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Correlations of folic acid, vitamin B12, homocysteine, and thrombopoietin to platelet count in HCV infection



The platelet count is known to decrease in proportion to the advancement of the stage of liver disease in chronic hepatitis C (CHC) viral infection. The platelet count is currently used as an index for fibrosis staging. The pathophysiology of thrombocytopenia (TCP) in patients with hepatitis C virus (HCV) infection is not completely understood.


This work aimed to study the correlations of folic acid (FA), vitamin B12 (Vit B12), homocysteine (Hcy), and thrombopoietin to the platelet count in HCV infection.

Patients and methods

Sixty-seven patients (51 men and 16 women) with HCV infection were included in this study. All patients were sero-negative for hepatitis B viral markers. In addition, 20 healthy volunteers, matched for sex and age, were included as a control group. All patients and control individuals were subjected to the following: assessment of medical history, thorough clinical examination, and laboratory investigations including the following: complete blood cell counts, viral hepatitis markers, liver and renal function tests, HCV-RNA by quantitative PCR, serum folate, Vit B12, thrombopoietin, and plasma Hcy. Abdominal ultrasonography and ultrasound-guided liver biopsy for histopathologic examinations were carried out for the patients. Patients were divided into two groups of 36 patients with CHC and 31 patients with cirrhosis with HCV liver cirrhosis (LC).


The results indicated a significant decrease in the platelet count in CHC and LC patients compared with the healthy control group. There was a highly significant decrease in the FA level in CHC and LC patients compared with the control group; also, a significant decrease in the platelet count was found in LC patients compared with CHC patients. Hcy was significantly increased in CHC and LC patients. There was a nonsignificant decrease in Vit B12 in CHC patients, whereas it was significantly increased in LC patients. There was a nonsignificant decrease in thrombopoietin in CHC patients compared with the control group, whereas in LC patients, there was a highly significant decrease. There was a highly significant positive correlation between the platelet count and FA, but an insignificant correlation between the platelet count and Hcy, Vit B12, thrombopoietin, and viral load.


This study concluded that TCP in HCV-related chronic liver diseases is multifactorial and decreased FA is involved in its pathogenesis as an independent risk factor. Increased Hcy may cause TCP through platelet activation and endothelial dysfunction.


  1. Chen SL, Morgan TR. The natural history of hepatitis C virus (HCV) infection. Int J Med Sci 2006; 3:47–48.

    Article  Google Scholar 

  2. Louie KS, Micallef JM, Pimenta JM, Forssen UM, et al. Prevalence of thrombocytopenia among patients with chronic hepatitis C: a systematic review. J Viral Hepat 2011; 18:1–7.

    Article  CAS  Google Scholar 

  3. Giannini EG. Thrombocytopenia in chronic liver disease and pharmacologic treatment options. Aliment Pharmacol Ther 2006; 23:1055–1065.

    Article  CAS  Google Scholar 

  4. Makoto O, Makoto K, Minoru S, Masumi E, Koichi T, Katsue S, et al. Causes of thrombocytopenia in chronic hepatitis C viral infection. Clin Appl Thromb Hemost 2012; 18:272–280.

    Article  Google Scholar 

  5. Weksler BB. Review article: the pathophysiology of thrombocytopenia in hepatitis C virus infection and chronic liver disease. Aliment Pharmacol Ther 2007; 26 (Suppl 1): 13–19.

    Article  CAS  Google Scholar 

  6. Kumar P, Clark M. Liver, biliary tract and pancreatic disease; Kumar and Clark’s Clinical Medicine 2011; 7:321–322.

    Google Scholar 

  7. Halifeoglu I, Gur B, Aydin S, Ozturk A. Plasma trace elements, vitamin B12, folate, and homocysteine levels in cirrhotic patients compared to healthy controls. Biochemistry (Mosc) 2004; 69 (693–696):14–15.

    Google Scholar 

  8. Adinolfi LE, Ingrosso D, Cesaro G, Cimmino A, D’Antò M, Capasso R, et al. Hyperhomocysteinemia and the MTHFR C677T polymorphism promote tea-tosis and fibrosis in chronic hepatitis C. Hepatology 2005; 41:995–1003.

