DOI QR코드

DOI QR Code

Hepatic Steatosis: Prevalence and Host/Viral Risk Factors in Iranian Patients with Chronic Hepatitis B Infection

  • Poortahmasebi, Vahdat (Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences) ;
  • Alavian, Seyed Moayed (Middle East Liver Diseases Center (MELD Centers)) ;
  • Keyvani, Hossein (Department of Virology, School of Medicine, Tehran University of Medical Sciences) ;
  • Norouzi, Mehdi (Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences) ;
  • Mahmoodi, Mahmood (Department of epidemiology, School of Public Health, Tehran University of Medical Sciences) ;
  • Jazayeri, Seyed Mohammad (Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences)
  • Published : 2014.05.15

Abstract

Background: In chronic hepatitis B (CHB), the presence of hepatic steatosis (HS) seems to be associated with known host and viral factors which may influence the long-term prognosis of chronic hepatitis B (CHB), probably leading to cirrhosis and hepatocellular carcinoma (HCC). Different from chronic hepatitis C (CHC), factors associated with HS in CHB are not clearly explored. Materials and Methods: 160 CHB patients were divided into two groups depending on the results of liver biopsy. Group I consisted of 71 patients with confirmed steatosis. Group II comprised 89 patients without steatosis. The groups were compared in terms of basal characteristics, body mass index (BMI), liver enzymes (ALT, AST, ALP), serum fasting blood sugar (FBS) and lipids, hepatitis B e antigen (HBeAg), viral load, and histological findings. Results: In terms of host factors, male gender, older age, BMI, high serum FBS and lipid levels were associated with HS. On the other hand, ALT levels, the HAI scores of necroinflammation and stage of fibrosis did not associate with HS. On multivariate analysis, parameters of sex, BMI, cholesterol and FBS levels were independently associated with HS. Regarding viral factors, HBeAg negativity was significantly associated with HS (81.7%, p value 0.006), but not HBV DNA level (p value 0.520). Conclusions: HS in CHB appears to be unrelated to the status of HBV replication. However, fibrosis progression in CHB is related to variable host factors. HS may be enhanced through these factors in HBV chronic patients.

