Treatment of hepatitis B: Is there still a role for interferon?

Viganò, Mauro; Grossi, G.; Loglio, Alessandro; Lampertico, Pietro

doi:10.1111/liv.13635

Cited by 53 publications

(49 citation statements)

References 26 publications

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“…However, a pooled estimate of their efficacy in achieving HBsAg loss has not been performed. On the other hand, pegylated IFNs working as immunomodulators are less effective at viral suppression but better in achieving HBeAg seroconversion 57 . They also have increased adverse events which lead to discontinuation of therapy in a significant number of patients.…”

Section: Discussionmentioning

confidence: 99%

The efficacy of hepatitis B treatments in achieving HBsAg seroclearance: A systematic review and meta‐analysis

Fonseca¹,

Ling

Al‐Siyabi

et al. 2020

Journal of Viral Hepatitis

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Current therapies for chronic hepatitis B (CHB) include nucleos(t)ide analogues (NAs) and interferon (IFN), but their relative efficacy as monotherapy or in combination has not been examined systematically for HBsAg loss (functional cure). Hence, we systematically reviewed the evidence for HBsAg loss in CHB patients treated with IFN, NA or the combination. We searched PubMed, EMBASE and abstracts from EASL, Asia Pacific Association for study of the Liver and American Association for the Study of Liver Disease for randomized controlled trials of CHB patients, comparing NA, IFN or the combination. The Cochrane Risk of Bias tool v2.0 and GRADE method were used. Analyses were stratified by NA genetic barrier, cirrhosis, type of combination therapy, HBeAg, treatment naivety, IFN dosage/duration and outcome duration. Sensitivity analysis was performed for selected strata, and HBsAg loss was measured at the end‐of‐study (EOS), end‐of‐treatment (EOT) or end‐of‐follow‐up (EOF). Effects were reported as risk differences (RD) with 95% confidence intervals (CI) using a random‐effects model. Forty‐five studies were included, all with low risk of bias. For HBsAg loss at EOS, when comparing combination vs IFN, RD = 1%, 95%CI‐1%, 2%; combination vs NA, RD = 5%, 95%CI 3%,7%; IFN vs NA, RD = 3%, 95%CI 2%,5%. Subgroup analysis showed a significant effect of standard IFN dose vs nonstandard; IFN duration ≥48 weeks vs <48 weeks, and loss of efficacy >2 years of follow‐up. Similar findings were seen in HBsAg seroconversion, but only three studies reported HBsAg seroreversion. In conclusion, IFN monotherapy/combination had a small but significant increase in HBsAg loss over NA, associated with standard dose of IFN and ≥48 weeks of therapy, although this effect faded over time.

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Section: Discussionmentioning

confidence: 99%

The efficacy of hepatitis B treatments in achieving HBsAg seroclearance: A systematic review and meta‐analysis

Fonseca¹,

Ling

Al‐Siyabi

et al. 2020

Journal of Viral Hepatitis

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“…Predictors of responsiveness to interferon therapy include a low baseline viral load, high ALT levels, younger age and HBV genotype amongst others. 71 In pivotal clinical trials of de novo combination therapy of pegylated interferon with lamivudine, [72][73][74] adefovir, 75 or entecavir 76 did not improve sustained virological response rates compared to monotherapy but recently interferon combined with tenofovir has been shown to improve post-treatment HBsAg clearance rates during longerterm follow-up, 77,78 and in long-term nucleoside/nucleotide suppressed patients a switch to interferon or interferon "add on" therapy may enhance response rates in selected patients. 71,79 This suggests that interferon-mediated immune clearance may be more effective in clearing the virus when the viral load has been reduced for extended periods.…”

Section: Discussionmentioning

confidence: 99%

A dendritic cell receptor-targeted chimeric immunotherapeutic protein (C-HBV) for the treatment of chronic hepatitis B

