Moving toward hepatitis B virus functional cure - the impact of on-treatment kinetics of serum viral markers

Liang, Lilian Yan; Wong, Vincent Wai‐Sun; Wong, Grace Lai–Hung; Yip, Terry Cheuk‐Fung

doi:10.3350/cmh.2022.0333

Cited by 4 publications

(4 citation statements)

References 19 publications

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“…Lower HBsAg level [10][11][12], a strong kinetic of HBsAg level decline [11,13,14], older age [12,15,16], negative hepatitis B e antigen (HBeAg) [10,16], and lower HBV DNA [10,12,17,18] are associated with an increased likelihood of HBsAg seroclearance. The Asian population with CHB also has a lower incidence of HBsAg seroclearance than the non-Asian population [11,19], which may be related to a different mode of infection and duration of chronic infection.…”

Section: Factors Associated With Hbsag Seroclearancementioning

confidence: 99%

“…Low quantitative HBsAg [10][11][12]19], e.g., < 100 IU/mL for Asians and < 1,000 IU/mL for Caucasians [12,30] Strong kinetic of HBsAg level decline [11,13] Low HBV DNA level, e.g., HBV DNA level < 2,000 IU/mL in untreated patients [12]; pretreatment HBV DNA level < 20,000 IU/mL [17]; HBV DNA level < 100 IU/mL at week 24 after antiviral treatment cessation [18] Negative HBeAg [10,16] Older age [11,12,16] Non-Asian population [11,19,30] HCV co-infection [21] Novel HBV treatments such as siRNA and ASO [31] Factors associated with a higher likelihood of HBsAg seroclearance…”

Section: Factors Descriptionsmentioning

confidence: 99%

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Hepatocellular carcinoma surveillance after HBsAg seroclearance

Lai,

Hui,

Wong

et al. 2024

Explor Dig Dis

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Hepatitis B surface antigen (HBsAg) seroclearance is considered the functional cure and the optimal treatment endpoint for chronic hepatitis B (CHB). Patients with CHB who cleared HBsAg generally have a favorable clinical course with minimal risk of developing hepatocellular carcinoma (HCC) or cirrhotic complications. Nevertheless, a minority of patients still develop HCC despite HBsAg seroclearance. While patients with liver cirrhosis are still recommended for HCC surveillance, whether other non-cirrhotic patients who achieved HBsAg seroclearance should remain on HCC surveillance remains unclear. This review provides an overview of the incidence of HBsAg seroclearance, the factors associated with the occurrence of HBsAg seroclearance, the durability of HBsAg seroclearance, the risk of developing HCC after HBsAg seroclearance, the risk factors associated with HCC development after HBsAg seroclearance, the role of HCC risk scores, and the implications on HCC surveillance. Existing HCC risk scores have a reasonably good performance in patients after HBsAg seroclearance. In the era of artificial intelligence, future HCC risk prediction models based on artificial intelligence and longitudinal clinical data may further improve the prediction accuracy to establish a foundation of a risk score-based HCC surveillance strategy. As different novel hepatitis B virus (HBV) antiviral agents aiming at HBsAg seroclearance are under active development, new knowledge is anticipated on the natural history and HCC risk prediction of patients treated with new HBV drugs.

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Section: Factors Associated With Hbsag Seroclearancementioning

confidence: 99%

Section: Factors Descriptionsmentioning

confidence: 99%

Hepatocellular carcinoma surveillance after HBsAg seroclearance

Lai,

Hui,

Wong

et al. 2024

Explor Dig Dis

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“… 11 Because HBsAg loss (defined as undetectable HBsAg with current assays) is associated with an improvement in liver-related outcomes 12 including a further decrease in hepatocellular carcinoma risk compared with HBV DNA suppression without HBsAg loss, 13 the suppression of both HBV DNA and HBsAg along with normal alanine aminotransferase (ALT) level (termed functional cure) is considered a desirable clinical endpoint. 14 However, the HBsAg loss rate with NUCs is <10% after many years of therapy. 15 …”

Section: Introductionmentioning

confidence: 99%

Rapid monophasic HBsAg decline during nucleic-acid polymer–based therapy predicts functional cure

