**4. Laboratory findings in liver sarcoidosis**

Both cholestasis and hepatocytolysis can appear in liver sarcoidosis. Abnormal liver tests are found in up to 40% of patients with sarcoidosis, with a predominance of cholestasis (increased alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (γGT) and minor increases in bilirubin levels) [34]. ALP can be increased in up to 90% of the patients with symptoms of hepatic disease, up to 10 times the upper normal limit [19]; by contrast, increases in transaminases are mild and less frequent. The severity of the cholestasis is associated with the degree of granulomatous inflammation [35].

Peripheral lymphopenia, especially noted in CD4+ positive cells, can be useful in suspecting sarcoidosis [31]. Hypercalcemia and hypercalciuria can also be found, but unrelated to liver involvement.

In cases with portal hypertension, frequent findings are pancytopenia [20, 31] with the predominance of thrombocytopenia. Hypoalbuminemia can also be encountered as a sign of liver disease.

Most laboratory determinations are aimed at excluding other causes of liver disease. Most commonly used are viral serology markers for hepatitis B and C infection, serum markers for Wilson's disease and hemochromatosis (especially in young patients), autoantibody determinations for celiac disease, primary biliary cirrhosis and autoimmune hepatitis. **Table 1** summarizes the main serum determinations to exclude other etiologies of liver disease [36].

Patients with active disease may present with increased levels of serum inflammation markers (such as erythrocyte sedimentation rate and C-reactive protein), regardless of the organs involved [37]. CRP may also be associated with fatigue in sarcoidosis. However, these tests are not specific in any way to sarcoidosis.

There are yet no serum markers for the clear diagnosis of sarcoidosis. High serum levels of angiotensin-converting enzyme have been associated with sarcoidosis and are present in about 60% of patients with active disease [19]. Nevertheless, the test is far from pathognomonic, with low positive and negative predicting values


#### **Table 1.**

*Biological parameters required in the etiology of liver disease (adapted from [36]).*

(84% and 74%, respectively). Normal ACE levels should not be used for exclusion of sarcoidosis-they can be encountered in patients with chronic disease or patients under corticoid therapy. High values are indicative of sarcoidosis and can be used in excluding other granulomatous diseases. However, inflammatory bowel disease can also manifest with high level of ACE, and the differential diagnosis is difficult, especially when primary biliary cirrhosis is associated. Increased levels of ACE can also be found in pulmonary silicosis, asbestosis, military tuberculosis, diabetes mellitus and hyperthyroidism [38].
