1
|
Elbaz T, Al-Naamani K, Abosheaishaa H, Alswat K, El-Kassas M. Leading Role of Sofosbuvir/Daclatasvir in Achieving Hepatitis C Elimination in Egypt. J Viral Hepat 2025; 32:e70032. [PMID: 40433912 DOI: 10.1111/jvh.70032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Revised: 01/09/2025] [Accepted: 05/03/2025] [Indexed: 05/29/2025]
Abstract
Chronic hepatitis C virus (HCV) management has historically been challenging, particularly in Egypt, the country with the highest global disease prevalence. The introduction of direct-acting antivirals (DAAs) has revolutionised treatment, providing high rates of sustained virologic response (SVR) with fewer adverse events compared to previous therapies. In Egypt, the locally produced generics of sofosbuvir/daclatasvir (SOF/DAC) have been integral to the national HCV elimination programme, treating millions effectively and affordably, demonstrating similar efficacy and safety to brand-name drugs. Although not currently present in most international guidelines, this cost-effective regimen offers a viable option for large-scale elimination programmes similar to Egypt's successful experience. This review synthesises real-world Egyptian data and highlights the efficacy and safety of the SOF/DAC combination in various population groups. High sustained virological response (SVR) rates were observed across diverse patient populations, including those with advanced liver disease. However, limitations regarding long-term follow-up, especially HCC surveillance, were identified, underscoring the need for further research. Additionally, the review underscores the success of local Egyptian pharmaceutical policies in reducing treatment costs and securing access for all infected individuals. The Egyptian experience offers valuable insights into the potential for replicating its success, particularly in other high-burden regions.
Collapse
Affiliation(s)
- Tamer Elbaz
- Endemic Hepatology and Gastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
- Hepatology and Gastroenterology Department, Faculty of Medicine, New Giza University, Cairo, Egypt
| | - Khalid Al-Naamani
- Department of Medicine, Division of Gastroenterology and Hepatology, The Medical City for Military and Security Services, Muscat, Oman
| | - Hazem Abosheaishaa
- Internal Medicine, Icahn School of Medicine at Mount Sinai, New York City Health and Hospitals, Queens Hospital Center, New York, New York, USA
| | - Khalid Alswat
- Liver Disease Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Mohamed El-Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt
| |
Collapse
|
2
|
Elmakhzangy HI, Rabie MA, Bahgat DMR, Attia DHS, Elsayed AET, Mohammed RHA. Autoimmune manifestations and direct-acting antiviral drugs in Egyptian patients with hepatitis C virus infection: A cohort study. J Int Med Res 2025; 53:3000605251339135. [PMID: 40391530 PMCID: PMC12092987 DOI: 10.1177/03000605251339135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Accepted: 04/14/2025] [Indexed: 05/21/2025] Open
Abstract
ObjectivesTo investigate the clinical and serological features of autoimmunity with chronic hepatitis C virus infection before and after direct-acting antiviral therapy and assess their relation to treatment response.MethodsA prospective cohort study was performed in adult patients aged ≥18 years who had chronic hepatitis C virus infection, as confirmed by polymerase chain reaction, and were eligible for direct-acting antiviral therapy. Patients with rheumatological disease prior to the onset of hepatitis C virus infection, decompensated cirrhosis, or hepatocellular carcinoma were excluded. All patients were treated with sofosbuvir (400 mg once daily) plus daclatasvir (60 mg once daily) for 3 months. Patients were assessed before and 12 weeks after treatment.ResultsNinety patients completed the follow-up (66.7% females, 33.3% males, mean age: 49.2 ± 12.3 years); 85.55% of them had immune-mediated manifestations prior to direct-acting antiviral therapy. In patients with sustained virologic response, autoimmune manifestations persisted in 66 of the 71 (92.9%) patients with an observable rise in posttreatment erythrocyte sedimentation rate and C-reactive protein level (p > 0.01). The predictors of persistence of autoimmune manifestation were age ≥49 years (p = 0.009), female sex (p = 0.026), and tobacco use (p = 0.043).ConclusionDirect-acting antiviral drugs were not associated with a significant short-term change in the prevalence of autoimmune manifestations in patients who had hepatitis C virus infection with sustained virologic response.
Collapse
Affiliation(s)
- Hesham I Elmakhzangy
- Department of Endemic Diseases and Hepato-Gastroenterology, School of Medicine–Cairo University, Egypt
| | - Mai A Rabie
- Rheumatology and Rehabilitation–Ministry of Health and Population, Egypt
| | - Dina MR Bahgat
- Department of Clinical & Chemical Pathology, School of Medicine–Cairo University, Egypt
| | - Doaa HS Attia
- Department of Rheumatology and Rehabilitation, School of Medicine–Cairo University, Egypt
| | - Ahmed ET Elsayed
- Department of Endemic Diseases and Hepato-Gastroenterology, School of Medicine–Cairo University, Egypt
| | - Reem Hamdy A Mohammed
- Department of Rheumatology and Rehabilitation, School of Medicine–Cairo University, Egypt
| |
Collapse
|
3
|
Wu M, Ma J, Wang X, Li S, Tan C, Xie O, Li A, Lim AG, Wan X. Cost-effectiveness and return on investment of hepatitis C virus elimination in China: A modelling study. Clin Mol Hepatol 2025; 31:394-408. [PMID: 39623958 PMCID: PMC12016657 DOI: 10.3350/cmh.2024.0664] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Revised: 11/12/2024] [Accepted: 12/02/2024] [Indexed: 04/18/2025] Open
Abstract
BACKGROUND/AIMS The World Health Organization set the goal of eliminating hepatitis C virus (HCV) by 2030, with 80% and 65% reductions in HCV incidence and mortality rates, respectively. We aimed to evaluate the health benefits, cost-effectiveness and return on investment (ROI) of HCV elimination. METHODS Using an HCV transmission compartmental model, we evaluated the benefits and costs of different strategies combining screening and treatment for Chinese populations. We identified strategies to achieve HCV elimination and calculated the incremental cost-effectiveness ratios (ICERs) per disability-adjusted life year (DALY) averted for 2022-2030 to identify the optimal elimination strategy. Furthermore, we estimated the ROI by 2050 by comparing the required investment with the economic productivity gains from reduced HCV incidence and deaths. RESULTS The strategy that results in the most significant health benefits involves conducting annual primary screening at a rate of 14%, re-screening people who inject drugs annually and the general population every five years, and treating 95% of those diagnosed (P14-R4-T95), preventing approximately 5.75 and 0.44 million HCV infections and deaths, respectively, during 2022-2030. At a willingness-to-pay threshold of $12,615, the P14-R4-T95 strategy is the most cost-effective, with an ICER of $5,449/DALY. By 2050, this strategy would have a net benefit of $120,997 million (ROI=0.868). CONCLUSION Achieving HCV elimination in China by 2030 will require significant investment in large-scale universal screening and treatment, but it will yield substantial health and economic benefits and is cost-effective.
Collapse
Affiliation(s)
- Meiyu Wu
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Institute of Clinical Pharmacy, Central South University, Changsha, Hunan, China
| | - Jing Ma
- Department of Infectious Diseases, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Xuehong Wang
- Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Sini Li
- The Nethersole School of Nursing, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Chongqing Tan
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Institute of Clinical Pharmacy, Central South University, Changsha, Hunan, China
| | - Ouyang Xie
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Institute of Clinical Pharmacy, Central South University, Changsha, Hunan, China
| | - Andong Li
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Institute of Clinical Pharmacy, Central South University, Changsha, Hunan, China
| | - Aaron G Lim
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Xiaomin Wan
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Institute of Clinical Pharmacy, Central South University, Changsha, Hunan, China
| |
Collapse
|
4
|
Basson AA, Weil C, Marx SE, Dylla DE, Collins M, Hadadi S, Chodick G, Rahamim-Cohen D, Lavi IK, Shibolet O. Road to Hepatitis C Elimination in Israel: Improvements in Linkage to Care (2009-2020). Adv Ther 2025; 42:1522-1536. [PMID: 39912989 PMCID: PMC11868148 DOI: 10.1007/s12325-024-03102-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Accepted: 12/20/2024] [Indexed: 02/07/2025]
Abstract
INTRODUCTION Disrupted linkage to care is a major barrier to hepatitis C virus (HCV) elimination leading to high attrition rates. This study aimed to describe (1) flow through the HCV care-cascade (2009-2020), and (2) monthly patterns in HCV care during the coronavirus disease 2019 (COVID-19) pandemic (2020) in Israel. METHODS Data were obtained from Maccabi Healthcare Services, a 2.6-million-member healthcare provider in Israel. Flow through the HCV care-cascade in 2009-2020 was described from individuals' first positive HCV antibody (Ab+) test to sustained virological response (SVR), and monthly data were obtained on individuals newly attaining a given stage in the HCV care-cascade in 2020. RESULTS Among 2809 new patients who were Ab+, 2651 (94.4%) had an HCV polymerase chain reaction (PCR) test, and 1417 (50.4%) were PCR+ during the study. Median time from Ab+ to PCR+ was 3.9 years, with 39.7% PCR+ within 12 months. Median time from PCR+ to HCV treatment was 3.3 years, with 639 (55.5%) of patients who were PCR+ purchasing direct-acting anti-viral agents (DAAs), and 413/416 patients attained SVR. A significant reduction was observed in the time from first HCV detection (Ab+) to HCV confirmation (PCR+) and from PCR+ test to HCV treatment purchase in the pre-DAA era compared to the post-DAA. Monthly data during 2020 (Part B) indicates a decline in the numbers of patients receiving HCV care during the first pandemic-related closure. CONCLUSION Real-world data from a nationally representative healthcare provider database suggest that HCV linkage to care improved over time alongside increased access to DAAs, despite observed declines in access to care in 2020.
Collapse
Affiliation(s)
| | - Clara Weil
- Maccabi Healthcare Services, Tel Aviv, Israel
| | - Steven E Marx
- AbbVie Inc, North Chicago, IL, USA.
- , 26525 Riverwoods Blvd, Mettawa, IL, 60048, USA.
| | | | | | | | - Gabriel Chodick
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
- Maccabi Healthcare Services, Tel Aviv, Israel
| | | | | | - Oren Shibolet
- Liver Unit, Department of Gastroenterology, Tel Aviv Medical Center, Tel-Aviv, Israel
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| |
Collapse
|
5
|
Shafiq AM, Taha NA, Zaky AH, Mohammed AH, Omran OM, Abozaid L, Ahmed HHT, Ameen MG. Prognostic significance of the tumor budding and tumor-infiltrating lymphocytes in survival of hepatocellular carcinoma patients. Int J Health Sci (Qassim) 2024; 18:10-19. [PMID: 39502429 PMCID: PMC11533185] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2024] Open
Abstract
Objective In spite of great advance in the management of hepatocellular carcinoma (HCC), the prognostic factors are still obviously not understood. The role of tumor budding (TB) and tumor-infiltrating lymphocytes (TILs) in HCC as pathological parameters affecting prognosis stands principally unknown. Methods Seventy-four surgical resection pathology specimens of HCC patients were used. Assessment of TB and TILs were performed using hematoxylin-eosin-stained slides. Follow-up data were collected over a 5-year period to determine disease-free survival rates, overall survival (OS) rates, and how they related to TB, TILs, and other clinicopathological factors. Results There was a significant statistical association between high-grade TB and lymphovascular embolization (LVE), tumor necrosis, and grade of HCC with P = 0.003, 0.036, and 0.017, respectively. The positive TILs group showed a statistically significant correlation with histological grade, LVE, and serum alpha-fetoprotein (AFP) level with P = 0.002, 0.006, and 0.043, respectively. Multivariate analysis using the Cox proportional hazard model revealed that TILs are not an independent pathological factor for disease-free and OS, although TB is an independent pathological factor for both. Conclusions In all HCC patients, TB was seen, and there was a significant link between the grade of the HCC and the presence of tumor necrosis, LVE, and high-grade TB. The majority (92%) of HCC patients had TILs, and there was a strong relationship between the histological grade, LVE, and serum AFP level. While TILs show variation of the immunologic reaction to the tumor, TB tends to suggest a hostile biologic nature and a bad prognosis.
Collapse
Affiliation(s)
- Ahmed Mahran Shafiq
- Department of Medical Oncology and Hematological Malignancies, South Egypt Cancer Institute, Assiut University, Assiut, Egypt
| | - Noura Ali Taha
- Department of Medical Oncology and Hematological Malignancies, South Egypt Cancer Institute, Assiut University, Assiut, Egypt
| | - Amen Hamdy Zaky
- Department of Medical Oncology and Hematological Malignancies, South Egypt Cancer Institute, Assiut University, Assiut, Egypt
| | - Abdallah Hedia Mohammed
- Department of Medical Oncology and Hematological Malignancies, South Egypt Cancer Institute, Assiut University, Assiut, Egypt
| | - Ola M. Omran
- Department of Pathology, Faculty of Medicine, Assiut University, Assiut, Egypt
- Department of Pathology, College of Medicine, Qassim University, Buraidah, Qassim Region, Saudi Arabia
| | - Lobaina Abozaid
- Department of Pathology, College of Medicine, Qassim University, Buraidah, Qassim Region, Saudi Arabia
| | - Hagir H. T. Ahmed
- Department of Pathology, College of Medicine, Qassim University, Buraidah, Qassim Region, Saudi Arabia
| | - Mahmoud Gamal Ameen
- Department of Oncologic Pathology, South Egypt Cancer Institute, Assiut University, Assiut Egypt
| |
Collapse
|
6
|
Gomaa A, Gomaa M, Allam N, Waked I. Hepatitis C Elimination in Egypt: Story of Success. Pathogens 2024; 13:681. [PMID: 39204281 PMCID: PMC11357586 DOI: 10.3390/pathogens13080681] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Revised: 08/06/2024] [Accepted: 08/09/2024] [Indexed: 09/03/2024] Open
Abstract
Egypt has long been overwhelmed by the hepatitis C virus (HCV) infection, and it used to be the country with the world's highest prevalence rates. The disease had been a significant public health problem, affecting millions of Egyptians and posing severe economic and social challenges. By the early 2000s, it was estimated that around 10% of the Egyptian population was infected with HCV. However, in recent years, with the availability of direct-acting antiviral therapies, the country has made enormous steps in combating this public health threat. The combination of innovative health strategies and political will enabled Egypt to establish a successful model of care for HCV management and to be the first country to eliminate hepatitis C, setting a model for the rest of the world. In 2023, Egypt became the first country to fulfill the World Health Organization's set programmatic criteria of reduction of hepatitis C incidence and mortalities to levels close to elimination of disease or achieve the "gold tier" status on the path to disease elimination.
