Effectiveness of second-generation direct-acting antivirals in patients infected with hepatitis c virus and factors associated with a nonsustained virological response

Mariana Ilha  Ziolkowski; Manoel Rodrigues da  Silva Neto; Raqueli Altamiranda  Bittencourt; Lucas Pitrez  Mocellin; Sandra Elisa  Haas

doi:10.1590/

Authors

Mariana Ilha Ziolkowski Graduate Program in Pharmaceutical Sciences, Federal University of Pampa, UNIPAMPA, Uruguaiana, Brazil; Municipal Health Secretariat of Uruguaiana, Rio Grande do Sul, Brazil
Manoel Rodrigues da Silva Neto Pharmacology and Pharmacometrics Laboratory, LABFAR, Federal University of Pampa, UNIPAMPA, Uruguaiana, Brazil
Raqueli Altamiranda Bittencourt Municipal Health Secretariat of Uruguaiana, Rio Grande do Sul, Brazil
Lucas Pitrez Mocellin College of Medicine, Federal University of Pampa, Uruguaiana, Brazil
Sandra Elisa Haas Graduate Program in Pharmaceutical Sciences, Federal University of Pampa, UNIPAMPA, Uruguaiana, Brazil; Pharmacology and Pharmacometrics Laboratory, LABFAR, Federal University of Pampa, UNIPAMPA, Uruguaiana, Brazil https://orcid.org/0000-0002-5687-6736

DOI:

https://doi.org/10.1590/

Keywords:

Hepatitis C, Antivirals, Sustained virologic response, Direct antiviral agents

Abstract

In Brazil, hepatitis C virus (HCV) treatment has gone through several stages until it reached the current schemes. This study aimed to evaluate the clinical, epidemiologic, and effectiveness of treatment with second-generation direct-acting antivirals (DAAs) for HCV-infected patients in southern Brazil. Medical records of a reference center of Uruguaiana-RS/Brazil were evaluated from December 2017 to August 2020. Data collected included demographics, disease severity and comorbidities, genotype, viral load, medications, treatment side effects, and sustained virological response (SVR). A multivariate linear regression model was developed to identify the factors associated with non-sustained virological response. The HCV-infected patients were predominantly male, white, Genotype 1, with initial liver fibrosis (F0/F1), and untreated patients. Laboratory parameters of the liver profile showed significant improvement after completion of treatment with second-generation DAA for 12 weeks. Significant results were found in the Genotype where 7.3 and 6.0 times more chances of Genotype 1a and Genotype 3, respectively, to present detectable SVR compared to Genotype 1b. Variable cardiovascular comorbidity also indicated a higher risk of absence of SVR compared to individuals without this comorbidity. Treatment with second-generation DAAs can contribute to the Brazilian hepatitis C elimination plan proposed by the World Health Organization.

Downloads

Download data is not yet available.

References

Bogdanos DP, Rigopoulou EI. Viral/self-mimicry and immunological cross-reactivity as a trigger of hepatic C virus associated autoimmune diabetes. Diabetes Res Clin Pract. 2007 Jul 1; 77(1): 155–6.

Brasil. Ministério da Saúde. Secretaria de Vigilância em Saúde. Departamento de DST, Aids e Hepatites Virais. Boletim Epidemiológico: Hepatites Virais. Brasília: Ministério da Saúde. 2020. Available at: http://antigo.aids.gov.br/pt-br/pub/2020/boletim-epidemiologico-hepatitesvirais-2020#:~:text=Boletim%20Epidemiol%C3%B3gico%20de%20Hepatites,Virais%20%202020%202.34%20MB .

» http://antigo.aids.gov.br/pt-br/pub/2020/boletim-epidemiologico-hepatitesvirais-2020#:~:text=Boletim%20Epidemiol%C3%B3gico%20de%20Hepatites,Virais%20%202020%202.34%20MB

Brasil. Ministério da Saúde. Secretaria de Vigilância em Saúde. Departamento de Vigilância Prevenção e Controle das IST do HIV/Aids e das Hepatites Virais. Protocolo Clínico e Diretrizes Terapêuticas para a prevenção da Transmissão Vertical de HIV, Sífilis e Hepatites Virais. Brasília: Ministério da Saúde. 2019. Available at: https://portaldeboaspraticas.iff.fiocruz.br/biblioteca/protocolo-clinico-e-diretrizesterapeuticas-para-prevencao-da-transmissao-vertical-do-hiv/ .

