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Endocrine, Metabolic & Immune Disorders - Drug Targets


ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Research Article

Predictors for Fibrosis Regression in Chronic HCV Patients after the Treatment with DAAS: Results of a Real-world Cohort Study

Author(s): Hanan Soliman, Dina Ziada, Marwa Salama, Manal Hamisa, Rehab Badawi, Nehad Hawash, Amal Selim and Sherief Abd-Elsalam*

Volume 20 , Issue 1 , 2020

Page: [104 - 111] Pages: 8

DOI: 10.2174/1871530319666190826150344


Introduction: The goal of treatment of chronic hepatitis C (HCV) is viral eradication. However, obtaining histological regression is even more important, because it will reduce the overall morbidity and mortality related to cirrhosis. Introduction of direct-acting antivirals (DAAs) in HCV improves rates of sustained virologic response (SVR). However, fibrosis regression has not been extensively assessed. The aim of this study was to detect the factors affecting fibrosis regression in chronic HCV patients treated with interferon containing regimens versus interferon-free DAA regimens.

Methods: This prospective observational cohort study was conducted at the Tropical Medicine and Infectious Diseases Department, Tanta University, Egypt, between October 2015 and December 2017. Transient elastography (FibroScan®) examination was performed before therapy, at SVR12, 6 months and 1 year after completing therapy for cured patients.

Results: Reduction in fibrosis was reported in; 46.7% and 49.3% of patients with moderate fibrosis, and 89% and 78.7% of patients with advanced fibrosis after one year of interferon containing and interferon free DAAs regimens respectively. Using multiple regression analysis; it was found that BMI, degrees of hepatic stiffness and steatosis were related to regression of hepatic fibrosis after therapy.

Conclusion: DAAs with or without interferon resulted in a significant reduction of liver fibrosis. BMI, steatosis and liver stiffness were independent factors for fibrosis regression in chronic HCV patients treated with DAAs. Further studies are needed to explore the mechanism by which steatosis affects HCV related fibrosis regression after treatment with DAAs.

Keywords: Hepatitis C virus, direct-acting antivirals, fibrosis, cirrhosis, steatosis, transient elastography.

