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Hepatitis C virus infection and development of type 2 diabetes mellitus: Systematic review and meta-analysis of the literature

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Abstract

Type 2 diabetes mellitus (T2DM) is an endocrine disorder encompassing multifactorial mechanisms, and chronic hepatitis C virus infection (CHC) is a multifaceted disorder, associated with extrahepatic manifestations, including endocrinological disorders. CHC and T2DM are associated, but the subject remains controversial. We performed a systematic review and meta-analysis evaluating such association, searching on PubMed until February 29, 2016. Inclusion criteria were: 1) presence of at least one internal control group age- and gender-matched (non-hepatopathic controls; and/or hepatopathic, not HCV-positive, controls); 2) sufficient data to calculate odds ratio and relative risk. Exclusion criteria were: 1) literature reviews on the topic; 2) publications regarding special populations [human immunodeficiency virus and human T-lymphotropic virus-1 coinfections, hepatocellular carcinoma (HCC), post-transplantation DM, gender selection]; 3) no clear differentiation among HCV patients with CHC, cirrhosis or HCC. Data from each study were independently extracted by two reviewers and cross-checked by AA. Our systematic review returned 544 records, and 33 were included in our meta-analysis. HCV infection is associated with an increased risk of T2DM independently from the severity of the associated liver disease, in CHC and cirrhotic HCV patients. As expected T2DM risk is higher in cirrhotic HCV patients, than CHC, and the prevalence of HCV infection in T2DM patients is higher than in non-diabetic controls. Regarding HBV infection prevalence, no difference exists in diabetic and non-diabetic subjects. An unequivocal CHC and T2DM association was shown. A proactive, integrated approach to HCV and T2DM therapies should maximize benefits of both diseases treatment.

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Abbreviations

CH:

Chronic hepatitis

CHC:

Chronic hepatitis C virus infection

DAA:

Direct-acting antiviral treatment

DM:

Diabetes mellitus

EHM:

Extra-hepatic manifestations

HCC:

Hepatocellular carcinoma

HBV:

Hepatitis B virus

HCV:

Hepatitis C virus

HIV:

Human immunodeficiency virus

HTLV:

Human T-lymphotropic virus

IR:

Insulin resistance

NIDDM:

Non-insulin dependent diabetes

OR:

Odds ratio

PTDM:

Post transplantation diabetes mellitus

RR:

Relative risk

SVR:

Sustained virological response

T2DM:

Type 2 diabetes mellitus

References

  1. Lauer GM, Walker BD. Hepatitis C virus infection. N Engl J Med. 2001;345(1):41–52. https://doi.org/10.1056/NEJM200107053450107.

    Article  CAS  Google Scholar 

  2. Zimmet P, Alberti KG, Shaw J. Global and societal implications of the diabetes epidemic. Nature. 2001;414(6865):782–7. https://doi.org/10.1038/414782a.

    Article  CAS  PubMed  Google Scholar 

  3. International Diabetes Federation Sixth Edition (2014). Available: http://www.idf.org/diabetesatlas.

  4. Ferrannini E, Mari A. β-cell function in type 2 diabetes. Metabolism. 2014;63(10):1217–27. https://doi.org/10.1016/j.metabol.2014.05.012.

    Article  CAS  PubMed  Google Scholar 

  5. Kahn SE, Cooper ME, Del Prato S. Pathophysiology and treatment of type 2 diabetes: Perspective on the past, present and future. Lancet. 2014;383(9922):1068–83. https://doi.org/10.1016/S0140-6736(13)62154-6.

    Article  CAS  PubMed  Google Scholar 

  6. East HE, Subauste JS, Gandhi A, Koch CA. About secondary causes of diabetes mellitus. J Miss State Med Assoc. 2012;53(11):380–3.

    PubMed  Google Scholar 

  7. Nati M, Haddad D, Birkenfeld AL, Koch CA, Chavakis T, Chatzigeorgiou A. The role of immune cells in metabolism-related liver inflammation and development of non-alcoholic steatohepatitis (NASH). Rev Endocr Metab Disord. 2016;17(1):29–39. https://doi.org/10.1007/s11154-016-9339-2.

    Article  CAS  PubMed  Google Scholar 

  8. Koch CA, Bornstein SR, Birkenfeld AL. Introduction to Hanefeld symposium: 40+ years of metabolic syndrome. Rev Endocr Metab Disord. 2016;17(1):1–4. https://doi.org/10.1007/s11154-016-9356-1.

