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Management of Transplant Patients Infected with HCV

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Hepatitis C: Care and Treatment

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Abstract

Hepatitis C virus (HCV) infection is a leading cause of cirrhosis and hepatocellular carcinoma and one of the main indications for liver transplantation (LT) [1]. Historically, viral recurrence occurred in all patients with viral replication at the time of LT. Graft fibrosis progression rate was accelerated leading to cirrhosis in around 30% of untreated patients within 5 years. HCV graft infection was the cause of two-thirds of graft failure in these patients and was the most frequent cause of death [2, 3]. Viral eradication using antiviral therapy improves patient and graft survival [4–6]. Pegylated interferon (PEG-IFN)-ribavirin (RBV) and first-generation NS3/4 protease inhibitors (PI): boceprevir (BOC) or telaprevir (TVR) associated to PEG-IFN-RBV are no more used to treat HCV infection post-LT related to lower efficacy, poor tolerability, and drug–drug interactions (DDI) with immunosuppressive therapy [7–10]. Since 2013, the use of Sofosbuvir (SOF), a NS5B polymerase inhibitor, with RBV has led to improvements in tolerability and efficacy [11, 12]. Further improvement in SVR rates was observed using SOF in combination with a second direct-acting antiviral (DAA): Simeprevir (SIM), Ledipasvir (LDV), Daclatasvir (DCV), Elbasvir (EBR), and RBV, or the regimen of Ombitasvir, Paritaprevir/Ritonavir, Dasabuvir (3D), and RBV [13–28]. Limitations of these regimens are suboptimal efficacy in some subgroups of patients, none are pangenotypic, mostly contain RBV, and some have the potential for clinically significant DDIs. More recently, a new wave of pangenotypic, RBV-free, DAA regimens including SOF–Velpatasvir (VEL), Glecaprevir (GLE)–Pibrentasvir (PIB), and Voxaliprevir (VOX), were approved [29, 30]. These regimens maintain activity against most of the common resistance-associated substitutions (RAS) of HCV genotypes 1–6 that are known to confer resistance to previously approved antiviral therapies.

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Abbreviations

ART:

Antiretroviral therapy

BOC:

Boceprevir

CH:

Cholestatic hepatitis

CNI:

Calcineurin inhibitors

CsA:

Cyclosporine

CYP:

Cytochrome

DAA:

Direct-acting antiviral

DCV:

Daclatasvir

DDI:

Drug-to-drug interactions

EBR:

Elbasvir

EPO:

Erythropoietin

EVR:

Early virological response

GLE:

Glecaprevir

GZR:

Grazoprevir

HCV:

Hepatitis C virus

HIV:

Human immunodeficiency virus

LDV:

Ledipasvir

LT:

Liver transplantation

NA:

Not available

PEG-IFN:

pegylated interferon

PI:

Protease inhibitors

PIB:

Pibrentasvir

RAS:

Resistance-associated substitution

RBV:

Ribavirin

RNA:

Ribonucleic acid

RVR:

Rapid virological response

SIM:

Simeprevir

SOF:

Sofosbuvir

SVR:

Sustained virological response

Tac:

Tacrolimus

TVR:

Telaprevir

VEL:

Velpatatsvir

VOX:

Voxilaprevir

2D:

Paritaprevir/r, ombitasvir

3D:

Paritaprevir/r, ombitasvir, dasabuvir

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Authors and Affiliations

  1. AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France

    Bruno Roche, Audrey Coilly & Didier Samuel

  2. University Paris-Sud, Villejuif, France

    Bruno Roche, Audrey Coilly & Didier Samuel

  3. Inserm, Villejuif, France

    Bruno Roche, Audrey Coilly & Didier Samuel

  4. Hepatinov, Villejuif, France

    Bruno Roche, Audrey Coilly & Didier Samuel

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  1. Department of Hygiene, Epidemiology and Medical Statistics, National and Kapodistrian University of Athens Medical School, Athens, Greece

    Angelos Hatzakis

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Roche, B., Coilly, A., Samuel, D. (2021). Management of Transplant Patients Infected with HCV. In: Hatzakis, A. (eds) Hepatitis C: Care and Treatment . Springer, Cham. https://doi.org/10.1007/978-3-030-67762-6_11

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