Antivirals for HBeAg-positive hepatitis B outside EASL 2025 criteria were linked to much less HCC

Design

Multicentre retrospective cohort with propensity score matching

Population

30,784 Chinese patients with chronic HBV outside EASL 2025 strong treatment criteria

Primary outcome

Incident cirrhosis and hepatocellular carcinoma

Effect

Phase-transition group: HCC HR 0.25 (0.16–0.41); high-replicative group: HCC HR 0.03 (0.01–0.21)

This cohort from 12 Chinese centres included 30,784 people with chronic hepatitis B who did not meet the 2025 EASL strong treatment criteria. They were grouped by phase: HBeAg-positive with very high viral load and normal ALT under 30 years; HBeAg-positive approaching phase transition, typically 30 or over; and two HBeAg-negative low-replicative groups.

Over up to five years (117,814 person-years), 635 developed cirrhosis and 164 HCC. Nucleos(t)ide analogue therapy was associated with lower cirrhosis (HR 0.18) and HCC (HR 0.03) in the young high-replicative group, and lower cirrhosis (HR 0.50) and HCC (HR 0.25) in the phase-transition group. No associations were seen in the HBeAg-negative groups. Propensity-matched analyses agreed.

Many clinicians, in India as elsewhere, defer treatment in HBeAg-positive patients with normal ALT. This adds to evidence that treating earlier in HBeAg-positive, high-viral-load patients may prevent cancer — though it is observational, and EASL has not changed its criteria.

• Consider treatment for HBeAg-positive patients with high viral load, especially from age 30, even with normal ALT.
• No benefit was seen in HBeAg-negative patients with low viral load and normal ALT; continue monitoring them.
• Current EASL strong criteria have not changed; discuss the evidence with the patient.
• Family history of HCC and fibrosis remain key reasons to treat.
• Long-term adherence matters; treatment is usually indefinite.

Why it matters

It challenges the long-standing practice of watching HBeAg-positive patients with normal ALT, in a disease common in India.

Don't overread it

Observational — treated and untreated patients may differ in ways adjustment cannot capture, and EASL guidance is unchanged.

The statistics, in plain English

A hazard ratio of 0.25 means a 75% lower rate of HCC over the follow-up; 0.03 suggests a very large reduction, but with few events its precision is limited (95% CI 0.01–0.21).

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