Skip to main content
SpringerLink
Log in

Recipient IL28B genotype CT is a predictor of new onset diabetes mellitus in liver transplant patients with chronic hepatitis C

  • Original Article
  • Published:
International Journal of Diabetes in Developing Countries Aims and scope Submit manuscript

Abstract

Background

New onset diabetes after liver transplantation (NODAT) is increasingly recognized as a complication that affects the quality of life. In addition to well-known risk factors for diabetes in such patients, little is known regarding the genetic predisposition for this condition.

Aims

To study the association of IL28B polymorphism with occurrence of new onset diabetes after liver transplantation in HCV patients.

Methods

A prospective cohort study. Fifty non-diabetic LDLT recipients were recruited from the Liver Transplantation Unit at El Manial, Cairo University Hospital. FBS was done at 0, 3, and 12 months; HBA1c was done after 6 months. IL28B rs12979860 polymorphism was done to all patients.

Results

According to FBS after 3 months and HBA1C, 20 patients developed diabetes, 21 patients prediabetes and 9 remained normal. IL28B CT genotype was 78%, CC 20% and TT 2%. Univariate regression showed that the CT genotype was significantly associated with higher blood glucose at 0 months (coefficient ± SE, 64 ± 4.7; p < 0.001), 3 (coefficient ± SE, 58 ± 4.0; p < 0.001), and 12 months (coefficient ± SE, 57 ± 3.2; p < 0.001), and with the development of diabetes and prediabetes after LDLT (coefficient ± SE, 0.6 ± 0.06; p < 0.001).

Conclusions

IL28B polymorphism is significantly associated with new onset diabetes after LDLT. CT genotype may represent a marker to identify high risk recipients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Veldt BJ, Chen W, Heathcote EJ, Wedemeyer H, Reichen J, Hofmann WP, et al. Increased risk of hepatocellular carcinoma among patients with hepatitis C cirrhosis and diabetes mellitus. Hepatol. 2008;47(6):1856–62.

    Article  Google Scholar 

  2. Watt KDS, Pedersen RA, Kremers WK, Heimbach JK, Charlton MR. Evolution of causes and risk factors for mortality post-liver transplant: results of the NIDDK long-term follow-up study. American Journal of Transplantation 2010 May 10;10(6):1420–7. http://www.ncbi.nlm.nih.gov/pubmed/20486907

  3. Veldt BJ, Poterucha JJ, Watt KDS, Wiesner RH, Hay JE, Rosen CB, et al. Insulin resistance, serum adipokines and risk of fibrosis progression in patients transplanted for hepatitis C. Am J Transplant. 2009;9(6):1406–13.

    Article  CAS  Google Scholar 

  4. Romero-Gómez M, Fernández-Rodríguez CM, Andrade RJ, Diago M, Alonso S, Planas R, et al. Effect of sustained virological response to treatment on the incidence of abnormal glucose values in chronic hepatitis C. J Hepatol. 2008;48(5):721–7.

    Article  Google Scholar 

  5. Khan MS, Shoukat A, Mudassar S, Kawoosa Z, Shah AH, Zargar SA. Impact of IL28B genetic variant’s and viral genotype on treatment outcome of hepatitis C infected patients. J Infect Develop Countries. 2018;12(09):762–70. https://doi.org/10.3855/jidc.10175.

    Article  CAS  Google Scholar 

  6. Krentz AJ, Dmitrewski J, Mayer D, Nattrass M. Effects of immunosuppressive agents on glucose metabolism. Clinical Immunotherapeutics. 1995 Aug;30;4(2):103–23. http://link.springer.com/https://doi.org/10.1007/BF03259076

  7. Stättermayer AF, Rutter K, Beinhardt S, Scherzer T-M, Stadlmayr A, Hofer H, et al. Association of the IL28B genotype with insulin resistance in patients with chronic hepatitis C. Journal of hepatology. 2012 Sep;57(3):492–8. http://www.ncbi.nlm.nih.gov/pubmed/22634340

  8. Skladaný Ĺ, Mesárošová Z, Bachová B, Stančík M, Dedinská I. Alcohol-related liver disease as a new risk factor for post-transplant diabetes after liver transplantation. Transpl Proc. 2019;51(10):3369–74.

