Non-alcoholic fatty liver diseases: Update on the challenge of diagnosis and treatment

Clinical and Molecular Hepatology

Volumn 22, Issue 3, 2016, Pages 327-335

  Oh, Hyunwoo ^a,b   Jun, Dae Won ^a   Saeed, Waqar K ^a   Nguyen, Mindie H ^c  

^a Hanyang University College of Medicine   (South Korea)

^b Army Cadet Military School   (South Korea)

^c STANFORD UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

Diagnosis; Non alcoholic fatty liver; Treatment

Indexed keywords

2 (2 CHLOROPHENYL) 4 [3 (DIMETHYLAMINO)PHENYL] 5 METHYL 1H PYRAZOLO[4,3 C]PYRIDINE 3,6(2H,5H) DIONE; ALPHA TOCOPHEROL; CENICRIVIROC; ELAFIBRANOR; EMRICASAN; GALECTIN 3; NONOXINOL 9; OBETICHOLIC ACID; SELONSERTIB; SIMTUZUMAB; BIOLOGICAL MARKER; CHENODEOXYCHOLIC ACID;

COMPUTER ASSISTED TOMOGRAPHY; DISEASE SEVERITY; HUMAN; LIFESTYLE MODIFICATION; LIVER FIBROSIS; NONALCOHOLIC FATTY LIVER; NUCLEAR MAGNETIC RESONANCE IMAGING; PREVALENCE; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; ANALOGS AND DERIVATIVES; CLINICAL TRIAL (TOPIC); DIAGNOSTIC IMAGING; ECHOGRAPHY; FATTY LIVER; FIBROSIS; LIVER; NON-ALCOHOLIC FATTY LIVER DISEASE; PATHOLOGY; X-RAY COMPUTED TOMOGRAPHY;

BIOMARKERS; CHENODEOXYCHOLIC ACID; CLINICAL TRIALS AS TOPIC; FATTY LIVER; FIBROSIS; HUMANS; LIVER; MAGNETIC RESONANCE IMAGING; NON-ALCOHOLIC FATTY LIVER DISEASE; TOMOGRAPHY, X-RAY COMPUTED; ULTRASONOGRAPHY; VITAMIN E;

EID: 85014810867     PISSN: 22872728     EISSN: 2287285X     Source Type: Journal    
DOI: 10.3350/cmh.2016.0049     Document Type: Review

References (56)

