Changes of hepatitis B virus (HBV) markers during prolonged recombinant interferon alpha-2A treatment of chronic HBV infection

Mora, Ignacio; Porres, Juan Carlos; Bartolomé, Javier; Quiroga, Juan Antonio; Gutiez, J; Guío, C Hernández; Bas, C.; Carréño, Vicente

doi:10.1016/s0168-8278(87)80006-5

Cited by 23 publications

(6 citation statements)

References 33 publications

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“…Moreover, as pre-S antigen levels are related to the presence of HBV-DNA and to the reactivation of viral replication, these markers could be useful in the monitoring of antiviral therapy and in the follow-up of treated patients. These results are in agreement with those previously observed by us (12) and others (13) using the detection of polymerized human serum albumin receptors (pHSA-R) (related to pre-S2 antigen) during rIFN therapy. In these studies a good correlation between the decrease of pHSA-R and the response to rIFN treatment was also demonstrated.…”

Section: Discussionsupporting

confidence: 93%

Detection of proteins encoded by the pre‐S region of hepatitis B virus in the sera of HBsAg carriers: relation to viral replication

Ibarra

Mora

Bartolomé

et al. 1989

Liver

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In order to determine the relationship between the presence of pre‐S1 and pre‐S2 proteins and the level of hepatitis B virus (HBV) replication, a study of 94 HBsAg chronic carriers, 15 anti‐HBe positive patients who suffered a viral reactivation and 12 HBeAg, HBV‐DNA positive cases under antiviral therapy, has been carried out. Pre‐S1 and pre‐S2 antigens were detected by RIA using polystyrene beads coated with anti‐preS1 or anti‐preS2 (Dr W. Gerlich, Göttingen) and 125I‐anti‐HBs as tracer. The presence of pre‐S1 and pre‐S2 antigens was detected in 74 (79%) and 85 (90%), respectively, out of the 94 HBsAg chronic carriers included. The level of these antigens was significantly higher in HBeAg, HBV‐DNA positive patients than in the other patients (p<0.05). Among anti‐HBe positive patients suffering a reactivation, a significant increase of pre‐S1 and pre‐S2 levels was observed, concurring with ALT exacerbation and HBV‐DNA positivity. After reactivation, the level of pre‐S antigens returned to the basal values. A significant decrease in pre‐S antigen levels (p<0.05) among patients who respond to recombinant interferon therapy was observed, while no changes were detected among non‐responder cases. The detection of pre‐S1 and pre‐S2 antigens in serum is more frequent in those patients with high viral replication. Furthermore, among anti‐HBe carriers with a viral reactivation, synthesis of pre‐S antigens takes place again.

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Section: Discussionsupporting

confidence: 93%

Detection of proteins encoded by the pre‐S region of hepatitis B virus in the sera of HBsAg carriers: relation to viral replication

Ibarra

Mora

Bartolomé

et al. 1989

Liver

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“…In several studies, including the present one, IFN-a treatment of chronic HBV infection has resulted in seroconversion to HBeAg negativity in 30 to 40% of patients (6)(7)(8)(9)(10). Two patients in the present study subsequently underwent reactivation of their disease (one patient on two separate occasions), thus providing further evidence that seroconversion, even when IFN-a-induced, is not necessarily a permanent transition in the biological state of chronic HBV infection (11)(12)(13)(14)(15).…”

Section: <001supporting

confidence: 65%

“…During the course of the disease, seroconversion from hepatitis B e antigen (HBeAg) positive to negative is usually associated with diminished necroinflammatory activity as indicated by a fall to normal of serum ALT levels and by decreased inflammatory activity as assessed histologically (2)(3)(4)(5). Such a change may occur spontaneously but appears to be more common with a-interferon (IFN-a) therapy (6)(7)(8)(9)(10). Conversely, serological relapse from HBeAg negative to positive is usually accompanied by a reactivation of the liver disease (11)(12)(13)(14)(15).…”

mentioning

confidence: 99%

Serial antipyrine clearance studies detect altered hepatic metabolic function during spontaneous and interferon-induced changes in chronic hepatitis B disease activity

