Letter to the Editor
Hepatocellular carcinoma after direct-acting antiviral therapy in kidney transplant recipients infected with hepatitis C virus
Carcinoma hepatocelular después del tratamiento con antivirales de acción directa en pacientes trasplantados renales infectados con el virus de la hepatitis C
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"Hepatocellular carcinoma after direct-acting antiviral therapy in kidney transplant recipients infected with hepatitis C virus" "tieneTextoCompleto" => true "saludo" => "Dear Editor," "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "675" "paginaFinal" => "676" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Rita Calça, Cristina Jorge, Luís Lebre, Eunice Cacheira, Sara Querido, Célia Nascimento, Teresa Adragão, Margarida Bruges, André Weigert, Domingos Machado" "autores" => array:10 [ 0 => array:4 [ "nombre" => "Rita" "apellidos" => "Calça" "email" => array:1 [ 0 => "arrcalca@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Cristina" "apellidos" => "Jorge" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Luís" "apellidos" => "Lebre" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "Eunice" "apellidos" => "Cacheira" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "Sara" "apellidos" => "Querido" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 5 => array:3 [ "nombre" => "Célia" "apellidos" => "Nascimento" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 6 => array:3 [ "nombre" => "Teresa" "apellidos" => "Adragão" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 7 => array:3 [ "nombre" => "Margarida" "apellidos" => "Bruges" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 8 => array:3 [ "nombre" => "André" "apellidos" => "Weigert" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 9 => array:3 [ "nombre" => "Domingos" "apellidos" => "Machado" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Department of Nephrology, Hospital Santa Cruz – Centro Hospitalar Lisboa Ocidental, Lisbon, Portugal" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Gastroenterology, Hospital Egas Moniz – Centro Hospitalar Lisboa Ocidental, Lisbon, 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" => "Carcinoma hepatocelular después del tratamiento con antivirales de acción directa en pacientes trasplantados renales infectados con el virus de la hepatitis C" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The success of direct-acting antivirals (DAA) against hepatitis C virus (HCV) was a major breakthrough in medicine. Many studies showed that DAA are safe and effective for chronic HCV infection treatment after kidney transplantation.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> In 2018 KDIGO updated the Guidelines on chronic HCV in chronic kidney disease (CKD) including the recommendation that all infected kidney transplant recipients (KTR) should be evaluated for treatment.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">About KTR treated in our kidney transplantation unit<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> we would like to report two fatal cases.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The first was a 71-year-old male with IgA nephropathy with prior HCV infection (genotype 1b), who underwent kidney transplantation in 1991. In 2016 hepatic fibrosis (fibroscan F3) was documented and HCV treatment with ledipasvir/sofosbuvir was prescribed reaching sustained viral response (SVR) at 12 weeks. One year after therapy, elevation of alpha-fetoprotein (AFP) from 2.9 to 10.9<span class="elsevierStyleHsp" style=""></span>ng/ml (reference value <8.8<span class="elsevierStyleHsp" style=""></span>ng/ml) was noticed, despite undetectable HCV viral load. Hepatic ultrasound found no abnormalities but computed tomography showed extensive hepatic nodular involvement and partial portal vein thrombosis, suggestive of hepatocellular carcinoma (HCC). The patient died four months after HCC diagnosis, before treatment with sorafenib was started.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The second patient was a 72-year-old female with CKD due to chronic pyelonephritis who underwent renal transplantation in 2003. She had prior chronic HCV infection (genotype 1a) and had documented hepatic cirrhosis (fibroscan F4). Treatment with sofosbuvir/ledipasvir/ribavirin was given 13 years after transplantation, reaching SVR at 24 weeks. Eleven months later, AFP increased (7.2–2864<span class="elsevierStyleHsp" style=""></span>ng/ml). Despite normal hepatic ultrasound, magnetic resonance imaging showed a nodular lesion compatible with HCC. The lesion was successfully embolized. Ten months later, bone metastasis was evident as she suffered a fracture on her left hip. Bone biopsy confirmed metastatic HCC. Although HCV viral load remained undetectable, the patient died 14 months after the diagnosis.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Even after HCV eradication by DAA, the risk of progression to HCC remains a threat. As illustrated in these two cases, the suspicion was raised by an increasingly AFP despite an unsuspected ultrasound.