PERSONALIZED APPROACH TO TREATING CHRONIC HEPATITIS C IN CHILDREN
https://doi.org/10.15690/pf.v11i2.960
Abstract
Predictors of positive virological response to interferon therapy in children have not been established, which is why it is necessary to identify them and subsequently develop individualized treatment regimens yielding the best possible results. Objective: form personalized chronic hepatitis C treatment regimens in children on the basis of identification of virological response predictors and retrospective evaluation of the conducted interferon therapy efficiency. Study participants: 98 children of 3-18 years of age (mean age – 10.0±0.8 years) with chronic hepatitis C: 65 of them had HCV 1 genotype (66.0%), 33 – HCV 2-3 genotype (34.0%). We measured anthropometric parameters (weight, height), determined viral load level in blood serum (polymerase chain reaction (PCR)), performed HCV genotyping (before the therapy) and analyzed lymphocytic immunophenotype parameters of all children before the interferon therapy course and over time (4, 12, 24 and 48 weeks after the therapy initiation). Results: Analysis of the obtained results demonstrated that the recombinant IFNα-2a therapy efficiency improves if recombinant IL2 (roncoleukin) is added to the treatment regimen: double increase in the rate of achievement of the primary virological remission (PVR) and sustained virological response (SVR) (p < 0.05). Use of a pegylated IFNα-2b in combination with ribavirin did not yield any significant difference in comparison with treatment with recombinant IFNα-2a and recombinant IL2. Interferon therapy is more effective in children of at least 30 kg of body weight and 134 cm of height without physical developmental delay than in younger children (of smaller weight and height) at the moment of interferon therapy initiation (p < 0.001). Thus, anthropometric parameters of patients may serve as PVR predictors regardless of the HCV genotype at the treatment initiation. If lymphocytes ≥ 2,500/mcl, the PVR achievement rate is 85.0%; if lymphocytes ≤ 2,000/mcl – 5.0% (p = 0.000). If the total amount of lymphocytes is 2,000-2,500, the examination should be repeated 12 weeks after the therapy initiation: increase in the number of lymphocytes in comparison with the initial values by 10.0% or more is positive prognostic SVR predictor. Conclusions: It is necessary to take into consideration parametric data and the child’s age at the moment of therapy initiation in order to schedule the launch of interferon therapy and choose a therapy regimen for chronic viral hepatitis C in children. Total amount of blood lymphocytes, child’s body weight and height at the moment of treatment initiation are predictors of positive virological response to treatment.
About the Authors
T. A. SkvortsovaRussian Federation
postgraduate of the gastroenterology department with a hepatology group of the Scientific Center of Children’s Health
G. V. Volynets
Russian Federation
E. L. Semikina
Russian Federation
References
1. Bortolotti F. Chronic hepatitis C in children: natural history and prognosis. Recenti Prog. Med. 2009 Feb; 100 (2): 97–102.
2. Mohan N., Gonzalez-Peralta R. P., Fujisawa T., Chang M. H., Heller S., Jara P., Kelly D., Mieli-Vergani G., Shah U., Murray K. F. Chronic hepatitis C virus infection in children. J Pediatr Gastroenterol Nutr. 2010; 50: 123–131.
3. Ghany M. G., Strader D. B., Thomas D. L., Seeff L. B. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology. 2009; 49: 1335–1374.
4. Bortolotti F., Iorio R., Resti M., Camma C., Marcellini M., Giacchino R., Marazzi M. G., Verucchi G., Zancan L., Barbera C., Maggiore G., Vajro P., Giannattasio A., Bartolacci S. Italian Observatory for HCV Infection and Hepatitis C in Children. Epidemiological profile of 806 Italian children with hepatitis C virus infection over a 15-year period. J. Hepatol. 2007 Aug; 47 (2): 311.
5. Bortolotti F., Resti M., Marcellini M., Giacchino R., Verucchi G., Nebbia G., Zancan L., Marazzi M. G., Barbera C., Maccabruni A., Zuin G., Maggiore G., Balli F., Vajro P., Lepore L., Molesini M., Guido M., Bartolacci S., Noventa F. Hepatitis C virus (HCV) genotypes in 373 Italian children with HCV infection: changing distribution and correlation with clinical features and outcome. Gut. 2005 Jun; 54 (6): 852–857.
