Loss Of HBV-DNA Research Articles

Interferon antibodies in patients with chronic HBV infection treated with recombinant interferon

In different trials, a total of 46 adults and 12 children suffering from chronic hepatitis B virus (HBV) and who were HBV-DNA- and HBeAg-positive were treated with recombinant interferon-α (rIFNα)-2A. The interferon was administered intramuscularly in different doses ranging from 1.5 MU to 20 MU/m 2 of body surface, two or three times weekly during 4–6 months. Specific detection of anti-IFN antibodies by enzymoimmunoassay (EIA), radioimmunoassay (RIA) and biological assays during treatment and follow-up periods were performed. None of the children developed anti-IFN antibodies. During therapy, 12 adult patients (26%) were found to have anti-IFN antibodies. A total of five patients became HBV-DNA-negative during therapy, but in three cases a reactivation of viral replication occurred subsequently. In these three patients, the appearance of anti-IFN antibodies occurred prior to or at the same time as HBV-DNA loss. The other seven patients did not respond to therapy. In conclusion, the development of anti-IFN antibodies during rIFNα treatment of chronic hepatitis B may modify the response to therapy, especially if they appear before HBV-DNA negativization.

Histological improvement after anti-viral treatment for chronic hepatitis B virus infection

Sequential liver biopsies were taken from 66 patients with chronic hepatitis 8 virus (HBV) infection being followed in randomised controlled trials of therapy with alpha interferons or adenine arabinoside 5′-monophosphate. In the group of 23 patients responding to treatment with the permanent loss of HBe antigen and HBV-DNA from their serum, there was a significant reduction in hepatic inflammatory activity and none developed cirrhosis. In contrast, inflammatory activity continued in the group of 24 patients that did not respond to therapy, and in the group of 19 patients who received no therapy. Two untreated controls progressed to cirrhosis. Further studies confirmed that in those clearing HBcAg and HBV-DNA from the serum, HBcAg and HBeAg were also lost from the liver. This study demonstrates that, as in natural seroconversion, successful treatment of chronic HBV infection is associated with loss of hepatic as well as serum markers of HBV replication, and is followed by a reduction in hepatic inflammation. Antiviral therapy may prevent progression to cirrhosis in some cases.

Clearance of pre-S2 antigen: a marker of successful interferon therapy in hepatitis B virus infection.

The relation between viral replication, the presence of HBsAg and pre-S2 in serum and eventual clinical outcome has been investigated in fourteen patients undergoing treatment with lymphoblastoid interferon for chronic hepatitis B virus (HBV) infection. In four patients permanent loss of pre-S2 was accompanied by loss of serum HBV-DNA in association with a marked elevation of serum aspartate aminotransferase activity and in each of these cases HBsAg was subsequently cleared from serum. In contrast there was no significant fluctuation in the concentration of either pre-S2 or HBsAg in four cases not responding to therapy although substantial or complete inhibition of viral replication had been observed during treatment. In the third group, permanent loss of HBV-DNA was observed but in these cases pre-S2 and HBsAg persisted in serum, albeit at lower concentrations, while in this group loss of HBV-DNA from serum was not accompanied by a flare in disease activity. These results suggest first, that assay of pre-S2 is a further measure of the response to interferon and second that in some cases interferon enhances immune recognition of both the pre-S2 and HBsAg polypeptides.

Pattern and duration of HBV DNA seropositivity in acute hepatitis B.

