Effect of treatment of chronic hepatitis c virus patients with direct-acting anti-retroviral drugs on semen and hormonal parameters.

Objective: Hepatitis C virus (HCV) infection is known to influence the seminal and hormonal parameters of infected men. This study was performed to assess the effects of HCV clearance using direct-acting antiviral (DAA) agents on semen and hormonal parameters. Methods: A total of 50 patients with chronic HCV were enrolled, and conventional semen analysis was performed according to World Health Organization guidelines. Basal levels of total testosterone, free testosterone (FT), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), prolactin, and sex hormone-binding globulin (SHBG) were assessed before and 3 months after treatment with DAAs. Results: Following DAA treatment, statistically significant increases were observed in sperm motility and the proportion of grade A sperm. Additionally, the percentage of abnormal forms was significantly decreased after treatment (p=0.000). However, no significant differences were observed in semen volume, concentration, or total sperm count. Sex hormone analysis of patients after DAA treatment revealed significant increases in FT, LH, and FSH levels, along with significant decreases in SHBG, prolactin, and E2 levels. Conclusion: Following HCV clearance, we noted an improvement in sperm motility and an increase in the percentage of sperm with normal morphology. Treatment with DAAs was also associated with increased levels of FT and LH, along with decreased levels of SHBG, prolactin, and E2.

Effect of evidence-based nursing practices training programme on the competency of nurses caring for mechanically ventilated patients: a randomised controlled trial.

BACKGROUND: Evidence-Based Practice (EBP) has been recognised worldwide as a standardised approach for enhancing the quality of healthcare and patient outcomes. Nurses play a significant role in integrating EBP, especially in Intensive Care Unit (ICU). Consequently, this study aims to examine the effect of an adapted evidence-based nursing practices training programme on the competency level of nurses caring for mechanically ventilated patients. METHODS: A prospective open-label parallel 1:1 randomised controlled trial was conducted on 80 nurses caring for ICU patients at the National Hepatology and Tropical Medicine Research Institute, Egypt. The trial was carried out between November 2022 and February 2023 under the registration number NCT05721664. The enrolled nurses were randomly divided into intervention and control groups. The intervention group received the evidence-based nursing practice training programme (EBNPTP) in accordance with the Johns Hopkins EBP conceptional model, whereas the control group received traditional in-service education. Four assessments (one pre- and three post-assessments) were conducted to evaluate nurses' competency level over time using the adapted evidence-based nursing competency assessment checklist. The primary endpoint was an increase the competency levels among nurses caring for mechanically ventilated patients. RESULTS: The current study results revealed statistically significant differences between intervention and control groups in relation to their level of competency across the three post-assessments, with (p <.001). The study also demonstrated that the nurses' competency level continued to decline significantly over time, with (p <.001). Additionally, a significant correlation was found between the nurses' pre-assessment and educational level, acting as independent variables (predictors), and the third endpoint assessment (p <.01), indicated by multiple linear regression. CONCLUSION: The EBP training programme demonstrated a significant increase in the nurses' level of competency compared with traditional in-service education. This suggests that by training the nurses in various settings with the essential skills and knowledge for EBP, their competency level can be enhanced, leading to the delivery of effective care and improving patient outcomes. However, the long-term sustainability of the EBP adoptions was insufficient; further studies are needed to investigate the factors that affect the durability of EBP adoption. TRIAL REGISTRATION: The study was registered with Clinical Trials.gov (Registration # NCT05721664) on 10/02/2023.

Molnupiravir for intra-household prevention of COVID-19: The MOVe-AHEAD randomized, placebo-controlled trial.

OBJECTIVES: To evaluate the efficacy and safety of molnupiravir for intra-household post-exposure prophylaxis (PEP) of COVID-19. METHODS: MOVe-AHEAD was a randomized, controlled, double-blind, phase 3 trial comparing molnupiravir (800 mg twice daily for 5 days) with placebo. Eligible participants were adult, unvaccinated, asymptomatic household contacts of patients with laboratory-confirmed COVID-19. The primary efficacy endpoint was the incidence of COVID-19 through day 14 in modified intention-to-treat (MITT) participants (those who received ≥1 dose of study intervention) without detectable SARS-CoV-2 at baseline, termed the MITT-VN population. Superiority of molnupiravir was prespecified as a stratified one-sided p-value of <0.0249 for the treatment difference in this endpoint. RESULTS: The MITT population comprised 763 participants randomized to molnupiravir and 764 to placebo; 83.6% had anti-SARS-CoV-2 antibodies at baseline. In the MITT-VN population, COVID-19 rates through day 14 were 6.5% with molnupiravir and 8.5% with placebo (one-sided p-value: 0.0848). In the molnupiravir arm, 25/35 of confirmed COVID-19 events (71.4%) occurred after completion of treatment (versus 17/49 [34.7%] for placebo). Adverse event rates were low and similar between molnupiravir and placebo. CONCLUSIONS: Molnupiravir was well-tolerated but did not meet the prespecified superiority criterion, possibly influenced in part by the high pre-existing immunity in the trial population.

