Virchows Archiv

, Volume 473, Issue 1, pp 23–31 | Cite as

Pathology of idiopathic non-cirrhotic portal hypertension

  • Maria Guido
  • Samantha Sarcognato
  • Diana Sacchi
  • Guido Colloredo
Review and Perspectives
Part of the following topical collections:
  1. Vascular liver lesions: contemporary views on long-recognized entities


Idiopathic non-cirrhotic portal hypertension is an under-recognized vascular liver disease of unknown etiology, characterized by clinical signs of portal hypertension in the absence of cirrhosis. By definition, any disorder known to cause portal hypertension in the absence of cirrhosis and any cause of chronic liver disease must be excluded to make a diagnosis of idiopathic non-cirrhotic portal hypertension. However, the diagnosis is often difficult because the disease resembles cirrhosis and there is no gold standard test. Liver biopsy is an essential tool: it is able to exclude cirrhosis and other causes of portal hypertension and it allows the identification of the characteristic lesions. Nonetheless, the histological diagnosis of idiopathic non-cirrhotic portal hypertension is not always straightforward, in particular by needle biopsy samples, because there is no pathognomonic lesion, but rather a variety of vascular changes which are unevenly distributed, very subtle, and not all necessarily identified in a single specimen. Pathologists should be able to recognize several patterns of injury, involving portal/periportal areas as well as parenchymal structures.The histological features of idiopathic non-cirrhotic portal hypertension are described in this review, focusing on their interpretation in needle biopsy specimens.


Idiopathic non-cirrhotic portal hypertension Vascular lesions Obliterative portal venopathy Incomplete septal cirrhosis Nodular regenerative hyperplasia 


