Long-Term Outcome in Children with Chronic Hepatitis B: A 24-Year Observation Period

Abstract

Background. Chronic hepatitis B seems to manifest as mild disease in children and young adults. However, data regarding the long-term course of hepatitis B in untreated and interferon-treated children are still scarce. This study investigates the long-term outcome of disease in a large series of untreated and treated children with hepatitis B virus (HBV) infection.Methods. Clinical, biochemical, virological, and histological features were evaluated in children (age range, 2-18 years) with chronic HBV infection who did not have concomitant chronic systemic diseases other than HBV infection and who were admitted to the liver unit in the Department of Pediatrics at University "Frederico II" (Naples, Italy) during the period 1981-2005.Results. One hundred eight consecutive patients observed for up to 24 years were studied. During the observation period, 67 children remained untreated, and 41 were treated with interferon-a. After a median period of observation of 12.1 years (range, 5-23 years), hepatitis B early antigen loss and serum HBV DNA clearance occurred in 43 untreated patients (69.3%) who were hepatitis B early antigen positive at study entry and in 33 treated children (80%; the P value is not statistically significant). In addition, 6 untreated patients (9.7%) and 4 treated patients (9.7%) became hepatitis B surface antigen positive at the end of the follow-up period. Histological assessment, evaluated for 57 children, showed mild-to-moderate disease in 91.2% of cases of HBV infection. No patient developed end-stage liver disease or hepatocellular carcinoma.Conclusions. Children with chronic HBV infection are symptom free, with morphologically mild liver disease. Considering that the overall long-term outcomes did not differ between treated and untreated patients, the real impact of therapy on the long-term course of HBV infection remains to be established. Additional studies are needed to confirm our conclusions.

Cirrhosis in children and adolescents: An overview

“…According to a study of the population-based prevalence of infections by the hepatitis B and C viruses (HBV and HCV), conducted between 2005 and 2009 in all Brazilian capitals and the Federal District, the frequency of viral hepatitis B and C in people between the ages of 10 and 69 was 7.4% and 1.38% respectively, which is consistent with low endemicity of these conditions [9] . Few studies have attempted long-term outcome of children with hepatitis B [10,11] . At least 50% of children infected by the vertical route (mother-to-child) test positive for viral replication in adulthood.…”

Chronic hepatitis B in children and adolescents

“…Chronic hepatitis B (CHB) in childhood is a mild disease, and infected children are mostly asymptomatic, have normal growth and a normal physical examination [53]. Most perinatally infected subjects present a positive HBeAg and high serum levels of HBV DNA, with normal or minimally elevated serum alanine aminotransferases (ALT).…”

“…The synthesis of large amounts of HBeAg by the wild type virus could be necessary to maintain the tolerance [57]. This immunotolerant phase is characterized by high viral replication and little liver damage, although in Italian children, after 7 years of disease, 7-10% of subjects showed severe hepatitis at liver biopsy and 1.7-4.5% had cirrhosis [53,58]. It lasts 10-30 years when infection is acquired perinatally, whereas it is of minimal duration in subjects infected later in life.…”

Treatment of children with HBeAg-positive chronic hepatitis B: A systematic review and meta-analysis

“…When considering a longer follow-up period (>5 years), a similar SRR was reported for children treated with IFN␣ compared with untreated groups, leading to the hypothesis that IFN␣ simply accelerated a spontaneous event [20,43,44]. Others reported a higher, despite not significant, rate of HBeAb seroconversion in the treated group [45].…”

“…On the other hand, clearance of HBsAg with IFN␣ during longterm follow-up was reported as significantly higher [43], or higher but not significant [45], or similar [44] compared with the untreated groups. These data were in agreement with a previous assumption stating that spontaneous viral clearance of HBsAg among children was usually less frequent than among the treated responders [6,43].…”