Analysis of intrahepatic total HBV DNA, cccDNA and serum HBsAg level in Chronic Hepatitis B patients with undetectable serum HBV DNA during oral antiviral therapy

Abstract

Background: This study aimed to investigate the relationship between intrahepatic cccDNA and serum HBsAg in chronic Hepatitis B (CHB) patients with undetectable serum HBV DNA during antiviral therapy.

Methods: We investigated HBsAg serum levels and their relationship to intrahepatic total cccDNA and HBV DNA in CHB patients with undetectable serum HBV DNA during oral antiviral therapy. Intrahepatic cccDNA and HBV DNA quantitation were performed in the same needle biopsy material, while serum HBsAg, HBeAg and HBV DNA levels were measured in samples drawn on the day of the liver biopsy.

Results: A total of 90 patients who had a liver biopsy were enrolled, including 80 patients with CHB and 10 patients with liver cirrhosis (LC). All the CHB patients were divided into HBeAg-positive and HBeAg-negative group. By using real-time PCR detection, we found that intrahepatic cccDNA and HBV DNA levels were higher in CHB patients than those in LC patients (Intrahepatic cccDNA: 6.15±1.19 vs. 6.12±0.36, HBV DNA: 7.26±0.49 vs. 5.59±0.45, both P<0.05). Intrahepatic cccDNA level was positively correlated with serum HBsAg in HBeAg-negative (r=0.66, P=0.02) and lower serum HBeAg (≤50S/CO) CHB patients (r=0.47, P=0.03), but not in higher serum HBeAg (>50S/CO) CHB patients (both P>0.05). In HBeAg negative patients, serum HBsAg level was correlated with intrahepatic total HBV DNA level (r=0.52, P=0.006). However, no relationship between HBsAg level and intrahepatic total HBV DNA level was found in HBeAg positive patients (both P>0.05).

Conclusions: Serum HBsAg can be used to predict intrahepatic cccDNA and HBV DNA level in CHB patients with low serum HBeAg statues, especially in HBeAg negative patients.