Thalia Medeiros1, Geórgia N Saraiva2, Laiz A Moraes3, Aline C Gomes4, Gilmar S Lacerda5, Paulo Ec Leite6, Eliane Bc Esberard7, Thaís G Andrade8, Analúcia R Xavier9, Thereza Quírico-Santos10, Natalia F Rosário11, Andrea A Silva12. 1. Laboratório Multiusuário de Apoio à Pesquisa em Nefrologia e Ciências Médicas Departamento de Medicina Clínica Faculdade de Medicina, Universidade Federal Fluminense, Niterói, Brazil. Electronic address: thaliamedeiros@id.uff.br. 2. Laboratório Multiusuário de Apoio à Pesquisa em Nefrologia e Ciências Médicas Departamento de Medicina Clínica Faculdade de Medicina, Universidade Federal Fluminense, Niterói, Brazil. Electronic address: georgiasaraiva@id.uff.br. 3. Laboratório Multiusuário de Apoio à Pesquisa em Nefrologia e Ciências Médicas Departamento de Medicina Clínica Faculdade de Medicina, Universidade Federal Fluminense, Niterói, Brazil. 4. Instituto de Biologia, Universidade Federal Fluminense, Niterói, Brazil. 5. Laboratório Multiusuário de Apoio à Pesquisa em Nefrologia e Ciências Médicas Departamento de Medicina Clínica Faculdade de Medicina, Universidade Federal Fluminense, Niterói, Brazil. Electronic address: gilmarlacerda@id.uff.br. 6. Laboratório de Bioengenharia e Toxicologia in Vitro Diretoria de Metrologia Aplicada às Ciências da Vida - Dimav Instituto Nacional de Metrologia Qualidade e Tecnologia - INMETRO, Duque de Caxias, Rio de Janeiro, Brazil. Electronic address: peleite@inmetro.gov.br. 7. Centro de Referência de Tratamento em Hepatites/HUAP Serviço de Gastroenterologia Departamento de Medicina Clínica Faculdade de Medicina, Universidade Federal Fluminense, Niterói, Brazil. 8. Centro de Referência de Tratamento em Hepatites/HUAP Serviço de Gastroenterologia Departamento de Medicina Clínica Faculdade de Medicina, Universidade Federal Fluminense, Niterói, Brazil. Electronic address: thaisguarana@id.uff.br. 9. Laboratório Multiusuário de Apoio à Pesquisa em Nefrologia e Ciências Médicas Departamento de Medicina Clínica Faculdade de Medicina, Universidade Federal Fluminense, Niterói, Brazil; Departamento de Patologia Faculdade de Medicina, Universidade Federal Fluminense, Niterói, Brazil. Electronic address: analuciaxavier@id.uff.br. 10. Instituto de Biologia, Universidade Federal Fluminense, Niterói, Brazil. Electronic address: tquirico@id.uff.br. 11. Laboratório Multiusuário de Apoio à Pesquisa em Nefrologia e Ciências Médicas Departamento de Medicina Clínica Faculdade de Medicina, Universidade Federal Fluminense, Niterói, Brazil. Electronic address: nataliarosario@id.uff.br. 12. Laboratório Multiusuário de Apoio à Pesquisa em Nefrologia e Ciências Médicas Departamento de Medicina Clínica Faculdade de Medicina, Universidade Federal Fluminense, Niterói, Brazil; Departamento de Patologia Faculdade de Medicina, Universidade Federal Fluminense, Niterói, Brazil. Electronic address: aasilva@id.uff.br.
Abstract
BACKGROUND AND AIMS: Disturbances in matrix metalloproteinases (MMPs) and corresponding tissue inhibitors (TIMPs) contribute to hepatitis C virus (HCV)-induced fibrosis. This study aimed to determine MMP-9/TIMP-1 levels in addition to MMP-2 and -9 activities; correlating with the improvement of liver fibrosis in patients under direct-acting antiviral (DAA) therapy. METHODS: Clinical and laboratory follow-up were performed before treatment and after 12 weeks post-treatment, referred as sustained viral response (SVR). We evaluated liver function including non-invasive fibrosis measurements; MMP activity by zymography; and MMP-9/TIMP-1 complex, inflammatory and pro-fibrogenic mediators by immunoenzymatic assays. RESULTS: Cohort included 33 patients (59.5 ± 9.3 years, 60.6% females) whose reached SVR and 11 control-paired subjects (42.5 ± 15 years, 54.5% females). Before treatment, HCV patients presented higher MMP-9/TIMP-1 levels (P < 0.05) when compared to controls, and the highest values were observed in patients with fibrosis (P < 0.05). In addition, MMP-9/TIMP-1 levels were significantly reduced after DAA therapy (P < 0.0001) and were associated with profibrogenic biomarkers. No differences were observed for MMP-2 and -9 activities; however, these biomarkers were significantly associated with inflammatory mediators. CONCLUSION: Our data suggest that MMP-9/TIMP-1 complex can be a promising biomarker of active fibrogenesis, being able to identify the interruption of fibrosis progression after HCV eradication.
BACKGROUND AND AIMS: Disturbances in matrix metalloproteinases (MMPs) and corresponding tissue inhibitors (TIMPs) contribute to hepatitis C virus (HCV)-induced fibrosis. This study aimed to determine MMP-9/TIMP-1 levels in addition to MMP-2 and -9 activities; correlating with the improvement of liver fibrosis in patients under direct-acting antiviral (DAA) therapy. METHODS: Clinical and laboratory follow-up were performed before treatment and after 12 weeks post-treatment, referred as sustained viral response (SVR). We evaluated liver function including non-invasive fibrosis measurements; MMP activity by zymography; and MMP-9/TIMP-1 complex, inflammatory and pro-fibrogenic mediators by immunoenzymatic assays. RESULTS: Cohort included 33 patients (59.5 ± 9.3 years, 60.6% females) whose reached SVR and 11 control-paired subjects (42.5 ± 15 years, 54.5% females). Before treatment, HCVpatients presented higher MMP-9/TIMP-1 levels (P < 0.05) when compared to controls, and the highest values were observed in patients with fibrosis (P < 0.05). In addition, MMP-9/TIMP-1 levels were significantly reduced after DAA therapy (P < 0.0001) and were associated with profibrogenic biomarkers. No differences were observed for MMP-2 and -9 activities; however, these biomarkers were significantly associated with inflammatory mediators. CONCLUSION: Our data suggest that MMP-9/TIMP-1 complex can be a promising biomarker of active fibrogenesis, being able to identify the interruption of fibrosis progression after HCV eradication.
Authors: Laura Pérez-Is; Julio Collazos; Belén de la Fuente; Luis Morano; Maria Rivas-Carmenado; Manuel Rodriguez; Adolfo Romero-Favela; Galilea de Jesús Fonseca-González; Santiago Melón; Eulalia Valle-Garay; Víctor Asensi Journal: Sci Rep Date: 2022-03-09 Impact factor: 4.379
Authors: Hairong Yao; Xuan Yang; Man Yan; Xueqin Fang; Yange Wang; Hong Qi; Li Sun Journal: Comput Math Methods Med Date: 2022-09-30 Impact factor: 2.809