    Article  PubMed  Google Scholar 

  9. Negro F, Forton D, Craxì A, Sulkowski MS, Feld JJ, Manns MP. Extrahepatic morbidity and mortality of chronic hepatitis C. Gastroenterology. 2015;149(6):1345–60. https://doi.org/10.1053/j.gastro.2015.08.035.

    Article  PubMed  Google Scholar 

  10. Fallahi P, Ferrari SM, Vita R, Benvenga S, Antonelli A. The role of human parvovirus B19 and hepatitis C virus in the development of thyroid disorders. Rev Endocr Metab Disord. 2016;17(4):529–35. https://doi.org/10.1007/s11154-016-9361-4.

    Article  CAS  PubMed  Google Scholar 

  11. Benvenga S, Guarneri F. Molecular mimicry and autoimmune thyroid disease. Rev Endocr Metab Disord. 2016;17(4):485–98. https://doi.org/10.1007/s11154-016-9363-2.

    Article  CAS  PubMed  Google Scholar 

  12. Alexander GJ. An association between hepatitis C virus infection and type 2 diabetes mellitus: What is the connection? Ann Intern Med. 2000;133(8):650–2. https://doi.org/10.7326/0003-4819-133-8-200010170-00018.

    Article  CAS  PubMed  Google Scholar 

  13. Mehta SH, Strathdee SA, Thomas DL. Association between hepatitis C virus infection and diabetes mellitus. Epidemiol Rev. 2001;23(2):302–12. https://doi.org/10.1093/oxfordjournals.epirev.a000808.

    Article  CAS  PubMed  Google Scholar 

  14. Mayo MJ. Extrahepatic manifestations of hepatitis C infection. Am J Med Sci. 2003;325(3):135–48. https://doi.org/10.1097/00000441-200303000-00006.

    Article  PubMed  Google Scholar 

  15. Lecube A, Hernández C, Genescà J, Simó R. Glucose abnormalities in patients with hepatitis C virus infection: Epidemiology and pathogenesis. Diabetes Care. 2006;29(5):1140–9. https://doi.org/10.2337/dc05-1995.

    Article  CAS  PubMed  Google Scholar 

  16. Noto H, Raskin P. Hepatitis C infection and diabetes. J Diabetes Complicat. 2006;20(2):113–20. https://doi.org/10.1016/j.jdiacomp.2006.01.001.

    Article  PubMed  Google Scholar 

  17. White DL, Ratziu V, El-Serag HB. Hepatitis C infection and risk of diabetes: A systematic review and meta-analysis. J Hepatol. 2008;49(5):831–44. https://doi.org/10.1016/j.jhep.2008.08.006.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Bernsmeier C, Heim MH. Insulin resistance in chronic hepatitis C: Mechanisms and clinical relevance. Swiss Med Wkly. 2009;139(47-48):678–84.

    CAS  PubMed  Google Scholar 

  19. Negro F, Alaei M. Hepatitis C virus and type 2 diabetes. World J Gastroenterol. 2009;15(13):1537–47. https://doi.org/10.3748/wjg.15.1537.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Naing C, Mak JW, Ahmed SI, Maung M. Relationship between hepatitis C virus infection and type 2 diabetes mellitus: Meta-analysis. World J Gastroenterol. 2012;18(14):1642–51. https://doi.org/10.3748/wjg.v18.i14.1642.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Ruhl CE, Menke A, Cowie CC, Everhart JE. Relationship of hepatitis C virus infection with diabetes in the U.S. population. Hepatology. 2014;60(4):1139–49. https://doi.org/10.1002/hep.27047.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Antonelli A, Ferrari SM, Giuggioli D, Di Domenicantonio A, Ruffilli I, Corrado A, et al. Hepatitis C virus infection and type 1 and type 2 diabetes mellitus. World J Diabetes. 2014;5(5):586–600. https://doi.org/10.4239/wjd.v5.i5.586.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Prummel MF, Laurberg P. Interferon-alpha and autoimmune thyroid disease. Thyroid. 2003;13(6):547–51. https://doi.org/10.1089/105072503322238809.

    Article  CAS  PubMed  Google Scholar 

  24. Antonelli A, Ferri C, Fallahi P, Ferrari SM, Ghinoi A, Rotondi M, et al. Thyroid disorders in chronic hepatitis C virus infection. Thyroid. 2006;16(6):563–72. https://doi.org/10.1089/thy.2006.16.563.

    Article  PubMed  Google Scholar 

  25. Ozyilkan E, Arslan M. Increased prevalence of diabetes mellitus in patients with chronic hepatitis C virus infection. Am J Gastroenterol. 1996;91(7):1480–1.

