Epidemiology and natural history of Wilson’s disease in the Chinese: A territory-based study in Hong Kong between 2000 and 2016

Table 1 International classification of diseases-9 code for outcome and covariates

Impaired or abnormal liver function	573.8, 794.8
Hepatitis	573.3, 571.40, 571.41
Chronic liver disease	571.9, 573.9
Acute liver failure	570
Chronic liver failure	571.8
Hepatocellular carcinoma	155.0
Cirrhosis	571.5
Viral hepatitis B carrier	V02.61:0
Viral hepatitis C carrier	V02.62:0
Sequalae of chronic liver disease	572.8
Esophageal varices	456.0, 456.1
Gastric varices	456.8
Ascites	789.5
Spontaneous bacterial peritonitis	567.2
Portal hypertension	572.3
Splenomegaly/Hypersplenism	789.1, 789.2, 789.4
Hepatic encephalopathy	572.2
Hepatorenal syndrome	572.4
Liver transplantation	V42.7
Parkinsonism	332
Tremor	781.0
Dystonic disorder	333.6
Convulsion	780.32
Tics	307.20
Dementia	290
Bipolar affective disorder	296.7
Depression	296.2, 296.3, 311
Anxiety	300.0
Organic affective syndrome	293.83
Psychosis	295, 293.83
Personality disorder	301
Suicide	E950
Hemolytic anemia	283.10
Alcoholism	291, 571.0, 571.1, 571.2, 571.3, 303, 305.0, 980.8, 980.9
Obesity	278.0, 278.1
Diabetes mellitus	249, 250
Hypertension	401-405
Dysplipidemia	272.0-272.4

Table 2 Clinical characteristics of patients with Wilson’s disease in Hong Kong [n = 211, n (%)]

Variables	Clinical characteristics
Age	27.9 (18.2-39.7)
Male	104 (49.3)
Drug	193 (91.5)
D-penicillamine1	129 (61.6)
Trientine2	22 (10.4)
Zinc	42 (19.9)
Hepatic disease	176 (83.4)
Cirrhosis	38 (21.6)
Cirrhotic complications	19 (10.8)
Ascites	10 (5.7)
Spontaneous bacterial peritonitis	5 (2.8)
Esophageal varices	10 (5.7)
Gastric varices	5 (2.8)
Hepatic encephalopathy	8 (4.5)
Hepatocellular carcinoma	3 (1.7)
Neurological disease	30 (14.2)
Parkinsonism	15 (50.0)
Tremor	3 (10.0)
Dystonia	4 (13.3)
Tics	1 (3.3)
Dementia	2 (6.7)
Seizure	7 (23.3)
Psychiatric disease	24 (11.4)
Depression	9 (37.5)
Anxiety	2 (8.3)
Bipolar disorder	4 (16.7)
Organic affective syndrome	3 (12.5)
Psychosis	4 (16.7)
Personality disorder	3 (12.5)
Suicide	4 (16.7)
Concomitant hepatic and neurological/psychiatric diseases	21 (10.0)
Non-immune hemolytic anemia	8 (3.8)
Viral hepatitis	7 (3.3)
Chronic hepatitis B infection	5 (71.4)
Chronic hepatitis C infection	2 (28.6)
Metabolic factors	17 (8.1)
Diabetes mellitus	3 (17.6)
Hypertension	7 (41.2)
Dyslipidemia	4 (23.5)
Obesity	4 (23.5)
Alcoholism	4 (23.5)
Liver transplantation	24 (11.3)
Death	26 (12.3)

¹Twenty four patients had concomitant zinc therapy during the initial treatment phase or maintenance phase;

²Eight patients had concomitant zinc therapy during the initial treatment phase or maintenance phase. Age was expressed as median (years) with interquartile range. Categorical variables were expressed as n (%).

Table 3 The use of different medications in patients with neurological and/or psychiatric involvement

Drugs
Anticonvulsants (carbamazepine and valproate)
Antidepressants (citalopram and fluoxetine)
Anti-parkinson agents (levodopa, bromocriptine, amantadine, ropinorole and benzhexol)
Antipyschotics (clozapine, olanzapine, quetiapine, perphenazine, paliperidone and trifluoperazine)
Baclofen
Benzodiazepines (clonazepam, diazepam and lorazepam)
Lithium
Propranolol
Tetrabenazine

Table 4 Clinical characteristics of patients with Wilson’s disease according to different age strata [n = 211, n (%)]

	Age < 20 (n = 65)	Age 20-39.9 (n = 94)	Age ≥ 40 (n = 52)	P value
Hepatic involvement	58 (89.2)	74 (78.7)	44 (84.6)	0.201
Cirrhosis	7 (10.8)	18 (19.1)	13 (25.0)	0.128
Cirrhotic complications	4 (6.2)	9 (9.6)	6 (11.5)	0.584
Hepatocellular carcinoma	0	0	3 (11.5)	0.014
Neurological involvement	9 (13.8)	16 (17.0)	5 (9.6)	0.469
Psychiatric involvement	6 (9.2)	12 (12.8)	6 (11.5)	0.787
Liver transplantation	11 (16.9)	11 (11.7)	2 (3.8)	0.066
Death	4 (6.2)	9 (9.6)	13 (25.0)	0.005

Significant P values were bolded.