Graphical Abstract
Flamm, S.L. Chronic hepatitis C virus infection. JAMA, 2003, 289(18), 2413-2417.
[] [PMID: 12746366]
Ahmed, O.A.; Elsebaey, M.A.; Fouad, M.H.A.; Elkadeem, M.; Badawi, R.; Khayyal, A.; Soliman, S.; Negm, M.S.; Abd-Elsalam, S. Outcomes of Treatment and Predictors of Response to Sofosbuvir plus Simeprevir in Hepatitis C Virus with Genotype-4 Infection. Infect. Disord. Drug Targets, 2018, 17. Epub ahead of print
[] [PMID: 30569878]
Waked, I.; Doss, W.; El-Sayed, M.H.; Estes, C.; Razavi, H.; Shiha, G.; Yosry, A.; Esmat, G. The current and future disease burden of chronic hepatitis C virus infection in Egypt. Arab J. Gastroenterol., 2014, 15(2), 45-52.
[] [PMID: 25097045]
Ahmed, O.A.; Kaisar, H.H.; Hawash, N.; Samir, H.; Shabana, S.S.T.; Hassan, A.; Fouad, M.; Rizk, F.; Abd-Elsalam, S. Efficacy of sofosbuvir plus ribavirin with or without peginterferon-alfa in treatment of a cohort of Egyptian patients with hepatitis C virus infection. Infect. Disord. Drug Targets, 2017, 17(2), 95-100.
[] [PMID: 28413993]
Abd-Elsalam, S.; Sharaf-Eldin, M.; Soliman, S.; Elfert, A.; Badawi, R.; Ahmad, Y.K. Efficacy and safety of sofosbuvir plus ribavirin for treatment of cirrhotic patients with genotype 4 hepatitis C virus in real-life clinical practice. Arch. Virol., 2018, 163(1), 51-56.
[] [PMID: 28983675]
Ahmed, O.A.; Kaisar, H.H.; Badawi, R.; Hawash, N.; Samir, H.; Shabana, S.S.; Fouad, M.H.A.; Rizk, F.H.; Khodeir, S.A.; Abd-Elsalam, S. Efficacy and safety of sofosbuvir-ledipasvir for treatment of a cohort of Egyptian patients with chronic hepatitis C genotype 4 infection. Infect. Drug Resist., 2018, 11, 295-298.
[] [PMID: 29535545]
Ahmed, O.A.; Elsebaey, M.A.; Fouad, M.H.A.; Elashry, H.; Elshafie, A.I.; Elhadidy, A.A.; Esheba, N.E.; Elnaggar, M.H.; Soliman, S.; Abd-Elsalam, S. Outcomes and predictors of treatment response with sofosbuvir plus daclatasvir with or without ribavirin in Egyptian patients with genotype 4 hepatitis C virus infection. Infect. Drug Resist., 2018, 11, 441-445.
[] [PMID: 29628768]
Ahmed, O.A.; Safwat, E.; Khalifa, M.O.; Elshafie, A.I.; Fouad, M.H.A.; Salama, M.M.; Naguib, G.G.; Eltabbakh, M.M.; Sherief, A.F.; Abd-Elsalam, S. Sofosbuvir Plus Daclatasvir in Treatment of Chronic Hepatitis C Genotype 4 Infection in a Cohort of Egyptian Patients: An Experiment the Size of Egyptian Village. Int. J. Hepatol., 2018. 20189616234
[] [PMID: 29755792]
Abd-Elsalam, S.; Badawi, R.; Elnawasany, S.; Yousef, M.; Mansour, L.; Hawash, N.; Elkhouly, R.A.; Soliman, S.; Selim, A.; Kobtan, A.; Elfert, A. Sofosbuvir, pegylated interferon and ribavirin in treatment of an Egyptian cohort with hepatitis C virus infection in real life clinical practice. Infect. Disord. Drug Targets, 2018, ••• Epub ahead of print
[] [PMID: 30207250]
Khattab, M.A.; Ferenci, P.; Hadziyannis, S.J.; Colombo, M.; Manns, M.P.; Almasio, P.L.; Esteban, R.; Abdo, A.A.; Harrison, S.A.; Ibrahim, N.; Cacoub, P.; Eslam, M.; Lee, S.S. Management of hepatitis C virus genotype 4: recommendations of an international expert panel. J. Hepatol., 2011, 54(6), 1250-1262.
[] [PMID: 21316497]
El Saadany, S.; Soliman, H.; Ziada, D.H.; Hamisa, M.; Hefeda, M.; Selim, A.; Goraba, H. Fibroscan versus liver biopsy in the evaluation of response among the Egyptian HCV infected patients to treatment. Egyptian Journal of Radiology and Nuclear Medicine, 2016, 47, 1-7.
Parsons, C.J.; Bradford, B.U.; Pan, C.Q.; Cheung, E.; Schauer, M.; Knorr, A.; Krebs, B.; Kraft, S.; Zahn, S.; Brocks, B.; Feirt, N.; Mei, B.; Cho, M.S.; Ramamoorthi, R.; Roldan, G.; Ng, P.; Lum, P.; Hirth-Dietrich, C.; Tomkinson, A.; Brenner, D.A. Antifibrotic effects of a tissue inhibitor of metalloproteinase-1 antibody on established liver fibrosis in rats. Hepatology, 2004, 40(5), 1106-1115.
[] [PMID: 15389776]
Yang, H.X.; Yi, Y.R. [Curative effect of interferon-alpha on rat liver fibrosis induced by CCl4] Zhong Nan Da Xue Xue Bao Yi Xue Ban, 2008, 33(10), 919-925.
[PMID: 19001734]
Yoshida, E.M.; Sulkowski, M.S.; Gane, E.J.; Herring, R.W., Jr; Ratziu, V.; Ding, X.; Wang, J.; Chuang, S.M.; Ma, J.; McNally, J.; Stamm, L.M.; Brainard, D.M.; Symonds, W.T.; McHutchison, J.G.; Beavers, K.L.; Jacobson, I.M.; Reddy, K.R.; Lawitz, E. Concordance of sustained virological response 4, 12, and 24 weeks post-treatment with sofosbuvir-containing regimens for hepatitis C virus. Hepatology, 2015, 61(1), 41-45.
[] [PMID: 25314116]