Egyptian Society of Liver Cancer Recommendation Guidelines for the Management of Hepatocellular Carcinoma.

Globally, hepatocellular carcinoma (HCC) is the fourth most common cause of death from cancer. The prevalence of this pathology, which has been on the rise in the last 30 years, has been predicted to continue increasing. HCC is the most common cause of cancer-related morbidity and mortality in Egypt and is also the most common cancer in males. Chronic liver diseases, including chronic hepatitis C, which is a primary health concern in Egypt, are considered major risk factors for HCC. However, HCC surveillance is recommended for patients with chronic hepatitis B virus (HBV) and liver cirrhosis; those above 40 with HBV but without cirrhosis; individuals with hepatitis D co-infection or a family history of HCC; and Nonalcoholic fatty liver disease (NAFLD) patients exhibiting significant fibrosis or cirrhosis. Several international guidelines aid physicians in the management of HCC. However, the availability and cost of diagnostic modalities and treatment options vary from one country to another. Therefore, the current guidelines aim to standardize the management of HCC in Egypt. The recommendations presented in this report represent the current management strategy at HCC treatment centers in Egypt. Recommendations were developed by an expert panel consisting of hepatologists, oncologists, gastroenterologists, surgeons, pathologists, and radiologists working under the umbrella of the Egyptian Society of Liver Cancer. The recommendations, which are based on the currently available local diagnostic aids and treatments in the country, include recommendations for future prospects.

Evaluation of circulating insulin-like growth factor-1, heart-type fatty acid-binding protein, and endotrophin levels as prognostic markers of COVID-19 infection severity.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) is a worldwide pandemic challenge spreading enormously within a few months. COVID-19 is characterized by the over-activation of the immune system causing cytokine storm. Insulin-like growth factor-1 (IGF-1) pathway can regulate the immune response via interaction with various implicated cytokines. Heart-type fatty acid-binding protein (H-FABP) has been shown to promote inflammation. Given the fact that coronavirus infections induce cytokines secretion leading to inflammatory lung injury, it has been suggested that H-FABP levels are affected by COVID-19 severity. Moreover, endotrophin (ETP), the cleavage product of collagen VI, may be an indicator of an overactive repair process and fibrosis, considering that viral infection may predispose or exacerbate existing respiratory conditions, including pulmonary fibrosis. This study aims to assess the prognostic capacity of circulating IGF-1, HFABP, and ETP, levels for COVID-19 severity progression in Egyptian patients. METHODS: The study cohort included 107 viral RNA-positive patients and an equivalent number of control individuals with no clinical signs of infection. Clinical assessments included profiling of CBC; serum iron; liver and kidney functions; inflammatory markers. Circulating levels of IGF-1; H-FABP, and ETP were estimated using the corresponding ELISA kits. RESULTS: No statistical difference in the body mass index was detected between the healthy and control groups, while the mean age of infected patients was significantly higher (P = 0.0162) than the control. Patients generally showed elevated levels of inflammatory markers including CRP and ESR concomitant with elevated serum ferritin; D dimer and procalcitonin levels, besides the COVID-19 characteristic lymphopenia and hypoxemia were also frequent. Logistic regression analysis revealed that oxygen saturation; serum IGF-1, and H-FABP can significantly predict the infection progression (P < 0.001 each). Both serum IGF-1 and H-FABP as well as O2 saturation showed remarkable prognostic potentials in terms of large AUC values, high sensitivity/specificity values, and wide confidence interval. The calculated threshold for severity prognosis was 25.5 ng/mL; 19.5 ng/mL, 94.5, % and for IGF-1, H-FABP, and O2 saturation; respectively. The calculated thresholds of serum IGF-1; H-FABP, and O2 saturation showed positive and negative value ranges of 79-91% and 72-97%; respectively, with 66-95%, 83-94% sensitivity, and specificity; respectively. CONCLUSION: The calculated cut-off values of serum IGF-1 and H-FABP represent a promising non-invasive prognostic tool that would facilitate the risk stratification in COVID-19 patients, and control the morbidity/mortality associated with progressive infection.

