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- Hepatitis B virus
- quantitative anti-HBc
- treatment response prediction
- hepatitis B
- hepatitis E
- infectious disease
- hepatitis C
- hepatocellular carcinoma
- hepatitis D
- liver disease in pregnancy
We read with interest the recent article by Dandri emphasising the use of novel quantitative biomarkers as tools for predicting treatment response and disease progression in chronic hepatitis B infection (CHB).1 The authors carried out a comprehensive review of the clinical implications of quantitative measurement of viral biomarkers both in blood and in liver, such as: serum HBsAg, serum HBeAg and intrahepatic cccDNA, based on current knowledge.1 In addition to these, we would like to propose a new potential prognostic biomarker in CHB: the quantitative hepatitis B core antibody (anti-HBc) level which may help predict treatment response in CHB patients.
Anti-HBc is one of most classical serological markers for HBV infection.2 However, the clinical significance of quantitative anti-HBc level is still largely unknown. By using a newly developed double-sandwich anti-HBc immunoassay validated by the WHO anti-HBc standards,3 ,4 we investigated its value in CHB patients.
In a cross-sectional cohort, we analysed the anti-HBc levels of 488 CHB patients and 350 healthy individuals with past HBV infection. The geometric mean level of anti-HBc in CHB patients was >1000-fold higher than that in individuals with past HBV infection (p<0.001, figure 1A). Among CHB patients, the anti-HBc levels in those who had elevated ALT levels (n=180) was significantly higher than those who had normal ALT levels (n=308) (p<0.001, figure 1A). Because elevated ALT levels in CHB is assumed to be due to a T-cell-mediated hepatocytolysis,5 the parallel increasing anti-HBc levels may reflect the host-adaptive anti-HBV immune activity. Moreover, the quantitative anti-HBc, thus, might also predict the response of patients receiving anti-HBV therapies.
To test this hypothesis, we further retrospectively investigated the usefulness of the baseline anti-HBc levels in predicting post-treatment response in two cohorts (A and B). Cohort A consisted of 49 HBeAg-positive patients treated with adefovir dipivoxil at 10 mg/day for 96 weeks and followed by a 12-week observation between years 2004–2007. Cohort B included 48 HBeAg-positive patients receiving peginterferon α-2a (180 μg/week) for 24 weeks, and followed by a 24-week observation in years 2005–2009 (Cohort B). As shown in table 1, patients with and without HBeAg seroconversion (SR) at the end of follow-up in the two cohorts had comparable (p>0.05) baseline values for age, gender, the levels of ALT (or stratification by 5×ULN), HBV DNA, HBsAg and anti-HBc-IgM. However, the SR(+) patients had a significantly higher baseline anti-HBc levels than SR(–) patients, either in cohort A (p=0.005) or B (p=0.011). The predictive value (indicated by area under the curve for SR of the baseline anti-HBc level was 0.810 (95% CI 0.675 to 0.948, p=0.004) and 0.710 (95% CI 0.564 to 0.855, p=0.013) in cohorts A and B, respectively. Figure 1B showed the SR rate among patient groups classified by baseline anti-HBc level using the optimal cut-off indicated by the inflection point of the receiver operating characteristic in both cohorts. Patients with high baseline anti-HBc levels (≥29 000 IU/ml for cohort A or ≥9000 IU/ml for cohort B) had a higher SR rate than those with lower baseline anti-HBc levels (RR=7.22, 95% CI 1.69 to 30.9, p=0.006 in Cohort A; RR=2.10, 95% CI 1.06 to 4.17, p=0.021 in Cohort B). These results suggested that the pre-treatment anti-HBc level may be an additional predictor for post-treatment SR both in interferon or nucleos(t)ide analogue therapy.
In summary, baseline anti-HBc levels may serve as a useful marker indicating an ongoing host-immune activity against HBV, and the new findings may have clinical implications warranting further investigation.
Funding Supported by grants from the National Scientific and Technological Major Project (2012ZX10002-005); and acknowledgement of Taiwan Liver Consortium for patients recruitment.
Competing interests P-J Chen is a consultant for Novartis and Roche. D-S Chen is a consultant for Novartis and GlaxoSmithKline. J-H Kao is a consultant for Bristol-Myers Squibb, GlaxoSmithKline, Novartis, Omrix, and Roche; and is a member of the Speaker's Bureau for Roche, Bristol-Myers Squibb, GlaxoSmithKline, and Novartis.
Patient consent Obtained.
Ethics approval This study was approved by the Ethics Committees of Zhongshan Hospital of Xiamen University.
Provenance and peer review Not commissioned; externally peer reviewed.