Hershkovich

Shekhtman

Bazinet³

et al. 2023

Hepatology Communications

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Background and Aims: Analyzing the interplay among serum HBV DNA, HBsAg, anti-HBs, and alanine aminotransferase (ALT) during nucleic-acid polymer (NAP)-based therapy for chronic hepatitis B provides a unique opportunity to identify kinetic patterns associated with functional cure. Methods: All participants with HBeAg-negative chronic HBV infection in the REP 401 study (NCT02565719) first received 24 weeks of tenofovir-disoproxil-fumarate (TDF) monotherapy. The early triple therapy group (n = 20) next received 48 weeks of TDF+pegylated interferon-α2a (pegIFN)+NAPs. In contrast, the delayed triple therapy group (n = 20) next received 24 weeks of TDF+pegIFN before 48 weeks of triple therapy. Three participants discontinued treatment and were excluded. Functional cure (HBsAg and HBV DNA not detectable with normal ALT) was assessed at 48 weeks post-treatment. Different kinetic phases were defined by at least a 2-fold change in slope. A single-phase decline was categorized as monophasic, and 2-phase declines were categorized as biphasic. Results: Fourteen (35%) participants achieved a functional cure. HBV DNA remained below or near undetectable for all participants by the end of TDF monotherapy and during subsequent combination therapies. Three HBsAg kinetic patterns were found in both the early and delayed groups, nonresponders (n = 4 and n = 4), monophasic (n = 11 and n = 11), and biphasic (n = 4 and n = 3), respectively. All participants who achieved a functional cure had a monophasic HBsAg kinetic pattern during triple therapy. Among participants with a monophasic HBsAg decline, those who had a functional cure had a shorter median time to HBsAg loss of 21 (interquartile range=11) weeks compared with those who did not achieve functional cure [median: 27 (7) weeks] (p = 0.012). Conclusions: Functional cure was associated with a rapid monophasic HBsAg decline during NAP-based therapy. A nonmonophasic HBsAg kinetic pattern had a 100% negative predictive value (NPV) for a functional cure.

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“…We sincerely appreciate the editorial piece from Liang et al [ 1 ] reviewing our recent paper on the role of early on-treatment decline in viral biomarkers in predicting favourable hepatitis surface antigen (HBsAg) response in chronic hepatitis B (CHB) infection, published in Clinical and Molecular Hepatology [ 2 ]. We agree with Liang and co-authors on the potential use of hepatitis B core-related antigen (HBcrAg) and hepatitis B virus (HBV) pre-genomic RNA (pgRNA) in multiple facets of management in the clinical context of CHB infection.…”

mentioning

confidence: 99%

Correspondence on Editorial regarding “HBV pgRNA and HBcrAg reductions at week 4 predict favourable HBsAg response upon long-term nucleos(t)ide analogue in CHB”

2023

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We sincerely appreciate the editorial piece from Liang, Wong, Wong and Yip 1 reviewing our recent paper on the role of early on-treatment decline in viral biomarkers in predicting favourable HBsAg response in chronic hepatitis B infection, published in Clinical and Molecular Hepatology. 2 We agree with Liang and co-authors on the potential use of hepatitis B core-related antigen (HBcrAg) and hepatitis B virus (HBV) pre-genomic RNA (pgRNA) in multiple facets of management in the clinical context of chronic hepatitis B (CHB) infection. Our study provided serum-liver correlations in the magnitude of decline in viral biomarkers upon nucleos(t)die analogue (NA) treatment

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Moving toward hepatitis B virus functional cure - the impact of on-treatment kinetics of serum viral markers

Cited by 4 publications

References 19 publications

Hepatocellular carcinoma surveillance after HBsAg seroclearance

Hepatocellular carcinoma surveillance after HBsAg seroclearance

Rapid monophasic HBsAg decline during nucleic-acid polymer–based therapy predicts functional cure

Correspondence on Editorial regarding “HBV pgRNA and HBcrAg reductions at week 4 predict favourable HBsAg response upon long-term nucleos(t)ide analogue in CHB”

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