- Design
- Multicentre retrospective cohort with propensity matching
- Population
- 30,784 people with chronic HBV outside EASL 2025 strong indications
- Primary outcome
- Incident cirrhosis and HCC up to 5 years
- Effect
- HBeAg+ transition: cirrhosis HR 0.50 (0.41–0.61), HCC HR 0.25 (0.16–0.41)
A Gut cohort study analysed 30,784 people with chronic hepatitis B across 12 Chinese centres who did not meet EASL 2025's strong treatment indications, followed for up to five years. It grouped them by phase and compared those who did and did not receive nucleos(t)ide analogues.
In young HBeAg-positive patients with very high HBV DNA, normal ALT and little fibrosis, treatment was associated with much lower cirrhosis (HR 0.18) and HCC (HR 0.03). In HBeAg-positive patients approaching phase transition — usually over 30, HBV DNA 6 log or higher, normal ALT — it was associated with lower cirrhosis (HR 0.50) and HCC (HR 0.25). In HBeAg-negative patients with low or modest viral load, normal ALT and little fibrosis, there was no association. Propensity-matched analyses agreed.
This supports the trend towards treating more HBeAg-positive patients, including the so-called immune-tolerant group, while confirming that low-replicative HBeAg-negative patients gain little. For Indian practice, where hepatitis B is common and generic tenofovir and entecavir are widely available, the question of who to treat earlier matters at scale.
The data are observational and treated patients may differ from untreated ones. EASL guidance has not changed on the basis of this study. Discuss treatment with HBeAg-positive patients over 30 with high viral load, and keep monitoring the rest.
- Consider discussing antiviral treatment with HBeAg-positive patients over 30 with HBV DNA of 6 log IU/mL or more, even with normal ALT
- Consider treatment for young HBeAg-positive patients with very high viral load, weighing lifelong therapy
- Continue monitoring rather than treating HBeAg-negative patients with low viral load, normal ALT and no significant fibrosis
- Follow current guideline indications while this evidence is assessed
- Keep HCC surveillance for all patients who meet surveillance criteria, treated or not
Why it matters
It challenges the practice of watching HBeAg-positive, high-viral-load patients with normal ALT without treatment.
Don't overread it
Observational: treated and untreated patients may differ, and the guideline itself has not changed.
The statistics, in plain English
An HCC HR of 0.03 in young HBeAg-positive patients comes from few events and is likely an overestimate of the true effect; the HR of 0.25 in the phase-transition group, with a narrower interval (0.16–0.41), is the more robust signal.
Read the rest in the app
You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.
Scan to keep reading on your phone. No account needed to start.
Tomorrow morning, before your first patient
One edition a day for gastroenterology & hepatology, written by the desk, every claim tied to its paper. Six minutes.
Get the app — free