Lamivudine/pegylated interferon alfa‐2b sequential combination therapy compared with lamivudine monotherapy in HBeAg‐negative chronic hepatitis B

Vassiliadis, Themistoklis; Τζιόμαλος, Κωνσταντίνος; Patsiaoura, Kalliopi; Zagris, Thomas; Γιουλεμέ, Όλγα; Soufleris, Konstantinos; Grammatikos, Nikolaos; Θεοδωρόπουλος, Κωνσταντίνος; Mpoumponaris, Alexandros; Dona, Konstantina; Zezos, Petros; Nikolaidis, Nikolaos; Orfanou-Koumerkeridou, Eleni; Balaska, Aikaterini; Eugenidis, Nikolaos

doi:10.1111/j.1440-1746.2007.05103.x

Cited by 14 publications

(8 citation statements)

References 49 publications

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“…In a 3-year follow-up of the HBeAg-negative patients, one third of those treated with peginterferon had maintained normal ALT levels and HBV DNA levels of \10,000 copies/ml [8]. Similar findings have been reported in studies of peginterferon alfa-2b in patients with HBeAgpositive [15,16] and HBeAg-negative CHB [17,18].…”

Section: Peginterferon Alfasupporting

confidence: 82%

Current approaches for treating chronic hepatitis B: when to start, what to start with, and when to stop

Chang

Suh

2008

Hepatol Int

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The natural course of hepatitis B virus (HBV) infection is variable, and chronic hepatitis B (CHB) disease exhibits itself through a spectrum of clinical manifestations. These factors contribute to the challenges faced when managing patients who live with HBV infection. Furthermore, conventional treatment options (e.g., interferon alfa-2a, lamivudine, and adefovir) are moderately effective and can be associated with problems, such as poor tolerability (interferon alfa-2a) and the development of drug resistance (lamivudine). Over the last 5 years, several antiviral agents including entecavir, peginterferon alfa-2a, and telbivudine which are more efficacious and have improved tolerability over previous drugs have become available. The availability of novel antiviral agents and advances in understanding resistance patterns of antiviral agents has resulted in refinement of CHB treatment recommendations and guidelines. More recently, evidence from clinical trials suggests the central importance of virologic suppression as an indicator of treatment outcome and the predictive value of on-treatment HBV DNA levels in response to antiviral therapy. This review highlights the goals of therapy and clinical experience with therapies that are newly licensed or in the late stages of clinical development. Current approaches for treating CHB and new strategies for optimizing response to therapy are also discussed.

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Section: Peginterferon Alfasupporting

confidence: 82%

Current approaches for treating chronic hepatitis B: when to start, what to start with, and when to stop

Chang

Suh

2008

Hepatol Int

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“…In spite of high rate of drug resistance, so far, lamivudine is the most widely used nucleoside analogues for HBV treatment owing to its low price, safety and effectiveness [30]. Many previous studies reported that a combination of IFN-α and lamivudine achieved some therapeutic effects [31,32]. Here, in comparison to the treatment with exogenously added hIFN-α combined with lamivudine, the combination of endogenously expressed hIFN-α and lamivudine could restrain HBV more effectively at a certain degree (Figure 6).…”

Section: Discussionmentioning

confidence: 99%

The anti-HBV effect mediated by a novel recombinant eukaryotic expression vector for IFN-α