    Article  CAS  Google Scholar 

  9. Hirsch S, Poniachick J, Avendaño M, Csendes A, Burdiles P, Smok G, et al. Serum folate and homocysteine levels in obese females with non-alcoholic fatty liver. Nutrition 2005; 21:137–141.

    Article  CAS  Google Scholar 

  10. Kaushansky K. Lineage-specific hematopoietic growth factors. N Engl J Med 2006; 354:2034–2045.

    Article  CAS  Google Scholar 

  11. Ishak K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F, et al. Histological grading and staging of chronic hepatitis. J Hepatol 1995; 22:696–699.

    Article  CAS  Google Scholar 

  12. Moller J, Ahola L, Abrahamsson L. Evaluation of DPC Immulite 2000 assay for total homocysteine in plasma. Scan J Clin Lab Invest 2002; 62:396–373.

    Google Scholar 

  13. Anwar WA, Khaled HM, Amra HA, El-Nezami H, Loffredo CA. Changing pattern of hepatocellular carcinoma (HCC) and its risk factors in Egypt: possibilities for prevention. Mutat Res 2008; 659:176–184,

    Article  CAS  Google Scholar 

  14. Testa R, Testa E, Giannini E, Borro P, Milazzo S, Isola L, et al. Noninvasive ratio indexes to evaluate fibrosis staging in chronic hepatitis C: role of platelet count/spleen diameter ratio index. J Intern Med 2006; 260:142–150.

    Article  CAS  Google Scholar 

  15. Kauf TL, Nelson DR, Schelfhout J, Delaney JA, Wang PF. Trends in the prevalence of thrombocytopenia among individuals infected with hepatitis C virus in the United States, 1999-2008. BMC Research Notes 2012; 5:142.

    Article  Google Scholar 

  16. Peck-Radosavljevic M. Thrombocytopenia in liver disease. Can J Gastro-enterol 2000; 14 (Suppl D): 60–66.

    Article  Google Scholar 

  17. Fusegawa H, Shiraishi K, Ogasawara F, Shimizu M, Haruki Y, Miyachi H, et al. Platelet activation in patients with chronic hepatitis C. Tokai J Exp Clin Med 2002; 27:101–106.

    PubMed  Google Scholar 

  18. Ezzat EO, Suliman SE, El-Yazeed SA, Ahmad FM, Said SK. Study of thrombopoietin level in egyptian patients with chronic liver diseases secondary to hepatitis C virus. Egypt J Int Med 2012; 24:5–11.

    Google Scholar 

  19. García-Tevijano ER, Berasain C, Rodríguez JA, Corrales FJ, Arias R, Martín-Duce A, et al. Hyperhomocysteinemia in liver cirrhosis, mechanisms and role in vascular and hepatic fibrosis. Hypertension 2001; 38: 1217–1221.

    Article  Google Scholar 

  20. Bosy-Westphal A, Ruschmeyer M, Czech N, Oehler G, Hinrichsen H, Plauth M, et al. Determinants of hyperhomocysteinemia in patients with chronic liver disease and after orthotopic liver transplantation. Am J Clin Nutr 2003; 77:1269–1277.

    Article  CAS  Google Scholar 

  21. Sanjo A, Satoi J, Ohnishi A, Maruno J, Fukata M, Suzuki N. Role of elevated platelet-associated immunoglobulin G and hypersplenism in thrombo-cytopenia of chronic liver diseases. J Gastroenterol Hepatol 2003; 18:638–644.

    Article  Google Scholar 

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Correspondence to Somayh S. Eissa.

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Eissa, S.S., Hendy, O.M., Younis, F. et al. Correlations of folic acid, vitamin B12, homocysteine, and thrombopoietin to platelet count in HCV infection. Egypt J Intern Med 24, 83–92 (2012).

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  • folic acid
  • homocysteine
  • thrombocytopenia and hepatitis C virus
  • thrombopoietin
  • vitamin B12