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Noninvasive Testing for NASH and NASH with Advanced Fibrosis: Are We There Yet?

  • Fatty Liver Disease (SA Harrison and J George, Section Editors)
  • Published:
Current Hepatology Reports Aims and scope Submit manuscript

Abstract

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent etiology of chronic liver disease in America. NAFLD can be broadly classified in two subtypes: nonalcoholic fatty liver (NAFL), which is generally considered a benign condition with negligible risk of progression to cirrhosis, and nonalcoholic steatohepatitis (NASH), which is generally considered to be progressive with substantial risk of progression to cirrhosis. Additionally, recent studies suggest the odds of liver mortality increases among NASH patients with advanced fibrosis (bridging fibrosis ± cirrhosis). Liver biopsy examination is the current gold standard to accurately discriminate between NAFL versus NASH as well as diagnose advanced fibrosis. However, due to its invasive nature, risk of bleeding (and even rarely death), prohibitive cost, and sampling error, liver biopsies are imperfect for diagnosis and monitoring of NAFLD. As a result, noninvasive biomarkers that can accurately detect NASH and advanced fibrosis without biopsy are needed. This article will discuss the most novel noninvasive biomarkers in diagnosing NASH and advanced fibrosis.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Adams LA, Lymp JF, St Sauver J, et al. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology. 2005;129:113–21.

    Article  PubMed  Google Scholar 

  2. Zelber-Sagi S, Nitzan-Kaluski D, Halpern Z, et al. Prevalence of primary non-alcoholic fatty liver disease in a population-based study and its association with biochemical and anthropometric measures. Liver Int. 2006;26:856–63.

    Article  PubMed  Google Scholar 

  3. Kleiner DE, Brunt EM, Van Natta M, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41:1313–21.

    Article  PubMed  Google Scholar 

  4. Singh S, Allen AM, Wang Z, et al. Fibrosis progression in nonalcoholic fatty liver vs nonalcoholic steatohepatitis: a systematic review and meta-analysis of paired-biopsy studies. Clin Gastroenterol Hepatol. 2014. This was the first study to document fibrosis progress rate in NAFLD and NASH.

  5. Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology. 2012;55:2005–23.

    Article  PubMed  Google Scholar 

  6. Stepanova M, Rafiq N, Makhlouf H, et al. Predictors of all-cause mortality and liver-related mortality in patients with non-alcoholic fatty liver disease (NAFLD). Dig Dis Sci. 2013;58:3017–23.

    Article  CAS  PubMed  Google Scholar 

  7. Williams CD, Stengel J, Asike MI, et al. Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study. Gastroenterology. 2011;140:124–31.

    Article  PubMed  Google Scholar 

  8. Ong JP, Pitts A, Younossi ZM. Increased overall mortality and liver-related mortality in non-alcoholic fatty liver disease. J Hepatol. 2008;49:608–12.

    Article  PubMed  Google Scholar 

  9. Söderberg C, Stål P, Askling J, et al. Decreased survival of subjects with elevated liver function tests during a 28-year follow-up. Hepatology. 2010;51:595–602.

    Article  PubMed  Google Scholar 

  10. Ekstedt M, Franzen LE, Mathiesen UL, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology. 2006;44:865–73.

    Article  CAS  PubMed  Google Scholar 

  11. Desmet VJ, Gerber M, Hoofnagle JH, et al. Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology. 1994;19:1513–20.

    Article  CAS  PubMed  Google Scholar 

  12. Bravo AA, Sheth SG, Chopra S. Liver biopsy. N Engl J Med. 2001;344:495–500.

    Article  CAS  PubMed  Google Scholar 

  13. Mato JM, Lu SC. Where are we in the search for noninvasive nonalcoholic steatohepatitis biomarkers? Hepatology. 2011;54:1115–7.

    Article  PubMed  Google Scholar 

  14. Ratziu V, Cadranel JF, Serfaty L, et al. A survey of patterns of practice and perception of NAFLD in a large sample of practicing gastroenterologists in France. J Hepatol. 2012;57:376–83.

