Wilson disease: Histopathological correlations with treatment on follow-up liver biopsies

Table 3 Review of the case series describing the evolution of hepatic histology in WD

Grand et al[18], 1975		Treatment: PCA
Interbiopsy interval 2-7 yr		Hepatic copper (μg/g dry weight)		AST/ALT		Histopathology
	Age at diagnosis (yr)	Before	After	Before	After	Before	After
1	24	NA	400	NA	NA	Inflammation 3+; connective tissue 13%; fatty vacuolization 0.5%	Inflammation 1+; connective tissue 7%; fatty vacuolization 0.5%
2	18	NA	80	NA	NA	Inflammation 2+; connective tissue NA; fatty vacuolization NA	Inflammation 2+; connective tissue 3%; fatty vacuolization 2%
3	11	1360	757	NA	NA	Inflammation 3+; connective tissue 17.6%; fatty vacuolization 5%	Inflammation 0/1+; connective tissue 7.6%; fatty vacuolization 3%
4	13.5	1112	90	NA	NA	Inflammation 4+; connective tissue 16%; fatty vacuolization 13%	Inflammation 0; connective tissue 14%; fatty vacuolization 8%
Sternlieb et al[19], 1976		Treatment: PCA
Interbiopsy interval 3-5 yr		Hepatic copper (μg/g dry weight)		AST/ALT		Histopathology
	Age at diagnosis (yr)	Before	After	Before	After	Before	After
1	15	821	109	52/59	39/20	Mild fibrosis; steatosis	Mild fibrosis; marked diminution of steatosis
2	9	1004	945	76/136	20/44	Steatosis	Marked diminution of steatosis
3	12	866	737	180/190	24/26	NA	NA
4	15	1123	239	22/94	16/22	Severe steatosis	Resolution of severe steatosis
5	10	832	453	57/88	53/48	Inflammation; mild fibrosis; steatosis	Resolution of inflammation; mild fibrosis; diminution of steatosis
6	12	1177	1050	65/85	45/43	Inflammation; severe fibrosis and steatosis	Resolution of inflammation; diminution of severe steatosis and fibrosis
7	14	NA	NA	75/82	50/35	Inflammation; steatosis; cirrhosis	Diminution of steatosis and inflammation; persistence of cirrhosis
Shiono et al[20], 2001		Treatment: PCA
Interbiopsy interval 3-8.5 yr		Hepatic copper (mg/g dry weight)		ALT (IU/L)		Histopathology (only stage of fibrosis)
	Age at diagnosis (yr)	Before	After	Before	After	Before	After
1	16	990	319	121	65	Cirrhosis with chronic active hepatitis	Cirrhosis
2	17	1025	200	241	109	Chronic active hepatitis	Chronic inactive hepatitis
3	19	524	190	17	25	Cirrhosis	Cirrhosis
4	23	540	129	19	18	Cirrhosis	Cirrhosis
Marcellini et al[12], 2005		Treatment: zinc sulfate
Interbiopsy interval 10 yr		Hepatic copper (median of 22 pts) (mg/g dry weight)		AST/ALT (mean of 22 pts)		Histopathology summary of 22 pts
		Before	After	Before	After	Before	After
Mean age at diagnosis (yr)		873 (670-982)	690 (600-890)	110/94	21.7/23.7	Inflammation grade 1 in 81% of pts, grade 0 in 19%; steatosis grade 1 in 50%, grade 2 in 22.7%, grade 3-4 in 27.3%; fibrosis stage 1 in 54%, stage 3 in 46%	Resolution of inflammation in all pts; steatosis grade 1 in 90%, grade 2 in 10%; fibrosis stage 1 in 81%, stage 3 in 19%
6.1 ± 2.5
Askari et al[13], 2003		Treatment: trientine + zinc, followed by long-term zinc
Interbiopsy interval 4.4-10 yr		Hepatic copper		Child Pugh score (AST/ALT not available)		Histopathology (only stage of fibrosis)
		Before	After	Before	After	Before	After
Mean age at diagnosis (yr)		NA	NA	9-13	5	Cirrhosis	Fibrosis stage 2-3
25.4 ± 3.9						Cirrhosis	Fibrosis stage 3-4
						Cirrhosis	Fibrosis stage 1
Linn et al[14], 2009		Treatment: zinc
Interbiopsy interval		Hepatic copper (mg/g dry weight)		ALT (U/L)		Histopathology
3-7 yr
	Age at diagnosis (yr)	Before	After	Before	After	Before	After
1	21	NA	NA	59	57	Mild fibrosis	Normal
2	13	1100	270	31	19	Normal	Cirrhosis