532 Significant Genotype-Specific Association of Hepatitis B Surface Antigen Level and Severity of Liver Disease in Patients With Chronic Hepatitis B

Martinot–Peignoux, Michelle; Carvalho-Filho, Roberto José de; Ferreira, Ariana Carolina; Cardoso, Netto; Lapalus, Martine; Lada, Olivier; Asselah, Tarik; Krause, Fr.; Marcellin, Patrick

doi:10.1016/s0168-8278(12)60545-5

Cited by 6 publications

(7 citation statements)

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“… found an association between higher HBsAg (≥25 000 IU/ml) serum levels and mild fibrosis (stage F ≤ 1) in a cohort of 140 Asian HBeAg (+) CHB patients (no indication of HBV genotype) with ALT ≤ 2 times the upper limit of normal. Similar results are reported in a cohort of 406 chronic hepatitis B patients with genotypes A–E . A negative correlation was found between the level of HBsAg and the stage of fibrosis, so that patients with no or mild fibrosis (F 0–1 Metavir score) could be distinguished from those with moderate or severe fibrosis (≥ F2), in HBeAg (+) patients, with a high NPV (91%).…”

Section: Natural Historysupporting

confidence: 86%

“…Rijckborst et al . confirmed these results in patients in the PARC study and performed external validation in the phase III registration study and the PegBeLiver study , both of which included patients with HBV genotypes A–D. There was a NPV ≥95% for SVR in both validation studies in the absence of a decrease in HBsAg or a decline in HBV DNA <2 log 10 IU/ml at week 12 of treatment.…”

Section: Hbsag Level and Therapysupporting

confidence: 53%

“…A negative correlation was found between the level of HBsAg and the stage of fibrosis, so that patients with no or mild fibrosis (F 0–1 Metavir score) could be distinguished from those with moderate or severe fibrosis (≥ F2), in HBeAg (+) patients, with a high NPV (91%). Furthermore, the authors describe a specific serum HBsAg cut‐off (3.85 log 10 IU/ml) to identify moderate to severe fibrosis (≥ F2) in HBeAg (+) CHB patients infected with HBV genotypes B or C. This association was not observed in HBeAg (−) patients . There was no association between HBsAg titre and histological grade found in either study.…”

Section: Natural Historymentioning

confidence: 82%

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The role of HBsAg quantification for monitoring natural history and treatment outcome

Martinot–Peignoux

Lapalus

Asselah

et al. 2013

Liver International

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Since its discovery by Blumberg in 1965, the hepatitis B virus antigen (HBsAg) is used as the fingerprint of hepatitis B infection. The HBsAg level is a reflection of the transcriptional activity of cccDNA. It is an important marker that not only indicates active hepatitis B infection but can also predict clinical and treatment outcomes. Assays for HBsAg quantification are fully automated and have high output. HBsAg titres are higher in HBe antigen (HBeAg)(+) than in HBeAg(À) patients and are negatively correlated with liver fibrosis in HBeAg(+) patients. In HBeAg(À) chronic hepatitis B, an HBsAg level <1000 IU/ml and an HBV DNA titre <2000 IU/ml accurately identify inactive carriers. During PEG-IFN treatment, HBsAg quantification is used to identify patients who will not benefit from therapy as early as week 12 on therapy, so that treatment may be stopped or switched-'week 12 stopping rule'. With nucleos(t)ide analogues (NA), the role of HBsAg quantification must be clarified. Several studies show that baseline and on-treatment HBsAg levels might identify patients that can be treated with no subsequent risk of reactivation. In clinical practice, HBsAg quantification is a simple and reproducible tool that can be used in association with HBV DNA to classify patients during the natural history of HBV and to monitor therapy.

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Section: Natural Historysupporting

confidence: 86%

Section: Hbsag Level and Therapysupporting

confidence: 53%

Section: Natural Historymentioning

confidence: 82%

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The role of HBsAg quantification for monitoring natural history and treatment outcome

Martinot–Peignoux

Lapalus

Asselah

et al. 2013

Liver International

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“…While it was also included in the present study, it was not found to be associated with any significant histology. Martinot-Peignoux et al [ 27 ] also found the same results with HBeAg-negative CHB patients with varying degrees of ALT [ 27 ]. These findings suggest that serum HBsAg level is not a potential tool in liver histology assessment in HBeAg-negative CHB patients.…”

Section: Discussionmentioning

confidence: 55%

HBV DNA level could predict significant liver fibrosis in HBeAg negative chronic hepatitis B patients with biopsy indication

et al. 2014

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BackgroundNon-invasive models and methods to substitute liver biopsy in chronic hepatitis B (CHB) patients were investigated but their roles as predictors of significant liver histology for diagnosis of HBeAg-negative CHB patients who had indication for liver biopsy according to The American Association for the Study of Liver Diseases (AASLD) and The Asian Pacific Association for the Study of the Liver (APASL) guidelines are still unknown. This study was designed to identify predictors of significant liver necroinflammation as defined by a Histology Activity Index of necroinflammatory score ≥ 4 or Metavir necroinflammatory activity score ≥ 2 and significant liver fibrosis as defined by a Metavir fibrosis score ≥ 2 in HBeAg-negative CHB patients that had a hepatitis B virus (HBV) DNA level ≥ 2,000 IU/ml and age ≥ 40 years or elevated alanine aminotransferase level between 1–2 times the upper limit of normal.MethodsTwenty-two patients were prospectively included and performed liver biopsies. Clinical and laboratory parameters including age, gender, underlying disease, family history of cirrhosis or hepatocellular carcinoma, body mass index (BMI), HBV DNA level, HBsAg level, liver function test, complete blood count, aspartate aminotransferase-to-platelet ratio index and transient elastography were collected and analyzed with liver histology profiles.ResultsFive patients (23%) had significant liver inflammation and 7 patients (32%) had significant liver fibrosis. Factors associated with significant liver inflammation were a lower BMI and higher alkaline phosphatase level while a factor associated with significant liver fibrosis was lower age. On multivariate analysis, only HBV DNA level > 5.5 log IU/ml could predict significant liver fibrosis (odds ratio 28.012, 95% CI, 1.631-481.240, p = 0.022) and its sensitivity, specificity, positive predictive value and negative predictive value were 71.4%, 93.3%, 83.3% and 87.5% respectively.ConclusionsAn HBV DNA level of > 5.5 log IU/ml was able to predict significant liver fibrosis for treatment of HBeAg-negative CHB patients that had indication for liver biopsy as recommended by AASLD and APASL guidelines.

