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Management of Hepatic Adenomatosis

  • Liver (B Bacon, Section Editor)
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Abstract

Hepatic adenomatosis (HeAs) is a rare clinical entity defined by the presence of 10 or more hepatic adenomas (HA) within the background of an otherwise normal liver parenchyma, in the absence of glycogen storage disease or anabolic steroid use. HA is a benign tumor associated with oral contraceptive use. Recent advances in pathogenesis and classification of HA have questioned the distinction between these two diseases. HA are currently classified into four different subtypes with genotypic and phenotypic correlation: HNF-1a inactivated HA, B-catenin activated HA, inflammatory HA, and undetermined subtype. The clinical presentation of HA depends on the lesion size and the subtype. MRI using hepatospecific contrast agents is helpful in diagnosing the most common subtypes. When diagnosis is uncertain, biopsy with immunohistochemistry is used to diagnose and classify the lesions. Management is governed by the molecular subtype and tumor size. Pregnancy is not routinely discouraged but management is individualized.

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References

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  1. Flejou JF, Barge J, Menu Y, Degott C, Bismuth H, Potet F, et al. Liver adenomatosis. An entity distinct from liver adenoma? Gastroenterology. 1985;89(5):1132–8.

    CAS  PubMed  Google Scholar 

  2. Zucman-Rossi J, Jeannot E, Nhieu JT, Scoazec JY, Guettier C, Rebouissou S, et al. Genotype-phenotype correlation in hepatocellular adenoma: new classification and relationship with HCC. Hepatology. 2006;43(3):515–24.

    Article  CAS  PubMed  Google Scholar 

  3. Bioulac-Sage P, Rebouissou S, Thomas C, Blanc JF, Saric J, Sa Cunha A, et al. Hepatocellular adenoma subtype classification using molecular markers and immunohistochemistry. Hepatology. 2007;46(3):740–8.

    Article  CAS  PubMed  Google Scholar 

  4. Frulio N, Chiche L, Bioulac-Sage P, Balabaud C. Hepatocellular adenomatosis: what should the term stand for. Clin Res Hepatol Gastroenterol. 2014;38(2).

  5. Rooks JB, Ory HW, Ishak KG, Strauss LT, Greenspan JR, Hill AP, et al. Epidemiology of hepatocellular adenoma: the role of oral contraceptive use. JAMA. 1979;242(7):644–8.

    Article  CAS  PubMed  Google Scholar 

  6. Nault JC, Bioulac-Sage P, Zucman-Rossi J. Hepatocellular benign tumors—from molecular classification to personalized clinical care. Gastroenterology. 2013;144(5):888–902. Review article summarizing current understanding of pathological classification of hepatic adenomas using novel immunohistochemical techniques. It also discusses the molecular pathways in adenoma development.

    Article  CAS  PubMed  Google Scholar 

  7. Agrawal S, Agarwal S, Arnason T, Saini S, Belghiti J. Management of hepatocellular adenoma: recent advances. Clin Gastroenterol Hepatol. 2014. doi:10.1016/j.cgh.2014.05.02.

    PubMed  Google Scholar 

  8. Barthelmes L, Tait IS. Liver cell adenoma and liver cell adenomatosis. HPB (Oxford). 2005;7(3):186–96.

    Article  Google Scholar 

  9. Bioulac-Sage P, Cubel G, Balabaud C, Zucman-Rossi J. Revisiting the pathology of resected benign hepatocellular nodules using new immunohistochemical markers. Semin Liver Dis. 2011;31(1):91–103. Description of immunohistochemistry techniques used to identify different subtypes of hepatocellular adenomas. It also discusses the performance characteristics of these techniques.

    Article  CAS  PubMed  Google Scholar 

  10. Edmondson HA, Reynold TB, Henderson B, Benton B. Regression of liver cell adenomas associated with oral contraceptives. Ann Int Med. 1977;86(2):180–2.