    Article  PubMed  Google Scholar 

  15. Corey KE, Lai M, Gelrud LG, et al. Non-high-density lipoprotein cholesterol as a biomarker for nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol. 2012;10:651–6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Alkhouri N, Carter-Kent C, Feldstein AE. Apoptosis in nonalcoholic fatty liver disease: diagnostic and therapeutic implications. Expert Rev Gastroenterol Hepatol. 2011;5:201–12.

    Article  PubMed Central  PubMed  Google Scholar 

  17. Joka D, Wahl K, Moeller S, et al. Prospective biopsy-controlled evaluation of cell death biomarkers for prediction of liver fibrosis and nonalcoholic steatohepatitis. Hepatology. 2012;55:455–64.

    Article  CAS  PubMed  Google Scholar 

  18. Cusi K, Chang Z, Harrison S, et al. Limited value of plasma cytokeratin-18 as a biomarker for NASH and fibrosis in patients with non-alcoholic fatty liver disease. J Hepatol. 2014;60:167–74.

    Article  CAS  PubMed  Google Scholar 

  19. Vuppalanchi R, Jain AK, Deppe R, et al. Relationship between changes in serum levels of keratin 18 and changes in liver histology in children and adults with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2014;12:2121–30.e1-2. This study demonstrated keratin 18 was not a good predictor of treatment response in NASH patients and did not perform any better than ALT.

    Article  CAS  PubMed  Google Scholar 

  20. Feldstein AE, Canbay A, Angulo P, et al. Hepatocyte apoptosis and fas expression are prominent features of human nonalcoholic steatohepatitis. Gastroenterology. 2003;125:437–43.

    Article  PubMed  Google Scholar 

  21. Tamimi TI, Elgouhari HM, Alkhouri N, et al. An apoptosis panel for nonalcoholic steatohepatitis diagnosis. J Hepatol. 2011;54:1224–9.

    Article  PubMed Central  PubMed  Google Scholar 

  22. Wang K. Molecular mechanisms of hepatic apoptosis. Cell Death Dis. 2014;5, e996.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Khan S, Subedi D, Chowdhury MM. Use of amino terminal type III procollagen peptide (P3NP) assay in methotrexate therapy for psoriasis. Postgrad Med J. 2006;82:353–4.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Tanwar S, Trembling PM, Guha IN, et al. Validation of terminal peptide of procollagen III for the detection and assessment of nonalcoholic steatohepatitis in patients with nonalcoholic fatty liver disease. Hepatology. 2013;57:103–11.

    Article  CAS  PubMed  Google Scholar 

  25. Wieckowska A, Papouchado BG, Li Z, et al. Increased hepatic and circulating interleukin-6 levels in human nonalcoholic steatohepatitis. Am J Gastroenterol. 2008;103:1372–9.

    Article  CAS  PubMed  Google Scholar 

  26. Wieckowska A, Papouchado BG, Li Z, et al. Role of interleukin-6 in human nonalcoholic steatohepatitis. Response to Dogru et al. Am J Gastroenterol. 2009;104:author reply 788.

  27. Mirza MS. Obesity, visceral fat, and NAFLD: querying the role of adipokines in the progression of nonalcoholic fatty liver disease. ISRN Gastroenterol. 2011;2011:592404.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Machado MV, Coutinho J, Carepa F, et al. How adiponectin, leptin, and ghrelin orchestrate together and correlate with the severity of nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol. 2012;24:1166–72.

    Article  CAS  PubMed  Google Scholar 

  29. Kowdley KV, Belt P, Wilson LA, et al. Serum ferritin is an independent predictor of histologic severity and advanced fibrosis in patients with nonalcoholic fatty liver disease. Hepatology. 2012;55:77–85.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Manousou P, Kalambokis G, Grillo F, et al. Serum ferritin is a discriminant marker for both fibrosis and inflammation in histologically proven non-alcoholic fatty liver disease patients. Liver Int. 2011;31:730–9.

