Chronic Hepatitis B In Children: Case Series From A Tertiary Paediatric Hospital

Abstract

Background Chronic hepatitis B (CHB) remains an important global public health problem. Seroconversion is highly correlated with favourable long-term outcome. There is no consensus on the treatment method, onset time and duration for paediatric CHB patients. In this study, we aimed to evaluate the course of children with CHB, to determine the characteristics of the patients who developed spontaneous seroconversion and treatment indications, and to compare the effectiveness of different treatment modalities.

Patients and Methods Patients aged 1–18 years with a diagnosis of CHB were included in this study and evaluated for the development of spontaneous hepatitis B envelope antigen (HBeAg)/surface antigen (HBsAg) seroconversion and treatment modalities. The treated patients were divided into two groups according to their treatment regimen.

Results Of the 114 patients, the median age at diagnosis was 8.4 years and median follow-up period was 5.2 years. Spontaneous HBeAg and HBsAg seroconversion developed in 18 (20.6%) of 87 HBeAg positive patients and two (1.8%) patients, respectively. Thirty-one patients were treated. The follow-up period was higher in the group with HBeAg seroconversion (p:0.005). There was no statistical difference between the patients in terms of seroconversion development and treatment status. The serum alanine aminotransferase (ALT) values at the time of diagnosis were statistically higher in treated patients.

Conclusion HBV infection and CHB continue to be an important problem for children in our country. Consensus on the appropriate ALT ULN is needed for the treatment of hepatitis in children.

Zusammenfassung

Hintergrund Die chronische Hepatitis B (CHB) stellt nach wie vor weltweit ein wichtiges Gesundheitsproblem dar. Die Serokonversion korreliert stark mit einem günstigen Langzeitergebnis. Über die Behandlungsmethode sowie den Zeitpunkt des Beginns und die Dauer der Behandlung von pädiatrischen Patienten mit CHB gehen die Meinungen auseinander. Ziel der vorliegenden Studie war es, den Verlauf bei Kindern mit CHB zu untersuchen, die Merkmale der Patienten, die eine spontane Serokonversion entwickelten, sowie die Behandlungsindikationen zu ermitteln und die Wirksamkeit der verschiedenen Behandlungsmethoden zu vergleichen.

Patienten und Methodik In die Studie, die die Entwicklung einer spontanen Hepatitis-B-Hüllantigen (HBeAg)-/Oberflächenantigen (HBsAg)-Serokonversion sowie die verschiedenen Therapieformen untersuchte, wurden Patienten im Alter von 1-18 Jahren aufgenommen, bei denen die Diagnose CHB gestellt worden war. Die behandelten Patienten wurden nach Therapieregime in zwei Gruppen eingeteilt.

Ergebnisse Bei den 114 Patienten lag das mediane Alter zum Zeitpunkt der Diagnosestellung bei 8,4 Jahren. Die mediane Nachbeobachtungszeit betrug 5,2 Jahre. Eine spontane HBeAg-Serokonversion trat bei 18 (20,6 %) von 87 HBeAg-positiven Patienten und eine spontane HBsAg-Serokonversion bei zwei (1,8 %) Patienten auf. Es wurden 31 Kinder behandelt. Die Nachbeobachtungszeit war in der Gruppe mit HBeAg-Seroconversion (p = 0,005) länger. Hinsichtlich der Entwicklung der Serokonversion und des Behandlungsstatus fanden sich keine statistisch signifikanten Unterschiede zwischen den Patienten. Bei den behandelten Patienten waren die Alanin-Aminotransferase (ALT)-Werte im Serum zum Zeitpunkt der Diagnosestellung statistisch signifikant höher.

Schlussfolgerung HBV-Infektionen und CHB stellen für Kinder in der Türkei nach wie vor ein großes Gesundheitsproblem dar. Für die Behandlung der Hepatitis im Kindesalter ist ein Konsensus über die geeignete obere Normgrenze für ALT-Werte erforderlich.

Keywords

children - chronic hepatitis b - interferon - lamivudine - spontaneous seroconversion

Schlüsselwörter

Kinder - Chronische Hepatitis B - Interferon - Lamivudin - Spontane Serokonversion

