Retrospective Cohort Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Nov 8, 2016; 8(31): 1318-1326
Published online Nov 8, 2016. doi: 10.4254/wjh.v8.i31.1318
Safe and effective sofosbuvir-based therapy in patients with mental health disease on hepatitis C virus treatment
Lydia Shuk Yee Tang, Jack Masur, Zayani Sims, Amy Nelson, Anu Osinusi, Anita Kohli, Sarah Kattakuzhy, Michael Polis, Shyam Kottilil
Lydia Shuk Yee Tang, Jack Masur, Amy Nelson, Sarah Kattakuzhy, Shyam Kottilil, Institute of Human Virology, Division of Infectious Diseases, University of Maryland School of Medicine, Baltimore, MD 21201, United States
Zayani Sims, Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892, United States
Anu Osinusi, Gilead Sciences Inc, Foster City, CA 94404, United States
Anita Kohli, Creighton University School of Medicine, St Joseph’s Hospital, Phoenix, AZ 85013, United States
Michael Polis, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, United States
Author contributions: Tang LSY, Masur J, Sims Z, Polis M and Kottilil S designed the research; Tang LSY, Masur J, Sims Z, Nelson A, Osinusi A, Kohli A and Kattakuzhy S performed the research; Tang LSY, Masur J, Sims Z and Kattakuzhy S analyzed the data; Tang LSY, Masur J, Sims Z and Kottilil S wrote the paper; all authors contributed critical revisions related to important intellectual content of the manuscript and had final approval of the version of the article to be published.
Institutional review board statement: Each study was approved by the institutional review board of NIAID and was conducted in compliance with the Good Clinical Practice guidelines, the Declaration of Helsinki and regulatory requirements. An independent safety monitor participated in the interim safety and efficacy analysis for SPARE. The Regulatory Compliance and Human Participants Protection Branch of NIAID served as the study sponsor and medical monitor.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: Dr. Lydia Shuk Yee Tang receives funding from Gilead Sciences’ Frontlines of Communities in the United States (FOCUS) program. Dr. Anu Osinusi is an employee of Gilead Sciences Inc. None of the other authors have any conflict of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Shyam Kottilil, MD, PhD, Professor of Medicine, Institute of Human Virology, Division of Infectious Diseases, University of Maryland School of Medicine, 725 West Lombard Street, Baltimore, MD 21201, United States.
Telephone: +1-410-7068614 Fax: +1-410-7061952
Received: May 29, 2016
Peer-review started: May 29, 2016
First decision: July 29, 2016
Revised: August 19, 2016
Accepted: September 8, 2016
Article in press: September 9, 2016
Published online: November 8, 2016

To study impact of baseline mental health disease on hepatitis C virus (HCV) treatment; and Beck’s Depression Inventory (BDI) changes with sofosbuvir- and interferon-based therapy.


This is a retrospective cohort study of participants from 5 studies enrolled from single center trials conducted at the Clinical Research Center of the National Institutes of Health, Bethesda, MD, United States. All participants were adults with chronic HCV genotype 1 infection and naïve to HCV therapy. Two of the studies included HCV mono-infected participants only (SPARE, SYNERGY-A), and 3 included human immunodeficiency virus (HIV)/HCV co-infected participants only (ERADICATE, PFINPK, and ALBIN). Patients were treated for HCV with 3 different regimens: Sofosbuvir and ribavirin in the SPARE trial, ledipasvir and sofosbuvir in SYNERGY-A and ERADICATE trials, and pegylated interferon (IFN) and ribavirin for 48 wk in the PIFNPK and ALBIN trials. Participants with baseline mental health disease (MHD) were identified (defined as either a DSM IV diagnosis of major depression, bipolar disorder, schizophrenia, generalized anxiety, and post-traumatic stress disorder or requiring anti-depressants, antipsychotics, mood stabilizers or psychotropics prescribed by a psychiatrist). For our first aim, we compared sustained virologic response (SVR) and adherence (pill counts, study visits, and in 25 patients, blood levels of the sofosbuvir metabolite, GS-331007) within each study. For our second aim, only patients with HIV coinfection were evaluated. BDI scores were obtained pre-treatment, during treatment, and post-treatment among participants treated with sofosbuvir-based therapy, and compared to scores from participants treated with interferon-based therapy. Statistical differences for both aims were analyzed by Fisher’s Exact, and t-test with significance defined as a P value less than 0.05.


Baseline characteristics did not differ significantly between all participants with and without MHD groups treated with sofosbuvir-based therapy. Among patients treated with sofosbuvir-based therapy, the percentage of patients with MHD who achieved SVR was the same as those without (SPARE: 60.9% of those MHD compared to 67.6% in those without, P = 0.78; SYNERGY-A: 100% of both groups; ERADICATE: 100% compared to 97.1%). There was no statistically significant difference in pill counts, adherence to study visits between groups, nor mean serum concentrations of GS-331007 for each group at week 2 of treatment (P = 0.72). Among patients with HIV co-infection, pre-treatment BDI scores were similar among patients treated with sofosbuvir, and those treated with interferon (sofosbuvir-based 5.24, IFN-based 6.96; P = 0.14); however, a dichotomous effect on was observed during treatment. Among participants treated with directly acting antiviral (DAA)-based therapy, mean BDI scores decreased from 5.24 (pre-treatment) to 3.28 during treatment (1.96 decrease, P = 0.0034) and 2.82 post-treatment. The decrease in mean score from pre- to post-treatment was statistically significant (-2.42, P = 0.0012). Among participants treated with IFN-based therapy, mean BDI score increased from 6.96 at pre-treatment to 9.19 during treatment (an increase of 2.46 points, P = 0.1), and then decreased back to baseline post-treatment (mean BDI score 6.3, P = 0.54). Overall change in mean BDI scores from pre-treatment to during treatment among participants treated with DAA-based and IFN-therapy was statistically significant (-1.96 and +2.23, respectively; P = 0.0032). This change remained statistically significant when analysis was restricted to participants who achieved SVR (-2.0 and +4.36, respectively; P = 0.0004).


Sofosbuvir-based therapy is safe and well tolerated in patients with MHD. A decline in BDI associated with sofosbuvir-based HCV treatment suggests additional MHD benefits, although the duration of these effects is unknown.

Keywords: Sofosbuvir, Direct acting antivirals, Directly acting antiviral, Hepatitis C, Mental health disease, Depression, Interferon, Beck’s Depression Inventory

Core tip: The prevalence of mental health disease (MHD) among patients with chronic hepatitis C virus (HCV) can be high. However, patients with MHD may be marginalized with respect to HCV therapy and MHD is one of the most frequently cited reason for exclusion from HCV therapy. HCV therapy has evolved from interferon-based to directly acting antiviral (DAA)-based therapy with excellent tolerability and efficacy. Our study found that baseline MHD did not impact efficacy nor treatment adherence to sofosbuvir-based therapy. Furthermore, we found that Becks Depression Inventory scores improved with sofosbuvir-based therapy, suggesting that HCV treatment with the newer DAA therapies may have additional mental health benefits.