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1838
Serum hepatitis B core-related antigen and surface
antigen levels are correlated with hepatic fibrosis and
inflammatory activity in treatment-naïve chronic hepatitis
B patients
Tetsuya Hosaka1, Fumitaka Suzuki1, Masahiro Kobayashi1,
Shunichiro Fujiyama1, Yusuke Kawamura1, Hitomi Sezaki1, Norio
Akuta1, Yoshiyuki Suzuki1, Satoshi Saitoh1, Yasuji Arase1, Kenji
Ikeda1, Mariko Kobayashi2, Hiromitsu Kumada1; 1Hepatology,
Toranomon Hospital, Tokyo, Japan; 2Research Institute for hepatology,
Toranomon Hospital, Kawasaki, Japan
Background: Serum hepatitis B core-related antigen (HBcrAg)
and surface antigen (HBsAg) have been known as surrogate
markers of intrahepatic covalently closed circular DNA
(cccDNA). It is unclear whether these serum markers have an
impact on histological progression. We examined whether
serum HBcrAg and HBsAg levels would be correlated with fibrosis
stage and inflammatory activity in patients who do not any
anti-viral treatment. Methods: We conducted a cross-sectional
study of 1499 Asian treatment-naïve CHB patients who underwent
liver biopsy. Serum HBcrAg and HBsAg levels around the
biopsy were measured in all patients using commercial assays.
Fibrosis stage and inflammatory activity were assessed according
to Metavir scoring system. We analyzed whether serum
HBcrAg and HBsAg levels would be correlated with histological
findings stratified by HBeAg status. Results: Of 898 HBeAg
positive patients, 335 (37%) patients had F0-1, 252 (28%)
had F2, 174 (19%) had F3, and 137 (15%) had F4 stage. Of
601 HBeAg negative patients, 196 (33%) patients had F0-1,
181 (30%) had F2, 97 (16%) had F3, and 127 (21%) had F4
stage, respectively. Median HBsAg levels were 4.26 log IU/
mL (IQR; 3.81-4.70) in F0-1, 3.91 (IQR; 3.55-4.33) in F2,
3.61 (IQR; 3.30-4.07) in F3, and 3.32 (IQR; 2.94-3.60) in F4
stage, and significant negative correlation between HBsAg levels
and fibrosis stage was observed in HBeAg positive patients
(P trend <0.0001). On the other hand, HBsAg levels were not
correlated with fibrosis in HBeAg negative patients. Regarding
inflammatory activity, significant negative correlation between
HBsAg levels and activity was also observed in HBeAg positive
patients (P trend <0.0001), but not in HBeAg negative patients.
Median HBcrAg levels were 3.8 log U/mL (IQR; <3.0-4.9) in
F0-1, 4.6 (IQR; 3.8-5.6) in F2, 4.7 (IQR; 3.9-6.0) in F3, and
5.1 (IQR; 4.4-5.9) in F4 stage, and significant positive correlation
between HBcrAg levels and fibrosis stage was observed in
HBeAg negative patients (P trend <0.0001), but not in HBeAg
positive patients because HBcrAg levels were above upper
limit of cut-off (6.8 log U/mL) in many HBeAg positive patients.
Regarding activity, median HBcrAg levels were 3.0 log U/
mL (IQR; <3.0-3.5) in A0, 4.3 (IQR; 3.1-5.2) in A1, 5.1 (IQR;
4.3-6.1) in A2-3 grade in HBeAg negative patients (P trend
<0.0001), but no correlation was observed in HBeAg positive
patients. Significant positive correlation between HBcrAg and
activity was also observed in HBeAg negative patients who
had low ALT levels. Conclusion: Treatment-naïve HBeAg negative
patients with high HBcrAg may have high risk of disease
progression.
Disclosures:
Fumitaka Suzuki - Speaking and Teaching: BMS
Yoshiyuki Suzuki - Speaking and Teaching: Bristol-Myers Squibb
Kenji Ikeda - Speaking and Teaching: Eisai company, Dainippon Sumitomo
Pharmaceutical company
Hiromitsu Kumada - Speaking and Teaching: Bristol-Myers Squibb,Pharma International,
MSD, Abbvie, Glaxosmithkline, Gilead Sciences, Diainippon Sumitomo
Pharma
The following people have nothing to disclose: Tetsuya Hosaka, Masahiro
Kobayashi, Shunichiro Fujiyama, Yusuke Kawamura, Hitomi Sezaki, Norio
Akuta, Satoshi Saitoh, Yasuji Arase, Mariko Kobayashi
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