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Noninvasive Evaluation of Prolonged‐Release Pirfenidone in Compensated Liver Cirrhosis. ODISEA Study, a Randomised Trial

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Muñoz‐Espinosa, Linda E., Torre, Aldo, Cisneros, Laura, Montalvo, Iaarah, Malé, René, Mejía, Scherezada, Aguilar, Juan Ramón, Lizardi, Javier +10 more·2025·Liver International
DOI 10.1111/liv.70131PMC PMC12097196
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Abstract

Background: Advanced liver fibrosis (ALF) predicts an adverse prognosis in chronic liver disease. In addition to etiological treatment, a new approach to stop or reverse residual fibrosis is desirable. Objective: To assess the efficacy and safety of prolonged‐release pirfenidone (PR‐PFD) versus placebo in compensated cirrhosis. Methods: 180 patients with ALF (F4) were randomly assigned to: placebo, 1200 mg/d, and 1800 mg/d PR‐PFD, plus standardised care, for 24mo. Frequency of lab tests: (3mo), liver stiffness measurement (LSM), FibroTest, ultrasound (US) (6mo), and endoscopy (annually). Results: Fibrosis evolution estimated from LSM was significantly lower only in the 1200 compared to placebo and 1800 groups (24.2 ± 2.4 vs. 15.4 ± 2.4; 27.6 ± 2.4 vs. 24.6 ± 2.4; 24.4 ± 2.3 vs. 23.3 ± 2.3 kPa, respectively, p < 0.001), in intergroup analysis, meeting the primary endpoint. Fibrotest was significantly lower only in the 1200 mg/d group, compared to baseline values (0.86 ± 0.02 vs. 0.83 ± 0.02 units, p < 0.001). Liver function test (LFT's) also improved as well as Model for End‐Stage Liver Disease (MELD) score and quality of life (QoL). Decompensations occurred in 19 patients: 12 ascites (more frequent in placebo, p = 0.003), 5 variceal bleeding, 4 encephalopathies, 4 hepatocarcinomas. Adverse events were mainly mild gastrointestinal (n = 35, 48 and 46, p = 0.010) and cutaneous (n = 12, 15, and 22, p = 0.0001) in placebo, 1200 and 1800 mg/day, respectively. Conclusion: PR‐PFD at a dose of 1200 mg significantly decreased non‐invasive liver fibrosis markers at 24 months and induced improvement in LFT's, MELD, and QoL in compensated cirrhosis, without safety concerns. Trial Registration: ClinicalTrials.gov identifier: NCT01046474

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  • Clinical studies in patients with compensated cirrhosis demonstrated acceptable safety and modest anti-fibrotic effects of pirfenidone.

    “While clinical studies in patients with compensated cirrhosis demonstrated acceptable safety and modest anti-fibrotic effects (140)”

    From Targeting macrophages in liver fibrosis (2026) · cites this paper as [140]

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Cited by

Sorted by citations

  • Targeting macrophages in liver fibrosis

    González del Barrio, L., Ipsen, D. H., Pfister, D. R., Hancz, D., & Scott, C. L. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1835489 · Cited by 3 · see citing works

    “While clinical studies in patients with compensated cirrhosis demonstrated acceptable safety and modest anti-fi brotic effects (140), these studies also highlighted the limitations of systemic pathway inhibition as systemic TGF-b blockade was associated with immune dysregulation, impaired tissue…”

Authors
Muñoz‐Espinosa, L. E., Torre, A., Cisneros, L., Montalvo, I., Malé, R., Mejía, S., Aguilar, J. R., Lizardi, J., Zuñiga‐Noriega, J., Eugenia Icaza, M., Gasca‐Díaz, F., Hernández‐Hernández, L., Cordero‐Pérez, P., Chi, L., Torres, L., Rodríguez‐Alvarez, F., Tapia, G., & Poo, J. L.
Affiliations
  • Universidad Autónoma de Nuevo León, “Dr. José E. González” University Hospital Monterrey Mexico
  • Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (MX)
  • Hospital Christus Muguerza Alta Especialidad (MX)
  • Liver Clinic Mérida Mexico
  • Digestive and Hepatic Disease Institute Guadalajara Mexico
  • Hospital Juárez de México (MX)
  • Mexican Group for the Study of Liver Diseases (PROMHEPA) Mexico City Mexico
  • Universidad Autónoma de Nuevo León (MX)
  • Instituto Nacional de Ciencias Médicas y Nutrición Ciudad de México Mexico
  • Universidad Nacional Autónoma de México (MX)
Corresponding author
Poo, Jorge Luis
ORCID
Venue
Liver International
Publisher
Wiley
Published
2025-05-22
Volume
45
Issue
6
Pages
e70131-e70131
ISSN
  • 0106-9543 (ISSN-L)
  • 1478-3223
  • 1478-3231
DOI
10.1111/liv.70131
PMC
PMC12097196
OpenAlex
W4410590470
Cited by
10
References
7
Citations by year
2026: 6 · 2025: 4
FWCI
6.93
Type
journal article
Language
en
Open access
Licence
Locations
  • Liver International (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
American Association for the Study of Liver Diseases
Topics
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
Keywords
pirfenidone, advanced liver fibrosis, compensated cirrhosis, antifibrotic therapy, liver stiffness measurement, FibroTest, MELD score, quality of life, adverse events, dose comparison, chronic liver disease, fibrosis regression, decompensated cirrhosis, hepatocellular carcinoma, variceal bleeding, ascites, encephalopathy
MeSH terms
Antifibrotic Agents, Adult, Delayed-Action Preparations, Double-Blind Method, Female, Humans, Liver, Liver Cirrhosis, Male, Middle Aged, Pyridones, Quality of Life, Treatment Outcome, Elasticity Imaging Techniques

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