Interferon alfa-2b treatment of HBeAg negative/serum HBV DNA positive chronic active hepatitis type B

doi:10.1016/0168-8278(90)90180-Y

Journal of Hepatology

Volume 11, Supplement 1, 1990, Pages S133-S136

https://doi.org/10.1016/0168-8278(90)90180-Y Get rights and content

Abstract

A randomized controlled trial of recombinant interferon alfa-2b has been initiated in patients with chrome active hepatitis who were negative for serum hepatitis B e antigen but positive for serum hepatitis B virus DNA and hepatitis B core antigen expression in the liver. Twenty-five patients received interferon alfa-2b 3 million units thrice weekly for 14–16 weeks and 25 served as untreated controls. Seventeen patients in the treatment and 18 in the control group have already completed a 12-month period of observation. Interferon alfa-2b was well tolerated by all patients. At the end of therapy, complete responses, defined as disappearance of hepatitis B virus DNA from serum and return of alanine aminotransferase to normal, were observed in 10 (59%) of the 17 treated patients compared to none in the control group (p < 0.01). Twelve months after the onset of interferon alfa-2b therapy, 11 (65%) of the 17 treated patients were complete responders compared to 2 (11%) of 18 in the control group (p < 0.01). Fifty per cent ( $48$ ) of complete responders to interferon alfa-2b therapy, followed for 16–24 months, experienced reactivations of hepatitis B virus replication with reappearance of serum hepatitis B virus DNA and a return of serum alanine aminotransferase activity. The response to interferon alfa-2b therapy appeared to be independent of pre-treatment serum alanine aminotransferase and hepatitis B virus DNA levels.

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Cited by (142)

