Alem, S. A., N. El Garhy, E. E. Khateeb, M. Khalil, A. Cordie, A. Elsharkawy, R. Fouad, G. Esmat, and M. S. Abdelbary, "Serial changes in renal indices in chronic HCV patients with and without HIV co-infection receiving sofosbuvir and tenofovir-based therapies.", Transactions of the Royal Society of Tropical Medicine and Hygiene, vol. 117, issue 4, pp. 285-296, 2023. Abstract

BACKGROUND: Sofosbuvir (SOF) is authorized for hepatitis C virus (HCV) patients. The nephrotoxicity of SOF on HCV mono-infected and HCV-human immunodeficiency virus (HIV) individuals receiving antiretroviral therapy (ART) remains controversial.

METHODS: A prospective study including 159 HCV mono-infected and 124 HCV-HIV individuals (47 were ART naïve and 77 were tenofovir [TDF]-based ART) who presented with an estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.73 m2 at baseline and were treated with SOF-daclatasvir for 12 weeks. The eGFR was estimated using the Chronic Kidney Disease Epidemiology Collaboration equation over the study period.

RESULTS: HCV patients had a progressive decline in median levels of eGFR compared with HCV-HIV patients who were ART naïve and those receiving TDF-based ART during and after discontinuing SOF-DAC treatment (96, 109 and 114 at baseline vs 94, 117 and 108 at the end of treatment [EOT]) vs 95, 114 and 115 ml/min/1.73 m2 at 12 weeks after treatment [SVR12], respectively). Moreover, the rate of eGFR stage worsening was more pronounced in HCV mono-infected compared with HCV-HIV individuals who were ART naïve and those receiving TDF-based ART (21.4% vs 8.5% and 14.3% at EOT; 21.4% vs 2.1% and 6.5% at SVR12, respectively). Multivariable regression analysis showed that baseline variables were not independent predictors of eGFR stage worsening either at EOT or SVR12.

CONCLUSIONS: Because the changes in eGFR were minimal and not of clinical significance, and TDF was not associated with an increase in renal dysfunction, SOF-based direct-acting antivirals could be safely used in HCV mono-infected and HCV-HIV individuals, even in those on TDF-based ART.

Morgan, J. R., E. Marsh, A. Savinkina, S. Shilton, S. Shadaker, T. Tsertsvadze, G. Kamkamidze, M. Alkhazashvili, T. Morgan, P. Belperio, et al., "Determining the lower limit of detection required for HCV viral load assay for test of cure following direct-acting antiviral-based treatment regimens: Evidence from a global data set.", Journal of viral hepatitis, vol. 29, issue 6, pp. 474-486, 2022. Abstract

Achieving global elimination of hepatitis C virus requires a substantial scale-up of testing. Point-of-care HCV viral load assays are available as an alternative to laboratory-based assays to promote access in hard to reach or marginalized populations. The diagnostic performance and lower limit of detection are important attributes of these new assays for both diagnosis and test of cure. Therefore, our objective was to determine an acceptable LLoD for detectable HCV viraemia as a test for cure, 12 weeks post-treatment (SVR12). We assembled a global data set of patients with detectable viraemia at SVR12 from observational databases from 9 countries (Egypt, the United States, United Kingdom, Georgia, Ukraine, Myanmar, Cambodia, Pakistan, Mozambique) and two pharmaceutical-sponsored clinical trial registries. We examined the distribution of HCV viral load at SVR12 and presented the 90th, 95th, 97th and 99th percentiles. We used logistic regression to assess characteristics associated with low-level virological treatment failure (defined as <1000 IU/mL). There were 5973 cases of detectable viraemia at SVR12 from the combined data set. Median detectable HCV RNA at SVR12 was 287,986 IU/mL. The level of detection for the 95th percentile was 227 IU/mL (95% CI 170-276). Females and those with minimal fibrosis were more likely to experience low-level viraemia at SVR12 compared to men (adjusted odds ratio AOR = 1.60 95% confidence interval [CI] 1.30-1.97 and those with cirrhosis (AOR = 1.49 95% CI 1.15-1.93). In conclusion, an assay with a level of detection of 1000 IU/mL or greater may miss a proportion of those with low-level treatment failure.

