Kronik Hepatit B enfeksiyonu açlık kan şekeri düzeylerini ve yağlı karaciğeri etkiler mi?

Öz

Amaç: Hepatit B virüsü (HBV) enfeksiyonu ile insülin direnci (ID) arasındaki ilişki kafa karıştırıcı görünmektedir. Bu çalışmada amaç, kronik aktif HBV enfeksiyonu olan hastalarda açlık kan şekeri (AKŞ) düzeyleri ile yağlı karaciğer (YK) sıklığını ID'nin bir yansıması olarak karşılaştırmak ve karaciğer fibrozunun AKŞ ve YK ile bir ilişkisi olup olmadığını belirlemekti.
Yöntemler: Bu çalışma vaka kontrol çalışması olarak planlandı. Çalışma grubu, 2000 IU/ml'nin üzerinde HBV DNA seviyesi olan 116 kronik HBV hastasından oluşturuldu. Yaş, cinsiyet ve vücut kitle indeksi uyumlu 120 sağlıklı bireyden bir kontrol grubu oluşturuldu.
Bulgular: Gruplar arasında AKŞ düzeyleri arasında fark yoktu (P=0,15), HBV'li hastalarda YK oranları anlamlı olarak daha yüksekti (P=0,01; OR: 2,13, %95 GA 1,26-3,61). Fibrozis şiddetine göre gruplar arasında AKŞ düzeyleri arasında anlamlı bir fark olmamasına rağmen, YK açısından anlamlı bir fark vardı (sırasıyla P=0,07 ve P<0,001). YK gelişimi ile fibrozisin şiddeti arasında pozitif bir korelasyon bulundu (rs=0,216, P=0,01).
Sonuç: AKŞ düzeyi kronik aktif HBV enfeksiyonundan etkilenmemiş gibi görünse de, bu hastalarda YK sıklığı belirgin şekilde artmaktadır. Metabolik faktörlerden ziyade viral faktörlerin YK gelişiminden sorumlu olması muhtemeldir.

Anahtar Kelimeler

• Yağlı karaciğer,Hepatit B,İnsülin direnci,NAFLD

Does chronic hepatitis B infection have an impact on fasting blood glucose levels and fatty liver development?

Abstract

Aim: The relationship between hepatitis B virus (HBV) infection and insulin resistance (IR) appears to be confusing. In this study, the goal was to compare fasting blood glucose (FBG) levels and fatty liver (FL) frequency as a reflection of IR in patients with chronic active HBV infection and to determine whether there is a relationship between liver fibrosis, FBG and FL.
Methods: In this case-control study, the study group consisted of 116 chronic HBV patients with HBV DNA levels above 2000 IU/ml. The control group included 120 healthy individuals with matching age, gender, and body mass indexes.
Results: There was no difference in FBG levels between the groups (P=0.15), but FL rates were significantly higher in patients with HBV (P=0.01; OR: 2.13, 95% CI 1.26-3.61). Although the FBG levels of groups with regards to severity of fibrosis were similar, there was a significant difference in terms of FL (P=0.07 and P<0.001, respectively). A positive correlation was found between the development of FL and the severity of fibrosis (rs=0.216, P=0.01).
Conclusion: While FBG level appears to be unaffected by chronic active HBV infection, the frequency of FL is markedly increased in these patients. Viral factors are likely responsible for the development of FL rather than metabolic factors.

Keywords

• Fatty liver,Hepatitis B,Insulin resistance,NAFLD

Kaynakça

1. 1. Schweitzer A, Horn J, Mikolajczyk RT, Krause G, Ott JJ. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet. 2015 Oct 17;386(10003):1546-55. doi: 10.1016/S0140-6736(15)61412-X.
2. 2. Kao JH, Chen DS. Global control of hepatitis B virus infection. Lancet Infect Dis. 2002 Jul;2(7):395-403. doi: 10.1016/s1473-3099(02)00315-8.
3. 3. European Association for the Study of the Liver. Electronic address: [e-mail]; European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017 Aug;67(2):370-98. doi: 10.1016/j.jhep.2017.03.021.
4. 4. Izquierdo AG, Crujeiras AB. Role of epigenomic mechanisms in the onset and management of insulin resistance. Rev Endocr Metab Disord. 2019 Mar;20(1):89-102. doi: 10.1007/s11154-019-09485-0.
5. 5. Bugianesi E, Salamone F, Negro F. The interaction of metabolic factors with HCV infection: does it matter? J Hepatol. 2012;56 Suppl 1:S56-65. doi: 10.1016/S0168-8278(12)60007-5.
6. 6. Kim K, Kim KH, Cheong J. Hepatitis B virus X protein impairs hepatic insulin signaling through degradation of IRS1 and induction of SOCS3. PLoS One. 2010 Mar 23;5(3):e8649. doi: 10.1371/journal.pone.0008649.
7. 7. Lee JG, Lee S, Kim YJ, Cho BM, Park JS, Kim HH, et al. Association of chronic viral hepatitis B with insulin resistance. World J Gastroenterol. 2012 Nov 14;18(42):6120-6. doi: 10.3748/wjg.v18.i42.6120.
8. 8. Wang CC, Hsu CS, Liu CJ, Kao JH, Chen DS. Association of chronic hepatitis B virus infection with insulin resistance and hepatic steatosis. J Gastroenterol Hepatol. 2008;23(5):779-82. doi:10.1111/j.1440-1746.2007.05216.x

