Thirty-six children with chronic hepatitis B were entered into a randomized controlled trial of recombinant human interferon-alpha. All patients had hepatitis B virus DNA and increased levels of aminotransferases in serum for at least 1 yr. Twelve children received 10 MU of interferon-alpha 2b/m2 body surface area three times a week (group I); 12 children received 5 MU/m2 under the same conditions (group II); and 12 children served as controls (group III). During 6 mo of therapy, 12 of 24 (50%) treated patients (7 from group I, 58%, and 5 from group II, 42%) and 2 of 12 (17%) controls lost hepatitis B virus DNA from serum and subsequently remained negative. Comparison of the rate of response in group I vs. controls showed a statistically significant difference (p less than 0.05). Eleven of 12 (92%) treated patients who cleared hepatitis B virus DNA from serum lost HBeAg, seroconverted to anti-HBe and had improvement in liver histological findings with loss of hepatitis B virus DNA from liver. In 10, serum ALT levels became normal. Interferon-alpha was well tolerated and all children finished therapy. These findings indicate that a 6-mo course of interferon-alpha is effective in inducing a serological, biochemical and histological remission of disease in approximately 50% of children with chronic hepatitis B.

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 ...

Twelve children with chronic non-A, non-B hepatitis were entered in a pilot trial of recombinant interferon-alpha. Although all the children had hepatitis C virus RNA in serum, only five had antibodies against this virus. Children received 3 MU/m2 body surface area interferon-alpha 3 times/wk for 6 mo; they were followed for 24 mo, including the therapy period. One child was dropped from the study, so the results are from the 11 children who completed the study. At the end of the therapy period, 36% of the children had normal ALT levels; this percentage increased to 90% at mo 15 of follow-up. Thereafter, relapse occurred in five children; thus ALT normalization was observed in 5 of 11 children at the 24th month. Moreover, two different ALT patterns were found: HCV antibody-negative children had significant peaks of ALT levels with respect to the basal samples (p less than 0.05) until the third month of the therapy; these levels later decreased. In contrast, HCV antibody-positive children had slight fluctuations of ALT until normal levels were reached. At the end of treatment, three children had HCV RNA; one demonstrated a rebound in ALT levels. Finally, histological activity had decreased significantly in the second liver biopsy specimen in all children. In summary, interferon treatment in children with chronic hepatitis C may be helpful, although these results should be confirmed in controlled trials.

virus infects patients with chronic viral hepatitis, intraveThe aim of this work was to study the presence of the nous drug abusers, and organ or blood recipients. 2,4,5 To our hepatitis GB virus type C (HGBV-C) in liver and serum knowledge, the presence of HGBV-C RNA in children with samples of children with chronic viral hepatitis, the time chronic viral hepatitis has not yet been reported. course of changes in viral RNA, and the possible acquisi-We have retrospectively analyzed the presence of HGBVtion routes of infection. Frozen serum and liver samples C RNA in paired serum and liver samples from 58 children from 58 children with chronic hepatitis B (n Å 33) or C with chronic hepatitis B or C. We have also studied the time (n Å 25) were analyzed using polymerase chain reaction.course of changes in serum HGBV-C RNA in both treated Twenty-seven children had been included in different and untreated children with chronic viral hepatitis as well interferon trials. Two additional serum samples from the as the possible routes of HGBV-C transmission in infected HGBV-C-positive children as well as serum samples from children. properly stored at 020ЊC (serum samples) or in liquid nitrogen (liver mother. In the 3 children receiving alpha-interferon, samples). The mean age of the children was 12.1 { 3.9 years (range: HGBV-C RNA became undetectable during treatment al-2-16 years). Forty-six of 58 children had had abnormal alanine amithough it reappeared in 2 of them after therapy. In con-notransferase (ALT) levels for at least 1 year before the study start clusion, we found that 15% of children with chronic viral ( 21. Twenty-seven children had been included in different interferon Studies of HGBV-C RNA prevalence have shown that this (IFN) trials; in these cases, the first sample analyzed corresponded to the baseline sample of the trial.In the HGBV-C RNA-positive children two additional serum samples, apart from the baseline sample, were analyzed. In the treated Abbreviations: HGBV-C, hepatitis GB virus type C; ALT, alanine aminotransferase; children, serum samples were taken at the end of treatment (range:anti-HBe, antibodies to hepatitis B e antigen; HCV, hepatitis C virus; HBV, hepatitis B 6-9 months) and follow-up period (range: 12-18 months after the virus; IFN, interferon; HBeAg, hepatitis B e antigen; RT-PCR, reverse transcription-nested end of treatment). In the untreated children, two additional serum polymerase chain reaction.samples taken 12 months and 18-30 months after the first sample infection.

SUMMARY In order to study the clinical, serological, and morphological evolution of chronic hepatitis B virus infection in childhood, a prospective study has been carried out. A total of 90 children with a chronic infection were followed up for a mean (SD)