» https://portaldeboaspraticas.iff.fiocruz.br/biblioteca/protocolo-clinico-e-diretrizesterapeuticas-para-prevencao-da-transmissao-vertical-do-hiv/

Brasil. Ministério da Saúde. Secretaria de Vigilância em Saúde. Departamento de Vigilância Prevenção e Controle das IST do HIV/Aids e das Hepatites Virais. Protocolo Clínico e Diretrizes Terapêuticas para a prevenção da Transmissão Vertical de HIV, Sífilis e Hepatites Virais. Brasília: Ministério da Saúde. 2023. Available at: https://www.gov.br/aids/pt-br/central-de-conteudo/boletins-epidemiologicos/2023/hepatites-virais/boletim-epidemiologico-hepatites-virais-_-2023.pdf .

» https://www.gov.br/aids/pt-br/central-de-conteudo/boletins-epidemiologicos/2023/hepatites-virais/boletim-epidemiologico-hepatites-virais-_-2023.pdf

Drazilova S, Gazda J, Janicko M, Jarcuska P. Chronic Hepatitis C Association with Diabetes Mellitus and Cardiovascular Risk in the Era of DAA Therapy. Can J Gastroenterol. 2018 Aug 13; 2018: 1–11.

Essa M, Sabry A, Abdelsameea E, Tharwa ES, Salama M. Impact of new direct-acting antiviral drugs on hepatitis C virus-related decompensated liver cirrhosis. Eur J Gastroen Hepat. 2019 Jan; 31(1): 53–8.

Faludi AA, Izar MCO, Saraiva JFK, Chacra APM, Bianco HT, Afiune Neto A et al. Atualização da Diretriz Brasileira de Dislipidemias e Prevenção da Aterosclerose – 2017. Arq Bras Cardiol 2017; 109(2Supl.1): 1-76.

Gong Y, Cun W. The Role of ApoE in HCV Infection and Comorbidity. Int. J. Mol. Sci. 2019 Apr 25; 20(8): 2037.

Hajarizadeh B, Lamoury FM, Feld JJ, Amin J, Keoshkerian E, Matthews GV, et al. Alanine aminotransferase, HCV RNA levels and pro-inflammatory and pro-fibrogenic cytokines/ chemokines during acute hepatitis C virus infection. Virol. J. 2016 Feb 24; 13(1).

Ibrahim Mohammed Ebid A, Ashraf Ahmed O, Hassan Agwa S, Mohamed Abdel-Motaleb S, Mohamed Elsawy A, Hagag RS. Safety, efficacy and cost of two direct- acting antiviral regimens: A comparative study in chronic hepatitis C Egyptian patients. J Clin Pharm Ther. 2019 Dec 31; 45(3): 539–46.

Kawaguchi T, Ide T, Taniguchi E, Hirano E, Itou M, Sumie S, et al. Clearance of HCV Improves Insulin Resistance, Beta- Cell Function, and Hepatic Expression of Insulin Receptor Substrate 1 and 2. AJG. 2007 Mar; 102(3): 570–6.

Lawitz E, Mangia A, Wyles D, Rodriguez-Torres M, Hassanein T, Gordon SC, et al. Sofosbuvir for Previously Untreated Chronic Hepatitis C Infection. N Engl J Med. 2013 May 16; 368(20): 1878–87.

Lobato CM de O, Codes L, Silva GF, Souza AFM, Coelho HSM, Pedroso MLA, et al. Direct antiviral therapy for treatment of hepatitis C: A real-world study from Brazil. Ann Hepatol. 2019 Nov; 18(6): 849–54.

Louie KS, St Laurent S, Forssen UM, Mundy LM, Pimenta JM. The high comorbidity burden of the hepatitis C virus infected population in the United States. BMC Infect Dis. 2012 Apr 11; 12(1).

