Advertisement

European Cytokine Network

, Volume 29, Issue 3, pp 112–120 | Cite as

Elevated adiponectin and sTNFRII serum levels can predict progression to hepatocellular carcinoma in patients with compensated HCV1 cirrhosis

  • Jean-Philippe BastardEmail author
  • Soraya Fellahi
  • Étienne Audureau
  • Richard Layese
  • Françoise Roudot-Thoraval
  • Carole Cagnot
  • Valérie Mahuas-Bourcier
  • Angela Sutton
  • Marianne Ziol
  • Jacqueline Capeau
  • Pierre Nahon
  • ANRS CO12 CirVir Group
Original Article
  • 2 Downloads

Abstract

Background and aims

An obesity-related altered adipose tissue secretion is suggested as a risk factor for hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV) cirrhosis. However, no prospective study has yet examined the predictive value of circulating adipokines and immuno-inflammatory biomarkers regarding this risk.

Methods

This was a case-control study nested in a prospective French national cohort of HCV-infected patients with biopsy-proven compensated cirrhosis.We selected 56 HCV1-infected patients who subsequently developed HCC (cases), and 96 controls matched for age, gender and diabetes, not developing HCC after a similar period. Adipokines and immuno-inflammatory biomarkers were determined on baseline frozen serum samples. Their influence on the occurrence of HCC was assessed using a mixed logistic regression model under univariate analysis and a backward stepwise procedure under multivariate analysis.

Results

The patients were mostly male (62.5%) with active HCV replication (83%) and had been followed for a median duration of 6.3 years during which 44.4% achieved a sustained viral response. Higher adiponectinemia levels were found in cases than in controls (P = 0.01). Levels of the immuno-inflammatory markers were similar in both groups except sTNFRII >5,000 pg/mL (52% cases versus 24% controls; P = 0.001). No marker was associated with histological steatosis. Under multivariate analysis, baseline adiponectin and sTNFRII levels were independently associated with the occurrence of HCC,alongside previous excessive alcohol intake and HCV viral load.

Conclusions

High baseline circulating adiponectin and sTNFRII levels were associated with an increased risk of HCC in patients with HCV1 cirrhosis, independently of their HCV replication status.

