Observational Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 7, 2023; 29(25): 4085-4098
Published online Jul 7, 2023. doi: 10.3748/wjg.v29.i25.4085
Real-world effectiveness and safety of direct-acting antivirals in hepatitis C virus patients with mental disorders
Dorota Dybowska, Dorota Zarębska-Michaluk, Piotr Rzymski, Hanna Berak, Beata Lorenc, Marek Sitko, Michał Dybowski, Włodzimierz Mazur, Magdalena Tudrujek-Zdunek, Justyna Janocha-Litwin, Ewa Janczewska, Jakub Klapaczyński, Anna Parfieniuk-Kowerda, Anna Piekarska, Barbara Sobala-Szczygieł, Krystyna Dobrowolska, Malgorzata Pawłowska, Robert Flisiak
Dorota Dybowska, Malgorzata Pawłowska, Department of Infectious Diseases and Hepatology, Faculty of Medicine, Nicolaus Copernicus University, Bydgoszcz 85-030, Poland
Dorota Zarębska-Michaluk, Department of Infectious Diseases and Allergology, Jan Kochanowski University, Kielce 25-317, Poland
Dorota Zarębska-Michaluk, Department of Infectious Diseases, Provincial Hospital, Kielce 25-317, Poland
Piotr Rzymski, Department of Environmental Medicine, University of Medical Sciences, Poznań 60-806, Poland
Piotr Rzymski, Integrated Science Association, Universal Scientific Education and Research Network, Poznań 60-806, Poland
Hanna Berak, Outpatient Clinic, Hospital for Infectious Diseases in Warsaw, Warsaw 01-201, Poland
Beata Lorenc, Pomeranian Center of Infectious Diseases, Medical University, Gdańsk 80-214, Poland
Marek Sitko, Department of Infectious and Tropical Diseases, Jagiellonian University, Kraków 31-088, Poland
Michał Dybowski, Utrecht University School of Economics, Utrecht University, Utrecht 3584 EC, Netherlands
Włodzimierz Mazur, Clinical Department of Infectious Diseases, Medical University of Silesia, Chorzów 41-500, Poland
Magdalena Tudrujek-Zdunek, Department of Infectious Diseases, Medical University of Lublin, Lublin 20-059, Poland
Justyna Janocha-Litwin, Department of Infectious Diseases and Hepatology, Medical University of Wrocław, Wrocław 50-367, Poland
Ewa Janczewska, Department of Basic Medical Sciences, Faculty of Public Health in Bytom, Medical University of Silesia, Katowice 40-007, Poland
Jakub Klapaczyński, Department of Internal Medicine and Hepatology, Central Clinical Hospital of the Ministry of Internal Affairs and Administration, Warsaw 00-241, Poland
Anna Parfieniuk-Kowerda, Robert Flisiak, Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok 15-089, Poland
Anna Piekarska, Department of Infectious Diseases and Hepatology, Medical University of Łódź, Łódź 91-347, Poland
Barbara Sobala-Szczygieł, Department of Infectious Diseases and Hepatology, Medical University of Silesia, Bytom 41-902, Poland
Krystyna Dobrowolska, Collegium Medicum, Jan Kochanowski University, Kielce 25-317, Poland
Author contributions: Dybowska D, Zarębska-Michaluk D, Rzymski P, Pawłowska M and Flisiak R conceived the study design; Dybowska D and Dybowski M cured data and prepared data for analysis; Dybowska D and Rzymski P analyzed and interpreted the data; Rzymski P performed the statistical analysis; Rzymski P prepared tables and figures; Dybowska D, Zarębska-Michaluk, Rzymski P, Pawłowska M, and Flisiak R drafted the manuscript; Dobrowolska K prepared the manuscript for submission; Berak H, Lorenc B, Sitko M, Dybowski M, Mazur W, Tudrujek-Zdunek M, Janocha-Litwin J, Janczewska E, Klapaczyński J, Parfieniuk-Kowerda A, Piekarska A, Sobala-Szczygieł Barbara, Dobrowolska K, and Pawłowska M acquired the data and approved the final version of the manuscript.
Institutional review board statement: According to local law (Pharmaceutical law of 6th September 2001, art.37al), non-interventional studies do not require ethics committee approval.
Informed consent statement: All study participants provided informed consent for antiviral treatment and processing of personal data according to the requirements of the therapeutic program.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Dataset available upon reasonable request to the corresponding author at dorota1010@tlen.pl.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Dorota Zarębska-Michaluk, PhD, Assistant Professor, Professor, Department of Infectious Diseases and Allergology, Jan Kochanowski University, Żeromskiego 5, Kielce 25-317, Poland. dorota1010@tlen.pl
Received: March 23, 2023
Peer-review started: March 23, 2023
First decision: March 28, 2023
Revised: April 1, 2023
Accepted: April 28, 2023
Article in press: April 28, 2023
Published online: July 7, 2023

