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Acta Diabetologica

, Volume 48, Issue 4, pp 337–343 | Cite as

HBV and HCV infection in type 2 diabetes mellitus: a survey in three diabetes units in different Italian areas

  • Valentina Soverini
  • Marcello Persico
  • Elisabetta Bugianesi
  • Gabriele Forlani
  • Federico Salamone
  • Mario Massarone
  • Vincenzo La Mura
  • Arianna Mazzotti
  • Alberto Bruno
  • Giulio MarchesiniEmail author
Original Article

Abstract

Viral infections and the metabolic syndrome may coexist in several individuals, due to the large prevalence of obesity and type 2 diabetes mellitus (T2DM). Antiviral therapy has changed the natural history of chronic viral hepatitis, but viral infection may remain undiagnosed in the absence of systematic screening. We determined the prevalence of HBV and/or HCV infection in an Italian cohort with T2DM (859 consecutive patients, 413 females) in three Italian centers: Turin, Bologna, and Naples. Screening for viral disease was coupled with the determination of parameters of metabolic syndrome. Fourteen patients were HBsAg-positive, 51 anti-HCV with a prevalence of genotype-1 infection in 58% of cases. Thirty cases had newly diagnosed viral markers, only one-third had already-diagnosed liver disease, 16 were being followed-up by a Liver Unit, and 9 cases had received antiviral treatment. Patients with viral markers had higher liver enzyme levels in comparison with virus-negative patients (P < 0.0001), whereas the prevalence of the metabolic syndrome was similar in the 2 groups. A positive correlation between BMI and alanine aminostransferase levels was only present in virus-negative cases, where the probability of enzyme levels above the upper limit of normal increased by 5% for unit of increase in BMI (OR: 1.05; 95% CI: 1.003–1.100, P = 0.037). In conclusion, the prevalence of HBV and HCV is non-negligible in patients with T2DM, but these cases may long remain undiagnosed. Elevated liver enzymes might be frequently disregarded in diabetes Units and ascribed to metabolic syndrome, thus excluding T2DM patients from specific disease-modifying antiviral treatment for hepatitis.

Keywords

Type 2 diabetes Viral infections Metabolic syndrome Liver enzymes Epidemiology 

Notes

Acknowledgments

Supported by a grant from Schering-Plough, Milan, Italy.

