Risk factors for very low-level viremia in patients with chronic hepatitis B virus infection: A single-center retrospective study

Background and aim

Several effective antiviral drugs are now available; however, the risk of liver-related complications is still present. Low-level viremia (LLV), defined as a hepatitis B virus (HBV) deoxyribonucleic acid (DNA) load lower than 2000 IU/mL, is one of the major factors responsible for these complications. It has been reported that 22.7–43.1% of patients with HBV experience LLV. Herein, we aimed to explore the risk factors for very LLV (VLLV) during antiviral treatment.

Methods

We collected data of patients with chronic hepatitis B (CHB) who received nucleos(t)ide analog treatment from October 2016 to April 2021. VLLV was defined as an HBV DNA load of 9–20 IU/mL. A total of 139 patients with LLV were matched with 139 patients with a sustained virological response at a 1:1 ratio according to age and gender.

Results

Seropositivity rates for hepatitis B e antigen (HBeAg) (45.3% vs. 17.3%, P < 0.001) and hepatitis B surface antigen (HBsAg, 3.11 ± 0.68 lg IU/mL vs. 2.54 ± 1.04 lg IU/mL, P < 0.001) and alanine aminotransferase levels (30.34 ± 15.08 U/L vs. 26.15 ± 16.66 U/L, P = 0.040) in the two groups were significantly different. The multivariate analysis showed that both HBeAg seropositivity (adjusted odd ratio (aOR), 3.63; 95% confidence interval (CI): 1.98–6.64; P < 0.001) and HBsAg levels (aOR, 2.21; 95% CI: 1.53–3.20; P < 0.001) are independent risk factors for VLLV. During the multivariate analysis in the subgroup of HBeAg-positive patients, male gender (aOR, 3.68; 95% CI: 1.23–10.76; P = 0.017) and high HBsAg (aOR, 4.86; 95% CI: 1.73–13.64; P = 0.003) levels were significantly correlated with VLLV. However, this was not the case in HBeAg-negative patients (P > 0.050). HBeAg seropositivity (aOR, 5.08; 95% CI: 2.15–12.02; P < 0.001 vs. aOR, 2.78; 95% CI: 1.16–7.00; P = 0.022) and HBsAg levels (aOR, 2.75; 95% CI: 1.41–5.37; P = 0.003 vs. aOR, 2.10; 95% CI: 1.27–3.46; P = 0.004) significantly increased the risk of VLLV, irrespective of the age group. Both HBsAg (area under the receiver operating characteristic curve (AUC), 0.681; 95% CI: 0.623–0.736; P < 0.001) and HBeAg (AUC, 0.640; 95% CI: 0.581–0.697; P < 0.001) had certain predictive value for VLLV.

Conclusion

HBeAg seropositivity and higher HBsAg levels were not only risk factors for VLLV but also predicted its occurrence. When a patient with CHB remains HBeAg seropositive with high HBsAg levels after antiviral treatment for 48 weeks, emphasis should be placed on the potential occurrence of VLLV, warranting the use of highly sensitive HBV DNA detection methods.