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Endocrine, Metabolic & Immune Disorders - Drug Targets

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

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Research Article

The Effect of HCV Eradication after Direct-Acting Antiviral Agents on Hepatic Steatosis: A Prospective Observational Study

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

Volume 22, Issue 1, 2022

Published on: 25 January, 2021

Page: [100 - 107] Pages: 8

DOI: 10.2174/1871530321666210125125500

Price: $65

Abstract

Background and Aim: Eradication of hepatitis C virus (HCV) by direct-acting-antiviral- agents (DAAs) was followed by fibrosis regression, but little is available about hepatic steatosis changes after DAAs. The aim of this work was to assess the prevalence of hepatic steatosis among HCV Egyptian patients and the long term changes occuring after viral eradication.

Methods: This prospective cohort study included 150 HCV patients with significant fibrosis. They were examined by Transient elastography to evaluate liver stiffness measurement (LSM) and hepatic steatosis before treatment, at SVR12 and 1 year after the end of therapy.

Results: LSM showed a significant positive correlation to pretreatment of hepatic steatosis. LSM significantly decreased and hepatic steatosis significantly increased both at SVR12 and one year after DAAs. Patients with steatosis showed significantly higher median LSM and controlled attenuation parameter (CAP) values at: baseline, SVR12, and one year after therapy. Also, the pretreatment steatosis and body mass index (BMI) had a significant negative correlation with fibrosis regression one year after therapy in all studied groups.

Conclusion: Hepatic steatosis is common in HCV Egyptian patients and increases after HCV eradication with DAAs. BMI and CAP values are negatively correlated to hepatic fibrosis regression and positively correlated to steatosis progression one year after DAAs. So, HCV patients with hepatic steatosis may need close follow up for atherosclerotic and HCC risk after DAAs, especially if they are overweight.

Keywords: HCV, steatosis, cirrhosis, direct acting antiviral drugs, BMI, Fibroscan.

