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Effect of Liver Steatosis on Therapeutic Response in Chronic Hepatitis C Virus Genotype 1 Infected Patients in Hungary

  • Published:
Pathology & Oncology Research

Abstract

Hepatic steatosis seems a frequent histological alteration seen in chronic hepatitis C virus infected patients. There is still a lot to learn about the exact mechanism of effect of liver steatosis and its influence on the progression of liver diseases. Our study involved 96 chronic hepatitis C genotype 1 infected Hungarian patients who received pegylated interferon and ribavirin treatment for the first time. Degree of steatosis, viral and host factors influencing its development and its effect on the efficiency of antiviral treatment were determined. In 61 (64%) of patients the liver tissue showed varying degree of steatosis, which did not show relationship with level of alcohol consumption (p = 0.5792), diabetes mellitus (p = 0.5925) or body mass index (p = 0.9685) in type 1 chronic hepatitis C patients. Degree of steatosis and virus titer showed strong relationship (OR = 2.1). Significant relationship was also found between degree of hepatic steatosis and stage (p = 0.0119), as well as between therapeutic response to combined pegylated interferon + ribavirin treatment and steatosis (p = 0.0012). Our results demonstrated that steatosis has clinical significance in hepatitis C virus genotype 1 infected patients.

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Abbreviations

CHC:

chronic hepatitis C

BMI:

body mass index

HCV:

hepatitis C virus

SVR:

sustained virological response

AST:

aspartate aminotransferase

ALT:

alanine aminotranserase

GGT:

gamma-glutamyl-transerase

AP:

alkaline phosphatase

Fe:

serum iron

TSH:

thyroid stimulating hormone

FT4:

free T4

FT3:

free T3

MTP:

microsomal trygliceride transfer protein

EVR:

early virological response

References

  1. Seeff LB, Buskell-Bales Z, Wright EC, National Heart, Lung and Blood Institute Study Group et al (1991) Long-term mortality after transfusion-associated non-A,non-B hepatitis. N Engl J Med 327:1906–1911

    Article  Google Scholar 

  2. Poynard T, Bedossa P, Opolon P (1997) Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups. Lancet 349(9055):825–832

    Article  CAS  PubMed  Google Scholar 

  3. Mihm S, Fayyazi A, Hartmann H et al (1997) Analysis of histopathological manifestations of chronic hepatitis C virus infection with respect to virus genotype. Hepatology 25:735–739

    Article  CAS  PubMed  Google Scholar 

  4. Czaja AJ, Carpenter HA, Santrach PJ et al (1998) Host- and disease-specific factors affecting steatosis in chronic hepatitis C. J Hepatol 29:198–206

    Article  CAS  PubMed  Google Scholar 

  5. Hourigan LF, Macdonald GA, Purdie D et al (1999) Fibrosis in chronic hepatitis C correlates significantly with body mass index and steatosis. Hepatology 29:1215–1219

    Article  CAS  PubMed  Google Scholar 

  6. Rubbia-Brandt L, Quadri R, Abid K et al (2000) Hepatocyte steatosis is a cytopathic effect of hepatitis C virus genotypes 3. J Hepatol 33:106–115

    Article  CAS  PubMed  Google Scholar 

  7. Adinolfi LE, Gambardella M, Andreana A et al (2001) Steatosis accelerates the progression of liver damage of chronic hepatitis C patients and correlates with specific HCV genotype and visceral obesity. Hepatology 33:1358–1364

    Article  CAS  PubMed  Google Scholar 

  8. Serfaty L, Andreani T, Giral P et al (2001) Hepatitis C virus induced hypobetalipoproteinemia: a possible mechanism for steatosis in chronic hepatitis C. J Hepatol 34:428–434

    Article  CAS  PubMed  Google Scholar 

  9. Monto A, Alonzo J, Watson JJ et al (2002) Steatosis in chronic hepatitis C: relative contribution of obesity, diabetes mellitus, and alcohol. Hepatology 36:729–736

    Article  PubMed  Google Scholar 

  10. Westin J, Nordlinder H, Lagging M et al (2002) Steatosis accelerates fibrosis development over time in hepatitis C virus genotype 3 infected patients. J Hepatol 37:837–842

    Article  PubMed  Google Scholar 

  11. Hui JM, Kench J, Farrell GC et al (2002) Genotype-specific mechanisms for hepatic steatosis in chronic hepatitis C infection. J Gastroenterol Hepatol 17:873–881