    CAS  PubMed  Google Scholar 

  26. Mangia A, Schiavone G, Lezzi G, Marmo R, Bruno F, Villani MR, et al. HCV and diabetes mellitus: Evidence for a negative association. Am J Gastroenterol. 1998;93(12):2363–7. https://doi.org/10.1111/j.1572-0241.1998.00688.x.

    Article  CAS  PubMed  Google Scholar 

  27. Knobler H, Schihmanter R, Zifroni A, Fenakel G, Schattner A. Increased risk of type 2 diabetes in noncirrhotic patients with chronic hepatitis C virus infection. Mayo Clin Proc. 2000;75(4):355–9. https://doi.org/10.4065/75.4.355.

    Article  CAS  PubMed  Google Scholar 

  28. Antonelli A, Ferri C, Fallahi P, Sebastiani M, Nesti C, Barani L, et al. Type 2 diabetes in hepatitis C-related mixed cryoglobulinaemia patients. Rheumatology (Oxford). 2004;43(2):238–40. https://doi.org/10.1093/rheumatology/keh011.

    Article  CAS  Google Scholar 

  29. Antonelli A, Ferri C, Fallahi P, Pampana A, Ferrari SM, Goglia F, et al. Hepatitis C virus infection: Evidence for an association with type 2 diabetes. Diabetes Care. 2005;28(10):2548–50. https://doi.org/10.2337/diacare.28.10.2548.

    Article  PubMed  Google Scholar 

  30. Grimbert S, Valensi P, Lévy-Marchal C, Perret G, Richardet JP, Raffoux C, et al. High prevalence of diabetes mellitus in patients with chronic hepatitis C. A case–control study. Gastroenterol Clin Biol. 1996;20(6-7):544–8.

    CAS  PubMed  Google Scholar 

  31. Caronia S, Taylor K, Pagliaro L, Carr C, Palazzo U, Petrik J, et al. Further evidence for an association between non-insulin-dependent diabetes mellitus and chronic hepatitis C virus infection. Hepatology. 1999;30(4):1059–63. https://doi.org/10.1002/hep.510300416.

    Article  CAS  PubMed  Google Scholar 

  32. Labropoulou-Karatza C, Goritsas C, Fragopanagou H, Repandi M, Matsouka P, Alexandrides T. High prevalence of diabetes mellitus among adult beta-thalassaemic patients with chronic hepatitis C. Eur J Gastroenterol Hepatol. 1999;11(9):1033–6. https://doi.org/10.1097/00042737-199909000-00014.

    Article  CAS  PubMed  Google Scholar 

  33. Mason AL, Lau JY, Hoang N, Qian K, Alexander GJ, Xu L, et al. Association of diabetes mellitus and chronic hepatitis C virus infection. Hepatology. 1999;29(2):328–33. https://doi.org/10.1002/hep.510290235.

    Article  CAS  PubMed  Google Scholar 

  34. Ryu JK, Lee SB, Hong SJ, Lee S. Association of chronic hepatitis C virus infection and diabetes mellitus in Korean patients. Korean J Intern Med. 2001;16(1):18–23. https://doi.org/10.3904/kjim.2001.16.1.18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Arao M, Murase K, Kusakabe A, Yoshioka K, Fukuzawa Y, Ishikawa T, et al. Prevalence of diabetes mellitus in Japanese patients infected chronically with hepatitis C virus. J Gastroenterol. 2003;38(4):355–60. https://doi.org/10.1007/s005350300063.

    Article  PubMed  Google Scholar 

  36. Lecube A, Hernández C, Genescà J, Esteban JI, Jardí R, Simó R. High prevalence of glucose abnormalities in patients with hepatitis C virus infection: A multivariate analysis considering the liver injury. Diabetes Care. 2004;27(5):1171–5. https://doi.org/10.2337/diacare.27.5.1171.

    Article  CAS  PubMed  Google Scholar 

  37. Imazeki F, Yokosuka O, Fukai K, Kanda T, Kojima H, Saisho H. Prevalence of diabetes mellitus and insulin resistance in patients with chronic hepatitis C: Comparison with hepatitis B virus-infected and hepatitis C virus-cleared patients. Liver Int. 2008;28(3):355–62. https://doi.org/10.1111/j.1478-3231.2007.01630.x.

    Article  CAS  PubMed  Google Scholar 

  38. Rouabhia S, Malek R, Bounecer H, Dekaken A, Bendali Amor F, Sadelaoud M, et al. Prevalence of type 2 diabetes in Algerian patients with hepatitis C virus infection. World J Gastroenterol. 2010;16(27):3427–31. https://doi.org/10.3748/wjg.v16.i27.3427.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Allison ME, Wreghitt T, Palmer CR, Alexander GJ. Evidence for a link between hepatitis C virus infection and diabetes mellitus in a cirrhotic population. J Hepatol. 1994;21(6):1135–9. https://doi.org/10.1016/S0168-8278(05)80631-2.

