Hepatic sarcoidosis: Current state of the problem

Abstract

Sarcoidosis is a systemic inflammatory disorder of unknown etiology characterized by the formation of non-caseating epithelioid cell granulomas and multisystem organ damage, which arise from an aberrant primarily Th1/Th17-mediated immune response in genetically predisposed individuals. Among the organs involved in extrathoracic sarcoidosis, the liver ranks first after the lymph nodes. However, the true prevalence of liver involvement is probably underestimated due to the asymptomatic course of the disease. The ante-mortem examinations reveal that hepatic granulomas are detected in 3.6–20% of cases, while autopsy results indicate a detection rate of up to 50–80%. The involvement of Kupffer cells in the aberrant immune response lies at the root of the pathogenesis, leading to the formation of granulomas predominantly at the portal/ periportal location, with intrahepatic cholestasis, progressive fibrosis, and, less commonly, noncirrhotic portal hypertension developing overtime. Clinical presentation can be highly variable, ranging from incidental finding of granulomas on liver biopsy to severe cholestatic liver injury leading eventually to liver cirrhosis. Laboratory test results typically show a cholestatic pattern with elevated alkaline phosphatase and gamma-glutamyl transpeptidase levels and less pronounced transaminases. Diagnostic imaging techniques reveal only nonspecific findings, that’s why histological assessment based on liver biopsy remains the gold standard for hepatic sarcoidosis, with a reported sensitivity of approximately 88%. The diagnosis is ultimately established only after the exclusion of alternative causes of hepatic granulomas. Glucocorticosteroids are typically used as a first-line treatment. Unfortunately, the therapeutic benefits of glucocorticoids are limited by the systemic side effects, and do not always result in regression of histological changes. The use of ursodeoxycholic acid is pathogenetically substantiated due to the pronounced cholangiopathic component of bile duct injury. The findings of the analysis of systematic reviews show that 57.5% patients treated with ursodeoxycholic acid achieved a complete clinical and biochemical response, which is superior to glucocorticosteroid monotherapy (42.8%), with a more favorable safety profile. Further data accumulation in prospective registries and randomized trials will refine the precise role of ursodeoxycholic acid in the treatment of hepatic sarcoidosis.