Kinetics of serum HBsAg and intrahepatic cccDNA during pegylated interferon therapy in patients with HBeAg-positive and HBeAg-negative chronic hepatitis B.
This study was aimed at comparing clinical applicability of serum HBsAg quantification in relation to intrahepatic covalently closed-circular DNA (cccDNA) in patients with HBeAg-positive and HBeAg-negative chronic hepatitis B (CHB) treated with pegylated interferon (PEG-IFN) monotherapy for 48 weeks. Overall, 32 and 36 patients with HBeAg-positive and HBeAg-negative CHB, respectively were recruited. Paired liver biopsies at baseline and end of therapy were analyzed for cccDNA. Virological response (VR) at 48 weeks post-treatment was defined as HBeAg clearance (for HBeAg-positive CHB) and HBV DNA <2,000 IU/ml (for both groups). The results demonstrated that baseline levels of all viral markers were higher in the HBeAg-positive group than the HBeAg-negative group. Baseline HBsAg correlated with cccDNA in the HBeAg-positive group (r = 0.452, P = 0.009) but not in the HBeAg-negative group (r = 0.018, P = 0.919). However, the magnitude of cccDNA and HBsAg decline at end of treatment was not different between groups. The reduction of HBsAg showed a positive correlation with cccDNA decline in HBeAg-positive and HBeAg-negative CHB (r = 0.544, P = 0.001 and r = 0.364, P = 0.029, respectively). Overall, responders had more decline in cccDNA and HBsAg levels compared with non-responders. Patients with serum HBsAg decline of >1.0 log10IU/ml during treatment archived VR and HBsAg clearance of 80% and 30%, respectively. In conclusion, serum HBsAg represented a better surrogate marker of intrahepatic cccDNA in patients with HBeAg-positive CHB compared to those with HBeAg-negative CHB. On-treatment, HBsAg reduction of 1.0 log10IU/mL was associated with a high probability of subsequent VR and HBsAg clearance in patients receiving PEG-IFN therapy. J. Med. Virol. 89:130-138, 2017. © 2016 Wiley Periodicals, Inc.
Research Unit of Hepatitis and Liver Cancer, Chulalongkorn University, Bangkok, Thailand.
Natthaya
N
Chuaypen
Research Unit of Hepatitis and Liver Cancer, Chulalongkorn University, Bangkok, Thailand.
Methee
M
Sriprapun
Research Unit of Hepatitis and Liver Cancer, Chulalongkorn University, Bangkok, Thailand.
Kesmanee
K
Praianantathavorn
Research Unit of Hepatitis and Liver Cancer, Chulalongkorn University, Bangkok, Thailand.
Sunchai
S
Payungporn
Department of Pathology, Chulalongkorn University, Bangkok, Thailand.
Naruemon
N
Wisedopas
Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Yong
Y
Poovorawan
Research Unit of Hepatitis and Liver Cancer, Chulalongkorn University, Bangkok, Thailand. pisittkvn@yahoo.com.
Pisit
P
Tangkijvanich
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D006513:Hepatitis B e Antigens / Q000097:blood*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D008099:Liver / Q000821:virology*; D008297:Male; D008875:Middle Aged; D044967:Serum / Q000737:chemistry; D016896:Treatment Outcome
D000998:Antiviral Agents; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D007372:Interferons
HBsAg; cccDNA; hepatitis B virus; pegylated-interferon; treatment response