    Article  CAS  PubMed  Google Scholar 

  40. Guerreo Igea FJ, Garrido Serrano A, Lepe Jiménez JA, Palomo Gil S. High prevalence of diabetes mellitus in patients with chronic hepatitis C virus infection. Med Clin (Barc). 1998;111(17):676–7.

    CAS  Google Scholar 

  41. Bigam DL, Pennington JJ, Carpentier A, Wanless IR, Hemming AW, Croxford R, et al. Hepatitis C-related cirrhosis: A predictor of diabetes after liver transplantation. Hepatology. 2000;32(1):87–90. https://doi.org/10.1053/jhep.2000.8270.

    Article  CAS  PubMed  Google Scholar 

  42. Zein NN, Abdulkarim AS, Wiesner RH, Egan KS, Persing DH. Prevalence of diabetes mellitus in patients with end-stage liver cirrhosis due to hepatitis C, alcohol, or cholestatic disease. J Hepatol. 2000;32(2):209–17. https://doi.org/10.1016/S0168-8278(00)80065-3.

    Article  CAS  PubMed  Google Scholar 

  43. Baid S, Cosimi AB, Farrel ML, Schoenfeld DA, Feng S, Chung RT, et al. Posttransplant diabetes mellitus in liver transplant recipients: Risk factors, temporal relationship with hepatitis C virus allograft hepatitis, and impact on mortality. Transplantation. 2001;72(6):1066–72. https://doi.org/10.1097/00007890-200109270-00015.

    Article  CAS  PubMed  Google Scholar 

  44. Garrido Serrano A, Guerrero Igea FJ, Lepe Jiménez JA, Palomo Gil S, Grilo Reina A. Hyperinsulinemia in cirrhotic patients infected with hepatitis C virus. Gastroenterol Hepatol. 2001;24(3):127–31. https://doi.org/10.1016/S0210-5705(01)70138-0.

    Article  CAS  PubMed  Google Scholar 

  45. Thuluvath PJ, John PR. Association between hepatitis C, diabetes mellitus, and race. A case-control study. Am J Gastroenterol. 2003;98(2):438–41. https://doi.org/10.1111/j.1572-0241.2003.07256.x.

    Article  PubMed  Google Scholar 

  46. Parolin MB, Zaina FE, Araújo MV, Kupka E, Coelho JC. Prevalence of new-onset diabetes mellitus in Brazilian liver transplant recipients: Association with HCV infection. Transplant Proc. 2004;36(9):2776–7. https://doi.org/10.1016/j.transproceed.2004.10.029.

    Article  CAS  PubMed  Google Scholar 

  47. Simó R, Hernández C, Genescà J, Jardí R, Mesa J. High prevalence of hepatitis C virus infection in diabetic patients. Diabetes Care. 1996;19(9):998–1000. https://doi.org/10.2337/diacare.19.9.998.

    Article  PubMed  Google Scholar 

  48. Rudoni S, Petit JM, Bour JB, Aho LS, Castaneda A, Vaillant G, et al. HCV infection and diabetes mellitus: Influence of the use of finger stick devices on nosocomial transmission. Diabetes Metab. 1999;25(6):502–5.

    CAS  PubMed  Google Scholar 

  49. Chen HF, Li CY, Chen P, See TT, Lee HY. Seroprevalence of hepatitis B and C in type 2 diabetic patients. J Chin Med Assoc. 2006;69(4):146–52. https://doi.org/10.1016/S1726-4901(09)70195-9.

    Article  PubMed  Google Scholar 

  50. Ocak S, Duran N, Kaya H, Emir I. Seroprevalence of hepatitis C in patients with type 2 diabetes mellitus and non-diabetic on haemodialysis. Int J Clin Pract. 2006;60(6):670–4. https://doi.org/10.1111/j.1368-5031.2006.00738.x.

    Article  CAS  PubMed  Google Scholar 

  51. Gulcan A, Gulcan E, Toker A, Bulut I, Akcan Y. Evaluation of risk factors and seroprevalence of hepatitis B and C in diabetic patients in Kutahya, Turkey. J Investig Med. 2008;56(6):858–63. https://doi.org/10.2310/JIM.0b013e3181788d28.

