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A Biomarker Panel for Non-alcoholic Steatohepatitis (NASH) and NASH-Related Fibrosis

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Abstract

Background

Patients with biopsy-proven NASH and especially those with fibrosis are at risk for progressive liver disease, emphasizing the clinical importance of developing non-invasive biomarkers for NASH and NASH-related fibrosis.

Aim

This study examines the performance of a new biomarker panel for NASH and NASH-related fibrosis with a combination of clinical and laboratory variables.

Methods

Enrolled patients had biopsy-proven NAFLD. Clinical data, laboratory data, and serum samples were collected at the time of biopsy. Fasting serum was assayed for adiponectin, resistin, glucose, M30, M65, Tissue inhibitor of metalloproteinases-1 (Timp-1), ProCollagen 3 N-terminal peptide (PIIINP), and hyaluronic acid (HA). Regression models predictive of NASH, NASH-related fibrosis, and NASH-related advanced fibrosis were designed and cross-validated.

Results

Of the 79 enrolled NAFLD patients, 40 had biopsy-proven NASH and 39 had non-NASH NAFLD. Clinical and laboratory data were from this cohort were used to develop a NAFLD Diagnostic Panel that includes three models (models for NASH, NASH-related fibrosis, and NASH-related advanced fibrosis). The model for predicting NASH includes diabetes, gender, BMI, triglycerides, M30 (apoptosis), and M65–M30 (necrosis) [AUC: 0.81, 95% CI, 0.70–0.89, 300 p value <9E 301 −06]. The NASH-related fibrosis prediction model includes the same predictors [AUC: 0.80, 95% CI 0.68–0.88, 307 p value <0.00014]. Finally, the NASH-related advanced fibrosis model includes type 2 diabetes, serum triglycerides, Timp-1, and AST [AUC: 0.81, 95% CI, 0.70–0.89; p value, 0.000062].

Conclusions

This NAFLD Diagnostic Panel based on a clinical and laboratory data has good performance characteristics and is easy to use. This biomarker panel could become useful in the management of patients with NAFLD.

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References

  1. Marchesini G, Bugianesi E, Forlani G, et al. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology. 2003;37:917–23.

    Article  PubMed  Google Scholar 

  2. Rafiq N, Younossi ZM. Evaluation and management of non-alcoholic fatty liver disease. Clin Liver Dis. 2009;13:249–66.

    Article  PubMed  Google Scholar 

  3. Younossi ZM, Diehl AM, Ong JP. Nonalcoholic fatty liver disease: an agenda for clinical research. Hepatology. 2002;35:746–52.

    Article  PubMed  Google Scholar 

  4. Younossi ZM, Gramlich T, Liu Y, et al. Non- alcoholic fatty liver: assessment of variability in the pathologic interpretations. Mod Pathol. 1998;11(6):560–5.

    CAS  PubMed  Google Scholar 

  5. Matteoni C, Younossi ZM, Gramlich T, et al. A non-alcoholic fatty liver disease: a spectrum of clinical and pathologic severity. Gastroenterology. 1999;116:1413–9.

    Article  CAS  PubMed  Google Scholar 

  6. Rafiq N, Bai CH, Fang Y, et al. Long-term follow-up of patients with non-alcoholic fatty liver. Clini Gastro Hepatol. 2009;7(2):234–8.

    Article  Google Scholar 

  7. Ekstedt M et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology. 2006;44:865.

    Article  CAS  PubMed  Google Scholar 

  8. Rosenberg WM, Voelker M, Thiel R, European Liver Fibrosis Group, et al. Serum markers detect the presence of liver fibrosis: a cohort study. Gastroenterology. 2004;127(6):1704–13.

    Article  PubMed  Google Scholar 

  9. Angulo P, Hui JM, Marchesini G, et al. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology. 2007;45(4):846–54.

    Article  CAS  PubMed  Google Scholar 

  10. Guha IN, Parkes J, Roderick P, et al. Noninvasive markers of fibrosis in nonalcoholic fatty liver disease: validating the European liver fibrosis panel and exploring simple markers. Hepatology. 2009;47(2):455–60.

    Article  Google Scholar 

  11. Wai CT, Greenson JK, Fontana RJ, et al. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology. 2003;38(2):518–26.

