Study of thrombopoietin levels in some Egyptian patients with chronic liver diseases secondary to the hepatitis C virus
The Egyptian Journal of Internal Medicine volume 24, pages 5–11 (2012)
The hepatitis C virus (HCV) is a leading cause of chronic liver disease (CLD), cirrhosis, and hepatocellular carcinoma, as well as the most common indication for liver transplantation in many countries.
This work was carried out to study of thrombopoietin (TPO) level in Egyptian patients with chronic hepatitis C and liver cirrhosis with HCV.
Patients and methods
This work was conducted on 40 patients proved to have chronic liver disease due to chronic HCV infection by positive HCV antibody by enzyme-linked immunosorbent assay, PCR for HCV RNA, abdominal ultrasonography, and histopathological examination. Twenty of these patients had chronic active hepatitis C (CAH) and the other 20 patietns had liver cirrhosis. Fifteen apparently healthy individuals (negative for HCV antibody) were included in a control group. None of the patients had received interferon therapy. Patients with other causes of CLD, chronic renal disease, diabetes, endocrinal hematological, and other debilitating diseases were excluded. All the patients studied were subjected to the following: complete medical history, full clinical examination, laboratory investigations including complete blood picture, liver function tests, fasting blood sugar, 2 h postprandial, HCV antibody and PCR for RNA of HCV; serum TPO level, abdominal ultrasonography, and liver biopsy for histopathological examination.
Our results showed a highly significant reduction in the platelet count in patients with CAH (192.55 ± 41.02) and cirrhotic patients (159.800 ± 86.189) in comparison with (322.67 ± 38.12) the control group (P < 0.01). There was nonsignificant increase in TPO in patients with CAH (115.93 ± 71.66) and a significant decrease in TPO in cirrhotic patients (77.504 ± 64.576) in comparison with (107.98 ± 52.53) the control group. In the cirrhotic patients, there was a significant positive correlation between TPO and platelet count, whereas there was no correlation between TPO level and liver enzymes (alanine aminotransferase and aspartate aminotransferase) in all patients. In addition, a significant decrease in TPO was found in cirrhotic patients in comparison with CAH patients.
Serum TPO level was elevated in patients with chronic viral C hepatitis as a compensatory response to the reduction of platelet count with still functionally active liver cells, but as the disease progress to cirrhosis which also is associated with thrombocytopenia, TPO production is impaired, with failure to compensate the low platelet count aggravating thrombocytopenia.
Chen SL, Morgan TR. The natural history of Hepatitis C Virus (HCV) infection. Int J Med Sci 2006; 3:47–52.
Meara M, Barry J, Mullen L. Epidemiology of hepatitis C infection. Ir Med J 2007; 100:365–366.
Giannini EG. Review article:Thrombocytopenia in chronic liver disease and pharmacologic treatment options. Alimen Pharmacol Therap 2006; 23:1055–1065.
Aster RH. Pooling of platelets in the spleen:Role in the pathogenesis of “hypersplenic” thrombocytopenia. J Clin Invest 1966; 45:645–657.
Peck Radosavljevic M. Thrombocytopenia in liver disease. Can J Gastro-enterol 2000; 14 (Suppl D):60D–66D.
Pockros PJ, Duchini A, McMillan R, Nyberg LM, McHutchison J, Viernes E. Immune thrombocytopenic purpura in patients with chronic hepatitis C virus infection. Am J Gastroenterol 2002; 97:2040–2045.
Kuter DJ. Thrombopoietin Biology and Clinical Applications. 2010; Available at:http://www.people.vcu.edu/~urdesai/atc.htm.
Chang MS, McNinch J, Basu R, Shutter J, Hsu RY, Perkins C, et al. Cloning and characterization of the human Megakaryocyte Growth and Development Factor (MGDF) gene. J Biol Chem 1995; 270:511–514.
Kaushansky K. Lineage-specific hematopoietic growth factors. N Engl J Med 2006; 354:2034–2045.
