Prednisone Withdrawal Followed by Recombinant Alpha Interferon in the Treatment of Chronic Type B Hepatitis

Perrillo, Robert P.; Regenstein, Fredric; Peters, Marion G.; DeSchryver-Kecskemeti, K; Bodicky, Carol J.; Campbell, Carolyn; Kuhns, Mary C.

doi:10.7326/0003-4819-109-2-95

Cited by 171 publications

(42 citation statements)

References 19 publications

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“…[20][21][22][23][24][25][26][27][28][29] In addition, histological assessments of patients in other studies of lamivudine have shown that liver biopsy features improve significantly during lamivudine-induced suppression of HBV replication. 5,30,31 Further controlled trials of prolonged lamivudine treatment are in progress to define the efficacy and safety of lamivudine therapy and maintenance of virological responses after drug withdrawal.…”

Section: Discussionmentioning

confidence: 99%

Extended lamivudine retreatment for chronic hepatitis B: Maintenance of viral suppression after discontinuation of therapy

Dienstag¹,

Schiff²,

Mitchell³

et al. 1999

Hepatology

188

128

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In patients with chronic hepatitis B, brief lamivudine therapy suppresses hepatitis B virus (HBV) DNA but results infrequently in sustained losses of virus replication posttreatment. We evaluated treatment response and its posttreatment durability during up to 18 months of lamivudine therapy (100 mg/d) in 24 patients who had hepatitis B e antigen (HBeAg) despite 1 to 3 months of prior therapy. Therapy was to be stopped after HBeAg loss or seroconversion (acquisition of antibody to HBeAg); posttreatment monitoring continued for 6 months. During therapy, which was well tolerated, HBV DNA became undetectable in all evaluable patients, accompanied by reduced alanine transaminase (ALT) activity. The cumulative 18-month confirmed loss of HBeAg during therapy was 9 of 24 (38%) and seroconversion was 5 of 24 (21%). Therapy was discontinued after HBeAg loss/seroconversion in 7 patients, and Chronic hepatitis B virus (HBV) infection occurs in approximately 5% of the world' s population and is among the top 10 causes of death. Although interferon alfa has been approved as therapy for chronic hepatitis B, such treatment is suboptimal, yielding clinical benefit in a minority of patients. Lamivudine is an oral dideoxynucleoside that inhibits reverse transcription by causing chain termination of nascent viral DNA in human immunodeficiency virus (HIV) and HBV infection. 1 As reported previously, phase-II dose-ranging trials in North American and western European patients with chronic hepatitis B included daily doses of 5 to 600 mg administered for 1 to 6 months. 2-4 Therapy was well tolerated, doses of 100 mg or more suppressed serum HBV DNA levels consistently during therapy, and no significant advantage was identified for doses above 100 mg. 3,4 A sustained response posttreatment, however, defined as the loss of hepatitis B e antigen (HBeAg) and failure of HBV DNA to reappear after discontinuation of therapy, occurred in only 4% to 12% of patients in these dose-ranging studies. In a recently completed placebo-controlled phase-III trial involving 358 Chinese patients, Lai et al. 5 reported that 12 months of lamivudine therapy at a dose of 100 mg/d was associated with histological improvement in 67% of patients and HBeAg seroconversion in 16%, which is significantly better than response rates observed in concurrent placebo controls. This study in Asian patients, however, did not address treatmentstopping criteria; regardless of HBeAg status at the end of 12 months of therapy, all patients were enrolled in a continuingtreatment follow-up study. 5 In the present study, we wished to determine whether prolonged lamivudine therapy in Western patients would be safe and tolerable and result in loss of HBeAg and HBeAg seroconversion in a higher proportion of patients compared with the shorter dosing regimens studied previously. We also sought to determine whether lamivudine therapy could be withdrawn after HBeAg loss or HBeAg seroconversion. Therefore, we undertook an extended-treatment trial in previously Abbreviations: HBV, hepatitis...

