Real-world results of direct-acting antivirals use for the treatment of chronic hepatitis C in old patients
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Key Summary Points
What are the real-world efficacy and safety of direct-acting antivirals (DAAs) in old chronic HCV population?
The overall sustained virological response rate was 98.9%. Higher albumin, higher platelet count, lower bilirubin and lower stage of fibrosis were among predictors of favorable response.
Different DAAs regimens were safe and effective in old patients with chronic HCV.
Background and aim
Old people with chronic hepatitis C (HCV) were considered a difficult-to-treat category with more frequent adverse events until recently. Interferon-free direct-acting antivirals (DAAs) improved treatment adherence and quality of life of old patients. In this study, we aimed at reporting the real-world efficacy and safety of DAAs, in addition to predictors of sustained virological response (SVR) in old chronic HCV population.
This is a prospective observational intention-to-treat analysis that included old chronic hepatitis C genotype-4 patients (> 65 years) treated in a single specialized viral hepatitis treatment center in Egypt. Treatment regimens were allocated according to national guidelines for treatment of hepatitis C. Primary outcome was undetectable HCV-RNA at 12-week post-treatment by PCR. Secondary outcomes were identification of predictors of SVR and assessment of safety related issues.
Our study included 864 patients (64% females) with mean age of 67.7 ± 2.8 years. Overall SVR rate was 98.9% while SVR rates for sofosbuvir/daclatasvir/ribavirin, paritaprevir/ombitasvir/ritonavir/ribavirin, sofosbuvir/daclatasvir, sofosbuvir/ledipasvir/ribavirin, sofosbuvir/simeprevir/daclatasvir/ribavirin, sofosbuvir/simeprevir, interferon/sofosbuvir/ribavirin and sofosbuvir/ribavirin were 100%, 100%, 100%, 100%, 100%, 99.3%, 98% and 94.2%, respectively. DAAs were well tolerated. None of the patients discontinued the treatment due to adverse effects. Higher albumin, higher platelet count, lower bilirubin and lower stage of fibrosis were among predictors of favourable response.
Different DAAs regimens were safe and effective in old Egyptian patients with chronic HCV.
KeywordsDirect-acting antivirals HCV Egypt Old
Hepatitis C virus
New Cairo Viral Hepatitis Treatment Center
- Peg IFN
Quality of life
Sustained virological response
Guarantor of the article: ME. Specific author contributions: ME, ZA, RE, MA, ME and SMA SM designed the research; ME, ZA, MNW, NY and SE performed the research; MT, LA and SMA contributed analytic tools; ME, ZA, MT and SMA analyzed the data; ME, ZA and SMA wrote the paper. All authors approved the final version of the manuscript.
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Compliance with ethical standards
Conflict of interest
None of the authors have any conflicts of interests or financial disclosures related to this work.
This research is approved by the Institutional Review Board for Human Subject Research at National Hepatology and Tropical Medicine Research Institute (Serial: 28-2015).
A written informed consent was obtained from all enrolled participants before enrolment to the study.
- 1.European Centre for Disease Prevention and Control, Hepatitis C—Annual Epidemiological Report for 2015 Stockholm: 2017. https://ecdc.europa.eu/en/publications-data/hepatitis-c-annual-epidemiological-report-2015. Accessed 12 Jan 2018
- 2.Ministry of Health and Population [Egypt], El-Zanaty and Associates [Egypt], and ICF International (2015) Egypt Health Issues Survey 2015. Ministry of Health and Population and ICF International, Cairo. https://dhsprogram.com/pubs/pdf/FR313/FR313.pdf. Accessed 15 Jan 2018
