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Reduction in Intrahepatic cccDNA and Integration of HBV in Chronic Hepatitis B Patients with a Functional Cure
Weiqiang Gan1,2, Na Gao1, Lin Gu1
1Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
Insights
Functional cure (FC) in chronic hepatitis B (CHB) significantly reduces intrahepatic covalently closed circular DNA (cccDNA) and hepatitis B virus (HBV) integration. Clearing cccDNA further lowers the risk of virological relapse in CHB patients.
Area of Science:
- Hepatology
- Virology
- Molecular Biology
Background:
- Functional cure (FC) for chronic hepatitis B (CHB) is defined by hepatitis B surface antigen (HBsAg) clearance.
- The persistence of intrahepatic covalently closed circular DNA (cccDNA) and hepatitis B virus (HBV) integration post-FC requires further investigation.
Purpose of the Study:
- To quantify intrahepatic cccDNA and HBV integration levels in CHB patients achieving FC.
- To assess the clinical significance of these markers in CHB treatment outcomes.
Main Methods:
- Two study sessions were conducted: one with 116 patients (FC, non-functional cure, CHB groups) and another with ten patients for whole-genome sequencing.
- Intrahepatic cccDNA and viral markers were analyzed; FC patients were monitored for relapse.
Main Results:
- 13 FC patients were negative for intrahepatic cccDNA; CHB patients had significantly higher cccDNA levels.
- HBV integration was detected in 33.3% of FC patients and 100% of CHB patients.
- Lower intrahepatic cccDNA and HBV integration correlated with reduced virological relapse rates post-FC.
Conclusions:
- Achieving FC in CHB significantly reduces intrahepatic cccDNA and HBV integration.
- Complete clearance of intrahepatic cccDNA post-FC is associated with a lower risk of virological relapse.
Background And Aims:
Functional cure (FC) is characterized by the clearance of the hepatitis B surface antigen from the serum of patients with chronic hepatitis B (CHB). However, the level of intrahepatic covalently closed circular DNA (cccDNA) and hepatitis B virus (HBV) integration remains unclear. We conducted this study to determine them and reveal their value in the treatment of CHB.
Methods:
There were two sessions to elucidate the changes in intrahepatic cccDNA and HBV integration after antiviral therapy. In the first session, 116 patients were enrolled and divided into FC, non-functional cure (NFC), and CHB groups, including 48 patients with functionally cured CHB, 27 with CHB without functional cure after antiviral treatment, and 41 with treatment-naïve CHB. Patients were tested for both intrahepatic cccDNA and other viral markers. All patients in the FC group were followed up for at least 24 weeks to observe relapse. In the second session, another ten patients were included for in-depth whole-genome sequencing to analyze HBV integration.
Results:
Thirteen patients in the FC group were negative for intrahepatic cccDNA. Intrahepatic cccDNA was much higher in the CHB group compared with the FC group. Seven patients had HBsAg seroreversion, including two with virological relapse. Integration of HBV was detected in one (33.3%) functionally cured patients and in seven (100%) with CHB. 28.0% of the HBV breakpoints were assigned in the 1,500 nt to 1,900 nt range of the HBV genome.
Conclusions:
After achieving an FC, the rate of intrahepatic cccDNA and HBV integration was significantly reduced in patients with CHB. For those patients who cleared intrahepatic cccDNA, the chances of developing virological relapse were even lower.
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