Wendling F, Vainchenker W. Thrombopoietin and its receptor. Eur Cytokine Network 1998; 9:221–231.
Jelkmann W. The role of the liver in the production of thrombopoietin compared with erythropoietin. Eur J Gastroenterol Hepatol 2001; 13:791–801.
Wendling F, Maraskovsky E, Debili N, Florindo C, Teepe M, Titeux M, et al. cMpl ligand is a humoral regulator of megakaryocytopoiesis. Nature 1994; 369:571–574.
Kaushansky K. Growth factors and hematopoietic cell fate:Introduction:A new feature:Controversies in hematology. Blood 1998; 92:345.
Stockelberg D, Andersson PO, Björnsson E, Björk S, Wadenvik H. Plasma thrombopoietin levels in liver cirrhosis and kidney failure. Journal of Internal Medicine 1999; 246:471–475.
Goulis J, Chau TN, Jordan S, Mehta AB, Watkinson A, Rolles K, et al. Thrombopoietin concentrations are low in patients with cirrhosis and thrombocytopenia and are restored after orthotopic liver transplantation. Gut 1999; 44:754–758.
Schö ffski P. The modulated oral fluoropyrimidine prodrug S-1 and its use in gastrointestinal cancer and other solid tumors. Anti-Cancer Drugs 2004; 15:85–106.
Hernandez F, Blanquer A, Linares M, Lopez A, Tarin F, Cervero A. Autoimmune thrombocytopenia associated with hepatitis C virus infection. Acta Haematol 1998; 99:217–220.
Alexander WS, Hyland C. Thrombopoietin bioassay. Methods Mol Biol 2004; 272:347–359.
Sungaran R, Chisholm OT, Markovic B, Khachigian LM, Tanaka Y, Chong BH. The role of platelet a-granular proteins in the regulation of thrombopoietin messenger RNA expression in human bone marrow stromal cells. Blood 2000; 95:3094–3101.
Kawasaki T, Takeshita A, Souda K, Kobayashi Y, Kikuyama M, Suzuki F, et al. Serum thrombopoietin levels in patients with chronic hepatitis and liver cirrhosis. Am J Gastroenterol 1999; 94:1918–1922.
Long MW, Hoffman R. Thrombocytopoiesis. In:Hoffman R, Benz EJ, Shattil SJ, Furie B, Cohen HJ, Silberstein LE, et al. editors. Hematology:Basic principles and practice. 3rd ed. New York:Churchill Livingstone; 2000. pp. 254–260.
Rios R, Sangro B, Herrero I, Quiroga J, Prieto J. The role of thrombopoietin in the thrombocytopenia of patients with liver cirrhosis. Am J Gastroenterol 2005; 100:1311–1316.
Shimodaira S, Ishida F, Ichikawa N, Tahara T, Kato T, Kodaira H, et al. Serum thrombopoietin (c-Mpl ligand) levels in patients with liver cirrhosis. Thromb Haemost 1996; 76:545–548.
Shiata G, Michiko O, Kawasaki H. Interferon increase serum TPO in patient with chronic active hepatitis. Br J Heamatol 1997; 97:340–342.
Kumar and Clrack’s. Clinical Medicine, Liver, biliary tract and pancreatic disease, liver functions. 2009; 7:321.
Desai UR. Anticoagulants and Mechanism of clotting. 2000. Available at: http://www.people.vcu.edu/urdesai/atc.htm.
Tahara T, Usuki K, Sato H, Ohashi H, Morita H, Tsumura H, et al. A sensitive sandwich ELISA for measuring thrombopoietin in human serum:Serum thrombopoietin levels in healthy volunteers and in patients with haemopoietic disorders. Br J Haematol 1996; 93:783–788.
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Ezzat, E.O., Suliman, S.E., El-Yazeed, S.A. et al. Study of thrombopoietin levels in some Egyptian patients with chronic liver diseases secondary to the hepatitis C virus. Egypt J Intern Med 24, 5–11 (2012). https://doi.org/10.7123/01.EJIM.0000415596.67959.9c