Wilson disease is an autosomal recessive disorder characterized by abnormal copper accumulation, diagnosed based on clinical and laboratory features and treated with copper chelation [1,2]. Recent studies show that transient elastography (TE) could be used to predict liver fibrosis and monitor the disease progression [3]; however, many other conditions may lead to overestimation of the liver stiffness. Herein, we report a large reduction of liver stiffness after chelation therapy, that might be suggestive of effect of D-penicillamine and zinc on reducing copper load.

A 13-year-old girl presenting with jaundice, poor scholastic performance and coagulopathy for 6 months, was referred to our hospital for liver transplantation. Physical examination revealed Kayser-Fliescher (KF) rings with naked eye examination, splenomegaly, and pedal edema. However, her neurological system was otherwise normal. Laboratory investigations for Wilson disease and its complications were performed including complete blood count (hemoglobin 11 g/dL, white blood cell count 3,790/µL and platelet count 68,000/µL); liver function tests (total bilirubin 3.8 mg/dL, direct bilirubin, 2.1 mg/dL, albumin 2.0 g/dL, globulin 3.6 g/dL, AST 85 units/L, ALT 56 units/L and ALP 419 units/L); serum copper 0.42 pm; zinc 0.296 pm; PT 31.5 sec, INR 2.68; ceruloplasmin 9 mg/dL; and 24-hour urine copper 115.2 µg. Liver biopsy was omitted due to uncorrectable coagulopathy. TE (FibroScan; Echosens, Paris, France) was measured in preprandial state by a trained operator which showed a value of 50.6 kilopascals (kPa).

Fig. 1 Trend of laboratory parameters and transient elastography (TE) in the index patient with Wilson disease.

The patient was diagnosed with Wilson disease with 6 marks from the scoring system and the Wilson index score (WI) of 7, which implies good outcome without liver transplantation. Hence, D-penicillamine and zinc were initiated, and child closely followed-up for deterioration, and worsening coagulopathy. Six weeks later, while her clinical features and laboratory parameters did not improve, the TE value dramatically decreased (36.8 kPa). After one year, she rejoined school and performed well academically; her attention and memory were improved as per feedback from parents and teachers. However, KF rings were still present, even though tests of liver function were normal. The TE value was 34.3, 22.8 and 15.7 kPa at 6, 12 and 18 months, respectively, after the chelation therapy.

TE was used to measure liver stiffness by using a share wave method which determines the fibrosis level. TE has been studied as a non-invasive parameter to assess change in hepatic fibrosis during treatment in patients with Wilson disease; the cut-off values of mild and significant hepatic fibrosis were 6.6 and 8.4 kPa, respectively [3,4]. The decreasing value after copper chelation was ascribed to reduction in hepatic fibrosis [4]. However, liver elasticity may be influenced not only by fibrosis but also by other factors such as liver inflammation, the accumulation of various materials in liver tissue [4,5] and liver congestion [6]. Mikund, et al. [6] found a rapid decrease of liver stiffness from 73 kPa to 31 kPa in patients diagnosed with Budd Chiari syndrome after endovascular procedure that suggested the usefulness of TE in assessing hepatic congestion. Stefanescu, et al. [4] also reported reduction of liver stiffness after one year of treatment in children diagnosed Wilson disease. This study implied that intrahepatic copper deposit might be involved in the high liver stiffness before chelation therapy was initiated [4]. The present case demonstrated the reduction of liver stiffness after chelation therapy, with values comparable with the previous studies [4-6].

Consequently, the very high value of TE in the present case might reflect not only fibrosis but also the copper accumulation and inflammation in liver. Unfortunately, we could not measure the liver copper content as the patient had uncorrectable coagulopathy at the time of presentation. However, after chelation therapy, the TE value steadily decreased, which was associated with an improving clinical status. This report suggests the possibility of using TE to represent hepatic copper accumulation and to monitor treatment of Wilson disease.

1. Ferenci P, Caca K, Loudianos G, Mieli-Vergani G, Tanner S, Sternleib I, et al. Diagnosis and phenotypic classification of Wilson disease. Liver Int. 2003;23:139-42.

2. Dhawan A, Taylor RM, Cheeseman P, De Silva P, Katsiyiannakis L, Mieli-Vergani G. Wilson’s disease in children: 37-year experience and revised King’s score for liver transplantation. Liver Transpl. 2005;11:441-8.

3. Sini, M., Sorbello O, Civolani A, Liggi M, Demelia L. Non-invasive assessment of hepatic fibrosis in a series of patients with Wilson’s Disease. Dig Liver Dis. 2012;44:487-91.

4. Stefanescu AC, Pop TL, Stefanescu H, Miu N. Transient elastography of the liver in children with Wilson’s disease: Preliminary results. J Clin Ultrasound. 2016;44:65-71.

5. Musallam KM, Motta I, Salvatori M, Fraguelli M, Marcon A, Taher AT, et al. Longitudinal changes in serum ferritin levels correlate with measures of hepatic stiffness in transfusion-independent patients with beta-thalassemia intermedia. Blood Cells Mol Dis. 2012;49:136-9.