Immunological Predictors of Nonresponse to Directly Acting Antiviral Therapy in Patients With Chronic Hepatitis C and Decompensated Cirrhosis. (3rd April 2017)

• Record Type: Journal Article
• Authors: Childs, Kate; Merritt, Elliot; Considine, Aisling; Sanchez-Fueyo, Alberto; Agarwal, Kosh; Martinez-Llordella, Marc; Carey, Ivana
• Is Part Of: Open forum infectious diseases. Volume 4:Number 2(2017)
• Publication Date: 2017-04-03
• Subjects: cirrhosis -- directly acting antiviral -- HCV -- hepatitis C.; Communicable diseases -- Periodicals; Medical microbiology -- Periodicals; Infection -- Periodicals; 616.9
• DOI: 10.1093/ofid/ofx067
• Languages: English
• ISSNs: 2328-8957

Abstract

Abstract: Background: Sustained virological response rates (SVRs) to directly acting antiviral (DAA) therapy for hepatitis C virus (HCV) are lower in decompensated cirrhosis. Markers of innate immunity predict nonresponse to interferon-based HCV treatment; however, whether they are associated with the response to DAAs in patients with decompensation is not known. Methods: Information on demographics, adherence, viral kinetics, and resistance were gathered prospectively from a cohort with decompensated cirrhosis treated with 12 weeks of DAAs. C-X-C motif chemokine-10 (CXCL-10) level and T-cell and natural killer (NK) cell phenotype were analyzed pretreatment and at 4 and 12 weeks of treatment. Results: Of 32 patients, 24 of 32 (75%) achieved SVR (responders). Eight of 32 (25%) experienced relapse after the end of treatment (nonresponders). There were no differences in demographics or adherence between groups. Nonresponders had higher CXCL-10; 320 pg/mL (179461) vs 109 pg/mL (88170) in responders ( P < .001) and differential CXCL-10 dynamics. Nonresponders had lower NK cell frequency, higher expression of activation receptor NKp30, and lower frequency of the NK subset CD56 − CD16 + . Conclusions: Nonresponders to DAAs displayed a different NK phenotype and CXCL-10 profile to responders. Nonresponders did not have poorer adherence or baseline virological resistance, and this shows that immunological parameters are associated with treatment response to interferon-free treatment for HCV in individuals with decompensated cirrhosis.