Long-Term HBV DNA Response Patterns Track Outcomes In Cirrhosis
Key Takeaways
- HBV DNA response patterns during the first two years of nucleos(t)ide analog therapy identified distinct long-term outcome groups in patients with HBV-related cirrhosis.
- Patients with maintained virological response had lower hepatocellular carcinoma incidence and lower liver-related mortality than those with virological breakthrough or partial virological response during follow-up.
Investigators evaluated 1,869 patients receiving nucleos(t)ide analog therapy between 2009 and 2019. Serum HBV DNA levels during the first two treatment years were used to classify the initial antiviral response in this real-world setting.
Patients who first reached complete virological response were then separated by later HBV DNA behavior into maintained virological response or virological breakthrough during follow-up. Primary outcomes were hepatocellular carcinoma, acute-on-chronic liver failure, and liver-related death, while secondary endpoints were recompensation and progression to decompensation over a median seven years.
Across the cohort, maintained virological response, virological breakthrough, and partial virological response occurred in 65.4%, 26.5%, and 8.1% of patients, respectively. In compensated cirrhosis, five- and ten-year cumulative HCC incidence was 10.1% and 14.2% with maintained response, versus 17.0% and 33.6% with the comparison patterns. In decompensated cirrhosis, the corresponding incidences were 19.5% and 25.7% with maintained response, versus 36.7% and 49.7% with the comparison patterns.
Cumulative serum HBsAg clearance reached 9.8% in the overall cohort, indicating that surface antigen loss was uncommon during prolonged antiviral follow-up. Clearance was more frequent, at 34.9%, among patients whose baseline HBsAg level was below 100 IU/mL. Hepatic recompensation was also more frequent with maintained virological response than with virological breakthrough, at 34.1% versus 22.5%, with P < 0.001. Functional cure was defined as HBsAg clearance together with undetectable serum HBV DNA during ongoing nucleos(t)ide analog therapy, and this group had the lowest cumulative HCC incidence, at 3.9% after five years and 8.7% after ten years.