Noninvasive testing for NASH and NASH with advanced fibrosis: Are we there yet?

Current Hepatitis Reports

Volumn 14, Issue 2, 2015, Pages 109-118

  Arulanandan, Ahilan ^a   Loomba, Rohit ^a,b  

^a UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Advanced fibrosis; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; Noninvasive biomarker

Indexed keywords

ADIPOCYTOKINE; BIOLOGICAL MARKER; CYTOKERATIN 18; FAS LIGAND; FERRITIN; PROCOLLAGEN; PROCOLLAGEN III; UNCLASSIFIED DRUG;

ARTICLE; BREATH ANALYSIS; CLINICAL PREDICTOR MODEL; DIAGNOSTIC IMAGING; DISEASE MARKER; HEREDITY; HUMAN; LIPOTOXICITY; LIVER FIBROSIS; NON INVASIVE PROCEDURE; NONALCOHOLIC FATTY LIVER; OXIDATIVE STRESS; PREDICTION; SCORING SYSTEM;

EID: 84943247934     PISSN: 15403416     EISSN: 15410706     Source Type: Journal    
DOI: 10.1007/s11901-015-0263-9     Document Type: Article

References (104)

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.
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.
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.
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.
6. Stepanova M, Rafiq N, Makhlouf H, et al. Predictors ofall-cause mortality and liver-related mortality in patients with non-alcoholic fatty liver disease (NAFLD). Dig Dis Sci. 2013;58:3017-23.
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: aprospective study. Gastroenterology. 2011;140:124-31.
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.
9. Soderberg C, Stal 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.
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.
11. Desmet VJ, Gerber M, Hoofnagle JH, et al. Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology. 1994;19:1513-20.
12. Bravo AA, Sheth SG, Chopra S. Liver biopsy. N Engl J Med. 2001;344:495-500.
13. Mato JM, Lu SC. Where are we in the search for noninvasive nonalcoholic steatohepatitis biomarkers? Hepatology. 2011;54: 1115-7.
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.
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.
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.
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.
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.
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.
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.
21. Tamimi TI, Elgouhari HM, Alkhouri N, et al. An apoptosis panel for nonalcoholic steatohepatitis diagnosis. J Hepatol. 2011;54: 1224-9.
22. Wang K. Molecular mechanisms of hepatic apoptosis. Cell Death Dis. 2014;5, e996.
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.
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.
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.
26. Wieckowska A, Papouchado BG, Li Z, et al. Role ofinterleukin-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.
28. Machado MV, Coutinho J, Carepa F, et al. How adiponectin, lep-tin, and ghrelin orchestrate together and correlate with the severity of nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol. 2012;24:1166-72.
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.
30. Manousou P, Kalambokis G, Grillo F, et al. Serum ferritin is a discriminant marker for both fibrosis and inflammation in histo-logically proven non-alcoholic fatty liver disease patients. Liver Int. 2011;31:730-9.
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.
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.
34. Dowman JK, Tomlinson JW, Newsome PN. Systematic review: the diagnosis and staging of non-alcoholic fatty liver disease and nonalcoholic steatohepatitis. Aliment Pharmacol Ther. 2011;33:525-40.
35. Adams LA, Feldstein AE. Non-invasive diagnosis of nonalcoholic fatty liver and nonalcoholic steatohepatitis. J Dig Dis. 2011;12:10-6.
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.
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.
38. Sanyal AJ, Chalasani N, Kowdley KV, etal. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med. 2010;362:1675-85.
39. Loomba R, Quehenberger O, Armando A, et al. Polyunsaturated fatty acid metabolites as novel lipidomic biomarkers for noninva-sive diagnosis of nonalcoholic steatohepatitis. J Lipid Res. 2015;56:185-92.This study identified polyunsaturated fatty acid metabolites that could differentiate NAFL from NASH.
40. Ratziu V, Giral P, Charlotte F, et al. Liver fibrosis in overweight patients. Gastroenterology. 2000;118:1117-23.
41. Angulo P, Keach JC, Batts KP, et al. Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology. 1999;30:1356-62.
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.
43. Noureddin M, Yates KP, Vaughn IA, et al. Clinical and histolog-ical determinants of nonalcoholic steatohepatitis and advanced fibrosis in elderly patients. Hepatology. 2013;58:1644-54.
44. Dixon JB, Bhathal PS, O'Brien PE. Nonalcoholic fatty liver disease: predictors ofnonalcoholic steatohepatitis and liverfibrosis in the severely obese. Gastroenterology. 2001;121:91-100.
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.
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.
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.
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.
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.
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.
51. Cao W, Zhao C, Shen C, et al. Cytokeratin 18, alanine aminotrans-ferase, platelets and triglycerides predict the presence of nonalcoholic steatohepatitis. PLoS One. 2013;8, e82092.
