Skip to main content
  • Original article
  • Open access
  • Published:

The effect of co-infection with hepatitis B and hepatitis C viruses on the prevalence of proteinuria and loss of renal function: a single-center experience

Abstract

Introduction and aim of the work

Patients infected with hepatitis B virus (HBV) or hepatitis C virus (HCV) are at increased risk of renal disease. This study compares factors associated with proteinuria and doubling of serum creatinine level in patients who were infected with HCV or HBV alone with those who were coinfected with HCV and HBV.

Materials and methods

The study was performed on 1243 patients who were diagnosed with HBV and/or HCV at the Cairo University Hospitals. All the included subjects underwent urine analysis for proteinuria and serum creatinine level. Clinical characteristics were recorded at baseline and at last follow-up.

Results

Of 1243 patients, 293 (23.6%) patients had proteinuria. Subset analysis of the patients with proteinuria showed that 10.6% were HBV infected, 63.8% were HCV infected, and the remaining 25.6% were coinfected with both HBV and HCV. Overall, coinfection with both viruses (P=0.01), lower serum albumin (P=0.001), hypertension (P=0.01), and diabetes (P=0.001) were associated with an increase in risk of proteinuria. Coinfection (P=0.001), presence of HBV (P=0.001), and increasing HCV RNA level in patients with HCV and in coinfected patients (P=0.05) was associated with doubling of serum creatinine level.

Conclusion

The patients coinfected with HBV and HCV are at greater risk of clinically significant proteinuria and loss of renal function owing to complex virological profile. Progressive loss of renal function in that population is associated with markers of viral activity such as proteinuria and increasing HCV RNA levels among HCV-infected patients.

References

  1. Gomaa A, Allam N, Elsharkway A, El Kassas M, Waked I. Hepatitis C infection in Egypt: prevalence, impact and management strategies. Hepat Med 2017; 9:17–25.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Khaled IA, Mahmoud OM, Saleh AF, Bioumie EE. Prevalence of HBV genotypes in Egypt among hepatitis patients. Mol Biol Rep 2011; 38:4353–4357.

    Article  CAS  PubMed  Google Scholar 

  3. Morales JM, Kamar N, Rostaing L. Hepatitis C and renal disease: epidemiology, diagnosis, pathogenesis and therapy. Contrib Nephrol 2012; 176:10.

    Article  PubMed  Google Scholar 

  4. Cacoub P, Comarmond C, Domont F, Savey L, Desbois AC, Saadoun D. Extrahepatic manifestations of chronic hepatitis C virus infection. Ther Adv Infect Dis 2016; 3:3–14.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Kappus MR, Richard K. Extrahepatic manifestations of acute hepatitis B virus infection. Gastroenterol Hepatol (N Y) 2013; 9:123–126.

    Google Scholar 

  6. Han SH. Extrahepatic manifestations of chronic hepatitis B. Clin Liver Dis 2004; 8:403–418.

    Article  PubMed  Google Scholar 

  7. Baig S, Alamgir M. The extrahepatic manifestations of hepatitis B virus. J Coll Physicians Surg Pak 2008; 18:451–457.

    PubMed  Google Scholar 

  8. Radhakrishnan J, Uppot RN, Colvin RB. Case records of the Massachusetts General Hospital. Case 5-2010. A 51-year-old man with HIV infection, proteinuria, and edema. N Engl J Med 2010; 362:636.

    CAS  PubMed  Google Scholar 

  9. McGuire BM, Julian BA, Bynon JS Jr, Cook WJ, King SJ, Curtis JJ, et al. Brief communication: Glomerulonephritis in patients with hepatitis C cirrhosis undergoing liver transplantation. Ann Intern Med 2006; 144:735.

    Article  PubMed  Google Scholar 

  10. Abbate M, Zoja C, Remuzzi G. How does proteinuria cause progressive renal damage?. J Am Soc Nephrol 2006; 17:2974–2984.

    Article  CAS  PubMed  Google Scholar 

  11. Peruzzi L, Trusolino L, Amore A, Gianoglio B, Cirina P, Basso G, et al. Tubulointerstitial responses in the progression of glomerular diseases: albuminuria modulates alpha v beta 5 integrin. Kidney Int 1996; 50:1310–1320.

    Article  CAS  PubMed  Google Scholar 

  12. Wang Y, Chen J, Chen L, Tay YC, Rangan GK, Harris DC. Induction of monocyte chemoattractant protein-1 in proximal tubule cells by urinary protein. J Am Soc Nephrol 1997; 8:1537–1545.

    Article  CAS  PubMed  Google Scholar 

  13. Burton CJ, Combe C, Walls J, Harris KP. Secretion of chemokines and cytokines by human tubular epithelial cells in response to proteins. Nephrol Dial Transplant 1999; 14:2628–2633.

    Article  CAS  PubMed  Google Scholar 

  14. Drumm K, Bauer B, Freudinger R, Gekle M. Albumin induces NF-kappaB expression in human proximal tubule-derived cells (IHKE-1). Cell Physiol Biochem 2002; 12:187–196.

