Clinical features of HBsAg seroclearance in hepatitis B virus carriers in South Korea: A retrospective longitudinal study

Table 1 Rate and time interval of hepatitis B surface antigen seroclearance from entry

Age group	Total number	1HBsAg seroclearance	Time interval to HBsAg seroclearance
	(sex ratio)	No. (rate/yr/sex ratio)	(yr, mean ± SD)
< 30	181 (1.8:1)	4 (2.2%/0.55%/3.0:1)	3.99 ± 2.91
30-40	423 (2.3:1)	11 (2.6%/0.45%/1.2:1)	5.79 ± 4.23
40-50	574 (2.9:1)	36 (6.3%/0.92%/4.0:1)	6.87 ± 3.5
50-60	455 (0.4:1)	22 (4.8%/0.79%/2.7:1)	6.15 ± 3.89
> 59	286 (1.1:1)	17 (5.9%/1.05%/0.9:1)	5.64 ± 3.14
Total	1919 (1.4:1)	90 (4.7%/0.76%/1.9:1)	6.2 ± 3.6

¹The overall rate of HBsAg seroclearance was 4.7%, and the estimated annual rate of HBsAg seroclearance was 0.76%. The rate of HBsAg seroclearance was significantly higher in the 40-50 and 50-60 year age groups than in the 20-30 and 30-40 year age groups (P = 0.001). Male predominance was observed in the 40s and 50s age groups but was not clear in the > 59 year age group. The time interval from entry to HBsAg loss was longer in the 40-50 and 50-60 year age groups than in the 20-30 and 30-40 year age groups.

Table 2 Comparison of the time interval to hepatitis B surface antigen seroclearance between carriers with and without hepatitis B e antigen at entry

	HBeAg-positive		HBeAg-negative
Age group	n (%)	Years (mean ± SD)	n (%)	Years (mean ± SD)
< 30	1 (25)	8.15	3 (75)	2.6 ± 1.06
30-40	4 (36.4)	5.87 ± 4.9	7 (63.6)	5.75 ± 4.21
40-50	6 (16.7)	9.24 ± 2.84	30 (83.3)	6.4 ± 3.46
50-60	2 (9.1)	9.22 ± 1.71	20 (90.9)	5.84 ± 3.93
> 59	3 (17.6)	3.38 ± 1.81	14 (82.4)	6.12 ± 3.2
Total	16 (17.8)	7.23 ± 3.71	74 (82.2)	5.98 ± 3.2

Overall, the time interval of HBsAg seroclearance did not differ between the two groups (P = 0.982). However, when limited to the 40s and 50s age groups, the time interval to HBsAg seroclearance was significantly longer in the HBeAg-positive group than in the HBeAg-negative group (P = 0.013), but it did not significantly differ in the other age groups. In the 60s age group, the time interval to HBsAg seroclearance did not differ between the HBeAg-positive and negative groups (P = 0.1208).

Table 3 Comparison of the time interval to hepatitis B surface antigen seroclearance in each age group with the serum hepatitis B virus DNA titer at entry

	HBV DNA < 201 IU/mL		HBV DNA 20-2000 IU/mL		HBV DNA > 2000 IU/mL
Age group	No.	Years (mean ± SD)	No.	Years (mean ± SD)	No.	Years (mean ± SD)
< 30	2	2.31 ± 1.32	2	5.67 ± 3.51	0	0
30-40	4	6.42 ± 4.82	4	3.72 ± 4.01	3	7.72 ± 3.92
40-50	12	5.73 ± 3.73	14	6.71 ± 3.36	10	8.47 ± 3.11
50-60	12	3.94 ± 2.99	6	8.36 ± 3.43	4	9.47 ± 3.11
> 59	9	5.07 ± 2.85	5	5.95 ± 3.28	3	6.82 ± 4.6
SUM	39	4.92 ± 3.36	31	6.45 ± 3.49	20	8.31 ± 3.26

¹The 20 IU/mL value is the cut-off level for HBV DNA detected by real-time polymerase chain reaction. The time interval to HBsAg seroclearance was very significantly reduced in the HBV DNA < 20 IU/mL group compared with the > 2000 IU/mL group (P = 0.0005). The difference in the time interval to HBsAg seroclearance was slightly significant between the HBV DNA < 20 IU/mL and 20-2000 IU/mL groups and between the HBV DNA > 2000 IU/mL and 20-2000 IU/mL groups (P = 0.0671 and P = 0.0624, respectively).

Table 4 Comparison of the time to hepatitis B surface antigen seroclearance in each age group with the ultrasonography stage of chronic liver disease

Age group	Normal US		Non-cirrhotic CLD		Cirrhotic US
	No.	Year (mean ± SD)	No.	Year (mean ± SD)	No.	Year (mean ± SD)
< 30	2	2.29 ± 1.28	2	5.7 ± 3.47	0	-
30-40	9	5.48 ± 4.59	1	5.56	1	5.6
40-50	9	5.7 ± 4.07	16	7.2 ± 3.63	11	7.35 ± 2.86
50-60	9	5 ± 4.23	8	6.59 ± 4.3	5	7.51 ± 2.38
> 59	3	3.81 ± 1.49	7	6.91 ± 3.17	7	5.14 ± 3.42
SUM	32	5.05 ± 3.92	34	6.86 ± 3.51	24	6.8 ± 2.98

Chronic liver disease (CLD) showing coarse parenchymal texture in ultrasonography (US). The time interval to HBsAg seroclearance was significantly shorter in the carriers with normal US than in those with non-cirrhotic CLD (US-CLD) or cirrhotic US (US-LC). There was no difference in the time interval to HBsAg seroclearance between the carriers with US-CLD and those with US-LC. Age did not significantly impact the difference in the time interval to the disappearance of HBsAg: normal US vs US-CLD, P = 0.0259; normal US vs US-LC, P = 0.0366; and US-CLD vs US-LC, P = 0.4724. However, there was no significant difference among the 40s and 50s age groups according to the stage of CLD: normal US vs US-CLD, P = 0.091; normal US vs US-LC, P = 0.0678; and US-CLD vs US-LC, P = 0.3579.