6. Bortolotti F., Iorio R., Nebbia G., Marcellini M., Giacchino R., Zancan L., Gussetti N., Barbera C., Maccabruni A., Verucchi G., Balli F., Vegnente A., Guido M., Bartolacci S. Interferon treatment in children with chronic hepatitis C: long-lasting remission in responders, and risk for disease progression in non-responders. Dig, Liver Dis. 2005 May; 37 (5): 336–341.
7. Guido M., Bortolotti F. Viral hepatitis: Treating hepatitis C in children: an open horizon. Nat. Rev. Gastroenterol. Hepatol. 2011 May; 8 (5): 247–8.
8. Volynets G.V., Potapov A.S., Pakhomovskaya N.L. Rossiiskii pediatricheskii zhurnal = Russian pediatric journal. 2011; 6: 9–13.
9. Potapov A.S., Pakhomovskaya N.L., Volynets G.V., Chetkina T.S. Farmateka = Pharmateca. 2009; 13: 67–71.
10. Volynets G.V., Potapov A.S., Pakhomovskaya N.L., Tsimbalova E.G., Surkov A.N., Polyakova S.I., Chetkina T.S. Sposob povysheniya effektivnosti interferonoterapii khronicheskogo gepatita S u detei. Patent na izobretenie RUS 2468815 08.08.2011 [Method of Increasing Interferon Therapy Efficacy for Chronic Hepatitis C in Children. Patent for invention RUS 2468815 of 08.08.2011].
11. Potapov A.S., Pakhomovskaya N.L., Volynets G.V. Voprosy sovremennoi pediatrii = Current pediatrics. 2009; 8(6): 101–105.
12. Wirth S., Ribes-Koninckx C., Calzado M. A., Bortolotti F., Zancan L., Jara P., Shelton M., Kerkar N., Galoppo M., Pedreira A., Rodriguez-Baez N., Ciocca M., Lachaux A., Lacaille F., Lang T., Kullmer U., Huber W. D., Gonzalez T., Pollack H., Alonso E., Broue P., Ramakrishna J., Neigut D., Valle-Segarra A. D., Hunter B., Goodman Z., Xu C. R., Zheng H., Noviello S., Sniukiene V., Brass C., Albrecht J. K. High sustained virologic response rates in children with chronic hepatitis C receiving peginterferon alfa-2b plus ribavirin. J. Hepatol. 2010 Apr; 52 (4): 501–7.
13. Bortolotti F., Indolfi G., Zancan L., Giacchino R., Verucchi G., Cam ma C., Barbera C., Resti M., Marazzi M. G., Guido M. Management of chronic hepatitis C in childhood: the impact of therapy in the clinical practice during the first 2 decades. Dig. Liver Dis. 2011 Apr; 43 (4): 325–9.
14. Volynets G.V., Potapov A.S., Pakhomovskaya N.L., Tsimbalova E.G., Skvortsova T.A., Semikina E.L. Sposob prognozirovaniya effektivnosti interferonoterapii khronicheskikh gepatitov S u detei. Patent na izobretenie RUS 2486526 15.05.2012 [Method of Prognosing Interferon Therapy Efficacy for Chronic Hepatitis C in Children. Patent for invention RUS 2486526 of 15.05.2012].
15. Lopatkina T.N. Gepatologicheskii forum. Prilozhenie k zhurnalu «Klinicheskaya farmakologiya i terapiya» - Hepatological forum. Supplement to journal “Clinical pharmacology and therapy”. 2011; 4: 15–20.
16. EASL Clinical Practice Guidelines: Management of hepatitis C virus infection. Journal of Hepatology. 2011. (European Association for the Study of the Liver, EASL).
Review
For citations:
Skvortsova T.A., Volynets G.V., Semikina E.L. PERSONALIZED APPROACH TO TREATING CHRONIC HEPATITIS C IN CHILDREN. Pediatric pharmacology. 2014;11(2):66-71. https://doi.org/10.15690/pf.v11i2.960