    Article  PubMed  Google Scholar 

  52. Nwokediuko SC, Oli JM, Hepatitis C. Virus infection in Nigerians with diabetes mellitus. Niger J Clin Pract. 2008;11(2):94–9.

    CAS  PubMed  Google Scholar 

  53. Sjöberg K, Widell A, Verbaan H. Prevalence of hepatitis C in Swedish diabetics is low and comparable to that in health care workers. Eur J Gastroenterol Hepatol. 2008;20(2):135–8. https://doi.org/10.1097/MEG.0b013e3282f476f5.

    Article  PubMed  Google Scholar 

  54. Kaabia N, Ben Jazia E, Slim I, Fodha I, Hachfi W, Gaha R, et al. Association of hepatitis C virus infection and diabetes in central Tunisia. World J Gastroenterol. 2009;15(22):2778–81. https://doi.org/10.3748/wjg.15.2778.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Jadoon NA, Shahzad MA, Yaqoob R, Hussain M. Ali N Seroprevalence of hepatitis C in type 2 diabetes: Evidence for a positive association. Virol J. 2010;7(1):304. https://doi.org/10.1186/1743-422X-7-304.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Chehadeh W, Kurien SS, Abdella N, Ben-Nakhi A, Al-Arouj M, Almuaili T, et al. Hepatitis C virus infection in a population with high incidence of type 2 diabetes: Impact on diabetes complications. J Infect Public Health. 2011;4(4):200–6. https://doi.org/10.1016/j.jiph.2011.05.004.

    Article  PubMed  Google Scholar 

  57. Korkmaz H, Kesli R, Onder Pamuk B, Ipekci SH, Terzi Y, Kebapcilar L. Assessment of evidence for positive association and seroprevalence of hepatitis B and C in diabetic patients in a developing country. J Investig Med. 2015;63(2):251–7. https://doi.org/10.1097/JIM.0000000000000126.

    Article  CAS  PubMed  Google Scholar 

  58. Younossi ZM, McCullough AJ. Metabolic syndrome, non-alcoholic fatty liver disease and hepatitis C virus: Impact on disease progression and treatment response. Liver Int. 2009;29:3–12. https://doi.org/10.1111/j.1478-3231.2008.01949.x.

    Article  PubMed  Google Scholar 

  59. Negro F. Facts and fictions of HCV and comorbidities: Steatosis, diabetes mellitus, and cardiovascular diseases. J Hepatol. 2014;61(Suppl 1):S69–78. https://doi.org/10.1016/j.jhep.2014.08.003.

    Article  PubMed  Google Scholar 

  60. Guo X, Jin M, Yang M, Liu K, Li JW. Type 2 diabetes mellitus and the risk of hepatitis C virus infection: A systematic review. Sci Rep. 2013;3(1):2981. https://doi.org/10.1038/srep02981.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. García-Compeán D, González-González JA, Lavalle-González FJ, González-Moreno EI, Villarreal-Pérez JZ, Maldonado-Garza HJ. Current concepts in diabetes mellitus and chronic liver disease: Clinical outcomes, hepatitis C virus association, and therapy. Dig Dis Sci. 2016;61(2):371–8. https://doi.org/10.1007/s10620-015-3907-2.

    Article  CAS  PubMed  Google Scholar 

  62. Fabrizi F, Lampertico P, Lunghi G, Mangano S, Aucella F, Martin P. Review article: Hepatitis C virus infection and type-2 diabetes mellitus in renal diseases and transplantation. Aliment Pharmacol Ther. 2005;21(6):623–32. https://doi.org/10.1111/j.1365-2036.2005.02389.x.

    Article  CAS  PubMed  Google Scholar 

  63. Knobler H, Stagnaro-Green A, Wallenstein S, Schwartz M, Roman SH. Higher incidence of diabetes in liver transplant recipients with hepatitis C. J Clin Gastroenterol. 1998;26(1):30–3. https://doi.org/10.1097/00004836-199801000-00009.

    Article  CAS  PubMed  Google Scholar 

  64. Boschi-Pinto C, Stuver S, Okayama A, Trichopoulos D, Orav EJ, Tsubouchi H, et al. A follow-up study of morbidity and mortality associated with hepatitis C virus infection and its interaction with human T lymphotropic virus type I in Miyazaki, Japan. J Infect Dis. 2000;181(1):35–41. https://doi.org/10.1086/315177.

    Article  CAS  PubMed  Google Scholar 

  65. Howard AA, Klein RS, Schoenbaum EE. Association of hepatitis C infection and antiretroviral use with diabetes mellitus in drug users. Clin Infect Dis. 2003;36(10):1318–23. https://doi.org/10.1086/374838.

