Need to Face Liver Cirrhosis after HCV Cure with Antivirals

Autor: Pablo Barreiro, Ana Arias, Laura Benitez, Vicente Soriano, Carmen de Mendoza
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Male
Liver Cirrhosis
PRI-724
Cirrhosis
Face (sociological concept)
lcsh:Medicine
Hepacivirus
0302 clinical medicine
Liver Function Tests
Wnt inhibitor
030212 general & internal medicine
HTLV
human T-cell leukemia virus
beta Catenin
lcsh:R5-920
HAI
histology activity index
General Medicine
Hepatitis C
Middle Aged
Viral Load
Treatment Outcome
HCV
hepatitis C virus
HCV
Female
030211 gastroenterology & hepatology
lcsh:Medicine (General)
Research Paper
Adult
medicine.medical_specialty
Genotype
CBP
CREB binding protein
MEDLINE
Pyrimidinones
Antiviral Agents
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
Text mining
CP
Child-Pugh
ALT
alanine aminotransferase
PT
prothrombin time
AUC
area under the concentration curve
medicine
Humans
Cmax
maximum concentration
ALB
albumin
Intensive care medicine
Aged
business.industry
lcsh:R
Hepatitis C
Chronic
Bridged Bicyclo Compounds
Heterocyclic
medicine.disease
CREB
cAMP-response element-binding protein
Tmax
time of maximum observed serum
Commentary
business
Zdroj: EBioMedicine, Vol 24, Iss C, Pp 24-25 (2017)
EBioMedicine
Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid
Consejería de Sanidad de la Comunidad de Madrid
ISSN: 2352-3964
Popis: Background There is currently no anti-fibrotic drug therapy available to treat hepatitis C virus (HCV) cirrhosis. The aim of this study was to assess the safety, tolerability, and anti-fibrotic effect of PRI-724, a small-molecule modulator of Wnt signaling, in patients with HCV cirrhosis. Methods In this single-center, open-label, phase 1 trial, we sequentially enrolled patients with HCV cirrhosis who were classified as Child-Pugh (CP) class A or B. PRI-724 was administered as a continuous intravenous infusion of 10, 40, or 160 mg/m2/day for six cycles of 1 week on and 1 week off. The primary endpoints were frequency and severity of adverse events. The secondary endpoint was efficacy of PRI-724 in treating cirrhosis based on CP score and liver biopsy. This study is registered with ClinicalTrials.gov (no. NCT02195440). Findings Between Sept 3, 2014 and May 2, 2016, 14 patients were enrolled: CP class A:B, 6:8; median age, 62 (range: 43 to 74) years; male:female, 10:4. Twelve of the 14 patients completed six cycles of treatment; one was withdrawn from the study due to possible study drug-related liver injury (grade 3) in the 160 mg/m2/day dose cohort and one withdrew for personal reasons. Serious adverse events occurred in three patients [21% (3/14)], one of which was possibly related to PRI-724. The most common adverse events were nausea [29% (4/14)] and fatigue [21% (3/14)]. After PRI-724 administration, the CP scores worsened by 1 point in two patients in the 10 mg/m2/day cohort, improved in three patients at 1, 1, and 2 points in the 40 mg/m2/day cohort, and improved in one patient by 3 points in the 160 mg/m2/day cohort. The histology activity index scores of the liver tissue improved in two patients and exacerbated in two patients in the 10 mg/m2/day cohort, and improved in one patient in the 40 mg/m2/day cohort. Interpretation This study showed that administration of 10 or 40 mg/m2/day intravenous PRI-724 over 12 weeks was well-tolerated by patients with HCV cirrhosis; however, liver injury as a possible related serious adverse event was observed in the 160 mg/m2/day cohort. Funding Source AMED.
Highlights • Safety, tolerability, pharmacokinetics, and anti-fibrotic effect of PRI-724 were assessed in patients with HCV cirrhosis. • PRI-724 was well tolerated, suggesting that the treatment is relatively safe against HCV liver cirrhosis. • Significant fibrosis reduction in hepatic lobules 12 weeks after PRI-724 treatment (40 mg/m2/day) in 3 CP class B patients. Liver cirrhosis is one of the leading causes of morbidity and mortality in developed countries and is the 14th most common cause of death in adults worldwide. However, there is currently no anti-fibrotic drug therapy available to treat hepatitis C virus (HCV) cirrhosis. This study showed that intravenous PRI-724 at 10 or 40 mg/m2/day over 12 weeks was well-tolerated by patients with HCV cirrhosis and resulted in an improvement of liver histology and CP class in several patients.
Databáze: OpenAIRE
Externí odkaz: