Quantitative hepatitis B core antibody level may help predict treatment response in chronic hepatitis B patients

Yuan, Quan; Song, Liu Wei; Liu, Chun‐Jen; Li, Zhuo; Liu, Ping Guo; Huang, Chaofan; Yan, Yan; Ge, Sheng; Wang, Ying Bin; Peng, Cheng Yuan; Zhang, Jun; Chen, Ding‐Shinn; Chen, Pei‐Jer; Xia, Ning

doi:10.1136/gutjnl-2012-302656

Cited by 72 publications

(68 citation statements)

References 4 publications

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“…Our validation study confirms in well characterized HBsAg-carriers infected with genotype-D-HBV the results obtained in Asian patients infected with genotype B and C [21]; the highest levels of total-anti-HBc were detected in CHB, both HBeAg-positive and HBeAg-negative and the lowest levels in inactive-carriers (Fig 1). Very low levels of the antibody were reported in the non-inflammatory, HBeAg-positive immune-tolerant-phase in genotype-B and-C infections [21][22][23]. Consistently in our HBeAg-positive-carriers total-antiHBc levels comparable to those of inactive-carriers were found only in an immune-tolerant carrier, whereas the remaining CHB-patients showed high antibody levels.…”

Section: Discussionsupporting

confidence: 89%

“…However, in HBeAgnegative CHB patients undergoing antiviral treatment HBsAg kinetics vary according to HBV genotype and genotype-specific monitoring timeframes and end-of-treatment thresholds have yet to be standardized for a proper response-guided treatment 19]. Recently a new assay based on double antigen sandwich method that detects total (IgG and IgM) anti-HBc was developed and proposed to monitor patients, chronically infected with genotype B and C HBV undergoing antiviral therapy [21][22][23][24]. We tested this assay in a validation study on a panel of sera from well characterized genotype D, HBsAg carriers.…”

Section: Introductionmentioning

confidence: 99%

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Total hepatitis B core antigen antibody, a quantitative non-invasive marker of hepatitis B virus induced liver disease

Moriconi

Yuan

Song

et al. 2015

Digestive and Liver Disease

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Non invasive immunologic markers of virus-induced liver disease are unmet needs. We tested the clinical significance of quantitative total and IgM-anti-HBc in well characterized chronic-HBsAg-carriers. Sera (212) were obtained from 111 HBsAg-carriers followed-up for 52 months (28-216) during different phases of chronic-HBV-genotype-D-infection: 10 HBeAg-positive, 25 inactive-carriers (HBV-DNA2000IU/ml, ALT<30U/L), 66 HBeAg-negative-CHB-patients and 10 with HDV-super-infection. In 35 patients treated with Peg-IFN ±nucleos(t)ide-analogues (NUCs) sera were obtained at baseline, end-of-therapy and week-24-off-therapy and in 22 treated with NUCs (for 60 months, 42-134m) at baseline and end-of-follow-up. HBsAg and IgM-anti-HBc were measured by Architect-assays (Abbott, USA); total-anti-HBc by double-antigen-sandwich-immune-assay (Wantai, China); HBV-DNA by COBAS-TaqMan (Roche, Germany). Total-anti-HBc were detectable in all sera with lower levels in HBsAg-carriers without CHB (immune-tolerant, inactive and HDV-superinfected, median 3.26, range 2.26-4.49 Log 10 IU/ml) versus untreated-CHB (median 4.68, range 2.76-5.54 Log 10 IU/ml), p<0.0001. IgM-anti-HBc positive using the chronic-hepatitis-cut-off" (0.130-S/CO) were positive in 102 of 212 sera (48.1%). Overall total-anti-HBc and IgM-anti-HBc correlated significantly (p<0.001, r=0.417). Total-anti-HBc declined significantly in CHB patients with response to Peg-IFN (p<0.001) and in NUCtreated patients (p<0.001); the lowest levels (median 2.68, range 2.12-3.08 Log 10 IU/ml) were found in long-term responders who cleared HBsAg subsequently. During spontaneous and therapy-induced fluctuations of CHB (remissions and reactivations) total-and IgM-anti-HBc correlated with ALT (p<0.001, r=0.351 and p=0.008, r=0.185 respectively). Total-anti-HBc qualifies as a useful marker of HBV-induced-liver-disease that might help to PLOS ONE |

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Total hepatitis B core antigen antibody, a quantitative non-invasive marker of hepatitis B virus induced liver disease

Moriconi

Yuan

Song

et al. 2015

Digestive and Liver Disease

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“…However, the clinical significance of quantitative anti-HBc (qAnti-HBc) measurements has not been carefully investigated. With a novel double-sandwich anti-HBc quantitative immunoassay [9], we recently demonstrated that the pretreatment anti-HBc level is a potential new predictor for treatment response in both adefovir dipivoxil and peginterferon therapy [10], and it is the strongest predictor for 2-year HBeAg seroconversion in HBeAg-positive subjects treated with telbivudine alone or in combination with adefovir [11]. This new finding highlights the prognostic value of the qAnti-HBc level in CHB subjects.…”