    Article  CAS  PubMed  Google Scholar 

  31. Yoneda M, Thomas E, Sumida Y, et al. Clinical usage of serum ferritin to assess liver fibrosis in patients with nonalcoholic fatty liver disease: proceed with caution. Hepatol Res. 2014.

  32. Oliveira CP, da Costa Gayotto LC, Tatai C, et al. Oxidative stress in the pathogenesis of nonalcoholic fatty liver disease, in rats fed with a choline-deficient diet. J Cell Mol Med. 2002;6:399–406.

    Article  CAS  PubMed  Google Scholar 

  33. Videla LA, Rodrigo R, Araya J, et al. Oxidative stress and depletion of hepatic long-chain polyunsaturated fatty acids may contribute to nonalcoholic fatty liver disease. Free Radic Biol Med. 2004;37:1499–507.

    Article  CAS  PubMed  Google Scholar 

  34. Dowman JK, Tomlinson JW, Newsome PN. Systematic review: the diagnosis and staging of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Aliment Pharmacol Ther. 2011;33:525–40.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Adams LA, Feldstein AE. Non-invasive diagnosis of nonalcoholic fatty liver and nonalcoholic steatohepatitis. J Dig Dis. 2011;12:10–6.

    Article  CAS  PubMed  Google Scholar 

  36. Feldstein AE, Lopez R, Tamimi TA, et al. Mass spectrometric profiling of oxidized lipid products in human nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. J Lipid Res. 2010;51:3046–54.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Alkhouri N, Berk M, Yerian L, et al. OxNASH score correlates with histologic features and severity of nonalcoholic fatty liver disease. Dig Dis Sci. 2014;59:1617–24.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Sanyal AJ, Chalasani N, Kowdley KV, et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med. 2010;362:1675–85.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Loomba R, Quehenberger O, Armando A, et al. Polyunsaturated fatty acid metabolites as novel lipidomic biomarkers for noninvasive diagnosis of nonalcoholic steatohepatitis. J Lipid Res. 2015;56:185–92. This study identified polyunsaturated fatty acid metabolites that could differentiate NAFL from NASH.

    Article  CAS  PubMed  Google Scholar 

  40. Ratziu V, Giral P, Charlotte F, et al. Liver fibrosis in overweight patients. Gastroenterology. 2000;118:1117–23.

    Article  CAS  PubMed  Google Scholar 

  41. Angulo P, Keach JC, Batts KP, et al. Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology. 1999;30:1356–62.

    Article  CAS  PubMed  Google Scholar 

  42. Marceau P, Biron S, Hould FS, et al. Liver pathology and the metabolic syndrome X in severe obesity. J Clin Endocrinol Metab. 1999;84:1513–7.

    Article  CAS  PubMed  Google Scholar 

  43. Noureddin M, Yates KP, Vaughn IA, et al. Clinical and histological determinants of nonalcoholic steatohepatitis and advanced fibrosis in elderly patients. Hepatology. 2013;58:1644–54.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  44. Dixon JB, Bhathal PS, O’Brien PE. Nonalcoholic fatty liver disease: predictors of nonalcoholic steatohepatitis and liver fibrosis in the severely obese. Gastroenterology. 2001;121:91–100.

    Article  CAS  PubMed  Google Scholar 

  45. Papadia FS, Marinari GM, Camerini G, et al. Liver damage in severely obese patients: a clinical–biochemical–morphologic study on 1,000 liver biopsies. Obes Surg. 2004;14:952–8.

    Article  PubMed  Google Scholar 

  46. 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;45:846–54.

    Article  CAS  PubMed  Google Scholar 

  47. Musso G, Gambino R, Cassader M, et al. Meta-analysis: natural history of non-alcoholic fatty liver disease (NAFLD) and diagnostic accuracy of non-invasive tests for liver disease severity. Ann Med. 2011;43:617–49.

    Article  PubMed  Google Scholar 

  48. Harrison SA, Oliver D, Arnold HL, et al. Development and validation of a simple NAFLD clinical scoring system for identifying patients without advanced disease. Gut. 2008;57:1441–7.

