附加PegIFN显著降低乙肝表面抗原, 基因型DHBeAg阴完全抑制口服

StephenW

Add-on Peginterferon Alfa-2a significantly reduces HBsAg levels in HBeAg-negative, genotype D chronic hepatitis B patients fully suppressed on nucleot(s)ide analogue treatment The HERMES Study
	Reported by Jules Levin EASL 2015 April 22-26 Vienna Austria Pietro Lampertico1, Maurizia R. Brunetto2, Antonio Craxì3, Giovanni B. Gaeta4, Mario Rizzetto5, Giulio Palmieri6, Massimo Colombo1 on behalf of the HERMES Study Team 1Division of Gastroenterology and Hepatology, Ospedale Maggiore Policlinico, University of Milan, Italy 2Liver Unit, Reference Centre for Chronic Liver Disease and HCC of the Tuscany Region, University Hospital of Pisa, Italy; 3Gastroenterology and Hepatology, Di.Bi.M.I.S., University of Palermo, Italy; 4Department of Internal Medicine, Section of Infectious Disease, Second University of Naples, Italy; 5Department of Gastroenterology, University of Turin, Italy; 6Roche S.p.A., Monza, Italy

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阳光醉人

谁总结一下啊，谢谢了！

bigben446

类似的研究

Adding pegylated interferon to entecavir for hepatitis B e antigen-positive chronic hepatitis B: A multicenter randomized trial (ARES study).
Brouwer WP, et al. Hepatology. 2015.
Show full citation
Abstract
Entecavir (ETV) is a potent inhibitor of hepatitis B viral replication, but long-term therapy may be required. We investigated whether adding on pegylated interferon (Peg-IFN) to ETV therapy enhances serological response rates. In this global investigator-initiated, open-label, multicenter, randomized trial, hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients with compensated liver disease started on ETV monotherapy (0.5 mg/day) and were randomized in a 1:1 ratio to either Peg-IFN add-on therapy (180 µg/week) from week 24 to 48 (n = 85) or to continue ETV monotherapy (n = 90). Response was defined as HBeAg loss with HBV DNA <200 IU/mL at week 48. Responders discontinued ETV at week 72. All patients were followed until week 96. Response was achieved in 16 of 85 (19%) patients allocated to the add-on arm versus 9 of 90 (10%) in the monotherapy arm (P = 0.095). Adjusted for HBV DNA levels before randomized therapy, Peg-IFN add-on was significantly associated with response (odds ratio: 4.8; 95% confidence interval: 1.6-14.0; P = 0.004). Eleven (13%) of the add-on-treated patients achieved disease remission after ETV cessation versus 2 of 90 (2%) of those treated with monotherapy (P = 0.007), which was 79% (11 of 14) versus 25% (2 of 8) of those who discontinued ETV (P = 0.014). At week 96, 22 (26%) patients assigned add-on versus 12 (13%) assigned monotherapy achieved HBeAg seroconversion (P = 0.036). Peg-IFN add-on led to significantly more decline in hepatitis B surface antigen, HBeAg, and HBV DNA (all P < 0.001). Combination therapy was well tolerated.

CONCLUSION: Although the primary endpoint was not reached, 24 weeks of Peg-IFN add-on therapy led to a higher proportion of HBeAg response, compared to ETV monotherapy. Add-on therapy resulted in more viral decline and appeared to prevent relapse after stopping ETV. Hence, Peg-IFN add-on therapy may facilitate the discontinuation of nucleos(t)ide analogs. (Hepatology 2015;61:1512-1522).

© 2014 by the American Association for the Study of Liver Diseases.
PMID 25348661 [PubMed - in process]

bigben446

Add-on peg-interferon leads to loss of HBsAg in patients with HBeAg-negative chronic hepatitis and HBV DNA fully suppressed by long-term nucleotide analogs.
Ouzan D, et al. J Clin Virol. 2013.
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Abstract
BACKGROUND AND OBJECTIVE: The aim of this study was to prospectively evaluate whether the addition of peg-IFN to a stable NA regimen leads to loss of HBsAg in HBeAg-negative patients with chronic hepatitis and HBV DNA fully suppressed by long-term NA treatment.

STUDY DESIGN: We analyzed HBsAg levels in 10 HBsAg-positive, HBeAg-negative patients who received peg-IFN alpha-2a in addition to a NA regimen. Treatment lasted a maximum of 96 weeks, according to changes in the HBsAg titer. Before peg-IFN therapy, HBV DNA levels had been below the limit of detection for at least three years.

RESULTS: HBsAg levels declined in nine patients. Among these nine, four became HBsAg-negative after 48 weeks of peg-IFN treatment; these patients received peg-IFN for only 48 weeks. NAs were stopped in these four patients, and these levels remained stable for at least 18 months (loss of HBsAg; HBV-DNA negative). HBs seroconversion was observed in two patients. The remaining five patients received 96 weeks of peg-IFN therapy. One patient became HBsAg-negative at the end of peg-IFN therapy; another became HBsAg-negative six months later. Three patients did not become HBsAg-negative. NAs were stopped in the two patients who became HBsAg-negative with no relapse during 12 months of follow up.