Collapse
Affiliation(s)
- Asmaa Gomaa
- Hepatology and Gastroenterology Department, National Liver Institute, Menofia University, Shebin El-Kom 32511, Egypt; (A.G.); (N.A.)
| | - Mohamed Gomaa
- Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC J1H 5N4, Canada;
| | - Naglaa Allam
- Hepatology and Gastroenterology Department, National Liver Institute, Menofia University, Shebin El-Kom 32511, Egypt; (A.G.); (N.A.)
| | - Imam Waked
- Hepatology and Gastroenterology Department, National Liver Institute, Menofia University, Shebin El-Kom 32511, Egypt; (A.G.); (N.A.)
| |
Collapse
|
7
|
Abdelhamed W, El-Kassas M. Hepatitis B virus in Egypt: the whole story. EGYPTIAN LIVER JOURNAL 2024; 14:56. [DOI: 10.1186/s43066-024-00362-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Accepted: 07/03/2024] [Indexed: 04/03/2025] Open
Abstract
AbstractHepatitis B virus (HBV) infection is a significant global public health threat with variable geographical distribution. Chronic infection with HBV could be complicated by chronic hepatitis state, progression to liver cirrhosis, and the development of hepatocellular carcinoma (HCC). For years, the magnitude of HBV problem in Egypt was masked by the great prevalence of hepatitis C virus in the country. The exact epidemiological data regarding HBV in Egypt are defective. The prevalence rate of HBV in Egypt has declined after the universal immunization program introduced for infants in 1992. This review addresses the whole story of HBV in Egypt: the epidemiology, risk factors, vaccination programs, and treatment efforts.
Collapse
|
8
|
Ibrahim AM, Wahba NMI, Zaghamir DEF, Mersal NA, Mersal FA, Ali RAES, Eltaib FA, Mohamed HAH. Impact of a comprehensive rehabilitation palliative care program on the quality of life of patients with terminal cancer and their informal caregivers: a quasi-experimental study. BMC Nurs 2024; 23:357. [PMID: 38812027 PMCID: PMC11138029 DOI: 10.1186/s12912-024-02028-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2023] [Accepted: 05/20/2024] [Indexed: 05/31/2024] Open
Abstract
BACKGROUND Palliative care schemes, which include pain management, symptom control, psychosocial support and rehabilitation, aim to boost patients' quality of life, ease the burden and anxiety of informal caregivers, and ultimately provide a comprehensive approach to enhance well-being during this challenging and sensitive period. This study aims to evaluate the impact of a comprehensive rehabilitation palliative care program on the quality of life of patients with terminal cancer and their informal caregivers. METHODS This quasi-experimental study, conducted from August 2023 to January 2024 at outpatient clinics affiliated with the Oncology Center at Mansoura University, Egypt, focused on cancer patients and their caregivers in the palliative care department. Employing pre- and post-test phases, data were gathered using a questionnaire, EORTC QLQ C30, Hospital Anxiety and Depression Scale, Short Form Health Survey, Caregiver Burden Inventory, and Beck Anxiety Inventory. The investigation evaluated a 16-week rehabilitation program comprising exercise, psychoeducation, individual counselling, and spiritual support. Exercises, led by a physiotherapist, targeted fatigue and stress through tailored aerobic and resistance training. Psychoeducation sessions aimed to bolster coping abilities, covering fatigue management and nutrition. Trained counsellors addressed spiritual and existential concerns. Personal advisory sessions were available for individual support. Caregivers received education on rehabilitation and palliative care protocols, ensuring comprehensive patient care. RESULTS The mean age for cancer patients was 65.79 ± 13.85. In contrast, the mean age for primary carers was 42.05 ± 11.15. The QOL for cancer patients during the pre-test phase was 77.8 ± 7.16 and rose to 87.34 ± 14.56 during the post-test phase. Additionally, the total anxiety level of patients before the rehabilitation palliative care program was conducted was 15.45 ± 3.05 compared to 6.12 ± 3.21 after the post test phase. Furthermore, the total depression levels of the patients during the pre-test phase were 20.89 ± 9.21. However, after implementing the rehabilitation palliative care program, it decreased to 15.5 ± 6.86. In regards to the total quality of life of informal caregivers, it was measured at 67.28 ± 32.09 before conducting the program. Nevertheless, it increased to 25.95 ± 40.29 after conducting it. Additionally, the total Caregiver Burden Inventory before implementing the program was 37.45 ± 25.7, and it decreased to 29.36 ± 16.4 after conducting it. Additionally, the total score on the Beck Anxiety Inventory decreased from 45.7 ± 4.3 during the initial testing phase to 17.35 ± 23.67. CONCLUSION The program for rehabilitation palliative care successfully achieved its goals by enhancing the overall quality of life for cancer patients and their caregivers. Additionally, it reduced the anxiety and depression levels among the patients, as well as the anxiety and caregiver burden among the caregivers. Continue research into the effectiveness of rehabilitation palliative care programs to identify best practices, improve existing programs, and expand access to these services.
Collapse
Affiliation(s)
- Ateya Megahed Ibrahim
- College of Nursing, Prince Sattam Bin Abdulaziz University, Al-Kharj, 11942, Saudi Arabia.
- Family and Community Health Nursing Department, Faculty of nursing, Port Said University, Port Said, 42526, Egypt.
| | - Nadia Mohamed Ibrahim Wahba
- College of Nursing, Prince Sattam Bin Abdulaziz University, Al-Kharj, 11942, Saudi Arabia
- Psychiatric Nursing and Mental Health Department, Faculty of Nursing, Port Said University, Port Said, 42526, Egypt
| | - Donia Elsaid Fathi Zaghamir
- College of Nursing, Prince Sattam Bin Abdulaziz University, Al-Kharj, 11942, Saudi Arabia
- Pediatric Nursing Department, Faculty of Nursing, Port Said University, Port Said, 42526, Egypt
| | - Nahed Ahmed Mersal
- Medical Surgical Nursing, Faculty of Nursing, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Fathia Ahmed Mersal
- Community Health Nursing Department, College of Nursing, Northern Border University, Arar, Saudi Arabia
| | - Rasmia Abd El-Sattar Ali
- Community Health Nursing Department, College of Nursing, Northern Border University, Arar, Saudi Arabia
| | - Fatma Abdou Eltaib
- Medical Surgical Nursing Department, Faculty of Nursing, Ain Shams University, Cairo, Egypt
| | - Heba Ali Hamed Mohamed
- Community Health Nursing Department, Faculty of Nursing, Mansoura University, Mansoura city, Dakahlia, Egypt
| |
Collapse
|
9
|
Sallam M, Khalil R. Contemporary Insights into Hepatitis C Virus: A Comprehensive Review. Microorganisms 2024; 12:1035. [PMID: 38930417 PMCID: PMC11205832 DOI: 10.3390/microorganisms12061035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 05/15/2024] [Accepted: 05/20/2024] [Indexed: 06/28/2024] Open
Abstract
Hepatitis C virus (HCV) remains a significant global health challenge. Approximately 50 million people were living with chronic hepatitis C based on the World Health Organization as of 2024, contributing extensively to global morbidity and mortality. The advent and approval of several direct-acting antiviral (DAA) regimens significantly improved HCV treatment, offering potentially high rates of cure for chronic hepatitis C. However, the promising aim of eventual HCV eradication remains challenging. Key challenges include the variability in DAA access across different regions, slightly variable response rates to DAAs across diverse patient populations and HCV genotypes/subtypes, and the emergence of resistance-associated substitutions (RASs), potentially conferring resistance to DAAs. Therefore, periodic reassessment of current HCV knowledge is needed. An up-to-date review on HCV is also necessitated based on the observed shifts in HCV epidemiological trends, continuous development and approval of therapeutic strategies, and changes in public health policies. Thus, the current comprehensive review aimed to integrate the latest knowledge on the epidemiology, pathophysiology, diagnostic approaches, treatment options and preventive strategies for HCV, with a particular focus on the current challenges associated with RASs and ongoing efforts in vaccine development. This review sought to provide healthcare professionals, researchers, and policymakers with the necessary insights to address the HCV burden more effectively. We aimed to highlight the progress made in managing and preventing HCV infection and to highlight the persistent barriers challenging the prevention of HCV infection. The overarching goal was to align with global health objectives towards reducing the burden of chronic hepatitis, aiming for its eventual elimination as a public health threat by 2030.
Collapse
Affiliation(s)
- Malik Sallam
- Department of Pathology, Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman 11942, Jordan
- Department of Clinical Laboratories and Forensic Medicine, Jordan University Hospital, Amman 11942, Jordan
| | - Roaa Khalil
- Department of Pathology, Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman 11942, Jordan
| |
Collapse
|
10
|
Elbadry M, Badawi M, Youssef N, Duracinsky M, Saleh SA, Funk A, Elessawy H, Rumpler E, Sayed K, Vasiliu A, Madec Y, Fontanet A, El-Kassas M. Impact of treating chronic hepatitis C with direct acting antivirals on health-related quality of life: a real-life Egyptian experience. EGYPTIAN LIVER JOURNAL 2024; 14:14. [DOI: 10.1186/s43066-024-00317-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Accepted: 02/14/2024] [Indexed: 04/03/2025] Open
Abstract
Abstract
Background
Chronic hepatitis C virus (HCV) infection negatively impacts health-related quality of life (HRQL). We aimed to assess patient-reported outcomes (PROs) to evaluate the impact of treating chronic HCV with directly acting antivirals (DAAs) on HRQL.
Methods
PROs were assessed prospectively using the PROQOL-HCV questionnaire before (week 0), at the end (week 12), and after DAA treatment at week 24. HRQL was measured in six different dimensions: physical health, emotional health, future uncertainty, intimate relationships, social health, and cognitive functions.
Results
A total of 500 HCV patients receiving DAAs were enrolled; of them, 399 were included in the analysis (median age 57 years, 59% females). HRQL increased significantly between baseline, end of treatment, and week 24 for all dimensions (P < 0.001), more often for physical health in females compared to males (OR = 1.69, 95% CI = 1.1–2.5), for future uncertainty among people with diabetes (1.75, 95% CI = 1.05–2.9), and for cognitive functions among obese patients (OR = 1.98; 95% CI = 1.1–3.3). Improvement in HRQL was less common for intimate relations among females (OR = 0.47; 95% CI = 0.3–0.7) and in patients with cirrhosis (OR = 0.35, 95% CI = 0.1–0.7). Improvement in HRQL was consistently higher in < 60 years compared to ≥ 60 years patients, with a significant difference in social health (P < 0.001) and future uncertainty (P < 0.049) HRQL domains.
Conclusion
HRQL improved with DAA therapy, a relation consistent across all HRQL dimensions up to 12 weeks after the end of treatment.
Collapse
|
11
|
Henriot P, Anwar WA, El Gaafary M, Abdo S, Rafik M, Hussein WM, Sos D, Magdy I, Jean K, Temime L. Preventing iatrogenic HCV infection: A quantitative risk assessment based on observational data in an Egyptian hospital. PLOS GLOBAL PUBLIC HEALTH 2024; 4:e0002821. [PMID: 38358962 PMCID: PMC10868760 DOI: 10.1371/journal.pgph.0002821] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Accepted: 01/25/2024] [Indexed: 02/17/2024]
Abstract
When compliance with infection control recommendations is non-optimal, hospitals may play an important role in hepatitis C (HCV) transmission. However, few studies have analyzed the nosocomial HCV acquisition risk based on detailed empirical data. Here, we used data from a prospective cohort study conducted on 500 patients in the Ain Shams hospital (Cairo, Egypt) in 2017 with the objective of identifying (i) high-risk patient profiles and (ii) transmission hotspots within the hospital. Data included information on patient HCV status upon admission, their trajectories between wards and the invasive procedures they underwent. We first performed a sequence analysis to identify different hospitalization profiles. Second, we estimated each patient's individual risk of HCV acquisition based on ward-specific prevalence and procedures undergone, and risk hotspots by computing ward-level risks. Then, using a beta regression model, we evaluated upon-admission factors linked to HCV acquisition risk and built a score estimating the risk of HCV infection during hospitalization based on these factors. Finally, we assessed and compared ward-focused and patient-focused HCV control strategies. The sequence analysis based on patient trajectories allowed us to identify four distinct patient trajectory profiles. The risk of HCV infection was greater in the internal medicine department, compared to the surgery department (0·188% [0·142%-0·235%] vs. 0·043%, CI 95%: [0·036%-0·050%]), with risk hotspots in the geriatric, tropical medicine and intensive-care wards. Upon-admission risk predictors included source of admission, age, reason for hospitalization, and medical history. Interventions focused on the most at-risk patients were most effective to reduce HCV infection risk. Our results might help reduce the risk of HCV acquisition during hospitalization in Egypt by targeting enhanced control measures to ward-level transmission hotspots and to at-risk patients identified upon admission.
Collapse
Affiliation(s)
- Paul Henriot
- MESuRS Laboratory, Conservatoire national des arts et métiers, Paris, France
- PACRI Unit, Conservatoire national des arts et métiers, Institut Pasteur, Paris, France
| | - Wagida A. Anwar
- Department of Community, Environmental and Occupational Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Maha El Gaafary
- Department of Community, Environmental and Occupational Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Samia Abdo
- Department of Clinical Pathology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mona Rafik
- Department of Clinical Pathology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Wafaa M. Hussein
- Department of Community, Environmental and Occupational Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Dalia Sos
- Department of Community, Environmental and Occupational Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Isis Magdy
- Department of Community, Environmental and Occupational Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Kévin Jean
- MESuRS Laboratory, Conservatoire national des arts et métiers, Paris, France
- PACRI Unit, Conservatoire national des arts et métiers, Institut Pasteur, Paris, France
| | - Laura Temime
- MESuRS Laboratory, Conservatoire national des arts et métiers, Paris, France
- PACRI Unit, Conservatoire national des arts et métiers, Institut Pasteur, Paris, France
| |
Collapse
|
12
|
Ahmed S, Méndez RY, Naveed S, Akhter S, Mushtaque I, Malik MA, Ahmad W, Figueroa RN, Younas A. Assessment of hepatitis-related knowledge, attitudes, and practices on quality of life with the moderating role of internalized stigma among hepatitis B-positive patients in Pakistan. Health Psychol Behav Med 2023; 11:2192782. [PMID: 37008419 PMCID: PMC10064821 DOI: 10.1080/21642850.2023.2192782] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/01/2023] Open
Abstract
Aim This study aimed to assess the Pakistani hepatitis B patients' knowledge, attitudes, and practices towards hepatitis management and the impact of self-management on the quality of life of hepatitis B patients as well as the moderating role of stigmatization. Methods A cross-sectional study design was used, and the data was collected from a total of 432 hepatitis B positive patients through a self-designed questionnaire. The studied subjects consisted of men (n = 205, 47%), women (n = 165, 38%), and transgender (n = 62, 14%). The obtained data were statistically analyzed using SPSS software version 26.0 for Windows. Results The mean age of the study participants was 48. Knowledge has a significant positive relationship with hepatitis self-management and quality of life, whereas knowledge has a negative relationship with stigmatization. Furthermore, multivariate analysis revealed that men were more knowledgeable about the disease than women and transgender people (6.14 ± 2.08 vs. 3.23 ± 1.61 vs. 1.03 ± 0.73, F = 8.2**, p = .000). On the scale of attitude and practice, significant gender differences were found. Women had more experience with hepatitis self-management than men or transgender (4.21 ± 13.0 vs. 2.17 ± 6.02 vs. 0.37 ± 0.31, F = 6.21**, p = .000). The regression analysis showed that self-management has a positive association with quality of life (B = 0.36, p = .001). The moderation analysis revealed that stigmatization negatively moderates the relationship between self-management and quality of life (B = -0.53, p = .001). Conclusion Generally, patients had good knowledge about the disease and its self-management. However, a societal and community-level awareness campaign should be organized on the quality of life and stigmatization of people with chronic illness regarding their human rights, dignity, and physical, mental, and social well-being.
