Unconventional T cells in chronic hepatitis B patients on long‐term suppressive therapy with tenofovir followed by a Peg‐<scp>IFN</scp> add‐on strategy: A randomized study

Cannizzo, Elvira S.; Tincati, Camilla; Binda, Francesca; Ronzi, Paola; Cazzaniga, Federico Angelo; Antinori, Spinello; Monforte, Antonella d’Arminio; Marchetti, Giulia; Milazzo, Laura

doi:10.1111/jvh.12820

Cited by 13 publications

(11 citation statements)

References 45 publications

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“…Out of the 43 studies included, 11‐39 7 were abstracts presented as posters 40‐46 in congresses and 7 full articles were published in Chinese 47‐53 . In 15 studies, patients received antivirals up till enrolment date while in 14 other studies, patients went through 3‐12 months of a washout period before being enrolled.…”

Section: Resultsmentioning

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: Resultsmentioning

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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“…In published RCTs, the loss rate for PEG IFN alone is usually around 4–10% [ 18 – 21 ], but has also been reported in some studies to be above 10% [ 95 , 96 ] (and these also vary by specific genotype [ 97 ]). PEG IFN in combination with a nucleoside analogue has been reported in some cases to be even higher: 20% (2/10 patients) at 60 weeks [ 22 ], and 21% (3/14 patients) at 48 weeks [ 23 ], although low sample sizes seem to have an influence. Also, an HBsAg loss rate of 18.8% (Wong et al [ 52 ]) seems relatively high compared with a rate of 0% (0/33) at 52 weeks [ 98 ], and 10% (7/72) at 48 weeks [ 6 ] as seen in two published RCTs.…”

Section: Discussionmentioning

confidence: 99%

“…This may lead to an under-reporting of FC in clinical trials, observational studies and health economic (HE) models. Most published randomised controlled trials (RCTs) record annual HBsAg loss rates that rarely reach > 4% for nucleoside therapies [12][13][14][15][16][17], and usually around 4-10% for PEG IFN [18][19][20][21] (though 20% [22] and 21% [23] have been seen in some cases, with low sample sizes appearing to have an influence, i.e., two and three patients experiencing HBsAg loss, respectively).…”

Section: Introductionmentioning

confidence: 99%

Are Published Health Economic Models for Chronic Hepatitis B Appropriately Capturing the Benefits of HBsAg Loss? A Systematic Literature Review

Wigfield¹,

Sbarigia

Hashim³

et al. 2019

PharmacoEconomics Open

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Objectives Sustained hepatitis B surface antigen (HBsAg) loss or 'functional cure' (FC) is considered an optimal treatment endpoint by international clinical guidelines for chronic hepatitis B (CHB), yet rarely is this achieved with current standard of care (SoC). This leads to an under-reporting of FC in clinical trials, observational studies and health economic (HE) models. This paper systematically identifies and assesses how FC is incorporated in published HE models of CHB. Methods A systematic literature review was conducted in PubMed and Embase (conducted February 2019) to review how HBsAg loss is captured in HE models. The following items were extracted: rate of (and transition probabilities to) HBsAg loss, HBsAg loss health state costs, and HBsAg loss health state utilities. Results Sixty-five economics evaluations were identified, and < 50% of these (27/65) incorporated HBsAg loss in their models. Only 15/27 stated HBsAg loss health state costs, 15/27 stated HBsAg loss health state utilities, and 11/27 mentioned treatment-specific transition probabilities to HBsAg loss. The majority of sources these inputs were derived from are not transparent. Conclusions The benefits of FC in current HE models are not well captured, as FC is often not reported or not directly related to modelled treatments. This has the potential for novel agents with higher efficacy compared with SoC to be overlooked and undervalued if their worth is not appropriately communicated. In order to ensure optimal access for patients to new and effective therapies, it is important that the benefits of FC are better assessed and captured within HE models.Peter Wigfield and Urbano Sbarigia contributed equally to the work.The benefits of functional cure in current health economic models are not well captured, as functional cure is often not reported or not directly related to modelled treatments.In order to ensure optimal access for patients to new and effective therapies, it is important that the benefits of functional cure are better assessed and captured within health economic models.

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“…Similarly, in patients primed with Peg‐IFNα prior to viral suppression, the maintenance of expanded functional CD56 bright NK cells has been shown to correlate with treatment response . It is noteworthy that the recovery of nonconventional T cells (iNKT and γδ T) was limited despite significant declines in HBsAg in a cohort of patients undergoing combination therapy …”

Section: Viral and Immune Aspects Of Therapymentioning

confidence: 99%

“…27 It is noteworthy that the recovery of nonconventional T cells (iNKT and γδ T) was limited despite significant declines in HBsAg in a cohort of patients undergoing combination therapy. 96 In a study of combination Peg-IFNα with ADV, those patients achieving HBsAg loss demonstrated increased frequency of TRAIL+, IFNγ+ NK cells at the end of treatment. This indicates that NK cells may play a role in the clearance of HBsAg with this therapeutic approach.…”

Section: Nucleos(t)ide Analoguesmentioning

confidence: 99%

The impact of currently licensed therapies on viral and immune responses in chronic hepatitis B: Considerations for future novel therapeutics

Gill

Kennedy

2018

Journal of Viral Hepatitis

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Summary Despite the availability of a preventative vaccine, chronic hepatitis B (CHB) remains a global healthcare challenge with the risk of disease progression due to cirrhosis and hepatocellular carcinoma. Although current treatment strategies, interferon and nucleos(t)ide analogues have contributed to reducing morbidity and mortality related to CHB, these therapies are limited in providing functional cure. The treatment paradigm in CHB is rapidly evolving with a number of new agents in the developmental pipeline. However, until novel agents with functional cure capability are available in the clinical setting, there is a pressing need to optimize currently licensed therapies. Here, we discuss current agents used alone and/or in combination strategies along with the impact of these therapies on viral and immune responses. Novel treatment strategies are outlined, and the potential role of current therapies in the employment of pipeline agents is discussed.

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Unconventional T cells in chronic hepatitis B patients on long‐term suppressive therapy with tenofovir followed by a Peg‐IFN add‐on strategy: A randomized study

Cited by 13 publications

References 45 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

Are Published Health Economic Models for Chronic Hepatitis B Appropriately Capturing the Benefits of HBsAg Loss? A Systematic Literature Review

The impact of currently licensed therapies on viral and immune responses in chronic hepatitis B: Considerations for future novel therapeutics

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