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Graphical Abstract

[1]
World Health Organization. Hepatitis C: factsheet., 2018. Available from: http://www.who.int/mediacentre/factsheets/fs164/en/ (Accessed on September 1, 2020).
[2]
El-Zanaty, F.; Way, A. Egypt Demographic and Health Survey; Ministry of Health, El-Zanaty and Associates, and Macro International, Cairo, Egypt, 2009.
[3]
Ministry of Health and Population [Egypt], El-Zanaty and Associates [Egypt] & and ICF International., 2015,
[4]
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.
[http://dx.doi.org/10.1016/j.jhep.2010.11.016] [PMID: 21316497]
[5]
Vuppalanchi, R.; Siddiqui, M.S.; Van Natta, M.L.; Hallinan, E.; Brandman, D.; Kowdley, K.; Neuschwander-Tetri, B.A.; Loomba, R.; Dasarathy, S.; Abdelmalek, M.; Doo, E.; Tonascia, J.A.; Kleiner, D.E.; Sanyal, A.J.; Chalasani, N. NASH Clinical Research Network. Performance characteristics of vibration-controlled transient elastography for evaluation of nonalcoholic fatty liver disease. Hepatology, 2018, 67(1), 134-144.
[http://dx.doi.org/10.1002/hep.29489] [PMID: 28859228]
[6]
Mikolasevic, I.; Orlic, L.; Franjic, N.; Hauser, G.; Stimac, D.; Milic, S. Transient elastography (FibroScan(®)) with controlled attenuation parameter in the assessment of liver steatosis and fibrosis in patients with nonalcoholic fatty liver disease - Where do we stand? World J. Gastroenterol., 2016, 22(32), 7236-7251.
[http://dx.doi.org/10.3748/wjg.v22.i32.7236] [PMID: 27621571]
[7]
Asselah, T.; Rubbia-Brandt, L.; Marcellin, P.; Negro, F. Steatosis in chronic hepatitis C: why does it really matter? Gut, 2006, 55(1), 123-130.
[http://dx.doi.org/10.1136/gut.2005.069757] [PMID: 16344578]
[8]
Adinolfi, L.E.; Rinaldi, L.; Guerrera, B.; Restivo, L.; Marrone, A.; Giordano, M.; Zampino, R. NAFLD and NASH in HCV infection: Prevalence and significance in hepatic and extrahepatic manifestations. Int. J. Mol. Sci., 2016, 17(6), 803.
[http://dx.doi.org/10.3390/ijms17060803] [PMID: 27231906]
[9]
Kumar, D.; Farrell, G.C.; Fung, C.; George, J. Hepatitis C virus genotype 3 is cytopathic to hepatocytes: Reversal of hepatic steatosis after sustained therapeutic response. Hepatology, 2002, 36(5), 1266-1272.
[http://dx.doi.org/10.1053/jhep.2002.36370] [PMID: 12395339]
[10]
Harrison, S.A.; Brunt, E.M.; Qazi, R.A.; Oliver, D.A.; Neuschwander-Tetri, B.A.; Di Bisceglie, A.M.; Bacon, B.R. Effect of significant histologic steatosis or steatohepatitis on response to antiviral therapy in patients with chronic hepatitis C. Clin. Gastroenterol. Hepatol., 2005, 3(6), 604-609.
[http://dx.doi.org/10.1016/S1542-3565(05)00246-6] [PMID: 15952103]
[11]
Dolmazashvili, E.; Abutidze, A.; Chkhartishvili, N.; Karchava, M.; Sharvadze, L.; Tsertsvadze, T. Regression of liver fibrosis over a 24-week period after completing direct-acting antiviral therapy in patients with chronic hepatitis C receiving care within the national hepatitis C elimination program in Georgia: results of hepatology clinic HEPA experience. Eur. J. Gastroenterol. Hepatol., 2017, 29(11), 1223-1230.
[http://dx.doi.org/10.1097/MEG.0000000000000964] [PMID: 28857900]
[12]
Noureddin, M.; Wong, M.M.; Todo, T.; Lu, S.C.; Sanyal, A.J.; Mena, E.A. Fatty liver in hepatitis C patients post-sustained virological response with direct-acting antivirals. World J. Gastroenterol., 2018, 24(11), 1269-1277.
[http://dx.doi.org/10.3748/wjg.v24.i11.1269] [PMID: 29568207]
[13]
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.
[http://dx.doi.org/10.1002/hep.27366] [PMID: 25314116]
[14]
Adinolfi, L.E.; Gambardella, M.; Andreana, A.; Tripodi, M.F.; Utili, R.; Ruggiero, G. Steatosis accelerates the progression of liver damage of chronic hepatitis C patients and correlates with specific HCV genotype and visceral obesity. Hepatology, 2001, 33(6), 1358-1364.