Collapse
|
13
|
Zheng W, Li H, Yang X, Wang L, Shi Y, Shan H, He L, Liu J, Chen H, Wang G, Zhao Y, Han C. Trends and prediction in the incidence rate of hepatitis C in Shandong Province in China from 2004 to 2030. Prev Med 2023; 177:107749. [PMID: 37918447 DOI: 10.1016/j.ypmed.2023.107749] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Revised: 10/28/2023] [Accepted: 10/30/2023] [Indexed: 11/04/2023]
Abstract
BACKGROUND Hepatitis C threatens human health and brings a heavy economic burden. Shandong Province is the second most populous province in China and has uneven regional economic development. Therefore, we analyzed the incidence rate trend and regional differences of hepatitis C in Shandong Province from 2004 to 2021. METHODS The monthly and annual incidence rates of hepatitis C in Shandong Province from 2022 to 2030 were predicted by fitting Autoregressive Integrated Moving Average model (ARIMA), Long Short-Term Memory (LSTM) and ARIMA-LSTM combined model. RESULTS From 2004 to 2021, annual new cases of hepatitis C in Shandong Province increased from 635 to 5834, with a total of 61,707 cases. The incidence rate increased from 0.69/100 thousand in 2004 to 6.40/100 thousand in 2019, with a slight decrease in 2020 and 2021. The average annual incidence rate was 3.47/100 thousand. In terms of regional distribution, the hepatitis C incidence rate in Shandong Province was generally high in the west and low in the east. It is estimated that the hepatitis C incidence rate in Shandong Province will be 9.21 per 100 thousand in 2030. CONCLUSION The hepatitis C incidence rate in Shandong Province showed an increasing trend from 2004 to 2019 and a decreasing trend in 2020 and 2021. Significant regional variations in incidence rate existed. An upward trend in incidence rate is predicted from 2022 to 2030. It is necessary to strengthen the prevention and control of hepatitis C to achieve the goal of eliminating viral hepatitis by 2030.
Collapse
Affiliation(s)
- Wanying Zheng
- School of Public Health and Management, Binzhou Medical University, Yantai, Shandong 264003, China
| | - Hongyu Li
- School of Public Health and Management, Binzhou Medical University, Yantai, Shandong 264003, China
| | - Xingguang Yang
- Shandong Center for Disease Control and Prevention, Jinan, Shandong 250013, China
| | - Luyang Wang
- School of Public Health and Management, Binzhou Medical University, Yantai, Shandong 264003, China
| | - Yukun Shi
- School of Public Health and Management, Binzhou Medical University, Yantai, Shandong 264003, China
| | - Haifeng Shan
- Zibo Mental Health Center, Zibo, Shandong, 255100, China
| | - Lianping He
- School of medicine, Taizhou University, Taizhou, Zhejiang 318000, China
| | - Junyan Liu
- School of Public Health and Management, Binzhou Medical University, Yantai, Shandong 264003, China
| | - Haotian Chen
- School of Public Health and Management, Binzhou Medical University, Yantai, Shandong 264003, China
| | - Guangcheng Wang
- School of Public Health and Management, Binzhou Medical University, Yantai, Shandong 264003, China
| | - Yang Zhao
- The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia; Digital Health and Stroke Program, The George Institute for Global Health, Beijing, China.
| | - Chunlei Han
- School of Public Health and Management, Binzhou Medical University, Yantai, Shandong 264003, China.
| |
Collapse
|
14
|
Sweed D, Holah NS, Karman E, Asaad N, Mahmoud S. Farnesoid X receptor in chronic liver diseases: an immunohistochemical study. J Immunoassay Immunochem 2023; 44:381-395. [PMID: 37665366 DOI: 10.1080/15321819.2023.2242920] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/05/2023]
Abstract
Chronic hepatitis C virus (HCV) related liver diseases are still an ongoing cause of hepatic failure despite the effective role of direct-acting anti-viral agents. Farnesoid X receptor (FXR) agonists have a potential therapeutic effect on the management of chronic liver diseases (CLD). However, data regarding FXR protein expression in human CLDs are limited and conflicting. We aimed to assess the immunohistochemical expression of FXR in HCV-related chronic hepatitis and cirrhosis in comparison with metabolic-associated fatty liver disease (MAFLD) and normal liver tissue. The expression of FXR was low both in hepatocytes and bile ducts of HCV-related chronic hepatitis and cirrhosis (p = .001, respectively). In addition, a significantly low expression of FXR was observed in HCV-related hepatitis and cirrhosis groups compared to MAFLD in hepatocytes (p < .001, for both) and bile ducts (p = .004 and p = .018). FXR expression in HCV-related cirrhosis was significantly associated with compensated liver function (p = .032) and low inflammatory activity (p = .022). FXR expression decreases in HCV-related CLDs. There was some evidence that FXR expression could protect against post-hepatitis cirrhosis.
Collapse
Affiliation(s)
- Dina Sweed
- Pathology Department, National Liver Institute, Menofia University, Shebin Elkom, Egypt
| | - Nanis Shawky Holah
- Pathology Department, Faculty of Medicine, Menofia University, Shebin Elkom, Egypt
| | - Esraa Karman
- Pathology Department, National Liver Institute, Menofia University, Shebin Elkom, Egypt
| | - Nancy Asaad
- Pathology Department, Faculty of Medicine, Menofia University, Shebin Elkom, Egypt
| | - Shereen Mahmoud
- Pathology Department, Faculty of Medicine, Menofia University, Shebin Elkom, Egypt
| |
Collapse
|
15
|
Abdelsattar S, Fahim SA, Kamel HFM, Al-Amodi H, Kasemy ZA, Khalil FO, Abdallah MS, Bedair HM, Gadallah ANAA, Sabry A, Sakr MA, Selim M, Gayed EMAE. The Potential Role of Circulating Long Miscellaneous RNAs in the Diagnosis and Prognosis of Hepatitis C Related Hepatocellular Carcinoma. Noncoding RNA 2023; 9:62. [PMID: 37888208 PMCID: PMC10609931 DOI: 10.3390/ncrna9050062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2023] [Revised: 10/04/2023] [Accepted: 10/08/2023] [Indexed: 10/28/2023] Open
Abstract
Ribonucleic acids (RNAs) are important regulators of gene expression and crucial for the progression of hepatocellular carcinoma (HCC). This study was designed to determine the diagnostic and prognostic utility of the circulating long miscellaneous RNAs; LINC01419, AK021443, and AF070632 in HCV-related HCC patients. Real-time PCR was used to measure their relative expression levels in the plasma of 194 HCV patients, 120 HCV-related HCC patients and 120 healthy controls. LINC01419 and AK021443 expression levels had significantly increasing linear trend estimates while AF070632 was dramatically downregulated in HCC compared to HCV. Interestingly, LINC01419 and AK021443 served as more significant diagnostic biomarkers for HCC than AF070632 and AFP. Multivariate analysis with cox regression revealed that the high expression of AK021443 [HR = 10.06, CI95%: 3.36-30.07], the high expression of LINC01419 [HR 4.13, CI95%: 1.32-12.86], and the low expression of AF070632 [HR = 2.70, CI95%: 1.07-6.81] were significant potential prognostic factors for HCC. Besides, the Kaplan-Meier analysis showed that HCC patients with high LIN01419 and AK021443 and low AF070632 expression levels had shorter OS. The circulating LINC01419 and AK021443 can be used as noninvasive potential biomarkers for diagnosis and prognosis of HCV-related HCC patients than AF070632 providing new targets for limiting the progression of the disease.
Collapse
Affiliation(s)
- Shimaa Abdelsattar
- Clinical Biochemistry and Molecular Diagnostics Department, National Liver Institute, Menoufia University, Shebin El-Kom 32511, Egypt
| | - Sally A. Fahim
- Biochemistry Department, School of Pharmacy, Newgiza University (NGU), Cairo 94114, Egypt;
| | - Hala F. M. Kamel
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt;
- Biochemistry Department, Faculty of Medicine, Umm Al-Qura University, Makkah 21955, Saudi Arabia;
| | - Hiba Al-Amodi
- Biochemistry Department, Faculty of Medicine, Umm Al-Qura University, Makkah 21955, Saudi Arabia;
| | - Zeinab A. Kasemy
- Department of Public Health and Community Medicine, Faculty of Medicine, Menoufia University, Shebin El-Kom 32511, Egypt;
| | - Fatma O. Khalil
- Clinical Microbiology and Immunology Department, National Liver Institute, Menoufia University, Shebin El-Kom 32511, Egypt;
| | - Mahmoud S. Abdallah
- Clinical Pharmacy Department, Faculty of Pharmacy, University of Sadat City (USC), Sadat City 32897, Egypt;
| | - Hanan M. Bedair
- Clinical Pathology Department, National Liver Institute, Menoufia University, Shebin El-Kom 32511, Egypt;
| | | | - Aliaa Sabry
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebin El-Kom 32511, Egypt;
| | - Mohamed A. Sakr
- Medical Microbiology and Immunology Department, Faculty of Medicine, Suez University, Suez 43512, Egypt;
| | - Mahmoud Selim
- Internal Medicine Department, Faculty of Medicine, Tanta University, Tanta 31111, Egypt;
| | - Eman M. Abd El Gayed
- Medical Biochemistry and Molecular Biology, Faculty of Medicine, Menoufia University, Shebin El-Kom 32511, Egypt;
| |
Collapse
|
16
|
Header DA, Ellakany WI, Ellakany AI. Fecal calprotectin level as a marker of esophageal varices in Egyptian HCV cirrhotic patients. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2023; 88:333-340. [PMID: 35810088 DOI: 10.1016/j.rgmxen.2022.06.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Accepted: 11/03/2021] [Indexed: 11/23/2022]
Abstract
INTRODUCTION AND AIM Esophageal varices are one of the complications of portal hypertension in cirrhotic patients that lead to high morbidity and mortality. Our aim was to assess the fecal calprotectin (FC) level in Egyptian cirrhotic patients as a non-invasive marker for the presence of esophageal varices. MATERIALS AND METHODS The current study included 250 participants in the period from June 2019 to November 2020, divided into three groups: group 1: 100 HCV cirrhotic patients with esophageal varices that would then be subdivided, according to the Paquet classification; group 2: 100 HCV cirrhotic patients without esophageal varices; group 3: 50 normal age and sex-matched healthy subjects as the control group. Patients with other causes of abnormal calprotectin results were excluded. RESULTS The comparison of FC in the three study groups revealed a statistically significant difference, with FC levels higher in groups 1 and 2 (mean 66.4±10.41 and 48.4±10.92, respectively). There was a significant difference in FC levels between the subgroups, subdivided according to the Paquet classification (P=.001). FC levels were higher in the grade III and IV subgroups. FC in the diagnosis of HCV cirrhotic patients with esophageal varices showed the best performance when the cut-off value was >55; AUC was 0.918, with 92% sensitivity, 95% specificity, and 93% accuracy. CONCLUSION FC levels serve as a screening tool for esophageal varices. FC was higher in cirrhotic patients with esophageal varices, especially in the grade III and IV subgroups, according to the Paquet classification.
Collapse
Affiliation(s)
- D A Header
- Departamento de Medicina Interna, Facultad de Medicina, Universidad de Alejandría, Alejandría, Egypt.
| | - W I Ellakany
- Departamento de Medicina Tropical, Facultad de Medicina, Universidad de Alejandría, Alejandría, Egypt
| | - A I Ellakany
- Departamento de Medicina Interna, Facultad de Medicina, Universidad de Alejandría, Alejandría, Egypt
| |
Collapse
|
17
|
Elabd WK, Elbakry MMM, Hassany M, Baki AA, Seoudi DM, El Azeem EMA. Evaluation of miRNA-7, miRNA-10 and miRNA-21 as diagnostic non-invasive biomarkers of hepatocellular carcinoma. Clin Exp Hepatol 2023; 9:221-227. [PMID: 37790691 PMCID: PMC10544064 DOI: 10.5114/ceh.2023.130547] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Accepted: 07/02/2023] [Indexed: 10/05/2023] Open
Abstract
Aim of the study Liver cancer (hepatocellular carcinoma - HCC) remains a serious health challenge; it is the fourth leading cause of death worldwide. Egypt ranks fifteenth worldwide and the third in Africa in terms of HCC burden. The present study aimed to assess some microRNAs (miRNAs) including miRNA-7, miRNA-10, and miRNA-21, serum markers such as cluster of differentiation-14 (CD-14) and transforming growth factor b1 (TGF-b1), and other biochemical parameters as non-invasive tools for HCC diagnosis. Material and methods The study included 100 participants divided into five groups: group I (20 normal subjects as a healthy group), group II (20 participants with chronic HCV infection but non-cirrhotic), group III (20 volunteers with chronic HCV infection and compensated cirrhosis), group IV (20 patients with chronic HCV infection and decompensated cirrhosis), and group V (20 participants with HCC). Levels of miR-7, miR-10, and miR-21 were evaluated using qRT-PCR. Serum ALT, AST, total bilirubin, total protein, albumin, PT, INR, and platelet count were determined. FIB-4 and APRI test levels were also calculated. CD-14 and TGF-β1 serum levels were estimated using enzyme-linked immunosorbent assay (ELISA) kits. Results The expression levels of miR-21 followed by miR-10 showed high sensitivity and specificity in predicting HCC. Serum CD-14 and TGF-b1 levels were significantly increased in all patient groups. Conclusions From the study, it is concluded that the expression level of miR-21 has the highest sensitivity and specificity, followed by miR-10, which has high sensitivity and low specificity as non-invasive markers for HCC detection, while miR-7 exhibits high sensitivity and reasonable specificity in fibrosis detection.
