Japan
| | - Nobuhiko Kurata
- Department of Transplant Surgery (Tohomide Hori, Yasuharu Onishi, Hideya Kamei, Nobuhiko Kurata, Yasuhiro Ogura), Nagoya University Hospital, Nagoya, Japan
| | - Masatoshi Ishigami
- Department of Gastroenterology and Hepatology (Masatoshi Ishigami), Nagoya University Hospital, Nagoya, Japan
| | - Yoji Ishizu
- Department of Gastroenterology and Hepatology (Masatoshi Ishigami), Nagoya University Hospital, Nagoya, Japan
| | - Yasuhiro Ogura
- Department of Transplant Surgery (Tohomide Hori, Yasuharu Onishi, Hideya Kamei, Nobuhiko Kurata, Yasuhiro Ogura), Nagoya University Hospital, Nagoya, Japan
| |
Collapse
|
|
18
|
Tanaka T, Akamatsu N, Kaneko J, Arita J, Tamura S, Hasegawa K, Sakamoto Y, Kokudo N. Daclatasvir and asunaprevir for recurrent hepatitis C following living donor liver transplantation with HIV co-infection. Hepatol Res 2016; 46:829-32. [PMID: 26508337 DOI: 10.1111/hepr.12614] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2015] [Revised: 10/05/2015] [Accepted: 10/19/2015] [Indexed: 02/06/2023]
Abstract
Antiviral treatment in liver transplant recipients co-infected with hepatitis C virus (HCV) and HIV remains a challenge. We herein report a case of HCV recurrence that was successfully treated using interferon-free anti-HCV therapy with daclatasvir and asunaprevir. A 48-year-old man underwent antiviral therapy with a 24-week course of daclatasvir and asunaprevir for biopsy-proven recurrent HCV 15 months after living donor liver transplantation, following non-response to pre-emptive antiviral treatment with pegylated interferon plus ribavirin. Anti-HIV and immunosuppressive regimens were modified safely. Renal function was feasibly preserved. The anti-HCV effect was remarkable with an undetectable viral load confirmed within 2 weeks, and this patient achieved a sustained virological response after 12 weeks of post-transplantation treatment. No serious adverse events were observed. This case indicates that daclatasvir and asunaprevir for recurrent HCV in a HIV co-infected recipient after liver transplantation is safe and effective.
Collapse
Affiliation(s)
- Tomohiro Tanaka
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo
| | - Nobuhisa Akamatsu
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo
| | - Junichi Kaneko
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo
| | - Junichi Arita
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo
| | - Sumihito Tamura
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo
| | - Kiyoshi Hasegawa
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo
| | - Yoshihiro Sakamoto
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo
| | - Norihiro Kokudo
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo
| |
Collapse
|
|
19
|
ARAI KEISUKE, KURAMITSU KAORI, FUKUMOTO TAKUMI, KIDO MASAHIRO, TAKEBE ATSUSHI, TANAKA MOTOFUMI, KINOSHITA HISOKA, AJIKI TETSUO, TOYAMA HIROCHIKA, ASARI SADAKI, GOTO TADAHIRO, KU YONSON. A Case Report of Drug-Induced Thrombocytopenia after Living Donor Liver Transplantation. THE KOBE JOURNAL OF MEDICAL SCIENCES 2016; 62:E9-E12. [PMID: 27492209 PMCID: PMC5433727] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 01/13/2016] [Accepted: 01/26/2016] [Indexed: 06/06/2023]
Abstract
There are few descriptions of severe thrombocytopenia during the early postoperative period after liver transplantation, and these have not been fully documented in the literature. Here, we report a case of drug-induced thrombocytopenia requiring transfusion of blood products after living donor liver transplantation. We determined that this was not caused by the interferon-free anti-viral therapy but by tacrolimus A 61-year-old woman with hepatitis C-related cirrhosis and hepatorenal syndrome underwent living donor liver transplantation using a left lobe graft from her son. After transplantation, immunosuppression consisted of tacrolimus and steroid. Seven weeks after transplantation, interferon-free therapy with daclatasvir and asunaprevir was started. Thirteen days thereafter, hepatitis C virus tested negative. However, the platelet count had begun to gradually decrease just before starting anti-viral therapy. Daclatasvir and asunaprevir were stopped because this was suspected to be a side-effect of these drugs, but the patient nonetheless went on to develop severe thrombocytopenia (platelet count 17,000/μL), which needed transfusions. Now suspecting tacrolimus as the inducer of this side effect, we changed to cyclosporin, after which the platelet count gradually recovered. Viral markers were still not detectable up to 2 months after discontinuation of the antiviral drugs. We conclude that when severe thrombocytopenia occurs, possible drug-induced thrombocytopenia as well as other disorders must be investigated.
Collapse
Affiliation(s)
- KEISUKE ARAI
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Hyogo, Japan
| | - KAORI KURAMITSU
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Hyogo, Japan
| | - TAKUMI FUKUMOTO
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Hyogo, Japan
| | - MASAHIRO KIDO
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Hyogo, Japan
| | - ATSUSHI TAKEBE
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Hyogo, Japan
| | - MOTOFUMI TANAKA
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Hyogo, Japan
| | - HISOKA KINOSHITA
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Hyogo, Japan
| | - TETSUO AJIKI
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Hyogo, Japan
| | - HIROCHIKA TOYAMA
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Hyogo, Japan
| | - SADAKI ASARI
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Hyogo, Japan
| | - TADAHIRO GOTO
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Hyogo, Japan
| | - YONSON KU
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Hyogo, Japan
| |
Collapse
|
|
20
|
|