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. 2025 Feb;45(2):e16175.
doi: 10.1111/liv.16175.

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

Lorenz Balcar  1   2   3 , Nina Dominik  1   2   3 , Behrang Mozayani  4 , Georg Semmler  1   2   3 , Emina Halilbasic  1 , Mattias Mandorfer  1   2   3 , Thomas Reiberger  1   2   3 , Michael Trauner  1   3 , Bernhard Scheiner  1   2   3 , Albert Friedrich Stättermayer  1   2
Affiliations

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

Lorenz Balcar et al. Liver Int. 2025 Feb.

Abstract

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.

Keywords: PSVD; WD; Wilson disease; cirrhosis; portal hypertension.

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Conflict of interest statement

The authors have nothing to disclose regarding the work under consideration for publication. The following authors disclose conflicts of interests outside the submitted work: L.B. has nothing to disclose. N.D. has nothing to disclose. B.M. has received speakers fees from Astellas Pharma and Springer Medicine. G.S. has nothing to disclose. C.W. has nothing to disclose. M.M. served as a speaker and/or consultant and/or advisory board member for AbbVie, Gilead, Collective Acumen, and W. L. Gore & Associates, Takeda and received travel support from AbbVie, Bristol‐Myers Squibb and Gilead. T.R. served as a speaker and/or consultant and/or advisory board member for AbbVie, Bayer, Boehringer Ingelheim, Gilead, Intercept, MSD, Roche, Siemens and W. L. Gore & Associates and received grants/research support from AbbVie, Boehringer Ingelheim, Gilead, MSD, Philips and W. L. Gore & Associates as well as travel support from Boehringer Ingelheim and Gilead. M.T. received speaker fees from BMS, Falk Foundation, Gilead, Intercept, Ipsen, Jannsen, Madrigal, MSD and Roche; he advised for AbbVie, Albireo, BiomX, Boehringer Ingelheim, Cymabay, Falk Pharma GmbH, Genfit, Gilead, Hightide, Intercept, Ipsen, Janssen, MSD, Novartis, Phenex, Pliant, Rectify, Regulus, Siemens and Shire. He further received travel support from AbbVie, Falk, Gilead, Intercept, and Jannsen and research grants from Albireo, Alnylam, Cymabay, Falk, Gilead, Intercept, MSD, Takeda and UltraGenyx. He is also a co‐inventor of patents on the medical use of norUDCA filed by the Medical Universities of Graz and Vienna. B.S. received travel support from AbbVie, Ipsen and Gilead. A.F.S. has nothing to disclose.

Figures

FIGURE 1
FIGURE 1
Study description.
FIGURE 2
FIGURE 2
Venn diagram showing the proportion of patients with cholestasis and elevated hepatic copper content and respective intersections.
FIGURE 3
FIGURE 3
Determination of the most adequate cut‐off assessing hepatic copper content for prognostication of first/further hepatic decompensation/liver‐related death using the maxstat package and stratifying patients according to the respective cut‐off in a Kaplan–Meier curve (hepatic copper content ≥ vs. < 90 μg/g).
See this image and copyright information in PMC

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