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“…HBsAg levels are typically highest in the earlier phases of infection and in HBeAg-positive individuals, frequently correlate with HBV DNA levels in CHB infection, and are associated with risk of subsequent reactivation (8). HBsAg may be a quantifiable risk factor for development of hepatocellular carcinoma (HCC) and chronic liver disease (9), although the relationship is not well defined: in some studies, higher HBsAg levels are associated with lower levels of fibrosis (10–12), while in others, lower baseline HBsAg levels are associated with reduced risk of both cirrhosis and HCC (13). HBsAg levels have also been used to classify individuals into those with inactive carriage (HBV DNA <2000 IU/ml and normal ALT (14, 15)) versus active CHB (with higher viral loads and elevated risks of inflammatory liver disease, fibrosis and cirrhosis (16–19)).…”

Section: Introductionmentioning

confidence: 99%

Data from an electronic health informatics pipeline to describe clearance dynamics of Hepatitis B surface antigen (HBsAg) and e-Antigen (HBeAg) in chronic HBV infection

Downs

Smith

Lumley

et al. 2018

Preprint

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56 57 3 58 ACKNOWLEDGEMENTS 59 This work has been facilitated by infrastructure development at Oxford Biomedical Research 60 Centre (BRC) funded by the NIHR Health Informatics Collaborative (HIC). 61An earlier version of this dataset was presented as a poster at the EASL International Liver 62 Congress meeting, Paris 2018 (https://f1000research.com/posters/7-917). 63. 64 ABBREVIATIONS 65 CHB Chronic Hepatitis B virus infection 66 EPR Electronic patient record 67 HBeAg Hepatitis B 'e' antigen 68 HBsAg Hepatitis B surface antigen 69 HBV Hepatitis B virus 70 HCV Hepatitis C virus 71 HIC Health Informatics Collaborative 72 HIV Human immunodeficiency virus 73 LFT Liver function tests 74 LIMS Laboratory information management system 75 NA Nucleos(t)ide analogues 76 NIHR National Institute for Health Research 77 PEG-IFNα Pegylated interferon alpha 2 78 TDF Tenofovir Disoproxil Fumarate 79 RBV Ribavirin 80 81 82 4 ABSTRACT 83 HBsAg and HBeAg have gained traction as biomarkers of control and clearance during chronic 84 hepatitis B virus infection (CHB). Improved understanding of clearance correlates of these proteins 85 could help inform improvements in patient-stratified care and advance insights into underlying 86 mechanisms of disease control, thus underpinning new cure strategies. We collected electronic 87 clinical data via an electronic pipeline supported by the National Institute for Health Research 88 Health Informatics Collaborative (NIHR-HIC), adopting an unbiased approach to generating a 89 robust longitudinal dataset for adults testing HBsAg-positive from a large UK teaching hospital over 90 a six year period (2011-2016 inclusive). From 553 individuals with CHB, longitudinal data were 91 available for 319, representing >107,000 weeks of clinical follow-up. Among these 319 individuals, 92 13 (4%) cleared HBsAg completely. Among these 13, HBsAg clearance rate was similar in 93 individuals on nucleos(t)ide analogue (NA) therapy (n=4 (31%)), median clearance time 150 94 weeks) vs those not on NA therapy (n=9 (69%), median clearance time 157 weeks). Those who 95 cleared HBsAg were significantly older, and less likely to be on NA therapy compared to non-96 clearers (p=0.003 and p=0.001, respectively). Chinese ethnicity was associated with HBeAg 97 positivity (p=0.025). HBeAg clearance occurred both on NA therapy (n=24, median time 49 weeks) 98 and off NA therapy (n=19, median time 52 weeks). Improved insights into the dynamics of these 99 biomarkers can underpin better prognostication and patient-stratified care. Our systematised 100 approach to data collection paves the way for scaling up efforts to harness clinical data to address 101 research questions and underpin improvements in clinical care. 102 103 IMPORTANCE 104 Advances in the diagnosis, monitoring and treatment of hepatitis B virus (HBV) infection are 105 urgently required if we are to meet international targets for elimination by the year 2030. Here we 106 demonstrate how routine clinical data can be harnessed through an unbiased electronic pipeline, 107...

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532 Significant Genotype-Specific Association of Hepatitis B Surface Antigen Level and Severity of Liver Disease in Patients With Chronic Hepatitis B

Cited by 6 publications

References 0 publications

The role of HBsAg quantification for monitoring natural history and treatment outcome

The role of HBsAg quantification for monitoring natural history and treatment outcome

HBV DNA level could predict significant liver fibrosis in HBeAg negative chronic hepatitis B patients with biopsy indication

Data from an electronic health informatics pipeline to describe clearance dynamics of Hepatitis B surface antigen (HBsAg) and e-Antigen (HBeAg) in chronic HBV infection

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