[http://dx.doi.org/10.1053/jhep.2001.24432] [PMID: 11391523]
[15]
Hui, J.M.; Sud, A.; Farrell, G.C.; Bandara, P.; Byth, K.; Kench, J.G.; McCaughan, G.W.; George, J. Insulin resistance is associated with chronic hepatitis C virus infection and fibrosis progression [corrected]. Gastroenterology, 2003, 125(6), 1695-1704.
[http://dx.doi.org/10.1053/j.gastro.2003.08.032] [PMID: 14724822]
[16]
Hickman, I.J.; Powell, E.E.; Prins, J.B.; Clouston, A.D.; Ash, S.; Purdie, D.M.; Jonsson, J.R. In overweight patients with chronic hepatitis C, circulating insulin is associated with hepatic fibrosis: implications for therapy. J. Hepatol., 2003, 39(6), 1042-1048.
[http://dx.doi.org/10.1016/S0168-8278(03)00463-X] [PMID: 14642624]
[17]
Kouyoumjian, SP; Chemaitelly, H; Abu-Raddad, LJ Characterizing hepatitis C virus epidemiology in Egypt: systematic reviews, meta-analyses, and meta-regressions. Sci. Rep., 2018, 8(1), 1661.
[18]
Bochud, P.Y.; Cai, T.; Overbeck, K.; Bochud, M.; Dufour, J.F.; Müllhaupt, B.; Borovicka, J.; Heim, M.; Moradpour, D.; Cerny, A.; Malinverni, R.; Francioli, P.; Negro, F. Swiss Hepatitis C Cohort Study Group. Genotype 3 is associated with accelerated fibrosis progression in chronic hepatitis C. J. Hepatol., 2009, 51(4), 655-666.
[http://dx.doi.org/10.1016/j.jhep.2009.05.016] [PMID: 19665246]
[19]
Negro, F. Abnormalities of lipid metabolism in hepatitis C virus infection. Gut, 2010, 59(9), 1279-1287.
[http://dx.doi.org/10.1136/gut.2009.192732] [PMID: 20660700]
[20]
Negro, F. Facts and fictions of HCV and comorbidities: steatosis, diabetes mellitus, and cardiovascular diseases. J. Hepatol., 2014, 61(Suppl. 1), S69-S78.
[http://dx.doi.org/10.1016/j.jhep.2014.08.003] [PMID: 25443347]
[21]
Byrne, C.D.; Targher, G. NAFLD: a multisystem disease. J. Hepatol., 2015, 62(Suppl. 1), S47-S64.
[http://dx.doi.org/10.1016/j.jhep.2014.12.012] [PMID: 25920090]
[22]
Miyanari, Y.; Atsuzawa, K.; Usuda, N.; Watashi, K.; Hishiki, T.; Zayas, M.; Bartenschlager, R.; Wakita, T.; Hijikata, M.; Shimotohno, K. The lipid droplet is an important organelle for hepatitis C virus production. Nat. Cell Biol., 2007, 9(9), 1089-1097.
[http://dx.doi.org/10.1038/ncb1631] [PMID: 17721513]
[23]
Syed, GH; Tang, H; Khan, M; Hassanein, T; Liu, J; Siddiqui, A Hepatitis C virus stimulates low-density lipoproteinreceptor expression to facilitate viral propagation. J. Virol., 2014, 88(5), 2519-2529.
[24]
Czaja, A.J.; Carpenter, H.A.; Santrach, P.J.; Moore, S.B. Host- and disease-specific factors affecting steatosis in chronic hepatitis C. J. Hepatol., 1998, 29(2), 198-206.
[http://dx.doi.org/10.1016/S0168-8278(98)80004-4] [PMID: 9722200]
[25]
Cheng, Y; Dharancy, S; Malapel, M; Desreumaux, P. Hepatitis C virus infection down-regulates the expression of peroxisome proliferator-activated receptor alpha and carnitine palmitoyl acyl-CoA transferase1A. World J Gastroenterol., 2005, 11(48), 7591-7596.
[26]
Tsukuda, Y.; Suda, G.; Tsunematsu, S.; Ito, J.; Sato, F.; Terashita, K.; Nakai, M.; Sho, T.; Maehara, O.; Shimazaki, T.; Kimura, M.; Morikawa, K.; Natsuizaka, M.; Ogawa, K.; Ohnishi, S.; Chuma, M.; Sakamoto, N. Anti-adipogenic and antiviral effects of l-carnitine on hepatitis C virus infection. J. Med. Virol., 2017, 89(5), 857-866.
[http://dx.doi.org/10.1002/jmv.24692] [PMID: 27664407]
[27]
Rout, G.; Nayak, B.; Patel, A.H.; Gunjan, D.; Singh, V.; Kedia, S. Shalimar, therapy with oral directly acting agents in hepatitis c infection is associated with reduction in fibrosis and increase in hepatic steatosis on transient elastography. J. Clin. Exp. Hepatol., 2019, 9(2), 207-214.
[http://dx.doi.org/10.1016/j.jceh.2018.06.009] [PMID: 31024203]
