scholarly journals Combination of Entecavir or Tenofovir with Pegylated Interferon-α for Long-Term Reduction in Hepatitis B Surface Antigen Levels: Simultaneous, Sequential, or Add-on Combination Therapy

2021 ◽  
Vol 22 (3) ◽  
pp. 1456
Author(s):  
Kanako Yoshida ◽  
Masaru Enomoto ◽  
Akihiro Tamori ◽  
Shuhei Nishiguchi ◽  
Norifumi Kawada
Keyword(s):  
Hepatitis B ◽  
Combination Therapy ◽  
Surface Antigen ◽  
Hepatitis B Surface Antigen ◽  
Hbv Dna ◽  
Hbv Infection ◽  
Interferon Α ◽  
Chronic Hepatitis B Virus ◽  
Hbsag Seroclearance

Seroclearance of hepatitis B surface antigen (HBsAg) (“functional cure”) is the optimal endpoint of antiviral therapy for chronic hepatitis B virus (HBV) infection. Currently available anti-HBV therapy includes nucleoside/nucleotide analogs (NAs) and peginterferon-α (Peg-IFNα). Combination of NAs and Peg-IFNα, each with different mechanisms of action, is an attractive approach for treating chronic HBV infection. In earlier studies, compared with monotherapy using IFNα, combination therapy showed greater on-treatment HBV DNA suppression but no difference in the sustained response. However, responses to the combination of non-pegylated IFNα with lamivudine or adefovir were not assessed based on HBsAg quantification but were defined by normal alanine aminotransferase levels, testing negative for hepatitis B e-antigen, and low HBV DNA load over a short term. Here, we reviewed previous reports regarding the effects of combination therapy of entecavir or tenofovir with Peg-IFNα, focusing on long-term reduction in HBsAg levels. Regimens of combination therapy were classified into “simultaneous” combination (“de novo” strategy); “sequential” combination, which involved starting with one therapy followed by the other (“switch-to” strategy); “add-on” combination, which involved adding Peg-IFNα to an ongoing NAs. Some studies have shown promising results, but there is no robust evidence that combination therapy is superior to monotherapy. Large studies are needed to assess the safety and efficacy of combination therapies to increase the rates of HBsAg seroclearance over the long term.

P679 LEVEL OF HEPATITIS B SURFACE ANTIGEN AND NOT HBV DNA LEVEL AFTER HBeAg SEROCLEARANCE IS PREDICTIVE OF HBsAg SEROCLEARANCE

2014 ◽  
Vol 60 (1) ◽  
pp. S295
Author(s):  
J. Fung ◽  
C.-L. Lai ◽  
D.K. Wong ◽  
W.-K. Seto ◽  
M. Kopaniszen ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Surface Antigen ◽  
Hepatitis B Surface Antigen ◽  
Hbv Dna ◽  
Hbsag Seroclearance

scholarly journals Persistent Loss of Hepatitis B Virus Markers in Serum without Cellular Immunity by Combination of Peginterferon and Entecavir Therapy in Humanized Mice

2017 ◽  
Vol 61 (9) ◽  
Author(s):  
Takuro Uchida ◽  
Michio Imamura ◽  
C. Nelson Hayes ◽  
Nobuhiko Hiraga ◽  
Hiromi Kan ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hepatitis B Surface Antigen ◽  
Hbv Dna ◽  
High Dose ◽  
Chimeric Mice ◽  
Chronic Hepatitis B Virus ◽  
B Virus ◽  
Ifn Treatment

ABSTRACT Nucleot(s)ide analogues and peginterferon (PEG-IFN) treatment are the only approved therapies for chronic hepatitis B virus (HBV) infection. However, complete eradication of the virus, as indicated by persistent loss of hepatitis B surface antigen (HBsAg), is rare among treated patients. This is due to long-term persistence of the HBV genome in infected hepatocytes in the form of covalently closed circular DNA (cccDNA). In this study, we investigated whether administration of a large dose of a nucleoside analogue in combination with PEG-IFN can achieve long-term loss of HBsAg in human hepatocyte chimeric mice. Mice were treated with a high dose of entecavir and/or PEG-IFN for 6 weeks. High-dose combination therapy with both drugs resulted in persistently negative HBV DNA in serum. Although small amounts of HBV DNA and cccDNA (0.1 and 0.01 copy/cell, respectively) remained in the mouse livers, some of the mice remained persistently negative for serum HBV DNA at 13 weeks after cessation of the therapy. Serum HBsAg and hepatitis B core-related antigen (HBcrAg) continued to decrease and eventually became negative at 12 weeks after cessation of the therapy. Analysis of the HBV genome in treated mice showed accumulation of G-to-A hypermutation and CpG III island methylation. Persistent loss of serum HBV DNA and loss of HBV markers by high-dose entecavir and PEG-IFN combination treatment in chimeric mice suggests that control of HBV can be achieved even in the absence of a cellular immune response.