Yosry, A., N. Zayed, R. M. Dawood, M. K. Ibrahim, M. Elsharkawy, S. M. Ekladious, A. Khairy, A. Elsharkawy, M. Khairy, S. A. Alem, et al., "Highly Sensitive Serum miRNA Panel for the Diagnosis of Hepatocellular Carcinoma in Egyptian Patients with HCV-Related HCC.", Laboratory medicine, vol. 53, issue 5, pp. 523-529, 2022. Abstract

OBJECTIVE: This study aimed at exploring the potential role of a panel of serum micro-RNA (miRNA) markers in liver fibrosis and hepatocellular carcinoma (HCC) diagnosis in patients with chronic hepatitis C virus (HCV) infection.

METHODS: The study included 157 chronic HCV patients and 62 HCC patients who presented to the Cairo University Center for Hepatic Fibrosis, Endemic Medicine Department, from 2015 to 2017. Relevant clinical and laboratory data were collected and sera were subjected to miRNA expression profiling. Eleven miRNA markers were studied and receiver operating characteristic curves were constructed to investigate the best cutoff values of the miRNAs that showed altered expression in HCC compared to HCV-associated advanced fibrosis.

RESULTS: miRNA expression profiling revealed 5 miRNAs (miR-124, miR-141, miR-205, miR-208a, miR-499a) were significantly upregulated and 2 miRNAs were significantly downregulated (miR-103a, miR-15a) in HCC compared to advanced fibrosis patients. No significant difference was observed in miRNA expression between advanced fibrosis and early hepatic fibrosis apart from a significant downregulation of miR-155-5p in advanced fibrosis.

CONCLUSION: Serum miRNAs could serve as potential diagnostic tools for the diagnosis of HCC.

Elsharkawy, A., R. Samir, and M. El-Kassas, "Fibrosis regression following hepatitis C antiviral therapy.", World journal of hepatology, vol. 14, issue 6, pp. 1120-1130, 2022. Abstract

Hepatitis C virus (HCV) infection is one of the most common causes of liver pathology. It is a major etiological factor of continuous liver injury by triggering an uncontrolled inflammatory response, causing liver fibrosis and cirrhosis. Liver fibrosis is a dynamic process that can be reversible upon timely cessation of the injurious agent, which in cases of HCV is represented by the sustained virological response (SVR) following antiviral therapies. Direct-acting antiviral therapy has recently revolutionized HCV therapy and minimized complications. Liver fibrosis can be assessed with variable invasive and non-invasive methods, with certain limitations. Despite the broad validation of the diagnostic and prognostic value of non-invasive modalities of assessment of liver fibrosis in patients with HCV, the proper interpretation of liver stiffness measurement in patients after SVR remains unclear. It is also still a debate whether this regression is caused by the resolution of liver injury following treatment of HCV, rather than true fibrosis regression. Regression of liver fibrosis can possess a positive impact on patient's quality of life reducing the incidence of complications. However, fibrosis regression does not abolish the risk of developing hepatocellular carcinoma, which mandates regular screening of patients with advanced fibrosis.

Esmat, G., T. Elbaz, A. Elsharkawy, M. Abdullah, and M. El Kassas, "Emerging from the screening of 57 million citizens and treating 4 million patients: future strategies to eliminate hepatitis C from Egypt.", Expert review of anti-infective therapy, vol. 18, issue 7, pp. 637-642, 2020. Abstract
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INTRODUCTION: Egypt succeeded in establishing a successful model of care for hepatitis C virus (HCV) management in the country with the highest worldwide disease prevalence. The Egyptian ministry of health announced an optimistic goal of near disease elimination. More steps are still required to achieve such a goal.

