Letter to the Editor
Successful treatment of chronic hepatitis C in a kidney transplant patient with only 2 weeks of direct-acting antiviral therapy
Eficacia del tiempo de tratamiento ultracorto con terapia antiviral de acción directa para la hepatitis C crónica en un paciente con trasplante de riñón: reporte de un caso
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[ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Rui Arlindo" "apellidos" => "Castro" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "Paulo" "apellidos" => "Carrola" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 4 => array:3 [ "nombre" => "Teresa Margarida Pinto Ribeiro" "apellidos" => "Morgado" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 5 => array:3 [ "nombre" => "Paula" "apellidos" => "Marques" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Nephrology Department, Centro Hospitalar Trás Montes e Alto Douro, Vila Real, Portugal" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Internal Medicine Department, Centro Hospitalar Trás Montes e Alto Douro, Vila Real, Portugal" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Eficacia del tiempo de tratamiento ultracorto con terapia antiviral de acción directa para la hepatitis C crónica en un paciente con trasplante de riñón: reporte de un caso" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Hepatitis C is an important health care problem, affecting 200 million people all over the world. About 1.8–8% of renal transplant patients are estimated to be infected with hepatitis C virus in developed countries.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> With the advent of direct-acting antivirals (DAAs) HCV treatment has evolved, allowing treatment with less systemic toxicity. As they were only recently approved for clinical use (in 2013), a lot of unanswered questions remain regarding their optimal clinical use, such as the minimum treatment duration. Their long-term effects are still unknown and the experience with these regimens on kidney transplant patients is still scarce<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a>.</p><p id="par0010" class="elsevierStylePara elsevierViewall">FS is a 44-year-old white male with a kidney transplant since January 2016. His maintenance immunosuppression was tacrolimus, mycophenolate mophetil and prednisolone. He developed stable chronic transplant dysfunction, with serum creatinine (sCr) of 1.8<span class="elsevierStyleHsp" style=""></span>mg/dl one month after transplant. In his period on hemodialysis, from 2009 to 2015, he always showed negative serologic tests for hepatitis B, C and HIV. In August 2015 hepatitis C antibodies were detected during routine screening. Following the detection of hepatitis C infection, he was referred to the Hepatology Department. At the time of his first appointment, in November 2015, genotype 1b was identified and the viral load of HCV RNA was 1.6<span class="elsevierStyleHsp" style=""></span>log<span class="elsevierStyleHsp" style=""></span>IU/ml. He missed subsequent appointments and did not comply with the scheduled exams. He got a kidney transplant in February 2016. In August he returned to his Hepatology department to complete investigation. The viral load was at this time 6.1<span class="elsevierStyleHsp" style=""></span>log<span class="elsevierStyleHsp" style=""></span>copy/ml. In January 2017 he began his treatment of eight weeks with ledispavir (90<span class="elsevierStyleHsp" style=""></span>mg per day) plus sofosbuvir (400<span class="elsevierStyleHsp" style=""></span>mg per day). Transient hepatic elastography revealed the value of 6.5<span class="elsevierStyleHsp" style=""></span>kPa and he maintained normal asparate aminotransferase (21<span class="elsevierStyleHsp" style=""></span>U/L) and alanine aminotransferase (19<span class="elsevierStyleHsp" style=""></span>U/L). Tacrolimus trough level was around 5–5.5<span class="elsevierStyleHsp" style=""></span>ng/mL.