Abstract :
Background: Serum hepatitis B surface antigen (HBsAg) level is a serum marker that correlates with
intrahepatic covalently closed circular DNA (cccDNA) and could also predict liver-related diseases but the role in
predicted significant liver histology in treatment naive HBeAg-negative CHB patients that had indication for liver
biopsy as AASLD and APASL guidelines is still unknown.
Aims: To evaluate the association of serum HBsAg level, intrahepatic HBsAg and other clinical and
laboratory parameters with significant liver necroinflammation as defined by histologic activity index (HAI)
necroinflammatory activity score ≥ 4 or Metavir necroinflammatory activity score ≥ 2 and significant liver fibrosis
as defined by Metavir fibrosis score ≥ 2 in treatment naïve HBeAg-negative CHB patients which had HBV DNA
level ≥ 2,000 IU/mL and age ≥ 40 years or ALT 40-79 U/L.
Methods: Twenty-two patients were prospectively included in the study. Serum HBsAg level that was
performed by enzyme immunoassay and other parameters were collected within 2 weeks of liver biopsy. Immunohistochemical
(IHC) staining for HBsAg in liver tissue was examined in terms of location, area of involvement and
intensity.
Results: Mean age of patients was 48±9 years. Male was equal to female. There were 5 patients (23%)
with significant liver inflammation and 7 patients (32%) with significant liver fibrosis. Serum HBsAg level did not
associated with both significant liver inflammation and fibrosis [median (IQR) 3.45 (0.45) vs. 3.50 (0.34), p =
0.225 and 3.35 (0.45) vs 3.50 (0.49), p = 0.698]. Intra-hepatic HBsAg also did not have association in all terms of
evaluation. Factors that associated with significant liver inflammation were lower BMI [21.55 (2.59) kg/m2 vs.
24.69 (5.21) kg/m2, p = 0.046] and higher alkaline phosphatase (85.0±16.7 vs. 59.4±11.7 U/L, p = 0.001). While
factor that associated significant liver fibrosis were lower age (42.7±8.4 vs. 50.7±8.2 years, p = 0.047). On multivariate
analysis, only HBV DNA level > 5.5 log IU/mL could predict significant liver fibrosis (OR 28.012, 95% CI,
1.631-481.240 p = 0.022) and its sensitivity, specificity, positive predictive value and negative predictive value
were 71.4%, 93.3%, 83.3% and 87.5% respectively. There were no factors which predict significant liver inflammation.
Conclusions: Serum HBsAg level and intrahepatic HBsAg didn’t associate with significant liver histology
in HBeAg-negative CHB patients that had indication for liver biopsy as recommendation by AASLD and
APASL guidelines. HBV DNA level > 5.5 log IU/mL was the only factor that could predict significant liver fibrosis
in this group of patients.
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