AREAS COVERED: This review covers the efforts made in treatment and prevention of HCV by the Egyptian National Committee for the Control of Viral Hepatitis (NCCVH) with emphasis on the extensive screening program that was able to screen more than 57 million citizens, and future strategies implemented to ensure eradicating the virus from the country.

EXPERT OPINION: Despite the great efforts and the proven success in controlling the HCV epidemic in Egypt, some facets of the Egyptian program still need to be upgraded to reach the HCV elimination goal. A significant workload with follow up programs for those who were successfully treated, and treatment failure cases are existing. More enhancement for the currently performed prevention and control measure is missing. Also, we strongly recommend conducting a recent nationwide survey to document the actual infection rates of HCV after all these efforts.

Waked, I., G. Esmat, A. Elsharkawy, M. El-Serafy, W. Abdel-Razek, R. Ghalab, G. Elshishiney, A. Salah, S. Abdel Megid, K. Kabil, et al., "Screening and Treatment Program to Eliminate Hepatitis C in Egypt.", The New England journal of medicine, vol. 382, issue 12, pp. 1166-1174, 2020.
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Elkabany, Z. A., R. T. Hamza, E. A. R. Ismail, A. Elsharkawy, A. Yosry, S. Musa, M. A. Khalaf, R. M. Elgawesh, and G. Esmat, "Serum visfatin level as a noninvasive marker for nonalcoholic fatty liver disease in children and adolescents with obesity: relation to transient elastography with controlled attenuation parameter.", European journal of gastroenterology & hepatology, vol. 32, issue 8, pp. 1008-1016, 2020. Abstract
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BACKGROUND: Obesity is associated with an increased risk of nonalcoholic fatty liver disease (NAFLD). Visfatin is an adipokine produced by visceral fat tissue and liver cells. Transient elastography with controlled attenuation parameter (CAP) noninvasively assesses liver fibrosis and steatosis.

AIM: To measure visfatin level in 80 children and adolescents with obesity as a potential biomarker for NAFLD and assess its relation to transient elastography.

METHODS: Abdominal ultrasound, liver stiffness and CAP measurements were performed for all patients. Fasting lipid profile, fasting blood glucose, insulin level, liver and kidney functions, coagulation profile and serum visfatin levels were assessed.

RESULTS: Among patients with obesity, 31 (38.8%) had NAFLD and 16 (20%) patients had elevated alanine aminotransferase (ALT), while 9 (11.2%) had both NAFLD and elevated ALT. Transient elastography showed that 12.5% had fibrosis stage F1, 2.5% had F2 and another 2.5% had F3 while none had F4. Using CAP, 23.8, 13.8 and 17.5% had S1, S2 and S3, respectively. Serum visfatin levels were significantly elevated in all patients compared with nonobese controls. Higher visfatin levels were found among patients with dyslipidemia, NAFLD, elevated ALT and steatosis defined by CAP. Serum visfatin was related to the degree of fibrosis and steatosis. Visfatin cutoff value 18 ng/mL could significantly detect the presence of NAFLD with 83.9% sensitivity and 81.4% specificity. Serum visfatin was positively correlated to BMI, waist circumference, waist/hip ratio, ALT, total cholesterol, liver stiffness and CAP.

CONCLUSIONS: Visfatin could be a promising serum biomarker for monitoring liver disease among pediatric patients with obesity.

Shereen Abdel Alem, Aisha Elsharkawy, W. E. A. A. A. O., M. E. K. Rabab Maamoun Salama, Manal Hamdy El-Sayed, F. A. D. Z. H. Mahmoud Anees, Mahmoud Shedeed, and I. W. G. E. W. D. & Yehia El Shazly, Magdy El-Serafy, "Liver stiffness measurements and FIB-4 are predictors of response to sofosbuvir-based treatment regimens in 7256 chronic HCV patients", Expert Review of Gastroenterology & Hepatology, vol. 13, issue 10, pp. 1009-1016, 2019.
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