LETTERS TO THE EDITOR Direct Acting Antiviral Treatment REFERENCES Selection in a Child With Hepatitis C 1. Indolﬁ G, Thorne C, El Sayed MH, et al. The challenge of treating Virus Infection and children with hepatitis C. J Pediatr Gastroenterol Nutr 2017;64:851–4. 2. Jonas MM. Hepatitis C virus infection in children. UptoDate Website. Compensated Cirrhosis https://www.uptodate.com/contents/hepatitis-c-virus-infection-in-children. Accessed May 25, 2017. 3. American Association for the Study of Liver Diseases. HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C. o the Editor: We read with interest the article by Indolfi et al 2016. www.hcvguidelines.org. Accessed May 5, 2016. (1) about the issue of treating children with hepatitis C virus 4. Goldschmidt I, Streckenbach C, Dingemann C, et al. Application and (HCV) infection, in connection with the approval, in April 2017, of limitations of transient liver elastography in children. J Pediatr Gastro- 2 new direct-acting antivirals (sofosbuvir plus ribavirin and sofos- enterol Nutr 2013;57:109–13. buvir-ledipasvir) for patients 12 years of age and older (1). How- ever, in some cases, as children in whom prior treatment has failed, little data is available about appropriate treatment selection, so it may be reasonable to consider adult guidelines (2). In this context, we report the case of a 12-year-old patient diagnosed with genotype 4 chronic HCV infection who had The Best Choice for Second-line received treatment with peg-interferon plus ribavirin when he was 6 years old with no response, and at this moment he had Agent in Standard Treatment- compensated cirrhosis histologically confirmed by liver biopsy. refractory Children With After discussing with the family, we requested a direct-acting antiviral treatment to the hospital drugs committee for off-label use. Autoimmune Hepatitis Following the American Association for the Study of Liver Dis- eases recommendations for adult patients with HCV genotype 4 infection with compensated cirrhosis, in whom prior treatment has o the Editor: Zizzo et al (1) report that 83% of standard failed, we proposed a daily fixed-dose combination of PrO (par- treatment-refractory patients with autoimmune hepatitis itaprevir 150 mg/ritonavir 100 mg/ombitasvir 25 mg) plus ribavirin T (AIH) respond to cyclosporine (CSA) after 6 months, whereas (3). The drug was approved and provided by the National Health 36% respond to mycophenolate mofetil (MMF). Service and our patient received it during 12 weeks, showing no The authors were concerned by the high frequency of CSA- side effects and excellent results (Table 1). related cosmetic side-effects and CSA level monitoring was con- sidered an added level of difficulty, not an opportunity to tailor TABLE 1. Evolution of our patient after receiving direct-acting antiviral dosage. treatment These reasons, together with MMF’s better safety profile, DAA AST, ALT, AFP, Bile Total HCV lead the authors to consider MMF as the primary choice for second- treatment U/mL U/mL ng/mL acids, bilirubin, PCR, Elastography, line agent in pediatric refractory AIH. timeline mmol/L mg/dL IU/mL kPa In our experience on prolonged treatment of autoimmune liver disease with CSA, all the 12 patients with a 35.6-month mean Week 0 113 159 105 127 1.58 6,064,299 21 duration of CSA treatment (8–89 months) and a 6.5-year median Week 12 25 39 4 12 0.36 Not – follow-up (1.5–15 years) achieved complete remission without detected treatment withdrawal due to side-effects. Cosmetic side-effects Week 24 26 36 3.6 — 0.42 Not 10.1 such as gingival hyperplasia and hypertrichosis were minor and detected transitory. In the only patient with a mild serum creatinine increase, renal function promptly normalized after CSA tapering (2). The Liver function tests, HCV real-time polymerase chain reaction (PCR) and mild and transient nature of CSA-related side-effects was also elastography results before treatment, and 12 and 24 weeks respectively after reported by Alvarez and Cuarterolo in a large series of children receiving PrO plus ribavirin treatment. HCV-PCR lower limit of detection with AIH (4,5). was 15 IU/mL. Normal liver stiffness measurements by elastography in healthy children according to age: 0 to 2 years: 2.8 to 8.2 kPa; 3 to 5 years: Although we do agree with Zizzo et al that the safety of CSA 3.5 to 6.8 kPa; 6 to 11 years: 3 to 6.6 kPa; >11 years: 2.8 to 8.9 kPa (4). in the long-term must be be confirmed in larger prospective studies, AFP ¼ alpha-fetoprotein; ALT ¼ alanine transaminase; AST ¼ aspartate because of its high efficacy, we cannot agree to consider MMF as transaminase; DAA ¼ direct-acting antiviral; HCV ¼ hepatitis C virus; the primary choice for refractory AIH. We agree with Czaja who PCR ¼ polymerase chain reaction. suggests that calcineurin inhibitors, particularly CSA, are the drugs of choice in case of steroid failure and that MMF is indicated for In the absence of strong evidence, in our opinion it is useful azathioprine intolerance (3). to consult adult guidelines to select the appropriate HCV treatment for children in special situations. Silvia Nastasio, Marco Sciveres, and Giuseppe Maggiore Section of Pediatrics, Department of Medical Sciences, Ignacio Ros, Marı´a Baranguan, Ruth Garcı´a-Romero, University of Ferrara, University Hospital and Eduardo Ubalde Arcispedale Sant’Anna, Ferrara Gastroenterology and Nutrition Unit, Miguel Servet Children’s Pediatric Hepatology and Liver Transplantation, Hospital, Zaragoza, Spain ISMETT UPMC Italy, Palermo, Italy e86 JPGN Volume 66, Number 3, March 2018 Copyright © ESPGHAN and NASPGHAN. All rights reserved.
Journal of Pediatric Gastroenterology & Nutrition – Wolters Kluwer Health
Published: Mar 1, 2018
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