Compliance with ethical standards

This review complies with ethical standards and does not involve human participants or animals.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    European Association for the Study of the Liver (2016) EASL clinical practice guidelines: vascular diseases of the liver. J Hepatol 64:179–202CrossRefGoogle Scholar
  2. 2.
    Mukta V, Panicker LC, Sivamani K, Goel A, Basu D, Dhanapathi H (2017) Non-cirrhotic portal fibrosis at a tertiary care centre in South India. Trop Dr 47:26–30Google Scholar
  3. 3.
    Sawada S, Sato Y, Aoyama H, Harada K, Nakanuma Y (2007) Pathological study of idiopathic portal hypertension with an emphasis on cause of death based on records of Annuals of Pathological Autopsy Cases in Japan. J Gastroenterol Hepatol 22:204–209CrossRefPubMedGoogle Scholar
  4. 4.
    Nayak NC, Ramalingaswami V (1969) Obliterative portal venopathy of the liver. Associated with so-called idiopathic portal hypertension or tropical splenomegaly. Arch Pathol 87:359–369PubMedGoogle Scholar
  5. 5.
    Mikkelsen WP, Edmondson HA, Peters RL, Redeker AG, Reynolds TB (1965) Extra- and intrahepatic portal hypertension without cirrhosis (hepatoportal sclerosis). Ann Surg 162:602–620CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Nayak NC, Jain D, Saigal S, Soin AS (2011) Non-cirrhotic portal fibrosis: one disease with many names? An analysis from morphological study of native explant livers with end stage chronic liver disease. J Clin Pathol 64:592–598CrossRefPubMedGoogle Scholar
  7. 7.
    Schouten JN, Garcia-Pagan JC, Valla DC, Janssen HL (2011) Idiopathic noncirrhotic portal hypertension. Hepatology 54:1071–1081CrossRefPubMedGoogle Scholar
  8. 8.
    Vakili C, Farahvash MJ, Bynum TE (1992) ‘Endemic’ idiopathic portal hypertension: report on 32 patients with non-cirrhotic portal fibrosis. World J Surg 16:118–125CrossRefPubMedGoogle Scholar
  9. 9.
    Sarin SK, Agarwal SR (1998) Idiopathic portal hypertension. Digestion 59:420–423CrossRefPubMedGoogle Scholar
  10. 10.
    Lee H, Rehman AU, Fiel MI (2016) Idiopathic noncirrhotic portal hypertension: an appraisal. J Pathol Transl Med 50:17–25CrossRefPubMedGoogle Scholar
  11. 11.
    Riggio O, Gioia S, Pentassuglio I, Nicoletti V, Valente M, d’Amati G (2016) Idiopathic noncirrhotic portal hypertension: current perspectives. Hepat Med 8:81–88CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Cazals-Hatem D, Hillaire S, Rudler M, Plessier A, Paradis V, Valla DC et al (2011) Obliterative portal venopathy: portal hypertension is not always present at diagnosis. J Hepatol 54:455–461CrossRefPubMedGoogle Scholar
  13. 13.
    Guido M, Sarcognato S, Sonzogni A, Lucà MG, Senzolo M, Colloredo G et al (2016) Obliterative portal venopathy without portal hypertension: an underestimated condition. Liver Int 36:454–460CrossRefPubMedGoogle Scholar
  14. 14.
    Okuda K, Nakashima T, Okudaira M, Kage M, Aida Y, Aikat BA et al (1982) Liver pathology of idiopathic portal hypertension. Comparison with non-cirrhotic portal fibrosis of India. The Japan idiopathic portal hypertension study. Liver 2:176–192CrossRefPubMedGoogle Scholar
  15. 15.
    Sarin SK, Kapoor D (2002) Non-cirrhotic portal fibrosis: current concepts and management. J Gastroenterol Hepatol 17:526–534CrossRefPubMedGoogle Scholar
  16. 16.
    Yilmaz G, Sari S, Egritas O, Dalgic B, Akyol G (2012) Hepatoportal sclerosis in childhood: some presenting with cholestatic features (a re-evaluation of 12 children). Pediatr Dev Pathol 15:107–113CrossRefPubMedGoogle Scholar
  17. 17.
    Franchi-Abella S, Fabre M, Mselati E, De Marsillac ME, Bayari M, Bernard O et al (2014) Obliterative portal venopathy: a study of 48 children. J Pediatr 165:190–193CrossRefPubMedGoogle Scholar
  18. 18.
    Sarin SK, Khanna R (2014) Non-cirrhotic portal hypertension. Clin Liver Dis 18:451–476CrossRefPubMedGoogle Scholar
  19. 19.
    Hillaire S, Bonte E, Denninger MH, Casadevall N, Cadranel JF, Degott C et al (2002) Idiopathic non-cirrhotic intrahepatic portal hypertension in the West: a re-evaluation in 28 patients. Gut 51:275–280CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Aggarwal S, Fiel MI, Schiano TD (2013) Obliterative portal venopathy: a clinical and histopathological review. Dig Dis Sci 58:2767–2776CrossRefPubMedGoogle Scholar
  21. 21.
    Goel A, Elias JE, Eapen CE, Ramakrishna B, Elias E (2014) Idiopathic non-cirrhotic intrahepatic portal hypertension (NCIPH)—newer insights into pathogenesis and emerging newer treatment options. J Clin Exp Hepatol 4:247–256CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Nakanuma Y, Tsuneyama K, Ohbu M, Katayanagi K (2001) Pathology and pathogenesis of idiopathic portal hypertension with an emphasis on the liver. Pathol Res Pract 197:65–76CrossRefPubMedGoogle Scholar
