Endocrine, Metabolic & Immune Disorders -Drug Targets Mohamed Alhefnawy 1 , Ahmed Mohey 1 , Ahmed Fathi 1 , Ahmed Mansour 2 , Sherief Abd-Elsalam 3,* , Ahmed Eissa 4 , Ayman Hagras 4 , Stefano Puliatti 5,6 and Khaled Almekaty 4 1 Urology Department, Faculty of Medicine, Benha University, Benha, Egypt; 2 Internal Medicine Department, Faculty of Medicine, Benha University, Benha, Egypt; 3 Tropical Medicine and Infectious Diseases Department, Tanta Universi- ty, Tanta, Egypt; 4 Urology Department; Faculty of Medicine; Tanta University; Tanta; Egypt; 5 Urology Department, University of Modena and Reggio Emilia, Modena, Italy; 6 ORSI Academy, Melle, Belgium ARTICLE HISTORY Received: October 21, 2020 Revised: December 15, 2020 Accepted: December 21, 2020 DOI: 10.2174/1871530321666210212143932 Abstract: Background & Objective: Erectile dysfunction (ED) is one of the extrahepatic manifes- tations of hepatitis C virus infection that greatly affects patients’ quality of life. Unfortunately, some of the drugs used for HCV treatment may have a negative impact on the patient’s erectile function, such as the pegylated interferon. Currently, with the introduction of direct-acting antiviral drugs, there is scarce data in the literature about its potential impact on erectile function. In these settings, we aimed to assess the impact of sofosbuvir-based therapy on male erectile function. Methods: This prospective interventional study was carried out in Benha University hospitals be- tween January 2019 and May 2020. The study included all consecutive HCV patients with simulta- neous ED coming to the hepatology outpatient clinic. Patients were divided into a study group who received sofosbuvir-based therapy (group A) or a control group who received silymarin therapy (group B). The International Index of Erectile Function-5 (IIEF-5) was used for the assessment of erectile function at different time points (pretreatment, 6 months, and 12 months after treatment). Different variables in both groups have been statistically analyzed. Results: Overall, 75 patients who received sofosbuvir-based therapy and a control group (n = 35) matched for age and pretreatment variables (Child–Turcotte–Pugh score and Fibrosis 4 score). There was no significant difference between both groups in the pretreatment data. On the other hand, the posttreatment IIEF-5 was significantly higher in the sofosbuvir arm compared to the sily- marin arm both at six months (p<0.001) and at 12 months (p<0.001). Furthermore, the age and the stage of liver fibrosis were negatively correlated with IIEF-5 at all-time points. Conclusion: The age and the stage of liver fibrosis are significantly correlated with the degree of ED. Furthermore, sofosbuvir-based therapy may be associated with significant improvement in pa- tients with erectile function. Keywords: Hepatitis C virus, Sofosbuvir, andrology, sexual dysfunction, erectile dysfunction, silymarin. 1. INTRODUCTION Erectile Dysfunction (ED) is a significant healthcare problem in adult males. A community-based study showed that the overall prevalence of ED is 23.5% among married Egyptian men. Furthermore, this study demonstrated that complete ED is significantly correlated with patients’ age (ranging from 8.5% to 52% among men in their 40s to 70s, respectively) [1]. Several risk factors are associated with in- creased risk of ED, including an unhealthy lifestyle and sys- temic diseases (like diabetes mellitus, hypertension, and car- diovascular disease) [2]. Interestingly, ED was found to be * Address correspondence to this author at the Tropical Medicine and Infec- tious Diseases Department, Tanta University, Tanta, Egypt; E-mail: sherif_tropical@yahoo.com more prevalent among hepatitis C virus (HCV) patients com- pared to the general population [3, 4]. Hunter SS et al. [4], demonstrated that ED was found in 29.3% of chronic HCV patients in Egypt with significantly higher prevalence in pa- tients with cirrhosis compared to chronic HCV patients with- out cirrhosis (92.3% versus 16.12%, respectively) [4]. Yet, ED is still considered an underrated condition in HCV pa- tients as the physicians usually tend to concentrate more on life-threatening diseases, and/or it may be embarrassing for the patient to discuss their sexual life and performance [5]. The relation between HCV infection and ED may be ex- plained by several theories, including the psychological and endocrinological disturbances in those patients, the effect of antiviral therapy like interferon, and the fear of the probabili- ty of HCV transmission through sexual intercourse [3, 6-8]. 2212-3873/22 $65.00+.00 © 2022 Bentham Science Publishers Send Orders for Reprints to reprints@benthamscience.net 310 Endocrine, Metabolic & Immune Disorders - Drug Targets, 2022, 22, 310-317 RESEARCH ARTICLE Effect of Direct-Acting Antiviral Drugs on Erectile Functions among Hep- atitis C Patients: A Prospective Interventional Study