Journal of Chemotherapy
ISSN: 1120-009X (Print) 1973-9478 (Online) Journal homepage: http://www.tandfonline.com/loi/yjoc20
Relation of Changes in Hepatitis B Virus Replication Markers to the Outcome of Interferon Treatment in Patients with Chronic Hepatitis S. Nardiello, M. Gargiulo, T. Pizzella, L. Digilio, L. Di Ottavio & B. Galanti To cite this article: S. Nardiello, M. Gargiulo, T. Pizzella, L. Digilio, L. Di Ottavio & B. Galanti (1992) Relation of Changes in Hepatitis B Virus Replication Markers to the Outcome of Interferon Treatment in Patients with Chronic Hepatitis, Journal of Chemotherapy, 4:2, 95-98, DOI: 10.1080/1120009X.1992.11739147 To link to this article: https://doi.org/10.1080/1120009X.1992.11739147
Published online: 15 Jul 2016.
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Citing articles: 2 View citing articles
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Journal of Chemotherapy
Relation of Changes in Hepatitis B Virus Replication Markers to the Outcome of Interferon Treatment in Patients with Chronic Hepatitis S. NARDIELLO - M. GARGIULO * T. PIZZELLA - L. DIGILIO L. DI OTTAVIO * - B. GALANTI
Summary - - - - - - - - - - - - - - - -
The relationship between the behavior of hepatitis B virus (HBV) replication markers and the response to treatment with recombinant alpha-2b interferon (IFN) was investigated in 11 patients with chronic hepatitis. At the end of 6 months of treatment, 4 patients showed a complete response to IFN: 2 more patients had seroconversion to HBeAb after 8 and 9 months of follow-up, respectively. The response to IFN was partial in the remaining patients. Pre-treatment levels of HBV DNA in patients showing complete response were lower than pre-treatment levels in patients with partial response: in addition, serum HBV DNA clearance during the treatment was associated with sustained remission more frequently than changes in the HBeAg/HBeAb system. Key words: Chronic HBV hepatitis, interferon, circulating HBV DNA.
l stituto di Clinica Malattie Infettive, Prima Facolta di Medicina, Universita di Napoli, Italy. * Sezione Malattie lnfettive, O spedale Civile di Teramo, Italy. Co"espondence: Dr. S. Nardiello, Istituto di Clinica Malattie Infettive, c/o Ospedale Gesu e Maria, Via D. Cotugno 1, 80135 Napoli, Italy. © Edizioni Rjviste Scientifiche - Firenze
Vol. 4 - n. 2 (95-98) - 1992
INTRODUCTION
Among the drugs utilized for the treatment of chronic hepatitis caused by hepatitis B virus (HBV), the best results have been obtained using interferon (IFN), and in particular using alpha IFN, both in adults 1 and pediatric patients 2 • However, only some patients respond completely to IFN treatment: in a review of the results from 14 independent sudies, it was reported that the rate of success with this treatment is between 30% and 40% 3 • The reduction or the disappearance of HBV replication is fundamental for the clinical response to IFN. As a matter of fact, the repression of viral replication is accompanied by a lessening or disappearance of hepatic inflammation 4 • In this study we have determined the levels of HBV DNA and the HBeAg/HBeAb system in the serum of patients with chronic HBV hepatitis treated with IFN , and we have compared the results of tests of HBV replication with the outcome of the treatment.
