Predictive Factors for HBsAg Loss in Chronic HBeAg-Negative Hepatitis B Virus Infection: Insights From a 5-Year French Cohort

Abstract

Prognostic factors for the long-term evolution of chronic hepatitis B e antigen (HBeAg)-negative hepatitis B virus (HBV) infection may vary depending on local epidemiology. We aimed to identify these factors in France, where the epidemiology is influenced by diverse immigration. Hepatitis B surface antigen (HBsAg)-positive, HBeAg-negative adults with normal transaminase levels and viral loads < 20,000 IU/mL for 1 year, without viral co-infection or advanced liver disease, were enrolled for a 5-year follow-up. A total of 564 patients were recruited from 23 centres (54.4% women, mean age 42.3 ± 12 years, 47.7% from sub-Saharan Africa). HBV DNA was detectable but < 2000 IU/mL for most (71.3%). Genotypes E (27.8%) and A (20.0%) were predominant. The mean HBsAg titre was 3.8 ± 3.4 log IU/mL, > 1000 IU/mL in 60% of cases, and higher in genotype E (p < 0.0001). During follow-up, 18 patients received antiviral treatment, 9 for viral reactivation (0.3% per year) and 9 preemptively. HBsAg loss occurred in 39 patients (1.4% per year). These patients were older (p < 0.0001), more frequently treated for dyslipidemia, hypertension or diabetes (p < 0.05), and had lower baseline HBV DNA (p = 0.0112) and HBsAg (p < 0.0001), but similar levels of HBcrAg compared to those who did not clear HBsAg. Baseline HBsAg was the only independent predictor of HBsAg loss (p = 0.009). In this cohort, HBsAg < 153 IU/mL predicted clearance with 87% sensitivity and specificity. In conclusion, baseline HBsAg accurately predicted seroclearance at 5 years in patients with chronic HBeAg-negative infection, regardless of genotype, sex, or geographical origin, indicating that this marker is widely applicable for reducing the frequency of patient monitoring.

Keywords: HBV genotype; HBV reactivation; HBV‐DNA; HBcrAg; HBeAg‐negative chronic HBV infection; HBsAg; HBsAg loss prediction.

FIGURE 1

Baseline HBsAg and HBcrAg levels, by genotype. (a) HBsAg titres (mean ± SD log IU/mL). Genotype A: 3.33 ± 0.8; B: 2.36 ± 0.9; C: 3.0 ± 0.2; D: 2.62 ± 1.1; E: 3.57 ± 0.9. HBsAg titres in genotype E were higher than titres in all other genotypes (p < 0.0001). (b) HBcrAg levels. The frequency of quantifiable HBcrAg levels was higher in genotypes B and C compared to genotypes A, D and E (p < 0.05).

FIGURE 2

Performance of baseline HBsAg and HBV DNA quantification to identify patients who will lose HBsAg during 5‐years follow‐up. Receiver operating characteristic curve (ROC) for prediction of HBsAg loss based on baseline serum levels of HBsAg and HBV DNA. Areas under the curve were 0.927 for HBsAg levels, and 0.771 for HBV DNA levels.