    Article  PubMed  Google Scholar 

  66. Butt AA, Fultz SL, Kwoh CK, Kelley D, Skanderson M, Justice AC. Risk of diabetes in HIV infected veterans pre- and post-HAART and the role of HCV coinfection. Hepatology. 2004;40(1):115–9. https://doi.org/10.1002/hep.20289.

    Article  PubMed  Google Scholar 

  67. Delgado-Borrego A, Casson D, Schoenfeld D, Somsouk M, Terella A, Jordan SH, et al. Hepatitis C virus is independently associated with increased insulin resistance after liver transplantation. Transplantation. 2004;77(5):703–10. https://doi.org/10.1097/01.TP.0000114283.04840.3A.

    Article  PubMed  Google Scholar 

  68. Wilson C, Hepatitis C. Infection and type 2 diabetes in American-Indian women. Diabetes Care. 2004;27(9):2116–9. https://doi.org/10.2337/diacare.27.9.2116.

    Article  PubMed  Google Scholar 

  69. Brar I, Shuter J, Thomas A, Daniels E, Absalon J. Minorities and Women's task force of Terry Beirn community programs for clinical research on AIDS. A comparison of factors associated with prevalent diabetes mellitus among HIV-infected antiretroviral-naive individuals versus individuals in the National Health and nutritional examination survey cohort. J Acquir Immune Defic Syndr. 2007;45(1):66–71. https://doi.org/10.1097/QAI.0b013e318031d7e3.

    Article  PubMed  Google Scholar 

  70. Jain MK, Aragaki C, Fischbach L, Gibson S, Arora R, May L, et al. Hepatitis C is associated with type 2 diabetes mellitus in HIV-infected persons without traditional risk factors. HIV Med. 2007;8(8):491–7. https://doi.org/10.1111/j.1468-1293.2007.00499.x.

    Article  CAS  PubMed  Google Scholar 

  71. Ledergerber B, Furrer H, Rickenbach M, Lehmann R, Elzi L, Hirschel B, et al. Factors associated with the incidence of type 2 diabetes mellitus in HIV-infected participants in the Swiss HIV cohort study. Clin Infect Dis. 2007;45(1):111–9. https://doi.org/10.1086/518619.

    Article  PubMed  Google Scholar 

  72. Stapleton JT, Bennett K, Bosch RJ, Polgreen PM, Swindells S. Effect of antiretroviral therapy and hepatitis c co-infection on changes in lipid levels in HIV-infected patients 48 weeks after initiation of therapy. HIV Clin Trials. 2007;8(6):429–36. https://doi.org/10.1310/hct0806-429.

    Article  CAS  PubMed  Google Scholar 

  73. Taura N, Ichikawa T, Miyaaki H, Yatsuhashi H, Ishibashi H, Nakao K. Prevalence of type 2 diabetes mellitus in Japanese patients with hepatocellular carcinoma. Exp Ther Med. 2011;2(1):81–4. https://doi.org/10.3892/etm.2010.167.

    Article  PubMed  Google Scholar 

  74. Visnegarwala F, Chen L, Raghavan S, Tedaldi E. Prevalence of diabetes mellitus and dyslipidemia among antiretroviral naive patients co-infected with hepatitis C virus (HCV) and HIV-1 compared to patients without co-infection. J Inf Secur. 2005;50:331–7.

    Google Scholar 

  75. Younossi Z, Stepanova M, Saab S, Trimble G, Mishra A, Henry L. The association of hepatitis C virus infection and post-liver transplant diabetes: Data from 17 000 HCV-infected transplant recipients. Aliment Pharmacol Ther. 2015;41(2):209–17. https://doi.org/10.1111/apt.13027.

    Article  CAS  PubMed  Google Scholar 

  76. El-Zayadi AR, Selim OE, Hamdy H, Dabbous H, Ahdy A, Moniem SA. Association of chronic hepatitis C infection and diabetes mellitus. Trop Gastroenterol. 1998;19:141–4.

    CAS  PubMed  Google Scholar 

  77. AlDosary AA, Ramji AS, Elliott TG, Sirrs SM, Thompson DM, Erb SR, et al. Post-liver transplantation diabetes mellitus: An association with hepatitis C. Liver transp. 2002;8:356–61.

    Article  Google Scholar 

  78. Yildiz A, Tutuncu Y, Yazici H, Akkaya V, Kayakan SM, Sever MS, et al. Association between hepatitis C virus infection and development of post-transplantation diabetes mellitus in renal transplant recipients. Transplantation. 2002;74(8):1109–13. https://doi.org/10.1097/00007890-200210270-00009.

