Pegylated Interferon Alfa-2b Add-on Treatment in Hepatitis B Virus Envelope Antigen-Positive Chronic Hepatitis B Patients Treated with Nucleos(t)ide Analogue: A Randomized, Controlled Trial (PEGON)

Chi, Heng; Hansen, Bettina E.; Guo, Simin; Zhang, Ning Ping; Qi, Xun; Chen, Liang; Guo, Qing; Arends, Pauline; Wang, Jiyao; Verhey, Elke; Knegt, Robert J. de; Xie, Qing; Janssen, Harry L.A.

doi:10.1093/infdis/jix024

Cited by 49 publications

(51 citation statements)

References 35 publications

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“…Consistent with previous clinical reports ( [15][16][17][18][19][20], combination treatment with both entecavir and PEG-IFN reduced serum HBV DNA, intrahepatic HBV DNA, and cccDNA levels (Fig. 1C).…”

Section: Persistent Loss Of Serum Hbv Markers In Micesupporting

confidence: 92%

“…1C). The observed baseline intrahepatic HBV DNA and cccDNA levels in HBV-infected mice were similar to those in chronic hepatitis B patients (17,24). Intrahepatic HBV DNA and cccDNA levels in mice treated with either entecavir or PEG-IFN alone did not differ significantly from those in untreated mice.…”

Section: Resultssupporting

confidence: 66%

“…PEG-IFN administration has been shown to lead to recruitment of transcriptional corepressors and hypoacetylation of cccDNA-associated histones, as well as inhibition of binding of host transcription factors such as STAT1 and STAT2 to cccDNA (13). Although an antiviral effect of the combination of an NA and PEG-IFN-␣-2a has been shown (15)(16)(17)(18), it has not yet been shown that the synergistic activity of the two drugs in combination is more likely to be effective in durably suppressing or eliminating cccDNA.…”

Section: Discussionmentioning

confidence: 99%

“…PEG-IFN monotherapy has been reported to result in hepatitis B e antigen (HBeAg) seroconversion in 29 to 32% of patients and in hepatitis B surface antigen (HBsAg) loss in 3 to 7% of patients at 24 weeks after completion of treatment (11,14). Combination therapy with both an NA and PEG-IFN-␣-2a has been shown to result in greater viral decline and HBeAg loss than NA therapy alone (15)(16)(17)(18) and resulted in reduced HBV cccDNA in chronic hepatitis B patients (19,20). Therefore, we hypothesized that combination therapy with high doses of NA and PEG-IFN could eliminate HBV infection in an immunodeficient animal model.…”

Section: H Epatitis B Virus (Hbv) Infection Is the Most Common Chronimentioning

confidence: 99%

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Persistent Loss of Hepatitis B Virus Markers in Serum without Cellular Immunity by Combination of Peginterferon and Entecavir Therapy in Humanized Mice

Uchida

Imamura

Hayes

et al. 2017

Antimicrob Agents Chemother

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Nucleot(s)ide analogues and peginterferon (PEG-IFN) treatment are the only approved therapies for chronic hepatitis B virus (HBV) infection. However, complete eradication of the virus, as indicated by persistent loss of hepatitis B surface antigen (HBsAg), is rare among treated patients. This is due to long-term persistence of the HBV genome in infected hepatocytes in the form of covalently closed circular DNA (cccDNA). In this study, we investigated whether administration of a large dose of a nucleoside analogue in combination with PEG-IFN can achieve long-term loss of HBsAg in human hepatocyte chimeric mice. Mice were treated with a high dose of entecavir and/or PEG-IFN for 6 weeks. High-dose combination therapy with both drugs resulted in persistently negative HBV DNA in serum. Although small amounts of HBV DNA and cccDNA (0.1 and 0.01 copy/cell, respectively) remained in the mouse livers, some of the mice remained persistently negative for serum HBV DNA at 13 weeks after cessation of the therapy. Serum HBsAg and hepatitis B corerelated antigen (HBcrAg) continued to decrease and eventually became negative at 12 weeks after cessation of the therapy. Analysis of the HBV genome in treated mice showed accumulation of G-to-A hypermutation and CpG III island methylation. Persistent loss of serum HBV DNA and loss of HBV markers by high-dose entecavir and PEG-IFN combination treatment in chimeric mice suggests that control of HBV can be achieved even in the absence of a cellular immune response.

