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Elevated Levels of Circulating Angiotensin Converting Enzyme in Patients with Hepatoportal Sclerosis

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Abstract

Background and Aims

Hepatoportal sclerosis (HPS) is a clinicopathologic condition that is clinically characterized by portal hypertension (varices and portosystemic collateral vessels), splenomegaly and pancytopenia, in the absence of cirrhosis. Although the etiology is obscure, a number of theories such as immunologic and vascular endothelial cellular abnormalities have been put forward to explain the underlying pathophysiology. Angiotensin-converting enzyme (ACE), an important molecule of the renin–angiotensin system (RAS), is also known as a regulatory molecule in systemic and portal circulation in distinct disorders. The aim of the present study was to investigate the possible role of the ACE in the context of RAS in HPS pathogenesis.

Materials and Methods

The study was conducted on 30 HPS patients (16 men, 14 women; median age 36 years, range 18–63) and 20 healthy controls. The clinical features of HPS patients including demographics, laboratory, and ultrasonography findings were summarized. Serum ACE levels were measured by using commercially available kits.

Results

Serum median ACE levels were 36 (8–174) U/l and 16 (8–43) U/l for the HPS patients and controls, respectively. Serum ACE levels were significantly higher in patients with HPS compared to the control group (P < 0.05).

Conclusion

ACE in the context of RAS may be associated with pathological endothelial occlusive events in the microenvironment of the portal circulation in HPS. Revealing the interactions between circulating and local RAS within the hepatic microenvironment would enlighten the biologic basis and clinical management of liver diseases.

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References

  1. Benhamou JP, Valla DC. Intrahepatic portal hypertension. In: Bircher J, Benhamou JP, McIntyre N, et al., eds. Oxford Textbook of Clinical Hepatology. 2nd ed. Oxford: Oxford University Press; 1999:661–670.

    Google Scholar 

  2. Hillaire S, Bonte E, Denninger MH, et al. Idiopathic non-cirrhotic intrahepatic portal hypertension in the West: a re-evaluation in 28 patients. Gut. 2002;51:275–280.

    Article  PubMed  CAS  Google Scholar 

  3. Banti BC. Ueber Morbus Banti. Folia Haematol. 1910;10:33–74.

    Google Scholar 

  4. Nayak NC, Ramalingaswami V. Obliterative portal venopathy of the liver. Associated with so-called idiopathic portal hypertension or tropical splenomegaly. Arch Pathol. 1969;87:359–369.

    PubMed  CAS  Google Scholar 

  5. Villeneuve JP, Huet PM, Joly JG, et al. Idiopathic portal hypertension. Am J Med. 1976;61:459–464.

    Article  PubMed  CAS  Google Scholar 

  6. Sama SK, Bhargava S, Gopi-Nath N, et al. Non-cirrhotic portal fibrosis. Am J Med. 1971;51:160–171.

    Article  PubMed  CAS  Google Scholar 

  7. Levison DA, Kingham JG, Dawson AM, Stansfeld AG. Slow cirrhosis—or no cirrhosis? A lesion causing benign intrahepatic portal hypertension. J Pathol. 1982;137:253–272.

    Article  PubMed  CAS  Google Scholar 

  8. Wanless IE. 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. 1990;11:787–797.

    Article  PubMed  CAS  Google Scholar 

  9. Kameda H, Yamazaki K, Imai F, et al. Obliterative portal venopathy: a comparative study of 184 cases of extrahepatic portal obstruction and 469 cases of idiopathic portal hypertension. J Gastroenterol Hepatol. 1986;1:139–149.

    Article  Google Scholar 

  10. Mikkelsen WP, Edmondson HA, Peters RL, Redeker AG, Reynolds TB. Extra- and intrahepatic portal hypertension without cirrhosis (hepatoportal sclerosis). Ann Surg. 1965;162:602–620.

    Article  PubMed  CAS  Google Scholar 

  11. Bioulac-Sage P, Le Bail B, Bernard PH, et al. Hepatoportal sclerosis. Semin Liver Dis. 1995;15:329–339.

    Article  PubMed  CAS  Google Scholar 

  12. Schiano TD, Kotler DP, Ferran E, et al. Hepatoportal sclerosis as a cause of noncirrhotic portal hypertension in patients with HIV. Am J Gastroenterol. 2007;102:2536–2540.