- 3.Blach S, Zeuzem S, Manns M, Altraif I, Duberg AS, Muljono DH, Waked I, Alavian SM, Lee MH, Negro F, Abaalkhail F (2017) Global prevalence and genotype distribution of hepatitis C virus infection in 2015: a modelling study. Lancet Gastroenterol Hepatol 2(3):161–176Google Scholar
- 4.Esmat G, El Kassas M, Hassany M, Gamil ME, El Raziky M (2013) How to optimize HCV therapy in genotype 4 patients. Liver Int 33:41–45Google Scholar
- 5.Esmat G, El Kassas M, Hassany M, Gamil M, El Raziky M (2014) Optimizing treatment for HCV genotype 4: PEG-IFN alfa 2a vs PEG-IFN alfa 2b; the debate continues. Liver Int 34:24–28Google Scholar
- 6.El-Akel W, El-Sayed MH, El Kassas M, El-Serafy M, Khairy M, Elsaeed K, Kabil K, Hassany M, Shawky A, Yosry A, Shaker MK (2017) National treatment programme of hepatitis C in Egypt: hepatitis C virus model of care. J Viral Hepat 24(4):262–267Google Scholar
- 7.El Kassas M, Elbaz T, Elsharkawy A, Omar H, Esmat G (2018) HCV in Egypt, prevention, treatment and key barriers to elimination. Expert Rev Anti-infective Ther 16(4):345–350Google Scholar
- 8.Omar H, El Akel W, Elbaz T, El Kassas M, Elsaeed K, El Shazly H, Said M, Yousif M, Gomaa AA, Nasr A, AbdAllah M (2018) Generic daclatasvir plus sofosbuvir, with or without ribavirin, in treatment of chronic hepatitis C: real-world results from 18 378 patients in Egypt. Aliment Pharmacol Ther 47(3):421–431Google Scholar
- 9.World Health Organization. Proposed working definition of an old person in Africa. http://www.who.int/healthinfo/survey/ageingdefnold/en/. Accessed 11 Jan 2018
- 10.Egypt demographic profile, CIA world fact book last updated January 2018. https://www.cia.gov/library/publications/the-world-factbook/geos/eg.html. Accessed 12 Jan 2018
- 11.Yang Z, Zhuang L, Yang L, Liu C, Lu Y, Xu Q, Chen X, Chen L (2014) Efficacy and safety of peginterferon plus ribavirin for patients aged ≥ 65 years with chronic hepatitis C: a systematic review and meta-analysis. Clin Res Hepatol Gastroenterol 38(4):440–450Google Scholar
- 12.Elbaz T, El-Kassas M, Esmat G (2015) New era for management of chronic hepatitis C virus using direct antiviral agents: a review. J Adv Res 6(3):301–310Google Scholar
- 13.El Kassas M, Elbaz T, Hafez E, Esmat G (2016) Safety of direct antiviral agents in the management of hepatitis C. Expert Opin Drug Saf 15(12):1643–1652Google Scholar
- 14.El Kassas M, Alboraie M, Omran D, Salaheldin M, Wifi MN, ElBadry M, El Tahan A, Ezzat S, Moaz E, Farid AM, Omar H, Abouelkhair M, Afify S, Elsaeed K, Shazly Y, Doss W, Esmat G (2018) An account of the real-life hepatitis C management in a single specialized viral hepatitis treatment centre in Egypt: results of treating 7042 patients with 7 different direct acting antiviral regimens. Expert Rev Gastroenterol Hepatol 24:1–8Google Scholar
- 15.Imai Y, Kasahara A, Tanaka H, Okanoue T, Hiramatsu N, Tsubouchi H, Yoshioka K, Kawata S, Tanaka E, Hino K, Hayashi K (2004) Interferon therapy for aged patients with chronic hepatitis C: improved survival in patients exhibiting a biochemical response. J Gastroenterol 39(11):1069–1077Google Scholar
- 16.American Association for the Study of Liver Diseases, Infectious Diseases Society of America (2016) Initial treatment of HCV infection. Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org/full-report/initial-treatment-hcv-infection. Accessed 8 Jan 2018
- 17.European Association for the Study of the Liver (2017) EASL recommendations on treatment of hepatitis C 2016. J Hepatol 66(1):153Google Scholar
- 18.Doss W, Shiha G, Hassany M, Soliman R, Fouad R, Khairy M, Samir W, Hammad R, Kersey K, Jiang D, Doehle B (2015) Sofosbuvir plus ribavirin for treating Egyptian patients with hepatitis C genotype 4. J Hepatol 63(3):581–585Google Scholar