Meta-analyses on Viral Hepatitis
2009, Infectious Disease Clinics of North America
Citation Excerpt :
No meta-analyses or systematic reviews of the use of interferon for patients who have HBeAg-negative chronic hepatitis B have been published. Four randomized trials with a total of 170 patients have reported the proportion of patients who achieve a 12-month sustained response (defined as loss of HBV DNA and normalization of ALT) with interferon compared with no intervention.43–46 The response rates in the individual trials vary considerably.
This article summarizes meta-analyses on interventions for acute and chronic viral hepatitis. The primary focus is on interventions assessed in systematic reviews and meta-analyses of randomized trials. The interventions assessed include active and passive immunization for hepatitis A and B and treatments for hepatitis B and C. The results of meta-analyses on conventional interferon-alpha, pegylated interferon alpha, lamivudine, adefovir, and interferon plus ribavirin are summarized.
Peginterferon for the treatment of chronic hepatitis B in the era of nucleos(t)ide analogues
2008, Best Practice and Research: Clinical Gastroenterology
Citation Excerpt :
Response was sustained in the majority of patients after therapy, reactivation occurred in 10–20%.11,22,23 Standard IFN-induced responses were less durable in HBeAg-negative chronic HBV, with sustained response in 10–47% (average 24%) at 12 months after cessation of therapy.24–28 Long-term follow-up studies showed better overall survival and lower incidence of hepatic decompensation and HCC in responders to standard IFN than in non-responders.11,23,29,30
The practising clinician is currently faced with a number of effective treatment options for chronic hepatitis B, including two formulations of interferon (standard IFN and pegylated IFN) and five nucleos(t)ide analogues (lamivudine, adefovir, entecavir, telbivudine and tenofovir). Treatment strategies can be divided into those aiming for sustained response after discontinuation of therapy and those that need to be maintained by prolonged antiviral therapy. Sustained response is particularly achieved with interferon-based therapy, while treatment-maintained response can be achieved with long-term nucleos(t)ide analogue therapy in the majority of patients. Of currently available drugs for the treatment of chronic hepatitis B, PEG-IFN seems to result in the highest rate of off-treatment sustained response after a 1-year course of therapy. Sustained transition to the immune-control phase (inactive HBsAg carrier state) can be achieved in 30–35% of HBeAg-positive patients and 20–25% of HBeAg-negative patients. Loss of HBsAg has been observed in 11% of both HBeAg-positive and HBeAg-negative patients after 3–4 years. Since hepatitis B virus (HBV) genotype is an important predictor of response to PEG-IFN, determination of HBV genotype is essential in patients in whom sustained off-treatment response is pursued. Aiming for sustained response is of particular interest because many HBV-infected patients are in need of antiviral therapy at a young age and may otherwise require indefinite antiviral therapy.
Treatment predictors of a sustained virologic response in hepatitis B and C
2008, Journal of Hepatology
Citation Excerpt :
This is owed, in part, to the heterogeneity of treatment options. Until recently, standard IFN and lamivudine (LAM) were the only approved drugs for use within the European Union and elsewhere [8,9,14–21]. However, more recent investigations have led to current drug approvals, including PEG IFN alfa-2a as well as the nucleos(t)ide analogues adefovir dipivoxil (ADV), entecavir (ETV), telbivudine (LdT), and tenofovir disoproxil fumarate (TDF) [22–32].
Treatment predictors are important tools for the management of therapy in patients with chronic hepatitis B and C virus (HBV, HCV) infection. In chronic hepatitis B, several pretreatment parameters have been identified for prediction of virologic response to interferon alfa-based antiviral therapies or treatment with polymerase inhibitors. In interferon alfa and pegylated interferon alfa-treated patients, low baseline HBV DNA concentrations, HBV genotype A (B), and high baseline ALT levels are significantly associated with treatment response. In patients treated with nucleos(t)ide analogues, low baseline HBV DNA but not viral genotype is positively associated with virologic response. During treatment the best predictor of response is HBV DNA kinetics. Early viral suppression is associated with favourable virologic response and reduced risk for subsequent resistance mutations. For the current standard treatment with pegylated interferon alfa and ribavirin in patients with chronic hepatitis C, infection with HCV genotypes 2 and 3, baseline viral load below 400,000–800,000 IU/ml, Asian and Caucasian ethnicity, younger age, low GGT levels, absence of advanced fibrosis/cirrhosis, and absence of steatosis in the liver have been identified as independent pretreatment predictors of a sustained virologic response. After initiation of treatment, initial viral decline with undetectable HCV-RNA at week 4 of therapy (RVR) is the best predictor of sustained virologic response independent of HCV genotype.
Treatment of chronic hepatitis B
2008, Gastroenterologie Clinique et Biologique
Le traitement de l’hépatite chronique B a nettement progressé au cours des dernières années. Plusieurs molécules sont actuellement disponibles pour le traitement de cette infection : les interférons α2a et 2b (IFN), l’interféron pégylé α2a (IFN-PEG α2a), la lamivudine, l’adéfovir, l’entécavir, la telbivudine et le ténofovir. Chaque traitement a des avantages et des inconvénients. L’IFN et l’IFN-PEG α2a peuvent induire une réponse virologique après une durée d’administration limitée. Cependant, ces traitements sont efficaces chez une minorité de patients et entraînent de nombreux effets secondaires. Les analogues nucléosidiques ou nucléotidiques ont l’avantage d’être administrés par voie orale avec une bonne tolérance, de présenter une forte efficacité antivirale et un bon profil de résistance. Cependant, ces thérapies antivirales nécessitent une administration à long terme. En effet, l’interruption du traitement est associée à une réactivation virale. L’efficacité de la lamivudine est limitée par l’émergence de virus résistants. L’incidence de la résistance à l’adéfovir est faible, mais son efficacité antivirale n’est pas optimale. L’entécavir présente une efficacité antivirale accrue, avec un profil de tolérance favorable et un taux d’incidence de la