Key words

HCV hepatocellular carcinoma adipokines immuno-inflammatory biomarkers 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Thrift AP, El-Serag HB, Kanwal F. Global epidemiology and burden of HCV infection and HCV-related disease. Nat Rev Gastroenterol Hepatol 2017; 14: 122–32.CrossRefGoogle Scholar
  2. 2.
    Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology 2011; 53: 1020–2.CrossRefGoogle Scholar
  3. 3.
    Nahon P, Bourcier V, Layese R, et al. Eradication of hepatitis C virus infection in patients with cirrhosis reduces risk of liver and non-liver complications. Gastroenterology 2017; 152: 142–156 e2.CrossRefGoogle Scholar
  4. 4.
    Younossi ZM, Kanwal F, Saab S, et al. The impact of hepatitis C burden: an evidence-based approach. Aliment Pharmacol Ther 2014; 39: 518–31.CrossRefGoogle Scholar
  5. 5.
    Davila JA, Morgan RO, Shaib Y, McGlynn KA, El-Serag HB. Diabetes increases the risk of hepatocellular carcinoma in the United States: a population based case control study. Gut 2005; 54: 533–9.CrossRefGoogle Scholar
  6. 6.
    N’Kontchou G, Paries J, Htar MT, et al. Risk factors for hepatocellular carcinoma in patients with alcoholic or viral C cirrhosis. Clin Gastroenterol Hepatol 2006; 4: 1062–8.CrossRefGoogle Scholar
  7. 7.
    Chen CL, Yang HI, Yang WS, et al. Metabolic factors and risk of hepatocellular carcinoma by chronic hepatitis B/C infection: a follow-up study in Taiwan. Gastroenterology 2008; 135: 111–21.CrossRefGoogle Scholar
  8. 8.
    Bastard JP, Maachi M, Lagathu C, et al. Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur Cytokine Netw 2006; 17: 4–12.Google Scholar
  9. 9.
    Font-Burgada J, Sun B, Karin M. Obesity and cancer: the oil that feeds the flame. Cell Metab 2016; 23: 48–62.CrossRefGoogle Scholar
  10. 10.
    Castello G, Scala S, Palmieri G, Crley SA, Izzo F. HCV-related hepatocellualr carcinoma: from chronic inflammation to cancer. Clin Immunol 2010; 134: 237–50.CrossRefGoogle Scholar
  11. 11.
    Maki A, KOno H, Gupta M, et al. Predictive power of biomarkers of oxidative stress and inflammation in patients with hepatitis C virus-associated hepatocellular carcinoma. Ann Surg Oncol 2007; 14: 1182–90.CrossRefGoogle Scholar
  12. 12.
    Liu D, Li S, Li Z. Adiponectin: a biomarker for chronic hepatitis C? Cytokine 2017; 89: 27–33.CrossRefGoogle Scholar
  13. 13.
    Nkontchou G, Bastard JP, Ziol M, et al. Insulin resistance, serum leptin, and adiponectin levels and outcomes of viral hepatitisCcirrhosis. J Hepatol 2010; 53: 827–33.CrossRefGoogle Scholar
  14. 14.
    Sandler NG, Koh C, Roque A, et al. Host response to translocated microbial products predicts outcomes of patients with HBV or HCV infection. Gastroenterology 2011; 141: 1220–30.CrossRefGoogle Scholar
  15. 15.
    Trinchet JC, Bourcier V, Chaffaut C, et al. Complications and competing risks of death in compensated viral cirrhosis (ANRS CO12 CirVir prospective cohort). Hepatology 2015; 62: 737–50.CrossRefGoogle Scholar
  16. 16.
    Nahon P, Lescat M, Layese R, et al. Bacterial infection in compensated viral cirrhosis impairs 5-year survival (ANRS CO12 CirVir prospective cohort). Gut 2017; 66: 330–41.CrossRefGoogle Scholar
  17. 17.
    Ganne-Carrie N, Layese R, Bourcier V, et al. Nomogram for individualized prediction of hepatocellular carcinoma occurrence in hepatitis C virus cirrhosis (ANRS CO12 CirVir). Hepatology 2016; 64: 1136–47.CrossRefGoogle Scholar
  18. 18.
    Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology 2005; 42: 1208–36.CrossRefGoogle Scholar
  19. 19.
    Bedossa P, Poitou C, Veyrie N, et al. Histopathological algorithm and scoring system for evaluation of liver lesions in morbidly obese patients. Hepatology 2012; 56: 1751–9.CrossRefGoogle Scholar
  20. 20.
    Arano T, Nakagawa H, Tateishi R, et al. Serum level of adiponectin and the risk of liver cancer development in chronic hepatitis C patients. Int J Cancer 2011; 129: 2226–35.CrossRefGoogle Scholar
  21. 21.
    Khattab MA, Eslam M, Mousa YI, et al. Association between metabolic abnormalities and hepatitis C-related hepatocellular carcinoma. Ann Hepatol 2012; 11: 487–94.Google Scholar
  22. 22.
    Michikawa T, Inoue M, Sawada N, et al. Plasma levels of adiponectin and primary liver cancer risk in middle-aged Japanese adults with hepatitis virus infection: a nested case-control study. Cancer Epidemiol Biomarkers Prev 2013; 22: 2250–7.CrossRefGoogle Scholar
  23. 23.
    Nakagawa H, Fujiwara N, Tateishi R, et al. Impact of serum levels of interleukin-6 and adiponectin on all-cause, liver-related, and liverunrelated mortality in chronic hepatitis C patients. J Gastroenterol Hepatol 2015; 30: 379–88.CrossRefGoogle Scholar