Collapse
Affiliation(s)
| | | | - Mohamed Hassany
- National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Amin Abdel Baki
- National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | | | | |
Collapse
|
18
|
Elsalahaty MI, Salama AF, Diab T, Ghazy M, Toraih E, Elshazli RM. Unleash Multifunctional Role of miRNA Biogenesis Gene Variants ( XPO5*rs34324334 and RAN*rs14035) with Susceptibility to Hepatocellular Carcinoma. J Pers Med 2023; 13:959. [PMID: 37373948 DOI: 10.3390/jpm13060959] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Revised: 06/02/2023] [Accepted: 06/05/2023] [Indexed: 06/29/2023] Open
Abstract
Numerous reports have explored the roles of different genetic variants in miRNA biogenesis mechanisms and the progression of various types of carcinomas. The goal of this study is to explore the association between XPO5*rs34324334 and RAN*rs14035 gene variants and susceptibility to hepatocellular carcinoma (HCC). In a cohort of 234 participants (107 HCC patients and 127 unrelated cancer-free controls) from the same geographic region, we characterized allelic discrimination using PCR-RFLP and performed subgroup analysis and multivariate regression. We found that the frequency of the XPO5*rs34324334 (A) variant was correlated with elevated risk of HCC under allelic (OR = 10.09, p-value < 0.001), recessive (OR = 24.1, p-value < 0.001), and dominant (OR = 10.1, p-value < 0.001) models. A/A genotype was associated with hepatitis C cirrhosis (p-value = 0.012), ascites (p-value = 0.003), and higher levels of alpha-fetoproteins (p-value = 0.011). Carriers of the RAN*rs14035 (T) variant were more likely to develop HCC under allelic (OR = 1.76, p-value = 0.003) and recessive (OR = 3.27, p-value < 0.001) models. Our results suggest that XPO5*rs34324334 and RAN*rs14035 variants are independent risk factors for developing HCC.
Collapse
Affiliation(s)
- Mohamed I Elsalahaty
- Biochemistry Division, Department of Chemistry, Faculty of Science, Tanta University, Tanta 31527, Egypt
| | - Afrah F Salama
- Biochemistry Division, Department of Chemistry, Faculty of Science, Tanta University, Tanta 31527, Egypt
| | - Thoria Diab
- Biochemistry Division, Department of Chemistry, Faculty of Science, Tanta University, Tanta 31527, Egypt
| | - Medhat Ghazy
- Department of Internal Medicine, Faculty of Medicine, Tanta University, Tanta 31527, Egypt
| | - Eman Toraih
- Endocrine and Oncology Division, Department of Surgery, School of Medicine, Tulane University, New Orleans, LA 70112, USA
- Department of Histology and Cell Biology, Genetics Unit, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt
| | - Rami M Elshazli
- Biochemistry and Molecular Genetics Unit, Department of Basic Sciences, Faculty of Physical Therapy, Horus University-Egypt, New Damietta 34517, Egypt
| |
Collapse
|
19
|
Mahmoud SA, Abdel-Aziz MM, Khafaga RHM, Hafez HA, Kamel MA, Shaker SA. The pre-conception maternal exposure to Sofosbuvir affects the mitochondrial biogenesis in prenatal fetal tissues: Experimental study on rats. Mol Med 2023; 29:71. [PMID: 37280507 PMCID: PMC10243043 DOI: 10.1186/s10020-023-00666-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Accepted: 05/19/2023] [Indexed: 06/08/2023] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) infection is a global public health problem and Egypt has the highest HCV prevalence worldwide. Hence, global efforts target to eliminate HCV by 2030. Sofosbuvir is a nucleotide analogue inhibitor of HCV polymerase essential for viral replication. Animal studies prove that Sofosbuvir metabolites cross the placenta and are excreted in the milk of nursing animals. We aimed to investigate the possible effects of preconception maternal exposure to Sofosbuvir on mitochondrial biogenesis in prenatal fetal liver, skeletal muscle, and placental tissues. METHODS The study was conducted on 20 female albino rats divided into a control group receiving a placebo and an exposed group receiving 4 mg/kg orally/day for 3 months of Sofosbuvir. At the end of the treatment period, pregnancy was induced in both groups by mating with healthy male rats overnight. At gestational day 17, all pregnant female rats were sacrificed. Each fetus was dissected to obtain the fetal liver, skeletal muscle, and placental tissues. RESULTS The results of our study indicated that the exposure of young female rats to Sofosbuvir affects pregnancy outcomes. Fetal liver and muscle showed lower mitochondrial DNA-copy number (mtDNA-CN) by about 24% and 29% respectively, peroxisome proliferator-activated receptor-gamma coactivator-1 alpha and its downstream targets; nuclear respiratory factor-1 and mitochondrial transcription factor A. While the placental tissues showed different patterns, particularly elevated in mtDNA-CN by about 43%. CONCLUSIONS The study provides preliminary evidence of the detrimental effects of Sofosbuvir on the pregnancy outcomes of the exposed females and may impair the placental and fetal organs' development. These effects may be mediated through modulating mitochondrial homeostasis and functions.
Collapse
Affiliation(s)
- Shimaa A Mahmoud
- Department of Biochemistry, Medical Research Institute, Alexandria University, 165 El-Horreya Avenue, EL-Hadara, P.O. Box 21561, Alexandria, Egypt.
| | - Maryam M Abdel-Aziz
- Department of Biochemistry, Medical Research Institute, Alexandria University, 165 El-Horreya Avenue, EL-Hadara, P.O. Box 21561, Alexandria, Egypt
| | - Rana H M Khafaga
- Department of Biochemistry, Medical Research Institute, Alexandria University, 165 El-Horreya Avenue, EL-Hadara, P.O. Box 21561, Alexandria, Egypt
| | - Hala A Hafez
- Department of Biochemistry, Medical Research Institute, Alexandria University, 165 El-Horreya Avenue, EL-Hadara, P.O. Box 21561, Alexandria, Egypt
| | - Maher A Kamel
- Department of Biochemistry, Medical Research Institute, Alexandria University, 165 El-Horreya Avenue, EL-Hadara, P.O. Box 21561, Alexandria, Egypt
| | - Sara A Shaker
- Department of Biochemistry, Medical Research Institute, Alexandria University, 165 El-Horreya Avenue, EL-Hadara, P.O. Box 21561, Alexandria, Egypt
| |
Collapse
|
20
|
El-Marakby MG, Solayman MH, Sabri NA. Evaluation of the Safety Profile of Direct-Acting Antivirals on Patients with Hepatitis C Virus: A Pharmacovigilance Study. Ther Innov Regul Sci 2023:10.1007/s43441-023-00537-x. [PMID: 37227588 PMCID: PMC10400676 DOI: 10.1007/s43441-023-00537-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Accepted: 05/05/2023] [Indexed: 05/26/2023]
Abstract
BACKGROUND Hepatitis C virus (HCV) is the primary contributor to chronic hepatic diseases. A rapid change in the situation took place with the advent of oral direct-acting antivirals (DAAs). However, a comprehensive review of the adverse event (AE) profile of the DAAs is lacking. This cross-sectional study aimed to analyze the reported Adverse Drug Reactions (ADRs) with DAA treatment using data from VigiBase, the WHO Individual Case Safety Report (ICSR) database. METHODS All ICSRs reported to VigiBase with sofosbuvir (SOF), daclatasvir (DCV), sofosbuvir /ledipasvir (SOF/LDV) and ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) in Egypt were extracted. Descriptive analysis was performed to summarize patients' and reactions' characteristics. Information components (ICs) and proportional reporting ratios (PRRs) for all reported ADRs were calculated to identify signals of disproportionate reporting. Logistic regression analysis was performed to identify the DAAs association with serious events of concern while adjusting for age, gender, pre-existing cirrhosis, and ribavirin use. RESULTS Out of 2925 reports, 1131 (38.6%) were serious. The most commonly reported reactions; anaemia (21.3%), HCV relapse (14.5%) and headache (14%). For the disproportionality signals; HCV relapse was reported with SOF/DCV (IC 3.65, 95% CrI 3.47-3.79) and SOF/RBV (IC 3.69, 95% CrI 3.37-3.92), while anaemia (IC 2.85, 95% CrI 2.26-3.27) and renal impairment (IC 2.12, 95% CrI 0.7-3.03) were reported with OBV/PTV/r. CONCLUSION The highest severity index and seriousness were reported with SOF/RBV regimen. A significant association was found for OBV/PTV/r with renal impairment and anaemia although being the superior regimen in terms of efficacy. The study findings call for further population-based studies for clinical validation.
Collapse
Affiliation(s)
- Mai G El-Marakby
- Clinical Pharmacy Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
| | - Mohamed H Solayman
- Clinical Pharmacy Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
| | - Nagwa A Sabri
- Clinical Pharmacy Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
| |
Collapse
|
21
|
Konyn P, Ahmed A, Kim D. The current trends in the health burden of primary liver cancer across the globe. Clin Mol Hepatol 2023; 29:358-362. [PMID: 36916167 PMCID: PMC10121285 DOI: 10.3350/cmh.2023.0092] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Revised: 03/08/2023] [Accepted: 03/11/2023] [Indexed: 03/16/2023] Open
Affiliation(s)
- Peter Konyn
- Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Donghee Kim
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| |
Collapse
|
22
|
El Menshawy N, Hassan N, Khariza M, AlAshery H, Baghat M, Ashour R. CD4/CD8 Ratio could be predictor of burden hepatocellular carcinoma in Egyptian chronic hepatitis C after combined sofosbuvir and daclatasvir therapy. Afr Health Sci 2023; 23:198-212. [PMID: 37545943 PMCID: PMC10398471 DOI: 10.4314/ahs.v23i1.22] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/08/2023] Open
Abstract
Background During the first years of the use of direct acting Hepatitis C antiviral drugs (DAAS), several studies reported a possible correlation between this new era of treatment and an increased risk of Hepatocellular carcinoma (HCC). Its development could possibly be favored by the changes in the immunological milieu and the different cellular behavior after eradication of HCV infection with them. For this reason, this study aimed to address the immunological effect of DAAS. Subject & methods Prospective paired -sample design, carried out on 90 naïve chronically infected HCV patients before and after receiving a combination therapy of sofosbuvir; at a dose of 400 mg once daily and daclatasvir; at a dose of 60 mg once daily for 12 weeks and follow up for one year. immunological tests including: total T cell count, T helper cell count, T cytotoxic cell count and natural killer cell count in peripheral blood through (CD3, CD3/CD4, CD3/CD8 and CD56 respectively) by Fluorochrome monoclonal antibodies labelled with specific dyes through Multiparameter, FACSCanto ™ II flow cytometer (Becton Dickinson, USA). Result Concerning the immunological changes, total T cells (CD3+), Natural killer cells showed non-significant decrease at end of therapy while significant decrease in T helper cells (CD3+CD4+) T cytotoxic cells (CD3+CD8+) compared to pre-treatment value. Long follow up revealed 26.6% developed focal HCC, in more addition, multivariate analysis show CD4/CD8 ratio could be predictor as well as sex for early development of HCC after combined DAAS therapy. Conclusion HCV treatment by DAAS produces significant decrease in T helper, T cytotoxic cells in CHC patients at the end of therapy. 26.6% developed focal HCC with independent CD4/CD8 predictor for burden malignancy. Further large extended population study is needed for clarify this concern.
Collapse
Affiliation(s)
| | - Noha Hassan
- Mansoura University Faculty of Medicine, Pharmacy
| | | | | | - Monir Baghat
- Mansoura University Faculty of Medicine, Internal Medicine
| | - Rehab Ashour
- Mansoura University Faculty of Medicine, Pharmacy
| |
Collapse
|
23
|
El-Ghandour A, Youssif T, Ibrahim W, Abdelsattar HA, Bawady SAE, Wagih M, El-Nakeep S. The effect of different direct antivirals on hepatic steatosis in nondiabetic and naïve hepatitis C-infected Egyptian patients. THE EGYPTIAN JOURNAL OF INTERNAL MEDICINE 2023; 35:12. [PMID: 36816629 PMCID: PMC9922615 DOI: 10.1186/s43162-023-00197-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Accepted: 01/28/2023] [Indexed: 02/24/2023] Open
Abstract
Background Hepatitis C is associated with metabolic effects and fatty liver disease. The effect of different direct antivirals on the liver steatosis, and the metabolic profile, still needs to be established. The aim of this study is to determine the effect of achieving the sustained virological response after 12 weeks (SVR-12 weeks) with different combinations of direct antiviral drugs, on the hepatic steatosis, and fibrosis presented by laboratory and transient elastography parameters. Our study population is nondiabetic, chronically infected HCV Egyptian patients and naïve to any form of HCV treatment. Methods This cohort study was carried on 100 nondiabetic HCV treatment-naïve patients attending the Hepatology Clinic, in the Gastroenterology and Hepatology Department, Ain Shams University, and Kobry El Koba Military Hospital. The patients were divided into four groups according to their treatment regimens as follows: group A: 25 patients who received sofosbuvir (400 mg) and daclatasvir (60 mg) daily for 12 weeks; group B: 25 patients who received sofosbuvir (400 mg) and ledipasvir (90 mg) daily for 12 weeks; group C: 25 patients who received ombitasvir (12.5 mg), paritaprevir (75 mg), and ritonavir (50 mg) daily for 12 weeks; and group D: 25 patients who received sofosbuvir (400 mg) and simeprevir (150 mg) daily for 12 weeks. All patients were subjected to the following investigations: HCV quantitative PCR before and after 12 weeks of treatment, clinical and laboratory metabolic evaluation including alfa-fetoprotein level, thyroid profile assessment, ferritin level, pelvi-abdominal ultrasound, and FibroScan examination. Results All patients achieved SVR after 12 weeks. FibroScan median decreased (P < 0.001) from 19.29 ± 6.97 kPa at baseline to 14.15 ± 6.48 kPa at SVR12. NAFLD score median increased from 1.88 (1.49-2.22) at baseline to 2.01 (1.61-2.33) after 12 weeks of treatment. The highest level of NAFLD score was in group C, and the lowest was in group B. The BMI mean decreased from 28.31 ± 1.53 at baseline to 28.07 ± 1.52 at SVR12. HbA1C level mean decreased from 5.73 ± 0.23 at baseline to 5.40 ± 0.24 at SVR12. In addition, liver enzymes, cholesterol, triglycerides, APRI score (AST-platelet ratio index), and HBA1C decreased after 12-week treatment with a statistically significant difference, while the mean LDL increased after 12 weeks of treatment. Conclusions DAAs affect the metabolic profile of the treated patients. There is a noticed improvement in the FibroScan, NAFLD score, and lipid profile after achieving the SVR-12 weeks. However, LDL is increased after viral cure, mostly due to viral-host molecular interaction.
