A proposed model for the prediction of intrahepatic covalently closed circular DNA level in patients with chronic hepatitis B.

BACKGROUND: We sought to create a prediction model for intrahepatic covalently closed circular DNA (IH-cccDNA) level in chronic hepatitis B (CHB) patients and to validate the model's predictive accuracy.

METHODS: Patients who did not receive previous nucleoside analogue (NA) therapy were assigned to the training cohort (n=57), and those who received previous NA therapy were assigned to the validation cohort (n=69). Factors linked to IH-cccDNA levels in the training cohort were analyzed and a formula to predict IH-cccDNA level was constructed. Next, the reproducibility of that formula was assessed.

RESULTS: In the multivariate analysis for the prediction of IH-cccDNA level in the training cohort, fasting blood sugar (FBS) (P=0.0227), hepatitis B e antigen (HBeAg) (P=0.0067) and Log10(HB surface antigen (HBsAg)) (P=0.0497) were significant, while HB core-related antigen (HBcrAg) tended to be significant (P=0.0562). The formula named the FBS-cres score based on the variables used (FBS, HBcrAg, HBeAg and HBsAg) was constructed. FBS-cres score was calculated as: 3.1686 - (0.0148×FBS) + (0.1982×HBcrAg) + (0.0008168×HBeAg) + (0.1761×log10(HBsAg)). In the training cohort, between HBcrAg level and IH-cccDNA level, significant correlation was noted (P<0.0001, r=0.67), while the FBS-cres score was more closely correlated to IH-cccDNA level (P<0.0001, r=0.81). In the validation cohort, between HBcrAg level and IH-cccDNA level, significant correlation was found (P=0.0012, r=0.38), while the FBS-cres score was more closely linked to IH-cccDNA levels (P<0.0001, r=0.51). Similar tendencies were observed in all subgroup analyses.

CONCLUSION: Our proposed model for the prediction of IH-cccDNA level may be helpful in CHB patients.