    Article  CAS  PubMed  Google Scholar 

  49. Lee TH, Han SH, Yang JD, et al. Prediction of advanced fibrosis in nonalcoholic fatty liver disease: an enhanced model of BARD score. Gut Liver. 2013;7:323–8. This study identified an enhance model of the BARD score which can help predict advanced fibrosis.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  50. Sumida Y, Yoneda M, Hyogo H, et al. Validation of the FIB4 index in a Japanese nonalcoholic fatty liver disease population. BMC Gastroenterol. 2012;12:2.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  51. Cao W, Zhao C, Shen C, et al. Cytokeratin 18, alanine aminotransferase, platelets and triglycerides predict the presence of nonalcoholic steatohepatitis. PLoS One. 2013;8, e82092.

    Article  PubMed Central  PubMed  Google Scholar 

  52. Wong GL. Update of liver fibrosis and steatosis with transient elastography (Fibroscan). Gastroenterol Rep (Oxf). 2013;1:19–26.

    Article  Google Scholar 

  53. Nobili V, Vizzutti F, Arena U, et al. Accuracy and reproducibility of transient elastography for the diagnosis of fibrosis in pediatric nonalcoholic steatohepatitis. Hepatology. 2008;48:442–8.

    Article  CAS  PubMed  Google Scholar 

  54. Lupsor M, Badea R, Stefanescu H, et al. Performance of unidimensional transient elastography in staging non-alcoholic steatohepatitis. J Gastrointestin Liver Dis. 2010;19:53–60.

    PubMed  Google Scholar 

  55. Palmeri ML, Wang MH, Rouze NC, et al. Noninvasive evaluation of hepatic fibrosis using acoustic radiation force-based shear stiffness in patients with nonalcoholic fatty liver disease. J Hepatol. 2011;55:666–72. This was a novel study on the utility of acoustic radiation force impulse imaging in biopsy-proven NAFLD.

    Article  PubMed Central  PubMed  Google Scholar 

  56. Bota S, Herkner H, Sporea I, et al. Meta-analysis: ARFI elastography versus transient elastography for the evaluation of liver fibrosis. Liver Int. 2013;33:1138–47.

    Article  PubMed  Google Scholar 

  57. Friedrich-Rust M, Romen D, Vermehren J, et al. Acoustic radiation force impulse-imaging and transient elastography for non-invasive assessment of liver fibrosis and steatosis in NAFLD. Eur J Radiol. 2012;81:e325–31.

    Article  PubMed  Google Scholar 

  58. Osaki A, Kubota T, Suda T, et al. Shear wave velocity is a useful marker for managing nonalcoholic steatohepatitis. World J Gastroenterol. 2010;16:2918–25.

    Article  PubMed Central  PubMed  Google Scholar 

  59. Ferraioli G, Tinelli C, Dal Bello B, et al. Accuracy of real-time shear wave elastography for assessing liver fibrosis in chronic hepatitis C: a pilot study. Hepatology. 2012;56:2125–33.

    Article  PubMed  Google Scholar 

  60. Poynard T, Munteanu M, Luckina E, et al. Liver fibrosis evaluation using real-time shear wave elastography: applicability and diagnostic performance using methods without a gold standard. J Hepatol. 2013;58:928–35.

    Article  PubMed  Google Scholar 

  61. Deffieux T, Gennisson JL, Bousquet L, et al. Investigating liver stiffness and viscosity for fibrosis, steatosis and activity staging using shear wave elastography. J Hepatol. 2014.

  62. Cassinotto C, Lapuyade B, Mouries A, et al. Non-invasive assessment of liver fibrosis with impulse elastography: comparison of supersonic shear imaging with ARFI and FibroScan®. J Hepatol. 2014;61:550–7. This was a novel comparison study between acoustic radiation force impulse imaging and FibroScan®.

    Article  PubMed  Google Scholar 

  63. Tutar O, Beşer Ö, Adaletli I, et al. Shear wave elastography in the evaluation of liver fibrosis in children. J Pediatr Gastroenterol Nutr. 2014;58:750–5.

