2026-07-08 | A 31-Year-Old Woman With Liver Cirrhosis Due to Wilson Disease and the Double Impact of Active Tuberculosis and Anti-Tuberculosis Therapy Resulting in Acute Liver Injury.

BACKGROUND In some patients with Wilson disease, there can be a combined impact of active tuberculosis (TB) and anti-tuberculosis therapy (ATT), a "double hit", due to drug-induced liver injury that can accelerate Wilson cirrhosis and result in acute liver failure. This report presents the case of a 31-year-old woman with liver cirrhosis due to Wilson disease and the combined impact of active TB and ATT resulting in acute liver injury. CASE REPORT A 31-year-old woman with genetically confirmed Wilson disease and Child-Pugh B liver cirrhosis presented in July 2025 with acute hepatic decompensation. Investigation revealed a positive QuantiFERON-TB Gold test result, lymphocytic exudative ascites, and a clinical picture consistent with extrapulmonary TB. Empiric ATT was initiated with rifampicin and isoniazid. Within 2 months, she re-presented with severe anti-TB drug-induced liver injury, which manifested as acute-on-chronic liver failure. The hepatotoxic regimen was immediately discontinued, and intensive supportive care was administered, resulting in gradual stabilization of liver function and clinical improvement. CONCLUSIONS This case demonstrates the critical "double-hit" vulnerability in Wilson disease, in which copper-mediated glutathione depletion leaves the liver unable to detoxify standard anti-TB drugs. Clinicians managing TB in patients with decompensated Wilson cirrhosis should avoid standard rifampicin-isoniazid regimens and use hepatosafe alternatives instead. A high index of suspicion for TB is warranted in all cirrhotic patients with fever, lymphocytic exudative ascites, and unexplained decompensation.

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2026-07-08 | Mechanisms of multi-organ damage in Wilson disease from the gut-liver-brain axis perspective: copper metabolism, gut microbiota, and metabolite communication.

Wilson disease (WD) is an autosomal recessive disorder of copper metabolism caused by ATP7B mutations, leading to pathological copper deposition in the liver, brain, and cornea. Although the gut-liver-brain axis plays a role, direct copper accumulation in multiple organs remains the primary cause of tissue damage. Recent years have seen growing attention to the gut microbiota in WD pathogenesis. Copper imbalance remodels gut microbiota composition and function, while dysbiosis, in turn, affects copper absorption and excretion, forming a vicious cycle that exacerbates multi-organ damage. Copper-induced intestinal barrier disruption, lipopolysaccharide translocation, and systemic inflammation are key links connecting local copper accumulation to systemic injury. This review summarizes the genetic basis of WD, mechanisms of copper toxicity, gut microbiota alterations, and their roles in liver injury and neurodegeneration. It highlights microbiota-derived metabolites-short-chain fatty acids, tryptophan metabolites, bile acids, sulfur-containing amino acids, and branched-chain amino acids-in inter-organ communication. The bidirectional interaction between WD therapies (chelators, zinc salts, dietary interventions) and the gut microbiota is analyzed, along with microbiota-based personalized therapies. However, most current evidence derives from animal models or small cross-sectional studies; large-scale longitudinal human data are critically lacking. A deeper understanding of the gut-liver-brain axis in WD may reveal novel biomarkers and therapeutic targets.

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2026-07-02 | The gut-liver-kidney-brain axis in Wilson disease: copper speciation-flux and barrier-mediated organ crosstalk.

Wilson disease (WD) has long been framed as a hepatocentric disorder of copper accumulation. That view is now giving way to a broader model centered on the gut-liver-kidney-brain axis. In WD, copper is not simply stored in tissues as an inert burden. It circulates in dynamic, bioactive pools-particularly relative exchangeable copper (REC)-that disrupt barrier structures, including the intestinal epithelium and blood-brain barrier, and spread toxicity through measurable biochemical mediators. Major pathogenic processes include copper-induced suppression of autophagy, disruption of FXR-regulated bile acid signaling, and direct injury to the intestinal barrier. Gut dysbiosis, supported by fecal microbiota transplantation (FMT) studies in ATP7B-deficient mice, further amplifies hepatic inflammation and favors copper retention. Renal tubular dysfunction and neurotoxicity appear to reflect copper species-dependent passage across biological barriers together with secondary metabolic disturbances, including the recently described pathway of cuproptosis. In the clinic, this shift has been accompanied by greater use of copper-species biomarkers such as ceruloplasmin oxidase activity and REC, along with advanced imaging approaches such as 64Cu-PET/CT. Treatment is also moving beyond conventional chelation alone, with increasing attention to biliary copper excretion, epithelial barrier repair, and microbiome-directed interventions. Viewed in this way, the axis model helps explain the marked phenotypic heterogeneity of WD and offers a mechanistic basis for more precise interventions aimed at breaking pathogenic feedback loops across organs.

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