Publication History

Article published online:
28 August 2023

• References

• 1 Sokal EM, Paganelli M, Wirth S. et al. European Society of Pediatric Gastroenterology, Hepatology and Nutrition. Management of chronic hepatitis B in childhood: ESPGHAN clinical practice guidelines: consensus of an expert panel on behalf of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition. J Hepatol 2013; 59: 814-829
• 2 Schweitzer A, Horn J, Mikolajczyk RT. et al. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet 2015; 386: 1546-1555
• 3 Özkan H. Epidemiology of Chronic Hepatitis B in Turkey. Euroasian J Hepatogastroenterol 2018; 8: 73-74
• 4 Kanra G, Tezcan S, Badur S. Turkish National Study Team. Hepatitis B measles seroprevalence among Turkish children. Turk J Pediatr 2005; 47: 105-110
• 5 Bortolotti F, Guido M, Bartolacci S. et al. Chronic hepatitis B in children after e antigen seroclearance: final report of a 29-year longitudinal study. Hepatology. 2006; 43: 556-562
• 6 Chang MH, Hsu HY, Hsu HC. et al. The significance of spontaneous hepatitis B e antigen seroconversion in childhood: with special emphasis on the clearance of hepatitis B e antigen before 3 years of age. Hepatology. 1995; 22: 1387-1392
• 7 European Association for the Study of the Liver. Electronic address: [e-mail]; European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol 2017; 67: 370-398 Epub 2017 Apr 18
• 8 Ishak K, Baptista A, Bianchi L. et al. Histological grading and staging of chronic hepatitis. J Hepatol 1995; 22: 696-699
• 9 Barut HS, Günal Ö, Göral A. et al HBsAg Pozitif Ebeveynlerin Çocuklarında Hepatit B Virusu Enfeksiyonu Prevalansı [Prevalence of hepatitis B virus infection in children of HBsAg positive parents]. Mikrobiyol Bul 2011; 45: 359-365 Turkish. Erratum in: Mikrobiyol Bul. 2011 Jul;45(3):580.
• 10 Doganci T, Uysal G, Kir T. et al. Horizontal transmission of hepatitis B virus in children with chronic hepatitis B. World J Gastroenterol 2005; 11: 418-420
• 11 Tasyaran MA. HBV EnfeksiyonuEpidemiyolojisiTekeli E, Balık Đ (editörler) Viral Hepatit 2003; 121-128
• 12 Terrault NA, Lok ASF, McMahon BJ. et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology 2018; 67: 1560-1599
• 13 Kanra G, Tezcan S, Badur S. Turkish National Study Team. Hepatitis A seroprevalence in a random sample of the Turkish population by simultaneous EPI cluster and comparison with surveys in Turkey. Turk J Pediatr 2002; 44: 204-210
• 14 Karadeniz A, Alasehir E, Yesilbag Z. et al. The Seroprevalence of Hepatitis A in İstanbul. Turkey. Marmara Med J. 2017; 30: 14-17
• 15 Akman AÖ, Burhan BY, Uzun AK. et al. Hepatitis A virus age-specific seroprevalence after the implementation of a Toddlers’ Vaccination in Turkey: Shifting susceptibility to adolescents. Turk PediatriArs 2020; 55: 370-375
• 16 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
• 17 Bortolotti F, Cadrobbi P, Crivellaro C. et al. Long-term outcome of chronic type B hepatitis in patients who acquire hepatitis B virus infection in childhood. Gastroenterology. 1990; 99: 805-810
• 18 Ahn SH, Park YN, Park JY. et al. Long-term clinical and histological outcomes in patients with spontaneous hepatitis B surface antigen seroclearance. J Hepatol 2005; 42: 188-194
• 19 Borgniet O, Parvaz P, Bouix C. et al. Clearance of serum HBsAg and anti-HBs seroconversion following antiviral therapy for chronic hepatitis B. J Med Virol 2009; 81: 1336-1342
• 20 Yuen MF, Wong DK, Fung J. et al. HBsAg Seroclearance in chronic hepatitis B in Asian patients: replicative level and risk of hepatocellular carcinoma. Gastroenterology. 2008; 135: 1192-1199
• 21 Hsu HY, Chang MH, Lee CY. et al. Spontaneous loss of HBsAg in children with chronic hepatitis B virus infection. Hepatology. 1992; 15: 382-386
• 22 Komatsu H, Inui A. Hepatitis B virus infection in children. Expert review of anti-infective therapy 2015; 13: 427-450
• 23 Usta M, Urgancı N, Yıldırmak ZY. et al. Chronic hepatitis B in children with or without malignancies: A 13-year follow-up. World Journal of Gastroenterology: WJG 2015; 21: 2073
• 24 Madan K, Batra Y, Jha J. et al. Clinical relevance of HBV DNA load in patients with chronic hepatitis B infection. Tropical Gastroenterology 2010; 29: 84-90
• 25 Pokorska-Śpiewak M, Kowalik-Mikołajewska B, Aniszewska M. et al. Is liver biopsy still needed in children with chronic viral hepatitis?. World J Gastroenterol 2015; 21: 12141-12149
• 26 Eren M. Correlation of Liver Enzymes and Liver Histology in Chronic Hepatitis B Virus Infection. Journal of Clinical and Analytical Medicine 2016; 7: 639-642
• 27 Nguyen MH, Garcia RT, Trinh HN. et al. Histological disease in Asian-Americans with chronic hepatitis B, high hepatitis B virus DNA, and normal alanine aminotransferase levels. The American journal of gastroenterology 2009; 104: 2206
• 28 Schwimmer JB, Dunn W, Norman GJ. et al. SAFETY study: alanine aminotransferase cutoff values are set too high for reliable detection of pediatric chronic liver disease. Gastroenterology. 2010; 138: 1357-1364. e2
• 29 Stinco M, Rubino C, Trapani S. et al. Treatment of hepatitis B virus infection in children and adolescents. World J Gastroenterol 2021; 27: 6053-6063
• 30 Gurakan F, Kocak N, Ozen H. et al. Lamivudine versus LMV+IFN alpha as initial therapy for children with choronic hepatitis B (First year results). J Hepatol 2001; 34: 176