  24. 24.
    Hung CH, Wang JH, Hu TH, et al. Insulin resistance is associated with hepatocellular carcinoma in chronic hepatitis C infection. World J Gastroenterol 2010; 16: 2265–71.CrossRefGoogle Scholar
  25. 25.
    Sumie S, Kawaguchi T, Kuromatsu R, et al. Total and high molecular weight adiponectin and hepatocellular carcinoma with HCV infection. PLoS One 2011; 6: e26840. doi: 10.1371/journal.pone.0026840.CrossRefGoogle Scholar
  26. 26.
    Siegel AB, Goyal A, Salomao M, et al. Serum adiponectin is associated with worsened overall survival in a prospective cohort of hepatocellular carcinoma patients. Oncology 2015; 88: 57–68.CrossRefGoogle Scholar
  27. 27.
    Wang SN, Yang SF, Tsai HH, Lee KT, Yeh YT. Increased adiponectin associated with poor survival in hepatocellular carcinoma. J Gastroenterol 2014; 49: 1342–51.CrossRefGoogle Scholar
  28. 28.
    Shen J, Yeh CC, Wang Q, Gurvich I, Siegel AB, Santella RM. Plasma adiponectin and hepatocellular carcinoma survival among patients without liver transplantation. Anticancer Res 2016; 36: 5307–14.CrossRefGoogle Scholar
  29. 29.
    Nakagawa H1, Maeda S, Yoshida H, et al. Serum IL-6 levels and the risk for hepatocarcinogenesis in chronic hepatitis C patients: an analysis based on gender differences. Int J Cancer 2009; 125: 2264–9.CrossRefGoogle Scholar
  30. 30.
    Kessel A, Elias G, Pavlotzky E, Zuckerman E, Rosner I, Toubi E. Anti-C-reactive protein antibodies in chronic hepatitis C infection: correlation with severity and autoimmunity. Hum Immunol 2007; 68: 844–8.CrossRefGoogle Scholar
  31. 31.
    Sjöwall C, Cardell K, Boström EA, et al. High prevalence of autoantibodies to C-reactive protein in patients with chronic hepatitis C infection: association with liver fibrosis and portal inflammation. Hum Immunol 2012; 73: 382–8.CrossRefGoogle Scholar
  32. 32.
    Waters JP, Pober JS, Bradley JR. Tumour necrosis factor in infectious disease. J Pathol 2013; 230: 132–47.CrossRefGoogle Scholar
  33. 33.
    Waters JP, Pober JS, Bradley JR. Tumour necrosis factor and cancer. J Pathol 2013; 230: 241–8.CrossRefGoogle Scholar
  34. 34.
    Spinas GA, Keller U, Brockhaus M. Release of soluble receptors for tumor necrosis factor (TNF) in relation to circulating TNF during experimental endotoxinemia. J Clin Invest 1992; 90: 533–6.CrossRefGoogle Scholar
  35. 35.
    Tornero C, Alberola J, Tamarit A, Navarro D. Effect of highly active anti-retroviral therapy and hepatitis C virus co-infection on serum levels of pro-inflammatory and immunoregulatory cytokines in human immunodeficiency virus-1-infected individuals. Clin Microbiol Infect 2006; 12: 555–60.CrossRefGoogle Scholar
  36. 36.
    Itoh Y, Okanoue T, Ohnishi N, et al. Serum levels of soluble tumor necrosis factor receptors and effects of interferon therapy in patients with chronic hepatitis C virus infection. Am J Gastroenterol 1999; 94: 1332–40.CrossRefGoogle Scholar
  37. 37.
    Fouad SA, Elsaaid NH, Mohamed NA, Abutaleb OM. Diagnostic value of serum level of soluble tumor necrosis factor receptor IIα in Egyptian patients with chronic hepatitis C virus infection and hepatocellular carcinoma. Hepat Mon 2014; 14(9): e19346. doi: 10.5812/hepatmon.19346.CrossRefGoogle Scholar
  38. 38.
    Zekri AR, Youssef AS, Bakr YM, et al. Serum biomarkers for early detection of hepatocellular carcinoma associated withHCVinfection in Egyptian patients. Asian Pac J Cancer Prev 2015; 16: 1281–7.CrossRefGoogle Scholar
  39. 39.
    Zekri AR, Alam El-Din HM, Bahnassy AA, et al. Serum levels of soluble Fas, soluble tumor necrosis factor-receptor II, interleukin-2 receptor and interleukin-8 as early predictors of hepatocellular carcinoma in Egyptian patients with hepatitis C virus genotype-4. Comp Hepatol 2010; 9: 1. doi: 10.1186/1476-5926-9-1.CrossRefGoogle Scholar
  40. 40.
    Kazankov K, Barrera F, Møller HJ, et al. Soluble CD163, a macrophage activation marker, is independently associated with fibrosis in patients with chronic viral hepatitis B and C. Hepatology 2014; 60: 521–30.CrossRefGoogle Scholar
  41. 41.
    Kazankov K, Rode A, Simonsen K, et al. Macrophage activation marker soluble CD163 may predict disease progression in hepatocellular carcinoma. Scand J Clin Lab Invest 2016; 76: 64–73.CrossRefGoogle Scholar
  42. 42.
    Waidmann O, Köberle V, Bettinger D, et al. Diagnostic and prognostic significance of cell death and macrophage activation markers in patients with hepatocellular carcinoma. J Hepatol 2013; 59: 769–79.CrossRefGoogle Scholar

