Dose–response relationship between qAnti‐HBc and liver inflammation in chronic hepatitis B with normal or mildly elevated alanine transaminase based on liver biopsy

Abstract

The proportion of chronic hepatitis B (CHB) patients with normal or mildly elevated alanine transaminase (NMALT) levels who have moderate to severe inflammation was not rare. However, we lacked appropriate biomarkers to evaluate liver inflammation in these populations. We aimed to explore the relationship between quantitative hepatitis B core antibody (qAnti-HBc) and hepatic histological inflammation. This multicenter cohort study enrolled participants from 34 Chinese hospitals including 1376 treatment-naive CHB patients with liver biopsy (934 with NMALT entered treatment-naive cohort; 423 with secondary liver biopsy entered treatment cohort). Using unadjusted and multivariate-adjusted generalized linear models, generalized additive models with smooth curve fitting, we evaluated the associations between qAnti-HBc and liver inflammation in these patients. In the treatment-naive patients, qAnti-HBc was positively associated with liver inflammation (histology activity index [HAI] evaluated by Ishak scoring system; fully adjusted model: β = 0.48, 95% confidence interval [CI] [0.30-0.66], p < 0.001). For per-SD increase in qAnti-HBc, the risk of moderate to severe inflammation (HAI ≥ 5) increased by 56% (odds ratio [OR] = 1.56, 95% CI [1.28-1.91], p < 0.001). The curve fitting indicated a significant "threshold effect" (inflection point was 4.5 log 10 IU/ml, p < 0.001). Subgroup analyses and interactions were not significant (all p > 0.05). In the treatment patients, there was no significant correlation between qAnti-HBc and liver inflammation, whether based on unadjusted, minimally adjusted, or fully adjusted models (all p > 0.100). Paired analyses showed a significant correlation between decreasing in qAnti-HBc and alleviation of liver inflammation. qAnti-HBc was positively correlated with liver inflammation in treatment-naive CHB patients with NMALT. The cutoff value of qAnti-HBc for the diagnosis of moderate to severe inflammation was 4.5 log 10 IU/ml. Decreasing in qAnti-HBc was positively correlated with liver inflammation relieving.

Quantitative hepatitis B core antibody and quantitative hepatitis B surface antigen: Novel viral biomarkers for chronic hepatitis B management

“…Several studies have looked at the additional role of qAnti-HBc in identifying immune activation status and inflammation in HBV-positive persons with normal ALT levels[ 88 , 89 ]. Zhang et al [ 90 ] found that in 1376 untreated CHB patients with normal ALT, there was a dose-responsive association between the degree of liver inflammation and qAnti-HBc. The qAnti-HBc cut-off value for identifying moderate and severe inflammation was around 4.5 Log10 IU/mL.…”

Clinical Utility of Quantitative HBV Core Antibodies for Solving Diagnostic Dilemmas

“…There is mounting evidence that qAnti-HBc level not only correlates positively with the severity of liver inflammation but also decreases with the improvement of inflammation severity in patients receiving therapy [ 19 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ]. It was shown that serum qAnti-HBc level, ALT and liver inflammation activity were closely related [ 44 , 47 ].…”

“…[ 21 , 37 , 39 , 40 ] (prediction of viral reactivation upon immunosuppression), refs. [ 19 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 ] (prediction of hepatic inflammation grade), refs. [ 50 , 51 , 52 , 53 ] (prediction of fibrosis stage), ref.…”

Hepatitis B Core Antibody Level: A Surrogate Marker for Host Antiviral Immunity in Chronic Hepatitis B Virus Infections

“…The commonly used marker for liver damage, ALT, carries a risk of missed detection, with 20–30% of patients with normal ALT experiencing moderate to severe liver inflammation. Extensive studies have investigated the additional role of qAnti-HBc in discriminating inflammation and immune activation status in individuals infected with HBV and with normal ALT levels [ 29 , 40 , 41 , 42 ]. In a multicenter study, Zhang et al revealed a dose-responsive relationship between qAnti-HBc and liver inflammation severity in 1376 untreated CHB patients with normal ALT (β = 0.48, p < 0.001), with the qAnti-HBc cut-off value for diagnosing moderate and severe inflammation at about 4.5 log10 IU/mL [ 41 ].…”

“…Extensive studies have investigated the additional role of qAnti-HBc in discriminating inflammation and immune activation status in individuals infected with HBV and with normal ALT levels [ 29 , 40 , 41 , 42 ]. In a multicenter study, Zhang et al revealed a dose-responsive relationship between qAnti-HBc and liver inflammation severity in 1376 untreated CHB patients with normal ALT (β = 0.48, p < 0.001), with the qAnti-HBc cut-off value for diagnosing moderate and severe inflammation at about 4.5 log10 IU/mL [ 41 ]. This study also noted that the decline of qAnti-HBc after NAs-treatment correlated with the alleviation of liver histological inflammation.…”