Keywords

References

  1. Altlparmak E, Koklu S, Yalinkilic M, et al (2005). Viral and host causes of fatty liver in chronic hepatitis B. World J Gastroenterol, 11, 3056-9. https://doi.org/10.3748/wjg.v11.i20.3056
  2. Ates F, Yalniz M, Alan S (2011). Impact of liver steatosis on response to pegylated interferon therapy in patients with chronic hepatitis B. World J Gastroenterol, 17, 4517-22. https://doi.org/10.3748/wjg.v17.i40.4517
  3. Bach N, Thung SN, Schaffner F (1992). The histological features of chronic hepatitis C and autoimmune chronic hepatitis: a comparative analysis. Hepatology, 15, 572-7. https://doi.org/10.1002/hep.1840150403
  4. Basaranoglu M, Basaranoglu G (2011). Pathophysiology of insulin resistance and steatosis in patients with chronic viral hepatitis. World J Gastroenterol, 17, 4055-62. https://doi.org/10.3748/wjg.v17.i36.4055
  5. Bondini S, Kallman J, Wheeler A, et al (2007). Impact of non-alcoholic fatty liver disease on chronic hepatitis B. Liver Int, 27, 607-11. https://doi.org/10.1111/j.1478-3231.2007.01482.x
  6. Bugianesi E (2007). Non-alcoholic steatohepatitis and cancer. Clin Liver Dis, 11, 191-207. https://doi.org/10.1016/j.cld.2007.02.006
  7. Cindoruk M, Karakan T, Unal S (2007). Hepatic steatosis has no impact on the outcome of treatment in patients with chronic hepatitis B infection. J Clin Gastroenterol, 41, 513-7. https://doi.org/10.1097/01.mcg.0000225586.78330.60
  8. Fujie H, Yotsuyanagi H, Moriya K, et al (1999). Steatosis and intrahepatic hepatitis C virus in chronic hepatitis. J Med Virol, 59, 141-5. https://doi.org/10.1002/(SICI)1096-9071(199910)59:2<141::AID-JMV3>3.0.CO;2-5
  9. Gordon A, Mclean CA, Pedersen JS, Bailey MJ, Roberts SK (2005). Hepatic steatosis in chronic hepatitis B and C: predictors, distribution and effect on fibrosis. J Hepatol, 43, 38-44. https://doi.org/10.1016/j.jhep.2005.01.031
  10. Harrison SA, Brunt EM, Qazi RA, et al (2005). Effect of significant histologic steatosis or steatohepatitis on response to antiviral therapy in patients with chronic hepatitis C. Clin Gastroenterol Hepatol, 3, 604-9. https://doi.org/10.1016/S1542-3565(05)00246-6
  11. Jiang J, Nilsson-Ehle P, Xu N (2006). Influence of liver cancer on lipid and lipoprotein metabolism. Lipids Health Dis, 5, 4. https://doi.org/10.1186/1476-511X-5-4
  12. Jin X, Chen YP, Yang YD, et al (2012). Association between hepatic steatosis and entecavir treatment failure in Chinese patients with chronic hepatitis B. PLoS One, 7, 34198. https://doi.org/10.1371/journal.pone.0034198
  13. Kim JY, Song EH, Lee HJ, et al (2010). HBx-induced hepatic steatosis and apoptosis are regulated by TNFR1- and NF-kappaB-dependent pathways. J Mol Biol, 397, 917-31. https://doi.org/10.1016/j.jmb.2010.02.016
  14. Kim KH, Shin HJ, Kim K, et al (2007). Hepatitis B virus X protein induces hepatic steatosis via transcriptional activation of SREBP1 and PPARgamma. Gastroenterology, 132, 1955-67. https://doi.org/10.1053/j.gastro.2007.03.039
  15. Kim YC, Song KS, Yoon G, Nam MJ, Ryu WS (2001). Activated ras oncogene collaborates with HBx gene of hepatitis B virus to transform cells by suppressing HBx-mediated apoptosis. Oncogene, 20, 16-23. https://doi.org/10.1038/sj.onc.1203840
  16. Lagging LM, Garcia CE, Westin J, et al (2002). Comparison of serum hepatitis C virus RNA and core antigen concentrations and determination of whether levels are associated with liver histology or affected by specimen storage time. J Clin Microbiol, 40, 4224-9. https://doi.org/10.1128/JCM.40.11.4224-4229.2002
  17. Lesmana LA, Lesmana CR, Pakasi LS, Krisnuhoni E (2012). Prevalence of hepatic steatosis in chronic hepatitis B patients and its association with disease severity. Acta Med Indones, 44, 35-9.
  18. Lonardo A, Adinolfi LE, Loria P, et al (2004). Steatosis and hepatitis C virus: mechanisms and significance for hepatic and extrahepatic disease. Gastroenterology, 126, 586-97. https://doi.org/10.1053/j.gastro.2003.11.020
  19. Lonardo A, Loria P, Adinolfi LE, Carulli N, Ruggiero G (2006). Hepatitis C and steatosis: a reappraisal. J Viral Hepat, 13, 73-80. https://doi.org/10.1111/j.1365-2893.2005.00669.x
  20. Malhotra V, Sakhuja P, Gondal R, et al (2000). Histological comparison of chronic hepatitis B and C in an Indian population. Trop Gastroenterol, 21, 20-1.
  21. Matteoni CA, Younossi ZM, Gramlich T, et al (1999). Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology, 116, 1413-9. https://doi.org/10.1016/S0016-5085(99)70506-8
  22. Minakari M, Molaei M, Shalmani HM, et al (2009). Liver steatosis in patients with chronic hepatitis B infection: host and viral risk factors. Eur J Gastroenterol Hepatol, 21, 512-6. https://doi.org/10.1097/MEG.0b013e328326792e
  23. Na TY, Shin YK, Roh KJ, et al (2009). Liver X receptor mediates hepatitis B virus X protein-induced lipogenesis in hepatitis B virus-associated hepatocellular carcinoma. Hepatology, 49, 1122-31. https://doi.org/10.1002/hep.22740
