- Design
- Post hoc individual participant data meta-analysis of eight prospective trials
- Population
- 581 patients with chronic hepatitis B on nucleos(t)ide analogue therapy receiving peg-interferon add-on; 44% HBeAg positive, 85% planned for 48 weeks
- Primary outcome
- HBsAg loss 6–12 months after the end of peg-interferon
- Effect
- Overall 8.6%; by baseline HBsAg <100 / 100–1000 / ≥1000 IU/mL: 37.7% / 9.8% / 2.3% (P < 0.001)
Peg-interferon added to nucleos(t)ide analogue therapy is used as a lead-in, a consolidation or a combination partner in hepatitis B cure strategies, without good estimates of what it achieves. This individual participant data meta-analysis pooled eight trials, 581 patients, with HBsAg loss at 6–12 months after the end of peg-interferon as the primary endpoint.
Overall, 50 patients (8.6%) achieved HBsAg loss. The number that matters is the stratification by HBsAg at the start of therapy: 37.7% where it was below 100 IU/mL, 9.8% between 100 and 1000, and 2.3% above 1000 (P < 0.001). The pattern held in both Caucasian and Asian patients (30.0/8.7/3.6% and 39.3/9.2/2.2%).
For patients starting above 1000 IU/mL, peg-interferon still did something: by 48 weeks, 47.5% had fallen below 1000 and 16.3% below 100. That reframes its role — not as a route to functional cure in that group, but as a way of moving patients into the range where novel agents are expected to work. The practical translation is a selection rule: check the HBsAg level before offering peg-interferon add-on, and say honestly what it is likely to achieve at that level.
- Measure quantitative HBsAg before offering peg-interferon add-on; it is the single best predictor of response here.
- Reserve the functional cure conversation for patients starting below 100 IU/mL, where nearly four in ten achieved HBsAg loss.
- Above 1000 IU/mL, frame peg-interferon as HBsAg reduction rather than clearance — 2.3% cleared.
- Counsel thoroughly on peg-interferon tolerability before starting; the response rates above make the risk-benefit calculation explicit.
- Quantitative HBsAg testing is not universally available in Indian practice, and this analysis makes the case for it as a treatment-selection test rather than a research assay.
Why it matters
Whether peg-interferon is worth its toxicity turns on one number that is often not measured before the decision.
Don't overread it
This is a post hoc meta-analysis of trials that were not designed to compare response by baseline HBsAg stratum.
The statistics, in plain English
The overall 8.6% figure is close to useless on its own, because it averages a group with a 37.7% response and a group with a 2.3% response. That is what stratified reporting is for. This was a post hoc pooled analysis of trials not designed to answer this question, so the strata were defined after the fact — the consistency across two ethnic groups is what makes the gradient credible rather than an artefact of how the cut points were chosen.
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