Hepatitis B virus infection in patients with Wilson disease: A large retrospective study

Table 1 Prevalence of hepatitis B infection in patients with Wilson disease stratified by gender and age

	Number of patients	Negative for HBVM (%)	Anti-HBs(+) alone (%)	Prior HBV infection (%)	Current HBV infection (%)
Total group	915	393 (43.0)	419 (45.8)	84 (9.2)	19 (2.1)
Sex
Male	532	228 (42.9)	239 (44.9)	52 (9.8)	13 (2.4)
Female	383	165 (43.1)	180 (47.0)	32 (8.4)	6 (1.6)
Age group (yr)
2-10	231	105 (45.5)	119 (51.5)	7 (3.0)	0 (0.0)
11-20	340	156 (45.9)	159 (46.8)	15 (4.4)	10 (2.9)
21-30	153	63 (41.2)	73 (47.7)	13 (8.5)	4 (2.6)
31-40	106	40 (37.7)	42 (39.6)	21 (19.8)	3 (2.8)
41-65	85	29 (34.1)	26 (30.6)	28 (32.9)	2 (2.3)

HBVM: Hepatitis B virus markers; HBV: Hepatitis B virus.

Table 2 Characteristics of patients with Wilson disease and chronic hepatitis B: The demographic characteristics and parameters of hepatitis B virus infection

Case	Sex	Age (yr)	History of HBV (yr)	HBsAg	HBeAg	Anti-HBe	HBV DNA
1	Female	16	2	+	-	+	< 100
2	Male	19	2	+	-	+	9.3e8
3	Female	19	2	+	-	-	< 100
4	Male	26	3	+	+	-	1.9e6
5	Male	43	3	+	-	+	5.6e5
6	Female	37	2	+		+	7.3e3
7	Male	19	3	+	-	+	< 100
8	Male	11	5	+	+	-	3.2e7
9	Male	26	20	+	-	+	1.9e4
10	Female	17	3	+	-	+	< 10
11	Male	20	10	+	+	-	2.3e4
12	Male	11	?	+	-	+	< 10
13	Female	32	?	+	-	+	81
14	Male	27	?	+	+	-	1.3e6
15	Male	24	16	+	+	-	2.1e8
16	Male	15	16	+	-	+	< 10
17	Male	65	30	+	-	+	22.3
18	Female	35	16	+	-	+	< 10
19	Male	15	10	+	+	-	1.8e6

HBV: Hepatitis B virus; HBsAg: Hepatitis B surface antigen; HBeAg: Hepatitis B e antigen.

Table 3 Characteristics of patients with Wilson disease and chronic hepatitis B: Diagnostic parameters of Wilson disease

Case	Neurologic signs	KF rings	Cerulo plasmin (mg/L)	Urinary copper/after PC (μg/24 h)	Hepatic copper (μg/g/dw)	Mutation analysis	WD score
1	No	P	65.0	177/1600	ND	ND	5
2	No	P	50.0	1222/4250	ND	ND	6
3	No	P	95.0	1818/2266	ND	ND	6
4	Yes	P	187.0	434/ND	ND	ND	7
5	No	P	172.0	107/1295	347	ND	6
6	No	P	216.0	431/1436	1165	ND	6
7	No	P	50.0	5171/15398	ND	ND	6
8	No	P	250.0	305/1933	1173	ND	6
9	No	N	74.0	474/1500	926	3532G>T/3532G>T	10
10	No	P	84.0	595/1725	ND	2755C>G/2975C>T	10
11	No	N	135.0	1297/2984	ND	588C>A/2333G>T	7
12	No	P	78.4	160/1773	741	2975C>T/2975C>T	11
13	No	P	129	855/2505	ND	ND	5
14	No	P	31.0	310/1984	1067	3809 >G/	9
15	No	N	104.0	187/1836	896	0	4
16	Yes	P	86.5	237/2374	404	ND	10
17	No	P	83.1	64/714	265	2975C>T/	7
18	No	P	43.0	155/171	906	2804C>T/2810delT	11
19	No	P	63.0	584/2473	ND	2666G>T/2333G>T	10

WD: Wilson disease; KF rings: Kayser-Fleischer rings; ND: Not done; PC: Penicillamine challenge; N: Negative; P: Positive.

