Exploratory longitudinal cohort study of modest bilirubin-driven biochemical liver alterations after SARS-CoV-2 infection in a selected subgroup of patients with Wilson's disease and liver cirrhosis.

backgroundWilson’s Disease (WD) is a rare genetic disorder characterized by impaired hepatic copper elimination, potentially leading to chronic liver disease and cirrhosis. Although SARS-CoV-2 primarily affects the respiratory tract, hepatic involvement has been described. Using WD as a well-characterized model of a rare chronic liver disease with standardized long-term follow-up, we exploratively assessed short- and intermediate-term associations between SARS-CoV-2 infection and liver function as well as copper metabolism in patients with and without cirrhosis.

methodsIn this longitudinal real-world study, we analyzed 71 WD patients (49 without cirrhosis, 22 with cirrhosis) with confirmed SARS-CoV-2 infection. Laboratory parameters, 24-hour urinary copper excretion (24-UCE), and transient elastography were assessed before infection (t0), shortly after infection (t1), and >12 months post-infection (t2). Effect sizes (r) were calculated for intraindividual comparisons. Clinical severity, vaccination status, and long-COVID symptoms were recorded.

resultsNo patient required hospitalization. In WD patients without cirrhosis, liver enzymes, cholestasis markers, and copper metabolism remained stable across all timepoints, with predominantly very small effect sizes (|r| < 0.3), indicating no clinically meaningful changes. In contrast, cirrhotic WD patients exhibited moderate to large short-term effects in transaminases and GGT (r up to 0.85) following infection. Bilirubin showed the most pronounced and persistent alteration in cirrhotic patients, with a sustained but only moderate effect (r ≈ 0.6) at long-term follow-up. Partial biochemical recovery was observed, yet normalization remained incomplete. Liver stiffness and copper parameters did not change significantly in either group.

conclusionsSARS-CoV-2 infection was associated with persistent biochemical alterations, particularly elevated bilirubin levels of moderate magnitude in WD patients with cirrhosis, while global liver function parameters remained largely stable. These findings highlight the need for close post-infection monitoring of WD patients with cirrhosis, even in mild SARS-CoV-2 infections, to mitigate potential hepatic complications and guide ongoing management in this vulnerable population. Nevertheless, these observations are hypothesis-generating and should be interpreted cautiously due to the small, selected cirrhotic subgroup, the lack of appropriate control groups, and the delayed timing of post-infection assessments.