PATIENTS AND METHODS
Eleven HBsAg/HBV DNA-positive patients (7 males, 4 females; age range 9-61 yrs) were studied. None of them was homosexual or a drug addict, and none had HIV (human immunodeficiency virus) or HDV (hepatitis D virus) infection. All patients had biopsy-proven chronic hepatitis: diagnoses included chronic persistent hepatitis (CPH) in 5 patients, chronic active hepatitis (CAH) in 4 patients, CAH with cirrhosis (CAH-C) in 2 patients. ISSN 1120-009X
96
S. NARDIELLO - M. GARGIULO - T. PIZZELLA - L. DIGILIO - L. Dl OTTAVIO - G. GALANTI
Patients were treated with recombinant IFN alpha-2b (lntron A, Schering-Plough) administered three times weekly in doses of 6 MU i.m. in 9 adults and 3 MU i.m. in 3 children for a period of 6 months. Ten patients were followed up after treatment discontinuation for a mean period of 13.4 months (range 6-24 months). Markers of HBV and HDV were tested by commercial ELISA or RIA kits (Abbott Laboratories, North Chicago, IL; Sarin Biomedica, Saluggia, Italy). Anti-HIV antibodies were detected by ELISA (Abbott). Serum HBV DNA was detected by slot-blot hybridization 5 , using as a probe a repurified, cloned HBV DNA insert (pH20), nick-translated with 32 P-dCTP (10 mCi/ml, Amersham, UK) to a specific activity of 1-2x10 8 cpm/IJ.g. Autoradiography was performed at - 70° C for 5 days. For quantitative analysis of HBV DNA, the autoradiographic slots of test samples (undiluted or diluted in human serum not reactive for HBV markers) were compared with those of different dilutions of a reference standard serum with known concentrations of HBV DNA (Genostics Hepatitis B Virus DNA positive control, Abbott) included in each assay. Levels of HBV DNA in test samples were equivalent to those of the reference serum giving the closest intensity of the autoradiographic slot, multiplied for the sample dilution factor. The sensitivity of the assay was about 1 pg of HBV DNA / ml of serum.
TABLE 1 - Characteristics and laboratory data of the patients at admission. Pt. no.
Sex Age
1 2 3 4 5 6 7 8 9 10
M M M M M
11
F
F F
M M F
10 19 19 61 26 9 45 14 18 16 29
SGPT Histol- HBV DNA HBeAg HBeAb (U/L; ogy (pgfml) N
ISSN: 1120-009X (Print) 1973-9478 (Online) Journal homepage: http://www.tandfonline.com/loi/yjoc20
Relation of Changes in Hepatitis B Virus Replication Markers to the Outcome of Interferon Treatment in Patients with Chronic Hepatitis S. Nardiello, M. Gargiulo, T. Pizzella, L. Digilio, L. Di Ottavio & B. Galanti To cite this article: S. Nardiello, M. Gargiulo, T. Pizzella, L. Digilio, L. Di Ottavio & B. Galanti (1992) Relation of Changes in Hepatitis B Virus Replication Markers to the Outcome of Interferon Treatment in Patients with Chronic Hepatitis, Journal of Chemotherapy, 4:2, 95-98, DOI: 10.1080/1120009X.1992.11739147 To link to this article: https://doi.org/10.1080/1120009X.1992.11739147
Published online: 15 Jul 2016.
Submit your article to this journal
View related articles
Citing articles: 2 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=yjoc20
Journal of Chemotherapy
Relation of Changes in Hepatitis B Virus Replication Markers to the Outcome of Interferon Treatment in Patients with Chronic Hepatitis S. NARDIELLO - M. GARGIULO * T. PIZZELLA - L. DIGILIO L. DI OTTAVIO * - B. GALANTI
Summary - - - - - - - - - - - - - - - -
The relationship between the behavior of hepatitis B virus (HBV) replication markers and the response to treatment with recombinant alpha-2b interferon (IFN) was investigated in 11 patients with chronic hepatitis. At the end of 6 months of treatment, 4 patients showed a complete response to IFN: 2 more patients had seroconversion to HBeAb after 8 and 9 months of follow-up, respectively. The response to IFN was partial in the remaining patients. Pre-treatment levels of HBV DNA in patients showing complete response were lower than pre-treatment levels in patients with partial response: in addition, serum HBV DNA clearance during the treatment was associated with sustained remission more frequently than changes in the HBeAg/HBeAb system. Key words: Chronic HBV hepatitis, interferon, circulating HBV DNA.
