#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

The diagnostic accuracy of liver fibrosis in non-viral liver diseases using acoustic radiation force impulse elastography: A systematic review and meta-analysis


Autoři: Yuanqiang Lin aff001;  Hequn Li aff001;  Chunxiang Jin aff001;  Hui Wang aff001;  Bo Jiang aff002
Působiště autorů: Department of Ultrasound, China-Japan Union Hospital, Jilin University, China aff001;  Department of General Surgery, Nanhu Hospital, China-Japan Union Hospital, Jilin University, China aff002
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0227358

Souhrn

Background

Acoustic radiation force impulse (ARFI) imaging is an ultrasound-based elastography method that has been studied in the staging of hepatic fibrosis, especially in chronic hepatitis. However, the diagnostic accuracy of ARFI in non-viral hepatopathies, such as autoimmune hepatitis and non-alcoholic fatty liver disease, has not been systematically determined.

Aim

To systematically assess the diagnostic accuracy of ARFI in non-viral hepatopathies.

Methods

The databases of PubMed, Embase, Cochrane Library and clinicaltrials.gov were systematically searched for candidate studies reporting the diagnostic accuracy of ARFI for hepatic fibrosis. The pooled estimates of the sensitivity, specificity, diagnostic odds ratio, and positive and negative likelihood ratios were calculated with the summary receiver operating curve (sROC) performed using STATA software.

Results

In detail, a total of 29 diagnostic studies were included for further analysis. The quality of the included studies was relatively high using QUADAS method. The pooled sensitivity and specificity were 0.79 (0.73, 0.83) and 0.81 (0.75, 0.86), with AUROC 0.87 (0.83, 0.89) for the staging of significant fibrosis (F≥2). Meanwhile, for the staging of severe fibrosis (F≥3), the pooled sensitivity and specificity were 0.92 (0.87, 0.95) and 0.85 (0.80, 0.89), with AUROC 0.94 (0.92, 0.96). Furthermore, the pooled sensitivity and specificity were 0.89 (0.79, 0.95) and 0.89 (0.85, 0.92), with AUROC 0.94 (0.92, 0.96) for ARFI in staging cirrhosis (F = 4), which were similar to the data for severe fibrosis. No significant publication bias was present in this study.

Conclusion

This meta-analysis demonstrated that ARFI exerted satisfactory diagnostic performance in staging non-viral hepatic fibrosis, especially severe fibrosis (F≥3) and cirrhosis (F = 4).

Klíčová slova:

Cirrhosis – Database searching – Diagnostic medicine – Fibrosis – Liver diseases – Liver fibrosis – Liver transplantation – Metaanalysis


Zdroje

1. Friedrich-Rust M, Nierhoff J, Lupsor M, Sporea I, Fierbinteanu-Braticevici C, Strobel D, et al. Performance of Acoustic Radiation Force Impulse imaging for the staging of liver fibrosis: a pooled meta-analysis. J Viral Hepat. 2012;19(2):e212–9. Epub 2012/01/14. doi: 10.1111/j.1365-2893.2011.01537.x 22239521.

2. Ying HZ, Chen Q, Zhang WY, Zhang HH, Ma Y, Zhang SZ, et al. PDGF signaling pathway in hepatic fibrosis pathogenesis and therapeutics (Review). Mol Med Rep. 2017;16(6):7879–89. Epub 2017/10/07. doi: 10.3892/mmr.2017.7641 28983598; PubMed Central PMCID: PMC5779870.

3. Anstee QM, Reeves HL, Kotsiliti E, Govaere O, Heikenwalder M. From NASH to HCC: current concepts and future challenges. Nat Rev Gastroenterol Hepatol. 2019. Epub 2019/04/28. doi: 10.1038/s41575-019-0145-7 31028350.

4. Czaja AJ. Review article: The prevention and reversal of hepatic fibrosis in autoimmune hepatitis. Aliment Pharmacol Ther. 2014;39(4):385–406. Epub 2014/01/07. doi: 10.1111/apt.12592 24387318.

