İnci Yaman BAJİN, Hülya DEMİR, İnci Nur Saltık TEMİZEL, Hasan ÖZEN, Aysel YÜCE

Long term follow-up of children with chronic hepatitis B: a single center experience

Chronic Hepatitis B infection is an important clinical issue because ofthe associated risk of developing cirrhosis and hepatocellular carcinoma.Especially in children, there is no consensus about the optimal treatment.Clinical features and long-term outcomes of 165 children diagnosed withchronic hepatitis B at our institution between January 1993 and June 2012were analysed retrospectively. Patients were divided into four groupsaccording to their treatment protocols. The first group received Interferon(IFN) only, the second group started lamivudine (LMV) first then IFN+LMVcombined and then continued with LMV only, the third group started withIFN+LMV combined then continued with LMV only and the fourth groupreceived LMV only. After a median follow-up period of 7 years (1-19 years)the highest e-seroconversion (the loss of HBeAg followed by gain of antiHBe antibody) rate, biochemical and virological response was observed withcombined (IFN+LMV) treatment regimens. Patients with higher ALT levelswere better treatment responders (p: 0.003). Identification of the patientswho need to be treated in order to determine the most effective therapy withoptimal treatment duration is important to reduce the risk of developingfuture complications like cirrhosis and hepatocellular carcinoma.

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1. Lampertico P, Agarwal K, Berg T, et al. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol 2017; 67: 370- 398.

2. Lok AS, Heathcote EJ, Hoofnagle JH. Management of hepatitis B: 2000 summary of a workshop. Gastroenterology 2001; 120: 1828-1853.

3. Ishak K, Baptista A, Bianchi L, et al. Histological grading and staging of chronic hepatitis. J Hepatol 1995; 22: 696-699.

4. Ott JJ, Stevens GA, Groeger J, Wiersma ST. Global epidemiology of hepatitis B virus infection: New estimates of age-specific HBsAg seroprevalence and endemicity. Vaccine 2012; 30: 2212-2219.

5. Raimondo G, Allain JP, Brunetto MR, et al. Statements from the Taormina expert meeting on occult hepatitis B virus infection. J Hepatol 2008; 49: 652-657.

6. Liaw YF, Sung JJ, Chow WC, et al; Cirrhosis Asian Lamivudine Multicentre Study Group. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med 2004; 351: 1521-1531.

7. Brechot C, Thiers V, Kremsdorf D, Nalpas B, Pol S, Paterlini-Bréchot P. Persistent hepatitis B virus infection in subjects without hepatitis B surface antigen: Clinically significant or purely "occult"? Hepatology 2001; 34: 194-203.

8. Brechot C. Pathogenesis of hepatitis B virus-related hepatocellular carcinoma: Old and new paradigms. Gastroenterology 2004; 127(5 Suppl 1): S56-S61.

9. Huo T, Wu JC, Hwang SJ, et al. Factors predictive of liver cirrhosis in patients with chronic hepatitis B: a multivariate analysis in a longitudinal study. Eur J Gastroenterol Hepatol 2000; 12: 687-693.

10. Wong GL, Wong VW, Choi PC, et al. Evaluation of alanine transaminase and hepatitis B virus DNA to predict liver cirrhosis in hepatitis B e antigen-negative chronic hepatitis B using transient elastography. Am J Gastroenterol 2008; 103: 3071-3081.

11. Fattovich G, Bortolotti F Donato F. Natural history of chronic hepatitis B: special emphasis on disease progression and prognostic factors. J Hepatol 2008; 48: 335-352.

12. Chen YC, Chu CM, Liaw YF. Age-specific prognosis following spontaneous hepatitis B e antigen seroconversion in chronic hepatitis B. Hepatology 2010; 51: 435-444.

13. Fujisawa T, Komatsu H, Inui A, et al. Long-term outcome of chronic hepatitis B in adolescents or young adults in follow-up from childhood. J Pediatr Gastroenterol Nutr 2000; 30: 201-206.

14. Iorio R, Giannattasio A, Cirillo F, D’Alessandro L, Vegnente A. Long-term outcome in children with chronic hepatitis B: a 24-year observation period. Clin Infect Dis 2007; 45: 943-949.

15. Vo Thi Diem H, Bourgois A, Bontems P, et al. Chronic hepatitis B infection: long term comparison of children receiving interferon alpha and untreated controls. J Pediatr Gastroenterol Nutr 2005; 40: 141- 145.

16. Sokal E. Drug treatment of pediatric chronic hepatitis B. Paediatr Drugs 2002; 4: 361-369.

17. Sokal E. Lamivudine for the treatment of chronic hepatitis B. Expert Opin Pharmacother 2002; 3: 329- 339.

18. Lok AS. Hepatitis B infection: Pathogenesis and management. J Hepatol 2000; 32(1 Suppl): 89-97.

19. Sokal EM, Conjeevaram HS, Roberts EA, et al. Interferon alfa therapy for chronic hepatitis B in children: a multinational randomized controlled trial. Gastroenterology 1998; 114: 988-995.

20. Lau DT, Khokhar MF, Doo E, et al. Long-term therapy of chronic hepatitis B with lamivudine. Hepatology 2000; 32(4 Pt 1): 828-834.

21. Hoofnagle JH, di Bisceglie AM. The treatment of chronic viral hepatitis. N Engl J Med 1997; 336: 347- 356.

22. Saltik-Temizel IN, Kocak N, Demir H. Interferonalpha and lamivudine combination therapy of children with chronic hepatitis B infection who were interferon-alpha nonresponders. Pediatr Infect Dis J 2004; 23: 466-468.

23. Gurakan F, Kocak N, Ozen H, Saltik-Temizel IN, Yuce A. Lamivudine versus LMV+IFN alpha as initial therapy for children with choronic hepatitis B (First year results). J Hepatol 2001; 34: 176.

24. Sokal EM, Kelly DA, Mizerski J, et al. Long-term lamivudine therapy for children with HBeAg-positive chronic hepatitis B. Hepatology 2006; 43: 225-232.

25. Saltik-Temizel IN, Koçak N, Demir H. Lamivudine and high-dose interferon-alpha combination therapy for naive children with chronic hepatitis B infection. J Clin Gastroenterol 2005; 39: 68-70.

26. Toy M, Onder FO, Idilman R, et al. The costeffectiveness of treating chronic hepatitis B patients in a median endemic and middle income country. Eur J Health Econ 2012; 13: 663-676.