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Section: Discussionmentioning

confidence: 99%

Extended lamivudine retreatment for chronic hepatitis B: Maintenance of viral suppression after discontinuation of therapy

Dienstag¹,

Schiff²,

Mitchell³

et al. 1999

Hepatology

188

128

View full text Add to dashboard Cite

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“…Therapeutic trials with adenine arabinoside or interferon have shown these agents to be relatively ineffective, and their use has been accompanied by considerable toxicity (1,3,16,20,21). However, prednisone withdrawal followed by treatment with recombinant alpha interferon has shown more promise in the treatment of chronic type B hepatitis (13). We chose the primary hepatocyte culture of DHBV (19) to screen for antiviral agents effective against hepadnaviruses.…”

mentioning

confidence: 99%

In vitro and in vivo comparison of the abilities of purine and pyrimidine 2',3'-dideoxynucleosides to inhibit duck hepadnavirus

Lee

Luo

Suzuki

et al. 1989

Antimicrob Agents Chemother

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Four purine and two pyrimidine 2',3'-dideoxynucleosides were studied for their ability to inhibit duck hepadnavirus replication. The purine 2',3'-dideoxynucleosides were more potent antiviral agents than the pyrimidine 2',3'-dideoxynucleosides. The concentration for 50% inhibition of viral replication (IC50) was determined for each of the effective agents. Two drugs with low IC50s, 2,6-diaminopurine 2',3'-dideoxyriboside and 2',3'-dideoxyadenosine, were chosen for in vivo studies. Animals received 10 mg/kg intramuscularly twice daily. Rapid clearance of hepadnavirus DNA from the sera of the animals was seen as a result of treatment with 2,6-diaminopurine 2',3'-dideoxyriboside; however, treatment with 2',3'-dideoxyadenosine did not clear the virus.

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“…Interferon has been used in a few cases, but is often prematurely withdrawn because of its hematologic toxicity. More importantly, it appears to lack efficacy in the prevention of HBV reactivation, especially in immunosuppressed patients [8,13,20,23,[34][35][36][37][38]. One of our patients, due to a lack to response to lamivudine, was given interferon, but he did not respond.…”

Section: Reactivation Of Hepatitis B In Patients With Chronicmentioning

confidence: 79%

Prevention of hepatitis B reactivation with lamivudine in hepatitis B virus carriers with hematologic malignancies treated with chemotherapy—A prospective case series

et al. 2005

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Administration of immunosuppressive treatment in hepatitis B virus carriers with malignancies is associated with the risk of hepatitis B reactivation. This complication is more frequent in patients with hematologic malignancies because administration of corticosteroids, the mainstay of treatment of these patients, is an independent risk factor for hepatitis B reactivation. When lamivudine is given prior to chemotherapy, it prevents the viral replication during the immunosuppression period; therefore, it might reduce the risk of hepatitis B exacerbation. We performed a prospective study to assess the efficacy of prophylactic administration of lamivudine in this setting. Ten hepatitis B virus carriers with hematologic malignancies were included in this study; seven were HBsAg positive, and three had isolated antiHBc and detectable HBV-DNA levels. Nine patients were given corticosteroids after the administration of lamivudine. Lamivudine was given per os at a dose of 100 mg once daily. In four patients that had not been previously treated with chemotherapy, lamivudine was started 19 days (median) (range, 0-35 days) prior to the onset of chemotherapy. The administration of lamivudine has not stopped since in any of our patients. After a median follow-up of 15 months (range 6-38 months), no hepatitis B reactivation was observed. HBV-DNA levels were decreased in all 6 patients who had detectable HBV-DNA at baseline. Lamivudine was well tolerated. Chemotherapy regimens were administered as planned, and their effectiveness was not compromised by lamivudine. In conclusion, prophylactic administration of lamivudine should be considered as a means of reducing the frequency of hepatitis B reactivation in hepatitis B virus carriers with hematologic malignancies who are being treated with chemotherapy. Am.

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Prednisone Withdrawal Followed by Recombinant Alpha Interferon in the Treatment of Chronic Type B Hepatitis

Abstract: The immunologic priming provided by a short course of prednisone used with alpha interferon may be an effective treatment for selected patients with chronic type B hepatitis.

Cited by 171 publications

References 19 publications

Extended lamivudine retreatment for chronic hepatitis B: Maintenance of viral suppression after discontinuation of therapy

Extended lamivudine retreatment for chronic hepatitis B: Maintenance of viral suppression after discontinuation of therapy

In vitro and in vivo comparison of the abilities of purine and pyrimidine 2',3'-dideoxynucleosides to inhibit duck hepadnavirus

Prevention of hepatitis B reactivation with lamivudine in hepatitis B virus carriers with hematologic malignancies treated with chemotherapy—A prospective case series

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