Mangia A, Piazzolla V, Giannelli A, Visaggi E, Minerva N, Palmieri V, et al. SVR12 rates higher than 99% after sofosbuvir/velpatasvir combination in HCV infected patients with F0-F1 fibrosis stage: A real world experience. Kanda T, editor. PLoS ONE. 2019 May 15; 14(5): e0215783.

Milner KL, Jenkins AB, Trenell M, Tid-Ang J, Samocha- Bonet D, Weltman M, et al. Eradicating hepatitis C virus ameliorates insulin resistance without change in adipose depots. J Viral Hepat. 2014 May 1; 21(5): 325–32.

Negro F. Facts and fictions of HCV and comorbidities: Steatosis, diabetes mellitus, and cardiovascular diseases. J Hepatol. 2014 Nov; 61(1): S69–78.

Nelson DR, Cooper JN, Lalezari JP, Lawitz E, Pockros PJ, Gitlin N, et al. All-Oral 12-Week Treatment With Daclatasvir Plus Sofosbuvir in Patients With Hepatitis C Virus Genotype 3 Infection: ALLY-3 Phase III Study. Hepatol. 2015 Apr 1; 61(4): 1127–35.

Parolin MB, Réa R, Vargas RM, Almeida ACR de, Baldanzi GR, Lopes RW. Prevalência de infecção pelo vírus da hepatite C em pacientes com diabetes melito tipo 2. Arq. gastroenterol. 2006 Jun; 43(2): 77–80.

Pena DZ, Anadão MF, Flores EF, Okada MN, Filho AMP, Ferro RS, et al. Clinical, Epidemiological, and Geospatial Characteristics of Patients Infected with Hepatitis C Virus Treated with Second-Generation Direct-Action Antivirals in a Reference Center in a Mesoregion of São Paulo State, Brazil. MIC. 2020 Oct 13; 8(10): 1575.

Pessoa MG, Ramalho-Madruga JV, Alves K, Nunes EP, Cheinquer H, Brandão-Mello CE, et al. Efficacy and Safety of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir ± Ribavirin for HCV in Brazilian Adults with Advanced Fibrosis. Ann Hepatol. 2018 Oct 16; 17(6): 959–68.

Sebastiani G. Chronic hepatitis C and liver fibrosis. World J Gastroenterol. 2014; 20(32): 11033.

Sociedade Brasileira de Diabetes. Diabetes Mellitus e Hepatites Virais. 2020. 418-429. Available at: https://portaldeboaspraticas.iff.fiocruz.br/biblioteca/diretrizes-da-sociedade-brasileira-de-diabetes-20192020/:~:text=Apresentadas%20de%20forma%20pr%C3%A1tica%2C%20as%20Diretrizes%20est%C3%A3o%20organizadas,do%20DM%20na%20gesta%C3%A7%C3%A3o%20e%20em%20complica%C3%A7%C3%B5es%20cr%C3%B4nicas .

» https://portaldeboaspraticas.iff.fiocruz.br/biblioteca/diretrizes-da-sociedade-brasileira-de-diabetes-20192020/:~:text=Apresentadas%20de%20forma%20pr%C3%A1tica%2C%20as%20Diretrizes%20est%C3%A3o%20organizadas,do%20DM%20na%20gesta%C3%A7%C3%A3o%20e%20em%20complica%C3%A7%C3%B5es%20cr%C3%B4nicas

WHO – World Health Organization. Hepatitis C. 2016. Available at: https://www.who.int/news-room/fact-sheets/detail/hepatitis-c .

» https://www.who.int/news-room/fact-sheets/detail/hepatitis-c

WHO. World Health Organization Collaborating Centre for Drug Statistics Methodology. 2003. Available at: https://www.who.int/publications/i/item/8280820396 .

» https://www.who.int/publications/i/item/8280820396

WHO. World Health Organization Global hepatitis report, 2017. Available at: https://www.who.int/publications/i/item/9789241565455 .

» https://www.who.int/publications/i/item/9789241565455