Natural YMDD-motif mutants affect clinical course of lamivudine in chronic hepatitis B

Table 1 Demographic data and clinical features of the study group n (%)

Characteristic	Total	YMDD variants	Without YMDD variants	P value
	(n = 1268)	(n = 288)	(n = 980)
Age (yr)	42.12 ± 13.24	42.42 ± 14.25	43 ± 12.15	0.812
Sex
Male	923 (72.79)	205 (71.18)	718 (73.26)	0.485
Female	345 (27.21)	83 (28.82)	262 (26.73)	0.485
Alcohol use
Yes	143 (11.3)	36 (12.5)	107 (10.9)	0.456
No	1125 (88.7)	252 (87.5)	873 (89.1)
Family history1
Yes	613 (48.3)	118 (41)	495 (50.5)	0.004
No	655 (51.7)	170 (59)	485 (49.5)
Aspartate aminotransferase (IU/L)	53 ± 25	56 ± 24	54 ± 23	0.963
Alanine aminotransferase (IU/L)	67 ± 26	63 ± 33	69 ± 31	0.012
Alkaline phosphatase (IU/L)	102 ± 45	106 ± 46	112 ± 54	0.064
Gamma-glutamyl transpeptidase (IU/L)	26 ± 4	25 ± 3	26 ± 3	0.852
HBV genotype
A	5 (0.4)	2 (0.7)	3 (0.3)	0.320
B	284 (22.4)	72 (25)	212 (21.6)
C	971 (76.6)	211 (73.3)	760 (77.6)
Others	8 (0.6)	3 (1.0)	5 (0.5)
HBeAg status
Positive	543 (42.8)	106 (36.8)	437 (44.6)	0.019
Negative	725 (57.2)	182 (63.2)	543 (55.4)
HBV DNA (LGE)	6.67 ± 2.47	7.27 ± 3.16	6.37 ± 2.64	0.024

Data are expressed as mean ± SD or as n (%).

¹Family history of positive hepatitis B surface antigen, including third-degree relatives. YMDD variants (n = 288, 22.71%), without YMDD variants (n = 980, 77.28%). LGE: Log10 genome equivalents; YMDD: Tyrosine-methionine-aspartic acid-aspartic acid; HBV: Hepatitis B virus; HBeAg: Hepatitis B e antigen.

Table 2 Characteristics of patients at the beginning of the lamivudine therapy

	Patients with YMDD variants (n = 40)	Patients without YMDD variants (n = 40)	P value
Age (yr)	42 ± 14	43 ± 12	NS
Sex (male/female)	23/17	23/17	Matched
Liver cirrhosis, n (%)	6 (15.0)	7 (17.5)	NS
Family history1, n (%)	21(52.5)	19 (47.5)	NS
Median duration of treatment (mo)	24 ± 6	24 ± 5	NS
Aspartate aminotransferase (IU/L)	81 ± 21	61 ± 27	NS
Alanine aminotransferase (IU/L)	132 ± 12	106 ± 16	NS
Serum bilirubin (μmol/L)	28.7 ± 13.4	31.8 ± 15.5	NS
Serum albumin (g/L)	38 ± 12	36 ± 13	NS
HBV-DNA (LGE/mL)	6.7 ± 2.7	6.8 ± 2.8	Matched
HBeAg positive, n (%)	15 (37.5)	15 (37.5)	Matched
HBV genotype (A/B/C/other)	1/4/33/2	0/4/32/4	NS

¹Family history of positive hepatitis B surface antigen, including third-degree relatives. YMDD: Tyrosine-methionine-aspartic acid-aspartic acid; NS: Not significant; HBV: Hepatitis B virus; LGE: Log10 genome equivalents; HBeAg: Hepatitis B e antigen.

Table 3 Multivariate logistic regression analysis of factors associated with natural tyrosine-methionine-aspartic acid-aspartic acid mutations

	Univariate		Multivariate
	OR (95%CI)	P value	OR (95%CI)	P value
Age (yr) (< 60, ≥ 60)	1.39 (0.57, 3.40)	0.4700	2.02 (0.72, 5.67)	0.1824
Gender (male, female)	1.41 (0.64, 3.12)	0.4850	1.24 (0.33, 4.59)	0.7518
Alcohol (yes, no)	1.75 (0.72, 4.24)	0.4560	1.27 (0.57, 2.85)	0.5608
Family history1 (yes, no)	2.45 (1.15, 5.25)	0.0040	1.77 (0.24, 3.84)	0.3254
Aspartate aminotransferase (IU/L; < 40, ≥ 40)	2.08 (0.91, 4.81)	0.9630	1.22 (0.28, 5.29)	0.7876
Alanine aminotransferase (IU/L; < 40, ≥ 40)	5.44 (1.45, 20.45)	0.0122	2.59 (1.24, 8.44)	0.0734
Alkaline phosphatase (IU/L; < 120, ≥ 120)	2.62 (0.67, 10.23)	0.9520	3.42 (0.81, 14.54)	0.0952
Gamma-glutamyl transpeptidase (IU/L; < 40, ≥ 40)	1.08 (0.47, 2.50)	0.8520	1.18 (0.35, 3.99)	0.7957
HBV genotype (A/B/C/other)	1.17 (0.55, 2.49)	0.3200	1.05 (0.40, 2.77)	0.5246
HBeAg state (+/-)	3.01 (1.37, 6.63)	0.0190	3.56 (1.55, 8.18)	0.0282
HBV DNA (LGE; < 5, ≥ 5)	2.45 (1.15, 5.25)	0.0240	2.70 (1.23, 5.92)	0.0133

HBV: Hepatitis B virus; HBeAg: Hepatitis B e antigen; LGE: Log10 genome equivalents.