van der Meer, A.J.; Veldt, B.J.; Feld, J.J.; Wedemeyer, H.; Dufour, J.F.; Lammert, F.; Duarte-Rojo, A.; Heathcote, E.J.; Manns, M.P.; Kuske, L.; Zeuzem, S.; Hofmann, W.P.; de Knegt, R.J.; Hansen, B.E.; Janssen, H.L. Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis. JAMA, 2012, 308(24), 2584-2593.
[] [PMID: 23268517]
Aleman, S.; Rahbin, N.; Weiland, O.; Davidsdottir, L.; Hedenstierna, M.; Rose, N.; Verbaan, H.; Stål, P.; Carlsson, T.; Norrgren, H.; Ekbom, A.; Granath, F.; Hultcrantz, R. A risk for hepatocellular carcinoma persists long-term after sustained virologic response in patients with hepatitis C-associated liver cirrhosis. Clin. Infect. Dis., 2013, 57(2), 230-236.
[] [PMID: 23616492]
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]
Lackner, C.; Struber, G.; Liegl, B.; Leibl, S.; Ofner, P.; Bankuti, C.; Bauer, B.; Stauber, R.E. Comparison and validation of simple noninvasive tests for prediction of fibrosis in chronic hepatitis C. Hepatology, 2005, 41(6), 1376-1382.
[] [PMID: 15915455]
Hoefs, J.C.; Shiffman, M.L.; Goodman, Z.D.; Kleiner, D.E.; Dienstag, J.L.; Stoddard, A.M. Rate of progression of hepatic fibrosis in patients with chronic hepatitis C: results from the HALT-C Trial. Gastroenterology, 2011, 141(3) 900-908.e1, 2.
[] [PMID: 21699796]
Elsharkawy, A.; Alem, S.A.; Fouad, R.; El Raziky, M.; El Akel, W.; Abdo, M.; Tantawi, O. 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), 1624-1630.
[] [PMID: 28177543]
Sharma, D.; Sudhamshu, K.C.; Shrestha, A.; Jaishi, B. Status of liver stiffness following directly acting antiviral treatment in patients with chronic hepatitis C: A Nepalese study. Journal of College of Medical Sciences-Nepal., 2017, 13(3), 302-305.
Mascia, C.; Vita, S.; Zuccalà, P.; Marocco, R.; Tieghi, T.; Savinelli, S.; Rossi, R.; Iannetta, M.; Pozzetto, I.; Furlan, C.; Mengoni, F.; Mastroianni, C.M.; Vullo, V.; Lichtner, M. Changes in inflammatory biomarkers in HCV-infected patients undergoing direct acting antiviral-containing regimens with or without interferon. PLoS One, 2017, 12(6)e0179400
[] [PMID: 28636655]
Mueller, S.; Sandrin, L. Liver stiffness: a novel parameter for the diagnosis of liver disease. Hepat. Med., 2010, 2, 49-67.
[] [PMID: 24367208]
Comarmond, C.; Garrido, M.; Pol, S.; Desbois, A.C.; Costopoulos, M.; Le Garff-Tavernier, M.; Si Ahmed, S.N.; Alric, L.; Fontaine, H.; Bellier, B.; Maciejewski, A.; Rosenzwajg, M.; Klatzmann, D.; Musset, L.; Poynard, T.; Cacoub, P.; Saadoun, D. Direct-Acting Antiviral Therapy Restores Immune Tolerance to Patients With Hepatitis C Virus-Induced Cryoglobulinemia Vasculitis. Gastroenterology, 2017, 152(8), 2052-2062.e2.
[] [PMID: 28274850]
Sasaki, R.; Meyer, K.; Moriyama, M.; Kato, N.; Yokosuka, O.; Ray, R.B.; Aurora, R.; Ray, R.; Kanda, T. Rapid hepatitis C virus clearance by antivirals correlates with immune status of infected patients. J. Med. Virol., 2019, 91(3), 411-418.
[] [PMID: 30192392]
Chekuri, S.; Nickerson, J.; Bichoupan, K.; Sefcik, R.; Doobay, K.; Chang, S.; DelBello, D.; Harty, A.; Dieterich, D.T.; Perumalswami, P.V.; Branch, A.D. Liver Stiffness Decreases Rapidly in Response to Successful Hepatitis C Treatment and Then Plateaus. PLoS One, 2016, 11(7)e0159413
[] [PMID: 27442255]
Vukobrat-Bijedic, Z.; Husic-Selimovic, A.; Mehinovic, L.; Mehmedovic, A.; Junuzovic, D.; Bjelogrlic, I.; Sofic, A.; Djurovic, A. Analysis of effect of antiviral therapy on regression of liver fibrosis in patient with HCV infection. Mater. Sociomed., 2014, 26(3), 172-176.
[] [PMID: 25126010]
Par, A.; Par, P.G.; Berki, T.; Miseta, A.; Hegedus, G.; Mozsyk, G.; Hunyady, B. Peg-IFN plus ribavirin therapy suppresses plasma TGF-1 beta, hyaluronic acid and procollagen-III peptide levels in patients with chronic hepatitis C independently of virological response. J. Hepatol., 2006, 44(2), 222.
[] [PMID: 17069924]
Abd-Elsalam, S.; Habba, E.; Elkhalawany, W.; Tawfeek, S.; Elbatea, H.; El-Kalla, F.; Soliman, H.; Soliman, S.; Yousef, M.; Kobtan, A.; El Nawasany, S.; Awny, S.; Amer, I.; Mansour, L.; Rizk, F. Correlation of platelets count with endoscopic findings in a cohort of Egyptian patients with liver cirrhosis. Medicine (Baltimore), 2016, 95(23)e3853
[] [PMID: 27281094]
Mansour, L.; El-Kalla, F.; El-Bassat, H.; Abd-Elsalam, S.; El-Bedewy, M.; Kobtan, A.; Badawi, R.; Elhendawy, M. Randomized controlled trial of scleroligation versus band ligation alone for eradication of gastroesophageal varices. Gastrointest. Endosc., 2017, 86(2), 307-315.
[] [PMID: 28082116]

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