Effect of D-penicillamine on liver fibrosis and inflammation in Wilson disease.
BACKGROUND
Wilson disease is a disorder of copper metabolism characterized by copper overload. A mutation in the ATP7B gene causes dysfunction of ATP7B protein and a reduction in copper excretion into the bile in hepatocytes. Excess copper accumulation leads to liver injury. D-penicillamine primarily can inhibit fibrogenesis and prevent the appearance of scar lesions in the liver. We studied this phenomenon in our patients.


METHODS
Pathology slides from the explanted livers of 26 patients diagnosed as having Wilson disease with hepatoneurologic manifestations between 2000 and 2008 who had undergone a liver transplant were investigated retrospectively. Patients were divided into 2 groups according to their history of D-penicillamine use before transplant. The degree of fibrosis and inflammation were classified as mild (1), moderate (2), and severe (3), and were reviewed by an impartial hepatopathologist.


RESULTS
Of 26 patients (20 male, 6 female) who had Wilson disease with a mean age of 17.6 -/+ 8.6 years, 69% (18/26) had a history of D-penicillamine use before liver transplant from 6 months to 9 years (mean, 3.4 -/+ 2.7 years). In the D-penicillamine group, 14 patients (77%) had grade 1 fibrosis. Grade 2 and 3 fibrosis was seen in 5.6% and 16% of patients, respectively. In the D-penicillamine group, inflammation was grade 3 in 44% (8/18), grade 2 in 44% (8/18), and grade 1 in 11% of the patients (2/18). In the non- D-penicillamine group (8 patients), grades of fibrosis were grade 3 (62%), grade 2 (25%), and grade 1 (12%); 87% of the patients had grade 2 and 3 inflammation. The degree of fibrosis was significantly lower in the D-penicillamine group than it was in the non-D-penicillamine group (P < .05).


CONCLUSIONS
D-penicillamine may reduce the rate of liver fibrogenesis in patients with Wilson disease.
Kazemi
Kourosh
K
Shiraz Organ Transplantation Center, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran.
Geramizadeh
Bita
B
Nikeghbalian
Saman
S
Salahi
Heshmatollah
H
Bahador
Ali
A
Reza Nejatollahi
Seyed Mohammad
SM
Dehghani
Seyed Mohsen
SM
Dehghani
Masood
M
Kakaei
Farzad
F
Malek-Hosseini
Seyed Ali
SA