Table 4 Characteristics of patients with Wilson disease and chronic hepatitis B: Parameters of liver disease

Case	ALT	AST	ALB	TBIL	GGT	ALP	INR	Severity of liver disease	Outcome
1	29	50	20.3	46.7	46	74	2.61	CTP: 13	Died
2	70	185	26.8	264	84	61	2.8	ACLF	Died
3	86	50	25.1	123	58	85	2.7	CTP: 13	Died
4	41	60	30.4	44.4	90	70	4.5	CTP: 13	Died
5	102	170	35.7	48.0	110	95	1.5	CTP: 10	Died
6	119	291	27.6	417	186	390	2.1	ACLF	Alive
7	79	123	31	456	45	57	4.1	ACLF	Died
8	231	237	37.5	16.5	353	105	1.2	CTP:6	Alive.
9	74	101	29.8	39.0	42	116	1.5	CTP:10	Alive
10	79	105	24.5	42.0	110	130	2.4	CTP:12	Alive
11	223	268	30.0	368	147	252	2.8	ACLF	Died
12	71	83	31.0	23.0	62	357	1.6	CTP:10	Alive
13	70	76	28.0	25.6	35	375	1.63	CTP:10	Alive
14	82	151	37.8	28.7	152	149	1.36	CTP:5	Alive
15	276	102	39.9	25.3	113	93	0.95	Hepatitis	Alive
16	22	47	36.5	16	32	219	1.25	Hepatitis	Alive
17	31	28	47.3	26.3	23	76	1.01	Hepatitis	Alive
18	56	34	42.0	22.0	90	60	1.01	Hepatitis	Alive
19	57	74	28.0	373	268	293	3.01	ACLF	Died

ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; ALB: Albumin; TBIL: Total bilirubin; GGT: Gamma-glutamyl transpeptidase; ALP: Alkaline phosphatase; INR: International normalized ratio; ACLF: Acute-on-chronic liver failure; CTP: Child-Turcotte-Pugh.

Table 5 Factors associated with severe liver disease at the Wilson disease diagnosis

Factors (at diagnosis)	OR	95%CI	P value
Gender
Male	1
Female	1. 945	1.402-2.698	0.000
Age at diagnosis (yr)
Group 1 (0-10)	1
Group 2 (11-20)	1.766	1.145-2.723	0.010
Group 3 (21-30)	0.757	0.423-1.352	0.346
Group 4 (31-40)	1.178	0.646-2.148	0.594
Group 5 (41-65)	1.455	0.777-2.724	0.241
HBV infection
WD alone	1
WD with previous HBV	5.255	3.159-8.739	0.000
WD with current HBV	7.748	2.890-20.774	0.000

Severe liver disease is defined as patients with acute-on-chronic liver failure or a Child-Turcotte-Pugh score ≥ 10 at the Wilson disease diagnosis, HBV: Hepatitis B virus; WD: Wilson disease; OR: Odds ratio; CI: Confidence interval.

Table 6 Comparison of hepatitis B surface antigen positivity rates among different age groups between patients with Wilson disease and the general population

Age groups (yr)	Wilson disease		General population (Henan)		P value
	Number tested	HBsAg(+) (n, %)	Number tested	HBsAg(+) (n, %)
1-4	40	0, 0.0	5474	26, 0.5	0.827
5-9	148	0, 0.0	4407	32, 0.7	0.625
10-14	191	3, 1.6	3376	40, 1.2	0.505
15-17	97	3, 3.1	Not done
18-34	298	9, 3.0	6764	220, 3.1	0.825
35-54	122	3, 2.5	6777	275, 4.7	0.490
55-74	19	1, 5.3	3144	147, 5.1	0.599
Total	915	19, 2.1	29892	740, 2.5	0.510

HBsAg: Hepatitis B surface antigen.