Table 5 Incidence rate and prevalence of Wilson’s disease in Hong Kong

Yr	Total population (million)			New cases			Total cases			Incidence rate (per million person-years)			Prevalence (per million)			Prevalence ratio of M/F
	M	F	T	M	F	T	M	F	T	M	F	T	M	F	T
2000	3.28	3.39	6.67	4	7	11	24	28	52	1.22	2.06	1.65	7.32	8.26	7.80	0.89
2001	3.28	3.43	6.71	6	9	15	28	36	64	1.83	2.62	2.24	8.54	10.5	9.54	0.81
2002	3.28	3.56	6.74	3	8	11	31	44	75	0.91	2.25	1.63	9.45	12.36	11.13	0.76
2003	3.26	3.47	6.73	11	7	18	40	51	91	3.37	2.02	2.67	12.27	14.7	13.52	0.83
2004	3.27	3.52	6.78	9	4	13	47	54	101	2.75	1.14	1.92	14.37	15.34	14.90	0.94
2005	3.26	3.55	6.81	4	5	9	51	57	108	1.23	1.41	1.32	15.64	16.06	15.86	0.97
2006	3.27	3.59	6.86	2	3	5	52	60	112	0.61	0.84	0.73	15.90	16.71	16.33	0.95
2007	3.28	3.63	6.92	2	3	5	54	63	117	0.61	0.83	0.72	16.46	17.36	16.91	0.95
2008	3.29	3.67	6.96	2	2	4	54	63	117	0.61	0.54	0.57	16.41	17.17	16.81	0.96
2009	3.28	3.69	6.97	6	10	16	60	72	132	1.83	2.71	2.30	18.29	19.51	18.94	0.94
2010	3.29	3.73	7.02	9	8	17	68	80	148	2.74	2.14	2.42	20.67	21.45	21.08	0.96
2011	3.30	3.77	7.07	8	3	11	75	83	158	2.42	0.80	1.56	22.73	22.02	22.35	1.03
2012	3.33	3.83	7.15	3	2	5	77	85	162	0.90	0.52	0.70	23.12	22.19	22.66	1.04
2013	3.33	3.86	7.19	2	3	5	79	87	166	0.60	0.78	0.70	23.72	22.54	23.09	1.05
2014	3.35	3.90	7.24	2	8	10	82	94	175	0.60	2.05	1.38	24.48	24.10	24.17	1.02
2015	3.37	3.94	7.31	6	0	6	86	93	179	1.78	0.00	0.82	25.52	23.60	24.49	1.08
2016	3.38	3.96	7.34	5	4	9	89	96	185	1.48	1.01	1.23	26.33	24.24	25.20	1.09

M: Male; F: Female; T: Total.

Table 6 Average age-specific incidence rate of Wilson’s disease in Hong Kong between 2000 and 2016

	Case number			Incidence rate (per million person-years)
Age group	M	F	T	M	F	T
0-4	6	7	13	2.81	3.38	2.61
5-9	3	7	10	1.35	2.73	2.02
10-14	4	9	13	1.30	2.94	2.09
15-19	10	12	22	2.70	3.43	3.06
20-24	10	10	20	2.64	2.52	2.58
25-29	9	6	15	2.33	1.21	1.71
30-34	11	8	19	2.72	1.45	1.97
35-39	9	10	19	1.92	1.70	1.80
40-44	10	9	19	1.92	1.54	1.74
45-49	4	5	9	0.81	0.92	0.86
≥ 50	7	4	11	0.36	0.21	0.29

M: Male; F: Female; T: Total.

Table 7 HRs and 95%CIs for the association between different covariates and overall survival, transplant-free survival

	Univariate analysis		Multivariate analysis
	HR	95%CI	HR	95%CI
Overall survival
Age1	1.04	1.02-1.07	1.03	0.99-1.08
Male sex	1.49	0.52-4.29
Hepatic disease	0.92	0.21-4.13
Cirrhosis	15.42	5.15-46.18	21.75	5.62-84.18
Hepatocellular carcinoma	12.42	2.71-56.93	2.23	0.38-13.32
Chronic viral hepatitis2	4.95	1.09-22.44	7.04	0.94-52.81
Neurological or psychiatric disease	1.11	0.35-3.55
Metabolic factors3	4.37	1.37-13.96	2.68	0.59-12.17
Drug
Penicillamine	Reference	-
Trientine	2.30	0.61-8.63
Zinc	0.30	0.04-2.39
transplant-free survival
Age1	1.04	1.01-1.07	1.03	0.98-1.07
Male sex	1.45	0.54-3.88
Hepatic disease	1.09	0.25-4.80
Cirrhosis	21.34	7.34-61.99	32.16	8.58-120.52
Hepatocellular carcinoma	11.25	2.48-50.92	1.93	0.34-11.07
Chronic viral hepatitis2	4.48	0.998-20.09	9.97	1.36-73.05
Neurological or psychiatric disease	1.27	0.44-3.66
Metabolic factors3	3.59	1.16-11.16	2.51	0.60-10.54
Drug
D-penicillamine	Reference	-
Trientine	1.97	0.54-7.17
Zinc	0.26	0.03-1.97

¹Age was treated as a continuous variable in the analysis;

²Chronic viral hepatitis was defined as the presence of either chronic hepatitis B or C infection;

³Metabolic factors were defined as the presence of one of the following: diabetes mellitus, hypertension, dyslipidemia, obesity or alcoholism. Significant risk factors were bolded.