Collapse
Affiliation(s)
- Ahmed El-Ghandour
- grid.7269.a0000 0004 0621 1570Hepatology and Gastroenterology Unit, Internal Medicine Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Tarek Youssif
- grid.7269.a0000 0004 0621 1570Hepatology and Gastroenterology Unit, Internal Medicine Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Wesam Ibrahim
- grid.7269.a0000 0004 0621 1570Hepatology and Gastroenterology Unit, Internal Medicine Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Hoda Ahmed Abdelsattar
- grid.7269.a0000 0004 0621 1570Clinical Pathology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Somia Abd elhamid Bawady
- grid.7269.a0000 0004 0621 1570Clinical Pathology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mariam Wagih
- grid.7269.a0000 0004 0621 1570Hepatology and Gastroenterology Unit, Internal Medicine Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt ,Armed Forces Medical Complex Kobry El Qobba, Cairo, Egypt
| | - Sarah El-Nakeep
- grid.7269.a0000 0004 0621 1570Hepatology and Gastroenterology Unit, Internal Medicine Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| |
Collapse
|
24
|
Characteristics and predictors of short-term mortality in decompensated cirrhotic patients with acute-on-chronic liver failure. Clin Exp Hepatol 2022; 8:300-308. [PMID: 36683875 PMCID: PMC9850305 DOI: 10.5114/ceh.2022.122332] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Accepted: 09/28/2022] [Indexed: 12/31/2022] Open
Abstract
Aim of the study We aimed to investigate the characteristics of acute-on-chronic liver failure (ACLF) and factors associated with 28-day mortality in patients with ACLF. Material and methods This prospective study included ACLF patients based on the European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) Consortium criteria, admitted between March 2021 and February 2022. We examined variables associated with 28-day mortality using multivariate Cox regression analysis. Results Of 326 patients admitted with acute decompensation (AD) of cirrhosis, 109 (33.44%) patients were diagnosed with ACLF (mean age 63.61 ±11.15 years, 65.14% males). Of these, 26.61%, 35.78%, and 37.61% of patients were in ACLF grades 1, 2, and 3 respectively. HCV (80.73%) was the main aetiology of cirrhosis. Upper gastrointestinal bleeding (25.69%) was the most common trigger. Kidney failure (73.39%) was the most common organ failure. The 28-day mortality rate was 66.97%. Cox regression analysis revealed that the existence of 2 (HR = 6.99, 95% CI: 2.68-18.25, p < 0.0001) or ≥ 3 (HR = 9.34, 95% CI: 3.6-24.74, p < 0.0001) organ failures, hepatic encephalopathy (HR = 2.96, 95% CI: 1.27-6.94, p = 0.01), and elevated serum bilirubin (HR = 1.03, 95% CI: 1.00-1.06, p = 0.04) were independent predictors for 28-day mortality, while shifting blood pH to the normal range was associated with a decrease in the HR of ACLF mortality (HR = 0.03, 95% CI: 0.002-0.44, p = 0.01). Conclusions ACLF has a very high 28-day mortality, which is associated with the existence of 2 or more organ failures, hepatic encephalopathy, elevated serum bilirubin, and low blood pH.
Collapse
|
25
|
Shousha HI, Abdelghafour R, Dabees H, AbdelRazek W, Said M. Three regimens for re-treatment failure of Sofosbuvir-based therapy for chronic hepatitis-C genotype-4: a cohort study. Rev Inst Med Trop Sao Paulo 2022; 64:e50. [PMID: 36074445 PMCID: PMC9448256 DOI: 10.1590/s1678-9946202264050] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2021] [Accepted: 03/30/2022] [Indexed: 12/24/2022] Open
Abstract
Despite the high sustained virologic response (SVR) rates of direct-acting antiviral (DAAs) therapy, a small number of patients does not eradicate the virus, and these patients represent a challenge. This study aims to compare the outcomes of three second-line regimens for DAAs-experienced patients with chronic hepatitis C (CHC). This prospective observational study was conducted at the Damanhur Viral Hepatitis Center from January 2017 to February 2020. We included patients with CHC who did not achieve SVR after the complete course of Sofosbuvir/Daclatasvir±Ribavirin (SOF/DAC±RBV). The primary endpoint was SVR-12 after re-treatment. This study included 360 patients (with a mean age of 51.53±11.38 years). Approximately 51.1% of the patients were males, and 65.5% had liver cirrhosis. All patients of group 1 (45 patients) received SOF/VEL/VOX over 12-weeks; SVR-12 was achieved in 44 patients (97.8%). Group 2 (28 patients) received SOF/DAC/RBV over 24-weeks; (one patient was lost during follow-ups and one patient discontinued treatment due to hepatic decompensation). SVR-12 was achieved in 25 patients (96.2%). Group 3 (287 patients) received SOF/Ombitasvir/Paritaprevir/Ritonavir/RBV) over 12-weeks. Eight patients were lost during follow-ups, and one patient discontinued treatment due to grade 4 adverse events. SVR-12 was achieved in 276 patients (99.3%). There was no difference between the groups regarding their age, gender distribution, baseline viral load or comorbidities. Adverse events (thrombocytopenia, anemia, hyperbilirubinaemia and prolonged INR) were significantly higher in group 3, while group 1 did not experience any. The three studied retreatment regimens can be used for DAAs treatment-experienced patients considering availability. The SOF/VEL/VOX combination had the least adverse events.
Collapse
Affiliation(s)
- Hend Ibrahim Shousha
- Cairo University, Faculty of Medicine, Endemic Medicine and Hepato-Gastroenterology Department, Cairo, Egypt
| | | | - Hosam Dabees
- National Medical Institute of Damanhour, Damanhour, Egypt
| | - Wael AbdelRazek
- Menofia University, National Liver Institute, Menofia, Egypt
| | - Mohamed Said
- Cairo University, Faculty of Medicine, Endemic Medicine and Hepato-Gastroenterology Department, Cairo, Egypt
| |
Collapse
|
26
|
Raslan E, AbdAllah M, Soliman S. The prevalence and determinants of hepatitis B among Egyptian adults: a further analysis of a country-representative survey. EGYPTIAN LIVER JOURNAL 2022. [DOI: 10.1186/s43066-022-00207-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Hepatitis B virus (HBV) infection is a major worldwide healthcare problem with subsequent serious complications including cirrhosis and hepatocellular carcinoma (HCC). Hence, taking cognizance of HBV impact is critical for future planning of its control and prevention.
Objectives
To assess the prevalence of HBV in Egypt, analyse the demographic characteristics of HBV-infected patients and examine the common routes of its transmission.
Methods
This is a cross-sectional study of data from the Egyptian Health Issues Survey (EHIS), which employed a nationally representative sample of 16,004 individuals. The survey participants were categorized into two groups: group A, HBV positive, and group B, HBV negative. Comparative analysis was performed to identify demographic features and define possible risk factors.
Results
The total number of participants included in the study was 16,004. The mean age (± SD) was 33.5 (± 12.4) years. The prevalence of HBV was 1.52%. Demographic analysis showed that HBV was more prevalent among males, married people, people with jobs and smokers (P = 0.0011, 0.002, < 0.001 and 0.0036) respectively. Employing an adjusted multivariate logistic regression model, we observed an increased likelihood of HBV infection in married adults who received cupping without blood and who did not know if they had schistosomiasis injection therapy.
Conclusion
The application of special screening programs to highly susceptible patients and treatment optimization is recommended for the elimination of HBV. EHIS indicates the likely success of the previous Egyptian control plan for viral hepatitis through reducing several risk factors.
Collapse
|
27
|
Zhao Z, Chu M, Guo Y, Yang S, Abudurusuli G, Frutos R, Chen T. Feasibility of Hepatitis C Elimination in China: From Epidemiology, Natural History, and Intervention Perspectives. Front Microbiol 2022; 13:884598. [PMID: 35722351 PMCID: PMC9201439 DOI: 10.3389/fmicb.2022.884598] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Accepted: 05/09/2022] [Indexed: 11/20/2022] Open
Abstract
Hepatitis C imposes a heavy burden on many countries, including China, where the number of reported cases and the incidence of hepatitis C virus (HCV) increased yearly from 2005 to 2012, with a stable trend after 2012. The geographical distribution of HCV infections varies widely in China, with the northwest and southwest regions and the Henan Province showing a high disease burden. Elderly, men, sexually active people, drug users, migrants, blood transfusion recipients, and renal dialysis patients have become the target populations for hepatitis C prevention and control. It is important to improve the diagnosis rate in high-risk groups and asymptomatic people. Identifying secondary HCV infections, especially in HCV patients co-infected with the human immunodeficiency virus (HIV) is a priority of hepatitis C prevention and control. Enhancing universal access to direct antiviral agents (DAAs) treatment regimens is an effective way to improve the cure rate of HCV infection. For China to contribute to the WHO 2030 global HCV elimination plan, strategic surveillance, management, and treatment program for HCV are needed.
Collapse
Affiliation(s)
- Zeyu Zhao
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, China
- CIRAD, Intertryp, Montpellier, France
| | - Meijie Chu
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, China
| | - Yichao Guo
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, China
| | - Shiting Yang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, China
| | - Guzainuer Abudurusuli
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, China
| | | | - Tianmu Chen
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, China
| |
Collapse
|
28
|
Abdelrahman SA, Abdelfatah MM, Keshta AT. Rapamycin-filgrastim combination therapy ameliorates portal hypertension-induced splenomegaly: Role of β actin and S100A9 proteins modulation. IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES 2022; 25:732-744. [PMID: 35949314 PMCID: PMC9320204 DOI: 10.22038/ijbms.2022.64034.14101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Accepted: 06/07/2022] [Indexed: 11/06/2022]
Abstract
Objectives Thioacetamide (TAA) was administered to induce an animal model of liver disease with secondary splenomegaly to assess the mechanisms underlying the effects of rapamycin and filgrastim when taken separately or in combination on the biochemical and histopathological aspects of the liver and spleen. Materials and Methods Thirty adult male albino rats were divided into five groups (control, TAA-treated group, TAA+rapamycin, TAA+filgrastim, and TAA+rapamycin+filgrastim group). We measured relative liver and spleen weights, serum levels of alanine transaminase (ALT), aspartate transaminase (AST), and albumin. Molecular docking modeling and histopathological examination of liver and spleen sections with hematoxylin and eosin and Masson trichrome staining with immunohistochemical detection of splenic CD3 and CD20 lymphocytes, S100A9 and β actin antibodies were detected. Morphometric and statistical analyses of the results were performed. Results TAA administration altered the histological structure of the liver and spleen and impaired liver function. It increased the expression of splenic CD3, CD20 lymphocytes, and S100A9 while diminishing the expression of β actin. Each of rapamycin and filgrastim, when administered separately, improved liver and spleen indices and liver function, but rapamycin did not affect the albumin level. They lowered splenic B and T lymphocyte levels. Expression levels of S100A9 showed down-regulation while β actin levels were up-regulated when compared with TAA. Combination therapy improved liver and spleen tissue pathology and significantly ameliorated the expression of splenic lymphocytes through regulation of S100A9 and β actin expression. Conclusion The synergistic effect of combination therapy was dependent on the regulation of splenic S100A9 and β actin levels.
Collapse
Affiliation(s)
- Shaimaa A. Abdelrahman
- Medical Histology and Cell Biology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt,Corresponding author: Shaimaa A. Abdelrahman. Department of Medical Histology and Cell Biology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
| | - Mohammed M. Abdelfatah
- Biochemistry Division, Chemistry Department, Faculty of Science, Zagazig University, Zagazig, Egypt
| | - Akaber T. Keshta
- Biochemistry Division, Chemistry Department, Faculty of Science, Zagazig University, Zagazig, Egypt
| |
Collapse
|
29
|
Waked I. Case study of hepatitis C virus control in Egypt: impact of access program. Antivir Ther 2022; 27:13596535211067592. [PMID: 35491550 DOI: 10.1177/13596535211067592] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
BACKGROUND Although Egypt was the country with the highest prevalence of hepatitis C in the world, the availability of sofosbuvir based therapies enabled Egypt to be the first country to eliminate hepatitis C and cure more than 4 million chronically infected patients. PURPOSE This is a small tribute to John Martin. METHODOLOGY AND CONCLUSION Here I present a summary of the HCV problem in Egypt, and how we, through Gilead's Access program under his leadership, were able to eliminate the disease.
Collapse
Affiliation(s)
- Imam Waked
- RinggoldID:68873National Liver Institute, Shebeen El Kom, Egypt
| |
Collapse
|
30
|
Pursuing Elimination of Hepatitis C in Egypt: Cost-Effectiveness and Economic Evaluation of a Country-Wide Program. Infect Dis Ther 2022; 11:1193-1203. [PMID: 35451742 PMCID: PMC9124269 DOI: 10.1007/s40121-022-00631-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Accepted: 03/24/2022] [Indexed: 12/02/2022] Open
Abstract
Introduction Hepatitis C virus (HCV) is a global public health crisis. Egypt presents the highest HCV global prevalence. Recently, three different HCV screening/testing/therapy programs were implemented: In 2014 (wave 1), major decisions on HCV therapy were enacted, accompanied by a 99% discount for the HCV therapy sofosbuvir. In 2016 (wave 2), a first testing program was launched to identify patients for free treatment. In 2018 (wave 3), population-wide screening was conducted using a WHO-prequalified finger prick rapid diagnostic test (RDT) to identify/treat all Egyptians with HCV. The financial advantages of HCV screening programs (wave 1–3 results) were estimated vs a baseline period of limited Egyptian HCV testing/therapeutic intervention (2008–2014). Methods Using published evidence and model-based estimates from real-world data, we evaluated the direct costs of the different HCV programs, accompanied by a conservative simulation of major HCV health consequences (i.e., liver-related deaths/life years lost) and related indirect costs. Total economic consequences of each HCV program were compared to each other and baseline from a societal perspective. Future costs and health effects were discounted by 3.5% per year. Results Discounted total costs (in US dollars) were $1,057 billion (baseline), $913 million (wave 1), $457 million (wave 2), and $396 million (wave 3). Discounted HCV-related life years lost were 418,000 (baseline), 377,000 (wave 1), 142,000 (wave 2), and 62,000 (wave 3). With each successive Egyptian HCV screening/testing/therapy wave, total costs and HCV-related mortality were reduced. Conclusion Use of the community-applied, WHO-prequalified RDT was the most dominant approach to cost-effectiveness. These results provide rationale for worldwide scalability of similar HCV elimination programs.
Collapse
|
31
|
Kamal A, Matta C, Mohsin HA, Elhadidi AS, Ghazy RM, Omar HH, Tahoun M, Mohamed NA. ASSESSING PREDICTORS OF DIRECTLY ACTING ANTIVIRALS' FAILURE AS A FURTHER STEP TOWARDS MORE EFFICIENT HCV ELIMINATION PROGRAMS: IL28B (IFNL4) GENE POLYMORPHISM HAS NO ROLE WHILE HIGHER ESTIMATED CREATININE CLEARANCE IS A FORGOTTEN FACTOR. ARQUIVOS DE GASTROENTEROLOGIA 2022; 59:177-183. [PMID: 35830025 DOI: 10.1590/s0004-2803.202202000-33] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Accepted: 01/17/2022] [Indexed: 06/15/2023]
Abstract
BACKGROUND Sustained virologic response (SVR) rates after directly acting antivirals (DAAs) for hepatitis C virus (HCV) exceed 95%. This encouraged policymakers to put plans to achieve HCV elimination by 2030. The remaining percentage of non-SVR12 can affect HCV eradication strategies in the real-world especially the compliance of large numbers of treated persons to follow up for assessment of virologic response cannot be guaranteed. OBJECTIVE We aimed to assess predictors of failure to achieve SVR after receiving sofosbuvir plus NS5A inhibitor as an important step towards achieving better HCV eradication strategies. METHODS During the period from 1st November 2018 to 1st November 2019, 1581 treatment-naive patients received sofosbuvir plus daclatasvir ± ribavirin at our unit and 10 patients were referred to us with HCV relapse after the same regimens. A total of 163 out of the 1581 patients were lost for follow-up before assessment of virologic response and excluded from the analysis. 20 out of the remaining patients failed to achieve SVR12. Data from the 30 patients with non-SVR12 were included in the case-control analysis. RESULTS Every unit increase in estimated creatinine clearance using modification of diet in renal disease study (MDRD) score, total bilirubin, and INR was associated with 1.03, 13.92, and 80.08 times greater odds of non-SVR12 (P<0.001, P=0.0016, P=0.02) respectively. The presence of liver cirrhosis on ultrasonography increases the odds by 10.03. (P=0.009). CONCLUSION Higher MDRD score, INR, total bilirubin, and presence of sonographic features of liver cirrhosis are predictors of failure to achieve SVR12 using sofosbuvir plus NS5A inhibitor.
