HBsAg loss in chronic hepatitis B: pointers to the benefits of curative therapy

Dusheiko, Geoffrey; Wang, Bo; Carey, Ivana

doi:10.1007/s12072-016-9738-1

Cited by 13 publications

(14 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…HBeAg seroconversion, also called serological response (SR), was defined as the disappearance of HBeAg accompanied by the gain of anti-HBe throughout the treatment-free follow-up [20]. HBsAg loss (HL) indicated the disappearance of HBsAg [14].…”

Section: Definitions Of Treatment Responsesmentioning

confidence: 99%

“…Third, to offer better responses, it remains unclear whether HBV RNA in combination with known HBV biomarkers could offer better predictive performance. Last, it remains unclear whether HBV RNA could predict HBsAg loss which is generally considered as a functional "cure" that signifies a favorable outcome of antiviral treatments [14,15]. To address the above questions, we assessed HBV RNA in a longitudinal cohort of 727 HBeAg-positive patients who randomly received PegIFNα-2a or PegIFNα-2b.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Rapidly decreased HBV RNA predicts responses of pegylated interferons in HBeAg-positive patients: a longitudinal cohort study

Zhang

Shang

et al. 2020

Hepatol Int

View full text Add to dashboard Cite

Background As an important anti-HBV drug, pegylated interferon α (PegIFNα) offers promising clinical efficacy, but biomarkers that accurately forecast treatment responses are yet to be elucidated. Here, we evaluated whether HBV RNA could act as an early monitor of pegylated interferon responses. Methods We analyzed a phase 3, multicenter, randomized cohort of 727 HBeAg-positive non-cirrhotic patients receiving a 48-week treatment of PegIFNα-2a or PegIFNα-2b and a 24-week treatment-free follow-up. Serum levels of HBV RNA, HBV DNA, HBeAg, and HBsAg were measured at weeks 0, 12, 24, 48, and 72. Results HBeAg seroconversion and HBsAg loss at week 72 were observed in 217 (29.8%) and 21 (2.9%) patients, respectively. During the 48-week treatment, HBV RNA decreased more rapidly than HBV DNA and HBsAg, but HBV RNA and HBeAg shared similar dynamics with positive correlations. Multivariate regression analyses consistently revealed the significance of HBV RNA at weeks 0, 12, 24, and 48 to monitor HBeAg seroconversion but not HBsAg loss. Although baseline HBV RNA only showed a modest AUC performance, HBV RNA with a significant increase of AUC at week 12 outperformed other HBV biomarkers to forecast HBeAg seroconversion (p value < 0.05). HBV RNA ≤ 1000 copies/mL was an optimized cutoff at week 12 that offered better prediction than other HBV biomarkers. This optimized cutoff plus patient age, HBV genotype B, and HBeAg offered a strong estimation of HBeAg seroconversion (accuracy 95.2%, true negative rate 99.8%). Conclusion HBV RNA at week 12 is an effective monitor of HBeAg seroconversion in HBeAg-positive patients treated with pegylated interferons.

show abstract

Section: Definitions Of Treatment Responsesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Rapidly decreased HBV RNA predicts responses of pegylated interferons in HBeAg-positive patients: a longitudinal cohort study

Zhang

Shang

et al. 2020

Hepatol Int

View full text Add to dashboard Cite

show abstract

“…Chronic hepatitis B virus (HBV) infection affects 292 million people worldwide, with 600 000 deaths occurring each year from cirrhosis or hepatocellular carcinoma . The hepatitis B surface antigen (HBsAg) is an abundant viral protein present in the blood of infected patients, and its clearance during treatment is a highly reliable indicator of the restoration of immune response and subsequent functional cure of chronic hepatitis B . From the pre‐S/S open reading frame (ORF), 3 proteins are translated: L (large), M (medium) and S (small)‐HBsAg (Figure ), all of which contain the major hydrophilic region (MHR) spanning amino acids (aa) 99‐169.…”

Section: Introductionmentioning

confidence: 99%

Variants of hepatitis B virus surface antigen observed during therapy with nucleic acid polymer REP 2139‐Ca have no influence on treatment outcome and its detection by diagnostic assays

