Treatment of HCV in children at risk of reinfection

Post by Master, Doctor Mai Vien Phuong - Department of Examination & Internal Medicine - Vinmec Central Park International General Hospital

The treatment of HCV in children with direct-acting antivirals before and after liver transplantation has resulted in a tremendous improvement in transplant outcomes. The type of immunosuppressive regimen following liver transplantation does not appear to affect response to direct-acting antiviral therapy. However, fluctuations in calcineurin inhibitor trough concentrations during treatment may cause graft immune-mediated dysfunction.
Chronic infection by hepatitis B virus (HBV) and hepatitis C virus (HCV) is a major cause of progressive liver disease as well as death worldwide. Although considered benign infections in children, their persistence through adulthood is certainly of concern.

The advent of direct-acting antivirals (DAAs) has radically changed the treatment approach to HCV eradication not only for healthy children but also for those with comorbidities.
The high safety of direct-acting antivirals has prompted extensive trial use for previously overlooked clinical conditions for which IFN-based treatment strategies have been banned.
HCV recurrence after liver transplantation is a matter of concern in older children, which can rapidly progress to graft cirrhosis and death. The treatment of HCV in children with direct-acting antivirals before and after liver transplantation has resulted in a tremendous improvement in transplant outcomes. The type of immunosuppressive regimen following liver transplantation does not appear to affect response to direct-acting antiviral therapy. However, fluctuations in calcineurin inhibitor trough concentrations during treatment may cause graft immune-mediated dysfunction.
To date, only 7 children who received direct-acting antivirals after hematopoietic stem cell transplantation (HSCT) for hematologic disease have been described in the literature. 1 child received HSCT for acute lymphoblastic leukemia (4 years, genotype 1a); Another child with sickle cell disease (15 years, genotype 4) was treated with the combination of sofosbuvir/simeprevir for 24 weeks and 12 weeks, respectively.
The children achieved stable viral clearance with calcineurin inhibitor-based regimens (cyclosporin + mycophenolate mofetil and tacrolimus + sirolimus, respectively). Another 5 children aged 5-12 years and who received heritable monogenic HSCT for refractory lymphoblastic leukemia genotype 1b, were being maintained on cyclosporin. All children were treated with 24 weeks of sofosbuvir/velpatasvir after a median HSCT follow-up of 15 months and achieved a 1-month SVR.
El-Shabrawi et al reported a 12-week course of sofosbuvir/daclatasvir in 20 genotype 4-infected children in complete remission of hematologic malignancy for more than 18 months. All children achieved SVR24 without noticeable side effects. Two groups of investigators reported on HCV-driven eradication of direct-acting antivirals in patients with thalassemia. In total, 25 children were enrolled, 14 children with genotype 3 received 12-wk sofosbuvir/daclatasvir and 11 children with genotype 4 received 12-week sofosbuvir/ledipasvir). All achieved SVR12 without any serious side effects.

Because of their effectiveness and safety, the use of direct acting antivirals is expanding into advanced treatments. Hematopoietic stem cell gene therapy (HSC-GT) as a life-saving option for congenital diseases is contraindicated in children infected with hepatitis C because of the risk of infection of the bone marrow cells used as starting materials for production.
A 12-week course of sofosbuvir/ledipasvir allows autologous HSC-GT to correct severe combined immunodeficiency due to adenosine deaminase deficiency as described in a pioneering study. Pediatric studies have not yet replicated the encouraging results with direct-acting antivirals in older children coinfected with HIV/HCV, even with longitudinal transmission not to treat HCV in patients receiving treatment. dialysis and kidney transplant patients.

References:
Nicastro E, Norsa L, Di Giorgio A, Indolfi G, D'Antiga L. Breakthroughs and challenges in the management of viral hepatitis in children. World J Gastroenterol 2021; 27 (20): 2474-2494 [DOI: 10.3748 / wjg.v27.i20.2474]