Distribution and factors associated with serum HBV pregenomic RNA levels in Chinese chronic hepatitis B patients

Abstract

Correlations between serum hepatitus B virus (HBV) pregenomic RNA (pgRNA), hepatitus B surface antigen (HBsAg), and hepatitus B core‐related antigen (HBcrAg) levels, and influencing factors of serum HBV pgRNA levels in Chinese chronic hepatitis B (CHB) patients are rarely reported. This was a retrospective cohort study consisting of 204 outpatients with CHB. Serum levels of HBV pgRNA, HBsAg, and HBcrAg were quantitative measured in frozen blood samples. The linear regression and multivariate logistic regression analysis were performed to determine associated factors of serum HBV pgRNA levels. In this cohort, the median serum HBV pgRNA level was 4.12 log10 copies/ml and 33.33% (68/204) of them had serum HBV pgRNA under low limit of detection (LLD) (<500 copies/ml); and the percentage of patients with serum HBV pgRNA under LLD in hepatitis B e antigen (HBeAg)‐positive patients was significantly lower than that in HBeAg‐negative patients (15.75% [23/46] vs. 77.59% [45/58], p < .001). Overall, serum HBV pgRNA strongly correlated with HBcrAg (r = 0.760, p < .001), and moderately correlated with HBV DNA (r = 0.663, p < .001) and HBsAg (r = 0.670, p < .001). As compared with HBsAg and HBV DNA, only HBcrAg showed stable correlation with serum HBV pgRNA both in HBeAg‐positive and HBeAg‐negative patients. Serum HBV pgRNA level differed between HBeAg‐positive and HBeAg‐negative patients; and it had better and more stable correlation with serum HBcrAg than serum HBV DNA and HBsAg, irrespective of HBeAg status.

Novel Biomarkers of Hepatitis B Virus and Their Use in Chronic Hepatitis B Patient Management

“…Additionally, a strong correlation between serum HBV DNA and serum HBV RNA levels in treated and untreated patients has been reported [ 22 , 32 , 40 , 42 ]. However, this correlation has not been consistently observed in treatment-naïve patients [ 39 , 43 ]. Serum HBV RNA was also found to correlate with HBcrAg [ 39 ] and moderately correlate with HBsAg and HBeAg quantities [ 40 ] in treatment-naïve patients.…”

“…Serum HBV RNA was also found to correlate with HBcrAg [ 39 ] and moderately correlate with HBsAg and HBeAg quantities [ 40 ] in treatment-naïve patients. Studies involving univariate analysis of treatment-naïve patients have shown that serum HBV RNA levels are significantly associated with age, HBeAg status, HBV genotype [ 40 , 43 ] as well as HBV DNA, HBsAg and HBcrAg levels [ 43 ]. The presence of pre-core or basal core promotor (BCP) mutations were also found to be positively associated with serum HBV RNA levels by multivariate linear regression [ 40 , 43 ].…”

“…Studies involving univariate analysis of treatment-naïve patients have shown that serum HBV RNA levels are significantly associated with age, HBeAg status, HBV genotype [ 40 , 43 ] as well as HBV DNA, HBsAg and HBcrAg levels [ 43 ]. The presence of pre-core or basal core promotor (BCP) mutations were also found to be positively associated with serum HBV RNA levels by multivariate linear regression [ 40 , 43 ]. Gao et al studied the correlation between cccDNA levels in the liver with serum HBV RNA and other HBV biomarkers to gauge transcriptional activity in relation to treatment.…”

“…In patients treated with ETV, the median annual HBcrAg decline was higher in HBeAg-positive patients and those with high serum HBV DNA levels at baseline [ 88 ]. HBcrAg correlates with serum pgRNA levels in treatment-naïve patients as well as those on NA therapy, a correlation that was maintained throughout 96 weeks of therapy [ 39 , 43 ]. This correlation was found to be stronger in HBeAg-positive patients [ 39 ].…”

“…Serum HBsAg levels have been shown to correlate with other markers of HBV infection. During antiviral treatment, HBsAg levels correlate with serum HBV DNA [ 106 , 107 , 108 ] and serum HBV RNA [ 43 ], although a stronger correlation is observed in HBeAg-positive patients than those who are HBeAg negative. No correlation between qHBsAg and HBV DNA was found in HBeAg-negative patients under 40 years of age, indicating that HBsAg secretion is related to age [ 108 ].…”