</p><p id="par0030" class="elsevierStylePara elsevierViewall">In patients with chronic HCV infection and cirrhosis, the risk of developing HCC remains uncertain. However this risk is significantly reduced compared to untreated patients or in the ones who did not achieve SVR.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a> The European Association for the Study of the Liver recommends that patients with advanced fibrosis or cirrhosis with SVR should undergo surveillance for HCC every 6 months by means of ultrasound.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a> However, in these two KTR cases, ultrasound was ineffective for detection of HCC, which occurred less than one year after apparently successful DAA therapy.</p><p id="par0035" class="elsevierStylePara elsevierViewall">The purpose of reporting these two cases is fourfold: (1) to alert for the need to fully evaluate patients who display an increase of AFP levels; (2) ultrasound may not be a sensitive method to HCC diagnosis; (3) to raise the possibility that immunosuppression may eventually increase the oncogenic potential of previous HCV infection; (4) as HCV infection lasted for many years and HCC developed shortly after DAA a causal relation cannot be discarded.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0040" class="elsevierStylePara elsevierViewall">The authors disclose no conflicts of interest.</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:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Treatment with ledipasvir–sofosbuvir for 12 or 24 weeks in kidney transplant recipients with chronic hepatitis C virus genotype 1 or 4 infection: a randomized trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Colombo" 1 => "A. Aghemo" 2 => "H. Liu" 3 => "J. Zhang" 4 => "H. Dvory-Sobol" 5 => "R. Hyland" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.7326/M16-1205" "Revista" => array:6 [ "tituloSerie" => "Ann Intern Med" "fecha" => "2017" "volumen" => "166" "paginaInicial" => "109" "paginaFinal" => "117" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27842383" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0035" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Executive summary of the 2018 KDIGO Hepatitis C in CKD Guideline: welcoming advances in evaluation and management" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Jadoul" 1 => "M.C. Berenguer" 2 => "W. Doss" 3 => "F. Fabrizi" 4 => "J. Izopet" 5 => "V. Jha" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.kint.2018.06.011" "Revista" => array:6 [ "tituloSerie" => "Kidney Int" "fecha" => "2018" "volumen" => "94" "paginaInicial" => "663" "paginaFinal" => "673" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30243313" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0040" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatitis C virus eradication in kidney transplant recipients: a single-center experience in Portugal" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Weigert" 1 => "S. Querido" 2 => "L. Carvalho" 3 => "L. Lebre" 4 => "C. Chagas" 5 => "P. Matias" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.transproceed.2018.02.017" "Revista" => array:6 [ "tituloSerie" => "Transplant Proc" "fecha" => "2018" "volumen" => "50" "paginaInicial" => "743" "paginaFinal" => "745" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29661427" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0045" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Association between sustained virological response and all-cause mortality among patients with chronic hepatitis c and advanced hepatic fibrosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A.J. Meer" 1 => "Van Der" 2 => "B.J. Veldt" 3 => "J.J. Feld" 4 => "H. Wedemeyer" 5 => "J.-F. Dufour" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "JAMA" "fecha" => "2012" "volumen" => "308" "paginaInicial" => "2584" "paginaFinal" => "2593" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0050" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "EASL recommendations on treatment of hepatitis C 2018" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.M. Pawlotsky" 1 => "F. Negro" 2 => "A. Aghemo" 3 => "M. Berenguer" 4 => "O. Dalgard" 5 => "G. Dusheiko" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jhep.2018.03.026" "Revista" => array:6 [ "tituloSerie" => "J Hepatol" "fecha" => "2018" "volumen" => "69" "paginaInicial" => "461" "paginaFinal" => "511" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29650333" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/02116995/0000004000000006/v1_202011280641/S0211699519302127/v1_202011280641/en/main.assets" "Apartado" => array:4 [ "identificador" => "48186" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Cartas al Director" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/02116995/0000004000000006/v1_202011280641/S0211699519302127/v1_202011280641/en/main.pdf?idApp=UINPBA000064&text.app=https://revistanefrologia.com/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0211699519302127?idApp=UINPBA000064" ]
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