show abstract

Section: Persistent Loss Of Serum Hbv Markers In Micesupporting

confidence: 92%

Section: Resultssupporting

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Section: H Epatitis B Virus (Hbv) Infection Is the Most Common Chronimentioning

confidence: 99%

See 2 more Smart Citations

Persistent Loss of Hepatitis B Virus Markers in Serum without Cellular Immunity by Combination of Peginterferon and Entecavir Therapy in Humanized Mice

Uchida

Imamura

Hayes

et al. 2017

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…Also, end‐of‐follow‐up HBsAg level was not reported . More recently, our group reported the results of the PEGON study that compared 48 weeks of PEG‐IFN add‐on to continuation of long‐term NA therapy, which demonstrated an increased response but only in patients naïve to PEG‐IFN . Nonetheless, no follow‐up data beyond week 96 are available yet.…”

Section: Discussionmentioning

confidence: 99%

Long‐term follow‐up of patients treated with entecavir and peginterferon add‐on therapy for HBeAg‐positive chronic hepatitis B infection: ARES long‐term follow‐up

Campenhout

Brouwer

Xie

et al. 2018

Journal of Viral Hepatitis

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Addition of peginterferon alpha (PEG-IFN add-on) to entecavir (ETV) treatment after a short lead-in phase results in more response than ETV monotherapy in HBeAg-positive chronic hepatitis B infection (CHB). This study is the first to assess long-term efficacy of this treatment strategy. Patients who received ETV ± 24 weeks of PEG-IFN add-on in a global trial (ARES study) and completed follow-up were eligible to participate in this observational LTFU study if they had at least one combined HBeAg and HBV DNA measurement beyond week 96 of the ARES study. The primary endpoint was combined response (HBeAg loss and HBV DNA <200 IU/mL) at LTFU. In total, 48 patients treated with PEG-IFN add-on and 48 patients treated with ETV monotherapy were included. The median follow-up duration was 226 (IQR 51) weeks, and 86/96 (90%) patients were initial non-responders. At LTFU, combined response was present in 13 (27%) vs 11 (23%) patients (P = 0.81), and 1 log HBsAg decline in 59% vs 28% (P = 0.02) for PEG-IFN add-on and ETV monotherapy, respectively. In 41 initial non-responders who continued ETV therapy, combined response at LTFU was present in 9 patients (PEG-IFN add-on: 5/22 [23%]; ETV monotherapy: 4/19 [21%]). Beyond week 96 of follow-up, rates of serological response became comparable between PEG-IFN add-on and ETV monotherapy. Although in this LTFU study initial non-responders were overrepresented in the add-on arm, PEG-IFN add-on possibly leads rather to accelerated HBeAg loss than to increased long-term HBeAg loss rates.

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Combination treatment of pegylated interferon and tenofovir versus tenofovir for people with chronic hepatitis B

Wang

Chai

et al. 2023

Cochrane Database of Systematic Reviews

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Pegylated Interferon Alfa-2b Add-on Treatment in Hepatitis B Virus Envelope Antigen-Positive Chronic Hepatitis B Patients Treated with Nucleos(t)ide Analogue: A Randomized, Controlled Trial (PEGON)

Abstract: NCT01532843.

Cited by 49 publications

References 35 publications

Persistent Loss of Hepatitis B Virus Markers in Serum without Cellular Immunity by Combination of Peginterferon and Entecavir Therapy in Humanized Mice

Persistent Loss of Hepatitis B Virus Markers in Serum without Cellular Immunity by Combination of Peginterferon and Entecavir Therapy in Humanized Mice

Long‐term follow‐up of patients treated with entecavir and peginterferon add‐on therapy for HBeAg‐positive chronic hepatitis B infection: ARES long‐term follow‐up

Combination treatment of pegylated interferon and tenofovir versus tenofovir for people with chronic hepatitis B

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