    Article  PubMed  Google Scholar 

  12. Castéra L, Hézode C, Roudot-Thoraval F et al (2003) Worsening of steatosis is an independent factor of fibrosis progression in untreated patients with chronic hepatitis C and paired liver biopsies. Gut 52:288–292

    Article  PubMed  Google Scholar 

  13. Poynard T, Ratziu V, McHutchinson J et al (2003) Effect of treatment with peginterferon or interferon alfa-2b and ribavirin on steatosis in patients infected with hepatitis C. Hepatology 38:75–85

    Article  CAS  PubMed  Google Scholar 

  14. Asselah T, Boyer N, Guimont MC et al (2003) Liver fibrosis is not associated with steatosis but with necroinflammation in French patients with chronic hepatitis C. Gut 52:1638–1643

    Article  CAS  PubMed  Google Scholar 

  15. Rubbia-Brandt L, Fabris P, Paganin S et al (2004) Steatosis affects chronic hepatitis C progression in a genotype-specific way. Gut 53:406–412

    Article  CAS  PubMed  Google Scholar 

  16. Patton HM, Patel K, Behling C et al (2004) The impact of steatosis on disease progression and early sustained treatment response in chronic hepatitis C patients. J Hepatol 40:484–490

    Article  PubMed  Google Scholar 

  17. Asselah T, Rubbia-Brandt L, Marcellin P et al (2006) Steatosis in chronic hepatitis C: why does it really matter? Gut 55:123–130

    Article  CAS  PubMed  Google Scholar 

  18. Allison ME, Wreghitt T, Palmer CR et al (1994) Evidence for a link between hepatitis C virus infection and diabetes mellitus in a cirrhotic population. J Hepatol 21:1135–1139

    Article  CAS  PubMed  Google Scholar 

  19. Caronia S, Taylor K, Pagliaro L et al (1999) Further evidence for an association between non-insulin-dependent diabetes mellitus and chronic hepatitis C virus infection. Hepatology 30:1059–1063

    Article  CAS  PubMed  Google Scholar 

  20. Mason AL, Lau JY, Hoang N et al (1999) Association of diabetes mellitus and chronic hepatitis C virus infection. Hepatology 29:328–333

    Article  CAS  PubMed  Google Scholar 

  21. Petit JM, Bour JB, Galland-Jos C et al (2001) Risk factors for diabetes mellitus and early insulin resistance in chronic hepatitis C. J Hepatol 35:279–283

    Article  CAS  PubMed  Google Scholar 

  22. Mehta SH, Brancati FL, Strathdee SA et al (2003) Hepatitis C infection and incident type 2 diabetes. Hepatology 38:50–56

    Article  PubMed  Google Scholar 

  23. Hui KQ, Esrailian E, Runyon B et al (2002) Clinical implication of hepatic steatosis in patients with chronic hepatitis C. Hepatology 34:187A

    Google Scholar 

  24. Kumar D, Farell GC, Fung C et al (2002) Hepatitis C virus genotype 3 is cytopathic to hepatocytes: reversal of hepatic steatosis after sustained therapeutic response. Hepatology 36:1266–1272

    Article  PubMed  Google Scholar 

  25. Moriya K, Yotsuyanagi H, Shintani Y et al (1997) Hepatitis C virus core protein induces hepatic steatosis in transgenic mice. J Gen Virol 78:1527–1531

    CAS  PubMed  Google Scholar 

  26. Kumar D, Farrell GC, Fung C et al (2002) Hepatitis C virus genotype 3 is cytopathic to hepatocytes: reversal of hepatic steatosis after sustained therapeutic response. Hepatology 36:1266–1272

    Article  PubMed  Google Scholar 

  27. Gervain J, Simon G, Papp I et al (2001) Determination of the type and subtype of the hepatitis virus C in chronic viral hepatitis patients in Hungary. Orv Hetil 142:1315–1319

    CAS  PubMed  Google Scholar 

  28. Tornai I, Dalmi L, Gervain J et al (2005) Treatment of patients with chronic hepatitis C, using pegylated interferon alfa-2a and ribavirin — the first experiences in Hungary based upon a multicentric, open, prospective study. LAM 15:807–813

    Google Scholar 

  29. Ishak K, Baptista A, Bianchi L et al (1995) Histological grading and staging of chronic hepatitis. J Hepatol 22:696–699