    Article  PubMed  Google Scholar 

  79. Huang JF, Dai CY, Hwang SJ, Ho CK, Hsiao PJ, Hsieh MY, et al. Hepatitis C viremia increases the association with type 2 diabetes mellitus in a hepatitis B and C endemic area: An epidemiological link with virological implication. Am J Gastroenterol. 2007;102(6):1237–43. https://doi.org/10.1111/j.1572-0241.2007.01181.x.

    Article  PubMed  Google Scholar 

  80. Wang CS, Wang ST, Yao WJ, Chang TT, Chou P, Hepatitis C. Virus infection and the development of type 2 diabetes in a community-based longitudinal study. Am J Epidemiol. 2007;166(2):196–203. https://doi.org/10.1093/aje/kwm061.

    Article  PubMed  Google Scholar 

  81. Schnier C, Wild S, Kurdi Z, Povey C, Goldberg DJ, Hutchinson SJ. Matched population-based study examining the risk of type 2 diabetes in people with and without diagnosed hepatitis C virus infection. J Viral Hepat. 2016;23(8):596–605. https://doi.org/10.1111/jvh.12520.

    Article  CAS  PubMed  Google Scholar 

  82. Brischetto R, Corno C, Amore MG, Leotta S, Pavone S, Bonsignore L, et al. Prevalence and significance of type-2 diabetes mellitus in chronic liver disease, correlated with hepatitis C virus. Ann Ital Med Int. 2003;18(1):31–6.

    PubMed  Google Scholar 

  83. Montenegro L, De Michina A, Misciagna G, Guerra V, Di Leo A. Virus C hepatitis and Type 2 diabetes: A cohort study in southern Italy. Am J Gastroenterol. 2013;108(7):1108–11. https://doi.org/10.1038/ajg.2013.90.

    Article  CAS  PubMed  Google Scholar 

  84. Amarapurkar DN, Patel ND. Increased prevalence of type II diabetes mellitus in hepatitis C virus infection in western India. Trop Gastroenterol. 2008;29(3):148–52.

    PubMed  Google Scholar 

  85. Elhawary EI, Mahmoud GF, El-Daly MA, Mekky FA, Esmat GG, Abdel-Hamid M. Association of HCV with diabetes mellitus: An Egyptian case-control study. Virol J. 2011;8(1):367. https://doi.org/10.1186/1743-422X-8-367.

    Article  PubMed  PubMed Central  Google Scholar 

  86. Ratziu V, Heurtier A, Bonyhay L, Poynard T, Giral P. Review article: An unexpected virus-host interaction--the hepatitis C virus-diabetes link. Aliment Pharmacol Ther. 2005;22(suppl 2):56–60. https://doi.org/10.1111/j.1365-2036.2005.02598.x.

    Article  PubMed  Google Scholar 

  87. Masini M, Campani D, Boggi U, Menicagli M, Funel N, Pollera M, et al. Hepatitis C virus infection and human pancreatic beta-cell dysfunction. Diabetes Care. 2005;28(4):940–1. https://doi.org/10.2337/diacare.28.4.940.

    Article  PubMed  Google Scholar 

  88. Fallahi P, Ferri C, Ferrari SM, Corrado A, Sansonno D, Antonelli A. Cytokines and HCV-related disorders. Clin Dev Immunol. 2012;2012:468107.

    Article  Google Scholar 

  89. Kita Y, Mizukoshi E, Takamura T, Sakurai M, Takata Y, Arai K, et al. Impact of diabetes mellitus on prognosis of patients infected with hepatitis C virus. Metabolism. 2007;56(12):1682–8. https://doi.org/10.1016/j.metabol.2007.07.011.

    Article  CAS  PubMed  Google Scholar 

  90. Wang CS, Yao WJ, Chang TT, Wang ST, Chou P. The impact of type 2 diabetes on the development of hepatocellular carcinoma in different viral hepatitis statuses. Cancer Epidemiol Biomark Prev. 2009;18(7):2054–60. https://doi.org/10.1158/1055-9965.EPI-08-1131.

    Article  CAS  Google Scholar 

  91. Alter MJ, Margolis HS, Krawczynski K, Judson FN, Mares A, Alexander WJ, et al. The natural history of community-acquired hepatitis C in the United States. The sentinel counties chronic non-a, non-B hepatitis study team. N Engl J Med. 1992;327(27):1899–905. https://doi.org/10.1056/NEJM199212313272702.