Collapse
Affiliation(s)
- Ahmed Kamal
- Internal Medicine and Hepatology department. Faculty of Medicine, Alexandria University, Egypt
| | - Cecil Matta
- Developmental Genetics department, Faculty of Science, Alexandria University, Egypt
| | - Heba Akram Mohsin
- Cell biology and genetics fellow, Faculty of Science, Alexandria University, Egypt
- College of pharmacy-Al-Zahraa University for Women, Iraq
| | - Abeer Shawki Elhadidi
- Clinical and chemical pathology department, Faculty of Medicine, Alexandria University, Egypt
| | - Ramy Mohamed Ghazy
- Tropical health department, High Institute of Public Health, Alexandria University, Egypt
| | - Heba Hany Omar
- Clinical Pharmacist at Alexandria Main University hospitals, Alexandria University, Egypt
- Microbiology department, Faculty of Pharmacy, AL Salam University, Egypt
| | - Mona Tahoun
- Clinical and chemical pathology department, Faculty of Medicine, Alexandria University, Egypt
| | | |
Collapse
|
32
|
El Kassas M, Eltabbakh M, Elbadry M, Tawheed A, Elbaz T. Establishing a research production line in real-life settings: the case of Hepatitis C management in a viral hepatitis specialized Egyptian center. Curr Med Res Opin 2022; 38:553-563. [PMID: 35118916 DOI: 10.1080/03007995.2022.2038489] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 01/23/2022] [Accepted: 02/02/2022] [Indexed: 11/03/2022]
Abstract
Efforts toward eradicating the Hepatitis C virus (HCV) have advanced rapidly, due to the development of direct-acting antivirals (DAAs), especially with the appearance of pan-genotypic combinations. Real-world studies, in particular, have verified the efficacy and safety of DAA combinations documented in registration trials. This review documents the results of using DAA combinations in real-life settings in everyday clinical practice in Egypt, the country with the highest prevalence of HCV. The significant number of treated patients in Egypt, which exceeded four million allowed tremendous data about the results of HCV management in real-life settings for different treatment regimens and disease conditions. DAA combinations have resulted in high sustained virologic response rates (SVR12) and few adverse reactions in real-life settings. SVR12 rates ranged from 90% to 100%, depending on the combination of drugs used, the HCV genotype, and the stage of liver disease. Most adverse reactions reported in real-world settings were mild and resulted in treatment discontinuation in only a minority of cases. Data from real-life studies covered most aspects of HCV management that were lacking after initial approval studies. More research is needed to tailor treatment and produce generic HCV combinations to overcome the residual limitations of the currently available DAAs.
Collapse
Affiliation(s)
- Mohamed El Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Mohamed Eltabbakh
- Tropical Medicine department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohamed Elbadry
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Ahmed Tawheed
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Tamer Elbaz
- Endemic Medicine and Hepatogastroenterology, Department, Faculty of Medicine, Helwan University, Cairo, Egypt
| |
Collapse
|
33
|
Shoun AA, Abozahra R, Baraka K, Mehrez M, Abdelhamid SM. Identifying Different Mutation Sites Leading to Resistance to the Direct-Acting Antiviral (DAA) Sofosbuvir in Hepatitis C Virus Patients from Egypt. Microorganisms 2022; 10:microorganisms10040679. [PMID: 35456731 PMCID: PMC9024585 DOI: 10.3390/microorganisms10040679] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Revised: 03/13/2022] [Accepted: 03/17/2022] [Indexed: 02/04/2023] Open
Abstract
The hepatitis C virus (HCV) is a major global health challenge and a leading cause of morbidity and mortality. Many direct-acting antivirals (DAAs) target essential macromolecules involved in the virus’ life cycle. Although such DAAs achieve great success in reducing the viral load in genotype 1 infections, other genotypes demonstrate different levels of response. This study focused on mutation sites associated with patients with genotype 4a infections that failed to respond to treatment with sofosbuvir. The genotyping of HCV samples from patients with virological failure, and responder patients, was conducted using Geno2Pheno webserver-based full NS5B sequences. We constructed 3D structural models for all the samples and used structural analysis to investigate the effect of amino acid substitution on the observed resistance to SOF-based treatment, and the docking of sofosbuvir into the active sites of the 10 models was performed. Finally, 10 molecular dynamic (MD) simulation experiments were conducted to compare the stability of the 3D models of the resistant samples against the stability of the 3D models of the responder samples. The results highlighted the presence of HCV subtype 4a in all ten samples; in addition, an amino acid (aa) substitution in the palm region may hinder HCV polymerase activity. In this study, we provide evidence that a mutation in the NS5B gene that induces resistance to sofosbuvir in patients with the S282T/C/R mutant virus is present in the Egyptian population. Overall, the docking and MD results support our findings and highlight the significant impact of the identified mutations on the resistance of HCV NS5B RNA-dependent RNA polymerase to direct-acting antivirals (DAAs).
Collapse
Affiliation(s)
- Aly Atef Shoun
- Microbiology and Immunology Department, Faculty of Pharmacy, Sinai University, El Arish 45518, Egypt
- Correspondence:
| | - Rania Abozahra
- Microbiology and Immunology Department, Faculty of Pharmacy, Damanhour University, Damanhour 22511, Egypt; (R.A.); (K.B.); (S.M.A.)
| | - Kholoud Baraka
- Microbiology and Immunology Department, Faculty of Pharmacy, Damanhour University, Damanhour 22511, Egypt; (R.A.); (K.B.); (S.M.A.)
| | - Mai Mehrez
- National Hepatology and Tropical Medicine Research Institute (NHTMRI), Cairo 11511, Egypt;
| | - Sarah M. Abdelhamid
- Microbiology and Immunology Department, Faculty of Pharmacy, Damanhour University, Damanhour 22511, Egypt; (R.A.); (K.B.); (S.M.A.)
| |
Collapse
|
34
|
Zakareya T, Akl M, Shibl S, El-Mazaly M, Abdel-Razek W. Utility of prognostic scores in predicting short-term mortality in patients with acute-on-chronic liver failure. EGYPTIAN LIVER JOURNAL 2022. [DOI: 10.1186/s43066-022-00183-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Acute-on-chronic liver failure (ACLF) is a distinct syndrome associated with high short-term mortality. Early identification of patients at high risk is essential to determine emergency for transplantation and decide and prioritize the need for intensive care unit (ICU). We aimed to evaluate the performance of the different prognostic scores in the prediction of in-hospital mortality in patients with ACLF. A total of 249 patients with ACLF were included and followed till discharge from the hospital. Univariate and Cox regression analyses were used to assess the performance of liver-specific (Child-Pugh and MELD) and ACLF prognostic scores (CLIF-C OF, CLIF-SOFA, CLIF-C AD, CLIF-C ACLF) in the prediction of in-hospital mortality.
Results
Patients were mostly males (71.1%) with a mean age of 53.9 ± 12.8 years. The etiology of pre-existing liver disease was HCV in 57.8%. Sepsis was the most common precipitating factor (49.8%) and the mortality rate was 74.3%. In univariate analysis, all scores were significantly higher in the deceased group (P<0.0001). AUROC were 0.897, 0.884, 0.870, 0.861, 0.861, and 0.850 for CLIF-C OF, CLIF-C AD, CLIF-C ACLF, Child-Pugh, CLIF-SOFA, and MELD scores, respectively. In multivariate analysis, 2 independent predictors of mortality were identified: CLIF-C ACLF score (OR 3.25, 95% CI 1.03–10.25, P<0.0001) and Child-Pugh class C (OR 1.04, 95% CI 1.02–1.06, P=0.044).
Conclusions
All the studied scores could predict in-hospital mortality of patients with ACLF. However, CLIF-C ACLF and Child-Pugh class performed better as they could significantly and independently predict mortality.
Collapse
|
35
|
Abbasy M, Zaghla H, Elhelbawy M, Ramadan M, Zakareya T. Predicting in-hospital mortality of cirrhotic patients hospitalized with hepatic encephalopathy. EGYPTIAN LIVER JOURNAL 2022. [DOI: 10.1186/s43066-022-00178-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Abstract
Background
Hepatic encephalopathy (HE) is a serious condition associated with high rates of mortality. Many scoring systems are used to predict the outcome of HE in patients admitted to the intensive care unit (ICU). The most used scores are Child-Turcotte-Pugh (CTP), Model for End-stage Liver Disease (MELD), Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA), and Acute Physiology and Chronic Health Evaluation II (APACHE II). These scores were thoroughly investigated in HE associated with acute liver failure (type A). In the present study, we aimed to evaluate the prognostic value of these scores in patients with HE on a background of liver cirrhosis (type C). Two hundred cirrhotic patients hospitalized with HE were included in the study. Diagnosis and classification of HE were based on the West Haven criteria. APACHE II, CLIF-SOFA, MELD, MELD-Na, and CTP scores were calculated for all patients within the first 24 h after admission. According to survival outcomes, patients were categorized into either improved or deceased. Demographic, clinical, and laboratory data as well as prognostic scores were compared in both deceased and improved groups. The receiver operating characteristic (ROC) curve was plotted, and the area under the ROC curve (AUROC) was calculated for each score. Backward logistic regression analysis was used to identify the predictors of mortality.
Results
60.5% of patients were males. The mean age was 61.09 ± 8.94 years. The main precipitating factors of HE was infections predominantly spontaneous bacterial peritonitis (n = 108, 54.0%) followed by variceal bleeding (n = 39, 19.5%). All scores were significantly higher in the deceased patients. AUROC were 0.734 (CI95% 0.666–0.803), 0.717 (CI95% 0.647–0.787), 0.663 (CI95% 0.589–0.738), 0.626 (CI95% 0.549–0.704), and 0.609 (CI95% 0.531–0.686) for CLIF-SOFA, MELD-Na, MELD, APACHE II, and CTP scores, respectively. MELD, MELD-Na, and CLIF-SOFA scores were the independent predictors of mortality. Among these scores, CLIF-SOFA was the strongest independent predictor of mortality (OR = 1.142, CI95% = 0.888–1.467, p = 0.001).
Conclusions
CLIF-SOFA score was superior to other prognostic scores in predicting mortality in hospitalized patients with HE type C.
Collapse
|
36
|
Mohamed EI, El-Ghnam SM, Bayoumi AM, Abdel-Mageed SM, Ghareeb DA, Ross B. Electronic nose versus quadrupole mass spectrometry for identifying viral hepatitis C patients. J Viral Hepat 2022; 29:147-155. [PMID: 34773341 DOI: 10.1111/jvh.13630] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Revised: 10/13/2021] [Accepted: 11/02/2021] [Indexed: 12/12/2022]
Abstract
Hepatitis C is a leading cause of liver disease and transplantation and is a significant burden on public health worldwide. This study aimed to apply the Electronic Nose (E-Nose) and quadrupole Mass Spectrometry (MS/MS) technologies for screening blood samples from hepatitis C patients and healthy controls. We analysed volatile organic compounds (VOCs) in the headspace over blood samples to identify those VOCs characteristic for diagnosing hepatitis C patients. The study comprised 150 acute hepatitis C patients with age range: 24-59 years, and mean age ±SD: 41.5 ± 12.8 years and 150 age-matched healthy controls (age range: 24-51 and mean age: 40.11 ± 4.89 years) from the Hospital of the Medical Research Institute, Alexandria University, Alexandria, Egypt. Collected blood samples were analysed qualitatively and quantitatively using the E-Nose and MS/MS techniques, respectively. Principal component analysis of the E-Nose 10-sensor responses accurately classified blood samples from hepatitis C patients and healthy controls. The first two principal components explained over 98.35% of the variance in signals with no false-positive (healthy controls) or false-negative (hepatitis C patients) results. MS/MS showed two fragmentation ions at m/z of 104 and 151 Da with the positive electrospray ionization mode (ESI+) in blood samples for hepatitis C patients, but not for healthy controls or background water samples. We identified the two specific fragmentation ions at m/z 104 and m/z 151 Da as malonic acid (MF: C3 H4 O4 ; MW: 104.06 g/mol) and monosaccharide pentose (MF: C5 H10 O5 ; MW: 150.13 g/mol) in VOCs of the headspace over blood samples for hepatitis C patients. This provides a rationale for developing diagnostic tests for hepatitis C virus based on altered trace VOCs concentrations using the relatively inexpensive, easy-to-use, portable and non-invasive E-Nose technology.
Collapse
Affiliation(s)
- Ehab I Mohamed
- Department of Medical Biophysics, Medical Research Institute, Alexandria University, Alexandria, Egypt
| | - Sameh M El-Ghnam
- Department of Physics, Faculty of Science, Alexandria University, Alexandria, Egypt
| | - Amani M Bayoumi
- Department of Physics, Faculty of Science, Alexandria University, Alexandria, Egypt
| | - Samir M Abdel-Mageed
- Department of Physics, Faculty of Science, Alexandria University, Alexandria, Egypt
| | - Doaa A Ghareeb
- Department of Biochemistry, Faculty of Science, Alexandria University, Alexandria, Egypt.,Pre-Clinical Center, Scientific Research and Technology Applications City, Borg Al-Arab, Alexandria, Egypt
| | - Brian Ross
- Northern Ontario School of Medicine, Lakehead University, Ontario, Canada
| |
Collapse
|
37
|
Motawi TMK, Sadik NAH, Sabry D, Fahim SA, Shahin NN. rs62139665 Polymorphism in the Promoter Region of EpCAM Is Associated With Hepatitis C Virus-Related Hepatocellular Carcinoma Risk in Egyptians. Front Oncol 2022; 11:754104. [PMID: 35070966 PMCID: PMC8766815 DOI: 10.3389/fonc.2021.754104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Accepted: 12/06/2021] [Indexed: 12/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a universal health problem that is particularly alarming in Egypt. The major risk factor for HCC is hepatitis C virus (HCV) infection which is a main burden in Egypt. The epithelial cell adhesion molecule (EpCAM) is a stem cell marker involved in the tumorigenesis and progression of many malignancies, including HCC. We investigated the association of -935 C/G single nucleotide polymorphism in EpCAM promoter region (rs62139665) with HCC risk, EpCAM expression and overall survival in Egyptians. A total of 266 patients (128 HCV and 138 HCC cases) and 117 age- and sex-matched controls participated in this study. Genotyping, performed using allelic discrimination and confirmed by sequencing, revealed a significant association between EpCAM rs62139665 and HCC susceptibility, with higher GG genotype and G allele distribution in HCC patients than in non-HCC subjects. Such association was not detected in HCV patients compared to controls. EpCAM gene expression levels, determined in blood by RT-qPCR, and its serum protein expression levels, determined by ELISA, were significantly higher in GG relative to GC+CC genotype carriers in HCV and HCC patients in a recessive model. ROC analysis of EpCAM protein levels revealed significant discriminatory power between HCC patients and non-HCC subjects, with improved diagnostic accuracy when combining α-fetoprotein and EpCAM compared to that of α-fetoprotein alone. Altogether, EpCAM rs62139665 polymorphism is significantly associated with HCC and with EpCAM gene and protein expression levels in the Egyptian population. Moreover, serum EpCAM levels may hold promise for HCC diagnosis and for improving the diagnostic accuracy of α-fetoprotein.