Farrell

1989

Hepatology

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The present study was performed to establish whether sequential determinations of antipyrine clearance, using a simplified two-point test, are sensitive and specific indicators of changes in chronic hepatitis B disease activity. Sixteen patients were studied on four or more occasions during 18 to 30 months. Eleven patients were treated with recombinant human alpha-interferon (2.5, 5.0 or 10 X 10(6) per m2, intramuscularly, three times per week, for 24 weeks), and five patients were untreated controls. Among seven patients, (six interferon-treated and one control) who lost hepatitis B e antigen from serum, antipyrine clearance improved by 46% (range: 20 to 160%) from 0.37 +/- 0.14 ml per kg per min (mean +/- S.D.) to 0.54 +/- 0.13 ml per kg per min, p less than 0.005. This change paralleled the loss of symptoms and reduction of serum ALT levels (from 206 +/- 189 IU per liter (mean +/- S.D.) to 38 +/- 12 IU per liter, p less than 0.005). Conversely, antipyrine clearance declined to previous levels when reactivation of chronic hepatitis B with reappearance of HBeAg in serum occurred. Regardless of changes in hepatitis B serology, when serum ALT values fluctuated by more than 20% (presumed to reflect fluctuations in necroinflammatory activity of the liver disease), antipyrine clearance also changed whereas serum albumin and bilirubin concentrations and prothrombin time did not. It is concluded that antipyrine clearance is a more sensitive and specific parameter than conventional indices for assessing hepatic metabolic function during changes in chronic hepatitis B disease activity. Remission in disease with loss of HBeAg from serum is associated with improved hepatic metabolic function as determined by the antipyrine clearance test.

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“…The reason for this discrepancy remains unclear, although one possible explanation is that, in spite of the fact that the children were treated with 32 Ruiz Moreno/Jimenez/Porres/Bartolomé/Moreno/Carreño high doses, the duration of therapy was no more than 3 months. It has been reported, however, that anti-IFN antibodies may ap pear soon after therapy (1-2 months) [16]. One possible explanation for this finding may be differences in the immune systems of children and adults, but this will have to be proven.…”

Section: Discussionmentioning

confidence: 96%

“…Furthermore, both groups were similar with respect to HBV-DNAp. HBV-DNA concentration, ALT and Knodell's index, which may, in fact, influence the rate of sero conversion [16]. It may be possible in the future to overcome this difficulty by includ ing a greater number of patients.…”

Section: Discussionmentioning

confidence: 99%

A Controlled Trial of Recombinant Interferon-Alpha in Caucasian Children with Chronic Hepatitis B

et al. 1990

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Twenty-four children with chronic active hepatitis due to hepatitis B virus (HBV) infection, who were positive for HB_eAg and had increased levels of transaminases, were included in a controlled study of treatment using recombinant interferon-α (rIFN-α), 10 MU/m2 body surface, intramuscularly, 3 times a week over a period of 3 months. During therapy, a significant decrease in HBV-DNAp was observed in the 12 patients treated. By the end of therapy, the HBV-DNA had disappeared in 3 children, the same occurring in 1 child (33 % overall) during the course of the 4th month. By this time, all the controls remained with HBV replication markers (p < 0.05). The 4 treated patients who responded became HB_eAg-negative, developing anti-HBe during the first 12 months after therapy. In the control group, the HBV-DNA disappeared in 3 children in the 7th month of follow-up. All of the children remained HB_sAg-positive. The therapy with rIFN-α was well tolerated, secondary effects consisting of a flu-like syndrome and a slight decrease in leukocytes and platelets. At the second biopsy, 15 months after the beginning of therapy, a significant decrease in Knodell’s index of histological activity was observed in the responders. In the light of these results and since treated children lost viral replication markers in a shorter period of time than the controls, who seroconverted spontaneously, we consider that rIFN-α may be useful in the treatment of chronic heptitis B in childhood.

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Changes of hepatitis B virus (HBV) markers during prolonged recombinant interferon alpha-2A treatment of chronic HBV infection

Cited by 23 publications

References 33 publications

Detection of proteins encoded by the pre‐S region of hepatitis B virus in the sera of HBsAg carriers: relation to viral replication

Detection of proteins encoded by the pre‐S region of hepatitis B virus in the sera of HBsAg carriers: relation to viral replication

Serial antipyrine clearance studies detect altered hepatic metabolic function during spontaneous and interferon-induced changes in chronic hepatitis B disease activity

A Controlled Trial of Recombinant Interferon-Alpha in Caucasian Children with Chronic Hepatitis B

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