    Article  CAS  PubMed  Google Scholar 

  11. Furlan A, van der Windt DJ, Nalesnik MA, Sholosh B, Ngan KK, Pealer KM, et al. Multiple hepatic adenomas associated with liver steatosis at CT and MRI: a case–control study. AJR Am J Roentgenol. 2008;191(5):1430–5.

    Article  PubMed  Google Scholar 

  12. Srirattanapong S, Angthong W, Kim BS, Hayashi PH, Gerber DA, Woosley JT, et al. Liver adenomatosis: serial investigation on MRI. Abdom Imaging. 2014;39(2):269–82. This is a retrospective series of 18 patients with liver adenomatosis and summarizes MRI findings and clinical course.

    Article  PubMed  Google Scholar 

  13. Bunchorntavakul C, Bahirwani R, Drazek D, Soulen MC, Siegelman ES, Furth EE, et al. Clinical history and natural history of hepatocellular adenomas: the impact of obesity. Aliment Pharmacol Ther. 2011;34(6):664–74. The authors evaluate the role of obesity and metabolic syndrome in the development of hepatic adenomas. These disorders play an important role in the inflammatory subtype of hepatic adenomas.

    Article  CAS  PubMed  Google Scholar 

  14. Bioulac-Sage P, Taouji S, Possenti L, Balabaud C. Hepatocellular adenoma sub-types: the impact of overweight and obesity. Liver Int. 2013;32(8):1217–21. The authors evaluate the role of obesity in hepatic adenoma development.

    Article  Google Scholar 

  15. Parker P, Burr I, Slonim A, Ghishan FK, Greene H. Regression of hepatic adenomas in type 1a glycogen storage disease with dietary therapy. Gastroenterology. 1981;81(3):534–6.

    CAS  PubMed  Google Scholar 

  16. Rebouissou S, Imbeaud S, Balabaud C, Boulanger V, Bertrand-Michel J, Terce F, et al. HNF-1a inactivation promotes lipogenesis in human hepatocellular adenoma independently of SREBP-1 and carbohydrate-response element-binding protein (ChREBP) activation. J Biol Chem. 2007;282(19):14437–46.

    Article  CAS  PubMed  Google Scholar 

  17. Bacq Y, Jacquemin E, Balabaud C, Jeannot E, Scotto B, Branchereau S, et al. Familial liver adenomatosis associated with hepatocyte nuclear factor 1alpha inactivation. Gastroenterology. 2003;125(5):1470–5.

    Article  PubMed  Google Scholar 

  18. Rebouissou S, Amessou M, Couchy G, Poussin K, Imbeaud S, Pilati C, et al. Frequent in-frame somatic deletions activate gp130 in inflammatory hepatocellular tumours. Nature. 2009;457:200–4.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Paradis V, Benzerkri A, Dargere D, Bieche I, Laurendeau I, Vilgrain V, et al. Telengiectatic focal nodular hyperplasia: a variant of hepatocellular adenoma. Gastroenterology. 2004;126(5):1323–9.

    Article  PubMed  Google Scholar 

  20. Sa Cunha A, Blanc JF, Lazaro E, Mellottee L, Le Bail B, Zucman-Rossi J, et al. Inflammatory syndrome with liver adenomatosis: the beneficial effects of surgical management. Gut. 2007;56(2):307–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Cho SW, Marsh J, Steel J. Surgical management of hepatocellular adenoma: take it or leave it? Ann Surg Oncol. 2008;15:2795–803.

    Article  PubMed  Google Scholar 

  22. Dokmak S, Paradis V, Vilgrain V, Sauvanet A, Farges O, Valla D, et al. A single-center surgical experience of 122 patients with single and multiple hepatocellular adenomas. Gastroenterology. 2009;137(5):1698–705.

    Article  PubMed  Google Scholar 

  23. Deneve JL, Pawlik TM, Cunningham S, Clary B, Reddy S, Scoggins CR, et al. Liver cell adenoma: a multicenter analysis of risk factors for rupture and malignancy. Ann Surg Oncol. 2009;16:640–8.