Anxiety, depression and coping strategies among chronic medical patients with coronavirus disease-2019: a multicenter follow-up cohort study.

BACKGROUND: Studies have shown that COVID-19 patients experience high levels of anxiety, depression, and stress during the pandemic. Patients adopt different coping strategies to reduce their psychological distress. AIM: To compare the immediate and long-term psychological impact of COVID-19 disease on patients with and without chronic medical illnesses (CMI) and identify coping styles of both groups during the peak of COVID-19 disease in Egypt. METHODS: This is a cohort follow-up study, that included an online survey consisting of General Health Questionnaire-12, Taylor Manifest Anxiety Scale, Beck Depression Inventory and Brief-COPE scale. The Post-Traumatic Stress Disorder (PTSD) Checklist was completed after 6 months. Questionnaires were distributed to adult patients with a confirmed diagnosis of SARS-CoV-2 virus infection during their quarantine in Egypt. RESULTS: There was no significant difference between the two groups regarding anxiety and depression during the acute infection. Patients without CMI relied significantly on the use of informational support to cope with COVID-19 disease. Patients with CMI continued to show significant depressive symptoms after 6 months without significant PTSD symptoms. CONCLUSIONS: COVID-19 has similar immediate psychological impact on patients with and without CMI. However, patients with CMI continue to show depression on long-term follow-up.

Survival and outcomes for co-infection of chronic hepatitis C with and without cirrhosis and COVID-19: A multicenter retrospective study.

BACKGROUND: Chronic liver disease, particularly cirrhosis, is associated with worse outcomes in patients infected with coronavirus disease 2019 (COVID-19). AIM: To assess outcomes of COVID-19 infection among patients with pre-existing hepatitis C with or without liver cirrhosis. METHODS: This multicenter, retrospective cohort study included all cases of confirmed co-infection of severe acute respiratory syndrome coronavirus 2 and chronic hepatitis C with or without liver cirrhosis who were admitted to six hospitals (Al-Sahel Hospital, Al-Matareya Hospital, Al-Ahrar Hospital, Ahmed Maher Teaching Hospital, Al-Gomhoreya Hospital, and the National Hepatology and Tropical Medicine Research Institute) affiliated with the General Organization for Teaching Hospitals and Institutes in Egypt. Patients were recruited from May 1, 2020, to July 31, 2020. Demographic, laboratory, imaging features, and outcomes were collected. Multivariate regression analysis was performed to detect factors affecting mortality. RESULTS: This retrospective cohort study included 125 patients with chronic hepatitis C and COVID-19 co-infection, of which 64 (51.20%) had liver cirrhosis and 40 (32.00%) died. Fever, cough, dyspnea, and fatigue were the most frequent symptoms in patients with liver cirrhosis. Cough, sore throat, fatigue, myalgia, and diarrhea were significantly more common in patients with liver cirrhosis than in non-cirrhotic patients. There was no difference between patients with and without cirrhosis regarding comorbidities. Fifteen patients (23.40%) with liver cirrhosis presented with hepatic encephalopathy. Patients with liver cirrhosis were more likely than non-cirrhotic patients to have combined ground-glass opacities and consolidations in CT chest scans: 28 (43.75%) vs 4 (6.55%), respectively (P value < 0.001). These patients also were more likely to have severe COVID-19 infection, compared to patients without liver cirrhosis: 29 (45.31%) vs 11 (18.04%), respectively (P value < 0.003). Mortality was higher in patients with liver cirrhosis, compared to those with no cirrhosis: 33 (51.56%) vs 9 (14.75%), respectively (P value < 0.001). All patients in Child-Pugh class A recovered and were discharged. Cirrhotic mortality occurred among decompensated patients only. A multivariate regression analysis revealed the following independent factors affecting mortality: Male gender (OR 7.17, 95%CI: 2.19-23.51; P value = 0.001), diabetes mellitus (OR 4.03, 95%CI: 1.49-10.91; P value = 0.006), and liver cirrhosis (OR 1.103, 95%CI: 1.037-1.282; P value < 0.0001). We found no differences in liver function, COVID-19 disease severity, or outcomes between patients who previously received direct-acting antiviral therapy (and achieved sustained virological response) and patients who did not receive this therapy. CONCLUSION: Patients with liver cirrhosis are susceptible to higher severity and mortality if infected with COVID-19. Male gender, diabetes mellitus, and liver cirrhosis are independent factors associated with increased mortality risk.

