HBsAg quantification predicts off-treatment response to interferon in chronic hepatitis B patients: a retrospective study of 250 cases

Abstract

Background: For chronic hepatitis B (CHB) patients without willingness to extend the routine duration of interferon (IFN) therapy, it is important to identify patients who will benefit from treatment cessation. Hepatitis B surface antigen (HBsAg) quantification is recommended for management of IFN therapy. At present, the understanding on end-of-treatment (EOT) HBsAg level predicting post-treatment response to IFN is still finite. Methods: A total of 2451 non-cirrhosis, HBsAg-postive patients treated with IFN-based therapy during the period from December 2010 to December 2017 at Nanfang Hospital were enrolled in this study. Serum HBsAg levels at EOT were measured to evaluate the associations between EOT HBsAg levels (Group 1, HBsAg > 0.05 and ≤ 10 IU/ mL; Group 2, HBsAg > 10 and ≤ 200 IU/mL; Group 3, HBsAg > 200 IU/mL) with post-treatment HBsAg loss. Chisquared, t-test,,Kaplan-Meier analysis, Cox regression analysis, and Multivariate Logistic regression analysis were used to analyse and evaluate differences between the there groups. Results: The cumulative HBsAg loss rates 5 years after treatment in Group 1-3 were 30.4% (17/56), 9.8%(4/41) and 0%(0/153) (p < 0.001). An EOT HBsAg level of > 10 IU/mL showed relatively high negative predictive value (NPV) of up to 97.9% for HBsAg loss. Low baseline HBsAg level < 25,000 IU/mL, on-treatment HBsAg decline > 1 log10IU/mL at week 24 and EOT HBsAg level ≤ 10 IU/mL were found significantly associated with HBsAg loss. A total of 6 patients have achieved HBsAg loss at EOT and 17 patients with EOT HBsAg level ≤ 10 IU/mL have achieved posttreatment HBsAg loss. Baseline characteristics, dynamic changes of on-treatment HBsAg and duration of IFN therapy were balanced across patients with EOT or post-treatment HBsAg loss. Conclusion: EOT HBsAg level can serve as a monitoring indicator for IFN therapy. EOT HBsAg level ≤ 10 IU/mL was found to lead to high rate of post-treatment HBsAg loss. For patients without willingness to extend IFN treatment, off-treatment follow-up could be considered when HBsAg level decreased to ≤10 IU/mL.

Chronic Hepatitis B Finite Treatment: Similar and Different Concerns With New Drug Classes

“…In the RETRACT-B study, HBsAg loss after 4 years off therapy was 43%, 7.4%, and 1.1% in those with EOT HBsAg <100, 100–1000, and >1000 IU/mL, respectively [ 8 ]. Wu et al [ 16 ] reported 5-year follow-up in 2451 patients who had received pegylated interferon: the cumulative rates of HBsAg loss were 30%, 10%, and 0% for patients with EOT HBsAg levels of <10, 10–100, and >100 IU/mL respectively. The negative predictive value of EOT HBsAg >10 IU/mL was 97.9% [ 16 ].…”

“…Wu et al [ 16 ] reported 5-year follow-up in 2451 patients who had received pegylated interferon: the cumulative rates of HBsAg loss were 30%, 10%, and 0% for patients with EOT HBsAg levels of <10, 10–100, and >100 IU/mL respectively. The negative predictive value of EOT HBsAg >10 IU/mL was 97.9% [ 16 ].…”

Intracellular interferon signalling pathways as potential regulators of covalently closed circular DNA in the treatment of chronic hepatitis B

“…HBV itself also significantly affects patient response to IFN therapy, as treatment outcomes are more efficacious in patients carrying the genotype A virus than the genotype D virus[ 64 ], and patients are also thrice more responsive to IFN treatment if they carry the genotype B virus than genotype C virus[ 65 ]. As further proof to the extent in which HBV alters patient sensitivity to IFN treatment, 30.4% of patients with low end-of-treatment HBs levels (< 10 IU/mL) achieve HBs clearance in a 5-year follow-up, in stark contrast to < 10% of patients achieving HBs clearance[ 66 ] when end-of-treatment HBs levels are ≥ 10 IU/mL. This is further supported by the association of greater PEG-IFN response in patients with HBV DNA levels of < 9 Log 10 copies/mL sera[ 67 ].…”

Identification and Mapping of HBsAg Loss-Related B-Cell Linear Epitopes in Chronic HBV Patients by Peptide Array

“…Persistent exposure to high sAg loading is associated with a dysfunctional HBV-specific immune response (16,17). Conversely, patients who achieve sAg loss following antiviral treatment always have a satisfactory off-treatment response and a low incidence of hepatocellular carcinoma (18)(19)(20). Hence, it is necessary to explore the dominant B-cell epitopes on HBV proteins among patients in different phases and evaluate the association between dominant epitopes and powerful immune responses or favorable treatment responses.…”