Benefits of prolonged-release pirfenidone plus standard of care treatment in patients with advanced liver fibrosis: PROMETEO study.

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.

[Double-balloon enteroscopy: experience in the Hospital de Especialidades del Centro Médico Nacional Siglo XXI IMSS, Mexico City]. / Enteroscopia de doble balón: experiencia en el hospital de Especialidades del Centro Médico Nacional Siglo XXI, IMSS, Ciudad de México.

UNLABELLED: The methods used for the study of the small bowel are not ideal. Double-balloon enteroscopy is a new alternative with therapeutic potential. OBJECTIVE: Evaluate the utility, efficacy and safety of double-balloon enteroscopy in Mexico. MATERIAL AND METHODS: Adult patients seen in the Hospital de Especialidades Centro Médico Nacional Siglo XXI, Mexico City who were being studied for: chronic diarrhea, obscure gastrointestinal hemorrhage, weight-loss and chronic anemia were included in the study. Anterograde (oral) and retrograde (anal) approaches were used and study time, findings and complications were evaluated. RESULTS: Thirty-one enteroscopies were performed, 15 were anterograde, 8 retrograde and 8 were performed via both routes, in 23 patients studied between February and October, 2004; 10 of them were women and 13 men with ages ranging from 25 to 80 years. Fourteen patients were sedated and 9 patients were anesthetized. Study time varied form 55 to 90 minutes. With the anterograde route the ileum was reached in 56.6% of cases, 39.1% the jejunum and only in one patient (4.3%) the whole intestine was explored. With the retrograde route in 62.5% of cases the jejunum was explored and 37.5% the ileum. Four patients with obscure gastrointestinal bleeding and 1 patient with chronic anemia had vascular ecstasies, and in 40% of patients there was no identifiable cause. In 2 patients with intestinal stenosis biopsies revealed intestinal lymphoma in one and ischemic injury in another one. The adverse effects were mild and transitoru. CONCLUSIONS: Double-balloon enteroscopy is a safe diagnostic and therapeutic method that is useful in cases of obscure hemorrhage, chronic anemia; small bowel pathology was found in 64.7% of cases.