1. Jeong EH, Jun DW, Cho YK, Choe YG, Ryu S, Lee SM, et al. Regional prevalence of non-alcoholic fatty liver disease in Seoul and Gyeonggi-do, Korea. Clin Mol Hepatol 2013;19:266-272.
2. Bohte AE, van Werven JR, Bipat S, Stoker J. The diagnostic accuracy of US, CT, MRI and 1H-MRS for the evaluation of hepatic steatosis compared with liver biopsy: a meta-analysis. Eur Radiol 2011;21:87-97.
3. Pickhardt PJ, Park SH, Hahn L, Lee SG, Bae KT, Yu ES. Specificity of unenhanced CT for non-invasive diagnosis of hepatic steatosis: implications for the investigation of the natural history of incidental steatosis. Eur Radiol 2012;22:1075-1082.
4. Kang BK, Yu ES, Lee SS, Lee Y, Kim N, Sirlin CB, et al. Hepatic fat quantification: a prospective comparison of magnetic resonance spectroscopy and analysis methods for chemical-shift gradient echo magnetic resonance imaging with histologic assessment as the reference standard. Invest Radiol 2012;47:368-375.
5. Henninger B, Zoller H, Rauch S, Schocke M, Kannengiesser S, Zhong X, et al. Automated two-point dixon screening for the evaluation of hepatic steatosis and siderosis: comparison with R2-relaxometry and chemical shift-based sequences. Eur Radiol 2015;25:1356-1365.
6. Hu HH, Bornert P, Hernando D, Kellman P, Ma J, Reeder S, et al. ISMRM workshop on fat-water separation: insights, applications and progress in MRI. Magn Reson Med 2012;68:378-388.
7. Noureddin M, Lam J, Peterson MR, Middleton M, Hamilton G, Le TA, et al. Utility of magnetic resonance imaging versus histology for quantifying changes in liver fat in nonalcoholic fatty liver disease trials. Hepatology 2013;58:1930-1940.
8. Loomba R, Sirlin CB, Ang B, Bettencourt R, Jain R, Salotti J, et al. Ezetimibe for the treatment of nonalcoholic steatohepatitis: assessment by novel magnetic resonance imaging and magnetic resonance elastography in a randomized trial (MOZART trial). Hepatology 2015;61:1239-1250.
9. Tang A, Desai A, Hamilton G, Wolfson T, Gamst A, Lam J, et al. Accuracy of MR imaging-estimated proton density fat fraction for classification of dichotomized histologic steatosis grades in nonalcoholic fatty liver disease. Radiology 2015;274:416-425.
10. Tang A, Tan J, Sun M, Hamilton G, Bydder M, Wolfson T, et al. Nonalcoholic fatty liver disease: MR imaging of liver proton density fat fraction to assess hepatic steatosis. Radiology 2013;267:422-431.
11. Bedogni G, Bellentani S, Miglioli L, Masutti F, Passalacqua M, Castiglione A, et al. The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population. BMC Gastroenterol 2006;6:33.
12. Poynard T, Ratziu V, Naveau S, Thabut D, Charlotte F, Messous D, et al. The diagnostic value of biomarkers (SteatoTest) for the prediction of liver steatosis. Comp Hepatol 2005;4:10.
13. Alaaeddine N, Sidaoui J, Hilal G, Serhal R, Abedelrahman A, Khoury S. TNF-alpha messenger ribonucleic acid (mRNA) in patients with nonalcoholic steatohepatitis. Eur Cytokine Netw 2012;23:107-111.
14. Tarantino G, Conca P, Pasanisi F, Ariello M, Mastrolia M, Arena A, et al. Could inflammatory markers help diagnose nonalcoholic steatohepatitis? Eur J Gastroenterol Hepatol 2009;21:504-511.
15. Fierbinteanu-Braticevici C, Baicus C, Tribus L, Papacocea R. Predictive factors for nonalcoholic steatohepatitis (NASH) in patients with nonalcoholic fatty liver disease (NAFLD). J Gastrointestin Liver Dis 2011;20:153-159.
16. Yoneda M, Uchiyama T, Kato S, Endo H, Fujita K, Yoneda K, et al. Plasma Pentraxin3 is a novel marker for nonalcoholic steatohepatitis (NASH). BMC Gastroenterol 2008;8:53.
17. Yoneda M, Nozaki Y, Endo H, Mawatari H, Iida H, Fujita K, et al. Serum ferritin is a clinical biomarker in Japanese patients with nonalcoholic steatohepatitis (NASH) independent of HFE gene mutation. Dig Dis Sci 2010;55:808-814.
18. Tamimi TI, Elgouhari HM, Alkhouri N, Yerian LM, Berk MP, Lopez R, et al. An apoptosis panel for nonalcoholic steatohepatitis diagnosis. J Hepatol 2011;54:1224-1229.