Ma¹,

Motyka

Gutfreund

et al. 2019

Human Vaccines & Immunotherapeutics

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In chronic Hepatitis B Virus (HBV) infections HBV-specific T cells are functionally impaired. Immunotherapy may restore HBV-specific T cell responses essential for sustained disease remission offtreatment and induction of a functional cure. Chimigen® Molecules are fusion proteins of antigen(s) with the Fc fragment of a xenotypic antibody designed to target specific receptors on dendritic cells (DCs). Here we describe the production and pre-clinical evaluation of Chimigen® HBV (C-HBV), containing HBV PreS1 and PreS2 peptide fragments, HBV core and murine Fc, produced in insect cells. C-HBV binding to immature DCs and internalization by endocytosis was FcγRII (CD32) and mannose receptor (CD206) dependent and led to increased MHC I and MHC II surface expression. Upon exposure of human T cells isolated from HBV un-infected healthy and chronically HBV-infected donors to C-HBV-pulsed mature DCs ex vivo, C-HBV induced vigorous T cell proliferation and enhanced expression of IFN-γ, TNF-α, perforin and granzyme B in both CD4 + and CD8 + T cell subsets. Re-stimulation of C-HBV-activated T cells from chronically infected donors with HBV PreS1/PreS2 and core overlapping peptides induced IFN-γ production in both CD4 + and CD8 + populations. C-HBV-activation of peripheral blood mononuclear cells (PBMCs) from chronically HBV-infected patients stimulated granzyme B production by CD4 + CD25 − T responder (Tresp) cells, accompanied by an increase in Annexin V staining on CD4 + CD25 + T regulatory (Treg) cell phenotype, consistent with apoptosis. The observed HBV-specific cellular responses induced by C-HBV ex vivo suggest that C-HBV is a promising immunotherapeutic candidate for the treatment of chronic HBV infections.

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“…Currently, the indications for antiviral treatment in chronic HBV infection are mainly based on a combination of the following three criteria: HBV DNA load, ALT levels, and severity of liver disease [ 6 ]. By preventing the progression of liver disease and early liver-related deaths, timely and valid therapy could be highly beneficial for improving quality of life and survival [ 39 ]. We speculate that the frequency of the CCR7 lo PD-1 hi Tfh subset in the blood, which was correlated to the immune status in chronic HBV infection, may help physicians determine when to initiate antiviral treatment.…”

Section: Discussionmentioning

confidence: 99%

Increased CCR7loPD-1hiC

Huang

Zhao

et al. 2018

Canadian Journal of Gastroenterology and Hepatology

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T follicular helper cells (Tfh cells) affect essential immune pathogenesis in chronic hepatitis B virus (HBV) infection. The CCR7loPD-1hi Tfh subset has a partial Tfh effector phenotype and is associated with active Tfh differentiation, whereas the CCR7hiPD-1lo Tfh subset is a resting phenotype. We recruited 20 healthy volunteers and 77 patients with chronic HBV infection, including those in the immune tolerant (IT) phase (n=19), immune clearance (IC) phase (n=20), low replicative (LR) phase (n=18), and reactivation (RA) phase (n=20). The expression of CD4, CXCR5, PD-1, and CCR7 was detected in T cells from peripheral blood by flow cytometry. The frequency of the CCR7loPD-1hi T subset was significantly higher in the patients than in the healthy controls (14.92±4.87% vs 12.23±2.95%, p=0.018). The frequency of this Tfh subset in the IC group (18.42%±3.08) was increased compared with the IT group (11.94±2.87%, p=0.001) and LR group (13.65±4.93%, p=0.031) and was higher in the RA group than in the IT group (16.03±5.37% vs 11.94±2.87%, p=0.030). We observed a weak positive correlation between the CCR7loPD-1hi Tfh subset population and the alanine transaminase (ALT) level (r=0.370, p=0.001). The CCR7loPD-1h Tfh subset in the chronic HBV-infected patients was elevated to various degrees among the different immune phases. CCR7loPD-1hiCXCR5+CD4+ T cells are correlated with the immune status of chronic HBV infection patients and may be developed as a potential indicator for antiviral treatment.

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Treatment of hepatitis B: Is there still a role for interferon?

Cited by 53 publications

References 26 publications

The efficacy of hepatitis B treatments in achieving HBsAg seroclearance: A systematic review and meta‐analysis

The efficacy of hepatitis B treatments in achieving HBsAg seroclearance: A systematic review and meta‐analysis

A dendritic cell receptor-targeted chimeric immunotherapeutic protein (C-HBV) for the treatment of chronic hepatitis B

Increased CCR7loPD-1hiC

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