Diagnostic value of elevated serum angiotensin-converting enzyme and lymphopenia in patients with granulomatous hepatitis

Main Article Content

Thomas El Jammal
François Dhelft
Pierre Pradat
François Bailly
Fabien Zoulim
Arnaud Hot
Maxime Fauter
Ayoub Drissi-Bakhkhat
Isabelle Durieu
Jean-Christophe Lega
Yvan Jamilloux
Pascal Sève


granulomatous hepatitis, sarcoidosis, angiotensin converting enzyme, lymphopenia


Background and aim : Granulomatous hepatitis (GH) is associated with various aetiologies, especially inflammatory and infectious disorders. Sarcoidosis is a granulomatous disease in which the liver is the fourth most affected organ. Since epithelioid cell granulomas are not specific to sarcoidosis and since most patients with hepatic sarcoidosis are asymptomatic, valuable diagnostic biomarkers are needed to support the diagnosis of sarcoidosis. This study proposes to assess the diagnostic value of serum angiotensin converting enzyme (sACE) and lymphopenia in GH for sarcoidosis.

Methods : We retrospectively analyzed the records of 90 patients referred to the internal medicine or hepatogastroenterology departments of the Lyon University Hospital (Lyon, France) between March 2002 and January 2020 in a context of GH.

Results : In our tertiary center, 38 patients with sarcoidosis were identified among 73 patients with GH. Lymphopenia had a high specificity (85.7%), which increased when combined with elevated (97.0%). Interestingly, specificity increased in patients under 50 years old (100%).

Conclusions: Those results suggests that lymphopenia and sACE may be valuable biomarkers for sarcoidosis diagnosis in GH when combined, especially in younger patients.


