Viral Hepatitis

You have full text access to this OnlineOpen article

Retinol-binding protein 4: A new marker of virus-induced steatosis in patients infected with hepatitis c virus genotype 1†

  1. Salvatore Petta1,‡,*,
  2. Calogero Cammà1,
  3. Vito Di Marco1,
  4. Nicola Alessi1,
  5. Francesco Barbaria1,
  6. Daniela Cabibi2,
  7. Rosalia Caldarella3,
  8. Stefania Ciminnisi1,
  9. Anna Licata1,
  10. Maria Fatima Massenti3,
  11. Alessandra Mazzola1,
  12. Giuseppe Tarantino1,
  13. Giulio Marchesini4,
  14. Antonio Craxì1

Article first published online: 10 MAR 2008

DOI: 10.1002/hep.22316

Issue

Hepatology

Hepatology

Volume 48, Issue 1, pages 28–37, July 2008

Additional Information

How to Cite

Petta, S., Cammà, C., Di Marco, V., Alessi, N., Barbaria, F., Cabibi, D., Caldarella, R., Ciminnisi, S., Licata, A., Massenti, M. F., Mazzola, A., Tarantino, G., Marchesini, G. and Craxì, A. (2008), Retinol-binding protein 4: A new marker of virus-induced steatosis in patients infected with hepatitis c virus genotype 1. Hepatology, 48: 28–37. doi: 10.1002/hep.22316

Author Information

  1. 1

    Cattedra ed Unità Operativa di Gastroenterologia, University of Palermo, Palermo, Italy

  2. 2

    Cattedra di Anatomia Patologica, University of Palermo, Palermo, Italy

  3. 3

    Dipartimento di Igiene e Microbiologia–Sezione Igiene, University of Palermo, Palermo, Italy

  4. 4

    Dipartimento di Medicina e Gastroenterologia, Alma Mater Studiorum, University of Bologna, Bologna, Italy

  1. ‡

    fax: 39 091 655 2156

*Gastroenterologia and Epatologia, Piazza delle Cliniche 2, 90127 Palermo, Italy

  1. †

    Potential conflict of interest: Nothing to report.

Publication History

  1. Issue published online: 20 JUN 2008
  2. Article first published online: 10 MAR 2008
  3. Accepted manuscript online: 10 MAR 2008 12:00AM EST
  4. Manuscript Accepted: 29 FEB 2008
  5. Manuscript Received: 21 DEC 2007

Funded by

  • Italian Association for the Study of the Liver

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article (HTML) Get PDF (212K)