References

  1. 1.
    Afdhal NH (2004) The natural history of hepatitis C. Semin Liver Dis 24(2):3–8PubMedCrossRefGoogle Scholar
  2. 2.
    Jadoon NA, Shahzad MA, Yaqoob R, Hussain M, Ali N (2010) Seroprevalence of hepatitis C in type 2 diabetes: evidence for a positive association. Virol J 7:304PubMedCrossRefGoogle Scholar
  3. 3.
    Chen HF, Li CY, Chen P, See TT, Lee HY (2006) Seroprevalence of hepatitis B and C in type 2 diabetic patients. J Chin Med Assoc 69:146–152PubMedCrossRefGoogle Scholar
  4. 4.
    Kaabia N, Ben Jazia E, Slim I, Fodha I, Hachfi W, Gaha R, Khalifa M, Hadj Kilani A, Trabelsi H, Abdelaziz A, Bahri F, Letaief A (2009) Association of hepatitis C virus infection and diabetes in central Tunisia. World J Gastroenterol 15:2778–2781PubMedCrossRefGoogle Scholar
  5. 5.
    Alberti A, Vario A, Ferrari A, Pistis R (2005) Review article: chronic hepatitis C–natural history and cofactors. Aliment Pharmacol Ther 22(Suppl 2):74–78PubMedCrossRefGoogle Scholar
  6. 6.
    Hui JM, Sud A, Farrell GC, Bandara P, Byth K, Kench JG, McCaughan GW, George J (2003) Insulin resistance is associated with chronic hepatitis C virus infection and fibrosis progression [corrected]. Gastroenterology 125:1695–1704PubMedCrossRefGoogle Scholar
  7. 7.
    Leandro G, Mangia A, Hui J, Fabris P, Rubbia-Brandt L, Colloredo G, Adinolfi LE, Asselah T, Jonsson JR, Smedile A, Terrault N, Pazienza V, Giordani MT, Giostra E, Sonzogni A, Ruggiero G, Marcellin P, Powell EE, George J, Negro F, The HCV MAID Study Group (2006) Relationship between steatosis, inflammation, and fibrosis in chronic hepatitis C: a meta-analysis of individual patient data. Gastroenterology 130:1346–1362CrossRefGoogle Scholar
  8. 8.
    Aytug S, Reich D, Sapiro LE, Bernstein D, Begum N (2003) Impaired IRS-1/PI3-kinase signaling in patients with HCV: a mechanism for increased prevalence of type 2 diabetes. Hepatology 38:1384–1392PubMedGoogle Scholar
  9. 9.
    Shintani Y, Fujie H, Miyoshi H, Tsutsumi T, Tsukamoto K, Kimura S, Moriya K, Koike K (2004) Hepatitis C virus infection and diabetes: direct involvement of the virus in the development of insulin resistance. Gastroenterology 126:840–848PubMedCrossRefGoogle Scholar
  10. 10.
    Bugianesi E, McCullough AJ, Marchesini G (2005) Insulin resistance: a metabolic pathway to chronic liver disease. Hepatology 42:987–1000PubMedCrossRefGoogle Scholar
  11. 11.
    Vanni E, Abate ML, Gentilcore E, Hickman I, Gambino R, Cassader M, Smedile A, Ferrannini E, Rizzetto M, Marchesini G, Gastaldelli A, Bugianesi E (2009) Sites and mechanisms of insulin resistance in nonobese, nondiabetic patients with chronic hepatitis C. Hepatology 50:697–706PubMedCrossRefGoogle Scholar
  12. 12.
    Kawaguchi T, Yoshida T, Harada M, Hisamoto T, Nagao Y, Ide T, Taniguchi E, Kumemura H, Hanada S, Maeyama M, Baba S, Koga H, Kumashiro R, Ueno T, Ogata H, Yoshimura A, Sata M (2004) Hepatitis C virus down-regulates insulin receptor substrates 1 and 2 through up-regulation of suppressor of cytokine signaling 3. Am J Pathol 165:1499–1508PubMedCrossRefGoogle Scholar
  13. 13.
    Kawaguchi T, Ide T, Taniguchi E, Hirano E, Itou M, Sumie S, Nagao Y, Yanagimoto C, Hanada S, Koga H, Sata M (2007) Clearance of HCV improves insulin resistance, beta-cell function, and hepatic expression of insulin receptor substrate 1 and 2. Am J Gastroenterol 102:570–576PubMedCrossRefGoogle Scholar
  14. 14.
    Persico M, Capasso M, Persico E, Svelto M, Russo R, Spano D, Croce L, La Mura V, Moschella F, Masutti F, Torella R, Tiribelli C, Iolascon A (2007) Suppressor of cytokine signaling 3 (SOCS3) expression and hepatitis C virus-related chronic hepatitis: insulin resistance and response to antiviral therapy. Hepatology 46:1009–1015PubMedCrossRefGoogle Scholar
  15. 15.
    Persico M, Russo R, Persico E, Svelto M, Spano D, Andolfo I, La Mura V, Capasso M, Tiribelli C, Torella R, Iolascon A (2009) SOCS3 and IRS-1 gene expression differs between genotype 1 and genotype 2 hepatitis C virus-infected HepG2 cells. Clin Chem Lab Med 47:1217–1225PubMedCrossRefGoogle Scholar
  16. 16.
    Hsu CS, Liu CJ, Liu CH, Wang CC, Chen CL, Lai MY, Chen PJ, Kao JH, Chen DS (2008) High hepatitis C viral load is associated with insulin resistance in patients with chronic hepatitis C. Liver Int 28:271–277PubMedCrossRefGoogle Scholar
