Retrospective evaluation of diagnosis, follow up, treatment and prognosis in naive children with chronic hepatitis B infection

Background and Aim: The spectrum of Chronic Hepatitis B infection in children ranges from asymptomatic carriage with minimal disease, to cirrhosis and risk of hepatocellular carcinoma in adulthood. Untreated infection may lead to natural seroconversion and reduced risk of further disease. Interferon-based therapies have limited efficacy in childhood. The aim of the present study was to evaluate naïve children with Chronic Hepatitis B infection and to compare the therapeutic efficacy of two different regimens in patients with Chronic Hepatitis B infection who had been followed-up in the Department of Pediatric Infectious Diseases of Cukurova University Faculty of Medicine. Patients and Methods: In this retrospective study, 227 naive children with chronic hepatitis B Chronic Hepatitis B infection who had been followed-up at the out-patient pediatric infectious disease clinics of Balcali Hospital from 2008 January to 2013 December were evaluated. These 227 children's demographic and clinical features; risk factors; biochemical, serological and virological feature were also evaluated. Of the total 227 pediatric patients who had Chronic Hepatitis B infection, while 70 ( 30.8% ) had spontanenous seroconversion, 157 (69.2%) did not have spontanenous seroconversion. Of the total 157 pediatric patients who had Chronic Hepatitis B infection, 49 ( 31.2% ) were treated with two different treatment modalities, 108 ( 68.8% ) had been followed-up with Chronic Hepatitis B infection. A total of 49 children were prospectively allocated to two random treatment groups i.e. monotherapy and combination therapy. In the monotherapy groups; 25 patients in the first group (Group 1) received interferon-alpha (IFN-α) in a dose of 5 MU/m², subcutaneous injection, thrice/weekly alone for 6 months. In the combination groups; 24 patients in the second group (Group 2) received Lamuvidin for 12 months (peroral, 4mg/kg per day dose, max.100 mg, daily) and IFN-α added to Lamuvidin for 6 months in a dose of 5 MU/m² (s.c., thrice/weekly ). All tests were done in the Laboratories of the Balcali Hospital of Cukurova University, Faculty of Medicine. Statistical analysis was performed by SPSS software program (version 20.0). Comparisons between the groups were made with Mann-Whitney U test, Chi square test, Ficher's Exact test, Kruskal-Wallis test. A two-tailed P value < 0.05 was considered significant. RESULTS In this study 227 naive children with Chronic Hepatitis B infection were evaluated retrospectively . Of the total 227 pediatric patients who have Chronic Hepatitis B infection, 70(30.8%) developed either spontaneous seroconversion or seroconversion during their six year follow-up period. Of 157 patients who did not develop spontaneous seroconversion, 49 were treated with two different treatment modalities as they met the treatment criteria. 56% of the patients were identified during family screening. The existence of hepatitis B in the family was 85,9%, maternal hepatitis B was 60,4% and vertical transmission rate was 54,6%. 74% of the patients were asemptomatic. When the patients who had spontaneous seroconversion and those who had no spontaneous seroconversion are examined, it is seen that the average age (192 months) and diagnosis period (132 months) in the patients with spontenous seroconversion was statistically higher and longer than those without spontenous seroconversion (156 vs 109, respectively) (p<0.01). The rate of spontaneous seroconversion in males was statistically lower (p<0.01). Spontaneous seroconversion was statistically greater in the patients who had lower viral load and ALT value at the time of the diagnosis and who had IgG antibodies against hepatitis A virus (p<0.01, p<0.05 respectively). The patients with no spontaneous seroconversion had statistically higher familial and vertical contamination (p<0.05). Discussion: The findings of this study suggest that long follow-up period (an avareage of 10 years) for the patients who have been diagnosed with chronic hepatitis B and who do not meet the treatment criteria is essential in terms of spontenous seroconversion development. Hepatitis A vaccination in seronegative patients may induce spontaneous seroconversion. However, more detailed research studies are needed about this subject. In this study, no statistically significant difference was found in terms of response to treatment between the two different treatment modalities given to the patients who met treatment criteria. The potential benefits of these two theuropatic regimens need to be futher investigated to confirm these results with larger number of patients.