Has recent data showing reduced HCC and cirrhosis risk with antiviral therapy changed your threshold to treat non-cirrhotic chronic HBV patients with ALT 1–2× ULN?

This is an interesting study that certainly warrants consideration and discussion with patients about when to initiate antiviral therapy for chronic hepatitis B. Historically, my threshold for initiating treatment has been guided by ALT elevations, HBV DNA levels, HBeAg status, and evidence of liver fibrosis or other risk factors. The 2025 AASLD/IDSA guidelines have already moved toward considering treatment in some patients who fall outside traditional treatment thresholds, emphasizing shared decision-making while acknowledging the low certainty of the available evidence.

This study adds to that evolving evidence base, but I would like to see these findings replicated in larger cohorts, with careful attention to potential confounding and t...

For question one, other considerations are US findings and the patient's goals of care.

It seems we're talking about the "grey zone" or indeterminate phase patients here, particularly when asking about ALT between 1-2xULN, who may not meet the traditional AASLD treatment thresholds for those who have active or reactivated HBV (eAg+, ALT >2xULN, HBV viral load >20K intnl units/mL or eAg-, ALT >2xULN, HBV viral load >2K intnl units/mL).

In addition to the prior responses, it's important to add that patients in the grey zone may transition to an active phase of HBV that warrants treatment or transition to an inactive phase that warrants just monitoring and HCC screening. In one highly cited study, over 10 years, 22% will transition to an active state, 53% stay in the grey zone, and 25% transition to an inactive state (PMID: 33465...