ABSTRACT
Background: Serum levels of aminotransferases ALT and AST are useful markers of hepatic injury. Serum levels of ALT and AST are elevated in most untreated Wilson Disease (WD) patients and during non-adherence to therapy. In some treated WD patients, ALT or AST may not normalize. We aimed to examine patterns of ALT and AST elevation, and hypothesize that there is a potential correlation with 24-hour urine copper excretion (UCE) in context of the current treatment regimen, and the trend of these values over the course of 3 years. Method(s): Patients at time of enrolment and up to year 3 in the WD Registry study with both ALT and AST and UCE available for analysis. Serum ALT and AST levels were classified as normal (10-35 IU), 1-2x the upper limit of normal (ULN), and 2-3x the ULN. Treatment regimens were included. Result(s): From enrolment to year 3 the number of adult patients was as follows: enrolment n=88, year 1 n= 61, year 2 n =42, year 3 n= 36. Average age was 41. The registry experienced a decrease in follow up related to the COVID-19 pandemic. Patients were on the following treatments: chelation therapy (Trientene or D-penicillamine) at time of enrolment n=56, year 1 n= 34, year 2 n=22, year 3 n= 15 zinc therapy, at enrolment n=30, year 1 n= 24, year 2 n=17, year 3 n= 17;and those on combination therapy at enrolment n=7, year 1 n= 4, year 2 n=3, year 3 n= 0. Average mean duration of treatment was 21 years at enrolment. When subdivided by the different treatment regimens and ALT and AST ranges, UCE fluctuated throughout the 3 years. Having normal to low 24-hour urine copper did not directly correlate directly with normalization of ALT and AST for the different treatment regimens (see Figure 1). Similarly, higher levels of UCE failed to show a linear correlation with ALT and AST. Conclusion(s): UCE and ALT and AST are laboratory measurements that have been used as a means for monitoring copper balance and therapeutic response for treating WD. The current data fails to support the hypothesis that UCE within target goals will exhibit direct correlation with normal ALT and AST values. Rather, the individual patient variability suggests that UCE cannot be used in isolation for treatment recommendations, supporting the need for better surrogate markers of copper balance. (Figure Presented).