5. Arab JP, Barrera F, Arrese M. The Evolving Role of Liver Biopsy in Non-alcoholic Fatty Liver Disease. Ann Hepatol. 2018;17(6):899–902. Epub 2019/01/03. doi: 10.5604/01.3001.0012.7188 30600304.

6. Nierhoff J, Chavez Ortiz AA, Herrmann E, Zeuzem S, Friedrich-Rust M. The efficiency of acoustic radiation force impulse imaging for the staging of liver fibrosis: a meta-analysis. Eur Radiol. 2013;23(11):3040–53. Epub 2013/06/27. doi: 10.1007/s00330-013-2927-6 23801420.

7. Rockey DC, Caldwell SH, Goodman ZD, Nelson RC, Smith AD, American Association for the Study of Liver D. Liver biopsy. Hepatology. 2009;49(3):1017–44. Epub 2009/02/27. doi: 10.1002/hep.22742 19243014.

8. Sumida Y, Nakajima A, Itoh Y. Limitations of liver biopsy and non-invasive diagnostic tests for the diagnosis of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. World J Gastroenterol. 2014;20(2):475–85. Epub 2014/02/28. doi: 10.3748/wjg.v20.i2.475 24574716; PubMed Central PMCID: PMC3923022.

9. Abdelhaleem H, Gamal Eldeen H, Nabeel MM, Abdelmoniem R, Elakel W, Zayed N, et al. Evaluation of acoustic radiation force impulse (ARFI) elastography as non-invasive diagnostic tool in living donor liver transplantation. Abdom Radiol (NY). 2019;44(2):464–72. Epub 2018/09/02. doi: 10.1007/s00261-018-1732-8 30171294.

10. Wu S, Yang Z, Zhou J, Zeng N, He Z, Zhan S, et al. Systematic review: diagnostic accuracy of non-invasive tests for staging liver fibrosis in autoimmune hepatitis. Hepatol Int. 2019;13(1):91–101. Epub 2018/11/18. doi: 10.1007/s12072-018-9907-5 30443702.

11. 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(2):518–26. Epub 2003/07/29. doi: 10.1053/jhep.2003.50346 12883497.

12. Sterling RK, Lissen E, Clumeck N, Sola R, Correa MC, Montaner J, et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006;43(6):1317–25. Epub 2006/05/27. doi: 10.1002/hep.21178 16729309.

13. Deng J, Zhou P, Tian SM, Zhang L, Li JL, Qian Y. Comparison of diagnostic efficacy of contrast-enhanced ultrasound, acoustic radiation force impulse imaging, and their combined use in differentiating focal solid thyroid nodules. PLoS One. 2014;9(3):e90674. Epub 2014/03/07. doi: 10.1371/journal.pone.0090674 24594879; PubMed Central PMCID: PMC3940946.

14. De Robertis R, D'Onofrio M, Demozzi E, Crosara S, Canestrini S, Pozzi Mucelli R. Noninvasive diagnosis of cirrhosis: a review of different imaging modalities. World J Gastroenterol. 2014;20(23):7231–41. Epub 2014/06/27. doi: 10.3748/wjg.v20.i23.7231 24966594; PubMed Central PMCID: PMC4064069.

15. Piscaglia F, Marinelli S, Bota S, Serra C, Venerandi L, Leoni S, et al. The role of ultrasound elastographic techniques in chronic liver disease: current status and future perspectives. Eur J Radiol. 2014;83(3):450–5. Epub 2013/07/31. doi: 10.1016/j.ejrad.2013.06.009 23891139.

16. D'Onofrio M, Crosara S, De Robertis R, Canestrini S, Demozzi E, Gallotti A, et al. Acoustic radiation force impulse of the liver. World J Gastroenterol. 2013;19(30):4841–9. Epub 2013/08/16. doi: 10.3748/wjg.v19.i30.4841 23946588; PubMed Central PMCID: PMC3740413.

17. Liu H, Fu J, Hong R, Liu L, Li F. Acoustic Radiation Force Impulse Elastography for the Non-Invasive Evaluation of Hepatic Fibrosis in Non-Alcoholic Fatty Liver Disease Patients: A Systematic Review & Meta-Analysis. PLoS One. 2015;10(7):e0127782. Epub 2015/07/02. doi: 10.1371/journal.pone.0127782 26131717; PubMed Central PMCID: PMC4489183.

18. Hu X, Qiu L, Liu D, Qian L. Acoustic Radiation Force Impulse (ARFI) Elastography for noninvasive evaluation of hepatic fibrosis in chronic hepatitis B and C patients: a systematic review and meta-analysis. Med Ultrason. 2017;19(1):23–31. Epub 2017/02/10. doi: 10.11152/mu-942 28180193.

19. Bota S, Herkner H, Sporea I, Salzl P, Sirli R, Neghina AM, et al. Meta-analysis: ARFI elastography versus transient elastography for the evaluation of liver fibrosis. Liver Int. 2013;33(8):1138–47. Epub 2013/07/19. doi: 10.1111/liv.12240 23859217.

20. Staub F, Tournoux-Facon C, Roumy J, Chaigneau C, Morichaut-Beauchant M, Levillain P, et al. Liver fibrosis staging with contrast-enhanced ultrasonography: prospective multicenter study compared with METAVIR scoring. Eur Radiol. 2009;19(8):1991–7. Epub 2009/03/05. doi: 10.1007/s00330-009-1313-x 19259683.

21. Whiting P, Rutjes AW, Reitsma JB, Bossuyt PM, Kleijnen J. The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC Med Res Methodol. 2003;3:25. Epub 2003/11/11. doi: 10.1186/1471-2288-3-25 14606960; PubMed Central PMCID: PMC305345.

22. Guo Y, Parthasarathy S, Goyal P, McCarthy RJ, Larson AC, Miller FH. Magnetic resonance elastography and acoustic radiation force impulse for staging hepatic fibrosis: a meta-analysis. Abdom Imaging. 2015;40(4):818–34. Epub 2014/04/09. doi: 10.1007/s00261-014-0137-6 24711064.

23. Leeflang MM, Deeks JJ, Gatsonis C, Bossuyt PM, Cochrane Diagnostic Test Accuracy Working G. Systematic reviews of diagnostic test accuracy. Ann Intern Med. 2008;149(12):889–97. Epub 2008/12/17. doi: 10.7326/0003-4819-149-12-200812160-00008 19075208; PubMed Central PMCID: PMC2956514.

24. Deeks JJ, Macaskill P, Irwig L. The performance of tests of publication bias and other sample size effects in systematic reviews of diagnostic test accuracy was assessed. J Clin Epidemiol. 2005;58(9):882–93. Epub 2005/08/09. doi: 10.1016/j.jclinepi.2005.01.016 16085191.

25. Wu Y, Wang F, Fan X, Bao R, Bo L, Li J, et al. Accuracy of plasma sTREM-1 for sepsis diagnosis in systemic inflammatory patients: a systematic review and meta-analysis. Crit Care. 2012;16(6):R229. Epub 2012/12/01. doi: 10.1186/cc11884 23194114; PubMed Central PMCID: PMC3672614.

26. Gao F, Chen YQ, Fang J, Gu SL, Li L, Wang XY. Acoustic Radiation Force Impulse Imaging for Assessing Liver Fibrosis Preoperatively in Infants With Biliary Atresia: Comparison With Liver Fibrosis Biopsy Pathology. J Ultrasound Med. 2017;36(8):1571–8. Epub 2017/04/14. doi: 10.7863/ultra.16.08043 28407283.

27. Tomita H, Ohkuma K, Masugi Y, Hosoe N, Hoshino K, Fuchimoto Y, et al. Diagnosing native liver fibrosis and esophageal varices using liver and spleen stiffness measurements in biliary atresia: a pilot study. Pediatr Radiol. 2016;46(10):1409–17. Epub 2016/06/15. doi: 10.1007/s00247-016-3637-4 27300741.

28. Canas T, Macia A, Munoz-Codoceo RA, Fontanilla T, Gonzalez-Rios P, Miralles M, et al. Hepatic and Splenic Acoustic Radiation Force Impulse Shear Wave Velocity Elastography in Children with Liver Disease Associated with Cystic Fibrosis. Biomed Res Int. 2015;2015:517369. Epub 2015/11/27. doi: 10.1155/2015/517369 26609528; PubMed Central PMCID: PMC4644813.

29. Karlas T, Neuschulz M, Oltmanns A, Guttler A, Petroff D, Wirtz H, et al. Non-invasive evaluation of cystic fibrosis related liver disease in adults with ARFI, transient elastography and different fibrosis scores. PLoS One. 2012;7(7):e42139. Epub 2012/08/01. doi: 10.1371/journal.pone.0042139 22848732; PubMed Central PMCID: PMC3405060.

30. Liao CC, Chen TY, Tsang LC, Ou SY, Yu CY, Hsu HW, et al. The acoustic radiation force impulse elastography evaluation of liver fibrosis in posttransplantation dysfunction of living donor liver transplantation. Transplant Proc. 2014;46(3):876–9. Epub 2014/04/29. doi: 10.1016/j.transproceed.2013.12.012 24767370.

31. Pinto J, Matos H, Nobre S, Cipriano MA, Marques M, Pereira JM, et al. Comparison of acoustic radiation force impulse/serum noninvasive markers for fibrosis prediction in liver transplant. J Pediatr Gastroenterol Nutr. 2014;58(3):382–6. Epub 2013/10/30. doi: 10.1097/MPG.0000000000000226 24164902.

32. Schmillevitch J, Chammas MC, Pugliese V, Abdala E, Rizzon AC, Alves V, et al. Acoustic radiation force impulse (ARFI) elastography compared with biopsy for evaluating hepatic fibrosis after liver transplantation: a cross-sectional diagnostic study. Sao Paulo Med J. 2016;134(6):513–8. Epub 2017/01/12. doi: 10.1590/1516-3180.2016.0158170816 28076629.

33. Tomita H, Hoshino K, Fuchimoto Y, Ebinuma H, Ohkuma K, Tanami Y, et al. Acoustic radiation force impulse imaging for assessing graft fibrosis after pediatric living donor liver transplantation: a pilot study. Liver Transpl. 2013;19(11):1202–13. Epub 2013/07/31. doi: 10.1002/lt.23708 23894066.

34. Wildner D, Strobel D, Konturek PC, Gortz RS, Croner RS, Neurath MF, et al. Impact of acoustic radiation force impulse imaging in clinical practice of patients after orthotopic liver transplantation. Med Sci Monit. 2014;20:2027–35. Epub 2014/10/25. doi: 10.12659/MSM.891126 25342166; PubMed Central PMCID: PMC4218901.

35. Yoshino K, Taura K, Okuda Y, Ikeno Y, Uemoto Y, Nishio T, et al. Efficiency of acoustic radiation force impulse imaging for the staging of graft fibrosis after liver transplantation. Hepatol Res. 2019;49(4):394–403. Epub 2018/11/25. doi: 10.1111/hepr.13289 30471140.

36. Attia D, Bantel H, Lenzen H, Manns MP, Gebel MJ, Potthoff A. Liver stiffness measurement using acoustic radiation force impulse elastography in overweight and obese patients. Aliment Pharmacol Ther. 2016;44(4):366–79. Epub 2016/07/02. doi: 10.1111/apt.13710 27363528.

37. Fierbinteanu Braticevici C, Sporea I, Panaitescu E, Tribus L. Value of acoustic radiation force impulse imaging elastography for non-invasive evaluation of patients with nonalcoholic fatty liver disease. Ultrasound Med Biol. 2013;39(11):1942–50. Epub 2013/08/13. doi: 10.1016/j.ultrasmedbio.2013.04.019 23932277.

38. Cassinotto C, Boursier J, de Ledinghen V, Lebigot J, Lapuyade B, Cales P, et al. Liver stiffness in nonalcoholic fatty liver disease: A comparison of supersonic shear imaging, FibroScan, and ARFI with liver biopsy. Hepatology. 2016;63(6):1817–27. Epub 2015/12/15. doi: 10.1002/hep.28394 26659452.

39. Cui J, Heba E, Hernandez C, Haufe W, Hooker J, Andre MP, et al. Magnetic resonance elastography is superior to acoustic radiation force impulse for the Diagnosis of fibrosis in patients with biopsy-proven nonalcoholic fatty liver disease: A prospective study. Hepatology. 2016;63(2):453–61. Epub 2015/11/13. doi: 10.1002/hep.28337 26560734; PubMed Central PMCID: PMC4818645.

40. Friedrich-Rust M, Romen D, Vermehren J, Kriener S, Sadet D, Herrmann E, 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(3):e325–31. Epub 2011/11/29. doi: 10.1016/j.ejrad.2011.10.029 22119555.

41. Guerra JA, Trippia M, Pissaia A, Teixeira BC, Ivantes CA. Acoustic Radiation Force Impulse Is Equivalent to Liver Biopsy to Evaluate Liver Fibrosis in Patients with Chronic Hepatitis C and Nonalcoholic Fatty Liver Disease. Arq Gastroenterol. 2015;52(3):234–8. Epub 2015/10/22. doi: 10.1590/S0004-28032015000300015 26486293.

42. Guzman-Aroca F, Frutos-Bernal MD, Bas A, Lujan-Mompean JA, Reus M, Berna-Serna Jde D, et al. Detection of non-alcoholic steatohepatitis in patients with morbid obesity before bariatric surgery: preliminary evaluation with acoustic radiation force impulse imaging. Eur Radiol. 2012;22(11):2525–32. Epub 2012/06/01. doi: 10.1007/s00330-012-2505-3 22648049.

43. Harris N, Nadebaum D, Christie M, Gorelik A, Nicoll A, Sood S, et al. Acoustic radiation force impulse accuracy and the impact of hepatic steatosis on liver fibrosis staging. J Med Imaging Radiat Oncol. 2016;60(5):587–92. Epub 2016/06/22. doi: 10.1111/1754-9485.12482 27324199.

44. Karlas T, Dietrich A, Peter V, Wittekind C, Lichtinghagen R, Garnov N, et al. Evaluation of Transient Elastography, Acoustic Radiation Force Impulse Imaging (ARFI), and Enhanced Liver Function (ELF) Score for Detection of Fibrosis in Morbidly Obese Patients. PLoS One. 2015;10(11):e0141649. Epub 2015/11/04. doi: 10.1371/journal.pone.0141649 26528818; PubMed Central PMCID: PMC4631322.

45. Lee MS, Bae JM, Joo SK, Woo H, Lee DH, Jung YJ, et al. Prospective comparison among transient elastography, supersonic shear imaging, and ARFI imaging for predicting fibrosis in nonalcoholic fatty liver disease. PLoS One. 2017;12(11):e0188321. Epub 2017/11/28. doi: 10.1371/journal.pone.0188321 29176844; PubMed Central PMCID: PMC5703509.

46. Osaki A, Kubota T, Suda T, Igarashi M, Nagasaki K, Tsuchiya A, et al. Shear wave velocity is a useful marker for managing nonalcoholic steatohepatitis. World J Gastroenterol. 2010;16(23):2918–25. Epub 2010/06/18. doi: 10.3748/wjg.v16.i23.2918 20556839; PubMed Central PMCID: PMC2887589.

47. Palmeri ML, Wang MH, Rouze NC, Abdelmalek MF, Guy CD, Moser B, 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(3):666–72. Epub 2011/01/25. doi: 10.1016/j.jhep.2010.12.019 21256907; PubMed Central PMCID: PMC3092839.

48. Yoneda M, Suzuki K, Kato S, Fujita K, Nozaki Y, Hosono K, et al. Nonalcoholic fatty liver disease: US-based acoustic radiation force impulse elastography. Radiology. 2010;256(2):640–7. Epub 2010/06/10. doi: 10.1148/radiol.10091662 20529989.

49. Zhang DK, Chen M, Liu Y, Wang RF, Liu LP, Li M. Acoustic radiation force impulse elastography for non-invasive assessment of disease stage in patients with primary biliary cirrhosis: A preliminary study. Clin Radiol. 2014;69(8):836–40. Epub 2014/05/20. doi: 10.1016/j.crad.2014.03.019 24837697.

50. Zhang HC, Hu RF, Zhu T, Tong L, Zhang QQ. Primary biliary cirrhosis degree assessment by acoustic radiation force impulse imaging and hepatic fibrosis indicators. World J Gastroenterol. 2016;22(22):5276–84. Epub 2016/06/15. doi: 10.3748/wjg.v22.i22.5276 27298571; PubMed Central PMCID: PMC4893475.

51. Kiani A, Brun V, Laine F, Turlin B, Morcet J, Michalak S, et al. Acoustic radiation force impulse imaging for assessing liver fibrosis in alcoholic liver disease. World J Gastroenterol. 2016;22(20):4926–35. Epub 2016/05/31. doi: 10.3748/wjg.v22.i20.4926 27239119; PubMed Central PMCID: PMC4873885.

52. Zhang D, Li P, Chen M, Liu L, Liu Y, Zhao Y, et al. Non-invasive assessment of liver fibrosis in patients with alcoholic liver disease using acoustic radiation force impulse elastography. Abdom Imaging. 2015;40(4):723–9. Epub 2014/05/09. doi: 10.1007/s00261-014-0154-5 24811766.

53. Park DW, Lee YJ, Chang W, Park JH, Lee KH, Kim YH, et al. Assessment of liver fibrosis in non-viral liver disease patients using acoustic radiation force impulse elastography. Hepatology. 2017;66(Supplement 1):349A.

54. Swets JA. Measuring the accuracy of diagnostic systems. Science. 1988;240(4857):1285–93. Epub 1988/06/03. doi: 10.1126/science.3287615 3287615.

55. Ebell MH. Probability of cirrhosis in patients with hepatitis C. Am Fam Physician. 2003;68(9):1831–3. Epub 2003/11/19. 14620604.

56. Dhyani M, Xiang F, Li Q, Chen L, Li C, Bhan AK, et al. Ultrasound Shear Wave Elastography: Variations of Liver Fibrosis Assessment as a Function of Depth, Force and Distance from Central Axis of the Transducer with a Comparison of Different Systems. Ultrasound Med Biol. 2018;44(11):2209–22. Epub 2018/08/26. doi: 10.1016/j.ultrasmedbio.2018.07.003 30143339.

57. Gani RA, Hasan I, Sanityoso A, Lesmana CRA, Kurniawan J, Jasirwan COM, et al. Evaluation of Acoustic Radiation Force Impulse (ARFI) for Fibrosis Staging in Chronic Liver Diseases. Acta Med Indones. 2017;49(2):128–35. Epub 2017/08/10. 28790227.

58. Pfeifer L, Adler W, Zopf S, Siebler J, Wildner D, Goertz RS, et al. Acoustic radiation force impulse elastography: comparison and combination with other noninvasive tests for the diagnosis of compensated liver cirrhosis. Eur J Gastroenterol Hepatol. 2017;29(5):524–30. Epub 2017/01/10. doi: 10.1097/MEG.0000000000000827 28067683.


Článek vyšel v časopise

PLOS One


2020 Číslo 1
Nejčtenější tento týden
Nejčtenější v tomto čísle
Kurzy

Zvyšte si kvalifikaci online z pohodlí domova

KOST
Koncepce osteologické péče pro gynekology a praktické lékaře
nový kurz
Autoři: MUDr. František Šenk

Sekvenční léčba schizofrenie
Autoři: MUDr. Jana Hořínková

Hypertenze a hypercholesterolémie – synergický efekt léčby
Autoři: prof. MUDr. Hana Rosolová, DrSc.

Svět praktické medicíny 5/2023 (znalostní test z časopisu)

Imunopatologie? … a co my s tím???
Autoři: doc. MUDr. Helena Lahoda Brodská, Ph.D.

Všechny kurzy
Kurzy Podcasty Doporučená témata Časopisy
Přihlášení
Zapomenuté heslo

Zadejte e-mailovou adresu, se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se

#ADS_BOTTOM_SCRIPTS#