Collapse
Affiliation(s)
| | | | - Dina Sabry
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Badr University in Cairo, Badr City, Egypt.,Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Sally Atef Fahim
- Biochemistry Department, School of Pharmacy, Newgiza University (NGU), Cairo, Egypt
| | - Nancy Nabil Shahin
- Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| |
Collapse
|
38
|
Ezzat R, Eltabbakh M, El Kassas M. Unique situation of hepatocellular carcinoma in Egypt: A review of epidemiology and control measures. World J Gastrointest Oncol 2021; 13:1919-1938. [PMID: 35070033 PMCID: PMC8713321 DOI: 10.4251/wjgo.v13.i12.1919] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 04/17/2021] [Accepted: 10/18/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the sixth most common primary malignancy worldwide, and the third most common cause of death among cancers worldwide. HCC occurs in several pre-existing conditions, including hepatitis C, hepatitis B virus, and non-alcoholic cirrhosis. Egypt used to be the country with the heaviest hepatitis C virus (HCV) burden. The relationship between HCV and HCC is an important research area. In Egypt, HCC is a significant public health problem. A possible cause for the increasing rates of detection of HCC in Egypt is the mass screening program that was carried by the government for detecting and treating HCV. A multidisciplinary approach is now widely applied to HCC management in health centers all over Egypt. Different treatment modalities are available in Egypt, with success rates comparable to global rates. The Egyptian health authorities have made the elimination of HCV from Egypt a special priority, and this approach should lead to a decrease in number of HCC cases in the near future. In this article we review the current situation of HCC in Egypt, including epidemiological aspects, relevant risk factors for HCC development, strategies, and efforts established by health authorities for the screening and prevention of both HCV and HCC in Egypt. We highlight the different modalities for HCC treatment.
Collapse
Affiliation(s)
- Reem Ezzat
- Internal Medicine Department, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
| | - Mohamed Eltabbakh
- Tropical Medicine Department, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt
| | - Mohamed El Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo 11795, Cairo, Egypt
| |
Collapse
|
39
|
Zaafan MA, Abdelhamid AM. Dasatinib ameliorates thioacetamide-induced liver fibrosis: modulation of miR-378 and miR-17 and their linked Wnt/β-catenin and TGF-β/smads pathways. J Enzyme Inhib Med Chem 2021; 37:118-124. [PMID: 34894966 PMCID: PMC8667920 DOI: 10.1080/14756366.2021.1995379] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Hepatic stellate cells activation (HSCs) plays a crucial role in the pathogenesis of liver fibrosis. Specific microRNAs have been suggested to affect the activation of HSCs via various signalling pathways including TGF-β/smads and Wnt/β-catenin pathways. Dasatinib is a multitarget inhibitor of many tyrosine kinases has recently studied for its anti-fibrotic effects in a variety of fibrous diseases. This study investigated the role of modulation of miRNA-378 and miRNA-17 in the pathogenesis of liver fibrosis through altering Wnt/β-catenin and TGF-β/smads pathways and evaluated the beneficial effect of the tyrosine kinase inhibitor, dasatinib, in thioacetamide-induced liver fibrosis model in mice. Treatment with dasatinib down-regulated miRNA-17 expression, leading to the restoration of WiF-1 and smad-7 which cause the inhibition of both Wnt/β-catenin and TGF-β/smads signalling. In addition, it upregulated miRNA-378 leading to the decrease of Wnt-10 which contributes to the suppression of activated HSCs.
Collapse
Affiliation(s)
- Mai A Zaafan
- Faculty of Pharmacy, Pharmacology and Toxicology Department, October University for Modern Sciences and Arts (MSA), Dokki, Egypt
| | - Amr M Abdelhamid
- Faculty of Pharmacy, Biochemistry Department, October University for Modern Sciences and Arts (MSA), Dokki, Egypt
| |
Collapse
|
40
|
Alsowey AM, Shehata SM. Non-invasive staging of liver fibrosis by two-dimensional shear wave elastography (2D-SWE) in patients with chronic hepatitis C and B. THE EGYPTIAN JOURNAL OF RADIOLOGY AND NUCLEAR MEDICINE 2021. [DOI: 10.1186/s43055-021-00502-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Non-invasive shear wave-based techniques have been developed for estimating liver fibrosis in patients with chronic liver diseases. Two-dimensional shear wave elastography provides in real-time, a tow dimensional quantitative map of tissue stiffness and enables measuring the stiffness by adjustment of a region of interest of tissue. The aim of this study was to highlight the role of tow dimensional shear wave elastography (2D-SWE) in detecting the degree of liver fibrosis in patients with chronic hepatitis C and B, in correlation with liver enzymes level and fibrotest.
Results
This study included 50 patients with chronic hepatitis C and B whose ages were (range, 30-65 years; mean, 48 years). Shear wave elastography cutoff values were 1.35 m/s, 5.48 KPa for (F>0); 1.66 m/s, 8.29 kPa for (F>1); 1.77 m/s, 9.40 kPa for (F>2); and 1.99 m/s, 11.9 kPa for (F>3). An excellent agreement was found between shear wave elastography and Fibrotest in staging of liver fibrosis in 88% of patients (κw=0.943, 95% CI, 0.88 to 1.00) achieving a highly statistical significance (P<0.001). There was a significant moderate positive concordance between US scoring and staging by 2D-SWE and staging by Fibrotest (rs, 0.49; P<0.01) and (rs, 0.48; P<0.01) respectively. However, no significant concordances were noticed between staging by AST and ALT and 2D-SWE and staging by Fibrotest (P>0.05).
Conclusions
2D shear wave elastography showed better diagnostic performance than visual assessment by conventional US for detection of chronic liver diseases, as well as for evaluation of their severity and prognosis. Elastograhy—Fibrotest combination gives best diagnostic performance in detecting the degree of fibrosis non-invasively and can be used reliably as a first-line pre-therapeutic evaluation of fibrosis in HCV and HBV-infected patients.
Collapse
|
41
|
Ehsan N, Sweed D, Elsabaawy M. Evaluation of HCV-related liver fibrosis post-successful DAA therapy. EGYPTIAN LIVER JOURNAL 2021; 11:56. [DOI: 10.1186/s43066-021-00129-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Accepted: 06/11/2021] [Indexed: 12/11/2022] Open
Abstract
Abstract
Background
The rapidly developing era of direct-acting antiviral regimens (DAAs) for more than one hepatitis C virus (HCV) genotype had certainly alleviated HCV burden all over the world. Liver fibrosis is the major dramatic complication of HCV infection, and its progression leads to cirrhosis, liver failure, and hepatocellular carcinoma. The impact of DAAs on liver fibrosis had been debatably evaluated with undetermined resolution.
Main body
The aim of this review is to accurately revise the effects of DAA regimens on liver fibrosis which can either be regression, progression, or non-significant association. Liver fibrosis regression is a genuine fact assured by many retrospective and prospective clinical studies. Evaluation could be concluded early post-therapy reflecting the dynamic nature of the process.
Conclusions
The ideal application of DAA regimens in treating HCV has to be accomplished with efficient non-invasive markers in differentiating proper fibrosis evaluation from necroinflammation consequences. Liver biopsy is the gold standard that visualizes the dynamic of fibrosis regression.
Collapse
|
42
|
El Kassas M, Abdeen N, Omran D, Alboraie M, Salaheldin M, Eltabbakh M, Farghaly R, Emadeldeen M, Afify S, Sweedy A, Ghalwash A, Abbass A, Ezzat S, Tahoon M, ELshazly HM, Hamdy H, Omar H. Safety and efficacy of sofosbuvir/ledipasvir and sofosbuvir/daclatasvir in the treatment of hepatitis C in patients with decompensated cirrhosis. Eur J Gastroenterol Hepatol 2021; 33:e877-e882. [PMID: 34560693 DOI: 10.1097/meg.0000000000002287] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
BACKGROUND Hepatitis C virus (HCV)-related decompensated cirrhosis is a severe life-threatening illness. The safety of direct-acting antivirals (DAAs) has opened a gate of hope for that subgroup of patients who were previously contraindicated for interferon therapy. OBJECTIVE We aimed at the investigation of the safety and efficacy of different DAAs regimens in the treatment of HCV-related decompensated cirrhosis patients, to determine sustained virological response (SVR)12 rates and to analyze the factors associated with response. METHODS A retrospective, single-center study including HCV-related decompensated cirrhosis patients who received DAAs. Demographic, laboratory and clinical data were analyzed. The SVR12 rate was the primary outcome measure. Secondary outcomes included the predictors of response, changes in the baseline model for end-stage liver disease and child-turcotte-pugh (CTP) scores, and fibroindices (APRI and fibrosis-4 index) at 12 weeks after treatment. RESULTS In total, 145 eligible patients (141 with CTP class B and 4 with class C) were enrolled in this study. SVR12 was achieved by 88.06% (118/134) of efficacy population on different DAAs regimens, Treatment was discontinued in 11 patients because of severe side effects without any deaths. Younger age showed a significant positive association with SVR12. CONCLUSIONS DAAs can be used for the treatment of HCV-related decompensated liver disease, with acceptable SVR12 rates and safety profiles.
Collapse
Affiliation(s)
- Mohamed El Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo
| | - Nermeen Abdeen
- Tropical medicine, Faculty of Medicine, Alexandria University, Alexandria
| | - Dalia Omran
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University
| | | | - Mohamed Salaheldin
- Tropical Medicine Department, Faculty of Medicine, Ain Shams University, Cairo
| | - Mohamed Eltabbakh
- Tropical Medicine Department, Faculty of Medicine, Ain Shams University, Cairo
| | - Rasha Farghaly
- Department of community medicine, Faculty of Medicine, Suez Canal University
| | - Mohammed Emadeldeen
- Hepatogastroenterology Department, National Hepatology & Tropical Medicine Research Institute, Cairo
| | - Shimaa Afify
- Hepatogastroenterology Department, National Hepatology & Tropical Medicine Research Institute, Cairo
| | - Ahmad Sweedy
- Gastroenterology Department, Damietta Cardiology and Gastroenterology Center, Damietta
| | - Ahmed Ghalwash
- Hepatology and Gastroenterology Department, AGOZA Police Hospital, Cairo
| | - Amr Abbass
- Hepatology and Gastroenterology Department, AGOZA Police Hospital, Cairo
| | - Sameera Ezzat
- Epidemiology and Preventive Medicine Department, National Liver Institute, Menoufia University, Menoufia, Egypt
| | - Marwa Tahoon
- Epidemiology and Preventive Medicine Department, National Liver Institute, Menoufia University, Menoufia, Egypt
| | - Helmy M ELshazly
- Hepatology and gastroenterology department, national liver institute.Menoufia University, Egypt
| | - Hassan Hamdy
- Tropical Medicine Department, Faculty of Medicine, Ain Shams University, Cairo
| | - Heba Omar
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University
| |
Collapse
|
43
|
Konyn P, Ahmed A, Kim D. Current epidemiology in hepatocellular carcinoma. Expert Rev Gastroenterol Hepatol 2021; 15:1295-1307. [PMID: 34624198 DOI: 10.1080/17474124.2021.1991792] [Citation(s) in RCA: 154] [Impact Index Per Article: 38.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Accepted: 10/07/2021] [Indexed: 01/27/2023]
Abstract
INTRODUCTION Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third-leading cause of cancer-related mortality in the world. AREAS COVERED This review will discuss risk factors, demographic differences, global trends, and the economic burden of HCC. Viral hepatitis, particularly hepatitis B virus (HBV) infection, is the most common underlying liver disease leading to HCC in those with cirrhosis. Other important risk factors include alcoholic liver disease, nonalcoholic fatty liver disease, metabolic syndrome, etc. With the introduction of direct-acting antiviral agents for hepatitis C virus infection, routine vaccination against HBV, and increasing support for robust public screening programs, the incidence rates for HCC due to viral hepatitis is falling in many countries. Meanwhile, the prevalence of obesity and metabolic syndrome are on the rise, as is NAFLD-related HCC incidence. Asia and Africa have the highest incidence rates of HCC. In multiethnic countries, racial and ethnic minorities experience disparities in HCC incidence as well as mortality, representing an essential area for improvement in terms of healthcare inequity. EXPERT OPINION Interventions to minimize the global burden of HCC aim to reduce rates of the most common risk factors and implement effective treatment of underlying etiology and comprehensive screening programs for HCC.
Collapse
Affiliation(s)
- Peter Konyn
- Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Donghee Kim
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| |
Collapse
|
44
|
Relation between levels of toll-like receptors 3 and 7 and clinical profile of Child-Pugh B cirrhotic patients. Clin Exp Hepatol 2021; 7:293-296. [PMID: 34712831 PMCID: PMC8527339 DOI: 10.5114/ceh.2021.109336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2020] [Accepted: 05/16/2021] [Indexed: 11/26/2022] Open
Abstract
Aim of the study Growing data show that toll-like receptors (TLRs) have considerable roles in the pathogenesis of many liver diseases. We aimed to study the relation between TLR3 and TLR7 levels and clinical manifestations of liver decompensation among hepatitis C virus (HCV)-infected Child-Pugh B patients. Material and methods This study included 60 adult patients with Child-Pugh B liver cirrhosis on top of untreated HCV infection. We performed a two-step clustering algorithm depending on TLR-3 gene expression, TLR-7 gene expression, and other influential patients’ characteristics. Results Patients were optimally divided into 2 clusters, each cluster containing 30 patients. The average silhouette score of the clustering algorithm was 0.52, indicating a good clustering power of the model. Patients in cluster 1 showed lower relative expression of TLR3 (0.188 vs. 0.29). The same was true of TLR7 (0.20 vs. 0.31). All patients within cluster 1 had lower limb edema and 93% of them had ascites. On the other hand, no one within cluster 2 had ascites or lower limb edema. The mean platelet count was lower in patients within cluster 1 (74,000 vs. 100,000 cell/mm3). The mean international normalized ratio (INR) level was higher in cluster 1 (1.61 vs. 1.3). The mean Model for End-Stage Liver Disease (MELD) score was higher in cluster 1 (15 vs. 10). Conclusions From these results, we can suggest that lower TLR3 and TLR7 can lead to worse clinical manifestations among patients with HCV-related liver cirrhosis. A deeper exploration of this point can open the door for new approaches for managing decompensated cirrhosis.