    Article  Google Scholar 

  9. Veldt BJ, Duarte-Rojo A, Thompson AJ, Watt KD, Heimbach JK, Tillmann HL, et al. Recipient IL28B polymorphism is an important independent predictor of posttransplant diabetes mellitus in liver transplant patients with chronic hepatitis C. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2012 Mar;12(3):737–44. http://www.ncbi.nlm.nih.gov/pubmed/22300408

  10. Duca AM, de la Fuente S, Citores MJ, Cuenca AB, Cisneros E, Escamilla N, et al. CC genotype at rs12979860 of IL28B is associated with lower risk of new-onset diabetes after transplantation in adult patients with liver transplantation for hepatitis C cirrhosis. Transplantation proceedings. 2014 Nov;46(9):3114–6. http://www.ncbi.nlm.nih.gov/pubmed/25420838

  11. Xue M, Lv C, Chen X, Liang J, Zhao C, Zhang Y, et al. Donor liver steatosis: a risk factor for early new-onset diabetes after liver transplantation. J Diabetes Investig. 2017;8:181–7.

    Article  Google Scholar 

  12. Lv C, Zhang Y, Chen X, Huang X, Xue M, Sun Q, et al. New-onset diabetes after liver transplantation and its impact on complications and patient survival. J Diabetes. 2015;7:881–90.

    Article  CAS  Google Scholar 

  13. Zayed RA, Bahgat MH, Wahab MA, El-Etreby S, Saad RA, Elmorsy FM. Prevalence and risk factors of new onset diabetes after liver transplantation (NODAT): a single Egyptian center experience. Arch Dig Disord. 2017;1(1):7–13.

    Google Scholar 

  14. Andrade AR, Bittencourt PL, Codes L, Evangelista MA, Castro AO, Boa SN, et al. New onset diabetes and non-alcoholic fatty liver disease after liver transplantation. Ann Hepatol. 2017;16(6):932–40.

    Article  CAS  Google Scholar 

  15. Liang J, Yi X, Xue M, Chen X, Huang X, Sun Q, et al. A retrospective cohort study of preoperative lipid indices and their impact on new-onset diabetes after liver transplantation. J Clin Lab Anal. 2020;34:e23192.

    Article  CAS  Google Scholar 

  16. Ling Qi Xu, Xiao WB, Lanjuan Li, Shusen Z. The origin of new-onset diabetes after liver transplantation. Transpl. 2016;100(4):808–13. https://doi.org/10.1097/TP.0000000000001111.

    Article  CAS  Google Scholar 

  17. Stockmann M, Konrad T, Nolting S, Hünerbein D, Wernecke KD, Döbling H, et al. Major influence of liver function itself but not of immunosuppression determines glucose tolerance after living-donor liver transplantation. Liver Transpl. 2006;12:535–43.

    Article  Google Scholar 

  18. Gebhardt S, Jara M, Malinowski M, Seehofer D, Puhl G, Pratschke J, Stockmann M. Risk factors of metabolic disorders after liver transplantation: an analysis of data from fasted patients. Transpl. 2015;99(6):1243–9.

    Article  CAS  Google Scholar 

  19. Watt KD, Dierkhising R, Fan C, Heimbach JK, Tillman H, Goldstein D, et al. Investigation of PNPLA3 and IL28B genotypes on diabetes and obesity after liver transplantation: insight into mechanisms of disease. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2013 Sep;13(9):2450–7. http://www.ncbi.nlm.nih.gov/pubmed/23859071

  20. Thompson AJ, Muir AJ, Sulkowski MS, Ge D, Fellay J, Shianna KV, et al. Interleukin-28B Polymorphism improves viral kinetics and is the strongest pretreatment predictor of sustained virologic response in genotype 1 hepatitis C virus. Gastroenterology. 2010 Jul;139(1):120–129.e18. https://linkinghub.elsevier.com/retrieve/pii/S0016508510005743

  21. Maher SG, Sheikh F, Scarzello AJ, Romero-Weaver AL, Baker DP, Donnelly RP, et al. IFNalpha and IFNlambda differ in their antiproliferative effects and duration of JAK/STAT signaling activity. Cancer biology & therapy. 2008 Jul;7(7):1109–15. http://www.ncbi.nlm.nih.gov/pubmed/18698163