    Article  CAS  PubMed  Google Scholar 

  15. Morigi M, Macconi D, Zoja C, Donadelli R, Buelli S, Zanchi C, et al. Protein overload-induced NF-kappaB activation in proximal tubular cells requires H2O2 through a PKC-dependent pathway. J Am Soc Nephrol 2002; 13:1179–1189.

    CAS  PubMed  Google Scholar 

  16. Nakajima H, Takenaka M, Kaimori J-Y., Nagasawa Y, Kosugi A, Kawamoto S, et al. Gene expression profile of renal proximal tubules regulated by proteinuria. Kidney Int 2002; 61:1577–1587.

    Article  CAS  PubMed  Google Scholar 

  17. Tang S, Leung JCK, Abe K, Wah Chan K, Chan LYY, Mao Chan T, et al. Albumin stimulates interleukin-8 expression in proximal tubular epithelial cells in vitro and in vivo. J Clin Invest 2003; 111:515–527.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Wohlfarth V, Drumm K, Mildenberger S, Freudinger R, Gekle M. Protein uptake disturbs collagen homeostasis in proximal tubule-derived cells. Kidney Int Suppl 2003; 84:S103–S109.

    Article  CAS  Google Scholar 

  19. Donadelli R, Zanchi C, Morigi M, Buelli S, Batani C, Tomasoni S, et al. Protein overload induces fractalkine upregulation in proximal tubular cells through nuclear factor kappaB- and p38 mitogen-activated protein kinase-dependent pathways. J Am Soc Nephrol 2003; 14:2436–2446.

    Article  CAS  PubMed  Google Scholar 

  20. Zandi-Nejad K, Eddy AA, Glassock RJ, Brenner BM. Why is proteinuria an ominous biomarker of progressive kidney disease?. Kidney Int Suppl 2004; 92:S76–S89.

    Article  CAS  Google Scholar 

  21. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (allhat). JAMA 2002; 288:2981–2997.

    Article  Google Scholar 

  22. Brown MJ, Castaigne A, Ruilope LM, Mancia G, Rosenthal T, de Leeuw PW, et al. INSIGHT: international nifedipine GITS study intervention as a goal in hypertension treatment. J Hum Hypertens 1996; 10 (Suppl 3): S157–S160.

    PubMed  Google Scholar 

  23. Segura J, Campo C, Ruilope L. Effect of proteinuria and glomerular filtration rate on cardiovascular risk in essential hypertension. Kid Internat 2004; 66 (Suppl 92): S45–S49.

    Article  Google Scholar 

  24. Dahlöf B, Devereux RB, Kjeldsen SE, Julius S, Beevers G, de Faire U, et al. Cardiovascular morbidity and mortality in the Losartan Intervention for Endpoint Reduction in Hypertension Study (LIFE): a randomised trial against atenolol. Lancet 2002; 359:995–1003.

    Article  PubMed  Google Scholar 

  25. Levy J. Proteinuria, renal impairment, and death. BMJ 2006; 332: 1402–1403.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Adinolfi L, Zampino R, Restivo L, Lonardo A, Guerrera B, Marrone A, et al. Chronic hepatitis C virus infection and atherosclerosis: clinical impact and mechanisms. World J Gastroenterol 2014; 20:3410–3417.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Aghemo A, Prati G, Rumi M, Soffredini R, D’Ambrosio R, Orsi E, et al. Sustained virological response prevents the development of insulin resistance in patients with chronic hepatitis C. Hepatology 2012; 56:1681–1687.

    Article  CAS  PubMed  Google Scholar 

  28. Levey AS, Atkins R, Coresh J, Cohen EP, Collins AJ, Eckardt KU, et al. Chronic kidney disease as a global public health problem: approaches and initiatives – a position statement from Kidney Disease Improving Global Outcomes. Kidney Int 2007; 72:247.

    Article  CAS  PubMed  Google Scholar 

  29. Castillo I, Martinez-Ara J, Olea T, Bartolomé J, Madero R, Hernández E, et al. High prevalence of occult hepatitis C virus infection in patients with primary and secondary glomerular nephropathies. Kidney Int 2014; 86:619.

    Article  CAS  PubMed  Google Scholar 

  30. Caccamo G, Saffioti F, Giovanni R. Hepatitis B virus and hepatitis C virus dual infection. World J Gastroenterol 2014; 20:14559–14567.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Hill NR, Fatoba ST, Oke JL, Hirst JA, O’Callaghan C, Lasserson DS, et al. Global prevalence of chronic kidney disease – a systematic review and meta-analysis. PLoS One 2016; 11:e0158765.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Tang S, Lai FM, Lui YH, Tang CS, Kung NN, Ho YW, et al. Lamivudine in hepatitis B-associated membranous nephropathy. Kidney Int 2005; 68:1750–1758.