Mijočević

Karimzadeh

Seebach

et al. 2018

Journal of Viral Hepatitis

View full text Add to dashboard Cite

Summary The treatment of patients suffering from HBeAg‐positive chronic hepatitis B with REP 2139‐Ca resulted in potent reductions in HBsAg and HBV DNA, seroconversion to anti‐HBs and the establishment of functional control of infection. In this cohort of 12 patients, we investigated whether differences between HBsAg sequences might explain the lack of response to REP 2139‐Ca observed in 3 of 12 patients. We also assessed if the reduction or complete loss of HBsAg in serum observed during therapy were caused by mutations in the “a” determinant preventing the detection of HBsAg by standard diagnostic assays. The complete pre‐S/S open reading frame (ORF) was sequenced and pre‐S1, pre‐S2 and S amino acid sequences were analysed. We found no major differences between pre‐S1, pre‐S2 and S sequences in responders and nonresponders correlated with low reduction in HBsAg. In addition, we found no mutations in the “a” determinant that would significantly affect the reactivity of HBsAg in diagnostic assays. These results demonstrate that the amino acid sequence of complete pre‐S/S ORF has no direct influence on response to REP 2139‐Ca therapy.

show abstract

“…considered the best indicator of the establishment of functional control over HBV infection which endures in the absence of therapy. (3)(4)(5) Currently approved treatments include nucleos(t)ide analogs (NUCs) that block the maturation of HBV by inhibiting the viral polymerase and interferon (IFN)-based therapy to improve host immune control of HBV infection. (6,7) However, although NUCs suppress HBV DNA and control the progression to fibrosis, they rarely result in HBsAg loss, and IFN-based therapy can only achieve HBsAg loss in a small fraction of treated patients, (8,9) indicating the need for new therapies capable of directly targeting HBsAg clearance from the blood.…”

mentioning

confidence: 99%

Nucleic acid polymer REP 2139 and nucleos(T)ide analogues act synergistically against chronic hepadnaviral infection in vivo in Pekin ducks

et al. 2018

View full text Add to dashboard Cite

Nucleic acid polymer (NAP) REP 2139 treatment was shown to block the release of viral surface antigen in duck HBV (DHBV)‐infected ducks and in patients with chronic HBV or HBV/hepatitis D virus infection. In this preclinical study, a combination therapy consisting of REP 2139 with tenofovir disoproxil fumarate (TDF) and entecavir (ETV) was evaluated in vivo in the chronic DHBV infection model. DHBV‐infected duck groups were treated as follows: normal saline (control); REP 2139 TDF; REP 2139 + TDF; and REP 2139 + TDF + ETV. After 4 weeks of treatment, all animals were followed for 8 weeks. Serum DHBsAg and anti‐DHBsAg antibodies were monitored by enzyme‐linked immunosorbent assay and viremia by qPCR. Total viral DNA and covalently closed circular DNA (cccDNA) were quantified in autopsy liver samples by qPCR. Intrahepatic DHBsAg was assessed at the end of follow‐up by immunohistochemistry. On‐treatment reduction of serum DHBsAg and viremia was more rapid when REP 2139 was combined with TDF or TDF and ETV, and, in contrast to TDF monotherapy, no viral rebound was observed after treatment cessation. Importantly, combination therapy resulted in a significant decrease in intrahepatic viral DNA (>3 log) and cccDNA (>2 log), which were tightly correlated with the clearance of DHBsAg in the liver. Conclusion: Synergistic antiviral effects were observed when REP 2139 was combined with TDF or TDF + ETV leading to control of infection in blood and liver, associated with intrahepatic viral surface antigen elimination that persisted after treatment withdrawal. Our findings suggest the potential of developing such combination therapy for treatment of chronically infected patients in the absence of pegylated interferon. (Hepatology 2018;67:2127‐2140).

show abstract

HBsAg loss in chronic hepatitis B: pointers to the benefits of curative therapy

Cited by 13 publications

References 21 publications

Rapidly decreased HBV RNA predicts responses of pegylated interferons in HBeAg-positive patients: a longitudinal cohort study

Rapidly decreased HBV RNA predicts responses of pegylated interferons in HBeAg-positive patients: a longitudinal cohort study

Variants of hepatitis B virus surface antigen observed during therapy with nucleic acid polymer REP 2139‐Ca have no influence on treatment outcome and its detection by diagnostic assays

Nucleic acid polymer REP 2139 and nucleos(T)ide analogues act synergistically against chronic hepadnaviral infection in vivo in Pekin ducks

Contact Info

Product

Resources

About