[28]
Kawagishi, N.; Suda, G.; Nakamura, A.; Kimura, M.; Maehara, O.; Suzuki, K.; Nakamura, A.; Ohara, M.; Izumi, T.; Umemura, M.; Nakai, M.; Sho, T.; Natsuizaka, M.; Morikawa, K.; Ogawa, K.; Kudo, Y.; Nishida, M.; Miyoshi, H.; Sakamoto, N. Liver steatosis and dyslipidemia after HCV eradication by direct acting antiviral agents are synergistic risks of atherosclerosis. PLoS One, 2018, 13(12), e0209615.
[http://dx.doi.org/10.1371/journal.pone.0209615] [PMID: 30576386]
[29]
Ichikawa, T.; Miyaaki, H.; Miuma, S.; Motoyoshi, Y.; Narita, S.; Toda, S.; Takahashi, Y.; Honda, T.; Yajima, H.; Uehara, R.; Hino, N.; Hori, T.; Hirata, R.; Taura, N.; Nakao, K. Carotid intima-media thickness and small dense low-density lipoprotein cholesterol increase after one year of treatment with direct-acting antivirals in patients with hepatitis C virus infection. Intern. Med., 2019, 58(9), 1209-1215.
[http://dx.doi.org/10.2169/internalmedicine.1514-18] [PMID: 30626818]
[30]
Tanaka, A.; Uegaki, S.; Kurihara, H.; Aida, K.; Mikami, M.; Nagashima, I.; Shiga, J.; Takikawa, H. Hepatic steatosis as a possible risk factor for the development of hepatocellular carcinoma after eradication of hepatitis C virus with antiviral therapy in patients with chronic hepatitis C. World J. Gastroenterol., 2007, 13(39), 5180-5187.
[http://dx.doi.org/10.3748/wjg.v13.i39.5180] [PMID: 17876888]
[31]
Kurosaki, M.; Hosokawa, T.; Matsunaga, K.; Hirayama, I.; Tanaka, T.; Sato, M.; Yasui, Y.; Tamaki, N.; Ueda, K.; Tsuchiya, K.; Kuzuya, T.; Nakanishi, H.; Itakura, J.; Takahashi, Y.; Asahina, Y.; Enomoto, N.; Izumi, N. Hepatic steatosis in chronic hepatitis C is a significant risk factor for developing hepatocellular carcinoma independent of age, sex, obesity, fibrosis stage and response to interferon therapy. Hepatol. Res., 2010, 40(9), 870-877.
[http://dx.doi.org/10.1111/j.1872-034X.2010.00692.x] [PMID: 20887591]
[32]
Tada, T.; Kumada, T.; Toyoda, H.; Sone, Y.; Takeshima, K.; Ogawa, S.; Goto, T.; Wakahata, A.; Nakashima, M.; Nakamuta, M.; Tanaka, J. Viral eradication reduces both liver stiffness and steatosis in patients with chronic hepatitis C virus infection who received direct-acting anti-viral therapy. Aliment. Pharmacol. Ther., 2018, 47(7), 1012-1022.
[http://dx.doi.org/10.1111/apt.14554] [PMID: 29424449]
[33]
Soliman, H.; Ziada, D.; Salama, M.; Hamisa, M.; Badawi, R.; Hawash, N.; Selim, A.; Abd-Elsalam, S. Predictors for fibrosis regression in chronic hcv patients after the treatment with daas: results of a real-world cohort study. Endocr. Metab. Immune Disord. Drug Targets, 2019, 19, 1-8.
[PMID: 31448717]
[34]
Singh, S; Facciorusso, A; Loomba, R; Falck-Ytter, YT Magnitude and kineticsof decrease in liver stiffness after anti-viral therapy in patients with chronic hepatitisC: a systematic review and meta-analysis. ClinGastroenterol Hepatol, 2018, 16(1), 27-38.e4.
[35]
Shimada, M.; Iwase, H.; Hirashima, N.; Ryuge, N.; Urata, N. Nutritional status and liver steatosis after direct-acting antiviral treatment for chronic hepatitis C virus infection. J. Transl. Sci., 2017, 3(5), 2-5.
[http://dx.doi.org/10.15761/JTS.1000194]
[36]
Ogasawara, N.; Kobayashi, M.; Akuta, N.; Kominami, Y.; Fujiyama, S.; Kawamura, Y.; Sezaki, H.; Hosaka, T.; Suzuki, F.; Saitoh, S.; Suzuki, Y.; Arase, Y.; Ikeda, K.; Kobayashi, M.; Kumada, H. Serial changes in liver stiffness and controlled attenuation parameter following direct-acting antiviral therapy against hepatitis C virus genotype 1b. J. Med. Virol., 2018, 90(2), 313-319.
[http://dx.doi.org/10.1002/jmv.24950] [PMID: 28906010]
[37]