    Article  PubMed  Google Scholar 

  12. Cales P, Laine F, Boursier J, Deugnier Y, Moal V, Oberti F, et al. Comparison of blood tests for liver fibrosis specific or not to NAFLD J Hepatol. 2009;50:165–73.

    PubMed  Google Scholar 

  13. Younossi ZM, Jarrar M, Nugent C, et al. A novel diagnostic biomarker panel for obesity-related nonalcoholic steatohepatitis (NASH). Obes Surg. 2008;18(11):1430–7.

    Article  PubMed  Google Scholar 

  14. Wieckowska A, Zein NN, Yerian LM, et al. In vivo assessment of liver cell apoptosis as a novel biomarker of disease severity in nonalcoholic fatty liver disease. Hepatology. 2006;44(1):27–33.

    Article  CAS  PubMed  Google Scholar 

  15. Baranova A, Younossi ZM. The future is around the corner: non-invasive diagnosis of the progressive nonalcoholic steatohepatitis. Hepatology. 2008;47(2):373–5.

    Article  PubMed  Google Scholar 

  16. Hossain N, Afendy A, Stepanova M, Nader F, Srishord M, Goodman Z, Younossi Z. Independent predictors of fibrosis in patients with non-alcoholic fatty liver disease. Clin Gastro Hepatol 2009;7(11):1224–9.

    Google Scholar 

  17. Bondini S, Kleiner DE, Goodman Z, et al. Pathologic assessment of non-alcoholic fatty liver disease. Clin Liver Dis. 2007;11:17–23.

    Article  PubMed  Google Scholar 

  18. Cadranel JF, Rufat P, Degos F. Practices of liver biopsy in France: results of a prospective nationwide survey. For the Group of Epidemiology of the French Association for the Study of the Liver (AFEF). Hepatology. 2000;32:477–81.

    Article  CAS  PubMed  Google Scholar 

  19. Ratziu V, Charlotte F, Heurtier A, et al. Sampling variability of liver biopsy in nonalcoholic fatty liver disease. Gastroenterology. 2005;128:1898–906.

    Article  PubMed  Google Scholar 

  20. Miele L, Forgione A, Gasbarrini G, et al. Noninvasive assessment of fibrosis in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Transl Res. 2007;149:114–25.

    Article  CAS  PubMed  Google Scholar 

  21. Ratziu V, Giral P, Munteanu M, et al. Screening for liver disease using non-invasive biomarkers (FibroTest, SteatoTest and NashTest) in patients with hyperlipidaemia. Aliment Pharmacol Ther. 2007;25:207–18.

    Article  CAS  PubMed  Google Scholar 

  22. Wieckowska A, Zein NN, Yerian LM, et al. In vivo assessment of liver cell apoptosis as a novel biomarker of disease severity in nonalcoholic fatty liver disease. Hepatology. 2006;44:27–33.

    Article  CAS  PubMed  Google Scholar 

  23. Chitturi S, Farell GC. Etiopathogenesis of nonalcoholic steatohepatitis. Semin Liver Dis. 2001;21(1):27–41.

    Article  CAS  PubMed  Google Scholar 

  24. Edmison J, McCullough AJ. Pathogenesis of non-alcoholic steatohepatitis: human data. Clinics in Liver Disease. 2007;11(1):75–104.

    Article  PubMed  Google Scholar 

  25. London R, George J. Pathogenesis of NASH: animal models. Clin Liver Dis. 2007;11(1):55–74.

    Article  PubMed  Google Scholar 

  26. Nugent C, Younossi ZM. Evaluation and management of obesity-related non-alcoholic fatty liver disease. Nat Clin Pract Gastroenterol Hepatol. 2007;14(No. 8):432–41.

    Article  Google Scholar 

  27. Lazo M, Clark JM. The epidemiology of nonalcoholic fatty liver disease: a global perspective. Semin Liver Dis. 2008;28(4):339–50.

    Article  PubMed  Google Scholar 

  28. Saadeh S, Younossi ZM, Remer EM, et al. The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology. 2002;123:745–150.

    Article  PubMed  Google Scholar 

  29. Charatcharoenwitthaya P, Lindor KD. Role of radiologic modalities in the management of NASH. Clin Liver Dis. 2007;11(1):37–54.

