scholarly journals Functional cure for chronic hepatitis B: accessibility, durability, and prognosis

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Aixin Song ◽  
Xiao Lin ◽  
Xinyue Chen
Keyword(s):  
Hepatitis B ◽  
Drug Withdrawal ◽  
Hepatitis B Surface Antigen ◽  
Antiviral Treatment ◽  
Treatment Strategies ◽  
Treatment Method ◽  
Recent Application ◽  
Functional Cure ◽  
Hbsag Clearance ◽  
The Ideal

AbstractHepatitis B surface antigen (HBsAg) clearance is regarded as the ideal endpoint for antiviral treatment in terms of drug withdrawal safety and improvements in prognosis. However, the overall rate of HBsAg clearance is low and differs based on treatment method and course. The recent application of combined and extended treatment strategies have improved the HBsAg clearance rate, and several patients achieved HBsAg clearance in clinical treatment. In addition, the durability of and clinical outcomes after HBsAg clearance have become the focus of both researchers and clinicians. This article reviews HBsAg clearance in terms of accessibility, durability, improvements in prognosis and relevant advances.

scholarly journals Hepatitis D virus in 2021: virology, immunology and new treatment approaches for a difficult-to-treat disease

Gut ◽  
2021 ◽  
pp. gutjnl-2020-323888
Author(s):  
Stephan Urban ◽  
Christoph Neumann-Haefelin ◽  
Pietro Lampertico
Keyword(s):  
Hepatitis B ◽  
Hepatitis B Surface Antigen ◽  
Treatment Strategies ◽  
Phase Iii ◽  
Interferon Α ◽  
T Cell Epitopes ◽  
The European Union ◽  
Hepatitis D ◽  
Hepatitis D Virus

Approximately 5% of individuals infected with hepatitis B virus (HBV) are coinfected with hepatitis D virus (HDV). Chronic HBV/HDV coinfection is associated with an unfavourable outcome, with many patients developing liver cirrhosis, liver failure and eventually hepatocellular carcinoma within 5–10 years. The identification of the HBV/HDV receptor and the development of novel in vitro and animal infection models allowed a more detailed study of the HDV life cycle in recent years, facilitating the development of specific antiviral drugs. The characterisation of HDV-specific CD4+ and CD8+T cell epitopes in untreated and treated patients also permitted a more precise understanding of HDV immunobiology and possibly paves the way for immunotherapeutic strategies to support upcoming specific therapies targeting viral or host factors. Pegylated interferon-α has been used for treating HDV patients for the last 30 years with only limited sustained responses. Here we describe novel treatment options with regard to their mode of action and their clinical effectiveness. Of those, the entry-inhibitor bulevirtide (formerly known as myrcludex B) received conditional marketing authorisation in the European Union (EU) in 2020 (Hepcludex). One additional drug, the prenylation inhibitor lonafarnib, is currently under investigation in phase III clinical trials. Other treatment strategies aim at targeting hepatitis B surface antigen, including the nucleic acid polymer REP2139Ca. These recent advances in HDV virology, immunology and treatment are important steps to make HDV a less difficult-to-treat virus and will be discussed.

scholarly journals Pegylated Interferon Treatment for the Effective Clearance of Hepatitis B Surface Antigen in Inactive HBsAg Carriers: A Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Aixin Song ◽  
Xiao Lin ◽  
Junfeng Lu ◽  
Shan Ren ◽  
Zhenhuan Cao ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Antiviral Therapy ◽  
Clearance Rate ◽  
Hepatitis B Surface Antigen ◽  
Meta Analysis ◽  
Pegylated Interferon ◽  
Hbsag Level ◽  
Hbsag Carriers ◽  
Hbsag Clearance ◽  
Ifn Treatment