Effect of disease stage and treatment outcomes on the dynamics of liver functions during and after treatment of hepatitis C with directly acting antivirals.

BACKGROUND: Virus C infection is recently treated successfully with plenty of direct antiviral agents (DAAs). We aimed to evaluate the effect of disease stage and treatment outcome on the dynamics of liver functions during treatment of hepatitis C with DAAs. METHODS: We reported the liver function in 2354 subjects diagnosed as chronic hepatitis C before, during and after treatment with different DAAs regimens. Patients were classified into two groups according to treatment response with further subclassification according to the presence or absence of cirrhosis, and changes in liver functions were compared in each group and subgroup. RESULTS: Totally 2213 (94%) achieved sustained virological response (SVR) to DAAs therapy with significant improvement in all liver biochemistry. Also, there was an improvement in the non-SVR group's liver enzymes in relapsers during and after treatment; however, there was no improvement in serum albumin. We noticed a slight increase in serum bilirubin at weeks 4 and 8 for both groups. CONCLUSION: DAAs therapy is associated with improvement of the liver biochemical profile and improved outcome in the majority of chronic hepatitis C virus patients due to suppression of viral replication. However, the long-term impact of DAAs therapy needs to be further evaluated.

Outcome of Laparoscopic Assisted Percutaneous Microwave Ablation for Exophytic Versus Non-exophytic Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies and is the third cause of cancer-related death worldwide. Surgery is the optimal treatment for early HCC; however, the majority of cases are not suitable for curative resection at the time of diagnosis. Surgical resection difficulties may be related to size, site, number of tumors, extrahepatic involvement, and patient general condition. Exophytic tumors were considered as relative contraindication for thermal ablation because of the risk of incomplete ablation or major complications as hemorrhage and seeding. AIM OF THIS STUDY: to evaluate the safety and efficacy of microwave ablation (MWA) of exophytic HCC in comparison with non-exophytic HCC. METHODS: Prospective comparative study carried on 30 patients having 30 exophytic (six of those patients had another non-exophytic lesion) and 32 patients having 44 non-exophytic HCC lesions (22 had single lesion, 8 patients had 2 lesions, and 2 patients had 3 lesions) within Milan criteria. All patients were child A or B, they were subjected to full clinical assessment, laboratory investigations, and radiological investigations. Laparoscopic assisted percutaneous MWA was the procedure of choice in our study for all patients either having exophytic or non-exophytic lesions using no-touch wedge technique for exophytic lesions and direct puncture for non-exophytic lesions. RESULTS: Technical success was 100% in both groups, all lesions were completely ablated as confirmed by LIOUS. There were no major complications or perioperative mortality and low incidence of local tumor progression in both exophytic and non-exophytic groups. CONCLUSION: Laparoscopic assisted MWA of exophytic HCC is safe and effective with comparable results to non-exophytic HCC. Exophytic HCC is not contraindication for MWA with proper technique selection.

COVID-19 Pandemic Preparedness in Egypt's Teaching Hospitals: A Needs Assessment Study.

INTRODUCTION: Regular collection and monitoring of data describing the dynamics of the utilization of healthcare services, especially in teaching hospitals (TH), which provide model quality medical services, are critical for COVID-19 pandemic preparedness. METHODS: The researchers analyzed data and information derived from service statistics reports from June 1st to July 15th, 2020 in terms of hospital resources, as well as utilization patterns of beds, ICU, and ventilators, for 11 screening hospitals affiliated with the General Organization of Teaching Hospitals and institutes in Egypt assigned by the Ministry of Health and Population to provide medical care for COVID-19 patients. Hospital indicators in terms of COVID-19 screening services, as well as utilization patterns of inpatient beds, ICU beds, and ventilators were computed. RESULTS: A total of 78,869 non-medical personnel and 2,176 medical personnel were presented with COVID-19 triage symptoms. Investigations conducted in the targeted 11 hospitals delineated that 22.2% of non-medical personnel and 27.9% of medical personnel were COVID-19 PCR-confirmed cases. The inpatient bed occupancy rate was 70% for non-medical patients and 67% for medical staff patients. For ICU, the bed occupancy rate was 92 % for non-medical patients and 88% for medical patients. Among the confirmed cases, 38% of medical patients utilized a ventilator vs. 36% of medical personnel cases. Hospital ranking according to utilization pattern among non-medical personnel, Hospital H ranked first in terms of the high load of screening services. Hospital C ranked first regarding the number of confirmed cases, whereas Hospital D ranked first for high ICU utilization among all teaching hospital ICU cases. With respect to medical personnel, Hospital G ranked first for the high load of screening services for the total studied cases. Hospital G ranked first for the number of confirmed cases. Hospital B ranked first regarding high ICU utilization among all teaching hospital ICU cases. CONCLUSION: Teaching hospitals have demonstrated preparedness for the COVID-19 pandemic by maintaining an inpatient bed occupancy rate of 70% or less and ventilator utilization at <40% of confirmed cases. However, the ICU bed occupancy rate was more than 90% indicating a shortage of resources. In addition, there is variance across hospitals regarding caseload for resource reallocation decisions.