    Article  PubMed  Google Scholar 

  30. Nguyen-Khac E, Capron D. Noninvasive diagnosis of liver fibrosis by ultrasonic transient elastography (Fibroscan). Eur J Gastroenterol Hepatol. 2006;18:1321–5.

    Article  PubMed  Google Scholar 

  31. Ong J, Elariny H, Collantes R, et al. Predictors of nonalcoholic steatohepatitis and advanced fibrosis in obese patients. Obesity Surgery. 2005;15(3):310–5.

    Article  PubMed  Google Scholar 

  32. Baranova A, Gowder SJ, Schlauch K, et al. Gene expression of leptin, resistin, and adiponectin in the white adipose tissue of obese patients with non-alcoholic fatty liver disease and insulin resistance. Obes Surg. 2006;16:1118–25.

    Article  PubMed  Google Scholar 

  33. Younossi ZM, Gorreta F, Ong JP, et al. Hepatic gene expression in patients with obesity-related non-alcoholic steatohepatitis. Liver Int. 2005;25:760–71.

    Article  CAS  PubMed  Google Scholar 

  34. Younossi ZM, Baranova A, Ziegler K, et al. A genomic and proteomic of study of the spectrum of non-alcoholic fatty liver disease. Hepatology. 2005;41(3):665–74.

    Article  Google Scholar 

  35. Calvert VS, Collantes R, Elariny H, et al. A systems biology approach to non alcoholic fatty liver disease pathogenesis using multiplexed cell signaling analysis. Hepatology. 2007;46(1):166–72.

    Article  CAS  PubMed  Google Scholar 

  36. Baranova A, Liotta L, Petricoin E, et al. The role of genomics and proteomics technologies in studying non-alcoholic fatty liver disease. Clin Liver Dis. 2007;11:209–20.

    Article  PubMed  Google Scholar 

  37. Itagaki T, Shimizu I, Cheng X, et al. Opposing effects of oestradiol and progesterone on intracellular pathways and activation processes in the oxidative stress induced activation of cultured rat hepatic stellate cells. Gut. 2005;54:1782–9.

    Article  CAS  PubMed  Google Scholar 

  38. Shimizu I, Kohno N, Tamaki K, et al. Female hepatology: favorable role of estrogen in chronic liver disease with hepatitis B virus infection. World J Gastroenterol. 2007;13:4295–305.

    CAS  PubMed  Google Scholar 

  39. Shimizu I, Ito S. Protection of estrogens against the progression of chronic liver disease. Hepatol Res. 2007;37:239–47.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This study has been supported by the Liver Disease Outcomes Fund of the Center for Liver Diseases at Inova Fairfax Hospital, Inova Health system. The authors acknowledge Dr. Stig Linder and Peviva, Bromma, Sweden for providing kits for M-30 and M-65.

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Authors and Affiliations

  1. Center for Liver Diseases, Inova Fairfax Hospital, 3300 Gallows Road, Falls Church, VA, 22042, USA

    Zobair M. Younossi, Nila Rafiq, Maria Stepanova, Arian Afendy, Zahra Younoszai, Zachary Goodman & Ancha Baranova

  2. Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA

    Zobair M. Younossi, Sandra Page, Nila Rafiq, Aybike Birerdinc, Maria Stepanova, Noreen Hossain, Arian Afendy, Zahra Younoszai & Ancha Baranova

  3. Center for the Study of Genomics in Liver Diseases, Molecular and Microbiology Department, George Mason University, Fairfax, VA, USA

    Zobair M. Younossi, Sandra Page, Aybike Birerdinc & Ancha Baranova

Authors
  1. Zobair M. Younossi
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  2. Sandra Page
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  3. Nila Rafiq
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  8. Zahra Younoszai
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  9. Zachary Goodman
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  10. Ancha Baranova
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Correspondence to Zobair M. Younossi.

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Younossi, Z.M., Page, S., Rafiq, N. et al. A Biomarker Panel for Non-alcoholic Steatohepatitis (NASH) and NASH-Related Fibrosis. OBES SURG 21, 431–439 (2011). https://doi.org/10.1007/s11695-010-0204-1

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  • DOI: https://doi.org/10.1007/s11695-010-0204-1

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