Ohya, K.; Akuta, N.; Suzuki, F.; Fujiyama, S.; Kawamura, Y.; Kominami, Y.; Sezaki, H.; Hosaka, T.; Kobayashi, M.; Kobayashi, M.; Suzuki, Y.; Saitoh, S.; Arase, Y.; Ikeda, K.; Kumada, H. Predictors of treatment efficacy and liver stiffness changes following therapy with Sofosbuvir plus Ribavirin in patients infected with HCV genotype 2. J. Med. Virol., 2018, 90(5), 919-925.
[http://dx.doi.org/10.1002/jmv.25023] [PMID: 29315652]
[38]
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.
[http://dx.doi.org/10.1053/j.gastro.2017.02.037] [PMID: 28274850]
[39]
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.
[http://dx.doi.org/10.1002/jmv.25310] [PMID: 30192392]
[40]
Anderson, N.; Borlak, J. Molecular mechanisms and therapeutic targets in steatosis and steatohepatitis. Pharmacol. Rev., 2008, 60(3), 311-357.
[http://dx.doi.org/10.1124/pr.108.00001] [PMID: 18922966]
[41]
Rasool, S.; Hamid, S.; Jafri, W.; Shah, H.; Abid, S.; Ahmed, Z. Etiology and Impact of Hepatic Steatosis in Pakistan: Role of HepatitisC Virus Genotype 3 Infection. International Journal of Medical Research &Health Sciences, 2019, 8(7), 97-103.
[42]
Sharma, P.; Balan, V.; Hernandez, J.; Rosati, M.; Williams, J.; Rodriguez-Luna, H.; Schwartz, J.; Harrison, E.; Anderson, M.; Byrne, T.; Vargas, H.E.; Douglas, D.D.; Rakela, J. Hepatic steatosis in hepatitis C virus genotype 3 infection: does it correlate with body mass index, fibrosis, and HCV risk factors? Dig. Dis. Sci., 2004, 49(1), 25-29.
[http://dx.doi.org/10.1023/B:DDAS.0000011597.92851.56] [PMID: 14992430]
[43]
Hino, K.; Hara, Y.; Nishina, S. Mitochondrial reactive oxygen species as a mystery voice in hepatitis C. Hepatol. Res., 2014, 44(2), 123-132.
[http://dx.doi.org/10.1111/hepr.12247] [PMID: 24112394]
[44]
Chitturi, S.; Abeygunasekera, S.; Farrell, G.C.; Holmes-Walker, J.; Hui, J.M.; Fung, C.; Karim, R.; Lin, R.; Samarasinghe, D.; Liddle, C.; Weltman, M.; George, J. NASH and insulin resistance: Insulin hypersecretion and specific association with the insulin resistance syndrome. Hepatology, 2002, 35(2), 373-379.
[http://dx.doi.org/10.1053/jhep.2002.30692] [PMID: 11826411]
[45]
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.
[http://dx.doi.org/10.2174/1871526517666170417143216] [PMID: 28413993]
[46]
Abdelmoemen, G.; Khodeir, S.A.; Abou-Saif, S.; Kobtan, A.; Abd-Elsalam, S. Prevalence of occult hepatitis C virus among hemodialysis patients in Tanta university hospitals: a single-center study. Environ. Sci. Pollut. Res. Int., 2018, 25(6), 5459-5464.
[http://dx.doi.org/10.1007/s11356-017-0897-y] [PMID: 29214477]
[47]
Tawfik, A.K.; Amin, A.M.; Yousef, M.; El-Sayd, N.M.; Elashry, H.; Elkadeem, M.; Abd-Elsalam, S. IL-1α correlates with severity of hepatitis C virus-related liver diseases. J. Inflamm. Res., 2018, 11, 289-295.
[http://dx.doi.org/10.2147/JIR.S166564] [PMID: 30022847]
[48]
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 the Treatment of an Egyptian Cohort with Hepatitis C Virus Infection in Real-Life Clinical Practice. Infect. Disord. Drug Targets, 2019, 19(2), 179-184.
[PMID: 30207250]
[49]
Wasfy, E.; Elkassas, G.; Elnawasany, S.; Elkasrawy, K.; Abd-Elsalam, S.; Soliman, S.; Badawi, R. Predicting Esophageal Varices in Cirrhotic Hepatitis C Virus Patients Using Noninvasive Measurement of Insulin Resistance Variables. Endocr. Metab. Immune Disord. Drug Targets, 2018, 18(6), 573-580.
[http://dx.doi.org/10.2174/1871530318666180803120428] [PMID: 30073932]
[50]
Mohamed, A.A.; El-Toukhy, N.E.R.; Said, E.M.; Gabal, H.M.R.; AbdelAziz, H.; Doss, W.; El-Hanafi, H.; El Deeb, H.H.; Mahmoud, S.; Elkadeem, M.; Shalby, H.S.; Abd-Elsalam, S. Hepatitis C Virus: Efficacy of New DAAs Regimens. Infect. Disord. Drug Targets, 2020, 20(2), 143-149.
[http://dx.doi.org/10.2174/1871526519666190121114003] [PMID: 30663575]

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