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

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.