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

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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Detection of the hepatitis B surface antigen in patients with occult hepatitis B using an assay with enhanced sensitivity

Journal of Clinical Microbiology ◽

10.1128/jcm.02204-21 ◽

2021 ◽

Author(s):

Danny Ka-Ho Wong ◽

Claire Chen ◽

Lung-Yi Mak ◽

James Fung ◽

Wai-Kay Seto ◽

...

Keyword(s):

Hepatitis B ◽

Surface Antigen ◽

Blood Donors ◽

Hepatitis B Surface Antigen ◽

Hbv Dna ◽

Hbv Reactivation ◽

Occult Hepatitis ◽

Hbsag Seroclearance ◽

Hbsag Detection ◽

Occult Hepatitis B

Patients with occult hepatitis B infection (OBI) have undetectable hepatitis B surface antigen (HBsAg) by conventional assays but detectable hepatitis B virus (HBV) DNA in blood/liver. We evaluated the key performance characteristics of a sensitive HBsAg assay (ARCHITECT HBsAg Next Qualitative Assay, referred as NEXT) with respect to HBsAg detection. Assay precision, sample carryover and seroconversion sensitivity of NEXT were evaluated. HBsAg was measured by NEXT in 1,138 individuals, including 1,038 patients who attended liver clinics in a tertiary hospital (200 HBV DNA-positive blood donors whose HBsAg was undetectable by conventional assays, and 38 patients receiving immunosuppressive therapy, 800 chronic hepatitis B patients with HBsAg seroclearance) and 100 HBsAg-negative subjects recruited from a community project. The within-run and within-laboratory coefficients of variation were <6% for the positive sample pools. In 9 seroconversion panels tested, NEXT allowed an earlier HBsAg detection than conventional assays. NEXT detected HBsAg in 10/200 (5%) HBsAg-negative blood donors, 1/20 (5%) and 0/18 HBsAg-negative patients with and without HBV reactivation respectively, and 59/800 (7.3%) patients with HBsAg seroclearance. HBsAg was detectable by NEXT in 27.8%, 8.2%, 6.9%, 3.8% and 1.9% samples at <3, 3–5, >5–8, >8–11, and >11 years after HBsAg seroclearance, respectively. Seven out of 100 HBsAg-negative community identified subjects was tested positive by NEXT. Comparing with conventional HBsAg assays, NEXT demonstrated a higher sensitivity and conferred an increment of 5–7% detection rate in patients with OBI, thereby helping in identifying HBV carriers and prevention of OBI-associated HBV transmission and reactivation.

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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

International Journal of Molecular Sciences ◽

10.3390/ijms22031456 ◽

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.

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Expression of hepatitis B surface antigen in unselected cell culture transfected with recircularized HBV DNA.

The EMBO Journal ◽

10.1002/j.1460-2075.1982.tb00015.x ◽

1982 ◽

Vol 1 (10) ◽

pp. 1213-1216 ◽

Cited By ~ 9

Author(s):

Y. Wang ◽

M. Schäfer-Ridder ◽

C. Stratowa ◽

T.K. Wong ◽

P.H. Hofschneider

Keyword(s):

Cell Culture ◽

Hepatitis B ◽

Surface Antigen ◽

Hepatitis B Surface Antigen ◽

Hbv Dna

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Hepatitis B surface antigen (HBsAg) levels in the prediction of spontaneous HBsAg seroclearance

Hepatology ◽

10.1002/hep.25999 ◽

2013 ◽

Vol 57 (4) ◽

pp. 1675-1675 ◽

Cited By ~ 2

Author(s):

Yi-Cheng Chen

Keyword(s):

Hepatitis B ◽

Surface Antigen ◽

Hepatitis B Surface Antigen ◽

Hbsag Seroclearance

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Serum hepatitis B surface antigen concentration correlates with HBV DNA level in patients with chronic hepatitis B

Antiviral Therapy ◽

10.3851/imp1696 ◽

2010 ◽

Vol 15 (8) ◽

pp. 1133-1139 ◽

Cited By ~ 58

Author(s):

Tung-Hung Su ◽

Ching-Sheng Hsu ◽

Chi-Ling Chen ◽

Chen-Hua Liu ◽

Yi-Wen Huang ◽

...

Keyword(s):

Chronic Hepatitis ◽

Hepatitis B ◽

Chronic Hepatitis B ◽

Surface Antigen ◽

Hepatitis B Surface Antigen ◽

Hbv Dna ◽

Serum Hepatitis ◽

Antigen Concentration

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Hepatitis B Virus Reactivation in Lymphoma Patients With Prior Resolved Hepatitis B Undergoing Anticancer Therapy With or Without Rituximab

Journal of Clinical Oncology ◽

10.1200/jco.2008.18.0182 ◽

2009 ◽

Vol 27 (4) ◽

pp. 605-611 ◽

Cited By ~ 436

Author(s):

Winnie Yeo ◽

Tung C. Chan ◽

Nancy W.Y. Leung ◽

Wai Y. Lam ◽

Frankie K.F. Mo ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Surface Antigen ◽

Hepatitis B Surface Antigen ◽

B Cell Lymphoma ◽

Anticancer Therapy ◽

Hbv Dna ◽

Core Antigen ◽

Hbv Reactivation ◽

B Virus

Purpose Reactivation of hepatitis B virus (HBV) infection is a well-recognized complication in cancer patients with chronic HBV (hepatitis B surface antigen [HBsAg] positive) undergoing cytotoxic chemotherapy. In patients who have resolved HBV (HBsAg negative and antibody to hepatitis B core antigen [anti-HBc] ± antibody to hepatitis B surface antigen [anti-HBs] positive), such incidence has been much less common until recent use of rituximab. In this study on HBsAg-negative/anti-HBc–positive lymphoma patients, the objectives were to determine the HBV reactivation rate in patients treated with rituximab-containing chemotherapy and to compare it with the rate in patients treated without rituximab. Patients and Methods Between January 2003 and December 2006, all patients diagnosed with CD20+ diffuse large B-cell lymphoma (DLBCL) had HBsAg determined before anticancer therapy. They were treated with either cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) alone or rituximab plus CHOP (R-CHOP). HBsAg-negative patients had anti-HBc determined; serum was stored for anti-HBs and HBV DNA. All patients were observed for HBV reactivation, which was defined as detectable HBV DNA with ALT elevation during and for 6 months after anticancer therapy. Results Among 104 CD20+ DLBCL patients, 80 were HBsAg negative. Of the latter, 46 patients (44.2%) were HBsAg negative/anti-HBc positive; 25 of these patients were treated with CHOP, and none had HBV reactivation. In contrast, among the 21 patients treated with R-CHOP, five developed HBV reactivation, including one patient who died of hepatic failure (P = .0148). Exploratory analysis identified male sex, absence of anti-HBs, and use of rituximab to be predictive of HBV reactivation. Conclusion Among HBsAg-negative/anti-HBc–positive DLBCL patients treated with R-CHOP, 25% developed HBV reactivation. Close monitoring until at least 6 months after anticancer therapy is required, with an alternative approach of prophylactic antiviral therapy to prevent this potentially fatal condition.

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