References

  • 1
    Bugianesi E, McCullough AJ, Marchesini G. Insulin resistance: a metabolic pathway to chronic liver disease. HEPATOLOGY 2005; 42: 987–1000.
    Direct Link:
  • 2
    Asselah T, Rubbia-Brandt L, Marcellin P, Negro F. Steatosis in chronic hepatitis C: why does it really matter? Gut 2006; 55: 123–130.
  • 3
    Bugianesi E, Marchesini G, Gentilcore E, Cua IH, Vanni E, Rizzetto M, et al. Fibrosis in genotype 3 chronic hepatitis C and nonalcoholic fatty liver disease: Role of insulin resistance and hepatic steatosis. HEPATOLOGY 2006; 44: 1648–1655.
    Direct Link:
  • 4
    Cammà C, Bruno S, Di Marco V, Di Bona D, Rumi M, Vinci M, et al. Insulin resistance is associated with steatosis in nondiabetic patients with genotype 1 chronic hepatitis C. HEPATOLOGY 2006; 43: 64–71.
    Direct Link:
  • 5
    Leandro G, Mangia A, Hui J, Fabris P, Rubbia-Brandt L, Colloredo G, et al. Relationship between steatosis, inflammation, and fibrosis in chronic hepatitis C: a meta-analysis of individual patient data. Gastroenterology 2006; 130: 1636–1642.
  • 6
    Poynard T, Ratziu V, McHutchison J, Manns M, Goodman Z, Zeuzem S, et al. Effect of treatment with peginterferon or interferon alfa-2b and ribavirin on steatosis in patients infected with hepatitis C. HEPATOLOGY 2003; 38: 75–85.
    Direct Link:
  • 7
    Choudhury J, Sanyal AJ. Insulin resistance and the pathogenesis of nonalcoholic fatty liver disease. Clin Liver Dis 2004; 8: 575–594.
  • 8
    Gordon A, McLean CA, Pedersen JS, Bailey MJ, Roberts SK. Hepatic steatosis in chronic hepatitis B and C: predictors, distribution and effect on fibrosis. J Hepatol 2005; 43: 38–44.
  • 9
    Yatsuji S, Hashimoto E, Kaneda H, Taniai M, Tokushige K, Shiratori K. Diagnosing autoimmune hepatitis in nonalcoholic fatty liver disease: is the International Autoimmune Hepatitis Group scoring system useful? J Gastroenterol 2005; 40: 1130–1138.
  • 10
    Clément S, Negro F. Hepatitis C virus: the viral way to fatty liver. J Hepatol 2007; 46: 985–987.
  • 11
    Adinolfi LE, Gambardella M, Andreana A, Tripodi MF, Utili R, Ruggiero G. Steatosis accelerates the progression of liver damage of chronic hepatitis C patients and correlates with specific HCV genotype and visceral obesity. HEPATOLOGY 2001; 33: 1358–1364.
    Direct Link:
  • 12
    Castéra L, Hézode C, Roudot-Thoraval F, Lonjon I, Zafrani ES, Pawlotsky JM, et al. Effect of antiviral treatment on evolution of liver steatosis in patients with chronic hepatitis C: indirect evidence of a role of hepatitis C virus genotype 3 in steatosis. Gut 2004; 53: 420–424.
  • 13
    Rubbia-Brandt L, Giostra E, Mentha G, Quadri R, Negro F. Expression of liver steatosis in hepatitis C virus infection and pattern of response to alpha-interferon. J Hepatol 2001; 35: 307.
  • 14
    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. Gastroenterology 2003; 125: 1695–1704.
  • 15
    Svegliati-Baroni G, Bugianesi E, Bouserhal T, Marini F, Ridolfi F, Tarsetti F, et al. Post-load insulin resistance is an independent predictor of hepatic fibrosis in virus C chronic hepatitis and in non-alcoholic fatty liver disease. Gut 2007; 56: 1296–1301.
  • 16
    Shintani Y, Fujie H, Miyoshi H, Tsutsumi T, Tsukamoto K, Kimura S, et al. Hepatitis C virus infection and diabetes: direct involvement of the virus in the development of insulin resistance. Gastroenterology 2004; 126: 840–848.
  • 17
    Pazienza V, Clément S, Pugnale P, Conzelman S, Foti M, Mangia A, et al. The hepatitis C virus core protein of genotypes 3a and 1b downregulates insulin receptor substrate 1 through genotype-specific mechanisms. HEPATOLOGY 2007; 45: 1164–1171.
    Direct Link:
  • 18
    van Dam RM, Hu FB. Lipocalins and insulin resistance: etiological role of retinol-binding protein 4 and lipocalin-2? Clin Chem 2007; 53: 5–7.
  • 19
    Blaner WS. Retinol-binding protein: the serum transport protein for vitamin A. Endocr Rev 1989; 10: 308–316.
  • 20
    Desvergne B. RXR: from partnership to leadership in metabolic regulations. Vitam Horm 2007; 75: 1–32.
  • 21
    Larter CZ, Farrell GC. Insulin resistance, adiponectin, cytokines in NASH: which is the best target to treat? J Hepatol 2006; 44: 253–261.
  • 22
    Yang Q, Graham TE, Mody N, Preitner F, Peroni OD, Zabolotny JM, et al. Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature 2005; 436: 356–362.
  • 23
    Graham TE, Yang Q, Blüher M, Hammarstedt A, Ciaraldi TP, Henry RR, et al. Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subjects. N Engl J Med 2006; 354: 2552–2263.
  • 24
