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Persistence of Virologic Response after Liver Transplant in Hepatitis C Patients Treated with Ledipasvir/Sofosbuvir Plus Ribavirin Pretransplant
Carmen Vinaixa
,§,
Corresponding author
vinaixa.carmen@gmail.com

Correspondence and reprint request:
, Marina Berenguer*,,,§
* Department of Gastroenterology, Hepatology and Liver Transplantation Unit, Hospital Universitari i Politècnic La Fe, Valencia (Spain)
Networking Biomedical Research Centre in Hepatic and Digestive Diseases (CIBEREHD), Spain
Department of Medicine, Universitat de València, Valencia (Spain)
§ Instituto de Investigación Sanitaria, Hospital Universitari i Politècnic La Fe, Valencia (Spain)
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="p0010" class="elsevierStylePara elsevierViewall">In the field of hepatitis C treatment&#44; currently almost all past issues are solved&#44; including treatment of special populations&#46; Nevertheless&#44; some aspects remain unanswered&#44; such as the controversial decision to treat pre <span class="elsevierStyleItalic">vs&#46;</span> post-liver transplantation &#40;LT&#41;&#44; the &#8220;point of no return&#8221; for improvement of hepatic function after antiviral treatment&#44; and optimizing treatment outcomes in some subgroups like genotype 3 infection in hemodialysis patients&#46;</p><p id="p0015" class="elsevierStylePara elsevierViewall">We read with interest the article by Eric M&#46; Yoshida&#44; <span class="elsevierStyleItalic">et al&#46;&#44;</span> which is a <span class="elsevierStyleItalic">post-hoc</span> analysis of the persistence of viral response &#40;pTVR&#41; after LT in patients included in the SOLAR trials<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">1&#44;2</span></a> who received antiviral treatment and subsequently underwent LT&#46; In the study by Yoshida&#44; <span class="elsevierStyleItalic">et al&#46;&#44;</span> all 17 were decompensated cirrhotic patients &#40;Child B or C&#41; with median MELD score of 16 who started treatment with Ledipasvir&#47;Sofosbuvir plus ribavirin &#40;RBV&#41; before LT&#46; Of these&#44; 10 patients completed their planned treatment duration before LT&#44; while 7 underwent LT before completing the 12 or 24 weeks of planned antiviral treatment&#46; Seventy-six percent of patients completed at least 12 weeks of antiviral treatment&#46; As a result&#44; all 17 patients achieved pTVR&#44; although one died shortly after LT &#40;unrelated to study drugs&#41;&#44; leading to a 94&#37; rate of pTVR-12&#46;</p><p id="p0020" class="elsevierStylePara elsevierViewall">The most obvious advantage for treating patients before LT is to prevent HCV recurrence in the post-transplant setting&#46; Nevertheless&#44; not many studies have examined this issue&#46; In the interferon era&#44; only one randomized controlled trial of treatment with pegylated interferon plus RBV for patients in the waiting list for LT was performed&#44;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">3</span></a> with only 22&#37; and 29&#37; pTVR&#44; for genotypes 1&#47;4&#47;6 and genotypes 2&#47;3&#44; respectively&#46; The only factor that emerged as predictor of pTVR was the number of weeks the patient remained with undetectable viral load before LT &#40;&#62; 16 weeks&#41;&#46; In the direct antiviral agent &#40;DAA&#41; era&#44; a study by Curry&#44; <span class="elsevierStyleItalic">et al&#46;</span><a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">4</span></a> examined the results of the administration of Sofosbuvir plus RBV in compensated cirrhotic patients listed for hepatocellular carcinoma &#40;HCC&#41;&#59; 70&#37; of patients achieved pTVR&#46; Once again&#44; the number of consecutive days &#40;&#62; 30 days&#41; with HCV RNA target not detected prior to transplant appeared to be the strongest predictor of post-transplant viral response&#46; In other words&#44; the amount of time the patient remains with undetectable HCV viral load before LT seems to be an important factor in order to prevent recurrence of HCV in the liver graft&#46; There are no specifically designed studies to examine this issue with 2 or more DAAs&#44; but existing data of treatment in compensated and decompensated cirrhotic patients with several DAA