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Serum HBV DNA plus RNA reflecting cccDNA level before and during NAs treatment in HBeAg positive CHB patients
Yang Wang1,2, Yanna Liu3, Hao Liao3,4
1Liver disease center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China.
Insights
Serum HBV DNA plus RNA is the best predictor of intrahepatic cccDNA in chronic hepatitis B patients on nucleos(t)ide analogues. This marker also correlates with cccDNA decline during treatment.
Area of Science:
- Hepatology
- Virology
- Molecular Biology
Background:
- Intrahepatic covalently closed circular DNA (cccDNA) is the template for HBV replication.
- Long-term nucleos(t)ide analogue (NA) treatment is standard for chronic hepatitis B (CHB).
- The correlation between serum viral markers and intrahepatic cccDNA during NA treatment requires further investigation.
Purpose of the Study:
- To evaluate the correlation between intrahepatic cccDNA and serum viral markers in HBeAg-positive CHB patients.
- To assess the association between serum viral markers and cccDNA during 60 months of NA treatment.
Main Methods:
- Fifty-four HBeAg-positive CHB patients receiving long-term NA treatment were enrolled.
- Serial serum samples were analyzed for HBsAg, HBV DNA, HBV RNA, and HBcrAg.
- Liver biopsy samples at baseline and 60 months were analyzed for intrahepatic HBV DNA and cccDNA.
Main Results:
- At baseline, serum HBV DNA plus RNA showed the highest correlation with intrahepatic cccDNA (r=0.698).
- During 60 months of NA treatment, correlations between serum markers and cccDNA were not significant.
- Decreased serum HBV DNA plus RNA was associated with cccDNA decline (β=0.172) and showed the strongest correlation with cccDNA changes (r=0.525).
Conclusions:
- Serum HBV DNA plus RNA is a superior marker for predicting intrahepatic cccDNA compared to other viral markers.
- HBV DNA plus RNA changes during NA therapy correlate with cccDNA decline in CHB patients.
Abstract:
Background & Aims: Correlations between serum viral markers and intrahepatic cccDNA in patients undergoing long-term nucleos(t)ide analogues (NAs) treatment haven't been fully explored. In this study, we evaluate the correlation between intrahepatic cccDNA and other serum viral markers and intrahepatic HBV DNA in HBeAg positive chronic hepatitis B (CHB) patients during 60-month treatment with NAs. Methods: Fifty-four HBeAg positive CHB patients received long-term NAs treatment were included in this study. Serial serum samples were regularly collected and quantitatively analyzed for HBsAg, HBV DNA, HBV RNA and HBcrAg. Histological samples from liver biopsy at baseline and month 60 were analyzed for intrahepatic HBV DNA and cccDNA. Results: At baseline, serum HBV DNA plus RNA was positively associated with intrahepatic cccDNA in multivariate regression analysis (β=0.205, P<0.001). In the correlation analysis between cccDNA and serum viral markers, HBV DNA plus RNA had the highest correlation coefficient (r=0.698, P<0.001), followed by serum HBV DNA (r=0.641, P<0.001), HBV RNA (r=0.590, P<0.001), and HBcrAg (r=0.564, P<0.001). At month 60, correlations between these serum viral markers and cccDNA were not observed (P>0.05). Multivariate regression analysis showed that only the decreased HBV DNA plus RNA was positively associated with cccDNA decline (β=0.172, P =0.006). Changes of HBV DNA plus RNA (r=0.525, P=0.001) was better correlated with cccDNA decline as compared to HBV RNA (r=0.384, P=0.008), HBV DNA (r=0.431, P=0.003), and HBsAg (r=0.342, P=0.029). Conclusions: Serum HBV DNA plus RNA better correlated with intrahepatic cccDNA than other viral makers before and during NAs treatment in HBeAg positive CHB patients.