CONCLUSIONS: In HBsAg-positive, HBeAg-negative patients with HBV DNA were fully suppressed by long-term NA treatment, the addition of peg-INF for a maximum of 96 weeks based on HBsAg-titer monitoring led to a loss of HBsAg and cessation of NA therapy in six out of ten patients, with no relapse for 12-18 months of follow up. HBs seroconversion was observed in two patients.

Copyright © 2013 Elsevier B.V. All rights reserved.
PMID 24183313 [PubMed - indexed for MEDLINE]

bigben446

Adding pegylated interferon to a current nucleos(t)ide therapy leads to HBsAg seroconversion in a subgroup of patients with chronic hepatitis B.
Kittner JM, et al. J Clin Virol. 2012.
Show full citation
Abstract
BACKGROUND: Nucleos(t)ides effectively halt disease progression in hepatitis B but require long-term medication.

OBJECTIVES: To determine whether add-on of peg-IFN to an ongoing nucleos(t)ide therapy accelerates decline of HBsAg and induces seroconversion.

STUDY DESIGN: We observed HBsAg kinetics in 12 patients on a stable oral therapy with undetectable HBV-DNA who additionally received peg-IFN-alfa 2a as an individualized therapy. 3 patients were HBeAg positive. Mean baseline HBsAg was 4695 (range 16-15,120)IU/ml.

RESULTS: A continuous decline of HBsAg was observed in 2 patients. The slope, respectively, became detectable at week 8 or 16. HBsAg had dropped by 2.90log(10) or 4.25log(10) fold at week 48, and anti-HBs appeared at week 40 or 32. Patient A - HBe-positive, genotype A, F3 fibrosis - had been HBV-DNA negative for 10 months receiving entecavir plus tenofovir. Previous therapy with peg-IFN had been unsuccessful, but now the patient experienced HBeAg seroconversion at week 24. Patient B - HBeAg negative, genotype D, cirrhosis - had a low initial HBsAg level of 16U/l. Receiving entecavir, his HBV-DNA had previously been non-detectable for 27 months. In the remaining 10 patients HBsAg declined only by a mean of 0.09log(10) (range 0.01-0.25log(10)) after 8-24 (mean 16.4) weeks, and therefore, peg-IFN was stopped. No unexpected side effects were observed.

DISCUSSION: We observed that the add-on of peg-IFN induced HBsAg seroconversion in 2 out of 12 patients. Response rates may have been higher with prolongation of therapy. The add-on concept merits to be evaluated in a clinical trial.

Copyright © 2012 Elsevier B.V. All rights reserved.
PMID 22365367 [PubMed - indexed for MEDLINE]

bigben446

[Short-term efficacy of adefovir dipivoxil as an add-on therapy in the pegylated IFNalpha-2a treatment for HBeAg positive chronic hepatitis B patients].
Chen LB, et al. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. 2010.
Authors
Chen LB1, Shu X, Jie YS, Yang XA, Zhang K, Li G, Xu QH.
Author information
1Department of Infectious Diseases, Third Affiliated Hospital of Sun Yet-sen University, Guangzhou, 510630, China.
Citation
Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. 2010 Feb;24(1):39-41.
Abstract
OBJECTIVE: To investigate whether the combination therapy of pegylated IFNalpha-2a plus adefovir dipivoxil (ADV) improve the efficacy of the treatment in CHB patients with HBeAg positive or not.

METHODS: 57 CHB patients with HBeAg positive received 48-week pegylated IFNalpha-2a therapy were enrolled into this study. If serum HBV DNA levels exceeded 1000 copies/ml at week 24, the patients were assigned to group A (pegylated IFN-alpha2a plus ADV, 21 cases) or group B (pegylated IFNalpha-2a only, 14 cases); otherwise, they received the unceasing monotherapy of pegylated IFNalpha-2a (group C, 22 cases).

RESULTS: At week 48, HBeAg seroconversion rates were 23.8%, 28.6% and 63.6% (A vs C,P = 0.014), but rates of aminotransferases normalization and HBV DNA suppression (< 1000 copies/ml) were not statistically significant among three groups. But during week 24 to week 48, rates of HBeAg seroconversion, aminotransferases normalization and HBV DNA suppression were also not statistically significant between group A and B. But amplitude of DNA drop in group A was much more than that in group B (2.60 +/- 1.37 vs 0.86 +/- 2.09, P = 0.005).

CONCLUSION: An ADV add-on therapy in pegylated IFNalpha-2a treatment seems able to improve the inhibition of HBV DNA in chronic hepatitis B patients with HBeAg positive. It requires a large, double-blind, randomized clinical trial to further provent.

PMID 20848847 [PubMed - indexed for MEDLINE]
Article in Chinese.

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阳光醉人 发表于 2015-5-16 17:26
谁总结一下啊，谢谢了！

核甘药物和干扰素联用有好处

阳光醉人

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