Quantitative intrahepatic HBV cccDNA correlates with histological liver inflammation in chronic hepatitis B virus infection.
BACKGROUND
The aim of this study was to determine the role of baseline hepatitis B virus (HBV) forming covalently closed circular DNA (HBV cccDNA) in liver inflammation in patients infected with HBV with serum alanine aminotransferase (ALT) levels under two times the upper limit of normal (2×ULN).


METHODS
After liver biopsy and serum virological and biochemical marker screening, patients diagnosed with chronic HBV infection with serum ALT levels under 2×ULN and histological liver inflammation of less than grade G2 were prospectively recruited into this study. Recruitment took place between March 2009 and November 2010 at the Center of Infectious Disease, Sichuan University. Patient virological and biochemical markers, as well as markers of liver inflammation, were monitored.


RESULTS
A total of 102 patients were recruited and 68 met the inclusion criteria; the median follow-up was 4.1 years (range 3.9-5.2 years). During follow-up, 41 patients (60.3%) exhibited signs of inflammation. Baseline HBV cccDNA >1 copy/cell (odds ratio 9.43, p=0.049) and liver inflammation grade ≥G1 (odds ratio 5.77, p=0.046) were both independent predictors of liver inflammation.


CONCLUSIONS
A higher baseline intrahepatic HBV cccDNA level may increase the risk of liver inflammation. Further investigations will be required to validate HBV cccDNA as an intrahepatic virological marker of patients who require extended outpatient management.
Center of Infectious Disease, State Key Laboratory of Biotherapy, West China Hospital, West China School of Medicine, Sichuan University, 37# Guoxue Lane, 610041 Chengdu, China; Division of General Practice, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, China.
Ling-Bo
LB
Liang
Center of Infectious Disease, State Key Laboratory of Biotherapy, West China Hospital, West China School of Medicine, Sichuan University, 37# Guoxue Lane, 610041 Chengdu, China.
Xia
X
Zhu
Center of Infectious Disease, State Key Laboratory of Biotherapy, West China Hospital, West China School of Medicine, Sichuan University, 37# Guoxue Lane, 610041 Chengdu, China.
Li-Bo
LB
Yan
Center of Infectious Disease, State Key Laboratory of Biotherapy, West China Hospital, West China School of Medicine, Sichuan University, 37# Guoxue Lane, 610041 Chengdu, China.
Ling-Yao
LY
Du
Center of Infectious Disease, State Key Laboratory of Biotherapy, West China Hospital, West China School of Medicine, Sichuan University, 37# Guoxue Lane, 610041 Chengdu, China.
Cong
C
Liu
Center of Infectious Disease, State Key Laboratory of Biotherapy, West China Hospital, West China School of Medicine, Sichuan University, 37# Guoxue Lane, 610041 Chengdu, China.
Juan
J
Liao
Center of Infectious Disease, State Key Laboratory of Biotherapy, West China Hospital, West China School of Medicine, Sichuan University, 37# Guoxue Lane, 610041 Chengdu, China. Electronic address: htang6198@hotmail.com.
Hong
H
Tang
D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D004270:DNA, Circular; D004279:DNA, Viral / Q000097:blood*; D005260:Female; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000473:pathology / Q000821:virology*; D006801:Humans; D007249:Inflammation; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D055815:Young Adult
D015415:Biomarkers; D004270:DNA, Circular; D004279:DNA, Viral; D000410:Alanine Transaminase
Covalently closed circular DNA; Hepatitis B virus; Histological liver inflammation; Rolling circle amplification