l stituto di Clinica Malattie Infettive, Prima Facolta di Medicina, Universita di Napoli, Italy. * Sezione Malattie lnfettive, O spedale Civile di Teramo, Italy. Co"espondence: Dr. S. Nardiello, Istituto di Clinica Malattie Infettive, c/o Ospedale Gesu e Maria, Via D. Cotugno 1, 80135 Napoli, Italy. © Edizioni Rjviste Scientifiche - Firenze
Vol. 4 - n. 2 (95-98) - 1992
INTRODUCTION
Among the drugs utilized for the treatment of chronic hepatitis caused by hepatitis B virus (HBV), the best results have been obtained using interferon (IFN), and in particular using alpha IFN, both in adults 1 and pediatric patients 2 • However, only some patients respond completely to IFN treatment: in a review of the results from 14 independent sudies, it was reported that the rate of success with this treatment is between 30% and 40% 3 • The reduction or the disappearance of HBV replication is fundamental for the clinical response to IFN. As a matter of fact, the repression of viral replication is accompanied by a lessening or disappearance of hepatic inflammation 4 • In this study we have determined the levels of HBV DNA and the HBeAg/HBeAb system in the serum of patients with chronic HBV hepatitis treated with IFN , and we have compared the results of tests of HBV replication with the outcome of the treatment.
PATIENTS AND METHODS
Eleven HBsAg/HBV DNA-positive patients (7 males, 4 females; age range 9-61 yrs) were studied. None of them was homosexual or a drug addict, and none had HIV (human immunodeficiency virus) or HDV (hepatitis D virus) infection. All patients had biopsy-proven chronic hepatitis: diagnoses included chronic persistent hepatitis (CPH) in 5 patients, chronic active hepatitis (CAH) in 4 patients, CAH with cirrhosis (CAH-C) in 2 patients. ISSN 1120-009X
96
S. NARDIELLO - M. GARGIULO - T. PIZZELLA - L. DIGILIO - L. Dl OTTAVIO - G. GALANTI
Patients were treated with recombinant IFN alpha-2b (lntron A, Schering-Plough) administered three times weekly in doses of 6 MU i.m. in 9 adults and 3 MU i.m. in 3 children for a period of 6 months. Ten patients were followed up after treatment discontinuation for a mean period of 13.4 months (range 6-24 months). Markers of HBV and HDV were tested by commercial ELISA or RIA kits (Abbott Laboratories, North Chicago, IL; Sarin Biomedica, Saluggia, Italy). Anti-HIV antibodies were detected by ELISA (Abbott). Serum HBV DNA was detected by slot-blot hybridization 5 , using as a probe a repurified, cloned HBV DNA insert (pH20), nick-translated with 32 P-dCTP (10 mCi/ml, Amersham, UK) to a specific activity of 1-2x10 8 cpm/IJ.g. Autoradiography was performed at - 70° C for 5 days. For quantitative analysis of HBV DNA, the autoradiographic slots of test samples (undiluted or diluted in human serum not reactive for HBV markers) were compared with those of different dilutions of a reference standard serum with known concentrations of HBV DNA (Genostics Hepatitis B Virus DNA positive control, Abbott) included in each assay. Levels of HBV DNA in test samples were equivalent to those of the reference serum giving the closest intensity of the autoradiographic slot, multiplied for the sample dilution factor. The sensitivity of the assay was about 1 pg of HBV DNA / ml of serum.
TABLE 1 - Characteristics and laboratory data of the patients at admission. Pt. no.
Sex Age
1 2 3 4 5 6 7 8 9 10
M M M M M
11
F
F F
M M F
10 19 19 61 26 9 45 14 18 16 29
SGPT Histol- HBV DNA HBeAg HBeAb (U/L; ogy (pgfml) N