    Article  CAS  PubMed  Google Scholar 

  92. Colombo M, Kuo G, Choo QL, Donato MF, Del Ninno E, Tommasini MA, et al. Prevalence of antibodies to hepatitis C virus in Italian patients with hepatocellular carcinoma. Lancet. 1989;2(8670):1006–8.

    Article  CAS  Google Scholar 

  93. Tsukuma H, Hiyama T, Tanaka S, Nakao M, Yabuuchi T, Kitamura T, et al. Risk factors for hepatocellular carcinoma among patients with chronic liver disease. N Engl J Med. 1993;328(25):1797–801. https://doi.org/10.1056/NEJM199306243282501.

    Article  CAS  PubMed  Google Scholar 

  94. El-Serag HB, Tran T, Everhart JE. Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma. Gastroenterology. 2004;126(2):460–8. https://doi.org/10.1053/j.gastro.2003.10.065.

    Article  PubMed  Google Scholar 

  95. Gao C, Yao SK. Diabetes mellitus: A “true” independent risk factor for hepatocellular carcinoma? Hepatobiliary Pancreat Dis Int. 2009;8(5):465–73.

    PubMed  Google Scholar 

  96. Elgouhari HM, Zein CO, Hanouneh I, Feldstein AE, Zein NN. Diabetes mellitus is associated with impaired response to antiviral therapy in chronic hepatitis C infection. Dig Dis Sci. 2009;54(12):2699–705. https://doi.org/10.1007/s10620-008-0683-2.

    Article  PubMed  Google Scholar 

  97. Nasrollah L, Backstedt DW, Pedersen MR, Choi M, Seetharam AB. Tu1022 Diabetes and Hyperlipidemia Compromise Practical Effectiveness of Direct Acting Antiviral HCV Therapy in Minority Populations. Gastroenterology. 2015;148 Suppl 1:S–1087.

  98. Knobler H, Malnick S. Hepatitis C and insulin action: An intimate relationship. World J Hepatol. 2016;8(2):131–8. https://doi.org/10.4254/wjh.v8.i2.131.

    Article  PubMed  PubMed Central  Google Scholar 

  99. Premji R, Roopnarinesingh N, Qazi N, Nylen ES. New-onset diabetes mellitus with exposure to Ledipasvir and Sofosbuvir. J Investig Med High Impact Case Rep. 2015;3:2324709615623300.

    PubMed  PubMed Central  Google Scholar 

  100. Pattullo V, Heathcote J. Hepatitis C and diabetes: One treatment for two diseases? Liver Int. 2010;30(3):356–64. https://doi.org/10.1111/j.1478-3231.2009.02185.x.

    Article  CAS  PubMed  Google Scholar 

  101. Milner KL, Jenkins AB, Trenell M, Tid-Ang J, Samocha-Bonet D, Weltman M, et al. Eradicating hepatitis C virus ameliorates insulin resistance without change in adipose depots. J Viral Hepat. 2014;21(5):325–32. https://doi.org/10.1111/jvh.12143.

    Article  CAS  PubMed  Google Scholar 

  102. Kawaguchi T, Ide T, Taniguchi E, Hirano E, Itou M, Sumie S, et al. Clearance of HCV improves insulin resistance, beta-cell function, and hepatic expression of insulin receptor substrate 1 and 2. Am J Gastroenterol. 2007;102(3):570–6. https://doi.org/10.1111/j.1572-0241.2006.01038.x.

    Article  PubMed  Google Scholar 

  103. Tallón de Lara P, Himschoot T, Frossard JL, Negro F. Does telaprevir possess a direct antidiabetic effect? Liver Int. 2014;34(6):967–9. https://doi.org/10.1111/liv.12440.

    Article  CAS  PubMed  Google Scholar 

  104. Vanni E, Bugianesi E, Saracco G. Treatment of type 2 diabetes mellitus by viral eradication in chronic hepatitis C: Myth or reality? Dig Liver Dis. 2016;48(2):105–11. https://doi.org/10.1016/j.dld.2015.10.016.

    Article  CAS  PubMed  Google Scholar 

  105. Younossi Z, Park H, Henry L, Adeyemi A, Stepanova M. Extrahepatic manifestations of hepatitis C: A meta-analysis of prevalence, quality of life, and economic burden. Gastroenterology. 2016;150(7):1599–608. https://doi.org/10.1053/j.gastro.2016.02.039.

    Article  PubMed  Google Scholar 

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Fabiani, S., Fallahi, P., Ferrari, S.M. et al. Hepatitis C virus infection and development of type 2 diabetes mellitus: Systematic review and meta-analysis of the literature. Rev Endocr Metab Disord 19, 405–420 (2018). https://doi.org/10.1007/s11154-017-9440-1

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