Long-term follow-up of clinical trial patients treated for chronic HCV infection with daclatasvir-based regimens

Autor: James E. Levin, Wayne Ghesquiere, Maurizia Rossana Brunetto, Zhaohui Liu, Simone I. Strasser, Stephanie Noviello, Joji Toyota, Misti Linaberry, Guido Gerken, Kazuaki Chayama, Marcelo Silva, Rong Yang, Jeong Heo, K. Rajender Reddy, Cheng Yuan Peng, Hiromitsu Kumada, Fiona McPhee, Paul J. Thuluvath, Eric Lawitz, Stanislas Pol, Adrián Gadano
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Liver Cirrhosis
Male
Cirrhosis
Pyrrolidines
Sustained Virologic Response
Viral Hepatitis
Medizin
Hepacivirus
medicine.disease_cause
Liver disease
0302 clinical medicine
Imidazoles
Valine
hepatocellular carcinoma
Middle Aged
Viral Load
Hepatocellular carcinoma
Disease Progression
RNA
Viral
030211 gastroenterology & hepatology
Drug Therapy
Combination
Female
medicine.drug
Adult
medicine.medical_specialty
Daclatasvir
Long term follow up
Hepatitis C virus
Antiviral Agents
03 medical and health sciences
Young Adult
Internal medicine
Drug Resistance
Viral
medicine
Humans
chronic hepatitis C virus
daclatasvir
NS5A
Aged
Hepatology
business.industry
Hepatitis C
Chronic
medicine.disease
Surgery
Clinical trial
030104 developmental biology
long‐term follow‐up
Carbamates
business
Follow-Up Studies
Zdroj: Liver International
Popis: Background & aims Daclatasvir has achieved high sustained virologic response (SVR) rates in diverse hepatitis C virus (HCV) populations. This study evaluated the long-term efficacy and safety of daclatasvir-based regimens administered during clinical studies. Methods Patients enrolled within 6 months of parent study completion or protocol availability at the study sites. The primary objective was durability of SVR at follow-up Week 12 (SVR12). Secondary objectives included analyzing HCV sequences in non-responders or responders who relapsed, and characterization of liver disease progression. Results Between 24-February-2012 and 17-July-2015, this study enrolled and began following 1503 recipients of daclatasvir-based regimens (follow-up cut-off, 13-October-2015); 60% were male, 18% aged ≥65 years, 87% had genotype-1a (42%) or -1b (45%) infection, and 18% had cirrhosis. Median follow-up from parent study follow-up Week 12 was 111 (range, 11-246) weeks. 1329/1489 evaluable patients were SVR12 responders; 1316/1329 maintained SVR until their latest visit. Twelve responders relapsed by (n=9) or after (n=3) parent study follow-up Week 24; one was reinfected. Relapse occurred in 3/842 (0.4%) and 9/487 (2%) responders treated with interferon-free or interferon-containing regimens, respectively. Hepatic disease progression and new hepatocellular carcinoma were diagnosed in 15 and 23 patients, respectively. Among non-responders, emergent non-structural protein-5A (NS5A) and -3 (NS3) substitutions were replaced by wild-type sequences in 27/157 (17%) and 35/47 (74%) patients, respectively. Conclusions SVR12 was durable in 99% of recipients of daclatasvir-based regimens. Hepatic disease progression and new hepatocellular carcinoma were infrequent. Emergent NS5A substitutions persisted longer than NS3 substitutions among non-responders. This article is protected by copyright. All rights reserved.
Databáze: OpenAIRE
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