Wilson Hastalarının Klinik Izlemi ve Uzun Dönem Tedavi Sonuçlarının Değerlendirilmesi

Abstract

Wilson's disease (WD) is characterized by degenerative changes in the brain, liver and cornea as a result of excessive accumulation of copper in tissues. While it is known as a chronic liver disease, early diagnosis and treatment of WD may provide a normal life course even in the presence of cirrhosis. World wide prevalence is 1/30.000 and carrier frequency is 1/90. The incidence is estimated as 1/50.000 to 1/100.000 in births. Most common diagnostic tools include; ceruloplasmin level, 24 hour urine copper excretion, presence of Kayser Fleischer ring and detection of liver tissue copper amount. Early diagnosis is particularly important in WD since the treatment maintains lifelong. The treatment aims reducing accumulation of copper in tissues. In this retrospective study we aimed to evaluate long term treatment outcomes and follow up features as well as initial clinical and laboratory findings in a group of 116 WD cases whom were followed up at least 36 months. Mean follow up duration was 71,3±38,7 months and 64 (55,2%) of participitants were male. The youngest patient with WD diagnosis was 17 months aged. Consanquinity rate was 52,6% while 45,7% of them reported to have at least one brother with WD. Contrary to synchronize involvement of 3 systems (hepatic, neurologic, renal) in 2 cases, single hepatic involvement was seen in 62,9% of them, hepatoneurologic involvement in 27,6% and hepato-renal involvement in 7,8%. Clinical and laboratory features such as hepatomegaly, splenomegaly, ascites, jaundice, presence of Kayser fleischer rings, mean ALT- AST-ALP-INR levels and total bilirubin levels were found to be significantly lower at the last control visit when compared to initial state (p<0.05). However mean ceruloplasmin and 24 hour urine copper levels belonging to last control visits were significantly elevated than the initial levels (p<0,05). Liver biopsy was done in 99 patients. Hepatic tissue copper values were more than 250 μgr/gr (normal=<50 μgr/gr) in 83 (83,8%) of patients. According to histopathological findings in biopsy 50,6% of cases were detected to had chronic hepatitis, 31,4% cirrhosis and 6% with increased fibrosis. Combination therapy of D-penisillamine and zinc were administered to 83,7% (n=97) of patients. D-penisillamine in 7 patients, zinc in 2 and trientine in 10 patients were used without combination. Adverse effects of drugs were observed in 10 patients. In 8 patients adverse effects were related with the D-penisillamin. These were nephrotic syndrome (25%), hypertransaminasemia (25%), pancytopenia (25%) and trombocytopenia (25%). Moreover some patients were detected to have impairments such as proteinuria (12,5%) and bicytopenia (12,5%). 10 of patients (8,6%) had been performed liver transplantation and 1 was suggested to have transplantation. During follow up only 1 (0,9%) case died due to acute liver failure caused by WD. Owing to the high frequency of consanquinity in our country, it is imperative to consider WD in differential diagnosis of children with acute or chronic liver diseases and corresponding neurologic impairments as well as increased transaminases. Moreover family screenings are crucial in terms of establishing early diagnosis and treatment of WD. Despite their some adverse effects D-penicillamine, trientin and zinc are beneficial drugs for recovery of clinical and laboratory findings.