19. Kayadibi H, Gültepe M, Yasar B, Ince AT, Ozcan O, Ipcioglu OM, et al. Diagnostic value of serum prolidase enzyme activity to predict the liver histological lesions in non-alcoholic fatty liver disease: a surrogate marker to distinguish steatohepatitis from simple steatosis. Dig Dis Sci 2009;54:1764-1771.
20. Cusi K, Chang Z, Harrison S, Lomonaco R, Bril F, Orsak B, 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;60:167-174.
21. Kwok R, Tse YK, Wong GL, Ha Y, Lee AU, Ngu MC, et al. Systematic review with meta-analysis: non-invasive assessment of non-alcoholic fatty liver disease--the role of transient elastography and plasma cytokeratin-18 fragments. Aliment Pharmacol Ther 2014;39:254-269.
22. Poynard T, Ratziu V, Charlotte F, Messous D, Munteanu M, Imbert-Bismut F, et al. Diagnostic value of biochemical markers (NashTest) for the prediction of non alcoholo steato hepatitis in patients with non-alcoholic fatty liver disease. BMC Gastroenterol 2006;6:34.
23. Younossi ZM, Jarrar M, Nugent C, Randhawa M, Afendy M, Stepanova M, et al. A novel diagnostic biomarker panel for obesity-related nonalcoholic steatohepatitis (NASH). Obes Surg 2008;18:1430-1437.
24. Younossi ZM, Page S, Rafiq N, Birerdinc A, Stepanova M, Hossain N, et al. A biomarker panel for non-alcoholic steatohepatitis (NASH) and NASH-related fibrosis. Obes Surg 2011;21:431-439.
25. Anty R, Iannelli A, Patouraux S, Bonnafous S, Lavallard VJ, Senni-Buratti M, et al. A new composite model including metabolic syndrome, alanine aminotransferase and cytokeratin-18 for the diagnosis of non-alcoholic steatohepatitis in morbidly obese patients. Aliment Pharmacol Ther 2010;32:1315-1322.
26. 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.
27. Angulo P, Hui JM, Marchesini G, Bugianesi E, George J, Farrell GC, et al. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology 2007;45:846-854.
28. Wai CT, Greenson JK, Fontana RJ, Kalbfleisch JD, Marrero JA, Conjeevaram HS, et al. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology 2003;38:518-526.
29. Guha IN, Parkes J, Roderick P, Chattopadhyay D, Cross R, Harris S, et al. Noninvasive markers of fibrosis in nonalcoholic fatty liver disease: Validating the European Liver Fibrosis Panel and exploring simple markers. Hepatology 2008;47:455-460.
30. Ratziu V, Massard J, Charlotte F, Messous D, Imbert-Bismut F, Bonyhay L, et al. Diagnostic value of biochemical markers (FibroTest-FibroSURE) for the prediction of liver fibrosis in patients with non-alcoholic fatty liver disease. BMC Gastroenterol 2006;6:6.
31. Harrison SA, Oliver D, Arnold HL, Gogia S, Neuschwander-Tetri BA. Development and validation of a simple NAFLD clinical scoring system for identifying patients without advanced disease. Gut 2008;57:1441-1447.
32. Wong VW, Wong GL, Chim AM, Tse AM, Tsang SW, Hui AY, et al. Validation of the NAFLD fibrosis score in a Chinese population with low prevalence of advanced fibrosis. Am J Gastroenterol 2008;103:1682-1688.
33. Sumida Y, Yoneda M, Hyogo H, Yamaguchi K, Ono M, Fujii 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;46:257-268.
34. Yu SJ, Kim DH, Lee JH, Chung GE, Yim JY, Park MJ, et al. Validation of P2/MS and other noninvasive fibrosis scoring systems in the Korean population with nonalcoholic fatty liver disease. Korean J Gastroenterol 2011;57:19-27.
35. Bonekamp S, Tang A, Mashhood A, Wolfson T, Changchien C, Middleton MS, et al. Spatial distribution of MRI-Determined hepatic proton density fat fraction in adults with nonalcoholic fatty liver disease. J Magn Reson Imaging 2014;39:1525-1532.
36. Brunt EM. Nonalcoholic fatty liver disease: pros and cons of histologic systems of evaluation. Int J Mol Sci 2016;17. Pii: E97.
37. 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;94:2467-2474.
38. 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;41:1313-1321.