Table 7 Comparison between Wilson disease patients alone and Wilson disease patients with hepatitis B virus infection

	WD alone (n = 812)	With previous HBV (n = 84)	With current HBV (n = 19)	P1	P2
Sex
Male (n, %)	467 (57.5)	46 (61.9)	12 (63.2)	0.509	0.797
Female (n, %)	345 (42.5)	32 (38.1)	7 (36.8)	0.509	0.797
Mean age (yr)	18.8 ± 12.0	33. ± 15.9	25.0 ± 13.	0.000	0.031
Diagnosis delay	12.1 ± 21.3	13.7 ± 26.1	34.6 ± 53.5	0.542	0.000
Phenotype
Pure H (n, %)	564 (69.5)	63 (75.0)	17 (89.5)	0.352	0.104
H and N (n, %)	195 (24.40)	21 (25.60)	2 (10.5)	0.352	0.104
Pure N (n, %)	35 (4.3)	0 (0.0)	0
Others (n, %)	18 (2.2)	0	0
Copper metabolic
KF positive	67.6%	84.1%	78.9%	0.102	0.456
Ceruloplasmin	64.1 ± 46.0	97.1 ± 60.3	105.0 ± 61.6	0.000	0.000
Urinary copper	502.4 ± 1030.5	916.3 ± 245.8	767.7 ± 1165.0	0.005	0.323
Urinary Cu after PC	2236.4 ± 1582.1	2283.7 ± 1287.8	2793.8 ± 3157.5	0.842	0.144
Hepatic Cu	832.2 ± 457.7	680.1 ± 407.7	789.0 ± 338.2	0.191	0.767
Mean WD score	7.4 ± 2.3	8.0 ± 2.2	7.8 ± 2.3	0.124	0.412
Biochemical
ALT (IU/L)	86.2 ± 105.7	63.3 ± 51.0	94.6 ± 71.1	0.0051	0.722
AST (IU/L)	84.25 ± 90.3	90.47 ± 70.4	125.3 ± 80.5	0.0532	0.058
Albumin (g/L)	38.5 ± 8.3	32.5 ± 7.6	32.1 ± 6.8	0.000	0.001
TBIL (μmol/L)	52.1 ± 131.0	104.7 ± 166.7	126.6 ± 158.3	0.001	0.002
GGT (IU/L)	90.9 ± 85.6	138.6 ± 112.3	109 ± 93.3	0000	0.399
ALP (IU/L)	186.7 ± 133.6	137.7 ± 87.7	171.9 ± 123.0	0.001	0.650
INR	1.42 ± 0.81	1.88 ± 0.86	2.09 ± 1.04	0.000	0.000
Liver disease severity
Hepatitis (n, %)	372 (45.8)	7 (8.3)	3 (15.8)	0.000	0.009
CTP5-6 (n, %)	189 (23.3)	18 (21.4)	3 (15.8)	0.702	0.444
CTP7-9 (n, %)	94 (11.6)	14 (16.7)	1 (5.3)	0.173	0.713
CTP10-14 (n, %)	120 (14.8)	34 (40.5)	7 (36.8)	0.000	0.008
ACLF (n, %)	37 (4.5)	11 (13.1)	5 (26.3)	0.001	0.000
Mortality (n, %),	33 (4.1)	13 (15.5)	7 (36.8)	0.000	0.000

HBV: Hepatitis B virus; WD: Wilson disease; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; TBIL: Total bilirubin; GGT: Gamma-glutamyl transpeptidase; ALP: Alkaline phosphatase; INR: International normalized ratio; ACLF: Acute-on-chronic liver failure; CTP: Child-Turcotte-Pugh; PC: Penicillamine challenge.