9. 9. Huang ZS, Huang TS, Wu TH, Chen MF, Hsu CS, Kao JH. Asymptomatic chronic hepatitis B virus infection does not increase the risk of diabetes mellitus: a ten-year observation. J Gastroenterol Hepatol. 2010;25(8):1420-5. doi:10.1111/j.1440-1746.2010.06268.x
10. 10. Hashimoto E, Tokushige K, Farrell GC. Histological features of non-alcoholic fatty liver disease: what is important? J Gastroenterol Hepatol. 2012 Jan;27(1):5-7. doi: 10.1111/j.1440-1746.2011.06957.x.
11. 11. Loomba R, Sanyal AJ. The global NAFLD epidemic. Nat Rev Gastroenterol Hepatol. 2013 Nov;10(11):686-90. doi: 10.1038/nrgastro.2013.171.
12. 12. Fung J, Yuen MF, Lai CL. The role of steatosis in HBsAg seroclearance for patients with chronic hepatitis B infection: fact or fiction? Dig Dis Sci. 2013 Jan;58(1):20-2. doi: 10.1007/s10620-012-2441-8.
13. 13. Yun JW, Cho YK, Park JH, et al. Hepatic steatosis and fibrosis in young men with treatment-naïve chronic hepatitis B. Liver Int. 2009;29(6):878-83. doi:10.1111/j.1478-3231.2009.01976.x.
14. 14. Desmet VJ, Gerber M, Hoofnagle JH, Manns M, Scheuer PJ. Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology. 1994 Jun;19(6):1513-20.
15. 15. Mathiesen UL, Franzen LE, Aselius H, Resjo M, Jacobsson L, Foberg U, et al. Increased liver echogenicity at ultrasound examination reflects degree of steatosis but not of fibrosis in asymptomatic patients with mild/moderate abnormalities of liver transaminases. Dig Liver Dis. 2002;34:516-22. doi: 10.1016/s1590-8658(02)80111-6.
16. 16. Petersen MC, Shulman GI. Mechanisms of Insulin Action and Insulin Resistance. Physiol Rev. 2018;98(4):2133-223. doi:10.1152/physrev.00063.2017.
17. 17. Shen Y, Zhang J, Cai H, Shao JG, Zhang YY, Liu YM, et al. Identifying patients with chronic hepatitis B at high risk of type 2 diabetes mellitus: a cross-sectional study with pair-matched controls. BMC Gastroenterol. 2015 Mar 19;15:32. doi: 10.1186/s12876-015-0263-9.
18. 18. Mavrogiannaki A, Karamanos B, Manesis EK, Papatheodoridis GV, Koskinas J, Archimandritis AJ. Prevalence of glucose intolerance in patients with chronic hepatitis B or C: a prospective case-control study. J Viral Hepat. 2009;16(6):430-6. doi:10.1111/j.1365-2893.2009.01077.x
19. 19. Hong YS, Chang Y, Ryu S, Cainzos-Achirica M, Kwon MJ, Zhang Y, et al. Hepatitis B and C virus infection and diabetes mellitus: A cohort study. Sci Rep. 2017 Jul 4;7(1):4606. doi: 10.1038/s41598-017-04206-6.
20. 20. Lu J, Hou X, Tu H, Tang Z, Xiang Y, Bao Y, et al. Chronic hepatitis B virus infection status is more prevalent in patients with type 2 diabetes. J Diabetes Investig. 2017 Jul;8(4):619-25. doi: 10.1111/jdi.12609.
21. 21. Hui JM, Sud A, Farrell GC, Bandara P, Byth K, Kench JG, et al. Insulin resistance is associated with chronic hepatitis C virus infection and fibrosis progression [corrected]. Gastroenterology. 2003 Dec;125(6):1695-704. doi: 10.1053/j.gastro.2003.08.032. Erratum in: Gastroenterology. 2004 Feb;126(2):634.
22. 22. Kim JY, Song EH, Lee HJ, Oh YK, Choi KH, Yu DY, et al. HBx-induced hepatic steatosis and apoptosis are regulated by TNFR1- and NF-kappaB-dependent pathways. J Mol Biol. 2010 Apr 9;397(4):917-31. doi: 10.1016/j.jmb.2010.02.016.
23. 23. Zhang J, Shen Y, Cai H, Liu YM, Qin G. Hepatitis B virus infection status and risk of type 2 diabetes mellitus: A meta-analysis. Hepatol Res. 2015;45(11):1100-9. doi:10.1111/hepr.12481
24. 24. Elkrief L, Rautou PE, Sarin S, Valla D, Paradis V, Moreau R. Diabetes mellitus in patients with cirrhosis: clinical implications and management. Liver Int. 2016;36(7):936-48. doi:10.1111/liv.13115
25. 25. Angulo P, Keach JC, Batts KP, Lindor KD. Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology. 1999;30(6):1356-62. doi:10.1002/hep.510300604
26. 26. Marchesini G, Bugianesi E, Forlani G, Cerrelli F, Lenzi M, Manini R, et al. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology. 2003 Apr;37(4):917-23. doi: 10.1053/jhep.2003.50161. Erratum in: Hepatology. 2003 Aug;38(2):536.
27. 27. Jarcuska P, Drazilova S, Fedacko J, Pella D, Janicko M. Association between hepatitis B and metabolic syndrome: Current state of the art. World J Gastroenterol. 2016;22(1):155-64. doi:10.3748/wjg.v22.i1.155
28. 28. Yoon JS, Lee HY, Chung SW, Kim SW, Chang Y, Lee YB, et al. Prognostic impact of concurrent nonalcoholic fatty liver disease in patients with chronic hepatitis B-related hepatocellular carcinoma. J Gastroenterol Hepatol. 2020 Mar 3. doi: 10.1111/jgh.15026. Epub ahead of print.