Copyright information

© John Libbey Eurotext 2018

Authors and Affiliations

  • Jean-Philippe Bastard
    • 1
    • 2
    • 3
    • 15
    Email author
  • Soraya Fellahi
    • 1
    • 2
    • 3
  • Étienne Audureau
    • 4
    • 5
  • Richard Layese
    • 4
    • 5
  • Françoise Roudot-Thoraval
    • 4
    • 5
  • Carole Cagnot
    • 6
  • Valérie Mahuas-Bourcier
    • 7
  • Angela Sutton
    • 8
    • 9
    • 10
  • Marianne Ziol
    • 11
    • 12
    • 13
  • Jacqueline Capeau
    • 2
    • 3
  • Pierre Nahon
    • 7
    • 12
    • 14
  • ANRS CO12 CirVir Group
  1. 1.AP-HP, hôpital Tenon, UF biomarqueurs inflammatoires et métaboliques, service de biochimieParisFrance
  2. 2.Sorbonne université, faculté de médecineParisFrance
  3. 3.Inserm, CRSA, UMR_S 938ParisFrance
  4. 4.AP-HP, hôpital Henri-Mondor, Public Health Department, Clinical Research Unit (URC-Mondor)CréteilFrance
  5. 5.université Paris-Est, UPEC, DHU A-TVB, IMRB-EA 7376 CEpiA (Clinical Epidemiology and Ageing Unit)CréteilFrance
  6. 6.Unit for Basic and Clinical Research on Viral HepatitisANRSParisFrance
  7. 7.AP-HP, hôpital Jean-Verdier, service d’hépatologieBondyFrance
  8. 8.CRB (Liver Disease Biobank), groupe hospitalier ParisSeine-Saint-Denis BB-0033-00027France
  9. 9.AP-HP, hôpital Jean-Verdier, service de biochimieBondyFrance
  10. 10.Inserm U1148université Paris 13BobignyFrance
  11. 11.Université Paris 13, Sorbonne Paris-CitéBobignyFrance
  12. 12.Inserm UMR_S 1162, « Génomique fonctionnelle des tumeurs solides »ParisFrance
  13. 13.APHP, hôpital Jean-Verdier, anatomie pathologiqueBondyFrance
  14. 14.Université Paris 13, Sorbonne Paris-Cité, « Équipe labellisée Ligue contre le cancer »Saint-DenisFrance
  15. 15.Hôpital Tenon, UF biomarqueurs inflammatoires et métaboliques, service de biochimie et hormonologieParis cedex 20France

Personalised recommendations