    CAS  PubMed  Google Scholar 

  64. Lupşor-Platon M, Stefănescu H, Mureșan D, et al. Noninvasive assessment of liver steatosis using ultrasound methods. Med Ultrason. 2014;16:236–45.

    PubMed  Google Scholar 

  65. Yoshioka K, Hashimoto S, Kawabe N. Measurement of liver stiffness as a non-invasive method for diagnosis of non-alcoholic fatty liver disease. Hepatol Res. 2014.

  66. Venkatesh SK, Ehman RL. Magnetic resonance elastography of liver. Magn Reson Imaging Clin N Am. 2014;22:433–46.

    Article  PubMed  Google Scholar 

  67. Huwart L, Sempoux C, Salameh N, et al. Liver fibrosis: noninvasive assessment with MR elastography versus aspartate aminotransferase-to-platelet ratio index. Radiology. 2007;245:458–66.

    Article  PubMed  Google Scholar 

  68. Huwart L, Sempoux C, Vicaut E, et al. Magnetic resonance elastography for the noninvasive staging of liver fibrosis. Gastroenterology. 2008;135:32–40.

    Article  PubMed  Google Scholar 

  69. Yin M, Talwalkar JA, Glaser KJ, et al. Assessment of hepatic fibrosis with magnetic resonance elastography. Clin Gastroenterol Hepatol. 2007;5:1207–13.e2.

    Article  PubMed Central  PubMed  Google Scholar 

  70. Loomba R, Wolfson T, Ang B, et al. Magnetic resonance elastography predicts advanced fibrosis in patients with nonalcoholic fatty liver disease: a prospective study. Hepatology. 2014. This was the first prospective study of biopsy-proven NAFLD paired with MRI and MRE imaging modalities.

  71. Chen J, Talwalkar JA, Yin M, et al. Early detection of nonalcoholic steatohepatitis in patients with nonalcoholic fatty liver disease by using MR elastography. Radiology. 2011;259:749–56. Early detection of nonalcoholic steatohepatitis in patients with nonalcoholic fatty liver disease by using MR elastography.

    Article  PubMed Central  PubMed  Google Scholar 

  72. Loomba R, Sirlin CB, Ang B, et al. Ezetimibe for the treatment of nonalcoholic steatohepatitis: assessment by novel MRI and MRE in a randomized trial (MOZART Trial). Hepatology. 2014.

  73. Lin SC, Heba E, Wolfson T, et al. Noninvasive diagnosis of nonalcoholic fatty liver disease and quantification of liver fat using a new quantitative ultrasound technique. Clin Gastroenterol Hepatol. 2014. This study identified a novel quantitative imaging biomarker, the quantitative ultrasound, for the diagnosis of NAFLD.

  74. Yu LF, Zhong J, Cheng SD, et al. Low-dose azathioprine effectively improves mucosal healing in Chinese patients with small bowel Crohn’s disease. J Dig Dis. 2014;15:180–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  75. Verdam FJ, Dallinga JW, Driessen A, et al. Non-alcoholic steatohepatitis: a non-invasive diagnosis by analysis of exhaled breath. J Hepatol. 2013;58:543–8.

    Article  CAS  PubMed  Google Scholar 

  76. Banasch M, Ellrichmann M, Tannapfel A, et al. The non-invasive (13)C-methionine breath test detects hepatic mitochondrial dysfunction as a marker of disease activity in non-alcoholic steatohepatitis. Eur J Med Res. 2011;16:258–64.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  77. Speliotes EK, Butler JL, Palmer CD, et al. PNPLA3 variants specifically confer increased risk for histologic nonalcoholic fatty liver disease but not metabolic disease. Hepatology. 2010;52:904–12.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  78. Rotman Y, Koh C, Zmuda JM, et al. The association of genetic variability in patatin-like phospholipase domain-containing protein 3 (PNPLA3) with histological severity of nonalcoholic fatty liver disease. Hepatology. 2010;52:894–903.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  79. Romeo S, Kozlitina J, Xing C, et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet. 2008;40:1461–5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  80. Liu YL, Patman GL, Leathart JB, et al. Carriage of the PNPLA3 rs738409 C >G polymorphism confers an increased risk of non-alcoholic fatty liver disease associated hepatocellular carcinoma. J Hepatol. 2014;61:75–81.