</p><p id="par0015" class="elsevierStylePara elsevierViewall">On a routine blood scan 14 days later, acute kidney dysfunction was diagnosed – sCr 2.2<span class="elsevierStyleHsp" style=""></span>mg/dl – and a low through level of tacrolimus was noted (3.8<span class="elsevierStyleHsp" style=""></span>ng/ml). Consensus between Hepatology and Nephrology departments was to withhold treatment with DAAs. He was admitted to Nephrology ward and, as kidney dysfunction persisted, a kidney biopsy was performed on January 30th. The histopathology showed acute cellular rejection stage IA Banff with negative C4d. DSA (donor specific anti-HLA antibodies) were negative. He was treated with intravenous methylprednisolone bolus and anti-thymocyte globulin infusion, but maintained a stable sCr of 2.2<span class="elsevierStyleHsp" style=""></span>mg/dl at the time of discharge. In his last kidney transplant routine appointment, sCr was 2.3<span class="elsevierStyleHsp" style=""></span>mg/dl and tacrolimus trough levels were 6.7<span class="elsevierStyleHsp" style=""></span>ng/ml.</p><p id="par0020" class="elsevierStylePara elsevierViewall">HCV viral load determinations at 3 weeks after the beginning of treatment and sustained viral response at 24 weeks were negative. Hence, cure for hepatitis C was assumed with an ultra-short treatment time of 14 days. SVR is associated with greater survival and less likelihood of developing hepatic disease. Smith Palmer et al.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> in a systematic review report a cure rate of 98–99% four years after achieving SVR. Meanwhile, information over identical follow up in kidney transplant (KT) patients is still scarce. Fernandez et al.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> in 2016, reported one of the largest retrospective series (103 patients) on kidney transplant patients treated with DAAs. Treatment with sofosbuvir and ledispavir or sofosbuvir and daclatasvir in KT patients achieved a 98% rate of SVR. Although immunosuppression levels needed adjustment in 55% of patients there were only three acute rejection episodes that quickly resolved with therapy. Levels of sCr, glomerular filtration rate and proteinuria did not differ significantly from baseline.</p><p id="par0025" class="elsevierStylePara elsevierViewall">In the immediate post-transplant period, the risk of acute rejection of the kidney transplant is not despisable. Post-KT population has an elevated risk of infectious, immunologic and neoplastic complications as well. KT patients represent a high level of financial investment and therefore require a larger effort in the management of their comorbidities.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Our case report shows cure of HCV infection only with 14 days of treatment. It seems to us to be the shortest treatment time with efficacy ever reported with ledispavir and sofosbuvir for treatment of HCV infection in a KT patient<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">5,6</span></a>. Short treatment times were also reported by Lau G et al.,<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> in a phase 2 study on a Chinese population without cirrhosis, but we stress that a triple (not double) regimen was used, for 3 weeks. Sawinski et al.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> report a patient, black race, who achieved negative viral load after 29 days of treatment of ledispavir and sofosbuvir. This is, to date, the shortest response ever reported with these two agents. Meissner et al.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> report a case of successful treatment with sofosbuvir and ribavirin for 27 days. More experience is needed on the treatment of chronic hepatitis C in kidney transplant patients. The opportunity of using shorter treatment times, in an effective and more tolerable way, will be a great driver for investment and research in this area.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0035" class="elsevierStylePara elsevierViewall">None.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:8 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "e0158431" "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy and safety of direct acting antivirals in kidney transplant recipients with chronic hepatitis C virus infection" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.V. Lin" 1 => "M.E. Sise" 2 => "M. Pavlakis" 3 => "B.M. Amundsen" 4 => "D. Chute" 5 => "A.E. Rutherford" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "PLOS ONE" "fecha" => "2016" "volumen" => "11" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0060" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Direct acting antivirals for chronic hepatitis C" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.C. Jakobsen" 1 => "E.E. Nielsen" 2 => "J. Feinberg" 3 => "K.K. Katakam" 4 => "K. Fobian" 5 => "G. 