  23. 23.
    Eapen CE, Nightingale P, Hubscher SG, Lane PJ, Plant T, Elias E et al (2011) Non-cirrhotic intrahepatic portal hypertension: associated gut diseases and prognostic factors. Dig Dis Sci 56:227–235CrossRefPubMedGoogle Scholar
  24. 24.
    Saito K, Nakanuma Y, Takegoshi K, Ohta G, Obata Y, Kameda H et al (1993) Non-specific immunological abnormalities and association of autoimmune diseases in idiopathic portal hypertension. A study by questionnaire. Hepato-Gastroenterology 40:163–166PubMedGoogle Scholar
  25. 25.
    Girard M, Amiel J, Fabre M, Pariente D, Lyonnet S, Jacquemin E (2005) Adams-Oliver syndrome and hepatoportal sclerosis: occasional association or common mechanism? Am J Med Genet A 135:186–189CrossRefPubMedGoogle Scholar
  26. 26.
    Roulot D (2013) Liver involvement in Turner syndrome. Liver Int 33:24–30CrossRefPubMedGoogle Scholar
  27. 27.
    Albuquerque A, Cardoso H, Lopes J, Cipriano A, Carneiro F, Macedo G (2013) Familial occurrence of nodular regenerative hyperplasia of the liver. Am J Gastroenterol 108:150–151CrossRefPubMedGoogle Scholar
  28. 28.
    Wanless IR, Godwin TA, Allen F, Feder A (1980) Nodular regenerative hyperplasia of the liver in hematologic disorders: a possible response to obliterative portal venopathy. A morphometric study of nine cases with an hypothesis on the pathogenesis. Medicine (Baltimore) 59:367–379CrossRefGoogle Scholar
  29. 29.
    Ludwig J, Hashimoto E, Obata H, Baldus WP (1993) Idiopathic portal hypertension; a histopathological study of 26 Japanese cases. Histopathology 22:227–234CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Nakanuma Y, Hoso M, Sasaki M, Terada T, Katayanagi K, Obata H et al (1996) Histopathology of the liver in non-cirrhotic portal hypertension of unknown aetiology. Histopathology 28:195–204CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Schouten JN, Verheij J, Seijo S (2015) Idiopathic non-cirrhotic portal hypertension: a review. Orphanet J Rare Dis 10:67CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Isabel Fiel M, Thung SN, Hytiroglou P, Emre S, Schiano TD (2007) Liver failure and need for liver transplantation in patients with advanced hepatoportal sclerosis. Am J Surg Pathol 31:607–614CrossRefPubMedGoogle Scholar
  33. 33.
    Krasinskas AM, Eghtesad B, Kamath PS, Demetris AJ, Abraham SC (2005) Liver transplantation for severe intrahepatic noncirrhotic portal hypertension. Liver Transpl 11:627–634CrossRefPubMedGoogle Scholar
  34. 34.
    Iber FL (1969) Obliterative portal venopathy of the liver and “idiopathic portal hypertension”. Ann Intern Med 71:660–661CrossRefPubMedGoogle Scholar
  35. 35.
    Elkrief L, Rautou PE (2016) Idiopathic non-cirrhotic portal hypertension: the tip of the obliterative portal venopathies iceberg? Liver Int 36:325–327CrossRefPubMedGoogle Scholar
  36. 36.
    Sarin SK, Kumar A, Chawla YK, Baijal SS, Dhiman RK, Jafri W, Lesmana LA, Guha Mazumder D, Omata M, Qureshi H, Raza RM, Sahni P, Sakhuja P, Salih M, Santra A, Sharma BC, Sharma P, Shiha G, Sollano J, Members of the APASL Working Party on Portal Hypertension (2007) Noncirrhotic portal fibrosis/idiopathic portal hypertension: APASL recommendations for diagnosis and treatment. Hepatol Int 1:398–413CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Sharma P, Agarwal R, Dhawan S, Bansal N, Singla V, Arora A et al (2017) Transient elastography (Fibroscan) in patients with non-cirrhotic portal fibrosis. J Clin Exp Hepatol 7:230–234CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Verheij J, Schouten JN, Komuta M, Nevens F, Hansen BE, Roskams T et al (2013) Histological features in western patients with idiopathic non-cirrhotic portal hypertension. Histopathology 62:1083–1091CrossRefPubMedGoogle Scholar
  39. 39.
    Krasinskas AM, Goldsmith JD, Burke A, Furth EE (2005) Abnormal intrahepatic portal vasculature in native and allograft liver biopsies: a comparative analysis. Am J Surg Pathol 29:1382–1388CrossRefPubMedGoogle Scholar
  40. 40.
    Zuo C, Chumbalkar V, Ells PF, Bonville DJ, Lee H (2017) Prevalence of histological features of idiopathic noncirrhotic portal hypertension in general population: a retrospective study of incidental liver biopsies. Hepatol Int 11:452–460CrossRefPubMedGoogle Scholar
  41. 41.
    Nakanuma Y, Kouda W, Nakano T, Uneno K, Tachibana S, Araki I (2001) A case report of early idiopathic portal hypertension. Pathol Res Pract 197:759–763CrossRefPubMedGoogle Scholar
  42. 42.
    Crawford AR, Lin XZ, Crawford JM (1998) The normal adult human liver biopsy: a quantitative reference standard. Hepatology 28:323–331CrossRefPubMedGoogle Scholar
  43. 43.
    Dhiman RK, Chawla Y, Vasishta RK, Kakkar N, Dilawari JB, Suri S et al (2002) Non-cirrhotic portal fibrosis (idiopathic portal hypertension): experience with 151 patients and a review of the literature. J Gastroenterol Hepatol 17:6–16CrossRefPubMedGoogle Scholar
