Treatment of chronic hepatitis B with interferon α-2b and interleukin-2

Bruch, Harald-Robert; Korn, Alex P.; Klein, Herman O.; Markus, Regina Pekelmann; Malmus, K.; Baumgarten, R; Müller, R.

doi:10.1016/s0168-8278(05)80424-6

Cited by 20 publications

(12 citation statements)

References 18 publications

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“…Moreover, all our patients were Caucasian; in the other studies, the patients were of Oriental origin, and racial differences may influence the response to treatment in chronic hepatitis B. In contrast, our results are in agreement with those obtained by Bruch et al [1993], who found that in Caucasian patients, the combination of alpha interferon and IL-2 did not improve the response rate obtained with interferon alone. Several of the patients who were included in the study, and treated with rIL-2, had not responded to a previous cycle of IFN alpha therapy, and also failed to respond to rIL-2.…”

Section: Discussionsupporting

confidence: 91%

Double-blind, randomized controlled trial of interleukin-2 treatment of chronic hepatitis B

et al. 1998

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Pilot studies have demonstrated that recombinant interleukin 2 (rIL-2) has an indirect antiviral activity against hepatitis B virus, but the minimal dose of rIL-2 for induction of this effect was not defined. The aim of the study was to ascertain the most efficient dose of rIL-2 for induction of the loss of detectable serum HBV-DNA or a 50% or greater decrease in its level. Thirty-one patients with chronic hepatitis B, hepatitis B e antigen and serum HBV-DNA positive were enrolled in this double-blind randomized controlled trial. Patients were divided: Group I (n = 8) placebo; Group II (n = 7) treated with 0.9 MU of rIL-2 subcutaneously administered daily for 8 weeks; Group III (n = 8) treated with 1.8 MU of rIL-2 under the same schedule; Group IV (n = 8) which received 3.6 MU of rIL-2 under the same conditions. At the end of treatment 25% of the patients in the placebo group, and 13% and 25% in rIL-2 groups III and IV, respectively, had a decrease in HBV-DNA higher than 50% of the basal value. None of the patients lost serum HBV-DNA. Only three patients (one from group II and two from group IV) normalized the ALT levels. Overall, during treatment, ALT levels decreased in the treated groups. This decrease occurred simultaneously with an increase in serum HBV-DNA concentration. Since the response rate in the treated groups was similar to that of the placebo group, rIL-2 is not useful as monotherapy for the treatment of chronic hepatitis B at the doses and schedules used in this study.

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Section: Discussionsupporting

confidence: 91%

Double-blind, randomized controlled trial of interleukin-2 treatment of chronic hepatitis B

et al. 1998

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“…Collectively, these data suggest that residual DHBV remained replication competent and was able to extremely rapidly spread amongst the liver cells of virus‐naïve ducklings inducing high‐titre infection. Our findings corroborate observations demonstrating that even very low serum HBV DNA dose (10 1 ) is sufficient to induce persistent infection in chimpanzees . Importantly, our results extend these observations and provide evidence that minute amounts of liver hepadnaviral DNA remain infectious and are able to transmit high‐titre persistent infection.…”

Section: Discussionsupporting

confidence: 90%

In vivo infectivity of liver extracts after resolution of hepadnaviral infection following therapy associating DNA vaccine and cytokine genes

Saade

Buronfosse

Guerret³

et al. 2012

Journal of Viral Hepatitis

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SUMMARY. DNA-based vaccination appears of promise for chronic hepatitis B immunotherapy, although there is an urgent need to increase its efficacy. In this preclinical study, we evaluated the therapeutic benefit of cytokine (IL-2, IFN-c) genes co-delivery with DNA vaccine targeting hepadnaviral proteins in the chronic duck hepatitis B virus (DHBV) infection model. Then, we investigated the persistence of replication-competent virus in the livers of apparently resolved animals. DHBV carriers received four injections of plasmids encoding DHBV envelope and core alone or co-delivered with duck IL-2 (DuIL-2) or duck IFN-c (DuIFN-c) plasmids. After long-term (8 months) follow-up, viral covalently closed circular (ccc) DNA was analysed in duck necropsy liver samples. Liver homogenates were also tested for in vivo infectivity in neonatal ducklings. Codelivery of DuIFN-c resulted in significantly lower mean viremia starting from week 21. Viral cccDNA was undetectable by conventional methods in the livers of 25% and 57% of animals co-immunized with DuIL-2 and DuIFN-c, respectively. Interestingly, inoculation of liver homogenates from 7 such apparently resolved animals, exhibiting cccDNA undetectable in Southern blotting and DHBV expression undetectable or restricted to few hepatocytes, revealed that three liver homogenates transmitted hightitre viremia (3-5910 10 vge/mL) to naïve animals. In conclusion, our results indicate that IFN-c gene co-delivery considerably enhances immunotherapeutic efficacy of DNA vaccine targeting hepadnaviral proteins. Importantly, we also showed that livers exhibiting only minute amounts of hepadnaviral cccDNA could induce extremely high-titre infection, highlighting the caution that should be taken in occult hepatitis B patients to prevent HBV transmission in liver transplantation context.

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“…A randomized trial of combination IL-2 and IFN-α2b versus IFN-α2b monotherapy in 37 patients also did not show any effect on serum HBV DNA clearance, HBeAg seroconversion or normalization of serum alanine transaminase (ALT) levels. However, side effects are higher in the combination group 30. Therefore, there is no strong evidence to demonstrate the effect of IL-2 on chronic HBV infection.…”

Section: Immunomodulatory Treatments Of Chronic Hepatitis B Infectionmentioning

confidence: 95%

Advances in immunomodulating therapy of HBV infection

Hui

Lau²

2005

Int. J. Med. Sci.

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Patients with chronic hepatitis B virus (HBV) infection have a higher risk of developing liver cirrhosis and hepatocellular carcinoma. Interferon-α, lamivudine and adefovir dipivoxil are the three approved treatment for chronic HBV infection and offers the only means of preventing the development of these complications. However, the efficacy of these agents, in terms of loss of Hepatitis B e antigen with or without seroconversion to Hepatitis B e antibody, normalization of serum alanine transaminase levels, loss of serum HBV DNA, and improvement in liver histology can only be achieved in 20-30% of those treated. Long-term treatment with either lamivudine or adefovir dipivoxil can result in the development of drug resistant mutants leading to an increased length of treatment with additional nucleoside analogues. These limitations of the current antiviral therapies underline the need for alternative therapies. Specific and nonspecific immunotherapeutic strategies to restore effective virus-specific T cell responses in those with chronic HBV infection offers an interesting alternative approach. These immunotherapeutic therapies include the adoptive transfer of HBV immunity, pegylated interferon and therapeutic vaccine therapies.

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Treatment of chronic hepatitis B with interferon α-2b and interleukin-2

Cited by 20 publications

References 18 publications

Double-blind, randomized controlled trial of interleukin-2 treatment of chronic hepatitis B

Double-blind, randomized controlled trial of interleukin-2 treatment of chronic hepatitis B

In vivo infectivity of liver extracts after resolution of hepadnaviral infection following therapy associating DNA vaccine and cytokine genes

Advances in immunomodulating therapy of HBV infection

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