    Klöting N, Graham TE, Berndt J, Kralisch S, Kovacs P, Wason CJ, et al. Serum retinol-binding protein is more highly expressed in visceral than in subcutaneous adipose tissue and is a marker of intra-abdominal fat mass. Cell Metab 2007; 6: 79–87.
  • 25
    von Eynatten M, Lepper PM, Liu D, Lang K, Baumann M, Nawroth PP, et al. Retinol-binding protein 4 is associated with components of the metabolic syndrome, but not with insulin resistance, in men with type 2 diabetes or coronary artery disease. Diabetologia 2007; 50: 1930–1937.
  • 26
    Takebayashi K, Suetsugu M, Wakabayashi S, Aso Y, Inukai T. Retinol binding protein-4 levels and clinical features of type 2 diabetes patients. J Clin Endocrinol Metab 2007; 92: 2712–2719.
  • 27
    Broch M, Vendrell J, Ricart W, Richart C, Fernández-Real JM. Circulating retinol-binding protein-4, insulin sensitivity, insulin secretion, and insulin disposition index in obese and nonobese subjects. Diabetes Care 2007; 30: 1802–1806.
  • 28
    Lee DC, Lee JW, Im JA. Association of serum retinol binding protein 4 and insulin resistance in apparently healthy adolescents. Metabolism 2007; 56: 327–331.
  • 29
    Wu H, Jia W, Bao Y, Lu J, Zhu J, Wang R, et al. Serum retinol binding protein 4 and nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus. Diabetes Res Clin Pract 2007; 79: 185–190.
  • 30
    Janke J, Engeli S, Boschmann M, Adams F, Böhnke J, Luft FC, et al. Retinol-binding protein 4 in human obesity. Diabetes 2006; 55: 2805–2810.
  • 31
    Seo JA, Kim NH, Park SY, Kim HY, Ryu OH, Lee KW, et al. Serum retinol-binding protein 4 levels are elevated in non-alcoholic fatty liver disease. Clin Endocrinol (Oxf) 2007; 68: 555–560.
    Direct Link:
  • 32
    Stefan N, Hennige AM, Staiger H, Machann J, Schick F, Schleicher E, et al. High circulating retinol-binding protein 4 is associated with elevated liver fat but not with total, subcutaneous, visceral, or intramyocellular fat in humans. Diabetes Care 2007; 30: 1173–1178.
  • 33
    Balagopal P, Graham TE, Kahn BB, Altomare A, Funanage V, George D. Reduction of elevated serum retinol binding protein in obese children by lifestyle intervention: association with subclinical inflammation. J Clin Endocrinol Metab 2007; 92: 1971–1974.
  • 34
    Yao-Borengasser A, Varma V, Bodles AM, Rasouli N, Phanavanh B, Lee MJ, et al. Retinol binding protein 4 expression in humans: relationship to insulin resistance, inflammation, and response to pioglitazone. J Clin Endocrinol Metab 2007; 92: 2590–2597.
  • 35
    Petta S, Cammà C, Di Marco V, Alessi N, Cabibi D, Caldarella R. Insulin resistance and diabetes increase fibrosis in the liver of patients with genotype 1-HCV infection. Am J Gastroenterol 2008. Available at: http://www.amjgastro.com.
  • 36
    Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412–419.
  • 37
    Ikeda Y, Suehiro T, Nakamura T, Kumon Y, Hashimoto K. Clinical significance of the insulin resistance index as assessed by homeostasis model assessment. Endocr J 2001; 48: 81–86.
  • 38
    Colloredo G, Guido M, Sonzogni A, Leandro G. Impact of liver biopsy size on histological evaluation of chronic viral hepatitis: the smaller the sample, the milder the disease. J Hepatol 2003; 39: 239–244.
  • 39
    Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. HEPATOLOGY 2005; 411: 313–321.
  • 40
    Brunt EM, Janney CG, Di Bisceglie AM, Neuschwander-Tetri BA, Bacon BR. Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol 1999; 9: 2467–2474.
    Direct Link:
  • 41
    Scheuer PJ. Classification of chronic viral hepatitis: a need for reassessment. J Hepatol 1991; 13: 372–374.
  • 42
    SAS Technical Report, SAS/STAT software: changes and enhancement, Release 6.07. Cary, NC: SAS Institute, Inc.; 1992.
  • 43
    Tsutsumi T, Suzuki T, Shimoike T, Suzuki R, Moriya K, Shintani Y, et al. Interaction of hepatitis C virus core protein with retinoid X receptor alpha modulates its transcriptional activity. HEPATOLOGY 2002; 35: 937–946.
    Direct Link:
  • 44
    Ost A, Danielsson A, Lidén M, Eriksson U, Nystrom FH, Strålfors P. Retinol-binding protein-4 attenuates insulin-induced phosphorylation of IRS1 and ERK1/2 in primary human adipocytes. FASEB J 2007; 21: 3696–3704.
  • 45
    Pontisso P, Bellati G, Brunetto M, Chemello L, Colloredo G, Di Stefano R, et al. Hepatitis C virus RNA profiles in chronically infected individuals: do they relate to disease activity? HEPATOLOGY 1999; 29: 585–589.
    Direct Link:
  • 46
    Gyamfi MA, He L, French SW, Damjanov I, Wan YJ. Hepatocyte retinoid X receptor alpha-dependent regulation of lipid homeostasis and inflammatory cytokine expression contributes to alcohol-induced liver injury. J Pharmacol Exp Ther 2007; 324: 443–453.
View Full Article (HTML) Get PDF (212K)