39. Brunt EM, Kleiner DE, Wilson LA, Belt P, Neuschwander-Tetri BA; NASH Clinical Research Network (CRN). Nonalcoholic fatty liver disease (NAFLD) activity score and the histopathologic diagnosis in NAFLD: distinct clinicopathologic meanings. Hepatology 2011;53:810-820.
40. Bedossa P; FLIP Pathology Consortium. Utility and appropriateness of the fatty liver inhibition of progression (FLIP) algorithm and steatosis, activity, and fibrosis (SAF) score in the evaluation of biopsies of nonalcoholic fatty liver disease. Hepatology 2014;60:565-575.
41. Bedossa P, Poitou C, Veyrie N, Bouillot JL, Basdevant A, Paradis V, et al. Histopathological algorithm and scoring system for evaluation of liver lesions in morbidly obese patients. Hepatology 2012;56:1751-1759.
42. Lazo M, Solga SF, Horska A, Bonekamp S, Diehl AM, Brancati FL, et al. Effect of a 12-month intensive lifestyle intervention on hepatic steatosis in adults with type 2 diabetes. Diabetes Care 2010;33:2156-2163.
43. Schafer S, Kantartzis K, Machann J, Venter C, Niess A, Schick F, et al. Lifestyle intervention in individuals with normal versus impaired glucose tolerance. Eur J Clin Invest 2007;37:535-543.
44. Vilar-Gomez E, Martinez-Perez Y, Calzadilla-Bertot L, Torres Gonzalez A, Gra Oramas B, Gonzalez Fabian L, et al. Weight Loss Through Lifestyle Modification Significantly Reduces Features of Nonalcoholic Steatohepatitis. Gastroenterology 2015;149:367-378.
45. Sanyal AJ, Chalasani N, Kowdley KV, McCullough A, Diehl AM, Bass NM, et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med 2010;362:1675-1685.
46. Neuschwander-Tetri BA, Loomba R, Sanyal AJ, Lavine JE, Van Natta ML, Abdelmalek MF, et al. Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial. Lancet 2015;385:956-965.
47. Lawlor DA, Callaway M, Macdonald-Wallis C, Anderson E, Fraser A, Howe LD, et al. Nonalcoholic fatty liver disease, liver fibrosis, and cardiometabolic risk factors in adolescence: a cross-sectional study of 1874 general population adolescents. J Clin Endocrinol Metab 2014;99:E410-E417.
48. Fang S, Suh JM, Reilly SM, Yu E, Osborn O, Lackey D, et al. Intestinal FXR agonism promotes adipose tissue browning and reduces obesity and insulin resistance. Nat Med 2015;21:159-165.
49. Aoyama T, Paik YH, Watanabe S, Laleu B, Gaggini F, Fioraso-Cartier L, et al. Nicotinamide adenine dinucleotide phosphate oxidase in experimental liver fibrosis: GKT137831 as a novel potential therapeutic agent. Hepatology 2012;56:2316-2327.
50. Yang RY, Rabinovich GA, Liu FT. Galectins: structure, function and therapeutic potential. Expert Rev Mol Med 2008;10:e17.
51. Lefebvre E, Gottwald M, Lasseter K, Chang W, Willett M, Smith PF, et al. Pharmacokinetics, Safety, and CCR2/CCR5 Antagonist Activity of Cenicriviroc in Participants With Mild or Moderate Hepatic Impairment. Clin Transl Sci 2016:9:139-148.
52. Barreyro FJ, Holod S, Finocchietto PV, Camino AM, Aquino JB, Avagnina A, et al. The pan-caspase inhibitor Emricasan (IDN-6556) decreases liver injury and fibrosis in a murine model of non-alcoholic steatohepatitis. Liver Int 2015;35:953-966.
53. Shiffman M, Freilich B, Vuppalanchi R, Watt K, Burgess G, Morris M, et al. A placebo-controlled, multicenter, double-blind, randomised trial of emricasan (IDN-6556) in subjects with non-alcoholic fatty liver disease (NAFLD) and raised transaminases. J Hepatol 2015;62(Suppl 2):S282.
54. Ratziu V, Harrison SA, Francque SM, Bedossa P, Serfaty L, Romero-Gomez M, et al. An international, phase 2 randomized controlled trial of the dual PPAR α-δ agonist GFT505 in adult patients with NASH. Hepatology 2015;62(Suppl 1): 262A-263A.
55. Xiang M, Wang PX, Wang AB, Zhang XJ, Zhang Y, Zhang P, et al. Targeting hepatic TRAF1-ASK1 signaling to improve inflammation, insulin resistance, and hepatic steatosis. J Hepatol 2016;64:1365-1377.
56. Barry-Hamilton V, Spangler R, Marshall D, McCauley S, Rodriguez HM, Oyasu M, et al. Allosteric inhibition of lysyl oxidase-like-2 impedes the development of a pathologic microenvironment. Nat Med 2010;16:1009-1017.