Chronic hepatitis B (CHB) infection affects 254 million people worldwide and led to 1.32 million deaths from cirrhosis and hepatocellular carcinoma (HCC) in 2024. Antiviral therapy can reduce the risk of complications, but viral biomarkers are crucial for evaluating treatment efficacy and long-term prognosis. Recently, Professor Mengfeng Yuan's team from Queen Mary Hospital, The University of Hong Kong, published a latest study in Clinical and Molecular Hepatology (IF=14). This study aims to describe the longitudinal changes in HBV RNA in CHB patients receiving five years of nucleos (t)ide analogue (NUC) therapy.

Research Background: HBV RNA is a novel biomarker for chronic hepatitis B (CHB), reflecting the transcriptional activity of covalently closed circular DNA (cccDNA) in the liver. In untreated patients, HBV RNA levels are typically 1–2 log lower than HBV DNA levels. The primary mechanism of nucleos(t)ide analogue (NUC) therapy is to inhibit the reverse transcription of HBV RNA into HBV DNA, leading to an inversion of the RNA-to-DNA ratio after treatment. While most studies have described the early kinetics of HBV RNA during antiviral therapy, the dynamic changes of HBV RNA under long-term NUC treatment remain unclear.

Research Methods: This study included 1,354 CHB patients from Queen Mary Hospital, Hong Kong, aged ≥18 years, and assessed plasma samples from those receiving first-line NUC therapy. The baseline was set at the initiation of NUC treatment (year 0), followed by evaluations at years 1, 3, and 5. The lower limit of detection (LLOD) and quantification (LLOQ) for HBV RNA were 0.8 log U/mL (~20 copies/mL).

Research Results:

A total of 1,354 patients were enrolled. At baseline, the median age was 49.8 years (interquartile range [IQR]: 40.2–57.3 years), with 65.2% being male. The majority (83.9%) were HBeAg-negative, and 28.6% had cirrhosis. The median HBV DNA and HBV RNA levels were 5.76 (IQR: 3.54–7.17) log IU/mL and 3.68 (IQR: 2.42–5.19) log U/mL, respectively.