    Article  PubMed  Google Scholar 

  13. Okudaira M, Ohbu M, Okuda K. Idiopathic portal hypertension and its pathology. Semin Liver Dis. 2002;22:59–72.

    Article  PubMed  Google Scholar 

  14. Isabel Fiel M, Thung SN, Hytiroglou P, et al. Liver failure and need for liver transplantation in patients with advanced hepatoportal sclerosis. Am J Surg Pathol. 2007;31:607–614.

    Article  PubMed  CAS  Google Scholar 

  15. Koksal AS, Koklu S, Ibis M, et al. Clinical features, serum interleukin-6, and interferon-gamma levels of 34 Turkish patients with hepatoportal sclerosis. Dig Dis Sci. 2007;52:3493–3498.

    Article  PubMed  CAS  Google Scholar 

  16. Sozer S, Fiel MI, Schiano T, et al. The presence of JAK2V617F mutation in the liver endothelial cells of patients with Budd-Chiari syndrome. Blood. 2009;113:5246–5249.

    Article  PubMed  CAS  Google Scholar 

  17. Cahill PA, Redmond EM, Sitzmann JV. Endothelial dysfunction in cirrhosis and portal hypertension. Pharmacol Ther. 2001;89:273–293.

    Article  PubMed  CAS  Google Scholar 

  18. Carvalho LT, Nascimento EA, Teixeira FO, et al. Hepatic conversion of angiotensin I and the portal hypertensive response to angiotensin II in normal and regenerating liver. J Gastroenterol Hepatol. 2007;22:1543–1548.

    Article  PubMed  Google Scholar 

  19. La Villa G, Gentilini P. Hemodynamic alterations in liver cirrhosis. Mol Aspects Med. 2008;29:112–118.

    Article  PubMed  CAS  Google Scholar 

  20. Tripodi A, Mannucci PM. Abnormalities of hemostasis in chronic liver disease: reappraisal of their clinical significance and need for clinical and laboratory research. J Hepatol. 2007;46:727–733.

    Article  PubMed  CAS  Google Scholar 

  21. Cobankara V, Ozturk MA, Kiraz S, et al. Renin and angiotensin-converting enzyme (ACE) as active components of the local synovial renin-angiotensin system in rheumatoid arthritis. Rheumatol Int. 2005;25:285–291.

    Article  PubMed  CAS  Google Scholar 

  22. Haznedaroglu IC, Beyazit Y. Pathobiological aspects of the local bone marrow renin-angiotensin system: a review. J Renin Angiotensin Aldosterone Syst. 2010;11:205–213.

    Article  PubMed  CAS  Google Scholar 

  23. Anthuber M, Farkas S, Rihl M, et al. Angiotensin-converting enzyme inhibition by enalapril: a novel approach to reduce ischemia/reperfusion damage after experimental liver transplantation. Hepatology. 1997;25:648–651.

    Article  PubMed  CAS  Google Scholar 

  24. Freise H, Palmes D, Spiegel HU. Inhibition of angiotensin-converting enzyme reduces rat liver reperfusion injury via bradykinin-2-receptor. J Surg Res. 2006;134:231–237.

    Article  PubMed  CAS  Google Scholar 

  25. Padrissa-Altes S, Franco-Gou R, Boillot O, et al. Effect of angiotensin II and bradykinin inhibition in rat reduced-size liver transplantation. Liver Transpl. 2009;15:313–320.

    Article  PubMed  Google Scholar 

  26. Koh SL, Ager EI, Christophi C. Liver regeneration and tumour stimulation: implications of the renin-angiotensin system. Liver Int. 2010;30:1414–1426.

    Article  PubMed  CAS  Google Scholar 

  27. Bataller R, Gines P, Nicolas JM, et al. Angiotensin II induces contraction and proliferation of human hepatic stellate cells. Gastroenterology. 2000;118:1149–1156.

