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. TGFß1 (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.
Subject(s)
Liver Cirrhosis , Liver Diseases , Liver , Pyridones , Quality of Life , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/adverse effects , Delayed-Action Preparations/administration & dosage , Delayed-Action Preparations/adverse effects , Disease Progression , Elasticity Imaging Techniques/methods , Female , Humans , Liver/diagnostic imaging , Liver/pathology , Liver Cirrhosis/diagnosis , Liver Cirrhosis/drug therapy , Liver Cirrhosis/etiology , Liver Cirrhosis/psychology , Liver Diseases/classification , Liver Diseases/complications , Liver Diseases/diagnosis , Male , Middle Aged , Proof of Concept Study , Pyridones/administration & dosage , Pyridones/adverse effects , Standard of Care , Treatment OutcomeABSTRACT
In this work, molecular modeling simulations are used to study the flotation process of copper, cadmium and zinc ions present in wastewater, acid mine drainage and others, with xanthate collector. Simulations were conducted by DFT technique, with M06 functional at 6-31G(d,p)/LanL2DZ level. Characterizations of the molecular and electronic structures of the complexes formed applying NPA, AIM and CLPO analysis of the coordination bonds show the kind of main interactions between metals and the ligand. Results confirm the experimental evidence and show the ability of this technique to study this process. The interaction energy of the studied complexes is -56,39 kcal/mol for Cu, -25,86 kcal/mol for Cd and -7,29 kcal/mol for Zn complex. It was found that xanthate binds to copper over zinc and cadmium elements. Experimental results show that for copper, cadmium and zinc, the flotation effectiveness are 94,68%; 67,18% and 36,92% respectively.
Subject(s)
Copper , Wastewater , Cadmium , Ions , ZincABSTRACT
Se anlistan 31 especies de boletáceos y gonfidiáceos del Estados de México. Se discute su comestibilidad, distribución ecológica, fenología y asociaciones ectomicorrizógenas. La comestibilidad de Chroogomphus jamaicensis (Murr.)O.KMiller, es registrada por primera vez
