Liver damage in sarcoidosis. Review

Abstract

Lungs are the most commonly affected organ in sarcoidosis, with extrapulmonary changes observed in 50 % of cases. We detect liver damage in 11—80 % of cases, with lower rates in clinically manifest cases and higher rates in incidental findings during liver biopsy. Despite all the achievements of world medicine, the exact cause of sarcoidosis remains unknown. Still, it is believed that the pathogenesis is multifactorial, including immunological and genetic mechanisms as well as the influence of environmental factors. Regarding the frequency of lesions in sarcoidosis, pathology of the lungs and lymph nodes predominates, with less often the liver. 90 % of patients with systemic sarcoidosis have liver granulomas detected. Contrary to bilateral intrathoracic adenopathy, sarcoid changes in the lung parenchyma more frequently accompany hepatic sarcoidosis. While the presence of hepatic granulomas indicates a diagnosis of hepatic sarcoidosis, it is important to consider liver granulomas in the differential diagnosis as they can also occur in various systemic diseases. Granulomas in hepatic sarcoidosis are characterized by aggregates of epithelioid histiocytic and multinucleated giant cells, with lymphocytes and fibrin deposits predominantly at the periphery. These lesions are small, multiple, and evenly distributed throughout the liver parenchyma (although predominantly in the periportal and portal areas) and have the same maturation stage. Usually, there is no necrosis, but in some atypical cases, one may observe small areas of necrosis. Longstanding lesions contain reticulin fibers within the granulomas, occasionally forming a prominent «cuff» of fibrosis. Large confluent granulomas may cause hyalinized scars. These changes, along with chronic intrahepatic cholestasis, may contribute to the development of micronodular biliary cirrhosis. Hepatic sarcoidosis may be presented with intrahepatic or extrahepatic cholestasis. Regarding histology, intrahepatic cholestasis in hepatic sarcoidosis looks like both primary biliary cholangitis and primary sclerosing cholangitis foci. Patients with hepatic sarcoidosis may develop noncirrhotic presinusoidal portal hypertension. Hepatic sarcoidosis is usually asymptomatic (50—80 %), but when symptoms are present, the clinical spectrum may be broad. About 15 % of cases exhibit pruritus and abdominal pain in chronic cholestasis. Jaundice is rare. 3—28 % of patients experience cholestasis and fever, while fatigue is common. 5—10 % of patients exhibit hepatomegaly and splenomegaly, particularly when portal hypertension is present. Predominantly elevated alkaline phosphatase levels (5—10 times the upper limit of normal) may be common. There is no specific serologic test to diagnose hepatic sarcoidosis. Since most patients with hepatic sarcoidosis are asymptomatic, they do not require specific drug therapy. However, in patients with symptoms of liver disease or patients with severe sarcoidosis and risk of liver complications or severe cholestasis, drug therapy should be considered. The most commonly used drug therapy options include corticosteroids and ursodeoxycholic acid. Secondline therapy includes azathioprine, methotrexate, and infliximab. Liver transplantation should be considered in complicated cases with significant liver dysfunction.