Elevated Hepatic Copper Content in Porto-Sinusoidal Vascular Disorder (PSVD): Leading Down a Wrong Track.

Background And Aims: Porto-sinusoidal vascular disorder (PSVD) is a rare vascular liver disorder characterised by specific histological findings in the absence of cirrhosis, which is poorly understood in terms of pathophysiology. While elevated hepatic copper content serves as diagnostic hallmark in Wilson disease (WD), hepatic copper content has not yet been investigated in PSVD.

Methods: Patients with a verified diagnosis of PSVD at the Medical University of Vienna and available hepatic copper content at the time of diagnosis of PSVD were retrospectively included. Elevated hepatic copper content was correlated with cholestatic changes and WD diagnostics in PSVD and analysed for liver-related outcomes (first/further hepatic decompensation/liver-related death).

Results: Overall, 92 patients were included into this study (mean age 49 ± 16; 57% male; median hepatic copper content was 30 [IQR: 18-55] μg/g) of whom 29 (32%) had moderately (≥ 50 μg/g) and 4 (4%) strongly (≥ 250 μg/g) elevated hepatic copper content. Elevated levels of hepatic copper were associated with younger age in multivariable linear regression analysis. After adjusting for age, decompensation status and albumin, hepatic copper content was significantly associated with the outcome of interest (log, per 10; aHR: 1.60 [95% CI: 1.14-2.25]; p = 0.007). A hepatic copper cut-off at ≥ 90 μg/g identified PSVD patients with considerable risk of liver-related outcomes (at 2 years: 51% vs. 12%).

Conclusion: Elevated hepatic copper seems frequent in patients with PSVD even in the absence of cholestatic features, especially in young patients, which makes differential diagnosis to WD challenging. Since PSVD patients with elevated hepatic copper content had increased risk for liver-related outcomes, the pathomechanisms underlying hepatic copper accumulation in PSVD should be investigated as this may open new therapeutic avenues.