Editor's Note: Chronic hepatitis B (CHB) is a global public health issue, with hepatocellular carcinoma (HCC) being one of its most severe complications. Traditional viral markers have limited efficacy in predicting HCC risk, highlighting the need for new viral predictive indicators. On June 5, 2024, at the European Association for the Study of the Liver (EASL) annual meeting in Milan, Italy, Professor Jian Sun's team from Nanfang Hospital, Southern Medical University, presented a compelling poster on the predictive role of serum HBV RNA reduction in HCC risk among CHB patients undergoing nucleos(t)ide analog (NA) therapy (Abstract No. LBP-037).Study Background and Objectives
Due to the limited predictive efficacy of traditional viral markers, HCC risk prediction models for CHB patients on NA therapy rarely include viral factors. This study aimed to investigate the role of serum HBV RNA, a novel biomarker, in predicting HCC risk in patients receiving NA therapy.
Methods
A total of 1,374 CHB patients treated with entecavir (ETV) or tenofovir disoproxil fumarate (TDF) from two prospective cohorts were included. Serum HBV RNA levels were quantified at baseline and at years 1, 2, and 3 of treatment, with a detection limit of 50 copies/mL. The Cox proportional hazards model was used to explore the correlation between dynamic changes in serum HBV RNA and HCC risk.
Results
After a median follow-up of 5.4 years, 76 patients developed HCC. The analysis showed a significant nonlinear parabolic relationship between baseline and year 1 serum HBV RNA levels and HCC risk (P for nonlinearity < 0.050). A similar trend was observed for year 2 serum HBV RNA levels, though with weaker statistical significance (P for nonlinearity = 0.114).
Notably, the early reduction in serum HBV RNA during treatment (years 1 and 2) was independently linearly associated with HCC risk (P for linear trend < 0.05). Patients with a year 1 HBV RNA reduction ≤ 0.4 log10 copies/mL had 2.22 times the HCC risk compared to those with a reduction > 0.4 log10 copies/mL. Similarly, patients with a year 2 reduction ≤ 0.6 log10 copies/mL had 2.09 times the HCC risk compared to those with a reduction > 0.6 log10 copies/mL. Incorporating early serum HBV RNA reduction into existing HCC risk models—PAGE B, mPAGE B, and aMAP—further improved their predictive efficacy.
Conclusion
Early reduction in serum HBV RNA (years 1 and 2) is significantly correlated with HCC risk in CHB patients. Integrating early HBV RNA reduction into HCC risk prediction models in antiviral therapy populations could serve as an effective tool for HCC monitoring in CHB patients.
Researcher’s Insight
Professor Jian Sun: This study indicates that the early reduction in serum HBV RNA during antiviral treatment is associated with HCC risk in CHB patients, helping doctors more accurately assess HCC risk in NA-treated patients and develop more personalized treatment plans. As research progresses, HBV RNA as a novel biomarker is expected to play an increasingly important role in clinical practice for HCC prediction and prevention.
Original Source: Jian Sun, et al. “Serum HBV RNA Reduction and Hepatocellular Carcinoma Risk in Chronic Hepatitis B Patients Undergoing NA Therapy.” EASL 2024 Abstract LBP-037.