    Article  CAS  PubMed  Google Scholar 

  81. Singal AG, Manjunath H, Yopp AC, et al. The effect of PNPLA3 on fibrosis progression and development of hepatocellular carcinoma: a meta-analysis. Am J Gastroenterol. 2014;109:325–34.

    Article  CAS  PubMed  Google Scholar 

  82. Petersen KF, Dufour S, Hariri A, et al. Apolipoprotein C3 gene variants in nonalcoholic fatty liver disease. N Engl J Med. 2010;362:1082–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  83. Verrijken A, Beckers S, Francque S, et al. A gene variant of PNPLA3, but not of APOC3, is associated with histological parameters of NAFLD in an obese population. Obesity (Silver Spring). 2013;21:2138–45.

    Article  CAS  Google Scholar 

  84. Sentinelli F, Romeo S, Maglio C, et al. Lack of effect of apolipoprotein C3 polymorphisms on indices of liver steatosis, lipid profile and insulin resistance in obese Southern Europeans. Lipids Health Dis. 2011;10:93.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  85. Kozlitina J, Smagris E, Stender S, et al. Exome-wide association study identifies a TM6SF2 variant that confers susceptibility to nonalcoholic fatty liver disease. Nat Genet. 2014;46:352–6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  86. Dongiovanni P, Petta S, Maglio C, et al. Transmembrane 6 superfamily member 2 gene variant disentangles nonalcoholic steatohepatitis from cardiovascular disease. Hepatology. 2015;61:506–14. This is a novel study that found a variant of TM6SF2 to be associated with cardiovascular disease risk.

    Article  CAS  PubMed  Google Scholar 

  87. Hernaez R. Genetic factors associated with the presence and progression of nonalcoholic fatty liver disease: a narrative review. Gastroenterol Hepatol. 2012;35:32–41.

    Article  PubMed  Google Scholar 

  88. Mehta R, Birerdinc A, Younossi ZM. Host genetic variants in obesity-related nonalcoholic fatty liver disease. Clin Liver Dis. 2014;18:249–67.

    Article  PubMed  Google Scholar 

  89. Ulitsky A, Ananthakrishnan AN, Komorowski R, et al. A noninvasive clinical scoring model predicts risk of nonalcoholic steatohepatitis in morbidly obese patients. Obes Surg. 2010;20:685–91.

    Article  PubMed  Google Scholar 

  90. Sumida Y, Yoneda M, Hyogo H, et al. A simple clinical scoring system using ferritin, fasting insulin, and type IV collagen 7S for predicting steatohepatitis in nonalcoholic fatty liver disease. J Gastroenterol. 2011;46:257–68.

    Article  CAS  PubMed  Google Scholar 

  91. Pearce SG, Thosani NC, Pan JJ. Noninvasive biomarkers for the diagnosis of steatohepatitis and advanced fibrosis in NAFLD. Biomark Res. 2013;1:7.

    Article  PubMed Central  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  93. Palekar NA, Naus R, Larson SP, et al. Clinical model for distinguishing nonalcoholic steatohepatitis from simple steatosis in patients with nonalcoholic fatty liver disease. Liver Int. 2006;26:151–6.

    Article  PubMed  Google Scholar 

  94. Chowdhury SD, Ramakrishna B, Eapen CE, et al. Fibrosis in non-alcoholic fatty liver disease: correlation with simple blood indices and association with tumor necrosis factor-alpha polymorphisms. Trop Gastroenterol. 2013;34:31–5.

    Article  PubMed  Google Scholar 

  95. McPherson S, Stewart SF, Henderson E, et al. Simple non-invasive fibrosis scoring systems can reliably exclude advanced fibrosis in patients with non-alcoholic fatty liver disease. Gut. 2010;59:1265–9.