  24. Nascimento AC, Maia DR, Neto SM, et al (2012). Nonalcoholic Fatty liver disease in chronic hepatitis B and C patients from Western Amazon. Int J Hepatol, 2012, 695950.
  25. Peng D, Han Y, Ding H, Wei L (2008). Hepatic steatosis in chronic hepatitis B patients is associated with metabolic factors more than viral factors. J Gastroenterol Hepatol, 23, 1082-8. https://doi.org/10.1111/j.1440-1746.2008.05478.x
  26. Petta S, Camma C, Di Marco V, et al (2011). Hepatic steatosis and insulin resistance are associated with severe fibrosis in patients with chronic hepatitis caused by HBV or HCV infection. Liver Int, 31, 507-15. https://doi.org/10.1111/j.1478-3231.2011.02453.x
  27. Powell EE, Jonsson JR,Clouston AD (2005). Steatosis: co-factor in other liver diseases. Hepatology, 42, 5-13.
  28. Rastogi A, Sakhuja P, Kumar A, et al (2011). Steatosis in chronic hepatitis B: prevalence and association with biochemical, histologic, viral, and metabolic parameters. Indian J Pathol Microbiol, 54, 454-9. https://doi.org/10.4103/0377-4929.85074
  29. Ratziu V, Trabut JB, Poynard T (2004). Fat, diabetes, and liver injury in chronic hepatitis C. Curr Gastroenterol Rep, 6, 22-9. https://doi.org/10.1007/s11894-004-0022-5
  30. Roberts JM, Searle JW, Cooksley WG (1993). Histological patterns of prolonged hepatitis C infection. Gastroenterol Jpn, 28, 37-41. https://doi.org/10.1007/BF02989202
  31. Sass DA, Chang P, Chopra KB (2005). Nonalcoholic fatty liver disease: a clinical review. Dig Dis Sci, 50, 171-80. https://doi.org/10.1007/s10620-005-1267-z
  32. Scheuer PJ, Ashrafzadeh P, Sherlock S, Brown D, Dusheiko G M (1992). The pathology of hepatitis C. Hepatology, 15, 567-71. https://doi.org/10.1002/hep.1840150402
  33. Schiff ER, Sorell MF, WC M (1999). Disease of the Liver., Philedelphia: Lippincot- Williams and Wilkins.
  34. Shi JP, Fan JG, Wu R, et al (2008). Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese patients with chronic hepatitis B infection. J Gastroenterol Hepatol, 23, 1419-25. https://doi.org/10.1111/j.1440-1746.2008.05531.x
  35. Starley BQ, Calcagno CJ, Harrison SA (2010). Nonalcoholic fatty liver disease and hepatocellular carcinoma: a weighty connection. Hepatology, 51, 1820-32. https://doi.org/10.1002/hep.23594
  36. Thomopoulos KC, Arvaniti V, Tsamantas AC, et al (2006). Prevalence of liver steatosis in patients with chronic hepatitis B: a study of associated factors and of relationship with fibrosis. Eur J Gastroenterol Hepatol, 18, 233-7. https://doi.org/10.1097/00042737-200603000-00002
  37. Tsochatzis E, Papatheodoridis GV, Manesis EK, et al (2007). Hepatic steatosis in chronic hepatitis B develops due to host metabolic factors: a comparative approach with genotype 1 chronic hepatitis C. Dig Liver Dis, 39, 936-42. https://doi.org/10.1016/j.dld.2007.07.151
  38. Walsh MJ, Vanags DM, Clouston AD, et al (2004). Steatosis and liver cell apoptosis in chronic hepatitis C: a mechanism for increased liver injury. Hepatology, 39, 1230-8. https://doi.org/10.1002/hep.20179
  39. Wan G, Ohnomi S, Kato N (2000). Increased hepatic activity of inducible nitric oxide synthase in rats fed on a high-fat diet. Biosci Biotechnol Biochem, 64, 555-61. https://doi.org/10.1271/bbb.64.555
  40. Yang S, Lin H, Diehl AM (2001). Fatty liver vulnerability to endotoxin-induced damage despite NF-kappaB induction and inhibited caspase 3 activation. Am J Physiol Gastrointest Liver Physiol, 281, 382-92. https://doi.org/10.1152/ajpgi.2001.281.2.G382
  41. Yang SQ, Lin HZ, Lane MD, Clemens M, Diehl AM (1997). Obesity increases sensitivity to endotoxin liver injury: implications for the pathogenesis of steatohepatitis. Proc Natl Acad Sci USA, 94, 2557-62. https://doi.org/10.1073/pnas.94.6.2557
  42. Yoon EJ, Hu KQ (2006). Hepatitis C virus (HCV) infection and hepatic steatosis. Int J Med Sci, 3, 53-6.
  43. Zheng RD, Xu CR, Jiang L, et al (2010). Predictors of hepatic steatosis in HBeAg-negative chronic hepatitis B patients and their diagnostic values in hepatic fibrosis. Int J Med Sci, 7, 272-7.

Cited by

  1. Transcatheter Arterial Chemoembolization Combined with Interferon-α is Safe and Effective for Patients with Hepatocellular Carcinoma after Curative Resection vol.16, pp.1, 2015, https://doi.org/10.7314/APJCP.2015.16.1.245
  2. Non-alcoholic Fatty Liver Disease (NAFLD) and Significant Hepatic Fibrosis Defined by Non-invasive Assessment in Patients with Type 2 Diabetes vol.16, pp.5, 2015, https://doi.org/10.7314/APJCP.2015.16.5.1789
  3. Preventive activity of banana peel polyphenols on CCl4-induced experimental hepatic injury in Kunming mice vol.11, pp.5, 2016, https://doi.org/10.3892/etm.2016.3155
  4. Is there an influence of hepatic steatosis on fibrosis and necroinflammation in young patients with chronic viral hepatitis B? vol.128, pp.7, 2016, https://doi.org/10.1080/00325481.2016.1221733