Multiple Low-level Viremia Suggest Hindered Liver Fibrosis Regression in Chronic Hepatitis B Patients during Antiviral Therapy

Abstract

Abstract Background:Low-level viremia (LLV) occurs in chronic hepatitis B (CHB) patients despite antiviral treatment, which may cause failed histological regression. Our study aims to investigate the impact of different LLV types on fibrosis regression. Methods: The prospective study enrolled CHB patients with paired liver biopsies before and after 260 weeks of entecavir treatment. Fibrosis regression was defined by the Ishak score or P-I-R system. Patients were grouped as the SVR (HBV DNA <20 IU/ml persistently) or LLV (HBV DNA between 20 to 2000 IU/mL), which were further grouped as very low-level viremia (VLLV, HBV DNA <50 IU/ml), occasionally LLV (OLLV, HBV DNA ≥50 IU/ml only once), and multiple LLV (MLLV, HBV DNA ≥50 IU/ml more than once). Logistic regression models were used to calculate the adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Results: The analysis included 111 CHB patients. In the SVR group (N=54), 39 (72.2%) patients had fibrosis regression, which was higher than the LLV (56.1%, p=0.080). The fibrosis regression rates for VLLV (30 patients), OLLV (17 patients), and MLLV (10 patients) were 70.0%, 52.9%, and 30.0%, respectively. Compared with SVR, VLLV (aOR=0.78; 95% CI: 0.28-2.21; p=0.644) was not associated with fibrosis regression, but patients with non-VLLV (aOR=0.27; 95% CI: 0.09-0.85; p=0.025), especially with MLLV (aOR=0.19; 95% CI: 0.04-0.97; p=0.046) is significantly associated with hindered fibrosis regression. Conclusions: Our study suggests that patients with detectable serum HBV DNA levels higher than 50 IU/mL need to be monitored carefully, especially in those with more than once.