OJNeph  Vol.5 No.2 , June 2015
Higher Endogenous Erythropoietin Levels in Hemodialysis Patients with Hepatitis C Virus Infection and Effect on Anemia
Abstract: Study for influence of chronic Hepatitis C (HCV) on endogenous erythropoietin production and on anemia in dialysis patients remains inconclusive. We hypothesize that chronic hemodialysis patients with co-existing Hepatitis C infection will have higher hemoglobin levels than chronic hemodialysis patients without hepatitis C infection. Secondly, we hypothesize that the higher hemoglobin levels will be associated with higher erythropoietin levels. Therefore we conducted a cross-sectional study of chronic hemodialysis patients with and without hepatitis C infection and evaluated associations with hemoglobin and erythropoietin levels. Our primary outcome was level of hemoglobin. Secondary outcome included association of hemoglobin and erythropoietin levels. 57 chronic hemodialysis patients (33 male, 24 female, mean age 46.05 ± 12.7 years) were included. The mean time spent on hemodialysis was 7.16 ± 6.2 years. None of the patients received any recombinant EPO therapy. Biochemical analyses include ALT, AST, Albumin, C-Reactive Protein, cholesterol levels and complete blood counts. Iron status of patients (transferrin saturation and serum ferritin levels) and parathyroid hormone were measured. Endogenous EPO serum levels were measured by a standardized enzyme-linked immunoassay. 23 of the hemodialysed patients (38.5%) were HCV (+). There was no difference in age, sex, distribution of primary renal diseases, iron status, albumin, C-Reactive-Protein and parathyroid hormone levels between HCV (+) and (-) patients. Mean duration time on dialysis was higher in HCV (+) than HCV (-) patients. Hemoglobin levels were similar between study groups. However serum endogenous erythropoietin levels were significantly higher in HCV (+) patients than HCV (-) patients (19.6 ± 10 mUI/ml vs 7.8 ± 7.7 mUI/ml, p = 0.03). No correlation has been found between the severity of anemia and HCV infection. However, HCV (+) hemodialysed patients had higher serum endogenous erythropoietin levels as compared to HCV (-) patients. Further studies are needed to clarify why high endogenous erythropoietin level does not improve anemia in HCV infected hemodialysis patients.
Cite this paper: Boubaker, K. , Mahfoudhi, M. , Battikh, A. , Bounemra, A. , Maktouf, C. and Kheder, A. (2015) Higher Endogenous Erythropoietin Levels in Hemodialysis Patients with Hepatitis C Virus Infection and Effect on Anemia. Open Journal of Nephrology, 5, 29-34. doi: 10.4236/ojneph.2015.52004.

[1]   Kuo, G., Choo, K.L., Alter, H.J., Gitnick, G.L., Redeker, A.G., Purcell, R.H., et al. (1989) An Assay for Circulating Antibodies to a Major Etiologic Virus of Human Non-A, Non-B Hepatitis. Science, 244, 362-364.

[2]   Pereira, B.J. (1999) Hepatitis C Virus Infection in Dialysis: A Continuing Problem. Artificial Organs, 23, 51-60.

[3]   Akpolat, T., Turkish Multicentre CAPD Study Group (TULIP) (2001) CAPD: A Control Strategy to Prevent Spread of HCV Infection and End Stage Renal Disease (Short Reports). Peritoneal Dialysis International, 21, 77-79.

[4]   Di Bisceglie, A.M., Axiotis, C.A., Hoofnagle, J.H. and Bacon, B.R. (1992) Measurement of Iron Status in Patients with Chronic Hepatitis. Gastroenterology, 102, 2108-2113.

[5]   Radovic, M., Jelkmann, W., Djukanovic, L. and Ostric, V. (1999) Serum Erythropoietin and Interleukin-6 Levels in Hemodialysis Patients with Hepatitis Virus Infection. Journal of Interferon & Cytokine Research, 19, 69-73.

[6]   Altintepe, L., Kurtoglu, E., Tonbul, Z., Yeksan, M., Yildiz, A. and Türk, S. (2004) Lower Erythropoietin and Iron Supplementation Are Required in Haemodialysis Patients with Hepatitis C Virus Infection. Clinical Nephrology, 61, 347-351.

[7]   Lin, Y.L., Lin, C.W., Lee, C.H., Lai, I.C., Chen, H.H. and Chen, T.W. (2008) Chronic Hepatitis Ameliorates Anemia in Haemodialysis Patients. Nephrology, 13, 289-293.