To determine the pattern and duration of HBV DNA seropositivity in acute hepatitis B, six patients were assessed during the incubation, clinical, and convalescent stages of their illness by DNA hybridization using a slot blot technique. Patients were identified by the detection of HBsAg nearly one month before the development of clinical and laboratory features of acute hepatitis (mean 22 +/- 4 days) and they were followed at one- to three-week intervals for 6 +/- 1 months. Each patient lacked antibody to delta virus. During the incubation period, HBV DNA was not detected in serum. At symptomatic onset, all were seropositive for HBV DNA and HBeAg. At peak biochemical disease, three patients had already cleared HBV DNA and five continued to harbor HBeAg. The duration of HBV DNA seropositivity was as short as one week. At the time of biochemical resolution, all patients had cleared HBV DNA, while four of five remained HBeAg-positive. Clearance of HBeAg and HBsAg occurred 4 +/- 2 months after loss of HBV DNA. We conclude that HBV DNA is not detectable in serum during the early incubation period but that it is present at the onset of symptoms. Its duration in serum can be brief and clearance is possible by the peak of aminotransferase activity. HBV DNA usually disappears before HBeAg, and it is invariably lost by the time of biochemical resolution. Its detection in serum coincides with the clinical illness, but it may be missed unless sampling is done early in the clinical course.

Natural history of chronic hepatitis b in children

Purpose:We investigated the spontaneous seroconversion rate of hepatitis B viral markers and predictive factors affecting seroconversion in children with chronic hepatitis B. Methods:The study population included 214 children diagnosed as chronic hepatitis B, with positive HBsAg, HBeAg and HBVDNA over six months, and all patients had a family history of chronic Hepatitis B. They were followed between May 1982 and Febrary 2003 in the Department of Pediatrics, Yonsei University College of Medicine. Serum HBsAg, HBeAg, anti-HBs, HBVDNA, and AST/ALT were measured every six months. Results:The mean age of patients was 7.44.5 years. The loss of HBeAg, HBVDNA and HBsAg were observed in 44(19.2%), 34(15.9%) and 3(1.4%) children respectively. The patients with serum ALT levels over three times normal and with HBVDNA less than 1,000 pg/dL showed significantly higher seroconversion rates of HBeAg and HBVDNA(P

Recombinant leucocyte interferon treatment of chronic hepatitis B: An analysis of two therapeutic trials

We have investigated the efficacy of recombinant alpha-interferon treatment of chronic hepatitis B virus (HBV) infection in two therapeutic trials. Forty-four patients positive for HBsAg, HBeAg, DNA polymerase and HBV-DNA were studied. Fourteen carriers were treated in the first trial with doses ranging from 18 to 50 million units (mu)/m2 3 times per week. Six of 14 treated carriers (43%) have a sustained loss of HBeAg, HBV-DNA and DNA polymerase. Four lost HBsAg (29%). Two of 11 (18%) untreated carriers lost HBeAg, but none lost HBsAg (P = 0.05). Nineteen patients were entered in a second trial to assess dose response. Fourteen were treated with doses ranging from 2.5 to 10 mu/m2. Five patients were untreated. Two treated patients seroconverted to anti-HBe, and a third cleared HBsAg and seroconverted to anti-HBs. None of the controls was anti-HBe-positive. Thus 9/28 (32%) carriers have lost replicating HBV versus 2/16 (13%) of untreated patients. Elevated pretreatment serum ALT concentrations and severe chronic active hepatitis were associated with inhibition of viral replication in treated patients suggesting that seroconversion may require an appropriate host response. The efficacy of recombinant interferon is restricted, but it may be of benefit in a proportion of carriers.

Lymphoblastoid and recombinant α-A Interferon therapy of chronic hepatitis B virus infection: The royal free hospital experience

Lymphoblastoid interferon (Wellferon), a combination of at least 8 alpha-interferons, has been shown to be effective therapy in male chronic carriers of HBV infection, resulting in the loss of HBeAg and HBV-DNA in 50% of those treated. However, 0/8 women (5 Chinese) treated in this trial responded to treatment. Patients with higher ASTs, CAH on biopsy and a history of acute hepatitis are more likely to respond to treatment. Recombinant alpha-A interferon has not been as successful in our particular group of patients. However, this may be explained by the observation that most of these patients are asymptomatic, homosexuals and have lower transaminases, less histological inflammation and a higher percentage of HTLV-III antibody positivity than the Wellferon group. In the HTLV-III-negative group of HBV carriers, the response to recombinant alpha-A interferon is similar to that achieved with lymphoblastoid interferon.