- 19.Ruane PJ, Ain D, Stryker R, Meshrekey R, Soliman M, Wolfe PR, Riad J, Mikhail S, Kersey K, Jiang D, Massetto B (2015) Sofosbuvir plus ribavirin for the treatment of chronic genotype 4 hepatitis C virus infection in patients of Egyptian ancestry. J Hepatol 62(5):1040–1046Google Scholar
- 20.Elsharkawy A, Eletreby R, Fouad R, Soliman Z, Abdallah M, Negm M, Mohey M, Esmat G (2017) Impact of different sofosbuvir based treatment regimens on the biochemical profile of chronic hepatitis C genotype 4 patients. Expert Rev Gastroenterol Hepatol 11(8):773–778Google Scholar
- 21.Sherigar JM, Gayam V, Khan A, Mukhtar O, Arefiev Y, Khalid M, Siddiqui I, Rangaraju AM, Budhathoki N, Mansour M, Guss D (2017) Clinical efficacy and tolerability of direct-acting antivirals in elderly patients with chronic hepatitis C. Eur J Gastroenterol Hepatol 29(7):767Google Scholar
- 22.El Raziky M, Gamil M, Hammad R, Hashem M, S, Khairy M, Elsharkawy A et al (2015) Treatment of hepatitis C genotype 4 patients with simeprevir and sofosbuvir: preliminary results from a phase IIa, partially randomised, open-label trial conducted in Egypt (OSIRIS). OSIRIS Poster. The Liver Meeting®, The annual meeting of the American Association for the Study of Liver Diseases. Abstract ID: 1163. OSIRIS posterGoogle Scholar
- 23.Willemse SB, Baak LC, Kuiken SD, Van der Sluys Veer A, Lettinga KD, van der Meer JT, Depla AC, Tuynman H, van Nieuwkerk CM, Schinkel CJ, Kwa D (2016) Sofosbuvir plus simeprevir for the treatment of HCV genotype 4 patients with advanced fibrosis or compensated cirrhosis is highly efficacious in real life. J Viral Hepat 23(12):950–954Google Scholar
- 24.Waked I, Shiha G, Qaqish RB, Esmat G, Yosry A, Hassany M, Soliman R, Mohey MA, Allam N, Zayed N, Asselah T (2016) Ombitasvir, paritaprevir, and ritonavir plus ribavirin for chronic hepatitis C virus genotype 4 infection in Egyptian patients with or without compensated cirrhosis (AGATE-II): a multicentre, phase 3, partly randomised open-label trial. Lancet Gastroenterol Hepatol 1(1):36–44Google Scholar
- 25.Vermehren J, Peiffer KH, Welsch C, Grammatikos G, Welker MW, Weiler N, Zeuzem S, Welzel TM, Sarrazin C (2016) The efficacy and safety of direct acting antiviral treatment and clinical significance of drug–drug interactions in elderly patients with chronic hepatitis C virus infection. Aliment Pharmacol Ther 44(8):856–865Google Scholar
- 26.Conti F, Brillanti S, Buonfiglioli F, Vukotic R, Morelli MC, Lalanne C, Massari M, Foschi FG, Bernabucci V, Serio I, Prati GM (2017) Safety and efficacy of direct-acting antivirals for the treatment of chronic hepatitis C in a real-world population aged 65 years and older. J Viral Hepat 24(6):454–463Google Scholar
- 27.Fabrizio C, Saracino A, Scudeller L, Milano E, Dell’Acqua R, Bruno G, Caputo SL, Monno L, Milella M, Angarano G (2017) The elderly and direct antiviral agents: constraint or challenge? Dig Liver Dis 49(9):1036–1042Google Scholar
- 28.Fabrizio C, Procopio A, Scudeller L, Dell’Acqua R, Bruno G, Milano E, Milella M, Saracino A, Angarano G (2017) HCV and diabetes: towards a ‘sustained’ glycaemic improvement after treatment with DAAs? Clin Microbiol Infect 23(5):342–343Google Scholar
- 29.Soriano V, Barreiro P, de Mendoza C (2016) Hypoglycemia in a diabetic patient during hepatitis C therapy. Hepatology 63(6):2065–2066Google Scholar
- 30.Maor Y, Malnick SD, Melzer E, Leshno M (2016) Treatment of chronic hepatitis c in the aged-does it impact life expectancy? A decision analysis. PLoS One 11(7):e0157832Google Scholar
- 31.Younossi ZM, Stepanova M, Nader F, Henry L (2016) Patient-reported outcomes of elderly adults with chronic hepatitis C treated with interferon-and ribavirin-free regimens. J Am Geriatr Soc 64(2):386–393Google Scholar
- 32.World Health Organization, Country profile: Egypt. https://www.who.int/countries/egy/en/. Accessed 21 Dec 2018