What will it take to cure hepatitis B?

Jeng, Wen–Juei; Lok, Anna S.

doi:10.1097/hc9.0000000000000084

Cited by 14 publications

(11 citation statements)

References 89 publications

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“…Functional cure is the ultimate objective of HBV infection treatment. HBsAg is a clinically available biomarker of functional cure, whereas hepatitis B core-related antigen (HBcrAg) and HBV RNA are not clinically available [5,15,16]. Importantly, patients who achieve HBsAg seroclearance exhibit better prognosis and are at a lower risk for HCC [17,18].…”

Section: Discussionmentioning

confidence: 99%

“…Despite its ability to suppress HBV replication and reduce hepatocellular inflammation, NUC therapy cannot completely eradicate HBV [2][3][4]. The ultimate goal for a functional HBV cure is rarely achieved, despite long-term NUC therapy [5]. In two cohort studies investigating outcomes following long-term entecavir or TDF treatment, the 8-and 10-year cumulative HBsAg seroclearance incidence rates were 1.69% and 2.11%, respectively [6,7].…”

Section: Introductionmentioning

confidence: 99%

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Long-Term Hepatitis B Surface Antigen Profile and Seroclearance Following Antiviral Treatment: A Single-Center, Real-World Cohort Study

Huang,

Yang,

et al. 2023

Biomedicines

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Hepatitis B surface antigen (HBsAg) seroclearance, an indicator of recovery from hepatitis B virus (HBV) infection, is uncommon in long-term nucleos(t)ide analog (NUC) therapy. We compared the incidence of HBsAg seroclearance in patients with and without NUC discontinuation to identify predictors of HBsAg seroclearance. This retrospective study enrolled adult patients with a chronic HBV infection followed for ≥12 months after NUC discontinuation (finite group) and those treated with NUCs for >3 years (non-finite group). Demographic, clinical, and laboratory data were analyzed. The study cohort included 978 patients, including 509 and 469 patients in the finite and non-finite groups, respectively. Cumulative HBsAg seroclearance incidence was significantly higher in the finite group than in the non-finite group (p = 0.006). The 5- and 10-year cumulative HBsAg seroclearance incidence were 6.6% and 18.9% in the finite group and 3% and 14.6% in the non-finite group, respectively. The likelihood of HBsAg seroclearance was higher in those with end of treatment (EOT) HBsAg levels of <100 IU/mL and in those without clinical relapse (CR). The cumulative 3-year CR incidence was 16.8%. The incidence of liver decompensation and hepatocellular carcinoma were 4.1 and 0.4 per 1000 person-years, respectively. The hepatocellular carcinoma incidence did not significantly differ between the finite and non-finite groups (p = 0.941). In conclusion, higher HBsAg seroclearance incidence in patients receiving finite therapy, and the increased likelihood of HBsAg seroclearance in those with EOT HBsAg levels of <100 IU/mL and in those without CR should be considered during decision-making of treatment options.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Long-Term Hepatitis B Surface Antigen Profile and Seroclearance Following Antiviral Treatment: A Single-Center, Real-World Cohort Study

Huang,

Yang,

et al. 2023

Biomedicines

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“…In fact, the complex interactions established early between virus and host make it difficult to obtain a therapy able to definitely eradicate HBV. A definitive cure from HBV infection should therefore provide for the destruction of the cccDNA and the integrated viral genome [131]. For these reasons, alternative therapeutic strategy targeting steps in the HBV life cycle other than its replication are being evaluated.…”

Section: Therapeutic Implicationsmentioning

confidence: 99%

“…A definitive "cure" for HBV infection able to induce not only HBsAg loss, but, above all, to eradicate cccDNA and the viral genome that has been integrated in that of the host, appears to be still far away. [131]. Numerous targeting virus entry molecules (bulevirtide), capsid assembly modulators (CAMs) and viral protein productions and HBV DNA replications (siRNAs and antisense oligonucleotides) are being researched in pre-clinical and clinical trials.…”