    Article  PubMed  Google Scholar 

  96. Williams AL, Hoofnagle JH. Ratio of serum aspartate to alanine aminotransferase in chronic hepatitis. Relationship to cirrhosis. Gastroenterology. 1988;95:734–9.

    CAS  PubMed  Google Scholar 

  97. Poynard T, Ratziu V, Naveau S, et al. The diagnostic value of biomarkers (SteatoTest) for the prediction of liver steatosis. Comp Hepatol. 2005;4:10.

    Article  PubMed Central  PubMed  Google Scholar 

  98. Loaeza-del-Castillo A, Paz-Pineda F, Oviedo-Cárdenas E, et al. AST to platelet ratio index (APRI) for the noninvasive evaluation of liver fibrosis. Ann Hepatol. 2008;7:350–7.

    CAS  PubMed  Google Scholar 

  99. Guha IN, Parkes J, Roderick P, et al. Noninvasive markers of fibrosis in nonalcoholic fatty liver disease: Validating the Liver European Fibrosis Panel and exploring simple markers. Hepatology. 2008;47:455–60.

    Article  PubMed  Google Scholar 

  100. Rosenberg WM, Voelker M, Thiel R, et al. Serum markers detect the presence of liver fibrosis: a cohort study. Gastroenterology. 2004;127:1704–13.

    Article  PubMed  Google Scholar 

  101. Shah AG, Lydecker A, Murray K, et al. Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2009;7:1104–12.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  102. Tahan V, Canbakan B, Balci H, et al. Serum gamma-glutamyltranspeptidase distinguishes non-alcoholic fatty liver disease at high risk. Hepatogastroenterology. 2008;55:1433–8.

    CAS  PubMed  Google Scholar 

  103. Calès P, Boursier J, Chaigneau J, et al. Diagnosis of different liver fibrosis characteristics by blood tests in non-alcoholic fatty liver disease. Liver Int. 2010;30:1346–54.

    Article  PubMed  Google Scholar 

  104. Alkhouri N, Mansoor S, Giammaria P, et al. The development of the pediatric NAFLD fibrosis score (PNFS) to predict the presence of advanced fibrosis in children with nonalcoholic fatty liver disease. PLoS One. 2014;9, e104558.

    Article  PubMed Central  PubMed  Google Scholar 

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Conflict of Interest

Ahilan Arulanandan declares no conflict of interest.

Rohit Loomba is a member of the clinical advisory board of Galmed Inc. and Arrowhead Research Inc. and has received consultancy fees from both as well as from Gilead Inc., Genentech Inc., Merck Inc., Alnylam Inc., Celgene Inc., RuiYi Inc., and DeutRx Inc. Rohit Loomba is supported in part by the American Gastroenterological Association (AGA) Foundation–Sucampo–ASP Designated Research Award in Geriatric Gastroenterology and by a T. Franklin Williams Scholarship Award; funding provided by Atlantic Philanthropies Inc., the John A. Hartford Foundation, the Association of Specialty Professors, and the American Gastroenterological Association and grant K23-DK090303. The study sponsor(s) had no role in the study design, collection, analysis, interpretation of the data, and/or drafting of the manuscript. All authors report that no conflicts of interest exist.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Author Contributions

Ahilan Arulanandan—analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript, approved final submission

Rohit Loomba—study concept and design, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript, study supervision, approved final submission

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Authors and Affiliations

  1. NAFLD Translational Research Unit, Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla, CA, USA

    Ahilan Arulanandan & Rohit Loomba

  2. Division of Epidemiology, Department of Family and Preventive Medicine, Department of Medicine, University of California, San Diego, La Jolla, CA, USA

    Rohit Loomba

  3. Division of Gastroenterology and Epidemiology, University of California, San Diego, 9500 Gilman Drive, MC 0063, La Jolla, CA, 92093, USA

    Rohit Loomba

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This article is part of the Topical Collection on Fatty Liver Disease

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Arulanandan, A., Loomba, R. Noninvasive Testing for NASH and NASH with Advanced Fibrosis: Are We There Yet?. Curr Hepatology Rep 14, 109–118 (2015). https://doi.org/10.1007/s11901-015-0263-9

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