Virological response to treatment with peginterferon alfa-2a in adolescents with chronic hepatitis B
Languages of publication
Background: There are few data on the efficacy and safety of pegylated interferon treatment in adolescents with chronic hepatitis B. Aim: We conducted a pilot study in 13 adolescents with chronic hepatitis B treated with peginterferon alfa-2a at 100 µg/m2 once weekly for 48 weeks. Methods: HBV DNA was assessed by qPCR method. Results: After four weeks of treatment six adolescents had undetectable HBV DNA (<12 IU/mL). Seven adolescents - including five HBV negatives at week 4 - had undetectable HBV DNA (<55 IU/mL) at week 24, and seven adolescents - including all HBV DNA negatives at week 4 - had undetectable HBV DNA at week 48 of treatment (<55 IU/mL). Five adolescents had undetectable HBV DNA (<55 IU/mL) after 24 weeks of follow-up (sustained viral response). HBeAg seroconversion was achieved in one patient. HBsAg loss was documented at the end of therapy in two of the six adolescents HBV DNA negative at week 4 of treatment. Three adolescents withdrew from the treatment (two because of adverse events, one because of withdrawal of parental consent). Leukopenia was reported in seven adolescents and three individuals experienced thrombocytopenia. Except for one patient who discontinued treatment due to leukopenia, no dose modifications for adverse events or laboratory abnormalities were required. Conclusion: This pilot study shows that 48 weeks of treatment with peginterferon alfa-2a can result in sustained HBV DNA suppression, HBeAg seroconversion and HBsAg loss in adolescents with CHB. Larger and longer trials are now required to better define the magnitude of the benefit in this group of patients.
- Bortolotti F, Cadrobbi P, Crivellaro C, Guido M, Rugge M, Noventa F, Calzia R, Realdi G (1990) Long-term outcome of chronic type B hepatitis in patients who acquire hepatitis B virus infection in childhood. Gastroenterology 99: 805-810.
- Bortolotti F, Guido M, Bartolacci S, Cadrobbi P, Crivellaro C, Noventa F, Morsica G, Moriondo M, Gatta A (2006) Chronic hepatitis B in children after e antigen seroclearance: final report of a 29-year longitudinal study. Hepatology 43: 556-562.
- Brunetto MR, Moriconi F, Bonino F, Lau GK, Farci P, Yurdaydin C, Piratvisuth T, Luo K, Wang Y, Hadziyannis S, Wolf E, McCloud P, Batrla R, Marcellin P (2009) Hepatitis B virus surface antigen levels: a guide to sustained response to peginterferon alfa-2a in HBeAg-negative chronic hepatitis B. Hepatology 49: 1141-1150.
- Chang MH, Chen PJ, Chen JY, Lai MY, Hsu HC, Lian DC, Liu YG, Chen DS (1991) Hepatitis B virus integration in hepatitis B virus-related hepatocellular carcinoma in childhood. Hepatology 13: 316-320.
- Chang MH, Chen CJ, Lai MS, Hsu HM, Wu TC, Kong MS, Liang DC, Shau WY, Chen DS (1997) Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children. Taiwan Childhood Hepatoma Study Group. N Engl J Med 336: 1855-1859.
- Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, Huang GT, Iloeje UH (2006) Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA 295: 65-73.
- European Association for the Study of the Liver (2009) EASL Clinical practice guidelines: management of chronic hepatitis B. J Hepatol 50: 227-242.
- Fujisawa T, Komatsu H, Inui A, Sogo T, Miyagawa Y, Fujitsuka S, Sekine I, Kosugi T, Inui M (2000) Long-term outcome of chronic hepatitis B in adolescents or young adults in follow-up from childhood. J Pediatr Gastroenterol Nutr 30: 201-206.
- Ghany MG, Doo EC (2006) Assessment and management of chronic hepatitis B. Infect Dis Clin North Am 20: 63-79.
- Iorio R, Giannattasio A, Cirillo F, Vegnente A (2007) Long-term outcome in children with chronic hepatitis B: a 24-year observation period. Clin Infect Dis 45: 943-949.
- Keeffe EB, Dieterich DT, Han SH, Jacobson IM, Martin P, Schiff ER, Tobias H (2008) A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: 2008 update. Clin Gastroenterol Hepatol 6: 1315-41.
- Lau GK, Piratvisuth T, Luo KX, Marcellin P, Thongsawat S, Cooksley G, Gane E, Fried MW, Chow WC, Paik SW, Chang WY, Berg T, Flisiak R, McCloud P, Pluck N (2005) Peginterferon Alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis B. N Engl J Med 352: 2682-2695.
- Liaw YF, Leung N, Kao JH, Piratvisuth T, Gane E, Han KH, Guan R, Lau GK, Locarnini S (2008) Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2008 update. Hepatol Int 2: 263-283.
- Lok AS, McMahon BJ (2007) Chronic hepatitis B. Hepatology 45: 507-539.
- Marcellin P, Lau GK, Bonino F, Farci P, Hadziyannis S, Jin R, Lu ZM, Piratvisuth T, Germanidis G, Yurdaydin C, Diago M, Gurel S, Lai MY, Button P, Pluck N (2004) Peginterferon alfa-2a alone, lamivudine alone, and the two in combination in patients with HBeAg-negative chronic hepatitis B. N Engl J Med 351: 1206-1217.
- Marcellin P, Piratvisuth T, Brunetto MR, Bonino F, Lau GK, Farci P, Yurdaydin C, Gurel S, Wu J, Popescu M (2009) Increasing rates of HBsAg clearance and seroconversion in patients with HBeAg-negative disease treated with peginterferon alafa-2a ± lamivudine: results of 5-year post-treatment follow-up. J Hepatol 50 (Suppl 1): S336 (A924).
- Marcellin P, Piratvisuth T, Brunetto M , Bonino F, Farci P, Yurdaydin C, Gurel S, Kapprell HP, Messinger D, Popescu M (2010) On-treatment decline in serum HBsAg levels predicts sustained immune control 1 year post-treatment and subsequent HBsAg clearance in HBeAg-negative hepatitis B virus-infected patients treated with peginterferon alfa-2a [40KD] (PEGASYS). Hepatol Int 4: PP209.
- Moucari R, Korevaar A, Lada O, Martinot-Peignoux M, Boyer N, Mackiewicz V, Dauvergne A, Cardoso AC, Asselah T, Chanoine MH, Vidaud M, Valla D, Bedossa P, Marcellin P (2009) High rates of HBsAg seroconversion in HBeAg-positive chronic hepatitis B patients responding to interferon: a long-term follow-up. J Hepatol 50: 1084-1092.
- Ni YH, Chang MH, Wang KJ, Hsu HY, Chen HL, Kao JH, Yeh SH, Jeng YM, Tsai KS, Chen DS (2004) Clinical relevance of hepatitis B virus genotype in children with chronic infection and hepatocellular carcinoma. Gastroenterology 127: 1733-1738.
- Perz JF, Armstrong GL, Farrington LA, Hutin YJ, Bell BP (2006) The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol 45: 529-538.
- Piratvisuth T, Lau GKK, Marcellin P, Brunetto MR, Kapprell HP, Popescu M (2010) On-treatment decline in serum HBsAg levels predicts sustained immune control and HBsAg clearance 6 months post-treatment in HBeAg-positive hepatitis B virus-infected patients treated with peginterferon alfa-2a [40KD] (PEGASYS). Hepatol Int 4: PP211.
Publication order reference