Fouad, Y., G. Esmat, R. Elwakil, S. Zakaria, A. Yosry, I. Waked, M. El-Raziky, W. Doss, M. El-Serafy, E. Mostafa, et al., "The egyptian clinical practice guidelines for the diagnosis and management of metabolic associated fatty liver disease.", Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association, vol. 28, issue 1, pp. 3-20, 2022. Abstract

The landscape of chronic liver disease in Egypt has drastically changed over the past few decades. The prevalence of metabolic-associated fatty liver disease (MAFLD) has risen to alarming levels. Despite the magnitude of the problem, no regional guidelines have been developed to tackle this disease. This document provides the clinical practice guidelines of the key Egyptian opinion leaders on MAFLD screening, diagnosis, and management, and covers various aspects in the management of MAFLD. The document considers our local situations and the burden of clinical management for the healthcare sector and is proposed for daily clinical practical use. Particular reference to special groups was done whenever necessary.

Raziky, M. E., S. Hamdy, Y. Hamada, N. M. Abdelaziz, M. Hassany, W. Doss, and Z. Zakaria, "Efficacy and safety of sofosbuvir and daclatasvir in patients with chronic hepatitis C virus induced cirrhosis with Child-Pugh class B", Egyptian Liver Journal, vol. 12, pp. Article number: 11, 2022.
El Raziky, M. E. S., N. A. Zayed, Y. S. Ibrahim, F. Elrashdy, R. M. H. Shahin, M. Hassany, M. E. Serafy, W. Doss, V. N. Uversky, A. Yosry, et al., "Association analysis of genetic variants of sodium taurocholate co-transporting polypeptide NTCP gene (SLC10A1) and HBV infection status in a cohort of Egyptian patients", Gastroenterology Insights, vol. 12, issue 4, pp. 384-393, 2021.
Raziky, M. E., H. A. Hafez, A. Elsharkawy, T. A. Moneer, S. M. EL-Sheikh, R. M. Maher, and S. A. Sharaf, "Serum level of cytokeratin 19 as a diagnostic and prognostic marker in patients with HCV-related hepatocellular carcinoma", Egyptian Liver Journal , vol. 11, pp. article number 57, 2021.
Saadi, G., K. Kalantar-Zadeh, P. Almasio, G. Ashuntantang, R. Barsoum, A. Bruchfeld, W. Doss, H. Elfishawy, M. E. Raziky, M. El-Serafy, et al., "Hepatitis C virus infection and global kidney health: the consensus proceedings of the International Federation of Kidney Foundations.", African journal of nephrology : official publication of the African Association of Nephrology. African Association of Nephrology, vol. 23, issue 1, pp. 159-168, 2020. Abstract

Hepatitis C virus (HCV) infection is an important cause of major morbidities including chronic liver disease, liver cancer, and acute kidney injury (AKI) as well as chronic kidney disease (CKD). HCV can affect kidney health; among CKD and AKI patients with HCV infection, the clinical outcomes are worse. The prevalence of HCV infection is exceptionally high among dialysis and kidney transplant patients throughout the globe. It is estimated that 5% to 25% or more of dialysis dependent patients are affected by chronic HCV, based on the region of the world. Almost half of all deaths in CKD patients, including HCV-infected patients, are due to cardiovascular disease, and HCV infected patients have higher mortality. Given the importance and impact of the HCV epidemic on CKD and global kidney health, and the status of Egypt as the nation with highest prevalence of HCV infection in the world along with its leading initiatives to eradicate HCV, the International Federation of Kidney Foundations (IFKF) convened a consensus conference in Cairo in December 2017. This article reflects the opinions and recommendations of the contributing experts and reiterates that with the current availability of highly effective and well tolerated pharmacotherapy; CKD patients should be given priority for treatment of HCV, as an important step towards the elimination of viral hepatitis as a public health problem by 2030 according to World Health Organization and IFKF. Every country should have an action plan with the goal to improve kidney health and CKD patient outcomes.

Shousha, H. I., M. Said, W. elakel, A. EL SHAFEI, G. Esmat, E. Waked, M. H. El Sayed, W. Doss, M. E. Razky, M. Mehrez, et al., "Assessment of facility performance during mass treatment of chronic hepatitis C in Egypt: Enablers and obstacles.", Journal of infection and public health, vol. 13, issue 9, pp. 1322-1329, 2020. Abstract

BACKGROUND: The national committee for control of viral hepatitis (NCCVH) in Egypt, settled by the Ministry of health, treated over one million patients in around 60 centers with chronological changes in drug combinations. This research aims to study the health care facilities and services provided by NCCVH treatment centers in Egypt and explore hinders faced.

