TY - JOUR
T1 - Benefits of prolonged-release pirfenidone plus standard of care treatment in patients with advanced liver fibrosis
T2 - PROMETEO study
AU - Poo, Jorge Luis
AU - Torre, Aldo
AU - Aguilar-Ramírez, Juan Ramón
AU - Cruz, Mauricio
AU - Mejía-Cuán, Luis
AU - Cerda, Eira
AU - Velázquez, Alfredo
AU - Patiño, Angélica
AU - Ramírez-Castillo, Carlos
AU - Cisneros, Laura
AU - Bosques-Padilla, Francisco
AU - Hernández, Larissa
AU - Gasca, Frida
AU - Flores-Murrieta, Francisco
AU - Treviño, Samuel
AU - Tapia, Graciela
AU - Armendariz-Borunda, Juan
AU - Muñoz-Espinosa, Linda E.
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/9/1
Y1 - 2020/9/1
N2 - Background and aims: Pirfenidone (PFD), an oral antifibrotic drug, has been authorized by the EMA and FDA for treatment of idiopathic pulmonary fibrosis. Few studies have addressed its use in advanced liver fibrosis (ALF). We evaluated a prolonged-release formulation (PR-PFD) plus standard of care on disease progression in ALF. Methods: 281 ALF patients from 12 centers receiving PR-PFD (600 mg bid) were screened; 122 completed 1 year of treatment. Additionally, 74 patients received only standard of care regimen. Average age was 64 ± 12 years, 58% female. 43.5% had fatty liver disease (NAFLD), 22.5% viral hepatitis C (VHC), 17% autoimmune hepatitis (AIH), and 17% alcoholic liver disease (ALD). Baseline fibrosis was F4 in 74% and F3 in 26%. Antifibrotic effects were assessed by transient elastography (Fibroscan®) and Fibro Test® (FT); Cytokines and PFD plasma levels were tracked and quality of life evaluated. Results: We found a significant reduction in fibrosis in 35% of PR-PFD patients and only in 4.1% in non PR-PFD patients. Child–Pugh score improved in 29.7%. Biochemical values remained stable; 40.6% and 43.3% decreased ALT or AST, respectively. TGFβ1 (pg/mL) levels were lower in PFD-treated patients. PFD serum concentration (µg/mL) was higher (8.2 ± 1.7) in fibrosis regression profile (FRP) patients compared to fibrosis progression profile (FPP) patients (4.7 ± 0.3 µg/mL, p < 0.01). 12% reported transient burning or nausea and 7% photosensitivity. Quality of life (Euro-Qol scale) improved from 62 ± 5 to 84 ± 3 (p < 0.001) and from 32 ± 3 to 42 ± 2 (p < 0.008) (FACIT scale). Conclusions: PR-PFD is efficacious and safe in ALF and associated with promising antifibrotic effects. Trial registration: Clinical trial number: NCT04099407.
AB - Background and aims: Pirfenidone (PFD), an oral antifibrotic drug, has been authorized by the EMA and FDA for treatment of idiopathic pulmonary fibrosis. Few studies have addressed its use in advanced liver fibrosis (ALF). We evaluated a prolonged-release formulation (PR-PFD) plus standard of care on disease progression in ALF. Methods: 281 ALF patients from 12 centers receiving PR-PFD (600 mg bid) were screened; 122 completed 1 year of treatment. Additionally, 74 patients received only standard of care regimen. Average age was 64 ± 12 years, 58% female. 43.5% had fatty liver disease (NAFLD), 22.5% viral hepatitis C (VHC), 17% autoimmune hepatitis (AIH), and 17% alcoholic liver disease (ALD). Baseline fibrosis was F4 in 74% and F3 in 26%. Antifibrotic effects were assessed by transient elastography (Fibroscan®) and Fibro Test® (FT); Cytokines and PFD plasma levels were tracked and quality of life evaluated. Results: We found a significant reduction in fibrosis in 35% of PR-PFD patients and only in 4.1% in non PR-PFD patients. Child–Pugh score improved in 29.7%. Biochemical values remained stable; 40.6% and 43.3% decreased ALT or AST, respectively. TGFβ1 (pg/mL) levels were lower in PFD-treated patients. PFD serum concentration (µg/mL) was higher (8.2 ± 1.7) in fibrosis regression profile (FRP) patients compared to fibrosis progression profile (FPP) patients (4.7 ± 0.3 µg/mL, p < 0.01). 12% reported transient burning or nausea and 7% photosensitivity. Quality of life (Euro-Qol scale) improved from 62 ± 5 to 84 ± 3 (p < 0.001) and from 32 ± 3 to 42 ± 2 (p < 0.008) (FACIT scale). Conclusions: PR-PFD is efficacious and safe in ALF and associated with promising antifibrotic effects. Trial registration: Clinical trial number: NCT04099407.
KW - Antifibrotic
KW - Cirrhosis
KW - Elastography
KW - Fibrosis
KW - Fibrosis-progression
KW - Fibrosis-regression
KW - Fibrotest
KW - Liver
KW - Pirfenidone
KW - Prolonged-release pirfenidone
UR - http://www.scopus.com/inward/record.url?scp=85089585427&partnerID=8YFLogxK
U2 - 10.1007/s12072-020-10069-3
DO - 10.1007/s12072-020-10069-3
M3 - Artículo
C2 - 32813194
AN - SCOPUS:85089585427
SN - 1936-0533
VL - 14
SP - 817
EP - 827
JO - Hepatology International
JF - Hepatology International
IS - 5
ER -