Introduction

Wilson’s disease (WD) is an inherited disorder of copper metabolism with hepatic, neurological, psychiatric and ophthalmological manifestations [1]. The mainstay of treatment for WD is a lifelong oral pharmacotherapy [2].
Adherence to therapy is a major concern in WD patients, given that non-adherence leads to progression of liver disease and neurological symptoms, and it is considered one of the most common causes of progression and death.
Nowadays liver stiffness measurement (LSM) by transient elastography (TE) is an useful tool for non-invasive fibrosis staging in patients with chronic liver diseases [3]. In WD patients LSM > 9.9 kPa demonstrated a good accuracy in identifying the presence of cirrhosis. LSM appears to be stable over time in most chronically treated WD patients and close monitoring could not be necessary [4].
The role of FIB-4 score (age+ASL+ALT+platelets count) for non invasive liver fibrosis assessment has been fully established in infectious, metabolic and NAFLD diseases [5], while it has not been assessed in WD.

Aims & Methods

Aim: To assess the role of LSM by TE in the long term follow up of adult WD patients.
To explore the possible role of FIB-4 score in non-invasive fibrosis staging and its relationship with LSM in adult WD patients.
Methods: From January 2010 to December 2022, 38 WD patients were admitted to our outpatient clinic [M/F 17/21; medium age 35 (range 18-71 years)]. Each patient underwent complete laboratory work-up together with LSM by TE at the beginning of follow up and then at 12 months intervals. A FIB-4 score was also calculated. All patients were given oral therapy for WD: 4 patients were treated with D-penicillamine, 8 with trientine, 24 with zinc salts, 2 with a combination of zinc salts and a chelator.

Results

FIB-4 test and LSM were calculated for all patients at baseline. 29/38 patients showed LSM < 9.9 kPa, while 9/38 patients showed LSM≥9.9 kPa. When we compared FIB-4 score to LSM, 24/29 patients with LSM < 9.9 kPa had FIB-4 values <1.3 (advanced fibrosis excluded), while 5/29 patients had a FIB-4 score ranging 1.3-2.67 (“grey area”: further investigation needed); 7/9 patients with LSM≥9.9 kPa had a FIB-4 > 2.67 (advanced fibrosis likely).
On the basis of a follow-up of at least 5 years by TE, 19/38 (50%) patients were evaluable as having a “long term elastographic follow-up”. 15/19 (79%) of these patients showed stable LSM values (medium value 7.3 kPa at baseline, 7.6 kPa at 5-years follow up) without signs of disease progression, while 4 patients (21%) showed a progressive increase in LSM (medium value 6.9 kPa at baseline, 11.2 kPa at 5-years follow up): 2 of these 4 patients had a poor compliance to therapy, 1 had an active alcohol consumption, 1 had a concurrent hereditary thrombophilia and portal thrombosis occurred during the course of follow up.

Conclusion

These preliminary results confirm that liver disease in WD patients remains stable in almost all patients with good compliance to therapy, as confirmed by LSM during the course of follow up, while a progression of disease and an increase in LSM values has been observed in presence of therapy non-adherence or comorbidities.
Non-invasive fibrosis scores, such as FIB-4, could represent a valid support to LSM in fibrosis staging of WD patients. These results, however, need further validation in a larger cohort of WD patients.

References

1. Gitlin JD. Wilson disease. Gastroenterology. 2003;125(6):1868-1877.
2. Schilsky ML, Roberts EA, Bronstein JM, Dhawan A, Hamilton JP, Rivard AM, Washington MK, Weiss KH, Zimbrean PC. A multidisciplinary approach to the diagnosis and management of Wilson disease: 2022 Practice Guidance on Wilson disease from the American Association for the Study of Liver Diseases. Hepatology. 2022 Dec 7.
3. Castera L, Forns X, Alberti A. Non-invasive evaluation of liver fibrosis using transient elastography. J Hepatol. 2008;48(5):835-847
4. Paternostro R, Pfeiffenberger J, Ferenci P, et al. Non-invasive diagnosis of cirrhosis and long-term disease monitoring by transient elastography in patients with Wilson disease. Liver Int. 2020;40:894–904
5. Sterling RK, Lissen E, Clumeck N, et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology (Baltimore, MD). 2006;43(6):1317-1325