Section: Open Issues and Perspectives In Hbv Infection Therapymentioning

confidence: 99%

HBV Infection and Host Interactions: The Role in Viral Persistence and Oncogenesis

Nevola

Beccia

Rosato³

et al. 2023

IJMS

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Hepatitis B virus (HBV) is a major cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Despite the advent of vaccines and potent antiviral agents able to suppress viral replication, recovery from chronic HBV infection is still an extremely difficult goal to achieve. Complex interactions between virus and host are responsible for HBV persistence and the risk of oncogenesis. Through multiple pathways, HBV is able to silence both innate and adaptive immunological responses and become out of control. Furthermore, the integration of the viral genome into that of the host and the production of covalently closed circular DNA (cccDNA) represent reservoirs of viral persistence and account for the difficult eradication of the infection. An adequate knowledge of the virus–host interaction mechanisms responsible for viral persistence and the risk of hepatocarcinogenesis is necessary for the development of functional cures for chronic HBV infection. The purpose of this review is, therefore, to analyze how interactions between HBV and host concur in the mechanisms of infection, persistence, and oncogenesis and what are the implications and the therapeutic perspectives that follow.

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“… 8 , 9 Many new drugs aiming for HBV functional cure such as direct-acting antivirals, viral antigen production/release inhibitors, and immunomodulators are in development, many of which are being or have been tested in Phase II clinical trials with some promising readouts. 10 …”

Section: Introductionmentioning

confidence: 99%

Awareness of HBV Functional Cure and Attitude Toward Related Clinical Trials Among Patients with Chronic Hepatitis B in China

Duan,

Dong,

Liu

et al. 2023

PPA

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Purpose HBV functional cure is an optimal treatment goal for chronic hepatitis B (CHB) at present and numerous new drugs aiming for HBV functional cure are in development. We carried out an internet-based survey to understand the treatment status, unmet needs, awareness of HBV functional cure and attitude toward related clinical trials among CHB patients in China. Patients and Methods An internet-based anonymous survey was conducted on CHB patients who reside in mainland China. Determinants of awareness and attitude were identified by logistic regression models. Results Of the 1220 CHB patients who completed the survey questionnaire, 11.1% (135/1220) were aware of HBV functional cure and 50.2% (612/1220) answered “definitely will” to participate in related clinical trials. Participants who knew their HBsAg level (HBsAg<1500 IU/mL: OR=3.03, 95% CI: 1.87–4.92; HBsAg≥1500 IU/mL: OR=2.57, 95% CI: 1.35–4.88), who expected to achieve HBsAg loss with treatment (OR=1.63, 95% CI: 1.07–2.50) and who were dissatisfied with current treatment due to the failure of achieving HBsAg loss (OR=1.67, 95% CI: 1.10–2.53) had better awareness of HBV functional cure. Participants who had HBsAg level less than 1500 IU/mL (OR=1.45, 95% CI: 1.05–1.99), treatment with pegylated interferon alpha with or without nucleos(t)ide (OR=1.68, 95% CI: 1.11–2.53) and better awareness of HBV functional cure (OR=1.62, 95% CI: 1.01–2.61) were more likely to say “definitely will” to participate in related clinical trials. Conclusion Chinese CHB patients reported a low awareness of HBV functional cure. Although CHB patients in China reported a low rate of HBV functional cure awareness, they had a high acceptance of related clinical trials.

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What will it take to cure hepatitis B?

Cited by 14 publications

References 89 publications

Long-Term Hepatitis B Surface Antigen Profile and Seroclearance Following Antiviral Treatment: A Single-Center, Real-World Cohort Study

Long-Term Hepatitis B Surface Antigen Profile and Seroclearance Following Antiviral Treatment: A Single-Center, Real-World Cohort Study

HBV Infection and Host Interactions: The Role in Viral Persistence and Oncogenesis

Awareness of HBV Functional Cure and Attitude Toward Related Clinical Trials Among Patients with Chronic Hepatitis B in China

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