résistance très faible. La telbivudine semble avoir une efficacité antivirale supérieure et un taux de résistance inférieure à la lamivudine, mais son taux de résistance reste sensiblement supérieur aux autres thérapies disponibles. Le ténofovir possède un profil de résistance et une efficacité antivirale supérieurs à l’adéfovir. Avec la puissante efficacité antivirale et un taux d’incidence de la résistance très faible des nouvelles molécules, il n’est pas certain que l’avenir du traitement de l’hépatite chronique B repose sur l’utilisation de combinaison de différents antiviraux. Les avantages éventuels des combinaisons thérapeutiques par rapport à la monothérapie devraient être des effets antiviraux additifs ou synergiques et une réduction de la survenue des résistances virales. Malheureusement, nous ne disposons actuellement que de très peu de données cliniques sur l’utilisation des combinaisons thérapeutiques. La seule combinaison ayant montré sa supériorité est l’association de l’interféron pégylé à la lamivudine. Les combinaisons associant l’interféron pégylé et un puissant analogue comme l’entécavir ou le ténofovir sont en cours d’évaluation. Elles devraient permettre d’améliorer l’efficacité, diminuer le risque de résistance et augmenter le taux de séroconversion HBs. La séroconversion HBs est l’objectif ultime du traitement puisqu’elle reflète une rémission complète et définitive. La quantification de l’antigène HBs devrait devenir un test très utile pour prédire la séroconversion HBs et faire donc partie du suivi du traitement. Il convient de définir le rôle et la place de l’interféron pégylé au sein des combinaisons thérapeutiques. D’avantage d’études visant à évaluer l’efficacité des combinaisons de nouveaux antiviraux plus puissants sont à réaliser, afin d’améliorer l’efficacité du traitement et de mieux comprendre les mécanismes entraînant une résistance.
In recent years, marked progress has been made in the treatment of chronic hepatitis B. Several agents have been approved: interferon α-(IFN), pegylated interferon α2a (PEG-IFN α2a), lamivudine, adefovir, entecavir, telbivudine and recently, tenofovir. Each drug has advantages and limitations. IFN and PEG-IFN α2a have the advantage of inducing a sustained virologic response after a defined, limited course of treatment. However, these drugs are only effective in a minority of patients and have frequent side effects. Analogues have the advantage of being administered orally, with good safety profiles and a potent antiviral effect. However, these drugs need to be administered indefinitely since withdrawal of therapy is generally associated with reactivation, and a sustained response is uncommon except in HBeAg positive patients who develop HBe seroconversion. In case of HBe seroconversion, therapy should usually be continued for at least another 24 weeks. The efficacy of lamivudine is limited by the emergence of lamivudine-resistant HBV. Adefovir is associated with a moderate incidence of resistance but its antiviral effect is not optimal. Entecavir has shown to be more effective with a favourable safety profile and a low incidence of resistance. Telbivudine is more potent and has a lower rate of resistance than lamivudine but the resistance rate is significantly higher than other approved drugs. Tenofovir has a potent antiviral effect with a good resistance profile. The future of chronic hepatitis B therapy appears to be different drug combinations. Normally the advantage of drug combinations versus monotherapy should be additive or synergistic antiviral effects and a decrease in viral resistance. Unfortunately, there are few data available and none of the evaluated analogue combinations have been shown to be better than monotherapy. The only combination which has shown a synergistic effect is of pegylated interferon α2a with lamivudine. Therefore, combinations of pegylated interferon with the most potent analogues need to be evaluated. The ultimate goal of therapy is HBsAg seroconversion which is more often observed with interferon. Indeed, quantification of serum HBsAg will be a useful tool to predict the treatment outcome. More potent drugs and new combinations as well as understanding the mechanisms of viral resistance should be evaluated to improve the efficacy of treatment.
Drug therapy: Hepatitis B virus infection
2008, New England Journal of Medicine
More effective and less resistance-prone antiviral agents are now available to treat hepatitis B virus (HBV) infection. Profound, durable, therapeutic HBV DNA suppression to slow and reverse the progression of chronic HBV infection is important, given the evidence linking high-level HBV replication and the late consequences of chronic HBV infection. This article reviews strategies for treating HBV infection.
Profound, durable, therapeutic HBV DNA suppression to slow and reverse the progression of chronic HBV infection is important, given the evidence linking high-level HBV replication and the late consequences of chronic HBV infection. This article reviews strategies for treating HBV infection.
Reports of successful antiviral therapy for chronic hepatitis B virus (HBV) infection appeared three decades ago,¹ and during the past decade, progress has accelerated dramatically. Along with progress, however, has come complexity. So much more is known now than at the dawn of the antiviral era about the protean clinical expressions of HBV infection that determining whom, when, and how to treat has become progressively more challenging.
Virologic and Epidemiologic Factors and Natural History
HBV, a DNA virus transmitted percutaneously, sexually, and perinatally, affects 1.25 million persons in the United States and 350 to 400 million persons worldwide. HBV infection . . .
Herbal medicine and its bioactive compounds for treatment of hepatitis B
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Interferon alfa-2b treatment of HBeAg negative/serum HBV DNA positive chronic active hepatitis type B

Abstract

Gastroenterology

Lancet

Anti-HBe positive chronic active hepatitis

Hepatitis B virus DNA in the sera of HBsAg carriers — a marker of active hepatitis B virus replication in the liver

Hepatology

Chronic hepatitis B: therapeutic controversies and randomized controlled trials

Castroenterol Intern

Analysis of liver disease, nuclear HBcAg, viral replication and hepatitis B virus DNA in liver and serum of HBcAg versus anti-HBe positive carriers of hepatitis B virus

Hepatology

Natural history of chronic hepatitis B virus infection in Taiwan: studies of hepatitis B virus DNA in serum

Hepatology