METHODS: A cross-sectional operational research study. Multistage random sampling technique was applied for Egyptian governorates. From each stratum one governorate was chosen from which one center was randomly selected. Quality of recorded data for each center in the central server (Data-oriented parameter), newly designed score to assess the overall performance of the centers was retrieved from computer based recording system. A self-administered questionnaire was completed by the centers head.

RESULTS: This study included 24 treatment centers from urban, rural areas, Upper and Lower Egypt. The Upper centers showed the best completeness of follow-up records and the least compliance rates. None of the centers had 100% completeness of follow-up data. Proportion of SVR is minimally less than proportion of patient with known outcome in all treatment centers. A novel indicator standardizing the comparisons of performance of different facilities was introduced: Total number of physicians/total number of SVR patients with completed records. The highest response rate: Monfiya Governorate (Lower Egypt), Aswan (Upper Egypt), Completeness of follow-up records: Kalyoubia (Lower Egypt), Sohag governorate (Upper Egypt). The average administrative score was 64%.

CONCLUSION: Challenges of NCCVH program: overcrowdings, resistant sociocultural background among rural patients, limited accessibility for internal migrants and incompleteness of data entry are system lacking points. Strengths include, clear patient pathway, well-established database online application, well-trained physicians and treatment availability.

El-Khayat, H., E. M. Kamal, H. Mahmoud, A. Gomaa, B. Ebeid, Y. Sameh, A. Hasseb, M. E. Raziky, M. E. Serafy, W. Doss, et al., "Retreatment of chronic hepatitis C virus genotype-4 patients after non-structural protein 5A inhibitors' failure: efficacy and safety of different regimens.", European journal of gastroenterology & hepatology, vol. 32, issue 3, pp. 440-446, 2020. Abstract

BACKGROUND: Nonstructural protein 5A (NS5A) is an important regimen for the treatment of chronic hepatitis C virus (HCV) genotype-4 infected patients. Retreatments for NS5A virologic failure are limited. The aim of this study is to provide real-life data regarding the effectiveness and safety of retreatment with different regimens after NS5A regimen virologic failure in GT4 patients.

PATIENTS AND METHODS: A total of 524 HCV patients (mean age 48 ± 11 years, 71% males), with virologic failure to sofosbuvir+daclatasvir, n = 450 and sofosbuvir/ledipasvir, n = 74 were included in this study. Patients were retreated with sofosbuvir + ombitasvir/paritaprevir/ritonavir + ribavirin, n = 278 and sofosbuvir + simeprevir + daclatasvir + ribavirin, n = 246. Response was evaluated 12 weeks after the end of treatment (SVR12).

RESULTS: Overall, SVR12 was 95.2% [95% confidence interval (CI) 93.3%-97.1%]. In sofosbuvir + ombitasvir/paritaprevir/ritonavir + ribavirin and sofosbuvir + simeprevir + daclatasvir + ribavirin, SVR12s were 94.9% (95% CI 92.5%-97.4%) and 95.5% (95% CI 92.8%-98%), respectively. In liver cirrhosis patients, SVR12s were 96.4% (95% CI 90.7%-100%) and 98% (95% CI 94.9%-100%), respectively. Relapse in the sofosbuvir + ombitasvir/paritaprevir/ritonavir + ribavirin was n = 14 patients, and n = 11 patients in sofosbuvir + simeprevir + daclatasvir + ribavirin. Three patients developed hepatic encephalopathy, haematemesis, lower limb oedema, and one patient died in the SOF + OBV/PTV/RTV + RIB. In the sofosbuvir + simeprevir + daclatasvir + ribavirin, three patients developed hepatocellular carcinoma and one patient died. No treatment discontinuation due to anaemia.

CONCLUSION: Salvage treatment for NS5A-treatment failure is effective and well tolerated in genotype-4 patients, in both noncirrhotic and compensated cirrhotic groups.

