Semin Respir Crit Care Med 2020; 41(05): 652-658
DOI: 10.1055/s-0040-1713799
Review Article

Hepatic Sarcoidosis: Current Concepts and Treatments

Geoffrey Rossi
1   Service de Médecine Interne, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique—Hôpitaux de Paris, Université Paris Est Créteil, Créteil, France
,
Marianne Ziol
2   Service d'anatomopathologie, Centre Hospitalier Jean-Verdier, Bondy, France
,
Dominique Roulot
3   Service d'Hépatologie, Centre Hospitalier Universitaire Avicenne, Bobigny, France
4   Service de Pneumologie, Centre Hospitalier Universitaire Avicenne, Université Sorbonne Paris Nord, APHP, Bobigny, France
,
Dominique Valeyre
4   Service de Pneumologie, Centre Hospitalier Universitaire Avicenne, Université Sorbonne Paris Nord, APHP, Bobigny, France
,
Matthieu Mahévas
1   Service de Médecine Interne, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique—Hôpitaux de Paris, Université Paris Est Créteil, Créteil, France
› Author Affiliations

Abstract

Hepatic sarcoidosis is a relatively common manifestation of extrapulmonary sarcoidosis. It occurs in 20 to 30% of cases and is rarely severe. However, a cluster of patients may develop severe complications such as cirrhosis and portal hypertension. In this review, we describe the current knowledge of clinical, biological, pathological, and radiological features of liver involvement in sarcoidosis and discuss essential clues for management and treatment.



Publication History

Article published online:
10 August 2020

© 2020. Thieme. All rights reserved.