    Article  PubMed  Google Scholar 

  24. Bioulac-Sage P, Laumonier H, Couchy G, Le Bail B, Sa Cunha A, Rullier A, et al. Hepatocellular adenoma management and phenotypic classification: the Bordeaux experience. Hepatology. 2009;50(2):481–9.

    Article  PubMed  Google Scholar 

  25. Foster JH, Berman MM. The malignant transformation of liver cell adenomas. Arch Surg. 1994;129(7):712–7.

    Article  CAS  PubMed  Google Scholar 

  26. Farges O, Ferreira N, Dokmak S, Belghiti J, Bedossa P, Paradis V. Changing trends in malignant transformation of hepatocellular adenoma. Gut. 2010;60(1):85–9.

    Article  Google Scholar 

  27. Gordon SC, Reddy KR, Livingstone AS, Jeffers LJ, Schiff ER. Resolution of a contraceptive-steroid-induced hepatic adenoma with subsequent evolution into hepatocellular carcinoma. Ann Int Med. 1986;105(4):547–9.

    Article  CAS  PubMed  Google Scholar 

  28. Tesluk H, Lawrie J. Hepatocellular adenoma: its transformation to carcinoma in a user of oral contraceptives. Arch Pathol Lab Med. 1981;105(6):296–9.

    CAS  PubMed  Google Scholar 

  29. Hussain SM, Semelka RC. Hepatic imaging: comparison of modalities. Radiol Clin N Am. 2005;43(5):929–47. doi:10.1016/j.rcl.2005.05.006. ix.

    Article  PubMed  Google Scholar 

  30. Hussain SM, Semelka RC. Liver masses. Magn Reson Imaging Clin N Am. 2005;13(2):255–75. doi:10.1016/j.mric.2005.03.007.

    Article  PubMed  Google Scholar 

  31. Terkivatan T, de Wilt JH, de Man RA, van Rijn RR, Zondervan PE, Tilanus HW, et al. Indications and long-term outcome of treatment for benign hepatic tumors: a critical appraisal. Arch Surg. 2001;136(9):1033–8.

    Article  CAS  PubMed  Google Scholar 

  32. Ichikawa T, Federle MP, Grazioli L, Nalesnik M. Hepatocellular adenoma: multiphasic CT and histopathologic findings in 25 patients. Radiology. 2000;214(3):861–8. doi:10.1148/radiology.214.3.r00mr28861.

    Article  CAS  PubMed  Google Scholar 

  33. Raman SP, Hruban RH, Fishman EK. Hepatic adenomatosis: spectrum of imaging findings. Abdom Imaging. 2013;38(3):474–81. The authors discuss the imaging characteristics and differential diagnosis of hepatic adenomas.

    Article  PubMed  Google Scholar 

  34. Grazioli L, Federle MP, Brancatelli G, Ichikawa T, Olivetti L, Blachar A. Hepatic adenomas: imaging and pathologic findings. Radiographics. 2001;21(4):877–92.

    Article  CAS  PubMed  Google Scholar 

  35. Giovanoli O, Heim M, Terracciano L, Bongartz G, Ledermann HP. MRI of hepatic adenomatosis: initial observations with gadoxetic acid contrast agent in three patients. AJR Am J Roentgenol. 2008;190(5):W290–3.

    Article  PubMed  Google Scholar 

  36. Shanbhogue A, Shan SN, Zaheer A, Prasad SR, Takahashi N, Vikram R. Hepatocellular adenomas: current update on genetics, taxonomy, and management. J Comput Assist Tomogr. 2011;35(2):159–66.

    Article  PubMed  Google Scholar 

  37. Laumonier H, Bioulac-Sage P, Laurent C, Zucman-Rossi J, Balabaud C, Trillaud H. Hepatocellular adenomas: magnetic resonance imaging features as a function of molecular pathological classification. Hepatology. 2008;48(3):808–18.