  22. Suppiah V, Moldovan M, Ahlenstiel G, Berg T, Weltman M, Abate ML, et al. IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy. Nature genetics. 2009 Oct;41(10):1100–4. http://www.ncbi.nlm.nih.gov/pubmed/19749758

  23. Tanaka Y, Nishida N, Sugiyama M, Kurosaki M, Matsuura K, Sakamoto N, et al. Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. Nature genetics. 2009 Oct;41(10):1105–9. http://www.ncbi.nlm.nih.gov/pubmed/19749757

  24. Honda M, Sakai A, Yamashita T, Nakamoto Y, Mizukoshi E, Sakai Y, et al. Hepatic ISG expression is associated with genetic variation in interleukin 28B and the outcome of IFN therapy for chronic hepatitis C. Gastroenterol. 2010;139(2):499–509.

    Article  CAS  Google Scholar 

  25. Urban TJ, Thompson AJ, Bradrick SS, Fellay J, Schuppan D, Cronin KD, et al. IL28B genotype is associated with differential expression of intrahepatic interferon-stimulated genes in patients with chronic hepatitis C. Hepatology. 2010 Dec;52(6):1888–96. http://www.ncbi.nlm.nih.gov/pubmed/20931559

  26. Dill MT, Duong FHT, Vogt JE, Bibert S, Bochud P, Terracciano L, et al. Interferon-induced gene expression is a stronger predictor of treatment response than IL28B genotype in patients with hepatitis C. Gastroenterology. 2011 Mar;140(3):1021–1031.e10. https://linkinghub.elsevier.com/retrieve/pii/S0016508510017294

  27. Kawaguchi T, Yoshida T, Harada M, Hisamoto T, Nagao Y, Ide T, et al. Hepatitis C virus down-regulates insulin receptor substrates 1 and 2 through up-regulation of suppressor of cytokine signaling 3. The American journal of pathology. 2004 Nov;165(5):1499–508. http://www.ncbi.nlm.nih.gov/pubmed/15509521

  28. Pazienza V, Clément S, Pugnale P, Conzelman S, Foti M, Mangia A, et al. The hepatitis C virus core protein of genotypes 3a and 1b downregulates insulin receptor substrate 1 through genotype-specific mechanisms. Hepatology. 2007 May;45(5):1164–71. http://www.ncbi.nlm.nih.gov/pubmed/17465001

  29. Vanni E, Abate ML, Gentilcore E, Hickman I, Gambino R, Cassader M, et al. Sites and mechanisms of insulin resistance in nonobese, nondiabetic patients with chronic hepatitis C. Hepatology. 2009 Sep;50(3):697–706. http://www.ncbi.nlm.nih.gov/pubmed/19582803

  30. Taniguchi CM, Emanuelli B, Kahn CR. Critical nodes in signalling pathways: insights into insulin action. Nature reviews Molecular cell biology. 2006 Feb;7(2):85–96. http://www.ncbi.nlm.nih.gov/pubmed/16493415

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Faculty of Medicine, Cairo University, 41 Manial Street, Cairo, 11451, Egypt

    Ula Mabid Al-Jarhi, Sherif Mogawer, Noha M. T. El Dessouky & Maha Rakha

  2. Department of Chemical Pathology, Faculty of Medicine, Cairo University, 41 Manial Street, Cairo, 11451, Egypt

    Mona Mohsen

  3. Department of Biochemistry, Faculty of Medicine, Cairo University, 41 Manial Street, Cairo, 11451, Egypt

    Mai A. Gouda

Authors
  1. Ula Mabid Al-Jarhi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sherif Mogawer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mona Mohsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Noha M. T. El Dessouky
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mai A. Gouda
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Maha Rakha
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ula Mabid Al-Jarhi.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Ethical approval

Research protocols were approved by the medical ethics committee of Kasr Alainy Medical School, Cairo University. The ethical committee certificate reference number: I–030414.

Informed consent 

A written informed consent was obtained from all participants. In case patients were unable to provide consent, it was taken from designated surrogates.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Al-Jarhi, U.M., Mogawer, S., Mohsen, M. et al. Recipient IL28B genotype CT is a predictor of new onset diabetes mellitus in liver transplant patients with chronic hepatitis C. Int J Diabetes Dev Ctries 42, 757–764 (2022). https://doi.org/10.1007/s13410-021-01015-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13410-021-01015-6

Keywords

Search

Navigation