A case study of a patient with acute liver failure (ALF) was admitted with some Wilson disease (WD) biomarkers but not others highlighting the need for better guidelines on the differential diagnosis of fulminate WD from ALF and acute-on-chronic liver failure (ACLF). The case report was published in ACG Case Reports Journal.
The 36-year-old male patient was admitted after experiencing a seizure. He had a history of seizures, chronic hepatitis B, alcohol use, and was HIV-positive. Initial imaging workup found hepatosplenomegaly, distension of the gallbladder with wall thickening, a mild reversal of flow in the hepatic portal vein, and ascites.
Read more about WD differential diagnosis
He received a heparin infusion for possible thrombosis of the portal vein and 2 units of red blood cells due to a hemoglobin level of 6.4 g/dL. He was managed for ACLF and acute liver injury, and an extensive laboratory workup revealed a ceruloplasmin (Cp) level of 6 mg/dL.
Further workup for fulminate WD (FWD) revealed no Kayser-Fleischer rings or sunflower cataracts on examination of the eyes, but 24-hour urine copper was elevated at 180 mg/L. Liver biopsy was negative for copper and showed some bridging fibrosis and patchy hepatocyte dropout but no definite cirrhosis. Hepatic copper levels were found to be 18 mcg/g.
MRI of the brain revealed no findings suggestive of WD but an increased T1 signal within the bilateral globus pallidi, which suggested chronic liver disease. Whole-exome sequencing found no pathogenic ATP7B variants normally associated with WD.
The Leipzig score, endorsed by the European Association for the Study of the Liver, was 3 for the patient, indicating that WD was possible but could not be ruled in. The diagnostic algorithm used by the American Association for the Study of Liver Diseases (AASLD) at the time of the patient’s presentation ruled out WD due to a hepatic liver level of less than 50 mcg/g.
In contrast, an algorithm that was inspired by both the AASLD and Leipzig scores would have ruled the patient in based on their elevated CP and 24-hour urine copper excretion levels. This algorithm is similar to the AASLD’s current algorithm, which was released after the patient’s discharge. Under this current AASLD algorithm, the patient would have been misdiagnosed with WD without the need for ATP7B sequencing or biopsy.
“Ultimately, we feel that alcohol-related hepatitis is a more probable diagnosis given biopsy findings and AT7B sequencing,” the authors wrote.
“Our case highlights the need for further research on copper dysregulation in ALF and ACLF. Although early treatment is vital for a good prognosis in FWD and FWD is relatively common in young patients with ALF/ACLF, little research on copper biomarkers in this setting hinders accurate diagnosis and prompt treatment,” they added.
The patient also experienced acute pancreatitis and acalculous cholecystitis during their hospital stay. Ultimately, the patient was deemed not suitable for liver transplant and was released to home hospice care. He died 2 months after discharge.
Diamond E, Newman J, Schalet R, Lap CJ, Abutaleb AO. Dysregulation of copper metabolism in a patient with acute-on-chronic liver failure worked up for fulminant Wilson disease. ACG Case Rep J. July 7, 2023. doi:10.14309/crj.0000000000001084