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.

HBV Reverse Seroconversion and Intervention with Vaccination after Allogeneic HSCT in Patients with Previous HBV Infection.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2921-2921
Author(s):  
Masahiro Onozawa ◽  
Hiroe Kanamori ◽  
Kaoru Kahata ◽  
Takeshi Kondo ◽  
Shuichi Ota ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Surface Antigen ◽  
Hepatitis B Surface Antigen ◽  
Hbv Dna ◽  
Hbv Infection ◽  
Carrier Status ◽  
Serological Markers ◽  
Hematopoietic Stem ◽  
Hbv Vaccine

Abstract Appearance of anti-hepatitis B surface antigen antibody (anti-HBs) and clearance of hepatitis B virus (HBV) from serum usually indicates resolution of hepatitis in patients infected with HBV. However, in most patients in whom HBV has been eliminated from serum, HBV DNA is still detectable in the liver using polymerase chain reaction. Reactivation of this dormant HBV in the liver is known as reverse seroconversion (RS). Previously, we reported that HBV-RS after allogeneic hematopoietic stem cell transplantation (allo-HSCT) was a frequent late-onset complication that can be predicted by careful monitoring of progressive disappearance of anti-HBs. RS hepatitis after allo-HSCT is thought to be a phenomenon caused by naive donor immunity after loss of recipient-oriented immunity against HBV. We speculated that vaccination could prevent reactivation of HBV in allo-HSCT recipients. Safety and efficacy of recombinant HBV vaccine in allo-HSCT recipients have already been confirmed. We studied HBV serological markers in 23 patients with anti-HBs and/or anti-HBc before allo-HSCT who were followed for more than 1 year. Patients’ characters are following; Age at HSCT 22 to 65 (median, 38) years; M:F ratio 14:9; Hematological disorders CML 6, AML 1, ALL 4, MDS 4, SAA 2, NHL 4, MM 1 and CAEBV 1; Serological markers anti-HBc(+) and anti-HBs(+) 17, anti-HBc(+) and anti-HBs(−) 3, anti-HBc(−) and anti-HBs(+) 3. No patients had a prior history of vaccination or HBV-specific immunoglobulin usage. All patients were negative for hepatitis B surface antigen (HBsAg) and were considered to have previous HBV infection. The follow-up period varied from 12 to 116 (median, 36) months. Eighteen patients were followed without intervention. Five patients were vaccinated with recombinant HBV vaccine by the standard three-dose protocol after cessation of immunosuppressant administration. RS was defined as disappearance of anti-HBs and appearance of HBsAg and HBV-DNA with or without clinical hepatitis. Progressive decreases in anti-HBs titer were observed in all pre-HSCT anti-HBs-positive recipients. In 18 of the 20 patients with pre-HSCT anti-HBs, anti-HBs titer decreased to less than the protective value (<10.0 mIU/ml) at 4 to 38 (median, 12) months after HSCT. RS occurred in 11 of the 18 patients without intervention (61%) at 12 to 51 (median, 20) months after HSCT. Timing of onset and severity of hepatitis were not correlated. In patients with RS, anti-HBs had disappeared 0 to 26 (median, 8) months prior to RS. Although re-seroconversion occurred in 7 patients, the remaining 4 patients remained in HBV carrier status after resolution of transient hepatitis. In the 7 patients with re-seroconversion, hepatitis subsided and HBsAg disappeared with acquisition of anti-HBe shortly after RS. On the other hand, reappearance of anti-HBs was delayed by 6 to 51 (median, 32) months after onset of RS. Four of the 5 patients with intervention were successfully immunized by HBV vaccine (80%), and none of those 5 patients had RS during the follow-up period (12–40 months; median, 20 months). In conclusion, all patients with previous HBV infection are considered to be at high risk for RS after allo-HSCT. Recombinant HBV vaccines effectively immunize allo-HSCT recipients and are protective against HBV-RS.

scholarly journals Hepatitis B surface antigen-negative, but HBV DNA-positive patients in Bangladesh

