Intrahepatic hepatitis B virus covalently closed circular DNA can be a predictor of sustained response to therapy

Area of Science:

• Hepatology
• Virology
• Molecular Biology

Background:

• Chronic hepatitis B (CHB) management requires reliable prediction of sustained virologic response (SVR).
• Current predictors often rely on serum markers, which may not fully reflect viral activity within hepatocytes.

Purpose of the Study:

• To evaluate intrahepatic hepatitis B virus (HBV) covalently closed circular (ccc) DNA and total HBV DNA levels as predictors of SVR.
• To compare the predictive power of intrahepatic viral DNA with serum HBV DNA levels at the end of therapy.

Main Methods:

• HBeAg-positive CHB patients received 1-year therapy (lamivudine or combination therapy).
• Liver biopsies were performed post-therapy to quantify intrahepatic HBV cccDNA and total HBV DNA.
• Serum HBV DNA, intrahepatic HBV cccDNA, and total HBV DNA were measured and correlated with SVR after 52 weeks of follow-up.

Main Results:

• Lower intrahepatic HBV cccDNA and total HBV DNA levels at therapy end were significantly associated with SVR.
• Intrahepatic HBV cccDNA and total HBV DNA levels were significantly lower in patients achieving SVR.
• Intrahepatic HBV cccDNA and total HBV DNA demonstrated significant predictive value for SVR (OR 5.3 and 4.4, respectively).

Conclusions:

• Intrahepatic HBV cccDNA and total HBV DNA levels are superior predictors of SVR compared to serum HBV DNA.
• Measuring intrahepatic viral DNA at therapy cessation provides a more accurate surrogate for predicting long-term treatment success in CHB.