  17. 17.
    Harrison SA (2006) Correlation between insulin resistance and hepatitis C viral load. Hepatology 43:1168–1169 Author replyPubMedCrossRefGoogle Scholar
  18. 18.
    Yoneda M, Saito S, Ikeda T, Fujita K, Mawatari H, Kirikoshi H, Inamori M, Nozaki Y, Akiyama T, Takahashi H, Abe Y, Kubota K, Iwasaki T, Terauchi Y, Togo S, Nakajima A (2007) Hepatitis C virus directly associates with insulin resistance independent of the visceral fat area in nonobese and nondiabetic patients. J Viral Hepat 14:600–607PubMedCrossRefGoogle Scholar
  19. 19.
    Browning JD, Horton JD (2004) Molecular mediators of hepatic steatosis and liver injury. J Clin Invest 114:147–152PubMedGoogle Scholar
  20. 20.
    Sanyal AJ, Chand N, Comar K, Mishahi F (2004) Hyperinsulinaemia blocks the inhibition of hepatitis C virus (HCV) replication by interferon: a potential mechanism for failure of interferon therapy in subjects with HCV and non-alcoholic fatty liver disease. Hepatology 40:179ACrossRefGoogle Scholar
  21. 21.
    Romero-Gomez M, Fernandez-Rodriguez CM, Andrade RJ, Diago M, Alonso S, Planas R, Sola R, Pons JA, Salmeron J, Barcena R, Perez R, Carmona I, Duran S (2008) Effect of sustained virological response to treatment on the incidence of abnormal glucose values in chronic hepatitis C. J Hepatol 48:721–727PubMedCrossRefGoogle Scholar
  22. 22.
    Arase Y, Suzuki F, Suzuki Y, Akuta N, Kobayashi M, Kawamura Y, Yatsuji H, Sezaki H, Hosaka T, Hirakawa M, Ikeda K, Kumada H (2009) Sustained virological response reduces incidence of onset of type 2 diabetes in chronic hepatitis C. Hepatology 49:739–744PubMedCrossRefGoogle Scholar
  23. 23.
    Giordanino C, Bugianesi E, Smedile A, Ciancio A, Abate ML, Olivero A, Pellicano R, Cassader M, Gambino R, Bo S, Ciccone G, Rizzetto M, Saracco G (2008) Incidence of type 2 diabetes mellitus and glucose abnormalities in patients with chronic hepatitis C infection by response to treatment: results of a cohort study. Am J Gastroenterol 103:2481–2487PubMedCrossRefGoogle Scholar
  24. 24.
    Mason AL, Lau JY, Hoang N, Qian K, Alexander GJ, Xu L, Guo L, Jacob S, Regenstein FG, Zimmerman R, Everhart JE, Wasserfall C, Maclaren NK, Perrillo RP (1999) Association of diabetes mellitus and chronic hepatitis C virus infection. Hepatology 29:328–333PubMedCrossRefGoogle Scholar
  25. 25.
    Sangiorgio L, Attardo T, Gangemi R, Rubino C, Barone M, Lunetta M (2000) Increased frequency of HCV and HBV infection in type 2 diabetic patients. Diabetes Res Clin Pract 48:147–151PubMedCrossRefGoogle Scholar
  26. 26.
    Picerno I, Di Pietro A, Spataro P, Di Benedetto A, Romano G, Scoglio ME (2002) Is diabetes mellitus a risk factor for HCV infection? Ann Ig 14:473–477PubMedGoogle Scholar
  27. 27.
    Balogun WO, Adeleye JO, Akinlade KS, Kuti M, Otegbayo JA (2006) Low prevalence of hepatitis-C viral seropositivity among patients with type-2 diabetes mellitus in a tertiary hospital. J Natl Med Assoc 98:1805–1808PubMedGoogle Scholar
  28. 28.
    Gulcan A, Gulcan E, Toker A, Bulut I, Akcan Y (2008) Evaluation of risk factors and seroprevalence of hepatitis B and C in diabetic patients in Kutahya, Turkey. J Investig Med 56:858–863PubMedGoogle Scholar
  29. 29.
    Forlani G, Di Bonito P, Mannucci E, Capaldo B, Genovese S, Orrasch M, Scaldaferri L, Di Bartolo P, Melandri P, Dei Cas A, Zavaroni I, Marchesini G (2008) Prevalence of elevated liver enzymes in Type 2 diabetes mellitus and its association with the metabolic syndrome. J Endocrinol Invest 31:146–152PubMedGoogle Scholar
  30. 30.
    Simo R, Hernandez C, Genesca J, Jardi R, Mesa J (1996) High prevalence of hepatitis C virus infection in diabetic patients. Diabetes Care 19:998–1000PubMedCrossRefGoogle Scholar
  31. 31.
    Cadranel JF, Di Martino V, Lambrey G, Mourlhon C, Nalet B, Anciaux ML, Richard C, Bigue JP, Barjon JN, Bories C, Barbare JC, Halimi C, Ribiere O, Eugene C, Pauwels A, Jeanne S, Donato L, Dumouchel P, Pariente A, Duverlie G, Devergie B, Arlot S, Capron D (2008) Prevalence of hepatitis C infection and risk factors in hospitalized diabetic patients: results of a cross-sectional study. Eur J Gastroenterol Hepatol 20:829–836PubMedCrossRefGoogle Scholar
  32. 32.
