Serum Hepatitis B Virus RNA Levels Predict HBeAg Seroconversion and Virological Response in Chronic Hepatitis B Patients with High Viral Load Treated with Nucleos(t)ide Analog

Figures & data

Table 1 Demographic and Baseline Characteristics of Patients

Variables	ALL	LAM+ADV	ETV	P
	N=66	N=31	N=35
Age, years^a	31.09±9.58	31.68±10.88	30.57±8.38	0.511
Male:female	54/12	24/7	30/5	0.383
ALT, U/L^b	216.50 (124.25–362.00)	202.00 (121.00–327.30)	267.00 (135.00–377.00)	0.220
HBV DNA, log10 IU/mL^a	7.85±0.71	7.87±0.71	7.83±0.73	0.354
HBV RNA, log10 copies/mL^a	9.07±1.07	8.97±1.22	9.15±0.92	0.114

Notes: ^aMean ± standard deviation; ^bmedian (IQR).

Abbreviations: LAM, lamivudine; ADV, adefovir dipivoxil; ETV, entecavir.

Table 2 Univariate and Multivariate Analyses of Associations Between the HBV RNA Level and HBeAg Seroconversion at Week 96

	HBeAg Seroconversion (N=12)
	Univariable			Multivariable
	OR	95% CI	p	OR	95% CI	P
Age (years)	0.979	0.919–1.043	0.506
Female/male	1.136	0.215–6.014	0.880
Type of treatment (LAM+ADV or ETV)	0.769	0.217–2.727	0.685
ALT (U/L) at baseline	0.999	0.995–1.003	0.699
HBV RNA (log10 copies/mL) at baseline	1.525	0.886–2.626	0.128
HBV RNA (log10 copies/mL) at week 12	3.192	1.419–7.179	0.005**	3.560	1.391–9.110	0.008**
HBV RNA (log10 copies/mL) at week 24	1.192	1.172–3.120	0.009**	0.898	0.552–1.459	0.664
HBV DNA (log10 IU/mL) at baseline	1.621	0.701–3.597	0.268
HBV DNA (log10 IU/mL) at week 12	0.400	0.104–1.533	0.181
HBV DNA (log10 IU/mL) at week 24	1.712	0.912–3.214	0.094

Note: **p<0.01.

Abbreviations: LAM, lamivudine; ADV, adefovir dipivoxil; ETV, entecavir; HBV, hepatitis B virus; ALT, alanine aminotransferase.

Figure 1 Serum level of HBV RNA at indicated time points: (A) Comparison of the serum HBV RNA level between the HBeAg-seroconversion group and non-HBeAg-seroconversion group. (B) Comparison of the serum HBV RNA level between the virologic response (VR) group and non-virologic response (NVR) group. Data are the mean ± SEM, and determined by the Mann–Whitney U-test. *p < 0.05, ***p < 0.001.

Figure 2 Analyses of receiver operating characteristic (ROC) curves of the sensitivity and specificity of the serum HBV RNA level at week 12 for the prediction of HBeAg seroconversion and the virologic response (VR).

Figure 3 Probability of HBeAg seroconversion based on the serum HBV RNA level at week 12.

Table 3 Univariate and Multivariate Analyses of Associations Between the HBV RNA Level and Virologic Response at Week 96

	Virologic Response (N=54)
	Univariate			Multivariate
	OR	95% CI	P	OR	95% CI	p
Age (years)	0.987	0.922–1.057	0.710
Female/male	1.667	0.376–7.394	0.502
Type of treatment (LAM+ADV or ETV)	2.000	0.538–7.438	0.301
ALT (U/L) at baseline	1.000	0.995–1.004	0.840
HBV RNA (log10 copies/mL) at baseline	1.112	0.595–2.079	0.740
HBV RNA (log10 copies/mL) at week 12	1.908	1.115–3.265	0.018*	1.908	1.115–3.265	0.018*
HBV RNA (log10 copies/mL) at week 24	1.449	0.928–2.423	0.098
HBV DNA (log10 IU/mL) at baseline	0.922	0.387–2.199	0.855
HBV DNA (log10 IU/mL) at week 12	1.932	0.608–6.142	0.265
HBV DNA (log10 IU/mL) at week 24	0.720	0.411–1.261	0.251

Note: *p<0.05.

Abbreviations: LAM, lamivudine; ADV, adefovir dipivoxil; ETV, entecavir; HBV, hepatitis B virus; ALT, alanine aminotransferase.

Figure 4 Dynamic changes in the HBV RNA level during NA therapy. (A) Trend in the total RNA level. (B) Grouping was based on whether HBeAg seroconversion occurred at week 96. (C) Grouping was based on whether a VR occurred at week 96. Data are the median value, and determined by the Mann–Whitney U-test. **p < 0.01, ***p < 0.001.