2013 ◽  
Vol 38 (3) ◽  
pp. 104-107 ◽  
Author(s):  
MA Mahtab ◽  
SMF Akbar ◽  
S Rahman
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Hepatitis B ◽  
Surface Antigen ◽  
Healthy Subjects ◽  
Hepatitis B Surface Antigen ◽  
Hbv Dna ◽  
Hbv Infection ◽  
B Virus ◽  
Control And Management

Hepatitis B surface antigen (HBsAg) is regarded as sole marker of hepatitis B virus (HBV) infection in Bangladesh and most other developing countries. However, some HBV-negative subjects may harbor HBV DNA and transfusion of their blood may cause HBV infection in recipients. HBV DNA was checked in 20 patients with cryptogenic liver cirrhosis, 10 patients with hepatocellular carcinoma without any known etiology, and 10 apparently healthy subjects with elevated levels of serum alanine aminotransferase (ALT). HBV DNA was detected in 8 of 20 patients with cryptogenic liver cirrhosis, 1 of 10 patients with hepatocellular carcinoma, and 2 of 10 apparent healthy subjects with elevated ALT. However, all of them were negative for HBsAg in the sera. This study indicates that some additional mechanisms should be developed for detection of HBsAg-negative HBV-infected subjects for efficient control and management of HBV infection in Bangladesh. DOI: http://dx.doi.org/10.3329/bmrcb.v38i3.14337 Bangladesh Med Res Counc Bull 2012; 38(3): 104-107 (December)

scholarly journals The Study of Correlation between Serum Vitamin D3 Concentrations and HBV DNA Levels and Immune Response in Chronic Hepatitis Patients

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1114
Author(s):  
Wang-Sheng Ko ◽  
Yen-Ping Yang ◽  
Fang-Ping Shen ◽  
Mu-Chen Wu ◽  
Chia-Ju Shih ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Viral Load ◽  
Hepatitis B ◽  
Surface Antigen ◽  
Vitamin D3 ◽  
Peripheral Blood ◽  
Hepatitis B Surface Antigen ◽  
Serum Vitamin ◽  
Hbv Dna ◽  
Hbv Infection

Chronic hepatitis B (CHB) is a common chronic disease. Previous studies have shown a link between 25-hydroxyvitamin D3 (vitamin D3) concentration and liver disease. Hepatitis B virus (HBV) infection has been attributed to the inappropriate functioning of cell-mediated immunity. However, the effects of vitamin D3, immune cell, and HBeAg status on HBV viral load in CHB patients are still unclear. We investigated the relationship between the serum concentration of vitamin D3, percentage of immune cells in peripheral blood, and the HBV viral load of CHB patients. Sixty CHB patients were recruited, and their blood samples were collected and analyzed. Vitamin D level was measured using a chemiluminescence assay. A level of 30 ng/mL or above was defined as a vitamin D3 sufficiency. We assigned vitamin D3 status as either normal (≥30 ng/mL), insufficient (20–30 ng/mL), or deficient (<20 ng/mL). T-lymphocyte and B-lymphocyte surface markers in peripheral blood were detected using flow cytometry. The factors associated with HBV viral load were analyzed using univariate and multivariate-adjusted models. The mean serum vitamin D3 concentration in the subjects was 20.9 ± 5.6 ng/mL. Up to 88.3% of the patients were either deficient in or had insufficient vitamin D3. The gender, BMI, hepatitis B surface antigen levels, and ALT levels were significantly related to serum vitamin D3 levels. Serum vitamin D3 concentration, HBe status, HBs levels, ALT, and AST levels showed a statistically significant correlation with the HBV DNA levels. Serum vitamin D3 concentrations and hepatitis B surface antigen levels were strongly correlated with HBV DNA levels. Vitamin D3 levels were significantly associated with CD19 numbers (β:−6.2, 95% CI: −10.5). In multivariate analysis, vitamin D3 levels in the deficient and insufficient groups, and the CD8, HBeAg, and WBC counts were significantly associated with HBV DNA levels. In the immune tolerance phase of HBeAg-negative chronic HBV infection, vitamin D3 may be a modulator of immune function via CD8, CD19, and HBV DNA.

scholarly journals Evaluating the independent influence of sexual transmission on HBV infection in China: a modeling study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Miaolei Li ◽  
Jian Zu ◽  
Mingwang Shen ◽  
Guihua Zhuang ◽  
Siyuan Chen ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Condom Use ◽  
Initial Conditions ◽  
Hepatitis B Surface Antigen ◽  
Sexual Transmission ◽  
Horizontal Transmission ◽  
Hbv Infection ◽  
Hbsag Seroclearance ◽  
Age And Sex