BackgroundExpanding antiviral therapy to benefit more populations and optimizing treatment to improve prognoses are two main objectives in current guidelines on antiviral therapy. However, the guidelines do not recommend antiviral therapy for inactive hepatitis B surface antigen (HBsAg) carriers (IHCs). Recent studies have shown that antiviral therapy is effective with good treatment outcomes in IHC populations. We conducted a systematic review and meta-analysis of HBsAg clearance and conversion in IHCs.MethodsWe searched PubMed, Embase, Medline, and Web of Science to retrieve articles on HBsAg clearance in IHCs published between January 2000 and August 2021. Data were collected and analysed using the random-effects model for meta-analysis.ResultsA total of 1029 IHCs from 11 studies were included in this analysis. The overall HBsAg clearance rate was 47% (95% confidence interval (CI): 31% - 64%), with a conversion rate of 26% (95% CI: 15% - 38%) after 48 weeks of Pegylated interferon (Peg-IFN) treatment. In the control group (including nucleos(t)ide analogue (NA) treatment or no treatment), the overall HBsAg clearance rate was only 1.54% (95% CI: 0.56% - 3.00%), which was markedly lower than that in the Peg-IFN group. Further analysis showed that a low baseline HBsAg level and long treatment duration contributed to a higher HBsAg clearance rate.ConclusionThis study showed that treatment of IHCs can be considered to achieve a clinical cure for chronic hepatitis B virus (HBV) infection. After Peg-IFN treatment, the HBsAg clearance rate was 47%, and the conversion rate was 26%, which are markedly higher than those reported by previous studies on Peg-IFN treatment in patients with chronic hepatitis B (CHB). A low baseline HBsAg level and long treatment duration were associated with HBsAg clearance in IHCs. Therefore, antiviral therapy is applicable for IHCs, a population who may be clinically cured.Systematic Review Registrationhttp://www.crd.york.ac.uk/PROSPERO, CRD): CRD42021259889.

Early Hepatitis B Surface Antigen Seroclearance Following Antiviral Treatment in Patients with Reactivation of Resolved Hepatitis B

2019 ◽  
Vol 64 (10) ◽  
pp. 2992-3000
Author(s):  
Hae Lim Lee ◽  
Jeong Won Jang ◽  
Ji Won Han ◽  
Sung Won Lee ◽  
Si Hyun Bae ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Surface Antigen ◽  
Hepatitis B Surface Antigen ◽  
Antiviral Treatment

scholarly journals Time to seroconversion of HBsAg to anti-HBs in individuals who lost HBsAg during follow-up

2016 ◽  
Vol 144 (12) ◽  
pp. 2648-2653 ◽  
Author(s):  
M. R. H. ROUSHAN ◽  
M. MOHAMMADPOUR ◽  
M. BAIANY ◽  
S. SOLEIMANI ◽  
A. BIJANI
Keyword(s):  
Hepatitis B ◽  
Surface Antigen ◽  
Hepatitis B Surface Antigen ◽  
Liver Function Tests ◽  
Hbsag Clearance ◽  
Positive Antibody ◽  
B Virus ◽  
The Mean ◽  
Cumulative Probabilities

SUMMARYTo determine the time to appearance of antibody against hepatitis B surface antigen (anti-HBs) after clearance of hepatitis B surface antigen (HBsAg) in chronically infected individuals, we followed up 3963 cases with positive antibody against hepatitis B e antigen (anti-HBe) from 1991 to 2014. Of these, 101 (67 males, 34 females) lost HBsAg. These serocleared cases were checked every 6-month interval regarding HBsAg, anti-HBs, liver function tests, and liver sonography. Hepatitis B virus DNA was assessed at the time of seroclearance or the appearance of anti-HBs. The mean age of these patients at entry to this study was 34·4 ± 13 years. The mean follow-up duration until seroclearance of HBsAg was 6·6 ± 4·3 years. After the mean follow-up of 43·7 ± 45 months, anti-HBs appeared in 64 (63·4%) cases. The cumulative probabilities of anti-HBs appearance for 2, 5 and 10 years were 24·3%, 58% and 78·2%, respectively. The appearance of anti-HBs was associated with age ⩾35 years and seroclearance of HBsAg (hazard ratio 1·96, 95% confidence interval 1·32–3·38,P= 0·016) but not with sex. The results show that anti-HBs may develop in 78·2% of cases within 10 years of HBsAg clearance. Age ⩾35 years at HBsAg loss was associated with earlier development of anti-HBs.