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Valentine" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s12879-015-0748-8" "Revista" => array:5 [ "tituloSerie" => "BMC Infect Dis" "fecha" => "2015" "volumen" => "15" "paginaInicial" => "19" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25596623" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0070" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy and tolerability of interferon-free antiviral therapy in kidney transplant recipients with chronic hepatitis C" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "I. Fernández" 1 => "R. Muñoz-Gómez" 2 => "J.M. Pascasio" 3 => "C. Baliellas" 4 => "N. Polanco" 5 => "N. Esforzado" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jhep.2016.12.020" "Revista" => array:6 [ "tituloSerie" => "J Hepatol" "fecha" => "2017" "volumen" => "66" "paginaInicial" => "718" "paginaFinal" => "723" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28039098" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0075" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Successful treatment of hepatitis C in renal transplant recipients with direct-acting antiviral agents" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "D. Sawinski" 1 => "N. Kaur" 2 => "A. 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 8 | 8 | 16 |
| 2024 Octubre | 52 | 39 | 91 |
| 2024 Septiembre | 90 | 26 | 116 |
| 2024 Agosto | 86 | 68 | 154 |
| 2024 Julio | 55 | 27 | 82 |
| 2024 Junio | 89 | 40 | 129 |
| 2024 Mayo | 78 | 28 | 106 |
| 2024 Abril | 85 | 42 | 127 |
| 2024 Marzo | 57 | 21 | 78 |
| 2024 Febrero | 52 | 34 | 86 |
| 2024 Enero | 47 | 18 | 65 |
| 2023 Diciembre | 37 | 32 | 69 |
| 2023 Noviembre | 66 | 45 | 111 |
| 2023 Octubre | 90 | 27 | 117 |
| 2023 Septiembre | 124 | 26 | 150 |
| 2023 Agosto | 55 | 27 | 82 |
| 2023 Julio | 73 | 35 | 108 |
| 2023 Junio | 69 | 26 | 95 |
| 2023 Mayo | 84 | 53 | 137 |
| 2023 Abril | 74 | 16 | 90 |
| 2023 Marzo | 69 | 48 | 117 |
| 2023 Febrero | 61 | 20 | 81 |
| 2023 Enero | 61 | 54 | 115 |
| 2022 Diciembre | 104 | 40 | 144 |
| 2022 Noviembre | 77 | 37 | 114 |
| 2022 Octubre | 113 | 69 | 182 |
| 2022 Septiembre | 82 | 54 | 136 |
| 2022 Agosto | 86 | 56 | 142 |
| 2022 Julio | 57 | 65 | 122 |
| 2022 Junio | 67 | 44 | 111 |
| 2022 Mayo | 65 | 35 | 100 |
| 2022 Abril | 77 | 81 | 158 |
| 2022 Marzo | 97 | 77 | 174 |
| 2022 Febrero | 64 | 49 | 113 |
| 2022 Enero | 62 | 48 | 110 |
| 2021 Diciembre | 69 | 54 | 123 |
| 2021 Noviembre | 48 | 42 | 90 |
| 2021 Octubre | 47 | 57 | 104 |
| 2021 Septiembre | 40 | 41 | 81 |
| 2021 Agosto | 36 | 52 | 88 |
| 2021 Julio | 48 | 52 | 100 |
| 2021 Junio | 30 | 35 | 65 |
| 2021 Mayo | 47 | 56 | 103 |
| 2021 Abril | 105 | 91 | 196 |
| 2021 Marzo | 55 | 34 | 89 |
| 2021 Febrero | 63 | 38 | 101 |
| 2021 Enero | 45 | 37 | 82 |
| 2020 Diciembre | 34 | 31 | 65 |
| 2020 Noviembre | 46 | 18 | 64 |
| 2020 Octubre | 31 | 34 | 65 |
| 2020 Septiembre | 34 | 22 | 56 |
| 2020 Agosto | 46 | 25 | 71 |
| 2020 Julio | 29 | 23 | 52 |
| 2020 Junio | 25 | 32 | 57 |
| 2020 Mayo | 46 | 21 | 67 |
| 2020 Abril | 38 | 26 | 64 |
| 2020 Marzo | 34 | 23 | 57 |
| 2020 Febrero | 42 | 34 | 76 |
| 2020 Enero | 50 | 35 | 85 |
| 2019 Diciembre | 46 | 32 | 78 |
| 2019 Noviembre | 50 | 35 | 85 |
| 2019 Octubre | 35 | 27 | 62 |
| 2019 Septiembre | 34 | 22 | 56 |
| 2019 Agosto | 22 | 31 | 53 |
| 2019 Julio | 35 | 27 | 62 |
| 2019 Junio | 38 | 22 | 60 |
| 2019 Mayo | 24 | 33 | 57 |
| 2019 Abril | 70 | 62 | 132 |
| 2019 Marzo | 40 | 32 | 72 |
| 2019 Febrero | 37 | 38 | 75 |
| 2019 Enero | 42 | 40 | 82 |
| 2018 Diciembre | 112 | 65 | 177 |
| 2018 Noviembre | 175 | 38 | 213 |
| 2018 Octubre | 83 | 14 | 97 |
| 2018 Septiembre | 98 | 23 | 121 |
| 2018 Agosto | 71 | 23 | 94 |
| 2018 Julio | 69 | 22 | 91 |
| 2018 Junio | 88 | 28 | 116 |
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