Clinical and Histological Outcome After Hepatitis B E Antigen to Antibody Seroconversion in Children With Chronic Hepatitis B

Abstract

Data regarding the outcome of children with chronic hepatitis B after seroconversion are scarce. We describe the long-term evolution of these patients. One hundred and three children with antibody against hepatitis B e antigen and normal alanine aminotransferase (ALT) levels were followed for 0.6 to 12.5 years (mean, 6.3 years). Paired liver biopsies (before and after seroconversion) were available in 83 cases. Final biopsies were obtained 0.5 to 12.5 years (mean, 4.5 years) after seroconversion. ALT levels remained normal in most of the children (79%) throughout the follow-up. All children, except five who lost hepatitis B surface antigen, had serum viral DNA detected by polymerase chain reaction. When comparing baseline and final liver biopsies, a significant improvement (P F .001) was found in the histological activity index and in the necrosis, cytolysis, inflammation, and fibrosis scores. The histological diagnosis improvement in the final biopsy was significantly related (P F .001) to the time from seroconversion to the biopsy performance. All children had viral DNA on their final liver biopsy. In summary, seroconversion and ALT normalization are quite stable findings in children, and no differences in the long-term outcome between treated and untreated children were found. In light of the histological outcome, it seems unnecessary to perform a follow-up liver biopsy in these cases.(HEPATOLOGY 1999;29:572-575.)Although the long-term outcome of patients with chronic hepatitis B (HBV) after hepatitis B e antigen to antibody (anti-HBe) seroconversion and normalization of serum alanine aminotransferase (ALT) levels has already been reported, 1-6 these reports include a relatively small number of liver biopsies. Thus, the information about the liver histological activity and hepatitis B virus DNA (HBV-DNA) status is scarce. In addition, the time when a liver biopsy should be taken after seroconversion to anti-HBe, to definitively establish the histological status, has not yet been defined. Furthermore, differences in the long-term outcome between hepatitis B surface antigen (HBsAg)-carriers who seroconvert to antiHBe spontaneously and those who do so because of interferon-␣ treatment have not been conclusively shown, especially in children with chronic HBV.We studied the long-term outcome of children with chronic HBV who had seroconverted to anti-HBe, either spontaneously or as a result of interferon-␣ treatment, by comparing the baseline and final liver biopsies obtained at different time periods after ALT normalization and by determining the liver HBV-DNA status. PATIENTS AND METHODS Patients.Patients with chronic HBV under 18 years of age who attended our pediatrics department between 1978 and 1996 were retrospectively eligible if the following inclusion criteria were fulfilled: (1) Strictly documented seroconversion to anti-HBe with serum HBV-DNA clearance (as detected by dot-blot hybridization) and normal ALT levels on two consecutive occasions, 6 months apart; (2) Histologic evidence of chronic hepatitis ...

Determinants for the Occurrence of Acute Exacerbation of Hepatitis B Virus Infection in Chinese Patients after HBeAg Seroclearance

“…In this study, it was further found that patients with later HBeAg seroclearance had higher frequencies of HBeAg seroreversion and acute exacerbation of chronic hepatitis B after HBeAg seroclearance. Consistent with this finding, the frequency of acute exacerbation after HBeAg seroclearance was reported to be low in previous studies of anti-HBe-positive children (5 to 20%) (5,16). Whether the frequent exacerbation after HBeAg seroclearance in the older age groups leads to the development of cirrhosis-related complications cannot be determined in the present study because of the relatively few complications that developed during the follow-up period.…”

Identification of Different States of Hepatitis B Virus Infection with a Quantitative PCR Assay

“…If, after termination of interferon treatment, serum HBV DNA concentration was found to be less than 10 4 copies/ml, hepatitis did not occur thereafter (12). However, even after loss of HBsAg and anti-HBs seroconversion, which are considered absolute markers of viral clearance, residual viremia was detected by PCR for several patients for a maximum of 12 months following treatment termination (5,9,18). Similar observations were made for patients with spontaneous loss of HBsAg (9,10,19).…”

Chronic hepatitis B

“…33,36,37 In sub-Saharan Africa, Alaska, and Mediterranean countries, transmission of HBV usually occurs from person to person in childhood, whereas perinatal transmission is less common (pattern 2). 25,[38][39][40] In these populations most children who are HBeAg positive have elevated ALT levels and seroconversion to anti-HBe is common near or shortly after the onset of puberty. The third pattern is usually observed in individuals who acquired HBV infection during adulthood.…”

“…This has been referred to as the "inactive carrier state." 29,32,33,39,40,43,45 The course and outcome of the inactive HBsAg carrier state is generally but not invariably benign depending on the duration and severity of the preceding chronic hepatitis. Because fluctuations in ALT and HBV DNA levels are common during the course of chronic HBV infection, serial tests should be performed before patients are determined to be in an inactive carrier state and periodically thereafter.…”