It is estimated that 58 million people worldwide are infected with the hepatitis C virus (HCV). Patients with severe psychiatric disorders could not be treated with previously available interferon-based therapies due to their unfavorable side effect profile. This has changed with the introduction of direct-acting antivirals (DAA), although their real-life tolerance and effectiveness in patients with different psychiatric disorders remain to be demonstrated.


To evaluate the effectiveness and safety of DAA in patients with various mental illnesses.


This was a retrospective observational study encompassing 14272 patients treated with DAA for chronic hepatitis C in 22 Polish hepatology centers, including 942 individuals diagnosed with a mental disorder (anxiety disorder, bipolar affective disorder, depression, anxiety-depressive disorder, personality disorder, schizophrenia, sleep disorder, substance abuse disorder, and mental illness without a specific diagnosis). The safety and effectiveness of DAA in this group were compared to those in a group without psychiatric illness (n = 13330). Antiviral therapy was considered successful if serum ribonucleic acid (RNA) of HCV was undetectable 12 wk after its completion [sustained virologic response (SVR)]. Safety data, including the incidence of adverse events (AEs), serious AEs (SAEs), and deaths, and the frequency of treatment modification and discontinuation, were collected during therapy and up to 12 wk after treatment completion. The entire study population was included in the intent-to-treat (ITT) analysis. Per-protocol (PP) analysis concerned patients who underwent HCV RNA evaluation 12 wk after completing treatment.


Among patients with mental illness, there was a significantly higher percentage of men, treatment-naive patients, obese, human immunodeficiency virus and hepatitis B virus-coinfected, patients with cirrhosis, and those infected with genotype 3 (GT3) while infection with GT1b was more frequent in the population without psychiatric disorders. The cure rate calculated PP was not significantly different in the two groups analyzed, with a SVR of 96.9% and 97.7%, respectively. Although patients with bipolar disorder achieved a significantly lower SVR, the multivariate analysis excluded it as an independent predictor of treatment non-response. Male sex, GT3 infection, cirrhosis, and failure of previous therapy were identified as independent negative predictors. The percentage of patients who completed the planned therapy did not differ between groups with and without mental disorders. In six patients, symptoms of mental illness (depression, schizophrenia) worsened, of which two discontinued treatments for this reason. New episodes of sleep disorders occurred significantly more often in patients with mental disorders. Patients with mental illness were more frequently lost to follow-up (4.2% vs 2.5%).


DAA treatment is safe and effective in HCV-infected patients with mental disorders. No specific psychiatric diagnosis lowered the chance of successful antiviral treatment.

Keywords: Hepatitis C, Mental disorders, Direct-acting antivirals

Core Tip: In the population of patients with mental illness, the prevalence of hepatitis C virus infection is many times higher than in the general population. In the era of interferon-based therapy, these patients had minimal access to antiviral treatment due to contraindications to interferon with the risk of exacerbation of psychiatric diseases. Their situation has improved with the introduction of direct-acting antivirals, but data from real-world studies are scarce. This retrospective analysis carried out in clinical practice confirmed that the good safety profile and treatment effectiveness are not inferior to those obtained in a population without mental disorders.