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  • References

  • 1 Iannuzzi MC, Rybicki BA, Teirstein AS. Sarcoidosis. N Engl J Med 2007; 357 (21) 2153-2165
  • 2 Baughman RP, Teirstein AS, Judson MA. , et al; Case Control Etiologic Study of Sarcoidosis (ACCESS) research group. Clinical characteristics of patients in a case control study of sarcoidosis. Am J Respir Crit Care Med 2001; 164 (10 Pt 1): 1885-1889
  • 3 Tadros M, Forouhar F, Wu GY. Hepatic sarcoidosis. J Clin Transl Hepatol 2013; 1 (02) 87-93
  • 4 Mañá J, Rubio-Rivas M, Villalba N. , et al. Multidisciplinary approach and long-term follow-up in a series of 640 consecutive patients with sarcoidosis: cohort study of a 40-year clinical experience at a tertiary referral center in Barcelona, Spain. Medicine (Baltimore) 2017; 96 (29) e7595
  • 5 Ebert EC, Kierson M, Hagspiel KD. Gastrointestinal and hepatic manifestations of sarcoidosis. Am J Gastroenterol 2008; 103 (12) 3184-3192 , quiz 3193
  • 6 Iwai K, Oka H. Sarcoidosis. Report of ten autopsy cases in Japan. Am Rev Respir Dis 1964; 90: 612-622
  • 7 Ricker W, Clark M. Sarcoidosis; a clinicopathologic review of 300 cases, including 22 autopsies. Am J Clin Pathol 1949; 19 (08) 725-749
  • 8 Ungprasert P, Crowson CS, Simonetto DA, Matteson EL. Clinical characteristics and outcome of hepatic sarcoidosis: a population-based study 1976-2013. Am J Gastroenterol 2017; 112 (10) 1556-1563
  • 9 Maddrey WC, Johns CJ, Boitnott JK, Iber FL. Sarcoidosis and chronic hepatic disease: a clinical and pathologic study of 20 patients. Medicine (Baltimore) 1970; 49 (05) 375-395
  • 10 Bilir M, Mert A, Ozaras R. , et al. Hepatic sarcoidosis: clinicopathologic features in thirty-seven patients. J Clin Gastroenterol 2000; 31 (04) 337-338
  • 11 Klatskin G, Yesner R. Hepatic manifestations of sarcoidosis and other granulomatous diseases; a study based on histological examination of tissue obtained by needle biopsy of the liver. Yale J Biol Med 1950; 23 (03) 207-248
  • 12 Nathan N, Marcelo P, Houdouin V. , et al; RespiRare and the French Sarcoidosis groups. Lung sarcoidosis in children: update on disease expression and management. Thorax 2015; 70 (06) 537-542
  • 13 Kahi CJ, Saxena R, Temkit M. , et al. Hepatobiliary disease in sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 2006; 23 (02) 117-123
  • 14 Kennedy PTF, Zakaria N, Modawi SB. , et al. Natural history of hepatic sarcoidosis and its response to treatment. Eur J Gastroenterol Hepatol 2006; 18 (07) 721-726
  • 15 Schupp JC, Freitag-Wolf S, Bargagli E. , et al. Phenotypes of organ involvement in sarcoidosis. Eur Respir J 2018; 51 (01) 1700991
  • 16 James WE, Koutroumpakis E, Saha B. , et al. Clinical features of extrapulmonary sarcoidosis without lung involvement. Chest 2018; 154 (02) 349-356
  • 17 John B, Nagpal SJS, Plesec T. , et al. Mo1901 evaluation of portal hypertension and cirrhosis in patients with hepatic sarcoidosis: a prospective single center study. Gastroenterology 2015; 148 (04) (Suppl. 01) S1078
  • 18 Ara N, Iijima K, Honda J. , et al. Endoscopically proven case of rapid esophagogastric variceal progression and rupture as a result of portal hypertension with liver sarcoidosis. Dig Endosc 2014; 26 (06) 745-748
  • 19 Sedki M, Fonseca N, Santiago P. , et al. Hepatic sarcoidosis: natural history and management implications. Front Med (Lausanne) 2019; 6: 232
  • 20 Valla D, Pessegueiro-Miranda H, Degott C, Lebrec D, Rueff B, Benhamou JP. Hepatic sarcoidosis with portal hypertension. A report of seven cases with a review of the literature. Q J Med 1987; 63 (242) 531-544
  • 21 Tan CB, Rashid S, Rajan D, Gebre W, Mustacchia P. Hepatic sarcoidosis presenting as portal hypertension and liver cirrhosis: case report and review of the literature. Case Rep Gastroenterol 2012; 6 (01) 183-189
  • 22 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; 26 (03) 554-560
  • 23 Deniz K, Ward SC, Rosen A, Grewal P, Xu R. Budd-Chiari syndrome in sarcoidosis involving liver. Liver Int 2008; 28 (04) 580-581
  • 24 Murphy JR, Sjogren MH, Kikendall JW, Peura DA, Goodman Z. Small bile duct abnormalities in sarcoidosis. J Clin Gastroenterol 1990; 12 (05) 555-561
  • 25 Alam I, Levenson SD, Ferrell LD, Bass NM. Diffuse intrahepatic biliary strictures in sarcoidosis resembling sclerosing cholangitis. Case report and review of the literature. Dig Dis Sci 1997; 42 (06) 1295-1301
  • 26 Momah N, Otesile A, Pawa R, Shedlofsky S. Sarcoidosis presenting as necrotizing sarcoid granulomatosis of the liver, sclerosing cholangitis, and gastric ulcer. ACG Case Rep J 2014; 1 (03) 164-166
  • 27 Judson MA. Hepatic, splenic, and gastrointestinal involvement with sarcoidosis. Semin Respir Crit Care Med 2002; 23 (06) 529-541
  • 28 Cremers J, Drent M, Driessen A. , et al. Liver-test abnormalities in sarcoidosis. Eur J Gastroenterol Hepatol 2012; 24 (01) 17-24
  • 29 Modaresi Esfeh J, Culver D, Plesec T, John B. Clinical presentation and protocol for management of hepatic sarcoidosis. Expert Rev Gastroenterol Hepatol 2015; 9 (03) 349-358
  • 30 Hercules HD, Bethlem NM. Value of liver biopsy in sarcoidosis. Arch Pathol Lab Med 1984; 108 (10) 831-834