    Article  PubMed  CAS  Google Scholar 

  28. Debernardi-Venon W, Martini S, Biasi F, et al. AT1 receptor antagonist Candesartan in selected cirrhotic patients: effect on portal pressure and liver fibrosis markers. J Hepatol. 2007;46:1026–1033.

    Article  PubMed  CAS  Google Scholar 

  29. Rimola A, Londono MC, Guevara G, et al. Beneficial effect of angiotensin-blocking agents on graft fibrosis in hepatitis C recurrence after liver transplantation. Transplantation. 2004;78:686–691.

    Article  PubMed  CAS  Google Scholar 

  30. Yoshiji H, Noguchi R, Kojima H, et al. Interferon augments the anti-fibrotic activity of an angiotensin-converting enzyme inhibitor in patients with refractory chronic hepatitis C. World J Gastroenterol. 2006;12:6786–6791.

    PubMed  CAS  Google Scholar 

  31. Garcia-Pagan JC, Salmeron JM, Feu F, et al. Effects of low-sodium diet and spironolactone on portal pressure in patients with compensated cirrhosis. Hepatology. 1994;19:1095–1099.

    Article  PubMed  CAS  Google Scholar 

  32. Sowers JR, Whaley-Connell A, Epstein M. Narrative review: the emerging clinical implications of the role of aldosterone in the metabolic syndrome and resistant hypertension. Ann Intern Med. 2009;150:776–783.

    PubMed  Google Scholar 

  33. Bataller R, Gabele E, Parsons CJ, et al. Systemic infusion of angiotensin II exacerbates liver fibrosis in bile duct-ligated rats. Hepatology. 2005;41:1046–1055.

    Article  PubMed  CAS  Google Scholar 

  34. Lisman T, Porte RJ. Rebalanced hemostasis in patients with liver disease: evidence and clinical consequences. Blood. 2010;116:878–885.

    Article  PubMed  CAS  Google Scholar 

  35. Acar K, Beyazit Y, Sucak A, et al. Alterations in the ‘local umbilical cord blood renin-angiotensin system’ during pre-eclampsia. Acta Obstet Gynecol Scand. 2007;86:1193–1199.

    Article  CAS  Google Scholar 

  36. Haznedaroglu IC, Ozturk MA. Towards the understanding of the local hematopoietic bone marrow renin-angiotensin system. Int J Biochem Cell Biol. 2003;35:867–880.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

We would like to thank to Dr. Sureyya Altunay for providing us an excellent illustration of circulating RAS within the hepatic microenvironment.

Conflict of interest

Authors declare no conflict of interest related to this article.

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Authors and Affiliations

  1. Department of Gastroenterology, Turkiye Yuksek İhtisas Education and Research Hospital, Sihhiye, 06100, Ankara, Turkey

    Yavuz Beyazit, Mehmet İbis, Murat Kekilli, Mevlut Kurt, Abdurrahim Sayilir & İbrahim Koral Onal

  2. Department of Gastroenterology, Ankara Numune Education and Research Hospital, Ankara, Turkey

    Tugrul Purnak

  3. Department of Biochemistry, Ankara Numune Education and Research Hospital, Ankara, Turkey

    Turan Turhan

  4. Department of Pathology, Turkiye Yuksek İhtisas Education and Research Hospital, Ankara, Turkey

    Nesrin Turhan

  5. Department of Gastroenterology, Ankara Education and Research Hospital, Ankara, Turkey

    Adnan Tas & Seyfettin Köklü

  6. Department of Hematology, Hacettepe University Faculty of Medicine, Ankara, Turkey

    İbrahim C. Haznedaroglu

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  1. Yavuz Beyazit
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  2. Mehmet İbis
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Correspondence to Yavuz Beyazit.

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Beyazit, Y., İbis, M., Purnak, T. et al. Elevated Levels of Circulating Angiotensin Converting Enzyme in Patients with Hepatoportal Sclerosis. Dig Dis Sci 56, 2160–2165 (2011). https://doi.org/10.1007/s10620-011-1580-7

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  • DOI: https://doi.org/10.1007/s10620-011-1580-7

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