Retrospective Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jun 27, 2025; 17(6): 105899
Published online Jun 27, 2025. doi: 10.4254/wjh.v17.i6.105899
Sex-related differences in patients with chronic hepatitis C infection treated with direct-acting antiviral drugs
Krystyna Dobrowolska, Dorota Zarębska-Michaluk, Malgorzata Pawłowska, Magdalena Tudrujek-Zdunek, Beata Lorenc, Hanna Berak, Ewa Janczewska, Włodzimierz Mazur, Justyna Janocha-Litwin, Jakub Klapaczyński, Marek Sitko, Dorota Dybowska, Anna Parfieniuk-Kowerda, Anna Piekarska, Jerzy Jaroszewicz, Robert Flisiak
Krystyna Dobrowolska, Collegium Medicum, Jan Kochanowski University, Kielce 25-317, Poland
Dorota Zarębska-Michaluk, Department of Infectious Diseases and Allergology, Jan Kochanowski University, Kielce 25-369, Poland
Malgorzata Pawłowska, Dorota Dybowska, Department of Infectious Diseases and Hepatology, Faculty of Medicine, Nicolaus Copernicus University, Bydgoszcz 85-030, Poland
Magdalena Tudrujek-Zdunek, Department of Infectious Diseases, Medical University of Lublin, Lublin 20-081, Poland
Beata Lorenc, Pomeranian Center of Infectious Diseases, Medical University of Gdańsk, Gdańsk 80-214, Poland
Hanna Berak, Outpatient Clinic, Hospital for Infectious Diseases, Warsaw 02-201, Poland
Ewa Janczewska, ID Clinic Mysłowice, Mysłowice 41-400, Poland
Włodzimierz Mazur, Department of Clinical Infectious Diseases in Chorzów, Medical University of Silesia, Katowice 40-055, Poland
Justyna Janocha-Litwin, Department of Infectious Diseases and Hepatology, Wrocław Medical University, Wrocław 50-367, Poland
Jakub Klapaczyński, Department of Internal Medicine and Hepatology, The National Institute of Medicine of the Ministry of Interior and Administration, Warsaw 02-507, Poland
Marek Sitko, Department of Infectious and Tropical Diseases, Jagiellonian University, Kraków 30-688, Poland
Anna Parfieniuk-Kowerda, Robert Flisiak, Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok 15-540, Poland
Anna Piekarska, Department of Infectious Diseases and Hepatology, Medical University of Łódź, Łódź 91-347, Poland
Jerzy Jaroszewicz, Department of Infectious Diseases and Hepatology, Medical University of Silesia, Bytom 41-902, Poland
Author contributions: Dobrowolska K, Zarębska-Michaluk D, and Flisiak R designed the study; Dobrowolska K, Zarębska-Michaluk D, Pawłowska M, Tudrujek-Zdunek M, Lorenc B, Berak H, Janczewska E, Mazur W, Janocha-Litwin J, Klapaczyński J, Sitko M, Dybowska D, Parfieniuk-Kowerda A, Piekarska A, Jaroszewicz J, and Flisiak R collected the data; Dobrowolska K conducted the statistical analysis; Dobrowolska K, Zarębska-Michaluk D, and Flisiak R were responsible for data interpretation; Dobrowolska K, Zarębska-Michaluk D, Pawłowska M, and Flisiak R prepared the manuscript; Dobrowolska K, Zarębska-Michaluk D, and Pawłowska M conducted the literature search; and all authors revised and approved the final version of the manuscript.
Institutional review board statement: The study was approved by the Ethics Committee of Jan Kochanowski University, resolution number 57/2024, date of approval July 25.
Informed consent statement: Due to the retrospective nature of the study, a waiver of consent was in effect.
Conflict-of-interest statement: Zarębska-Michaluk D has acted as a speaker and advisor for AbbVie and Gilead. Pawłowska M has acted as a speaker for AbbVie and Gilead. Berak H has acted as a speaker for Abbvie. Janczewska E has acted as a speaker and/or advisor for AbbVie, Gilead, MSD, and Ipsen, and has received funding for clinical trials from AbbVie, Allergan, BMS, Celgene, Cymabay, Dr Falk Pharma, Exelixis, GSK, and MSD. Mazur W has acted as a speaker and/or advisor for AbbVie, Gilead, and Merck, and has received funding for clinical trials from AbbVie, Gilead, and Janssen. Klapaczyński J has acted as a speaker for Gilead and AbbVie. Sitko M has acted as a speaker for AbbVie and Gilead. Piekarska A has acted as a speaker and/or advisor for AbbVie, Gilead, Merck, and Roche; Jaroszewicz J has acted as a speaker and/or advisor for AbbVie, Gilead, Merck, Roche, Alfasigma, MSD, Gilead, and PRO.MED. Flisiak R has acted as a speaker and/or advisor and has received funding for clinical research from AbbVie, Gilead, Merck, Roche, and Novo Nordisk. Dobrowolska K, Tudrujek-Zdunek M, Janocha-Litwin J, and Dybowska D have no conflict to declare.
Data sharing statement: Data supporting reported results can be provided upon request from the corresponding author.
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, Professor, Department of Infectious Diseases and Allergology, Jan Kochanowski University, Żeromskiego 5, Kielce 25-369, Poland. dorota1010@tlen.pl
Received: February 10, 2025
Revised: April 18, 2025
Accepted: May 24, 2025
Published online: June 27, 2025
Processing time: 136 Days and 2 Hours
Abstract
BACKGROUND

Sex is one of the known factors influencing the risk of hepatitis C virus (HCV) infection and the natural course of the disease.

AIM

To evaluate sex-related differences in the characteristics and outcomes of direct-acting antiviral (DAA) treatment in HCV-infected patients.

METHODS

The study included consecutive 9457 women and 9529 men, treated with DAA for chronic HCV infection from July 2015 to the end of 2023 whose data were collected in the nationwide multicenter retrospective Epiter-2 project. Women were divided into pre-menopausal (15-44 years), menopausal (45-55 years) and post-menopausal (> 55 years) and compared with age-matched men.

RESULTS

Regardless of age, women had a significantly lower body mass index, prevalence of genotype 3 infection and proportion of cirrhosis compared to men. Psychiatric disorders (except depression), hepatitis B virus and human immunodeficiency virus co-infections, as well as alcohol and drug addiction, were significantly less common in women than in men in all age groups. The sustained virologic response was significantly higher in women compared to men in each age group and amounted to 98.4% and 96.6%, respectively (P < 0.001). Independent predictors of treatment failure in women were genotype 3 infection, cirrhosis and postmenopausal age. Mild adverse events were reported significantly more often by women, regardless of age with the highest percentage in the postmenopausal group.

CONCLUSION

DAA treatment is more effective in women than in men, regardless of age, but in postmenopausal women, the effectiveness is relatively the lowest.

Keywords: Women; Hepatitis C virus; Direct-acting antivirals; Menopause; Chronic hepatitis C

Core Tip: Sex is the factor influencing the risk of hepatitis C virus infection and the natural course of the disease. An analysis of nearly 19000 patients treated with direct-acting antivirals for chronic hepatitis C according to sex and reproductive status documented that regardless of age, women have lower body mass index, less frequent infection with genotype 3, less frequent co-infections with hepatitis B and human immunodeficiency viruses, and less advanced liver disease. Antiviral treatment is more effective in women than in men, irrespective of age, but postmenopausal women have relatively the lowest effectiveness and the highest incidence of adverse events.