[8]   Khurana, A., Nickel, A.E., Narayanan, M. and Foulks, C.J. (2008) Effect of Hepatitis C Infection on Hemodialysis Patients. Hemodialysis International, 12, 94-99.

[9]   Brown, S., Caro, J., Erslev, A.J. and Murray, T.G. (1980) Spontaneous Increase in Erytropoietin and Hematocrit Value Associated with Transient Liver Enzyme Abnormalities in an Anephric Patient Undergoing Hemodialysis. The American Journal of Medicine, 68, 280-284.

[10]   Brown, S., Caro, J., Erslev, A.J. and Murray, T.G. (1999) Impact of Hepatitis B and C Virus on Kidney Transplantation Outcome. Hepatology, 29, 257-263.

[11]   Natov, S.N. and Pereira, B.J.G. (1994) Hepatitis C Infection in Patients on Dialysis. Seminars in Dialysis, 7, 360-368.

[12]   Weiner, A.J., Kuo, G., Bradley, D.W., Bonino, F., Saracco, G., Lee, C., et al. (1990) Detection of Hepatitis C Viral Sequences in Non A, Non-B Hepatitis. The Lancet, 335, 1-3.

[13]   Hardy, N.M., Sandroni, S., Danielson, S. and Wilson, W.J. (1992) Antibody to Hepatitis C Virus Increases with the Time on Dialysis. Clinical Nephrology, 38, 44-48.

[14]   Medici, G., Depetri, G.C. and Mileti, M. (1992) Anti-Hepatitis C Virus Positivity and Clinical Correlations in Hemodialyzed Patients. Nephron, 61, 363-364.

[15]   Pereira, B.J. and Levey, A.S. (1999) Hepatitis C Virus Infection in Dialysis and Renal Transplantation. Kidney International, 51, 981-999.

[16]   Chan, N., Barton, C.H., Mirahmadi, M.S., Gordon, S. and Vaziri, N.D. (1984) Erythropoiesis Associated with Viral Hepatitis in End-Stage Renal Disease. The American Journal of the Medical Sciences, 287, 56-57.

[17]   Pololi-Anagnostou, A., Westenfelder, C. and Anagnostou, A. (1981) Marked Improvement of Erythropoiesis in an Anephric Patient. Nephron, 29, 277-279.

[18]   Simon, P., Meyrier, A., Tanquerel, T. and Ang, K.S. (1980) Improvement of Anaemia in Haemodialyzed Patients after Viral or Toxic Hepatic Cytolysis. British Medical Journal, 280, 892-894.

[19]   Sahin, I., Arabaci, F. and Sahin, H.A. (2003) Does Hepatitis C Virus Infection Increase Hematocrit and Haemoglobin Levels in Hemodialyzed Patients? Clinical Nephrology, 60, 401-404.

[20]   Jelkmann, W. (1992) Erythropoietin: Structure, Control of Production and Function. Physiological Reviews, 72, 449-489.

[21]   Zadrazil, J., Bachleda, P. and Zahálková, J. (1997) Endogenous Erythropoietin in Patients on Regular Dialysis Therapy. Vnitrní Lékarství, 43, 649-654.

[22]   Kato, A., Hishida, A., Kumagai, H., Furuya, R., Nakajima, T. and Honda, N. (1994) Erythropoietin Production in Patients with Chronic Renal Failure. Renal Failure, 16, 645-651.

[23]   Kew, M.C. and Fisher, J.W. (1986) Serum Erythropoietin Concentrations in Patients with Hepatocellular Carcinoma. Cancer, 58, 2485-2488.<2485::AID-CNCR2820581122>3.0.CO;2-N

[24]   Brox, A.G., Zhang, F., Guyda, H. and Gagnon, R.F. (1996) Subtherapeutic Erythropoietin and Insulin-Like Growth Factor-1 Correct the Anemia of Chronic Renal Failure in the Mouse. Kidney International, 50, 937-943.

[25]   Bondurant, M.C. and Koury, M.J. (1985) Anemia Induces Accumulation of Erythropoietin mRNA in the Kidney and Liver. Molecular and Cellular Biology, 6, 2731-2733.

[26]   Birgegard G. (1989) Erythropoiesis and Inflammation. Contrib Nephrol, 76, 330-339; discussion 339-341.

[27]   Mecans, R.T. and Krantz, S.B. (1992) Progress in Understanding the Pathogenesis of the Anemia of Chronic Disease. Blood, 80, 1639-1647.