title: Patient-reported Outcomes in Asian Patients With Chronic Hepatitis C Treated With Ledipasvir and Sofosbuvir.
abstract: Prevalence of chronic hepatitis C (CH-C) infection in patients of Asian ancestry ranges between 1% and 20%. Interferon (IFN)- and ribavirin (RBV)-containing regimens for CH-C have a negative impact on patient-reported outcomes (PROs) during treatment. The aim of this study was to assess the impact of IFN-free RBV-free sofosbuvir (SOF)-based regimens on PROs in CH-C patients of Asian ancestry. In this observational retrospective study, the PRO data from 12 multicenter multinational phase 3 clinical trials (2012-2015, conducted in Europe, North America, Australia, and New Zealand) of SOF-based regimens with and without IFN, ledipasvir (LDV), and/or RBV were used. At baseline, during treatment, and post-treatment, patients completed 4 validated PRO questionnaires (SF-36, CLDQ-HCV, FACIT-F, and WPAI:SHP). The resulting PROs in Asian patients were compared across the treatment regimens. Of 4485 of the trials' participants, 106 patients were of Asian ancestry (55.7% male, 69.8% treatment-naïve, 17.0% cirrhotic). In comparison with other patients, the Asian CH-C cohort was younger, had lower BMI, and lower rates of pre-treatment psychiatric comorbidities (anxiety, depression, sleep disorders) (all P < .05). At baseline, Asian patients also had lower SF-36 physical functioning scores (on average, by -5.6% on a normalized 0-100% PRO scale, P = .001). During treatment, Asian CH-C patients experienced a decline in their PRO scores while receiving IFN and/or RBV-containing regimens (up to -19.6%, P < .001). In contrast, patients receiving LDV/SOF experienced no PRO decrement and improvement of some PRO scores during treatment (+9.0% in general health of SF-36, P = .03). After achieving SVR-12, some of the PRO scores in Asian patients improved regardless of the regimen (up to +9.3%, P < .001). In multivariate analysis of Asian patients, the use of LDV/SOF was independently associated with higher PRO scores during and soon after the end of treatment (betas +15.0% to +29.3%, all P < .05). Other predictors of PRO impairment included depression, type 2 diabetes mellitus, and cirrhosis. The use of IFN- and RBV-free LDV/SOF regimens leads to PRO improvement in Asian patients with CH-C during treatment. Achieving SVR-12 results in improvement of PRO scores.
authors.affiliation: From the Department of Medicine, Center for Liver Diseases (ZMY); Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA (ZMY); Center for Outcomes Research in Liver Disease, Washington DC (MS, LH); Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong (HLYC); Institute of Clinical Medicine, National Yang Ming University, Taipei (MHL); Hepatobiliary division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan (M-LY); University Medicine Cluster, National University Hospital, Singapore (YYD); and Division of Gastroenterology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gongno-gu, Seoul, South Korea (MSC).
authors.forename: Zobair M
authors.initials: ZM
authors.lastname: Younossi
authors.forename: Maria
authors.initials: M
authors.lastname: Stepanova
authors.forename: Henry L Y
authors.initials: HLY
authors.lastname: Chan
authors.forename: Mei H
authors.initials: MH
authors.lastname: Lee
authors.forename: Ming-Lung
authors.initials: ML
authors.lastname: Yu
authors.forename: Yock Y
authors.initials: YY
authors.lastname: Dan
authors.forename: Moon S
authors.initials: MS
authors.lastname: Choi
authors.forename: Linda
authors.initials: L
authors.lastname: Henry
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use; D001208:Asia / Q000453:epidemiology; D001562:Benzimidazoles / Q000627:therapeutic use*; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D005449:Fluorenes / Q000627:therapeutic use*; D016174:Hepacivirus / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000453:epidemiology / Q000523:psychology / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D063868:Patient Outcome Assessment; D011788:Quality of Life; D000069474:Sofosbuvir / Q000627:therapeutic use*; D011795:Surveys and Questionnaires
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D005449:Fluorenes; C586541:ledipasvir; D000069474:Sofosbuvir