    Spada E, Mele A, Ciccozzi M, Tosti ME, Bianco E, Szklo A, Ragni P, Gallo G, Balocchini E, Sangalli M, Lopalco PL, Moiraghi A, Stroffolini T (2001) Changing epidemiology of parenterally transmitted viral hepatitis: results from the hepatitis surveillance system in Italy. Dig Liver Dis 33:778–784PubMedCrossRefGoogle Scholar
  33. 33.
    Gaeta GB, Stornaiuolo G, Precone DF, Lobello S, Chiaramonte M, Stroffolini T, Colucci G, Rizzetto M (2003) Epidemiological and clinical burden of chronic hepatitis B virus/hepatitis C virus infection. A multicenter Italian study. J Hepatol 39:1036–1041PubMedCrossRefGoogle Scholar
  34. 34.
    Bellentani S, Tiribelli C (2001) The spectrum of liver disease in the general population: lesson from the Dionysos study. J Hepatol 35:531–537PubMedCrossRefGoogle Scholar
  35. 35.
    Stroffolini T, Sagnelli E, Almasio P, Ferrigno L, Craxi A, Mele A (2004) Characteristics of liver cirrhosis in Italy: results from a multicenter national study. Dig Liver Dis 36:56–60PubMedCrossRefGoogle Scholar
  36. 36.
    Stroffolini T, Chiaramonte M, Craxi A, Franco E, Rapicetta M, Trivello R, De Mattia D, Mura I, Giammanco A, Rigo G et al (1991) Baseline sero-epidemiology of hepatitis B virus infection in children and teenagers in Italy. A survey before mass hepatitis B vaccination. J Infect 22:191–199PubMedCrossRefGoogle Scholar
  37. 37.
    Stroffolini T (2005) The changing pattern of hepatitis B virus infection over the past three decades in Italy. Dig Liver Dis 37:622–627PubMedCrossRefGoogle Scholar
  38. 38.
    Marchesini G, Forlani G, Rossi E, Berti A, De Rosa M (2010) The direct economic cost of pharmacologically-treated diabetes in Italy-2006. The ARNO observatory. Nutr Metab Cardiovasc Dis (in press)Google Scholar
  39. 39.
    Binkin N, Fontana G, Lamberti A, Cattaneo C, Baglio G, Perra A, Spinelli A (2010) A national survey of the prevalence of childhood overweight and obesity in Italy. Obes Rev 11:2–10PubMedCrossRefGoogle Scholar
  40. 40.
    Manco M, Giordano U, Turchetta A, Fruhwirth R, Ancinelli M, Marcellini M, Nobili V (2009) Insulin resistance and exercise capacity in male children and adolescents with non-alcholic fatty liver disease. Acta Diabetol 46:97–104PubMedCrossRefGoogle Scholar
  41. 41.
    Fabris P, Baldo V, Baldovin T, Bellotto E, Rassu M, Trivello R, Tramarin A, Tositti G, Floreani A (2008) Changing epidemiology of HCV and HBV infections in Northern Italy: a survey in the general population. J Clin Gastroenterol 42:527–532PubMedCrossRefGoogle Scholar
  42. 42.
    Seeff LB, Ghany MG (2010) Management of untreated and nonresponder patients with chronic hepatitis C. Semin Liver Dis 30:348–360PubMedCrossRefGoogle Scholar
  43. 43.
    Lagiou P, Kuper H, Stuver SO, Tzonou A, Trichopoulos D, Adami HO (2000) Role of diabetes mellitus in the etiology of hepatocellular carcinoma. J Natl Cancer Inst 92:1096–1099PubMedCrossRefGoogle Scholar
  44. 44.
    Pollak M (2008) Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer 8:915–928PubMedCrossRefGoogle Scholar
  45. 45.
    Moucari R, Asselah T, Cazals-Hatem D, Voitot H, Boyer N, Ripault MP, Sobesky R, Martinot-Peignoux M, Maylin S, Nicolas-Chanoine MH, Paradis V, Vidaud M, Valla D, Bedossa P, Marcellin P (2008) Insulin resistance in chronic hepatitis C: association with genotypes 1 and 4, serum HCV RNA level, and liver fibrosis. Gastroenterology 134:416–423PubMedCrossRefGoogle Scholar
  46. 46.
    Marchesini G, Brizi M, Morselli-Labate AM, Bianchi G, Bugianesi E, McCullough AJ, Forlani G, Melchionda N (1999) Association of nonalcoholic fatty liver disease with insulin resistance. Am J Med 107:450–455PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Valentina Soverini
    • 1
  • Marcello Persico
    • 2
  • Elisabetta Bugianesi
    • 3
  • Gabriele Forlani
    • 1
  • Federico Salamone
    • 3
  • Mario Massarone
    • 2
  • Vincenzo La Mura
    • 2
  • Arianna Mazzotti
    • 1
  • Alberto Bruno
    • 4
  • Giulio Marchesini
    • 1
    Email author
  1. 1.Unit of Metabolic Diseases and Clinical Dietetics“Alma Mater Studiorum” University of BolognaBolognaItaly
  2. 2.Division of Internal Medicine and HepatologyII° University of NaplesNaplesItaly
  3. 3.Division of Gastroenterology and HepatologyUniversity of TurinTurinItaly
  4. 4.Division of Diabetology and Metabolic DiseasesS. Giovanni Battista HospitalTurinItaly

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