‘Silver man’ – A first case report of silver associated steatohepatitis (SASH) and discussion of its pathomechanism

Abstract

A 47-year-old Chinese man, who worked as a clerk in the electronics industry, presented with gait instability and glove-and-stocking sensation. He had anaemia, deranged liver function, low ceruloplasmin (0.05 g/L; ref 0.18–0.35), high 24-urine copper (2.02 μmol/L; ref <0.5 μmol/L), low iron level (5 umol/L; ref 9–33), high ferritin (4521 pmol/L; ref 52–738) and low transferrin saturation (11%; ref 16–45). MRI liver and pancreas showed homogenous T2 hypointensity, a feature of iron deposition. MRI brain showed artefacts in bilateral globus pallidi that suggested mineralisation. Sequencing of ATP7B gene did not reveal any pathogenic variants. Further clarification of the clinical history revealed that colloidal silver was prescribed by his private practitioner for over a year. His blood silver level was about a thousand times above that of controls. In the liver tissues, there were patchy lymphocytic infiltrates with periportal and focal bridging fibrosis, moderate haemosiderin deposits and presence of silver. Clinical symptoms and biochemical results were improved after silver exposure was stopped. Silver binds with ceruloplasmin and loses its ferroxidase activity, so Fe2+ cannot be oxidised to Fe3+ and cannot be carried by transferrin. This leads to intracellular iron overload in the liver, pancreas and neuronal tissues.