  44. 44.
    Chawla Y, Dhiman RK (2008) Intrahepatic portal venopathy and related disorders of the liver. Semin Liver Dis 28:270–281CrossRefPubMedGoogle Scholar
  45. 45.
    Bioulac-Sage P, Le Bail B, Bernard PH, Balabaud C (1995) Hepatoportal sclerosis. Semin Liver Dis 15:329–339CrossRefPubMedGoogle Scholar
  46. 46.
    Fukuda K, Kage M, Arakawa M, Nakashima T (1985) Portal vein or hepatic vein? A curious aberrant vasculature in the liver with idiopathic portal hypertension. Acta Pathol Jpn 35:885–897PubMedGoogle Scholar
  47. 47.
    Ohbu M, Okudaira M, Watanabe K, Kaneko S, Takai T (1994) Histopathological study of intrahepatic aberrant vessels in cases of noncirrhotic portal hypertension. Hepatology 20:302–308CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Okudaira M, Ohbu M, Okuda K (2002) Idiopathic portal hypertension and its pathology. Semin Liver Dis 22:59–72CrossRefPubMedGoogle Scholar
  49. 49.
    Brunt EM, Gouw AS, Hubscher SG, Tiniakos DG, Bedossa P, Wanless IR et al (2014) Pathology of the liver sinusoids. Histopathology 64:907–920CrossRefPubMedGoogle Scholar
  50. 50.
    Kakar S, Kamath PS, Burgart LJ (2004) Sinusoidal dilatation and congestion in liver biopsy: is it always due to venous outflow impairment? Arch Pathol Lab Med 128:901–904PubMedGoogle Scholar
  51. 51.
    Marzano C, Cazals-Hatem D, Rautou PE, Valla DC (2015) The significance of nonobstructive sinusoidal dilatation of the liver: impaired portal perfusion or inflammatory reaction syndrome. Hepatology 62:956–963CrossRefPubMedGoogle Scholar
  52. 52.
    Berzigotti A, Magalotti D, Zappoli P, Rossi C, Callea F, Zoli M (2006) Peliosis hepatis as an early histological finding in idiopathic portal hypertension: a case report. World J Gastroenterol 12:3612–3615CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Terada T, Hoso M, Nakanuma Y (1989) Microvasculature in the small portal tracts in idiopathic portal hypertension. A morphological comparison with other hepatic diseases. Virchows Archiv A Pathol Anat Histopathol 415:61–67CrossRefGoogle Scholar
  54. 54.
    Popper H (1966) What are the major types of hepatic cirrhosis? In: Ingelfinger F, Relman A, Finland M (eds) Controversy in internal medicine. WB Saunders, Philadelphia, pp 233–243Google Scholar
  55. 55.
    Millward-Sadler GH (1994) Liver cirrhosis. In: McSween RNM, Anthony PP, Scheuer PJ, Burt AD, Portmann BC (eds) Pathology of the liver. Churchill Livingstone, New York, pp 397–424Google Scholar
  56. 56.
    Wanless IR, Nakashima E, Sherman M (2000) Regression of human cirrhosis. Morphologic features and the genesis of incomplete septal cirrhosis. Arch Pathol Lab Med 124:1599–1607PubMedGoogle Scholar
  57. 57.
    Schinoni MI, Andrade Z, de Freitas LA, Oliveira R, Paranà R (2004) Incomplete septal cirrhosis: an enigmatic disease. Liver Int 24:452–456CrossRefPubMedGoogle Scholar
  58. 58.
    Steiner PE (1959) Nodular regenerative hyperplasia of the liver. Am J Pathol 35:943–953PubMedPubMedCentralGoogle Scholar
  59. 59.
    Hartleb M, Gutkowski K, Milkiewicz P (2011) Nodular regenerative hyperplasia: evolving concepts on underdiagnosed cause of portal hypertension. World J Gastroenterol 17:1400–1409CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Barge S, Grando V, Nault JC, Broudin C, Beaugrand M, Ziol M et al (2016) Prevalence and clinical significance of nodular regenerative hyperplasia in liver biopsies. Liver Int 36:1059–1066CrossRefPubMedGoogle Scholar
  61. 61.
    Wanless IR (1990) Micronodular transformation (nodular regenerative hyperplasia) of the liver: a report of 64 cases among 2,500 autopsies and a new classification of benign hepatocellular nodules. Hepatology 11:787–797CrossRefPubMedGoogle Scholar
  62. 62.
    Reshamwala PA, Kleiner DE, Heller T (2006) Nodular regenerative hyperplasia: not all nodules are created equal. Hepatology 44:7–14CrossRefPubMedGoogle Scholar
  63. 63.
    Jharap B, van Asseldonk DP, de Boer NK, Bedossa P, Diebold J, Jonker AM et al (2015) Diagnosing nodular regenerative hyperplasia of the liver is thwarted by low interobserver agreement. PLoS One 10:e0120299CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Delladetsima I, Sakellarriou S, Kokkori A, Tiniakos D (2016) Atrophic hepatocytes express keratin 7 in ischemia-associated liver lesions. Histol Histopathol 31:1089–1094PubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Maria Guido
    • 1
  • Samantha Sarcognato
    • 1
  • Diana Sacchi
    • 1
  • Guido Colloredo
    • 2
  1. 1.Surgical Pathology & Cytopathology Unit, Department of Medicine – DIMEDUniversity of PadovaPaduaItaly
  2. 2.Department of Internal Medicine, San Pietro HospitalPonte San PietroItaly

Personalised recommendations