    Article  PubMed  Google Scholar 

  38. Vetelainen R, Erdogan D, de Graaf W, ten Kate F, Jansen PL, Gouma DJ, et al. Liver adenomatosis: re-evaluation of aetiology and management. Liver Int. 2008;28(4):499–508.

    Article  PubMed  Google Scholar 

  39. Greaves WO, Bhattacharya B. Hepatic adenomatosis. Arch Pathol Lab Med. 2008;132(12):1951–5.

    PubMed  Google Scholar 

  40. Dhingra S, Fiel MI. Update on the new classification of hepatic adenomas: clinical, molecular, and pathologic characteristics. 2014. The authors review the molecular and genetic biology of hepatic adenomas along with immunohistochemical and histopathological charaterstics.

  41. Van Aalten SM WC, de Man RA, Ijzermans JN, Terkivatan T. Can a decision-making model be justified in the management of hepatocellular adenoma? Liver Int. 2012;32(31):28–37. Summarized current diagnostic and current treatment options for hepatic adenomas. The authors propose a decision model for adenoma management.

    Article  PubMed  Google Scholar 

  42. Wilson CH, Manas DM, French JJ. Laparoscopic liver resection for hepatic adenoma in pregnancy. J Clin Gastroenterol. 2011;45:828–33.

    Article  PubMed  Google Scholar 

  43. Yoshidome H, Morita K, Edwards M. Management issues regarding hepatic adenomatosis. Am Surg. 1999;65:1070–6.

    CAS  PubMed  Google Scholar 

  44. Ribeiro A, Burgart LJ, Nagorney DM, Gores GJ. Management of liver adenomatosis: results with a conservative surgical approach. Liver Transplant Surg. 1998;4(5):388–98.

    Article  CAS  Google Scholar 

  45. Jenkins RL, Johnson L, Lewis D. Surgical approach to benign liver tumors. Semin Liver Dis. 1994;14:178–89.

    Article  CAS  PubMed  Google Scholar 

  46. Marrero JA, Ahn J, Reddy R. ACG clinical guideline: the diagnosis and management of focal liver lesions. Am J Gastroenterol. 2014;109(9):1328–47.

    Article  PubMed  Google Scholar 

  47. Venkatesh SK, Vishal C, Lewis RR. Liver masses: a clinical, radiological, and pathologic perspective. Clin Gastroenterol Hepatol. 2014;12(9):1414–29.

    Article  PubMed  Google Scholar 

  48. Huurman VA, Schaapherder AF. Management of ruptured hepatocellular adenoma. Dig Surg. 2010;27:56–60.

    Article  PubMed  Google Scholar 

  49. Kobayashi S, Sakaguchi H, Takatsuka M, Suekane M, Iwai S, Morikawa H, et al. Two cases of hepatocellular adenomatosis treated with transcatheter arterial embolization. Hepatol Int. 2009;3:416–20.

    Article  PubMed Central  PubMed  Google Scholar 

  50. Rhim H, Lim HK, Kim YS, Choi D. Percutaneous radiofrequency ablation of hepatocellular adenoma: initial experience in 10 patients. J Gastroenterol Hepatol. 2008;23(8 Pt 2):e422–7.

    Article  PubMed  Google Scholar 

  51. Fujita S, Kushihata F, Herrmann GE, Mergo PJ, Liu C, Nelson D, et al. Combined hepatic resection and radiofrequency ablation for multiple hepatic adenomas. J Gastroenterol Hepatol. 2006;21(8):1351–4.

    Article  PubMed  Google Scholar 

  52. Van Aalten SM, Terkivatan T, van der Linden E, Verheij J, de Man RA, Ijzermans JN. Management of liver adenomatosis by radiofrequency ablation. Dig Surg. 2011;28(3):173–7.

    Article  PubMed  Google Scholar 

  53. Marino IR, Scantlebury VP, Bronsther O, Iwatsuki S, Starzl TE. Total hepatectomy and liver transplant for hepatocellular adenomatosis and focal nodular hyperplasia. Transpl Int. 1992;5 Suppl 1:S201–5.

    PubMed Central  PubMed  Google Scholar 

  54. Yunta PJ, Moya A, San-Juan F, Lopez-Andujar R, De Juan M, Orbis F, et al. A new case of hepatic adenomatosis treated with orthotopic liver transplantation. Ann Chir. 2001;126(7):672–4.

    Article  CAS  PubMed  Google Scholar 

  55. Wellen JR, Anderson CD, Doyle M, Shenoy S, Nadler M, Turmelle Y, et al. The role of liver transplantation for hepatic adenomatosis in the pediatric population: case report and review of the literature. Pediatr Transplant. 2010;14(3):E16–9.

    Article  CAS  PubMed  Google Scholar 

  56. Lerut JP, Ciccarelli O, Sempoux C, Danse E, DeFlandre J, Horsmans Y, et al. Glycogenosis storage type I diseases and evolution adenomatosis: an indication for liver transplantation. Transpl Int. 2003;16(12):879–84.

    Article  PubMed  Google Scholar 

  57. Van Aalten SM, Verheij J, Terkivatan T, Dwarkasing RS, De Man RA, Ijzermans JN. J Hepatol. 2011;55(1):120–5.

    Article  PubMed  Google Scholar 

  58. Kent DR, Nissen ED, Nissen SE, Ziehm DJ. Effect of pregnancy on liver tumor associated with oral contraceptives. Obstet Gynecol. 1978;51(2):148–51.

    CAS  PubMed  Google Scholar 

  59. Shaked O, Siegelman ES, Olthoff K, Reddy KR. Biologic and clinical features of benign solid and cystic lesions of the liver. Clin Gastroenterol Hepatol. 2011;9(7):547–62.

    Article  PubMed  Google Scholar 

  60. Broker ME, Ijzermans JN, Van Aalten SM, De Man RA, Terkivatan T. The management of pregnancy in women with hepatocellular adenoma: a plea for an individualized approach. Int J Hepatol. 2012:1–3. The article summarizes the management of hepatic adenomas in pregnant patients and proposes an algorithm for management.

  61. Noels JE, Van Aalten SM, Van der Windt DJ, Kok NF, De Man RA, Terkivatan T, et al. Management of hepatocellular adenoma during pregnancy. J Hepatol. 2011;54(3):553–8. This article describes the outcomes of 17 pregnancies in 12 patients previously diagnosed with hepatic adenomas. The authors make suggestions for management based on their experience.

    Article  PubMed  Google Scholar 

  62. Cristiano A, Dietrich A, Spina JC, Ariles V, De Santibanes E. Focal nodular hyperplasia and hepatic adenoma: current diagnosis and management. Updat Surg. 2013;66(1):9–21.

    Article  Google Scholar 

  63. Poussin K, Pilati C, Couchy G, Calderado J, Bioulac-Sage P, Bacq Y, et al. Biochemical and functional analyses of gp130 mutants unveil JAK1 as a novel therapeutic target in human inflammatory hepatocellular adenoma. Oncoimmunology. 2013;2(12):e27090.

    Article  PubMed Central  PubMed  Google Scholar 

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Acknowledgments

The authors would like to acknowledge the help of Dr. David Reich, Dr. Santiago Munoz, and Dr. Nancy Moshen for their guidance and edits

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All authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Medicine, Drexel University College of Medicine, Philadelphia, PA, 19142, USA

    Manish Thapar, Oleg Grapp & Constantine Fisher

  2. Division of Gastroenterology & Hepatology, Drexel University College of Medicine, 216 N Broad Street, 5 Feinstein, MS 1001, Philadelphia, PA, 19102, USA

    Manish Thapar

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Correspondence to Manish Thapar.

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This article is part of the Topical Collection on Liver

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Thapar, M., Grapp, O. & Fisher, C. Management of Hepatic Adenomatosis. Curr Gastroenterol Rep 17, 12 (2015). https://doi.org/10.1007/s11894-015-0434-4

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