scholarly journals Cessation of nucleos(t)ide analogues therapy in chronic hepatitis B: a systematic review and meta-analysis

2020 ◽  
Author(s):  
Yandi Xie ◽  
Rui Jin ◽  
Guangjun Song ◽  
Hui Ma ◽  
Bo Feng
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Virological Response ◽  
Hepatitis B Surface Antigen ◽  
Meta Analysis ◽  
Hbsag Clearance ◽  
Virological Relapse ◽  
Antigen Loss

Abstract Background To address the possibility of safe cessation of nucleos(t)ide analogues (NAs) therapy in chronic hepatitis B (CHB) and to identify factors associated with off-NAs virological relapse (VR). Methods A published work search was performed to identify all published studies including patients who ceased NAs and were followed for ≥12 months. A meta-analysis was performed. Results Twenty-six studies involving 2573 patients who discontinued NAs were included. The pooled rate of off-NAs VR was 0.63, being lower in initially hepatitis B e antigen (HBeAg)-positive than HBeAg-negative patients (0.57 versus 0.62, P = 0.732). The pooled rates of VR were 0.47, 0.55, 0.61, 0.51, 0.73 and 0.64 at 6, 12, 24, 36, 48 and 60 months after NAs cessation, respectively, being relatively lower in initially HBeAg–positive (0.31, 0.45, 0.55, 0.44, 0.48, 0.52) than HBeAg-negative patients (0.50, 0.55, 0.69, 0.57, 0.53, 0.68) (P = 0.405). The pooled rate of biochemical relapse was 0.44, being lower in initially HBeAg-positive than HBeAg-negative patients (0.43 versus 0.48, P = 0.554). The pooled rates of hepatitis B surface antigen loss and seroconversion was 0.09 and 0.06, respectively. The pooled rates of VR at 12 months after NAs cessation were significant different between duration of on-NAs virological response ≤24 months and >24 months in all patients (0.55 versus 0.41, P = 0.011), initially HBeAg-positive patients (0.59 versus 0.41, P = 0.031), and initially HBeAg-negative patients (0.53 versus 0.37, P = 0.025). Conclusions Safe cessation of NAs therapy seems to be feasible in a substantial proportion of CHB patients. On-NAs virological response >24 months reduces the risk of off-NAs VR. Stopping NAs treatment may have an impact on long-term HBsAg decline and also HBsAg clearance.

scholarly journals The role of hepatitis B surface antibodies in HBV infection, disease and clearance

2020 ◽  
Vol 15 (5) ◽  
pp. 293-306
Author(s):  
Nadia Warner ◽  
Stephen Locarnini ◽  
Hui Xu
Keyword(s):  
Hepatitis B ◽  
Viral Entry ◽  
Hepatitis B Surface Antigen ◽  
Hbv Infection ◽  
Functional Cure ◽  
Direct Acting Antiviral ◽  
Active Viral Replication ◽  
Infection Disease ◽  
Direct Acting

The clinical sequelae associated with chronic HBV infection is generally regarded as a consequence of an inadequate and inappropriate immune response to active viral replication, predominantly at the T-cell level. However, recent studies on hepatitis B surface antigen (HBsAg)-specific B cells and hepatitis B surface antibody (anti-HB) responses have identified their previously unrecognized role in the pathogenesis of chronic hepatitis B (CHB). These studies have also uncovered novel therapeutic approaches to more effectively target HBsAg loss and seroconversion, an important end point and regarded as a functional cure. Anti-HBs IgG has also been shown to have multiple direct acting antiviral roles with the Fab component directly blocking viral entry, and release while the Fc component has been linked to antibody dependent cellular cytotoxicity. Likewise, the HBsAg-specific B-cell dysfunctionality can be reversed providing new therapeutic opportunities to achieve functional cure in CHB.

scholarly journals Missed Opportunities for Prevention of Perinatal Transmission of Hepatitis B: A Retrospective Cohort Study