combinations show sustained viral response &#40;SVR&#41; rates over 90&#37; with viral negativity achieved in most cases within the first month of treatment initiation&#44; suggesting that the required duration of HCV undectectability could be even shorter&#46; However&#44; this question remains to date unanswered&#46; The current study is interesting as it provides data related to patients successfully treated with ledipasvir&#47;sofosbuvir &#177; RBV in the pretransplant setting who present no HCV recurrence post-transplant&#46;</p><p id="p0025" class="elsevierStylePara elsevierViewall">An alternative for patients not finishing the established duration of therapy before transplantation is to &#8220;bridge&#8221; treatment&#44; i&#46;e&#46; to continue therapy during the peritrans-plant period&#46; To date&#44; two studies summarizing limited data of patients treated before&#44; during and after transplantation are available&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">5&#44;6</span></a> Both studies&#44; one based on sofosbu-vir plus RBV and the second based on several DAA combinations&#44; have shown that this is a feasible and effective strategy&#46;</p><p id="p0030" class="elsevierStylePara elsevierViewall">An interesting and still controversial issue is whether antiviral treatment might avoid transplantation in HCV-in-fected patients with decompensated cirrhosis&#46; All 17 de-compensated patients in the SOLAR study underwent LT&#44; suggesting that not all patients improve to a point where transplantation is prevented&#46; However&#44; even in these cases&#44; it is likely that the condition of the patient is globally improved leading to better post-transplant outcomes&#46; Nevertheless&#44; the particularities of each waiting list &#40;WL&#41; are different and must be taken into account&#46; For example&#44; in settings where donors are scarce&#44; a MELD improvement may result in worse patient access to LT &#40;the so-called &#8220;MELD purgatory&#8221;&#41;&#46;</p><p id="p0035" class="elsevierStylePara elsevierViewall">In our center around 40&#37; of waitlisted patients have HCV infection&#44; with or without HCC&#46; In the last three years&#44; almost 50 patients in the WL for LT have received antiviral treatment and 30&#37; of these have been delisted after confirming clinical and laboratory data improvement&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">7</span></a></p><p id="p0040" class="elsevierStylePara elsevierViewall">In essence&#44; although more studies are needed to determine the optimal timing of treatment with DAA combinations before LT&#44; this is clearly an interesting strategy which may ultimately lead not only to prevention of viral recurrence but also to clinical improvement and potentially avoidance of LT&#46; Given the rapidity at which DAA-based antiviral treatment is being applied in patients with advanced liver disease&#44; at least in the western world and in countries with access to LT&#44; it is unlikely that studies specifically designed at determining the best timing of treatment initiation will be undertaken&#44; and studies like the one by Yoshida&#44; <span class="elsevierStyleItalic">et al&#46;</span> published in this issue will help understanding the benefits and limitations of such a strategy&#46;</p></span>"
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Article information
ISSN: 16652681
Original language: English
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2022 May 6 3 9
2022 April 11 8 19
2022 March 15 10 25
2022 February 11 3 14
2022 January 13 4 17
2021 December 4 4 8
2021 November 6 4 10
2021 October 4 10 14
2021 September 6 4 10
2021 August 6 7 13
2021 July 6 5 11
2021 June 5 5 10
2021 May 8 4 12
2021 April 5 11 16
2021 March 7 6 13
2021 February 4 4 8
2021 January 3 7 10
2020 December 3 5 8
2020 November 6 8 14
2020 October 11 4 15
2020 September 12 6 18
2020 August 3 5 8
2020 July 2 4 6
2020 June 6 3 9
2020 May 4 4 8
2020 April 4 3 7
2020 March 1 1 2
2020 February 4 5 9
2020 January 5 2 7
2019 December 3 5 8
2019 November 4 3 7
2019 October 1 0 1
2019 September 1 1 2
2019 August 1 1 2
2019 July 7 6 13
2019 June 0 9 9
2019 May 1 5 6
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es en pt

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos