Liver Fibrosis Regression on Acoustic Radiation Force Impulse Elastography after Successful Direct-Acting Antiviral Therapy: 1-Year Follow-Up.

Ahmed Zeid, Mohamed El-Shafei, Mohamed Bakosh, Assem El-Shendidi

Abstract


Aim: Acoustic radiation force impulse (ARFI) is an ultrasound elastography that delineates liver stiffness measurement (LSM) non-invasively. Data on the utility of ARFI in monitoring hepatic fibrosis evolution after hepatitis C virus (HCV) cure are still lacking. This study was designed to investigate the serial changes of ARFI-LSM and serum-based fibrosis scores in HCV-infected patients who achieved sustained virologic response (SVR) after direct-acting antivirals (DAAs) therapy.Material and Methods: This study included 174 treatment-naïve HCV-infected patients who achieved SVR after DAAs. ARFI was performed in addition to fibrosis-4 (FIB-4) and aspartate aminotransferase-to-platelet count ratio index (APRI) scores for patients at baseline, end of therapy (EOT), 12, 24 and 48 weeks after EOT.Results: Serum aminotransferases declined significantly overtime till 12 weeks after the EOT. Platelet count showed continuous significant increase over the follow-up period. Both FIB-4 and APRI scores demonstrated a continuous significant decline between the baseline and 48 weeks after EOT, except the period between EOT and 12 weeks after EOT when there was no significant change observed in FIB-4. There was a continuous significant decline of ARFI-LSM from the baseline over the follow-up period. In non-cirrhotic patients, the higher baseline ARFI-LSM was an independent predictor of fibrosis regression at 48 weeks after EOT. Absent portal hypertension and compensated liver disease at baseline were associated with ARFI-LSM improvement at 48 weeks after EOT in cirrhotic patients.Conclusions: Continuous improvement in LSM after HCV eradication occurred due to resolution of liver injury and fibrosis regression. ARFI is a feasible and promising non-invasive method for hepatic fibrosis assessment.

Keywords


Hepatitis C Virus; Fibrosis regression; Direct-acting antivirals; Acoustic radiation force impulse elastography; Liver stiffness.

References


Webster DP, Klenerman P, Dusheiko GM. Hepatitis C. Lancet 2015; 385:1124-35.[PMCID: PMC4878852][DOI:10.1016/S0140-6736(14)62401-6]

Hajarizadeh B, Grebely J, Dore GJ. Epidemiology and natural history of HCV infection. Nat Rev Gastroenterol Hepatol 2013;10:553-62. [PMID: 23817321] [DOI: 10.1038/nrgastro.2013.107]

D’Amico G, Garcia-Tsao G, Pagliaro L. Natural history and prognostic indicators of survival in cirrhosis: A systematic review of 118 studies. J Hepatol 2006; 44: 217-31. [PMID: 16298014] [DOI: 10.1016/j.jhep.2005.10.013]

Marcellin P, Asselah T, Boyer N. Fibrosis and disease progression in hepatitis C. Hepatology 2002; 36(5-1): 47-56. [PMID: 12407576] [DOI: 10.1053/jhep.2002.36993]

Manne V, Akhtar E, Saab S. Cirrhosis regression in patients with viral hepatitis B and C: A systematic review. J Clin Gastroenterol 2014;48:76-84. [PMID: 24921210][DOI: 10.1097/MCG.0000000000000162]

Morisco F, Granata R, Stroffolini T, Guarino M, Donnarumma L, Gaeta L, Loperto I, Gentile I, Auriemma F, Caporaso N. Sustained virological response: A mile-stone in the treatment of chronic hepatitis C. World J Gastroenterol 2013;19: 2793-8. [PMCID: PMC3653153][DOI: 10.3748/wjg.v19.i18.2793]

Poynard T, McHutchison J, Manns M, Trepo C, Lindsay K, Goodman Z, Ling M,Albrecht J. Impact of pegylated interferon alfa-2b and ribavirin on liver fibrosis in patients with chronic hepatitis C. Gastroenterology 2002;122:1303-13. [PMID: 11984517][DOI: 10.1053/gast.2002.33023]

George SL, Bacon BR, Brunt EM, Mihindukulasuriya KL, Hoffmann J, Di Bisceglie AM. Clinical, virologic, histologic, and biochemical outcomes after successful HCV therapy: A 5-year follow-up of 150 patients. Hepatology 2009;49:729-38. [PMCID: PMC2731713][DOI: 10.1002/hep.22694]

Pawlotsky JM, Aghemo A, Back D, Dusheiko G, Forns X, Negro F, Pouti M, Sarrazin C. European Association for the Study of the Liver. EASL recommendations on treatment of hepatitis C. J Hepatol 2017; 66: 153-194. [PMID: 27667367][DOI: 10.1016/j.jhep.2016.09.001]

Sáez-Royuela F, Badia E. Hepatitis C: Is regression of advanced fibrosis possible after treatment? EMJ 2016;1:126-32.

Rockey DC, Caldwell SH, Goodman ZD, Nelson RC, Smith AD. Liver biopsy. Hepatology 2009;49:1017-44. [PMID: 19243014] [DOI: 10.1002/hep.22742]

Castera L, Chan HLY, Arrese M, Afdhal N, Bedossa P, Friedrich-Rust M, Han K, Pinzani M. European Association for the Study of the Liver. EASL-ALEH Clinical Practice Guidelines: Non-invasive tests for evaluation of liver disease severity and prognosis. J Hepatol 2015;63:237-64. [PMID: 25911335] [DOI: 10.1016/j.jhep.2015.04.006]

Bonnard P, Elsharkawy A, Zalata K, Delarocque-Astagneau E, Biard L, Le Fouler L, Hassan A B, Abdel-Hamid M, El-Daly M, Gamal M E, El Kassas M, Bedossa P, Carret F, Fontanet A, Esmat G. Comparison of liver biopsy and non-invasive techniques for liver fibrosis assessment in patients infected with HCV-genotype 4 in Egypt. J Viral Hepat 2015; 22:245-53. [PMID: 25073725] [DOI: 10.1111/jvh.12285]

Afdhal NH, Bacon BR, Patel K, Lawitz EJ, Gordon SC, Nelson DR, Challies TL, Nasser I, Garg J, Wei L, McHutchison J G. Accuracy of fibroscan, compared with histology, in analysis of liver fibrosis in patients with hepatitis B or C: A United States multicenter study. Clin Gastroenterol Hepatol 2015;13:772-9. [PMID: 25528010][DOI: 10.1016/j.cgh.2014.12.014]

Terrault NA, Hassanein TI. Management of the patient with SVR. J Hepatol 2016;65(1):S120-9.[ PMID: 27641982][DOI: 10.1016/j.jhep.2016.08.001]

Nightingale K, Soo MS, Nightingale R, Trahey G. Acoustic radiation force impulse imaging: In vivo demonstration of clinical feasibility. Ultrasound Med Biol 2002; 28:227-35. [PMID: 11937286][DOI: 10.1016/s0301-5629(01)00499-9]

Takahashi H, Ono N, Eguchi Y, Eguchi T, Kitajima Y, Kawaguchi Y, Nakashita S, Ozaki I, Mizuta T, Toda S, Kudo S, Miyoshi A, Miyazaki K, Fujimoto k. Evaluation of acoustic radiation force impulse elastography for fibrosis staging of chronic liver disease: A pilot study. Liver Int 2010;30:538-45. [PMID: 19874490][DOI: 10.1111/j.1478-3231.2009.02130.x]

Yoon KT, Lim SM, Park JY, Kim DY, Ahn SH, Han KH, Chon CY, Cho M, Lee JW, Kim SU. Liver stiffness measurement using acoustic radiation force impulse (ARFI) elastography and effect of necroinflammation. Dig Dis Sci 2012;57:1682-91. [PMID: 22302243][DOI: 10.1007/s10620-012-2044-4]

Tachi Y, Hirai T, Kojima Y, Miyata A, Ohara K, Ishizu Y, Honda T, Kuzuya T, Hayashi K, Ishigami M, Goto H. Liver stiffness measurement using acoustic radiation force impulse elastography in hepatitis C virus-infected patients with a sustained virological response. Aliment Pharmacol Ther 2016; 44: 346-55. [PMID: 27291657][DOI: 10.1111/apt.13695]

Foster GR, Irving WL, Cheung MCM, Walker AJ, Hudson BE, Verma S, MaLauchlan J, Mutimer DJ, Brown A, Gelson WTH, MacDonald DC, Agarwal K, HCV Researsh,UK. Impact of direct acting antiviral therapy in patients with chronic hepatitis C and decompensated cirrhosis. J Hepatol 2016; 64: 1224-31. [PMID: 26829205][DOI: 10.1016/j.jhep.2016.01.029]

Sterling RK, Lissen E, Clumeck N, Sola R, Correa MC, Montaner J, Sulkowski MS, Torriani FJ, Dieterich DJ, Thomas DL, Messinger D, Nelson M, APRICOT Clinical Investigators. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology 2006; 43(6): 1317-25. [PMID: 16729309] [DOI: 10.1002/hep.21178]

Wai CT, Greenson JK, Fontana RJ, Kalbfleisch JD, Marrero JA, Conjeevaram HS, Lok AS-F. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology 2003;38(2):518-26. [PMID: 12883497][DOI: 10.1053/jhep.2003.50346]

Okawa O, Suda T, TokutomiN,Shirahashi R, Tamano M. Shear Wave Velocity Improves in Hepatitis C Patients Treated with Direct-Acting Antiviral Agents. J Gastroenterol Hepatol 2018;3(2):1040.

Tada T, Kumada T, Toyoda H, Mizuno K, Sone Y, Kataoka S, Hashinokuchi S. Improvement of liver stiffness in patients with hepatitis C virus infection who received direct-acting antiviral therapy and achieved sustained virological response. J Gastroenterol Hepatol 2017; 32(12): 1982-8. [PMID: 28299813][DOI: 10.1111/jgh.13788]

Hsu W-F, Lai H-C, Su W-P, Lin C-H, Chuang P-H, Chen S-H, Chen H-Y, Wang H-W, Huang G-T, Peng C-Y. Rapid decline of noninvasive fibrosis index values in patients with hepatitis C receiving treatment with direct-acting antiviral agents. BMC Gastroenterol 2019; 19(1):63. [PMID: 31029101] [DOI: 10.1186/s12876-019-0973-5]

Pietsch V, Deterding K, Attia D, Ringe KI, Heidrich B, Cornberg M, Gebel M, Manns MP, Wedemeyer H, Potthoff A. Long-term changes in liver elasticity in hepatitis C virus-infected patients with sustained virologic response after treatment with direct-acting antivirals. United European Gastroenterol J 2018; 6(8):1188-98. [PMID: 30288281][DOI: 10.1177/2050640618786067]

Elsharkawy A, Alem SA, Fouad R, El Raziky M, El Akel W, Abdo M, Tantawi M, AbdAllah M, Bourliere M, Esmat G. Changes in liver stiffness measurements and fibrosis scores following sofosbuvir based treatment regimens without interferon. J Gastroenterol Hepatol 2017;32(9):1624-30. [PMID: 28177543] [DOI: 10.1111/jgh.13758]

Karasu Z, Tekin F, Ersoz G, Gunsar F, Batur Y, Ilter T, et al. Liver fibrosis is associated with decreased peripheral platelet count in patients with chronic hepatitis B and C. Dig Dis Sci 2007;52(6):1535-9. [PMID: 17464564][DOI: 10.1007/s10620-006-9144-y]

Mallet V, Gilgenkrantz H, Serpaggi J, Verkarre V, Vallet-Pichard A, Fontaine H, Pol S. Brief communication: the relationship of regression of cirrhosis to outcome in chronic hepatitis C. Ann Intern Med 2008;149(6):399-403. [PMID: 18794559][DOI: 10.7326/0003-4819-149-6-200809160-00006]

D'ambrosio R, Aghemo A, Rumi MG, Ronchi G, Donato MF, Paradis V, Colombo M, Bedossa P. A morphometric and immunohistochemical study to assess the benefit of a sustained virological response in hepatitis C virus patients with cirrhosis. Hepatology 2012; 56(2): 532-43. [PMID: 22271347] [DOI: 10.1002/hep.25606]

Kobayashi N, Iijima H, Tada T, Kumada T, Yoshida M, Aoki T, Nishimura T, Nakano C, Takata R, Yoh K, Ishii a, Takashima T, Sakai Y, Aizawa N, Nishikawa H, Ikeda N, Iwata Y, Enomoto H, Hirota S, FujimotoJ, Nishiguchi S. Changes in liver stiffness and steatosis among patients with hepatitis C virus infection who received direct-acting antiviral therapy and achieved sustained virological response. Eur J Gastroenterol Hepatol 2018;30(5):546-51. [PMID: 29494353] [DOI: 10.1097/MEG.0000000000001106]

Singh S, Facciorusso A, Loomba R, Falck-Ytter YT. Magnitude and Kinetics of Decline in Liver Stiffness After Anti-Viral Therapy in Patients with Chronic Hepatitis C: A Systematic Review and Meta-Analysis. Gastroenterology 2017; 152(5): S1164. [PMID: 28479504] [DOI: 10.1016/j.cgh.2017.04.038]

Ogawa E, Furusyo N, Toyoda K, Takeoka H, Maeda S, Hayashi J. The longitudinal quantitative assessment by transient elastography of chronic hepatitis C patients treated with pegylated interferon alpha-2b and ribavirin. Antiviral Res 2009; 83: 127-34. [PMID: 19443053] [DOI: 10.1016/j.antiviral.2009.04.002]

Sporea I, Sirli R, Deleanu A, Popescu A, Focsa M, Danila M, Tudora A. Acoustic radiation force impulse elastography as compared to transient elastography and liver biopsy in patients with chronic hepatopathies. Ultraschall Med 2011;32(Suppl 1):S46-52. [PMID: 20603783][DOI: 10.1055/s-0029-1245360]

Martinez SM, Fernández Varo G, González P, Sampson E, Bruguera M, Navasa M, Jimenez W, Sanchez-Tapias J M, Forns X. Assessment of liver fibrosis before and after antiviral therapy by different serum marker panels in patients with chronic hepatitis C. Aliment Pharmacol Ther 2011;33(1):138-48. [PMID: 21083589][DOI: 10.1111/j.1365-2036.2010.04500.x]

Kohla MAS, El Fayoumi A, Akl M, Abdelkareem M, Elsakhawy M, Waheed S, Abozeid M et al. Early fibrosis regression by shear wave elastography after successful direct-acting anti-HCV therapy. Clin Exp Med 2020; 20:143-8. [PMID: 31792631] [DOI: 10.1007/s10238-019-00597-0]

Bachofner JA, Valli PV, Krög.er A, Bergamin I, Künzler P, Baserga A, Braun D, Seifert B, Moncsek A, Fehr J, Semela D, Magenta L, Mullhaupt B, Beretta-Piccoli BT, Mertens JC. Direct antiviral agent treatment of chronic hepatitis C results in rapid regression of transient elastography and fibrosis markers fibrosis-4 score and aspartate aminotransferase to platelet ratio index. Liver Int 2017;37(3):369-76. [PMID: 27678216][DOI: 10.1111/liv.13256]

Chen S-H, Lai H-C, Chiang I-P, Su W-P, Lin C-H, Kao J-T, Chuang P-H, Hsu W-F, Wang H-W, Chen H-Y, Huang G-T, Peng C-Y. Changes in liver stiffness measurement using acoustic radiation force impulse elastography after antiviral therapy in patients with chronic hepatitis C. PloS One 2018;13(1):e0190455.[PMID: 29293628] [DOI: 10.1371/journal.pone.0190455]

Attia D, Deterding K, Cornberg J, Gebel MJ, Cornberg M, Manns MP, Wedemeyer H, Potthoff A. Different kinetics of liver stiffness using shear wave elastography in patients with chronic hepatitis C infection treated with interferon-free regimens. Eur J Gastroenterol Hepatol 2019;31(1):67-74. [PMID: 30239347][DOI: 10.1097/MEG.0000000000001259]

Fraquelli M, Rigamonti C, Casazza G, Donato MF, Ronchi G, Conte D, Rumi M, Lampertico P, Colombo M. Etiology-related determinants of liver stiffness values in chronic viral hepatitis B or C. J Hepatol 2011; 54(4):621-8.[ PMID: 21146243] [DOI: 10.1016/j.jhep.2010.07.017]

Rizzo L, Calvaruso V, Cacopardo B, Alessi N, Attanasio M, Petta S, Fatuzzo F, Montineri A, Mazzola A, L'abbate L, Nunnari G, Bronte F, Marco V Di, Craxi A, Camma C. Comparison of transient elastography and acoustic radiation force impulse for non-invasive staging of liver fibrosis in patients with chronic hepatitis C. Am J Gastroenterol 2011;106(12):2112-20. [PMID: 21971536][DOI: 10.1038/ajg.2011.341]

Bota S, Sporea I, Sirli R, Popescu A, Jurchis A. Factors which influence the accuracy of acoustic radiation force impulse (ARFI) elastography for the diagnosis of liver fibrosis in patients with chronic hepatitis C. Ultrasound Med Biol 2013; 39(3):407-12. [PMID: 23245820] [DOI: 10.1016/j.ultrasmedbio.2012.09.017]

Mandorfer M, Kozbial K, Schwabl P, Freissmuth C, Schwarzer R, Stern R, Chromy D, Stattermayar AF, Rieberger T, Beinhardt S, Sieghart W, Trauner M, Hofer H, Ferlitsch A, Ferenci P, Peck-Radosavljevic M.. Sustained virologic response to interferon-free therapies ameliorates HCV-induced portal hypertension. J Hepatol 2016;65(4):692-9. [PMID: 27242316][DOI: 10.1016/j.jhep.2016.05.027]

Puente Á, Cabezas J, López Arias MJ, Fortea JI, Arias MT, Estébanez Á, Casafont F, Fabrega E, Crespo J. Influence of sustained viral response on the regression of fibrosis and portal hypertension in cirrhotic HCV patients treated with antiviral triple therapy. Rev Esp Enferm Dig 2017;109(1):17-25. [PMID: 27990835][DOI: 10.17235/reed.2016.4235/2016]

Tachi Y, Hirai T, Kojima Y, Ishizu Y, Honda T, Kuzuya T, Hayashi K, Ishigami M, Goto H. Liver stiffness reduction correlates with histological characteristics of hepatitis C patients with sustained virological response. Liver Int 2018;38(1):59-67. [PMID: 28557143][DOI: 10.1111/liv.13486]


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