2014 ◽  
Vol 28 (10) ◽  
pp. 525-528 ◽  
Author(s):  
Julie van Schalkwyk ◽  
Melica Nourmoussavi ◽  
Andrea Massey ◽  
Reka Gustafson ◽  
Elizabeth Brodkin ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Hepatitis B Surface Antigen ◽  
Antiviral Treatment ◽  
Perinatal Transmission ◽  
Hbv Dna ◽  
Missed Opportunities ◽  
Positive Hbsag ◽  
Hbv Prevalence ◽  
Lost To Follow Up ◽  
Hbv Transmission

BACKGROUND: Perinatal transmission of hepatitis B virus (HBV) can occur despite postexposure prophylaxis (PEP). Recent literature suggests that antiviral treatment during pregnancy when maternal HBV DNA levels are elevated can further decrease vertical transmission. However, HBV DNA screening is not routinely performed antenatally.OBJECTIVE: To determine the rates of HBV prevalence and perinatal transmission in an antenatal cohort.METHODS: A retrospective review of public health records (December 2008 to December 2010) was performed for both mothers and newborns.RESULTS: A total of 725 mother-infant pairs were included. Of these, 574 of 715 (80%) women had antenatal hepatitis B e antigen (HBeAg) testing performed, and 127 of 574 (22%) were HBeAg positive (HBeAg+). Of babies born to hepatitis B surface antigen-positive (HBsAg+) mothers, only 573 of 725 (79%) received complete PEP. In addition, 172 of 725 (24%) infants did not receive post-PEP blood testing or were lost to follow-up. Of the 552 infants with results available, seven cases (1.3%) of mother-to-child HBV transmission were observed, six of which involved infants born to HBeAg+ women.CONCLUSIONS: Our findings suggest that routine HBeAg screening could identify a subset of mother-infant pairs among HBsAg+ pregnant women who are at higher risk for vertical HBV transmission. Determination of viral load in expectant HBeAg+ mothers may provide more precise insight into HBV transmission to their infants.

scholarly journals Usefulness of a Hepatitis B Surface Antigen-Based Model for the Prediction of Functional Cure in Patients with Chronic Hepatitis B Virus Infection Treated with Nucleos(t)ide Analogues: A Real-World Study

2021 ◽  
Vol 10 (15) ◽  
pp. 3308
Author(s):  
Gian Paolo Caviglia ◽  
Yulia Troshina ◽  
Enrico Garro ◽  
Marcantonio Gesualdo ◽  
Serena Aneli ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Surface Antigen ◽  
Hepatitis B Surface Antigen ◽  
Functional Cure ◽  
Hbsag Loss ◽  
Chronic Hepatitis B Virus ◽  
Long Term Treatment ◽  
Hbsag Seroclearance

In patients with chronic hepatitis B (CHB) under long-term treatment with nucleso(t)ide analogues (NAs), the loss of hepatitis B surface antigen (HBsAg) is a rare event. A growing body of evidence supports the use of quantitative HBsAg for the prediction of functional cure, although these results are mainly derived from studies performed on Asian patients with hepatitis B e antigen (HBeAg)-positive CHB. Here, we investigated the clinical role of quantitative HBsAg in a real-life cohort of CHB patients under treatment with NAs in a tertiary care center from North-West Italy. A total of 101 CHB patients (HBeAg-negative, n = 86) undergoing NAs treatment were retrospectively enrolled. HBsAg was measured at baseline (T0), 6 months (T1), 12 months (T2) and at the last follow-up (FU). Median FU was 5.5 (3.2–8.3) years; at the end of FU, 11 patients lost the HBsAg (annual incidence rate = 1.8%). Baseline HBsAg levels were significantly different between patients with no HBsAg loss and those achieving a functional cure (3.46, 2.91–3.97 vs. 1.11, 0.45–1.98 Log IU/mL, p < 0.001). Similarly, the HBsAg decline (Δ) from T0 to T2 was significantly different between the two groups of patients (0.05, −0.04–0.13, vs. 0.38, 0.11–0.80 Log IU/mL, p = 0.002). By stratified cross-validation analysis, the combination of baseline HBsAg and ΔHBsAg T0–T2 showed an excellent accuracy for the prediction of HBsAg loss (C statistic = 0.966). These results corroborate the usefulness of quantitative HBsAg in Caucasian CHB patients treated with antivirals for the prediction of HBsAg seroclearance.

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