AbstractBackgroundThe long-term impact of sexual transmission on the hepatitis B virus (HBV) infection in China remains unclear. This study aims to estimate the independent influence of sexual transmission on HBV infection.MethodsBased on the natural history of HBV infection and three national serosurvey data of hepatitis B in China, we developed an age- and sex-specific discrete model to describe the transmission dynamics of HBV. The initial conditions of the model were determined according to the age- and sex-specific national serosurvey data in 1992. Based on the national survey data of hepatitis B in 1992 and 2006, by using the Markov Chain Monte Carlo (MCMC) method, we estimated the age- and sex-specific seroclearance rates of hepatitis B surface antigen (HBsAg) and the horizontal transmission rates as well as their 95% confidence intervals (CI). Then we used the age- and sex-specific national serosurvey data of hepatitis B in 2014 to test the accuracy of our model-based estimation. Finally, we evaluated the independent impact of sexual transmission on HBV infection and discussed the long-term effect of promotion of condom use in China.ResultsWe estimated that the annual rates of HBsAg seroclearance for males and females aged 1–59 years were respectively 1.04% (95% CI, 0.49–1.59%) and 1.92% (95% CI, 1.11–2.73%). Due to sexual transmission, in 2014, the total number of chronic HBV infections in people aged 0–100 years increased 292,581, of which males increased 189,200 and females increased 103,381. In 2006, the acute HBV infections due to sexual transmission accounted for 24.76% (male: 31.33%, female: 17.94%) and in 2014, which accounted for 34.59% (male: 42.93%, female: 25.73%). However, if the condom usage rate was increased by 10% annually starting in 2019, then compared with current practice, the total number of acute HBV infections from 2019 to 2035 would be reduced by 16.68% (male: 21.49%, female: 11.93%). The HBsAg prevalence in people aged 1–59 years in 2035 would be reduced to 2.01% (male: 2.40%, female: 1.58%).ConclusionsSexual transmission has become the predominant route of acute HBV infection in China, especially for men. The promotion of condom use plays a significant role in reducing the cases of acute HBV infection.

Role of serum HBV RNA and hepatitis B surface antigen levels in identifying Asian patients with chronic hepatitis B suitable for entecavir cessation

Gut ◽  
2020 ◽  
pp. gutjnl-2020-321116 ◽  
Author(s):  
Wai-Kay Seto ◽  
Kevin SH Liu ◽  
Lung-Yi Mak ◽  
Gavin Cloherty ◽  
Danny Ka-Ho Wong ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Surface Antigen ◽  
Hepatitis B Surface Antigen ◽  
Hbv Dna ◽  
Treatment Cessation ◽  
Serum Hbsag ◽  
Median Serum ◽  
Hbsag Seroclearance ◽  
Chronic Hbv

BackgroundTreatment cessation in chronic HBV infection may be durable in certain patient subgroups before hepatitis B surface antigen (HBsAg) seroclearance. The role of serum HBV RNA in determining treatment cessation suitability has not been well-investigated.MethodsNucleos(t)ide analogue (NUC) treatment was discontinued in non-cirrhotic patients with chronic HBV with serum HBsAg <200 IU/mL and fulfilling internationally recommended criteria for treatment cessation. Patients were monitored till 48 weeks with baseline and serial measurements of serum HBsAg, HBV RNA and hepatitis B core-related antigen. NUCs were resumed when HBV DNA reaches >2000 IU/mL regardless of alanine aminotransferase (ALT) levels.Results114 entecavir-treated patients (median age 58.4 years, median serum HBsAg 54.4 IU/mL) with median treatment duration of 6.7 years were recruited. The 48-week cumulative rate of HBV DNA >2000 IU/mL was 58.1%. End-of-treatment serum HBV RNA and off-treatment serial HBV RNA were both independently associated with HBV DNA >2000 IU/mL (HR 2.959, 95% CI 1.776 to 4.926, p<0.001; HR 2.278, 95% CI 1.151 to 4.525, p=0.018, respectively). Patients with HBV RNA ≥44.6 U/mL had a cumulative 48-week rate of 93.2%, while combining HBV RNA undetectability and HBsAg <10 IU/mL had a cumulative 48-week rate of 9.1%. 24 patients (38.7%) developed off-treatment ALT elevation, highest peak ALT was 1515 U/L. 8 patients (median serum HBsAg 2.6 IU/mL) developed HBsAg seroclearance.ConclusionSerum HBV RNA measurement is essential for deciding on entecavir cessation in patients with chronic HBV, especially with low HBsAg levels. Patients can be stratified on their risk of off-treatment relapse based on both viral determinants.Trial registration numberNCT02738554

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