    Article  CAS  PubMed  Google Scholar 

  33. Kong X-L., Ma X-J., Su H, Xu D-M. Relationship between occult hepatitis B virus infection and chronic kidney disease in a Chinese population-based cohort. Chronic Dis Transl Med 2016; 2:55–60.

    PubMed  PubMed Central  Google Scholar 

  34. Huang JF, Chuang WL, Dai CY, Ho CK, Hwang SJ, Chen SC, et al. Viral hepatitis and proteinuria in an area endemic for hepatitis B and C infections: another chain of link?. J Intern Med 2006; 260:255–262.

    Article  PubMed  Google Scholar 

  35. Daw MA, Shabash A, El-Bouzedi A, Dau A. A seroprevalence of HBV, HCV & HIV co-infection and risk factors analysis in Tripoli-Libya. PLoS One 2014; 9:e98793. https://doi.org/10.1371/journal.pone.0098793.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Pallas JR, Farinas-Alvarez C, Prieto D, Delgado-Rodríguez M. Coinfections by HIV, hepatitis B and hepatitis C in imprisoned injecting drug users. Eur J Epidemiol 1999; 15:699–704.

    Article  CAS  PubMed  Google Scholar 

  37. Reddy GA, Dakshinamurthy KV, Neelaprasad P, Gangadhar T, Lakshmi V. Prevalence of HBV and HCV dual infection in patients on haemodialysis. Indian J Med Microbiol 2005; 23:41–43.

    Article  CAS  PubMed  Google Scholar 

  38. Aroldi A, Lampertico P, Montagnino G, Patrizia P, Margherita V, Maria CR., et al. Natural history of hepatitis B and C in renal allograft recipients. Transplantation 2005; 79:1132–1136.

    Article  PubMed  Google Scholar 

  39. Kalinowska-Nowak A, Bociąga-Jasik M, Garlicki A. Prevalence of hepatotropic viruses HBV and HCV in HIV-infected patients from Southern region of Poland. Acta Virologica 2000; 44:23–28.

    Google Scholar 

  40. Irshad M, Peter S. Spectrum of viral hepatitis in thalassemic children receiving multiple blood transfusions. Indian J Gastroenterol 2002; 21:183–184.

    PubMed  Google Scholar 

  41. Viswanathan V, Tilak P, Kumpatla S. Risk factors associated with the development of overt nephropathy in type 2 diabetes patients: a 12 years observational study. Indian J Med Res 2012; 136:46–53.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Deray G, Buti M, Gane E, Jia JD, Lik Yuen Chan H,Craxi A, et al. Hepatitis B virus infection and the kidney: renal abnormalities in HBV patients, antiviral drugs handling, and specific follow-up. Advances Hepatol 2015; 2015:596829.

    Article  Google Scholar 

  43. Bhimma R, Hammond MG, Coovadia HM, Adhikari Catherine M, Connolly A. HLA class I and II in black children with hepatitis B virus-associated membranous nephropathy. 61 2002; 61:1510–1515.

    Google Scholar 

  44. Perico N, Cattaneo D, Bikbov B, Remuzzi G. Hepatitis C infection and chronic renal diseases. CJASN 2009; 4:207–220.

    Article  CAS  PubMed  Google Scholar 

  45. Chen YC, Su YC, Li CY, Wu CP, Lee MS. A nationwide cohort study suggests chronic hepatitis B virus infection increases the risk of end-stage renal disease among patients in Taiwan. Kidney Int 2015; 87:1030–1038.

    Article  PubMed  Google Scholar 

  46. Lee JJ, Lin MY, Yang YH MHA, Yang YH, Lu SN, Chen HC, et al. Association of hepatitis C and B virus infection with CKD in an endemic area in Taiwan: a cross-sectional study. Am J Kidney Dis 2010; 56:23–31.

    Article  PubMed  Google Scholar 

  47. Dalrymple LS, Koepsell T, Sampson J, Dominitz JA, Young B, Kestenbaum B. Hepatitis C Virus Infection and the Prevalence of Renal Insufficiency. CJASN 2007; 2:4715–4721.

    Article  CAS  Google Scholar 

  48. Wörnle M, Schmid H, Banas B, Merkle M, Henger A, Roeder M, et al. Novel role of toll-like receptor 3 in hepatitis C-associated glomerulonephritis. Am J Pathol 2006; 168:370–385.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Fabrizi F. Hepatitis C virus, cryoglobulinemia, and kidney: novel evidence. Scientifica 2012; 2012:128382.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Cohen DL, Townsend RR. What should the physician do when creatinine increases after starting an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker?. JCH 2008; 10:803–804.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Rabab M. Ahmed MD.

Additional information

This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

Rights and permissions

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Soliman, A.R., Ahmed, R.M., Soliman, M. et al. The effect of co-infection with hepatitis B and hepatitis C viruses on the prevalence of proteinuria and loss of renal function: a single-center experience. Egypt J Intern Med 30, 271–275 (2018). https://doi.org/10.4103/ejim.ejim_51_18

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.4103/ejim.ejim_51_18

Keywords