Hepatitis B surface antigen (HBsAg) clearance is recognized as a key marker of functional cure in chronic hepatitis B virus (HBV), as it is associated with a substantially reduced risk of progression to advanced liver disease. A recent meta-analysis conducted by researchers from China demonstrated that pegylated interferon-α therapy can significantly enhance HBsAg clearance in different chronic HBV infection groups, providing important evidence to support personalized treatment strategies.
Chronic hepatitis B virus (HBV) infection remains a major global public health challenge. Achieving a functional cure can significantly reduce the risk of end-stage liver disease and improve patients' quality of life. Hepatitis B surface antigen (HBsAg) clearance or seroconversion is widely recognized as a key indicator of functional cure in chronic hepatitis B (CHB). However, spontaneous HBsAg clearance is rare, with an annual rate of only about 1% in both children and adults. Currently, therapy based on pegylated interferon-alpha (PegIFNα) is regarded as one of the most promising options for attaining clinical cure. However, most prior studies have concentrated on single-dimensional analysis of specific subgroups without a comprehensive evaluation of the overall treatment population.
To address this gap, Professor Enqiang Chen from West China Hospital, along with a team of researchers, conducted the first comprehensive systematic review and meta-analysis summarizing HBsAg clearance and seroconversion rates in different chronic HBV infections at different treatment durations and follow-up periods after therapy discontinuation. Their findings were made available online on August 24, 2026, in the Chinese Medical Journal .
"PegIFNα can enhance HBsAg clearance in different chronic HBV infection groups," Prof. Chen explained. "In particular, nucleos(t)ide analogs (NAs)-experienced patients, inactive HBsAg carriers (IHCs), and children with chronic hepatitis B (CHB) had significantly higher HBsAg clearance rate than that observed with spontaneous clearance and long-term NAs therapy."
For example, PegIFNα therapy achieves an HBsAg clearance rate of 57% in IHCs, compared with only 1.54% in patients on NA monotherapy or untreated cohorts. In children with CHB, PegIFNα increases the HBsAg clearance rate to 22%, markedly higher than the spontaneous annual clearance rate of ~1% observed in untreated children. In NA-treated CHB patients, HBsAg-negative individuals tend to exhibit higher clearance rates. Specifically, in HBsAg-negative CHB patients with baseline HBsAg levels ≤1500 IU/mL or <1000 IU/mL, clearance rates can reach up to 35% and 45%, respectively. In contrast, with NA monotherapy, the HBsAg clearance rate remains low, averaging ~0.22% per year, amounting to ~2.11% over a 10-year period.
Chronic HBV infection is particularly prevalent in endemic regions of Asia and sub-Saharan Africa. Asian experts (72% of the included studies) were among the pioneers in recognizing the significance of HBsAg clearance. Over nearly two decades of clinical experience, extensive research has been conducted on PegIFNα across different chronic HBV infection populations. They have conducted comprehensive investigations into HBsAg clearance following PegIFNα treatment for CHB. We conducted subgroup analyses focusing on Asian populations (predominantly Chinese) and other ethnic groups. The rates of HBsAg clearance and seroconversion in Asian patients were 21% and 18%, respectively.
CHB is characterized by profound clinical heterogeneity, influenced by both viral and host immune factors. To elucidate the sources of variability, the researchers performed a meta-regression analysis, revealing that heterogeneity was partially explained by treatment strategy, publication year, baseline HBeAg status, and study design. Clinically, these findings highlight that combining PegIFNα with NAs significantly improves the likelihood of achieving HBsAg clearance (functional cure) compared to PegIFNα monotherapy. Moreover, treatment duration beyond 48 weeks and baseline HBeAg-negative status were identified as strong predictors of favorable outcomes, providing a data-driven framework for precision HBV management and patient stratification.
However, the HBsAg clearance rate in treatment-naive CHB patients is around 5%. Ongoing research is exploring broader treatment populations and optimizing strategies—such as extending therapy duration, intermittent dosing, and combination regimens involving novel agents—to improve clearance rates toward functional cure. Preliminary evidence suggests that combining new drugs with PegIFNα could yield promising results, though confirmation of sustained high rates of clearance requires further investigation.
"PegIFNα remains the cornerstone in pursuing a functional cure for hepatitis B," Prof. Chen concluded. "PegIFNα therapy provides an opportunity for HBsAg clearance in different chronic HBV infections. Due to the diverse characteristics of individuals with HBV infection, personalized treatment is key."
