Nucleos(t)ide Analogue Cessation in HBeAg-Negative Chronic Hepatitis B (STOP-NUC Trial)

Source: Excerpts from "STOP-NUC.pdf" - A multicenter randomized-controlled trial of nucleos(t)ide analogue cessation in HBeAg-negative chronic hepatitis B. Journal of Hepatology 2023.

Executive Summary

The STOP-NUC trial, a multicenter, randomized-controlled study, investigated the efficacy and safety of discontinuing nucleos(t)ide analogues (NUCs) in HBeAg-negative chronic hepatitis B patients who had achieved long-term viral suppression. The study found that cessation of NUC treatment was associated with a significantly higher rate of HBsAg loss (functional cure) compared to continued NUC treatment (10.1% vs 0%, p = 0.006). This beneficial effect was largely concentrated in patients with lower baseline HBsAg levels (<1,000 IU/ml), where the HBsAg loss rate reached 28%. The trial concluded that controlled NUC discontinuation is an effective and safe approach for achieving functional cure in a relevant proportion of HBeAg-negative patients without cirrhosis, especially those with low HBsAg levels at the time of cessation.

Key Findings:

• HBsAg Loss (Functional Cure): 10.1% of patients who stopped treatment achieved HBsAg loss vs 0% who continued (p = 0.006). The effect was more striking in patients with baseline HBsAg <1,000 IU/ml—28% achieved HBsAg loss in this group.
• HBsAg Seroconversion: 7.6% developed protective anti-HBs antibodies after stopping NUCs, compared to none in the continuation group.
• Sustained Remission Without Retreatment: 41% of patients who stopped NUCs maintained viral control (HBV DNA <2,000 IU/ml and normal ALT) over 96 weeks.
• Predictors of Success: Lower end-of-treatment HBsAg levels were strongly predictive of cure. HBsAg loss was not influenced by the specific NUC (TDF or ETV) used.
• Safety: While ALT flares occurred in 35.4% of those who stopped therapy, most were mild and self-resolving. Only 13.9% required retreatment. No serious adverse events related to cessation were reported.

What This Means for Patients: The findings suggest that in HBeAg-negative patients with sustained viral suppression and low HBsAg levels, stopping NUC treatment under medical supervision could lead to a real chance at functional cure—something rarely achieved with lifelong therapy. The mechanism may involve a kind of “immune reset” triggered by controlled viral reactivation.

Limitations & Future Directions:

• The study included only European patients; future trials are needed in Asia and Africa to assess applicability across HBV genotypes.
• The trial highlights the need for better biomarkers to predict who will benefit most from cessation.
• Long-term follow-up is underway to confirm durability of cure and safety beyond 96 weeks.

Bottom Line: The STOP-NUC trial has opened the door to a more personalized, finite treatment approach in chronic hepatitis B. For select patients, stopping therapy might not just be safe—it might offer the best shot at a cure.

This episode analyses the current landscape of chronic hepatitis B (CHB) clinical guidelines across five major regions—United States (AASLD), Canada (CASL), China, Japan (JSH), and Europe (EASL)—alongside the World Health Organization (WHO) guidelines. The analysis highlights significant variations in treatment thresholds, diagnostic approaches, implementation strategies, and market access opportunities, all of which are critical for pharmaceutical commercialization and strategic planning for CHB therapies.

Key themes include:

• Divergent Treatment Initiation Criteria: China has the most liberal treatment thresholds, aiming for WHO elimination targets by 2030, while other regions maintain more conservative approaches.
• Emphasis on Non-Invasive Assessment: There's a growing trend towards non-invasive fibrosis assessment, led by EASL and WHO.
• Functional Cure as a Goal: While functional cure (sustained HBsAg loss with undetectable HBV DNA) is consistently defined, China uniquely positions it as the primary treatment goal.
• Regional Healthcare System Impact: Variations in healthcare infrastructure, cost barriers, and specialist requirements significantly influence guideline implementation and patient access.
• EASL's Strategic Middle Ground: The European guidelines represent a balanced and progressive approach, offering a template for global development strategies.

This episode reviews the key updates and strategic changes introduced in the European Association for the Study of the Liver (EASL) 2025 Clinical Practice Guidelines for Hepatitis B Virus (HBV) management. These revisions aim to simplify algorithms, integrate novel biomarkers, expand treatment criteria, and support global HBV elimination targets, while improving patient outcomes through evidence-based recommendations.

UK's NHS Opt-Out Testing

Italy's Community Testing and Cultural Mediators

French Reflex Hepatitis Testing in Paris and Marseilles

Spain's Mobile Hepatitis Testing

Bordeaux's Hepatitis Elimination Program - 5 June 2025

Germany's Check-Up 35 Program - 5 Jun 25