Abstract
BackgroundThis study aimed to investigate the relationships of intrahepatic cccDNA with serum HBsAg and with HBV DNA in treatment-naive patients throughout acute and chronic HBV infection.MethodsA total of 120 patients who had a liver biopsy were enrolled, including 19 with acute hepatitis B (AHB), and 101 patients with chronic HBV infection (CHB) of whom were 10 in immune-tolerant (IT) phase, 59 in immune-clearance (IC) phase, 8 in low-replicative (LR) phase, and 24 in HBeAg-negative hepatitis (ENH) phase. Intrahepatic cccDNA, serum HBsAg and serum HBV DNA levels were comparatively analyzed.ResultsThe median intrahepatic cccDNA levels were 0.18 4.80, 3.81, 0.22 and 0.97 copies/cell for patients with AHB, CHB-IT, CHB-IC, CHB-LR, and CHB-ENH, respectively. In AHB patients, intrahepatic cccDNA was positively correlated with serum HBsAg (r = 0.665, P = 0.003), as well as serum HBV DNA (r = 0.536, P = 0.022). In CHB patients, intrahepatic cccDNA was positively correlated with serum HBsAg in the IC phase (r = 0.392, P = 0.005), and with serum HBV DNA in the IC phase (r = 0.301, P = 0.036) and ENH phase (r = 0.588, P = 0.013). HBV replicative efficiency, defined as the ratio of serum HBV DNA to intrahepatic cccDNA, was obviously lower in AHB and CHB-LR patients than in CHB-IT, CHB-IC and CHB-ENH patients (0.70 and 0.53 vs. 1.12, 1.09 and 0.99, P<0.001, values were logarithmic transformed for analysis). In CHB-IC patients, HBV replicative efficiency was positively correlated with histological activity index of liver inflammation (r = 0.308, P = 0.009).ConclusionSerum HBsAg and HBV DNA levels may reflect the amount of active intrahepatic cccDNA in treatment-naive AHB and CHB-IC patients. Reduced intrahepatic cccDNA and HBV replicative efficiency may imply effective immune control of HBV infection.
Highlights
Chronic hepatitis B virus (HBV) infection remains a serious health problem
One crucial step in HBV life cycle is the formation of covalently closed circular DNA, which serves as original template for viral replication and plays an important role in the persistence of HBV infection [4,5,6]
This study aimed to investigate the relationship between intrahepatic closed circular DNA (cccDNA) and serum viral markers including HBV surface antigen (HBsAg) and HBV DNA throughout natural phases of acute and chronic HBV infection
Summary
Chronic hepatitis B virus (HBV) infection remains a serious health problem. Chronic HBV infection is associated with high risk of developing liver cirrhosis and hepatocellular carcinoma [3]. Quantitation of intrahepatic HBV cccDNA is suggested to be valuable in evaluating anti-HBV therapeutic efficacy and estimating treatment endpoint [7,8,9,10,11,12]. HBV cccDNA level is considered to be a valuable marker for HBV recurrence after liver transplantation and extrahepatic HBV infection [13,14]. This study aimed to investigate the relationships of intrahepatic cccDNA with serum HBsAg and with HBV DNA in treatment-naive patients throughout acute and chronic HBV infection
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