A longitudinal study on the natural history of serum hepatitis B surface antigen changes in chronic hepatitis B

Chan, Henry Lik‐Yuen; Wong, Vincent Wai‐Sun; Wong, Grace Lai–Hung; Tse, Chi‐Shing; Chan, Hoi–Yun; Sung, Joseph J.Y.

doi:10.1002/hep.23803

Cited by 228 publications

(226 citation statements)

References 30 publications

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“…Previous reports have suggested that HBsAg may reflect the content of intrahepatic HBV DNA and/or cccDNA, which serve as an intracellular template for viral RNA transcription, and it has been proposed as a surrogate marker for HBV-infected hepatocytes (58)(59)(60). However, other studies using the same HBsAg quantification platform could not confirm the association between HBsAg levels and cccDNA or intrahepatic HBV DNA in HBeAg ( À ) hepatitis B (61)(62)(63).…”

Section: Hbsag: Controversiesmentioning

confidence: 98%

Quantification of hepatitis B surface antigen: a new concept for the management of chronic hepatitis B

Moucari

Marcellin

2011

Liver International

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HBsAg is a very important clinical test that might not only indicate active hepatitis B virus (HBV) infection but might also be used to predict clinical and treatment outcome. Clearance of HBsAg in patients with chronic HBV infection is associated with a much better clinical outcome, although surveillance for early detection of hepatocellular carcinoma (HCC) should continue. HBV DNA quantification is currently used for selecting candidates for therapy, monitoring response to therapy and detecting the emergence of drug resistance. Assays for HBsAg quantification are less expensive than HBV DNA and fully automated with a high throughput capacity. HBsAg titering may be a useful tool to manage patients with chronic HBV, to more clearly define which patients may, and more importantly, may not, benefit from treatment. Baseline and on-treatment HBsAg quantification may help to refine future treatment algorithms for both immune-modulator therapy and nucleos(t)ide analogues. Both HBV markers provide complementary information on the status of HBV infection. However, the relevance of serum HBsAg levels and its use as a reliable replacement for both covalently closed circular DNA and HBV DNA remain unclear.

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Section: Hbsag: Controversiesmentioning

confidence: 98%

Quantification of hepatitis B surface antigen: a new concept for the management of chronic hepatitis B

Moucari

Marcellin

2011

Liver International

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“…The relative lack of relationship between HBsAg level and disease activity might reflect an uncoupling of HBV DNA and HBsAg production in the HBeAg-negative phase. In line with natural history studies, a reduction in HBsAg is probably reflecting a stepping up of immune clearance [8], which is a logical predictor of response to peginterferon therapy in HBeAg-negative patients.…”

mentioning

confidence: 62%

“…In a previous report among 19 HBeAg-negative patients with active disease (elevated ALT and/or HBV DNA [10,000 copies/ml), the HBsAg level could range from 1.57 to 3.85 log IU/ml [14]. In another case series, the range of the HBsAg level among 46 HBeAg-negative patients with elevated ALT varied from -0.42 to 4.09 log IU/ml [8]. The relative lack of relationship between HBsAg level and disease activity might reflect an uncoupling of HBV DNA and HBsAg production in the HBeAg-negative phase.…”

mentioning

confidence: 89%

“…The exact reason for this observation is uncertain, but could be related to the production of HBsAg by integrated HBV surface gene fragments in the host chromosome or the uncoupling on the regulation of HBsAg and HBV DNA production after HBeAg seroconversion. Nonetheless, in natural history studies, a lower HBsAg level is associated with inactive hepatitis [8,9] and a higher chance of spontaneous seroclearance of HBsAg [10], suggesting that a lower HBsAg level is associated with better immune control of the virus.…”

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confidence: 99%

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Are we ready to use the hepatitis B surface antigen level to guide peginterferon treatment in HBeAg-negative chronic hepatitis B?

Chan

2012

Hepatol Int

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In chronic hepatitis B virus (HBV) infection, hepatitis B e antigen (HBeAg) seroconversion often indicates host immune clearance. Approximately 30 % of patients, however, still have active viremia and fluctuating alanine aminotransferase (ALT) levels in the HBeAg-negative phase [1]. These patients with HBeAg-negative chronic hepatitis B probably have an immune escape by the virus; a further attempt of immune modulator therapy by interferon might be difficult and the post-treatment relapse rate is high. Early experience in Europe using 12-month interferon-alpha combined with lamivudine only yielded a sustained viral suppression (undetectable by nonpolymerase chain reaction assay) rate of approximately 15 % at 6-12 months post-treatment [2,3]. With 12-month peginterferon alfa-2a with/without lamivudine combination in the phase III international trial for HBeAg-negative chronic hepatitis B, approximately 22.6 % of patients could achieve sustained viral suppression to B10,000 copies/ml at 3-year post-treatment [4]. Owing to the inconvenient subcutaneous route of administration, potential adverse effects, and a high drug cost of peginterferon, one should select patients who have a higher chance of response to the peginterferon therapy. On the other hand, peginterferon is not preferred or should be stopped earlier if the chance of response is too low.On post hoc analysis of the phase III trial of peginterferon alfa-2a (with/without lamivudine combination), HBeAg-negative patients at a younger age and those who had lower HBV DNA at baseline had a higher chance of achieving a response, which was defined as HBV DNA B20,000 copies/ml at 24-week post-treatment [5]. Patients infected by genotype C HBV also have a better response than those infected by genotype D HBV. Nonetheless, the differences in response between patients with different baseline predictive factors were too small to guide patient selection for treatment. For example, the mean baseline HBV DNA was 7

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“…Recent studies have also shown the important role of HBsAg quantification in the natural history of CHB. HBsAg levels evolve along with the natural courses of CHB [7]. The HBsAg level is highest in the IT phase and starts to decline from the entry of the IC phase toward an LR phase, unless reactivation of HBV occurs.…”

mentioning

confidence: 99%

Looking into the crystal ball: biomarkers for outcomes of HBV infection

Yang

Kao

2016

Hepatol Int

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A longitudinal study on the natural history of serum hepatitis B surface antigen changes in chronic hepatitis B

Abstract: HBsAg remained stable in HBeAg-positive patients and tended to reduce slowly in HBeAg-negative patients. Reduction of HBsAg for >1 log IU/mL could reflect improved immune control.

Cited by 228 publications

References 30 publications

Quantification of hepatitis B surface antigen: a new concept for the management of chronic hepatitis B

Quantification of hepatitis B surface antigen: a new concept for the management of chronic hepatitis B

Are we ready to use the hepatitis B surface antigen level to guide peginterferon treatment in HBeAg-negative chronic hepatitis B?

Looking into the crystal ball: biomarkers for outcomes of HBV infection

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