The Effectiveness of Ledipasvir/Sofosbuvir in Youth With Genotype 4 Hepatitis C Virus: A Single Egyptian Center Study.

BACKGROUND: Licensure of ledipasvir/sofosbuvir for chronic hepatitis C virus (HCV) infection in adolescents was based on clinical trials on patients mainly with genotype 1. We aimed to evaluate the effectiveness and short-term safety of this newly approved antiviral in adolescents with HCV genotype 4. METHODS: This was a study of 51 HCV-infected adolescents, who received the adult dose of ledipasvir/sofosbuvir, once daily for 12 weeks, and were followed-up for 12 weeks post-treatment. Laboratory tests, quantitation of HCV RNA, HCV genotyping, IL-28rs gene polymorphism and transient elastography were performed at baseline. Follow-up visits were done for blood testing and adverse events recording. RESULTS: The mean age was 14.7 ± 1.5 years (11-17.5), with a male to female ratio of 1.7:1. All patients were genotype 4a, and 76.5% had the CC IL-28 gene polymorphism. About 50% gave a history of HCV-infected mother, and 31% were treatment-experienced. Liver stiffness was F0 in 72.5%, F0-F1 in 13.7% and F1-F2 in 13.7%. Adverse events were mainly abdominal pain in 72.5%, headache in 64.7% and diarrhea in 53% of patients; these were mild. A reversible increase in creatinine level with a concomitant decline in estimated glomerular filtration rate was observed in the first month of treatment. By the end of week 12, a significant decline in liver enzymes was observed. All patients achieved an early, end of treatment, and a sustained virologic response. CONCLUSIONS: Adolescent patients with genotype 4 chronic HCV infection achieved a good response rate with good ontreatment tolerability for ledipasvir/sofosbuvir therapy.

Assessment of the Relation Between SNP in MxA Gene and the Responsiveness of Egyptian HCV Genotype 4 Patients to Pegylated Interferon and Ribavirin Treatment.

BACKGROUND: Pegylated interferon (PegIFN) is used in the treatment of chronic hepatitis C virus (HCV) patients especially in resource limited countries. Treatment with PegIFN stimulates the expression of a number of host genes encoding enzymes with antiviral activities, including myxovirus resistance gene-A (MxA gene). MxA gene was found to have a single nucleotide polymorphism (SNP) at position -88 in the promoter region that affects the expression of MxA gene protein and was suggested to affect the treatment outcome. The aim of the work was to assess the relation between the SNP in the MxA gene and its impact on treatment of chronic HCV patients with PegIFN and ribavirin. METHODS: We therefore genotyped the biallelic G/T SNP in the promoter region of MxA gene at position -88 from the transcription start site by restriction fragment length polymorphism (RFLP) in 70 chronic HCV genotype 4 interferon naive Egyptians and 40 healthy controls. RESULTS: G allele was the prevalent one in both HCV patients group (105, 74.5%) and control group (66, 82.5%), while T allele was less expressed in patients group (36, 25.5%) and control group (14, 17.5%). There is no correlation between genotypes and response to IFN-alpha therapy: GG (OR: 0.958, 95% CI: 0.541 - 1.698, P = 0.884), GT (OR: 0.667, 95% CI: 0.188 - 2.362, P = 0.530), and TT (OR: 0.300, 95% CI: 0.083 - 1.090, P = 0.067). CONCLUSION: MxA nt-88 SNP did not affect the sustained virological response (SVR) rates after PegIFN and ribavirin combined treatment and did not act as a biological marker to potentially identify responders and non-responders to treatment. Our results call for additional large studies and/or meta-analysis of all currently available data to examine the role of MxA nt-88 SNP in predicting response to PegIFN and ribavirin in patients with IFN-alpha naive HCV genotype 4.