At the 2024 Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), Dr. Hui Wang’s team from the Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University, presented groundbreaking research on novel hepatitis B biomarkers. Their study, which investigated the predictive value of serum HBV RNA and HBcrAg for low-level viremia (LLV) in chronic hepatitis B (CHB) patients undergoing nucleos(t)ide analog (NAs) therapy, was accepted for poster presentation (No. 1367).This research is the first to conduct dynamic monitoring of HBV RNA and HBcrAg in CHB patients treated with NAs. The results revealed that compared to patients who achieved sustained virological response (MVR), those with LLV consistently exhibited higher serum levels of HBV RNA and HBcrAg throughout the 96-week follow-up period. These findings establish HBV RNA and HBcrAg as valuable predictive biomarkers, providing clinicians with new tools for the antiviral treatment monitoring of CHB patients. Regular monitoring of these markers offers the potential to identify LLV early, enabling timely prevention and intervention to mitigate disease progression. Moreover, the study provides strong evidence supporting the necessity of long-term treatment for this patient population.
Some CHB Patients Fail to Achieve Sustained Virological Response Despite 48 Weeks of First-Line NAs Treatment
Despite undergoing at least 48 weeks of first-line nucleos(t)ide analogs (NAs) treatment, some chronic hepatitis B (CHB) patients fail to achieve sustained virological response (MVR) and develop low-level viremia (LLV). LLV has been associated with an increased risk of adverse long-term clinical outcomes, including liver fibrosis, cirrhosis, and hepatocellular carcinoma. Evidence suggests that serum HBV RNA and hepatitis B core-related antigen (HBcrAg) can reflect intrahepatic cccDNA transcription activity in CHB patients. This study aimed to evaluate the predictive value of these novel serological markers in monitoring LLV, providing a new non-invasive method for disease assessment and follow-up in CHB patients, particularly for the early identification of LLV.
Retrospective Analysis of 270 CHB Patients Treated with NAs for ≥48 Weeks
This study retrospectively analyzed clinical data from 270 CHB patients who received NAs treatment for at least 48 weeks. Based on HBV DNA levels at week 48 of NAs treatment, the patients were divided into two groups:
- MVR Group: Patients with HBV DNA below the lower limit of quantification (<10 IU/mL), achieving sustained virological response.
- LLV Group: Patients with HBV DNA levels between 10 IU/mL and 2000 IU/mL.
Epidemiological data, clinical characteristics, and levels of HBV RNA and HBcrAg were analyzed in these groups.
Key Findings from the Study
- Of the 270 patients, 90 achieved MVR, while 180 experienced LLV.
- Biochemical Differences: LLV patients had higher levels of ALT, AST, and bile acids compared to MVR patients, while total protein, albumin, and serum calcium levels were significantly lower (P<0.05).
- Virological Characteristics: LLV patients exhibited higher quantitative HBsAg and HBeAg levels than MVR patients, while HBsAb levels were lower (P<0.05). Additionally, the proportion of male patients was higher in the LLV group than in the MVR group.
- HBV RNA and HBcrAg Levels: HBeAg-positive patients had higher HBV RNA levels than HBeAg-negative patients. Among HBeAg-positive CHB patients, LLV patients showed significantly higher HBV RNA levels than MVR patients.
- Correlation Analysis: In the MVR group, HBV RNA correlated with HBV DNA and HBcrAg, but no significant correlation was observed between HBV DNA and HBcrAg. In the LLV group, significant correlations were observed among HBV DNA, HBV RNA, and HBcrAg.
Throughout the 96-week follow-up, LLV patients consistently exhibited higher levels of HBV RNA and HBcrAg compared to MVR patients. HBV RNA levels in MVR patients demonstrated a more substantial decline from week 12 to week 48 than those in LLV patients. Even in LLV patients who eventually achieved virological response, HBV RNA and HBcrAg levels remained higher than those in patients who maintained MVR throughout the 48 weeks of NAs treatment.
Implications for Clinical Practice
The study highlights that LLV patients consistently maintain higher serum levels of HBV RNA and HBcrAg during follow-up compared to MVR patients. These findings suggest that regular monitoring of HBV RNA and HBcrAg levels could serve as valuable predictive markers in the antiviral treatment follow-up of CHB patients. Such monitoring can help clinicians identify LLV early, allowing timely interventions to prevent disease progression. Moreover, the study provides robust evidence supporting the necessity for long-term treatment in this patient population.