52. Wong GL. Update of liver fibrosis and steatosis with transient elastography (Fibroscan). Gastroenterol Rep (Oxf). 2013;1:19-26.
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.
54. Lupsor M, Badea R, Stefanescu H, et al. Performance of unidi-mensional transient elastography in staging non-alcoholic steatohepatitis. J Gastrointestin Liver Dis. 2010;19:53-60.
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.
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.
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.
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.
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.
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.
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 assess-ment 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®.
63. Tutar O, Beser O, Adaletli I, et al. Shear wave elastography in the evaluation of liver fibrosis in children. J Pediatr Gastroenterol Nutr. 2014;58:750-5.
64. Lupsor-Platon M, Stefanescu H, Muresan D, et al. Noninvasive assessment of liver steatosis using ultrasound methods. Med Ultrason. 2014;16:236-45.
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.
67. Huwart L, Sempoux C, Salameh N, et al. Liver fibrosis: noninva-sive assessment with MR elastography versus aspartate aminotransferase-to-platelet ratio index. Radiology. 2007;245: 458-66.
68. Huwart L, Sempoux C, Vicaut E, et al. Magnetic resonance elastography for the noninvasive staging of liver fibrosis. Gastroenterology. 2008;135:32-40.
69. Yin M, Talwalkar JA, Glaser KJ, et al. Assessment of hepatic fibro-sis with magnetic resonance elastography. Clin Gastroenterol Hepatol. 2007;5:1207-13.e2.
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 nonalcohol-ic 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.
72. 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 non-alcoholic 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.
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.
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.
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.
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.
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.
80. Liu YL, Patman GL, Leathart JB, et al. Carriage of the PNPLA3 rs738409 C >G polymorphism confers an increased risk of nonalcoholic fatty liver disease associated hepatocellular carcinoma. J Hepatol. 2014;61:75-81.
81. Singal AG, Manjunath H, Yopp AC, et al. The effect ofPNPLA3 on fibrosis progression and development of hepatocellular carcinoma: a meta-analysis. Am J Gastroenterol. 2014;109:325-34.
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.
83. Verrijken A, Beckers S, Francque S, et al. A gene variantofPNPL A3, but not of APOC3, is associated with histological parameters of NAFLD in an obese population. Obesity (Silver Spring). 2013;21:2138-45.
84. Sentinelli F, Romeo S, Maglio C, et al. Lack of effect of apolipo-protein C3 polymorphisms on indices of liver steatosis, lipid profile and insulin resistance in obese Southern Europeans. Lipids HealthDis. 2011;10:93.
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.
86. Dongiovanni P, Petta S, Maglio C, et al. Transmembrane 6 super-family member 2 gene variant disentangles nonalcoholic steatohepatitis from cardiovascular disease. Hepatology. 2015;61: 506-14.This is anovel studythatfound avariant of TM6SF2 to be associated with cardiovascular disease risk.
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.
88. Mehta R, Birerdinc A, Younossi ZM. Host genetic variants in obesity-related nonalcoholic fatty liver disease. Clin Liver Dis. 2014;18:249-67.
89. Ulitsky A, Ananthakrishnan AN, Komorowski R, et al. A nonin-vasive clinical scoring model predicts risk of nonalcoholic steatohepatitis in morbidly obese patients. Obes Surg. 2010;20: 685-91.
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.
91. Pearce SG, Thosani NC, Pan JJ. Noninvasive biomarkers for the diagnosis of steatohepatitis and advanced fibrosis in NAFLD. Biomark Res. 2013;1:7.
92. Younossi ZM, Jarrar M, Nugent C, et al. A novel diagnostic bio-marker panel for obesity-related nonalcoholic steatohepatitis (NASH). Obes Surg. 2008;18:1430-7.
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.
94. Chowdhury SD, Ramakrishna B, Eapen CE, et al. Fibrosis in nonalcoholic fatty liver disease: correlation with simple blood indices and association with tumor necrosis factor-alpha polymorphisms. Trop Gastroenterol. 2013;34:31-5.
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.
96. Williams AL, Hoofnagle JH. Ratio of serum aspartate to alanine aminotransferase in chronic hepatitis. Relationship to cirrhosis. Gastroenterology. 1988;95:734-9.
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.
98. Loaeza-del-Castillo A, Paz-Pineda F, Oviedo-Cardenas E, et al. AST to platelet ratio index (APRI) for the noninvasive evaluation of liver fibrosis. Ann Hepatol. 2008;7:350-7.
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.
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.
101. Shah AG, Lydecker A, Murray K, et al. Comparison of noninva-sive markers of fibrosis in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2009;7:1104-12.
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.
103. Cales 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.
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.