Collapse
|
45
|
Long-Term Impact of Hepatitis C Virus Eradication on Liver Stiffness in Egyptian Patients. Can J Gastroenterol Hepatol 2021; 2021:4961919. [PMID: 34589447 PMCID: PMC8476245 DOI: 10.1155/2021/4961919] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2021] [Revised: 08/25/2021] [Accepted: 08/26/2021] [Indexed: 12/11/2022] Open
Abstract
METHODS Liver stiffness measurements (LSM) have been serially assessed 1, 3, and 5 years after HCV clearance in 655 patients who have been treated with DAAs. RESULTS The mean age was 51.44 ± 10 years. 73% of patients were males. 48% were cirrhotics. In noncirrhotics, the mean LSM was significantly decreased from 8.29 ± 2.3 kPa to 4.03 ± 1.0 kPa (p < 0.0001) at the end of the follow-up. Likewise, LSM decreased in cirrhotics from 29.66 ± 14.25 kPa to 22.50 ± 11.16 kPa (p < 0.0001). The proportions of F1, F2, F3, and F4 patients at the baseline were 17.7%, 17.9%, 16.6%, and 47.8%, which became 56.5%, 4.1%, 4.9%, and 34.5%, respectively, with a substantial reversal of cirrhosis in 87 patients (27.7%) at the end of follow-up. CONCLUSIONS There was an overall significant regression of liver stiffness in all patients after sustained HCV eradication. Liver stiffness reflecting mild fibrosis (F0-F2) usually improves shortly after treatment, while measurements reflecting advanced fibrosis (F3-F4) take a longer time to regress to lower fibrosis stages.
Collapse
|
46
|
El-Kebbi IM, Bidikian NH, Hneiny L, Nasrallah MP. Epidemiology of type 2 diabetes in the Middle East and North Africa: Challenges and call for action. World J Diabetes 2021; 12:1401-1425. [PMID: 34630897 PMCID: PMC8472500 DOI: 10.4239/wjd.v12.i9.1401] [Citation(s) in RCA: 67] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 06/21/2021] [Accepted: 08/02/2021] [Indexed: 02/06/2023] Open
Abstract
Type 2 diabetes continues to be a serious and highly prevalent public health problem worldwide. In 2019, the highest prevalence of diabetes in the world at 12.2%, with its associated morbidity and mortality, was found in the Middle East and North Africa region. In addition to a genetic predisposition in its population, evidence suggests that obesity, physical inactivity, urbanization, and poor nutritional habits have contributed to the high prevalence of diabetes and prediabetes in the region. These risk factors have also led to an earlier onset of type 2 diabetes among children and adolescents, negatively affecting the productive years of the youth and their quality of life. Furthermore, efforts to control the rising prevalence of diabetes and its complications have been challenged and complicated by the political instability and armed conflict in some countries of the region and the recent coronavirus disease 2019. Broad strategies, coupled with targeted interventions at the regional, national, and community levels are needed to address and curb the spread of this public health crisis.
Collapse
Affiliation(s)
- Imad M El-Kebbi
- Department of Internal Medicine, Division of Endocrinology, American University of Beirut Medical Center, Faculty of Medicine, Beirut 11072020, Lebanon
- Department of Internal Medicine, Sheikh Shakhbout Medical City, Abou Dhabi 11001, United Arab Emirates
| | - Nayda H Bidikian
- School of Medicine, American University of Beirut, Faculty of Medicine, Beirut 11072020, Lebanon
| | - Layal Hneiny
- University Libraries, Saab Medical Library, American University of Beirut, Beirut 11072020, Lebanon
| | - Mona Philippe Nasrallah
- Department of Internal Medicine, Division of Endocrinology, American University of Beirut Medical Center, Faculty of Medicine, Beirut 11072020, Lebanon
| |
Collapse
|
47
|
Naguib GG, Farid A, Hassan M, Elshafie A, Shazly YE, Shaker MK, Ezzat H, Safwat E, Ahmed OA, Dabbous H, Sherief AF, Hassany M, Elserafy M, Elsayed MH. Direct-acting antiviral regimens in Egyptian patients with chronic hepatitis C virus infection: A real-world single-center experience. Arab J Gastroenterol 2021; 22:285-291. [PMID: 34531135 DOI: 10.1016/j.ajg.2021.06.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Revised: 04/30/2021] [Accepted: 06/01/2021] [Indexed: 01/13/2023]
Abstract
BACKGROUND AND STUDY AIMS Chronic hepatitis C virus (HCV) infection has always been identified as a major health threat and a potential cause of liver cirrhosis, portal hypertension, and other associated problems. The introduction of direct-acting antiviral agents (DAAs) has represented a paradigm shift in HCV management. In this study, we aim to observe the rate of sustained virologic response (SVR12) in a large scale of patients at a single center as well as record the post-treatment changes in the hematologic, hepatic, and renal biochemical profiles. PATIENTS AND METHODS In total, 1933 chronic HCV genotype 4 mono-infected non-HCC patients who completed the treatment with six different DAA regimens in the Faculty of Medicine, Ain Shams University Research Institute (MASRI), were retrospectively enrolled in this study. The rate of sustained virologic response after 12 weeks off-therapy (SVR12) was assessed. The baseline characteristics to predict the SVR12 were then analyzed. The post-treatment changes in many profiles were recorded and analyzed. RESULTS The overall SVR12 rate was 96.2% (after excluding 84 cases who were lost to follow-up). It was achieved in 346/375 patients (92.3%), 466/477 patients (97.7%), 60/62 patients (96.8%), 11/11 patients (100%), 532/545 patients (97.6%), and 445/463 patients (96.1%) who received sofosbuvir/daclatasvir (SOF/DCV), sofosbuvir/daclatasvir/ribavirin (SOF/DCV/RBV), sofosbuvir/ledipasvir (SOF/LDV), sofosbuvir/ledipasvir/ribavirin (SOF/LDV/RBV), sofosbuvir/simeprevir (SOF/SMV), and ombitasvir/paritaprevir/ritonavir/ribavirin (OBV/PTV/r + RBV), respectively. In total, 73 patients (3.8%) failed to achieve SVR12. The baseline aspartate aminotransferase (AST), cirrhotic status, and treatment regimen were determined to have a significant impact on SVR12. In the overall treated population, the levels of serum AST, alanine aminotransferase, albumin, creatinine, bilirubin, and hemoglobin and platelet count improved significantly after treatment. Furthermore, sustained virologic response was strongly related to cirrhosis and its degree. CONCLUSION The interferon-free DAA regimens offered high SVR12 rates in Egyptian patients with chronic HCV infection. They were associated with a significant improvement in the hematologic, hepatic, and renal biochemical profiles. The baseline AST, liver cirrhosis, and treatment regimen might have an impact on achieving SVR.
Collapse
Affiliation(s)
- Gina Gamal Naguib
- Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Ain Shams University, Cairo, Egypt.
| | - Amir Farid
- Department of Tropical Medicine and Infectious Disease, Ain Shams University, Cairo, Egypt
| | - Mohamed Hassan
- Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Ain Shams University, Cairo, Egypt; Armed Forces College of Medicine, Egypt
| | - Ahmed Elshafie
- Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Ain Shams University, Cairo, Egypt; Armed Forces College of Medicine, Egypt
| | - Yehia El Shazly
- Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Ain Shams University, Cairo, Egypt
| | - Mohamed Kamal Shaker
- Department of Tropical Medicine and Infectious Disease, Ain Shams University, Cairo, Egypt
| | - Haitham Ezzat
- Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Ain Shams University, Cairo, Egypt
| | - Eslam Safwat
- Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Ain Shams University, Cairo, Egypt
| | - Ossama Ashraf Ahmed
- Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Ain Shams University, Cairo, Egypt
| | - Hany Dabbous
- Department of Tropical Medicine and Infectious Disease, Ain Shams University, Cairo, Egypt
| | - Ahmed Fouad Sherief
- Department of Tropical Medicine and Infectious Disease, Ain Shams University, Cairo, Egypt
| | - Mohamed Hassany
- National Hepatology & Tropical Medicine Research Institute, Dept Trop Med, Cairo, Egypt
| | - Magdy Elserafy
- Department of Tropical Medicine, Faculty of Medicine, Cairo University, Egypt
| | - Manal Hamdy Elsayed
- Department of Pediatrics and Clinical Research Center, Faculty of Medicine, Ain Shams University, Egypt
| |
Collapse
|
48
|
Shawky H, El-Shenawy R, Helmy NM. Circulating macrophage inflammatory protein-1β/IL-12p40 ratio predicts sofosbuvir-based treatment outcome in HCV- genotype 4 patients. Hum Antibodies 2021; 29:263-274. [PMID: 34511496 DOI: 10.3233/hab-211504] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
This study aimed to evaluate the prognostic value of baseline macrophage inflammatory protein (MIP)-1β/IL12p40 ratio for antiviral treatment outcome in HCV genotype 4 patients. METHODS Sera of 450 treatment-naïve chronic HCV patients and 50 healthy individuals were collected. Liver transaminases, total bilirubin and albumin were biochemically tested, viral RNA was quantified, and circulating MIP-1β and IL-12p40 were estimated using human anti-MIP-1β and IL-12p40 antibodies in Sandwich ELISA. RESULTS No difference was observed in the baseline chemokines levels between responders and relapsers, but the later had a significantly higher MIP-1β/IL-12p40 ratio (P< 0.0001). Multivariate regression analysis of baseline characteristics showed that gender, age, viral load, albumin level and chemokine ratios can significantly predict treatment outcome (P= 0.0114, 0.0095, 0.042, 0.0004 and < 0.0001; respectively). Accordingly, a predictive threshold of baseline chemokine ratio was calculated and it showed an AUC of 0.6917 (P= 0.0108; 95% CI: 0.5566 to 0.8268). The calculated threshold for predicting virologic response was 8.245, with positive and negative predictive values of 92.98% and 100%; respectively. The chemokine ratios had significant correlations with liver transaminases in treated groups whether pre or post-treatment. CONCLUSION Baseline MIP-1β/IL-12p40 ratio represents a non-invasive prognostic biomarker that would provide shorter treatment duration and minimizes the emergence of drug-resistant variants in HCV genotype 4-patients.
Collapse
Affiliation(s)
- Heba Shawky
- Therapeutic Chemistry Department, Division of Pharmaceutical Industries and Drug Research, National Research Centre, Dokki, Cairo, Egypt
| | - Reem El-Shenawy
- Microbial Biotechnology Department, Division of Genetic Engineering and Biotechnology, National Research Centre, Dokki, Cairo, Egypt
| | - Naiera M Helmy
- Microbial Biotechnology Department, Division of Genetic Engineering and Biotechnology, National Research Centre, Dokki, Cairo, Egypt
| |
Collapse
|
49
|
Ahmed MM, O Shaarawy H, Anwar I, Sarhan MD. Barriers to Completing Therapy for Hepatitis C with Direct-Acting Antivirals: A Real-Life Experience from a Single Treatment Center in Egypt. J Prim Care Community Health 2021; 12:21501327211008051. [PMID: 33813925 PMCID: PMC8020227 DOI: 10.1177/21501327211008051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
Introduction Interferon-based therapies against the hepatitis C virus had a poor adherence
profile. On the other hand, new direct-acting antivirals (DAAs) are orally
administered medications, show high efficacy against the hepatitis C virus
in addition to a high safety profile. Therefore, adherence to this treatment
is expected to improve. Assessment for treatment adherence is mandatory to
assess the feasibility of achieving viral hepatitis elimination. Aim The study aims to assess the adherence rate and causes of non-adherence in
Egyptian hepatitis C patients who received interferon-free treatment
regimens. Methods Retrospective data analysis for 668 hepatitis C patient’s records from August
2014 to October 2019 was done. Assessment of treatment adherence was done by
revising the records and phone calls. However, 172 patients were excluded
due to the absence of contact data. Rest of patients (n = 496) was
categorized into 2 groups: Adherent (n = 432) and non-adherent (n = 64). For
whom comparative analysis was done. Results The adherent group (87%) achieved 100 % sustained virological response after
12 weeks (SVR 12). Non-adherence was reported in 12.9% of patients. Low
awareness was the main cause of non-adherence (43.75%). BMI was the only
significant risk factor for poor adherence
(P = .04). Other Patient demographics,
clinical, and laboratory data didn’t show any significant differences
between both groups. Conclusion Interferon-free regimens are tolerable. Raising awareness is mandatory for
proper treatment adherence and, subsequently, good clinical outcomes.
Collapse
Affiliation(s)
| | | | - Ismail Anwar
- Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mai D Sarhan
- Faculty of Medicine, Cairo University, Cairo, Egypt
| |
Collapse
|
50
|
El Kassas M, Salah E, Gad A, Hosny A. Improvement of sexual dysfunction in patients after treatment of hepatitis C virus using directly acting antivirals. Curr Med Res Opin 2021; 37:967-972. [PMID: 33688780 DOI: 10.1080/03007995.2021.1901677] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Revised: 02/23/2021] [Accepted: 03/08/2021] [Indexed: 12/17/2022]
Abstract
OBJECTIVE The impact on male and female sexual dysfunction of treating hepatitis C virus (HCV) using direct-acting antiviral agents (DAAs) has not been sufficiently studied. The aim of this study was to assess the impact of HCV clearance with DAAs on sexual dysfunction (SD) in both sexes. METHODS In chronic HCV patients who were eligible for DAAs, 100 sexually active men completed the Arabic version of the international index of erectile function questionnaire (IIEF-5), and the same number of sexually active women completed Female Sexual Function Index (FSFI), before, at the end of, and 3 months after, treatment for HCV. RESULT The mean of the IIEF-5 scores for male patients was 16.29 ±.07 before treatment, 16.88 ± 3.63 3 months after treatment (p < .01), and was significantly higher, at 19.06 ± 3.31 6 months after treatment cessation (p < .01). In female patients, the mean total FSFI score at baseline was 19.22 ± 2.40 and after 3 months of treatment was 21.61 ± 3.45 (p < .01), with a significant increase (25.09 ± 4.52) after 6 months (p < .01). No difference in the improvement of sexual function was reported either after 3 months or at the end of treatment between males and females (p > .05). CONCLUSIONS Significant improvement in SD associated with HCV infection in both sexes was recorded following viral clearance using DAAs treatment.
Collapse
Affiliation(s)
- Mohamed El Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Eman Salah
- Department of Dermatology and Andrology, Sexual Medicine and STDs, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Aya Gad
- Department of Dermatology and Andrology, Sexual Medicine and STDs, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Ahmed Hosny
- Department of Dermatology and Andrology, Sexual Medicine and STDs, Faculty of Medicine, Helwan University, Cairo, Egypt
| |
Collapse
|