Antivirals linked to less cirrhosis and HCC in HBeAg-positive patients outside EASL 2025 strong criteria

Design

Multicentre retrospective cohort with propensity score matching

Population

30,784 people with chronic HBV infection, 12 Chinese centres

Primary outcome

Incident cirrhosis and hepatocellular carcinoma

Effect

HBeAg+ high replicative: cirrhosis HR 0.18, HCC HR 0.03; HBeAg+ ≥30 y: cirrhosis HR 0.50, HCC HR 0.25

The 2025 EASL guidance broadened treatment for chronic hepatitis B, but many patients with normal ALT and no significant fibrosis still fall outside its strong recommendations. This Chinese cohort, published in Gut on 7 October, followed 30,784 people with chronic HBV infection across 12 centres for up to five years, focusing on four groups outside the strong criteria.

In HBeAg-positive patients under 30 with very high viral load (HBV DNA ≥8 log IU/mL), normal ALT and little fibrosis, nucleos(t)ide therapy was associated with much lower risk of cirrhosis (HR 0.18) and hepatocellular carcinoma (HR 0.03). In HBeAg-positive patients typically over 30 with DNA ≥6 log IU/mL and normal ALT, the associations were also strong (cirrhosis HR 0.50, HCC HR 0.25). In HBeAg-negative patients with low or modest viral load, there was no association. Propensity-matched analyses agreed.

This is observational: treated patients may differ in ways not captured, and the HR of 0.03 for cancer rests on few events. The guideline has not changed on the basis of this study. But it supports a lower threshold for treating HBeAg-positive adults, particularly those over 30 or with a family history. Generic tenofovir and entecavir are inexpensive in India.

• Do not dismiss HBeAg-positive patients with normal ALT as 'inactive'; check HBV DNA and fibrosis.
• In HBeAg-positive adults over 30 with HBV DNA ≥6 log IU/mL, discuss starting tenofovir or entecavir even with normal ALT.
• Family history of hepatocellular carcinoma strengthens the case for treatment.
• HBeAg-negative patients with low viral load and no fibrosis can generally continue monitoring rather than treatment.
• Whatever the decision, keep regular ALT, HBV DNA and fibrosis assessment going.

Why it matters

It suggests the 'immune-tolerant' label may be leaving people at real risk of cirrhosis and liver cancer untreated.

Don't overread it

Observational data from China; it supports, but does not prove, benefit from treating these groups.

The statistics, in plain English

Hazard ratios of 0.18 to 0.50 for cirrhosis mean 50–82% lower rates in treated patients. The cancer hazard ratio of 0.03 is based on very few events, so its interval is wide and the true effect is probably smaller.

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