Revisiting the topic of histochemically detectable copper in various liver diseases with special focus on venous outflow impairment

We surveyed histochemically detectable copper in various liver diseases with emphasis on chronic biliary disease (CBD) and venous outflow impairment. Using rhodanine, we graded copper accumulation in 298 liver specimens: venous outflow impairment (n = 64), CBD (n = 123), Wilson disease (WD) (n = 12), chronic hepatitis C (n = 32), steatohepatitis (n = 28), sarcoidosis (n = 15), cholestatic hepatitis (n = 12), and acute large bile duct obstruction (n = 12). Copper was detected in 39% of specimens; all had chronic liver disease. Copper increased with increasing fibrosis. CBD accumulated copper more frequently than other chronic diseases (except WD), both in early (61% vs 3%) and late (94% vs 59%) stages and in larger amounts. Rhodanine was positive in 73% of livers with CBD, 20% with sarcoidosis, 9% with chronic hepatitis C, and 7% with steatohepatitis. Copper was detected in 14% of chronic venous outflow impairment specimens; with 1 exception, stainable copper was absent in early stages but detected in 38% of cirrhotic livers. In conclusion, rhodanine helps differentiate CBD from other conditions, including venous outflow impairment; in the absence of advanced fibrosis, rhodanine positivity strongly favors CBD. In contrast, rhodanine positivity is nonspecific in cirrhosis, but the absence of copper in that setting excludes CBD.