Darweesh, S. K., K. Elsaeed, H. Omar, M. E. Raziky, W. elakel, M. E. Serafy, S. A. Ismail, A. A. Gomaa, M. Mehrez, M. Elkassas, et al., "High SVR rate following retreatment of non-sustained virological responders to sofosbuvir based anti-HCV therapies regardless of RAS testing: A real-life multicenter study.", Expert review of gastroenterology & hepatology, vol. 13, issue 9, pp. 907-914, 2019. Abstract

Evaluation of the efficacy and safety of sofosbuvir/daclatasvir/ribavirin (SOF/DCV/RBV) in treating non-sustained virological responders (non-SVR12) to prior sofosbuvir-based therapy, in absence of RAS testing in mass treatment, and determination of the optimal timing to start re-treatment. Real-life prospective observational study included prior non-responders to 24-weeks SOF-RBV (n = 679, 67%) or 12-weeks SOF- RBV- PEG (n = 335, 33%). Patients were re-treated with daily SOF/DCV/RBV for 12 (n = 270) or 24 weeks (n = 744). The primary efficacy endpoint was SVR12. The primary safety endpoints were reported adverse events (AEs) from baseline to SVR12 time point. We included 1,014 patients [age 52 ± 9 years, 58.48% men]. Cirrhosis was documented in 46.98% and 27.5% of SOF-RBV and SOF-RBV-PEG non-responders respectively. Overall, SVR12 was 90.6% [92.2% for 12 weeks therapy and 90.05% for 24 weeks therapy]. Mild AEs occurred in 5.13% (n=52) and 3.1% (n=32) discontinued treatment including eight on-treatment mortalities. Higher baseline FIB-4 and shorter interval before starting retreatment (<6 months) were independent predictors of non-SVR12 on multivariate regression analysis. SOF/DCV/RBV is an effective and safe treatment option for non-responders to prior sofosbuvir-based therapy. Six months interval before retreatment is optimal for achieving favorable SVR.

Elsharkawy, A., M. El-Raziky, W. El-Akel, K. El-Saeed, R. E. Etreby, M. Hassany, M. H. El-Sayed, K. Kabil, S. A. Ismail, M. El-Serafy, et al., "Planning and prioritizing direct-acting antivirals treatment for HCV patients in countries with limited resources: Lessons from the Egyptian experience.", Journal of hepatology, vol. 68, issue 4, pp. 691-698, 2018. Abstract

BACKGROUND AND AIMS: The introduction of direct-acting antivirals for hepatitis C virus (HCV) in Egypt led to massive treatment uptake, with Egypt's national HCV treatment program becoming the largest in the world. The aim of this paper is to present the Egyptian experience in planning and prioritizing mass treatment for patients with HCV, highlighting the difficulties and limitations of the program, as a guide for other countries of similarly limited resources.

METHODS: Baseline data of 337,042 patients, treated between October 2014 to March 2016 in specialized viral hepatitis treatment centers, were grouped into three equal time intervals of six months each. Patients were treated with different combinations of direct-acting antivirals, with or without ribavirin and pegylated interferon. Baseline data, percentage of patients with known outcome, and sustained virological response at week 12 (SVR12) were analyzed for the three cohorts. The outcomes of 94,258 patients treated in the subsequent two months are also included.

RESULTS: For cohort-1, treatment was prioritized for patients with advanced fibrosis (F3-F4 fibrosis, liver stiffness ≥9.5 kPa, or Fibrosis-4 ≥3.25). Starting cohort-2, all stages of fibrosis were included (F0-F4). The prioritization strategy in the initial phase caused delays in enrollment and massive backlogs. Cohort-1 patients were significantly older, and more had advanced fibrosis compared to subsequent cohorts. The percentage of patients with known SVR12 results were low initially, and increased with each cohort, as several methods to capture patient results were adopted. Sofosbuvir-ribavirin therapy for 24 weeks had the lowest SVR12 rate (82.7%); while other therapies were associated with SVR12 rates between 94% and 98%.

CONCLUSION: Prioritization based on fibrosis stage was not effective and enrollment increased greatly only after including all stages of fibrosis. The availability of generic drugs reduced costs, and helped massively increase uptake of the program. Post-treatment follow-up was initially very low, and although this has increased, further improvement is still needed.

LAY SUMMARY: We are presenting the largest national program for HCV treatment in the world. We clearly demonstrate that hepatitis C can be cured efficiently in large scale real-life programs. This is a clear statement that global HCV eradication is foreseeable, providing a model for other countries with limited resources and prevalent HCV. Moreover, the availability of generic products has influenced the success of this program.

El-Raziky M, Khairy M, F. S. E. T. A. A. A. O., "Effect of Direct-Acting Agents on Fibrosis Regression in Chronic Hepatitis C Virus Patients' Treatment Compared with Interferon-Containing Regimens.", J Interferon Cytokine Res., vol. 38, issue 3, pp. 129-136, 2018.