1、Longitudinal profile of serum HBV RNA in patients with chronic hepatitis B infection on long-term nucleoside analogues
Research Institution: The University of Hong Kong
Authors: Lung Yi Mak, Mark Anderson, Michael Stec, Danny Wong, Rex Wan-Hin, Hui Wai-Kay Seto, Gavin Cloherty, Man-Fung Yuen
Summary
——Background——
Serum hepatitis B virus RNA (HBV RNA) is a novel biomarker for chronic hepatitis B (CHB). This study investigates the long-term dynamics of HBV RNA in CHB patients undergoing nucleos(t)ide analogue (NUC) therapy and identifies influencing factors.
——Methods——
Sequential samples from 1,354 CHB patients initiating first-line NUC therapy were evaluated. Baseline was set at the initiation of NUC therapy (Year 0), with subsequent assessments at Years 1, 3, and 5. The lower limit of quantification (LLOQ) for HBV RNA was 0.8 log U/mL (~20 copies/mL), and the lower limit of detection (LLOD) for HBV DNA was 20 IU/mL.
——Results——
Among the 1,354 participants, the median baseline age was 49.8 years (interquartile range [IQR]: 40.2–57.3), with 65.2% being male. According to the FIB-4 criterion (>3.25), 9.9% of patients were classified as having cirrhosis. Baseline median HBV RNA and DNA levels were 3.68 log IU/mL (IQR: 2.42–5.19) and 5.76 log IU/mL (IQR: 3.54–7.17), respectively.
After initiating NUC therapy, median serum HBV RNA levels at Years 1, 3, and 5 were 2.45 log IU/mL (IQR: 1.82–3.62), 2.23 log IU/mL (IQR: 1.67–3.05), and 2.14 log IU/mL (IQR: 1.48–2.86), with corresponding reductions of 0.82, 1.20, and 1.54 log IU/mL. By contrast, HBV DNA levels decreased to 1 log IU/mL (IQR: 1–2.23) at Year 1 and remained stable at 1 log IU/mL (IQR: 1–1) during Years 3 and 5.
At Years 1, 3, and 5, 13.5%, 15.9%, and 20.1% of patients achieved HBV RNA levels below the limit of detection (LOD), compared to 69.2%, 88.9%, and 93.0% of patients achieving HBV DNA levels below the LOD, respectively.The correlation between RNA and DNA levels weakened over time with NUC treatment, with correlation coefficients of 0.553, 0.257, 0.276, and 0.224 at baseline, Year 1, Year 3, and Year 5, respectively.
Cirrhosis was associated with lower serum HBV RNA levels, though the association was not statistically significant. Age was negatively correlated with both RNA (r = -0.277) and DNA (r = -0.206), and older patients were more likely to achieve HBV RNA levels below the LOD.
——Conclusion——
The decline of serum
HBV RNA levels during NUC therapy is significantly slower than that of HBV DNA, supporting the hypothesis that NUCs gradually reduce the number of infected hepatocytes through indirect mechanisms. As
only 20% of patients achieved HBV RNA levels below the detection limit after 5 years of NUC therapy, monitoring HBV RNA may play a crucial role in evaluating treatment efficacy and guiding therapeutic decisions in CHB management.
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2、Apply HBV RNA and HBcrAg to follow-up of patients with chronic hepatitis B receiving nucleos(t)ide analogs
Research Institution: Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University
Authors: Mingyang Feng, Kehui Liu, Wanqing Chi, Baoyan An, Lanyi Lin, Yezhou Ding, Yumin Xu, Hui Wang
Summary
——Background——
Some chronic hepatitis B (CHB) patients may still experience low-level viremia (LLV) even after more than 48 weeks of first-line oral antiviral treatment, which could lead to disease progression and adverse clinical outcomes, such as increased risks of hepatocellular carcinoma (HCC) and liver cirrhosis.
——Methods——
This single-center retrospective study analyzed clinical data from 270 CHB patients who received first-line nucleos(t)ide analogues (NAS) therapy for more than 48 weeks at a tertiary hospital infectious disease outpatient clinic. CHB patients were divided into two groups: those who achieved maintained virological response (MVR), with HBV DNA levels below the lower limit of detection (10 IU/mL), and those with LLV, where HBV DNA was detectable but below 2,000 IU/mL. The study examined the demographic and clinical characteristics of these patients, as well as factors associated with LLV. Additionally, HBV RNA and HBcrAg levels were assessed.
——Results——
In this cohort, 90 patients achieved maintained virological response (MVR), while 180 patients developed low-level viremia (LLV). Among the first-line nucleos(t)ide analogues (NA)-naive CHB patients, 79.5% were in the MVR group, and 66.8% were in the LLV group (p = 0.031). Compared to MVR patients, LLV patients had higher ALT, AST, and bile acid levels, but lower total protein, albumin, and serum calcium levels (all p < 0.05). LLV patients also had higher levels of HBV surface antigen (HBsAg), HBeAg, and HBeAb, but lower levels of HBsAb (all p < 0.05).
From baseline to 96 weeks of follow-up, LLV patients consistently had higher HBV RNA and HBcrAg levels compared to those who achieved MVR.
Even among LLV patients who ultimately achieved MVR, their HBV RNA and HBcrAg levels remained higher than those of patients who maintained MVR after more than 48 weeks of NA treatment. Our study found that HBV RNA levels in MVR patients significantly decreased from Week 12 to Week 48, while LLV patients showed only a moderate decline during the same period.
——Conclusion——
These results
suggest that continuous monitoring of HBV RNA and HBcrAg levels is essential in the disease assessment and long-term follow-up of CHB patients, to
facilitate the early detection and intervention of LLV.
