Benefits of prolonged-release pirfenidone plus standard of care treatment in patients with advanced liver fibrosis: PROM
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ORIGINAL ARTICLE
Benefits of prolonged‑release pirfenidone plus standard of care treatment in patients with advanced liver fibrosis: PROMETEO study Jorge Luis Poo1,2 · Aldo Torre1,3 · Juan Ramón Aguilar‑Ramírez1 · Mauricio Cruz1 · Luis Mejía‑Cuán1 · Eira Cerda1 · Alfredo Velázquez1 · Angélica Patiño1 · Carlos Ramírez‑Castillo1 · Laura Cisneros1,2 · Francisco Bosques‑Padilla1,2 · Larissa Hernández7 · Frida Gasca1 · Francisco Flores‑Murrieta4 · Samuel Treviño5 · Graciela Tapia6 · Juan Armendariz‑Borunda2,7 · Linda E. Muñoz‑Espinosa1,8 Received: 10 January 2020 / Accepted: 22 June 2020 © The Author(s) 2020
Abstract 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 12 months of treatment 71 subjects without complete fibrosis evaluation methods 122 with two fibrosis evaluation methods
Fig. 1 Inclusion and exclusion criteria
Hepatology International
fibrosis despite sustained viral response (SVR) at 12 months. All patients with AIH were receiving the lowest possible dose of prednisone and/or azathioprine in order to induce low necroinflammatory activity or biochemical remission. Considering the advance fibrosis stage (F3–F4) of our patient’s cohort, none of them presented ALT or AST values higher than twofold ULN. Patients were 52–76 years of age (mean 64 ± 12 years old). All subjects had a complete medical history, lab results, hepatic ultrasound, and upper-gastrointestinal endoscopy at baseline and 12 months (M12) after pharmacological intervention. Patients were negative for hepatocellular carcinoma (HCC) as determined by hepatic ultrasound and had the following lab values: hematocrit > 30%, hemoglobin > 10 g/dL, platelet count > 30 × 109/L, white blood cell count > 3 × 109/L, and
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