Download data is not yet available.
Abstract 45 | PDF Downloads 38


1. Coash M, Forouhar F, Wu CH, Wu GY. Granulomatous liver diseases: a review. J Formos Med Assoc. 2012 Jan;111(1):3–13.
2. Deutsch-Link S, Fortuna D, Weinberg EM. A Comprehensive Review of Hepatic Sarcoid. Semin Liver Dis. 2018;38(3):284–97.
3. Gaya DR, Thorburn D, Oien KA, Morris AJ, Stanley AJ. Hepatic granulomas: a 10 year single centre experience. J Clin Pathol. 2003 Nov;56(11):850–3.
4. Geri G, Cacoub P. [Hepatic granulomas]. Rev Med Interne. 2011 Sep;32(9):560–6.
5. Wainwright H. Hepatic granulomas. European Journal of Gastroenterology & Hepatology. 2007 Feb;19(2):93–5.
6. Syed U, Alkhawam H, Bakhit M, Companioni RAC, Walfish A. Hepatic sarcoidosis: pathogenesis, clinical context, and treatment options. Scand J Gastroenterol. 2016 Sep;51(9):1025–30.
7. Branson JH, Park JH. Sarcoidosis—hepatic involvement: presentation of a case with fatal liver involvement, including autopsy findings and review of the evidence for sarcoid involvement of the liver as found in the literature. Annals of Internal Medicine. 1954 Jan 1;40(1):111–45.
8. Judson MA. Hepatic, splenic, and gastrointestinal involvement with sarcoidosis. Semin Respir Crit Care Med. 2002 Dec;23(6):529–41.
9. Morimoto T, Azuma A, Abe S, Usuki J, Kudoh S, Sugisaki K, et al. Epidemiology of sarcoidosis in Japan. Eur Respir J. 2008 Feb;31(2):372–9.
10. Judson MA, Boan AD, Lackland DT. The clinical course of sarcoidosis: presentation, diagnosis, and treatment in a large white and black cohort in the United States. Sarcoidosis Vasc Diffuse Lung Dis. 2012 Oct;29(2):119–27.
11. Cozier YC, Berman JS, Palmer JR, Boggs DA, Serlin DM, Rosenberg L. Sarcoidosis in black women in the United States: data from the Black Women’s Health Study. Chest. 2011 Jan;139(1):144–50.
12. Kennedy PTF, Zakaria N, Modawi SB, Papadopoulou AM, Murray-Lyon I, du Bois RM, et al. Natural history of hepatic sarcoidosis and its response to treatment. Eur J Gastroenterol Hepatol. 2006 Jul;18(7):721–6.
13. Iwai K, Oka H. SARCOIDOSIS. REPORT OF TEN AUTOPSY CASES IN JAPAN. Am Rev Respir Dis. 1964 Oct;90:612–22.
14. Lieberman J. Elevation of serum angiotensin-converting-enzyme (ACE) level in sarcoidosis. Am J Med. 1975 Sep;59(3):365–72.
15. K A, Jf K. Diagnostic value of serum angiotensin converting enzyme activity in lung diseases. Thorax. 1976 Oct 1;31(5):552–7.
16. Silverstein E, Friedland J, Kitt M, Lyons HA. Increased serum angiotensin converting enzyme activity in sarcoidosis. Isr J Med Sci. 1977 Oct;13(10):995–1000.
17. Studdy P, Bird R, James DG. Serum angiotensin-converting enzyme (SACE) in sarcoidosis and other granulomatous disorders. Lancet. 1978 Dec 23;2(8104–5):1331–4.
18. Nosal A, Schleissner LA, Mishkin FS, Lieberman J. Angiotensin-I-converting enzyme and gallium scan in noninvasive evaluation of sarcoidosis. Ann Intern Med. 1979 Mar;90(3):328–31.
19. Sweiss NJ, Salloum R, Gandhi S, Ghandi S, Alegre ML, Sawaqed R, et al. Significant CD4, CD8, and CD19 lymphopenia in peripheral blood of sarcoidosis patients correlates with severe disease manifestations. PLoS ONE. 2010 Feb 5;5(2):e9088.
20. Grunewald J, Grutters JC, Arkema EV, Saketkoo LA, Moller DR, Müller-Quernheim J. Sarcoidosis. Nat Rev Dis Primers. 2019 04;5(1):45.
21. Hunninghake GW, Costabel U, Ando M, Baughman R, Cordier JF, du Bois R, et al. ATS/ERS/WASOG statement on sarcoidosis. American Thoracic Society/European Respiratory Society/World Association of Sarcoidosis and other Granulomatous Disorders. Sarcoidosis Vasc Diffuse Lung Dis. 1999 Sep;16(2):149–73.
22. Crouser ED, Maier LA, Wilson KC, Bonham CA, Morgenthau AS, Patterson KC, et al. Diagnosis and Detection of Sarcoidosis. An Official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med. 2020 Apr 15;201(8):e26–51.
23. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of cholestatic liver diseases. Journal of Hepatology. 2009 Aug;51(2):237–67.
24. Flamm SL. Granulomatous liver disease. Clin Liver Dis. 2012 May;16(2):387–96.
25. Moreno-Merlo F, Wanless IR, Shimamatsu K, Sherman M, Greig P, Chiasson D. The role of granulomatous phlebitis and thrombosis in the pathogenesis of cirrhosis and portal hypertension in sarcoidosis. Hepatology. 1997 Sep;26(3):554–60.
26. Bihari C, Rastogi A, Kumar N, Rajesh S, Sarin SK. Hepatic Sarcoidosis: Clinico-pathological characterization of symptomatic cases. Acta Gastroenterol Belg. 2015 Sep;78(3):306–13.
27. Bunting PS, Szalai JP, Katic M. Diagnostic aspects of angiotensin converting enzyme in pulmonary sarcoidosis. Clin Biochem. 1987 Jun;20(3):213–9.
28. Ungprasert P, Carmona EM, Crowson CS, Matteson EL. Diagnostic Utility of Angiotensin-Converting Enzyme in Sarcoidosis: A Population-Based Study. Lung. 2016 Feb;194(1):91–5.
29. Baudin B. L’enzyme de conversion de l’angiotensine I (ECA) dans le diagnostic de la sarcoïdose. Pathologie Biologie. 2005 Apr 1;53(3):183–8.
30. Crouser ED, Lozanski G, Fox CC, Hauswirth DW, Raveendran R, Julian MW. The CD4+ lymphopenic sarcoidosis phenotype is highly responsive to anti-tumor necrosis factor-{alpha} therapy. Chest. 2010 Jun;137(6):1432–5.
31. Gupta D, Rao VM, Aggarwal AN, Garewal G, Jindal SK. Haematological abnormalities in patients of sarcoidosis. Indian J Chest Dis Allied Sci. 2002 Dec;44(4):233–6.
32. C B, C L, B W. [Biological manifestations of sarcoidosis]. Ann Med Interne (Paris). 2001 Feb 1;152(1):34–8.
33. Morell F, Levy G, Orriols R, Ferrer J, De Gracia J, Sampol G. Delayed cutaneous hypersensitivity tests and lymphopenia as activity markers in sarcoidosis. Chest. 2002 Apr;121(4):1239–44.
34. Vagts C, Ascoli C, Fraidenburg DR, Baughman RP, Huang Y, Edafetanure-Ibeh R, et al. Unsupervised Clustering Reveals Sarcoidosis Phenotypes Marked by a Reduction in Lymphocytes Relate to Increased Inflammatory Activity on 18FDG-PET/CT. Frontiers in Medicine [Internet]. 2021 [cited 2022 Jun 11];8. Available from: https://www.frontiersin.org/article/10.3389/fmed.2021.595077
35. Cotte P, Pradat P, Kodjikian L, Jamilloux Y, Seve P. Diagnostic value of lymphopaenia and elevated serum ACE in patients with uveitis. Br J Ophthalmol. 2021 Oct;105(10):1399–404.
36. Eurelings LEM, Miedema JR, Dalm VASH, van Daele PLA, van Hagen PM, van Laar JAM, et al. Sensitivity and specificity of serum soluble interleukin-2 receptor for diagnosing sarcoidosis in a population of patients suspected of sarcoidosis. PLoS One. 2019;14(10):e0223897.
37. Dourakis SP, Saramadou R, Alexopoulou A, Kafiri G, Deutsch M, Koskinas J, et al. Hepatic granulomas: a 6-year experience in a single center in Greece. European Journal of Gastroenterology & Hepatology. 2007 Feb;19(2):101–4.

Most read articles by the same author(s)