Section: Introductionmentioning

confidence: 87%

Quantitative hepatitis B core antibody levels in the natural history of hepatitis B virus infection

Song

Liu

et al. 2015

Clinical Microbiology and Infection

108

118

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We previously demonstrated that pretreatment quantitative anti-hepatitis B core protein (qAnti-HBc) levels can predict the treatment response for both interferon and nucleoside analogue therapy, but the characteristics of qAnti-HBc during chronic hepatitis B virus (HBV) infection remain poorly understood. To understand this issue, the qAnti-HBc levels were evaluated in individuals with past HBV infection, occult HBV infection and chronic HBV infection in the immune tolerance phase, immune clearance phase, low-replicative phase and hepatitis B e antigen (HBeAg)-negative hepatitis phase. Individuals with hepatitis B surface antigen (n = 598, 3.74 ± 0.90 log10 IU/mL) had significantly higher (p < 0.001, approximately 1000-fold) serum qAnti-HBc levels than those who had occult HBV, and serum qAnti-HBc levels were significantly higher in the occult HBV group than in the past HBV infection group (p < 0.001). qAnti-HBc levels were positively correlated with alanine aminotransferase levels (R = 0.663, p < 0.001), and subjects with an abnormal alanine aminotransferase level had a higher qAnti-HBc level (p < 0.001). Serum qAnti-HBc level varied in different phases of HBV infection, as determined by host immune status. Serum qAnti-HBc level is strongly associated with hepatitis activity in subjects with chronic HBV infection.

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“…This hypothesis has been demonstrated in two small sample size cohorts, the results of which showed that pretreatment anti-HBc could be an additional predictor for HBeAg seroconversion both in the IFN and NUC treated cohorts. 17 Due to limited sample size and insufficient control of the cohorts, these new findings warranted a more rigorous validation.…”

Section: Significance Of This Studymentioning

confidence: 99%

Baseline quantitative hepatitis B core antibody titre alone strongly predicts HBeAg seroconversion across chronic hepatitis B patients treated with peginterferon or nucleos(t)ide analogues

Fan

Sun

Yuan

et al. 2015

Gut

Self Cite

112

109

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ObjectiveThe investigation regarding the clinical significance of quantitative hepatitis B core antibody (anti-HBc) during chronic hepatitis B (CHB) treatment is limited. The aim of this study was to determine the performance of anti-HBc as a predictor for hepatitis B e antigen (HBeAg) seroconversion in HBeAg-positive CHB patients treated with peginterferon (Peg-IFN) or nucleos(t)ide analogues (NUCs), respectively.DesignThis was a retrospective cohort study consisting of 231 and 560 patients enrolled in two phase IV, multicentre, randomised, controlled trials treated with Peg-IFN or NUC-based therapy for up to 2 years, respectively. Quantitative anti-HBc evaluation was conducted for all the available samples in the two trials by using a newly developed double-sandwich anti-HBc immunoassay.ResultsAt the end of trials, 99 (42.9%) and 137 (24.5%) patients achieved HBeAg seroconversion in the Peg-IFN and NUC cohorts, respectively. We defined 4.4 log10 IU/mL, with a maximum sum of sensitivity and specificity, as the optimal cut-off value of baseline anti-HBc level to predict HBeAg seroconversion for both Peg-IFN and NUC. Patients with baseline anti-HBc ≥4.4 log10 IU/mL and baseline HBV DNA <9 log10 copies/mL had 65.8% (50/76) and 37.1% (52/140) rates of HBeAg seroconversion in the Peg-IFN and NUC cohorts, respectively. In pooled analysis, other than treatment strategy, the baseline anti-HBc level was the best independent predictor for HBeAg seroconversion (OR 2.178; 95% CI 1.577 to 3.009; p<0.001).ConclusionsBaseline anti-HBc titre is a useful predictor of Peg-IFN and NUC therapy efficacy in HBeAg-positive CHB patients, which could be used for optimising the antiviral therapy of CHB.

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Quantitative hepatitis B core antibody level may help predict treatment response in chronic hepatitis B patients

Cited by 72 publications

References 4 publications

Total hepatitis B core antigen antibody, a quantitative non-invasive marker of hepatitis B virus induced liver disease

Total hepatitis B core antigen antibody, a quantitative non-invasive marker of hepatitis B virus induced liver disease

Quantitative hepatitis B core antibody levels in the natural history of hepatitis B virus infection

Baseline quantitative hepatitis B core antibody titre alone strongly predicts HBeAg seroconversion across chronic hepatitis B patients treated with peginterferon or nucleos(t)ide analogues

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