  • 31 Devaney K, Goodman ZD, Epstein MS, Zimmerman HJ, Ishak KG. Hepatic sarcoidosis. Clinicopathologic features in 100 patients. Am J Surg Pathol 1993; 17 (12) 1272-1280
  • 32 Britt AR, Francis IR, Glazer GM, Ellis JH. Sarcoidosis: abdominal manifestations at CT. Radiology 1991; 178 (01) 91-94
  • 33 Warshauer DM, Dumbleton SA, Molina PL, Yankaskas BC, Parker LA, Woosley JT. Abdominal CT findings in sarcoidosis: radiologic and clinical correlation. Radiology 1994; 192 (01) 93-98
  • 34 Hoeffel C, Bokemeyer C, Hoeffel JC, Gaucher H, Galanski M, Fornes P. CT hepatic and splenic appearances with sarcoidosis. Eur J Radiol 1996; 23 (02) 94-96
  • 35 Tana C, Schiavone C, Ticinesi A. , et al. Ultrasound imaging of abdominal sarcoidosis: state of the art. World J Clin Cases 2019; 7 (07) 809-818
  • 36 Ferreira A, Ramalho M, de Campos ROP. , et al. Hepatic sarcoidosis: MR appearances in patients with chronic liver disease. Magn Reson Imaging 2013; 31 (03) 432-438
  • 37 Fetzer DT, Rees MA, Dasyam AK, Tublin ME. Hepatic sarcoidosis in patients presenting with liver dysfunction: imaging appearance, pathological correlation and disease evolution. Eur Radiol 2016; 26 (09) 3129-3137
  • 38 Folz SJ, Johnson CD, Swensen SJ. Abdominal manifestations of sarcoidosis in CT studies. J Comput Assist Tomogr 1995; 19 (04) 573-579
  • 39 Kessler A, Mitchell DG, Israel HL, Goldberg BB. Hepatic and splenic sarcoidosis: ultrasound and MR imaging. Abdom Imaging 1993; 18 (02) 159-163
  • 40 Soussan M, Augier A, Brillet P-Y, Weinmann P, Valeyre D. Functional imaging in extrapulmonary sarcoidosis: FDG-PET/CT and MR features. Clin Nucl Med 2014; 39 (02) e146-e159
  • 41 Judson MA, Costabel U, Drent M. , et al. The WASOG Sarcoidosis Organ Assessment Instrument: an update of a previous clinical tool. Sarcoidosis Vasc Diffuse Lung Dis 2014; 31 (01) 19-27
  • 42 Kusielewicz D, Duchatelle V, Valeyre D. , et al. Obstructive jaundice caused by granulomatous stenosis of the extrahepatic bile ducts in sarcoidosis [in French]. Gastroenterol Clin Biol 1988; 12 (8-9): 664-667
  • 43 Martin-Blondel G, Camara B, Selves J. , et al. Etiology and outcome of liver granulomatosis: a retrospective study of 21 cases [in French]. Rev Med Interne 2010; 31 (02) 97-106
  • 44 Gaya DR, Thorburn D, Oien KA, Morris AJ, Stanley AJ. Hepatic granulomas: a 10 year single centre experience. J Clin Pathol 2003; 56 (11) 850-853
  • 45 Drebber U, Kasper H-U, Ratering J. , et al. Hepatic granulomas: histological and molecular pathological approach to differential diagnosis--a study of 442 cases. Liver Int 2008; 28 (06) 828-834
  • 46 Valla DC, Benhamou JP. Hepatic granulomas and hepatic sarcoidosis. Clin Liver Dis 2000; 4 (01) 269-285 , ix–x
  • 47 Lagana SM, Moreira RK, Lefkowitch JH. Hepatic granulomas: pathogenesis and differential diagnosis. Clin Liver Dis 2010; 14 (04) 605-617
  • 48 Stanley NN, Fox RA, Whimster WF, Sherlock S, James DG. Primary biliary cirrhosis or sarcoidosis--or both. N Engl J Med 1972; 287 (25) 1282-1284
  • 49 Aravinthan A, Gelson W, Limbu A, Brais R, Richardson P. Hepatic sarcoidosis complicating treatment-naive viral hepatitis. World J Hepatol 2012; 4 (12) 402-405
  • 50 Peixoto A, Martins Rocha T, Santos-Antunes J. , et al. Etanercept-induced granulomatous hepatitis as a rare cause of abnormal liver tests. Acta Gastroenterol Belg 2019; 82 (01) 93-95
  • 51 Zen Y, Chen YY, Jeng YM, Tsai HW, Yeh MM. Immune-related adverse reactions in the hepatobiliary system: second-generation check-point inhibitors highlight diverse histological changes. Histopathology 2020; 76 (03) 470-480
  • 52 Aggarwal A, Jaswal N, Jain R, Elsiesy H. Amoxicillin-clavulanate-induced granulomatous hepatitis: case report and review of the literature. J Clin Transl Hepatol 2019; 7 (03) 280-283
  • 53 Lower EE, Baughman RP. The use of low dose methotrexate in refractory sarcoidosis. Am J Med Sci 1990; 299 (03) 153-157
  • 54 Alenezi B, Lamoureux E, Alpert L, Szilagyi A. Effect of ursodeoxycholic acid on granulomatous liver disease due to sarcoidosis. Dig Dis Sci 2005; 50 (01) 196-200
  • 55 Bécheur H, Dall'osto H, Chatellier G. , et al. Effect of ursodeoxycholic acid on chronic intrahepatic cholestasis due to sarcoidosis. Dig Dis Sci 1997; 42 (04) 789-791
  • 56 Baratta L, Cascino A, Delfino M. , et al. Ursodeoxycholic acid treatment in abdominal sarcoidosis. Dig Dis Sci 2000; 45 (08) 1559-1562
  • 57 Bakker GJ, Haan YCL, Maillette de Buy Wenniger LJ, Beuers U. Sarcoidosis of the liver: to treat or not to treat?. Neth J Med 2012; 70 (08) 349-356
  • 58 Lipson EJ, Fiel MI, Florman SS, Korenblat KM. Patient and graft outcomes following liver transplantation for sarcoidosis. Clin Transplant 2005; 19 (04) 487-491
  • 59 Cengiz C, Rodriguez-Davalos M, deBoccardo G. , et al. Recurrent hepatic sarcoidosis post-liver transplantation manifesting with severe hypercalcemia: a case report and review of the literature. Liver Transpl 2005; 11 (12) 1611-1614
  • 60 Bilal M, Satapathy SK, Ismail MK, Vanatta JM. Long-term outcomes of liver transplantation for hepatic sarcoidosis: a single center experience. J Clin Exp Hepatol 2016; 6 (02) 94-99