Hou

Han

et al. 2013

Virol J

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BackgroundChronic hepatitis B is a primary cause of liver-related death. Interferon alpha (IFN-α) is able to inhibit the replication of hepadnavirus, and the sustained and stable expression of IFN-α at appropriate level may be beneficial to HBV clearance. With the development of molecular cloning technology, gene therapy plays a more and more important role in clinical practice. In light of the findings, an attempt to investigate the anti-HBV effects mediated by a eukaryotic expression plasmid (pSecTagB-IFN-α) in vitro was carried out.MethodsHBV positive cell line HepG2.2.15 and its parental cell HepG2 were transfected with pSecTagB-IFN-α or empty plasmid by using Lipofectamine™ 2000 reagent. The expression levels of IFN-α were determined by reverse transcriptase polymerase chain reaction (RT-PCR) and ELISA methods. The effects of pSecTagB-IFN-α on HBV mRNA, DNA and antigens were analyzed by real-time fluorescence quantitative PCR (qRT-PCR) and ELISA assays. RT-PCR, qRT-PCR and western blot were employed to investigate the influence of pSecTagB-IFN-α on IFN-α-induced signal pathway. Furthermore, through qRT-PCR and ELISA assays, the suppressive effects of endogenously expressed IFN-α and the combination with lamivudine on HBV were also examined.ResultspSecTagB-IFN-α could express efficiently in hepatoma cells, and then inhibited HBV replication, characterized by the decrease of HBV S gene (HBs) and HBV C gene (HBc) mRNA, the reduction of HBV DNA load, and the low contents of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg). Mechanism research showed that the activation of Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signal pathway, the up-regulation of IFN-α-induced antiviral effectors and double-stranded (ds) RNA sensing receptors by delivering pSecTagB-IFN-α, could be responsible for these phenomena. Furthermore, pSecTagB-IFN-α vector revealed effectively anti-HBV effect than exogenously added IFN-α. Moreover, lamivudine combined with endogenously expressed IFN-α exhibited stronger anti-HBV effect than with exogenous IFN-α.ConclusionOur results showed that endogenously expressed IFN-α can effectively and persistently inhibit HBV replication in HBV infected cells. These observations opened a promising way to design new antiviral genetic engineering drugs based on IFN-α.

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“…There was no interruption in LAM therapy before randomization. We chose a 3:1 ratio for patient assignment on the basis of preliminary data, suggesting that interferon/LAM combination treatment is more effective than LAM monotherapy and delays the development of LAM resistance 23,24 . We extrapolated that ADV/LAM combination would also be superior to LAM monotherapy, and therefore, opted to treat most patients with ADV plus LAM.…”

Section: Methodsmentioning

confidence: 99%

Adefovir plus lamivudine are more effective than adefovir alone in lamivudine‐resistant HBeAg^‐ chronic hepatitis B patients: A 4‐year study

Vassiliadis¹,

Γιουλεμέ²,

Koumerkeridis

et al. 2009

J of Gastro and Hepatol

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Lamivudine/pegylated interferon alfa‐2b sequential combination therapy compared with lamivudine monotherapy in HBeAg‐negative chronic hepatitis B

Abstract: Sequential combination treatment is able to improve sustained biochemical response rates and prevent the emergence of lamivudine-resistant mutants in patients with HBeAg-negative chronic hepatitis B.

Cited by 14 publications

References 49 publications

Current approaches for treating chronic hepatitis B: when to start, what to start with, and when to stop

Current approaches for treating chronic hepatitis B: when to start, what to start with, and when to stop

The anti-HBV effect mediated by a novel recombinant eukaryotic expression vector for IFN-α

Adefovir plus lamivudine are more effective than adefovir alone in lamivudine‐resistant HBeAg^‐ chronic hepatitis B patients: A 4‐year study

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Lamivudine/pegylated interferon alfa‐2b sequential combination therapy compared with lamivudine monotherapy in HBeAg‐negative chronic hepatitis B

Abstract: Sequential combination treatment is able to improve sustained biochemical response rates and prevent the emergence of lamivudine-resistant mutants in patients with HBeAg-negative chronic hepatitis B.

Cited by 14 publications

References 49 publications

Current approaches for treating chronic hepatitis B: when to start, what to start with, and when to stop

Current approaches for treating chronic hepatitis B: when to start, what to start with, and when to stop

The anti-HBV effect mediated by a novel recombinant eukaryotic expression vector for IFN-α

Adefovir plus lamivudine are more effective than adefovir alone in lamivudine‐resistant HBeAg‐ chronic hepatitis B patients: A 4‐year study

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Adefovir plus lamivudine are more effective than adefovir alone in lamivudine‐resistant HBeAg^‐ chronic hepatitis B patients: A 4‐year study