    Article  CAS  PubMed  Google Scholar 

  30. Brunt EM, Janney CG, Di Bisceglie AM et al (1999) Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol 94:2467–2474

    Article  CAS  PubMed  Google Scholar 

  31. Jármay K, Karácsony G, Nagy A et al (2005) Changes in lipid metabolism in chronic hepatitis C. World J Gastroenterol 11:6422–6428

    PubMed  Google Scholar 

  32. Abid K, Pazienza V, de Gottardi A et al (2005) An in vitro model of hepatitis C virus genotype 3a-associated triglycerides accumulation. J Hepatol 42:744–751

    Article  CAS  PubMed  Google Scholar 

  33. Barba G, Harper F, Harada T et al (1997) Hepatitis C core protein shows a cytoplasmic localization and associates to cellular lipid storage droplets. Proc Nat Acad Sci USA 94:1200–1205

    Article  CAS  PubMed  Google Scholar 

  34. Shi ST, Polyak SJ, Tu H et al (2002) Hepatitis C virus NS5A colocalizes with the core protein on lipid droplets and interacts with apolipoproteins. Virology 292:198–210

    Article  CAS  PubMed  Google Scholar 

  35. Perlemuter G, Sabile A, Letteron P et al (2002) Hepatitis C core protein inhibits microsomal triglycerid transfer protein activity and very low density lipoprotein secretion: a model of viral-related steatosis. FASEB J 16:185–194

    Article  CAS  PubMed  Google Scholar 

  36. Fartoux L, Chazouilleres O, Wendum D et al (2005) Impact of steatosis on progression of fibrosis in patients with mild hepatitis C. Hepatology 41:82–87

    Article  PubMed  Google Scholar 

  37. Day CP, James OFW (1998) Steatohepatitis: a tale of two “hits”? Gastroenterology 114:842–845

    Article  CAS  PubMed  Google Scholar 

  38. Lee KS, Buck M, Houglum K et al (1995) Activation of hepatic stellate cells by TGF alpha and collagen type I is mediated by oxidative stress through c-myb expression. J Clin Invest 96:2461–2468

    Article  CAS  PubMed  Google Scholar 

  39. Bedossa P, Houglum K, Trautwein C et al (1994) Stimulation of collagen alpha 1(1) gene expression is associated with lipid peroxidation in hepatocellular injury: a link to tissue fibrosis? Hepatology 19:1262–1271

    CAS  PubMed  Google Scholar 

  40. Parola M, Pinzani M, Casini A et al (1993) Stimulation of lipid peroxidation or 4-hydroxynonenal treatment increases procollagen alpha 1 (1) gene expression in human liver fat-storing cells. Biochem Biophys Res Commun 194:1044–1050

    Article  CAS  PubMed  Google Scholar 

  41. Farinati F, Cardin R, De Maria N et al (1995) Iron strorage, lipid peroxidation and glutathion turnover in chronic anti-HCV positive hepatitis. J Hepatol 22:449–456

    Article  CAS  PubMed  Google Scholar 

  42. Paradis V, Mathurin P, Kollinger M et al (1997) In situ detection of lipid peroxidation in chronic hepatitis C: correlation with pathological features. J Clin Pathol 50:401–406

    Article  CAS  PubMed  Google Scholar 

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Conflict of interest statement

The authors of the present study confirm that there is no conflict of interest to be declared.

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Authors and Affiliations

  1. 2nd Department of Internal Medicine, Semmelweis University, Szentkirályi u. 46, 1088, Budapest, Hungary

    Klara Werling & Zsolt Tulassay

  2. 2nd Department of Pathology, Semmelweis University, Budapest, Hungary

    Zsuzsa Schaff

  3. Medical Department, EGIS Pharmaceuticals PLC, Budapest, Hungary

    Elek Dinya

Authors
  1. Klara Werling
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  2. Zsuzsa Schaff
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  3. Elek Dinya
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  4. Zsolt Tulassay
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Correspondence to Klara Werling.

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Werling, K., Schaff, Z., Dinya, E. et al. Effect of Liver Steatosis on Therapeutic Response in Chronic Hepatitis C Virus Genotype 1 Infected Patients in Hungary. Pathol. Oncol. Res. 16, 149–157 (2010). https://doi.org/10.1007/s12253-009-9195-4

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  • DOI: https://doi.org/10.1007/s12253-009-9195-4

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