Hashem, M. B., Aleem S. A., Elsharkawy A., Fouad R., Esmat G., & abdellatif Z. (2023).  Performance of Albumin-Bilirubin (ALBI) score in comparison to other non-invasive markers in the staging of liver fibrosis in chronic HCV patients. Egyptian Liver Journal. 13(1), 40.
Yosry, A., Zayed N., Dawood R. M., Ibrahim M. K., Elsharkawy M., Ekladious S. M., et al. (2022).  Highly Sensitive Serum miRNA Panel for the Diagnosis of Hepatocellular Carcinoma in Egyptian Patients with HCV-Related HCC.. Laboratory medicine. 53(5), 523-529. 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.

Etreby, R. E., Elraouf M. A., Fouad A., Nasser M., Bassiouni M. A., Zayed N., et al. (2021).  Screening for chronic hepatitis C and chronic hepatitis B infections among pregnant females: a cross-sectional study. Egyptian Liver Journal. 11(43), 1-5.
Shaker, O. G., Mohammed S. R., Mohammed A. M., & Mahmoud Z. (2018).  Impact of microRNA-375 and its target gene SMAD-7 polymorphism on susceptibility of colorectal cancer.. Journal of clinical laboratory analysis. 32(1),  Abstract

BACKGROUND: Colorectal cancer (CRC) has a high morbidity and mortality. Many studies reported that mir-375 is frequently down-regulated in many cancers including esophageal cancer, hepatocellular carcinoma, breast cancer and leukemias.

AIM: Our aim was to study the expression of microRNA-375 and its target gene SMAD-7 polymorphisms (rs4939827) in CRC patients in comparison to control subjects and to correlate these results with clinical data of patients to elucidate their role in pathogenesis and early diagnosis of CRC.

MATERIAL AND METHODS: The present study was conducted on 122 subjects divided into 86 patients with CRC and 36 age- and sex-matched controls. The followings were done to all subjects: full history taking, full clinical examination, complete blood picture, serum (ALT, AST), serum albumin, CEA, TLC, PLT, and creatinine. Gene expression of miRNA-375 from serum was done by real-time PCR. Gene polymorphism SNPs of SMAD7 (rs4939827) was also done in DNA extracted from blood by real-time PCR.

RESULTS: As regards the polymorphism of SMAD7, we found that CC (wild) genotype has high percentage in controls compared to CRC cases (36.1% vs 15.1%). Meanwhile, the mutant and heterozygotes genotypes showed high percentage among cases compared to controls (33.7%, and 51.2% respectively) vs (22.2%, and 41.7% respectively) with no significant statistical analysis. There was a statistically significant high T-allelic frequency among cases and C-allelic frequency among controls. There was a statistically significant association between fold change in micro RNA (-375) and the susceptibility to CRC as there is down-regulation of the microRNA-375 in CRC group with fold change in 0.42±0.27.

CONCLUSION: Micro RNA-375 and rs4939827 SNP in SMAD7 could be considered as potential markers for detecting and early diagnosing CRC patients.

Etreby, R. E., Said M., abdellatif Z., Saad Y., Serafy M. E., Dabes H., et al. (2018).  High prevalence of HCV (GT4)-related TSH abnormality among 13402 Egyptian patients treated with direct acting antiviral therapy.. Hepatology international. 12(2), 143-148. Abstract

BACKGROUND: HCV is associated with several extra hepatic diseases including thyroid dysfunction. This study aims at evaluating prevalence of thyroid dysfunction and its possible predictors in a large cohort of HCV GT4-infected patients, and the role of thyroid dysfunction as a predictor of response in the setting of direct acting antivirals (DAAs).

METHODS: Patients registered on the web-based registry system to receive therapy for chronic HCV in Beheira governorate viral hepatitis specialized treatment center affiliated to the National committee for control of viral hepatitis (NCCVH), Ministry of health, Egypt in the period from January 2015 to October 2016. Their data were exported and analyzed for the prevalence of thyroid dysfunction and its associated variables.

RESULTS: Out of 13,402 patients, 2833 (21.1%) had elevated TSH level > 4.5 mIU/l (hypothyroidism). Female gender (62.7%), older age, higher FIB4, AST, and BMI and lower albumin were significantly associated with elevated TSH level on univariate analysis, while liver stiffness measured by fibroscan was not significantly associated. On the other hand, 466 patients (3.5%) showed low TSH level < 0.4 mIU/l (hyperthyroidism). Older age (median 52 years) and male gender (51.5%) were the only significantly associated variables. No association was found between SVR and baseline TSH level. Follow-up of 236 patients after SVR revealed improvement in TSH level in 80% of them.

CONCLUSION: Hypothyroidism is prevalent in patients with chronic HCV GT4, and is influenced by patient gender and age. Pretreatment TSH does not affect SVR after DAAs. Despite limited data SVR achievement after DAAs improves thyroid dysfunction.

Omar, H., Said M., Etreby R. E., Mehrez M., Bassam M., abdellatif Z., et al. (2018).  Longitudinal assessment of hepatic fibrosis in responders to direct-acting antivirals for recurrent hepatitis C after liver transplantation using noninvasive methods.. Clinical transplantation. 32(8), e13334. Abstract

Successful eradication of recurrent hepatitis C virus (HCV) infection following liver transplantation (HCV) improves graft survival. This study aimed at evaluation of hepatic fibrosis changes among long-term responders to DAA therapy for recurrent HCV after liver transplantation using noninvasive methods. Patients with significant hepatic fibrosis (≥F2) who achieved SVR12 after treatment with DAAs for recurrent HCV were included (n = 52). Hepatic fibrosis status was assessed, noninvasively, by calculation of fibrosis-4 score (FIB-4) and Aspartate Aminotransferase Platelet Ratio Index (APRI) and by measurement of graft stiffness using FibroScan at baseline and 12 and 18 months post-treatment. Acoustic radiation force imaging (ARFI) was done for all patients 12 and 18 months post-treatment. Patients were classified into two groups based on baseline liver stiffness measurement (LSM) by FibroScan; significant fibrosis (F2; n = 28) and advanced fibrosis groups (≥F3). Over 18-month follow-up period, there was serial improvement of FIB-4, APRI, and LSM by FibroScan in both groups. Higher baseline LSM and delayed initiation of antiviral therapy were significant predictors of lack of fibrosis regression (P-value 0.01 and 0.04, respectively). Fibroindices and LSM improved over time in liver transplant recipients who responded to DAAs. Baseline LSM can predict post-treatment fibrosis regression.

Alem, S. A., Said M., Anwar I., abdellatif Z., Elbaz T., Etreby R. E., et al. (2018).  Improvement of liver stiffness measurement, acoustic radiation force impulse measurements, and noninvasive fibrosis markers after direct-acting antivirals for hepatitis C virus G4 recurrence post living donor liver transplantation: Egyptian cohort.. Journal of medical virology. 90(9), 1508-1515. Abstract

Progression of recurrent hepatitis C is accelerated in liver transplant (LT) recipients. Direct-acting antivirals (DAAs) have recently emerged as a promising therapeutic regimen for the treatment of hepatitis C virus infection. Rates of sustained virological response (SVR) have drastically improved since the introduction of DAAs. The aim is to elucidate the changes in liver stiffness measurement (LSM) by transient elastography (TE) as well as acoustic radiation force impulse (ARFI) elastography and fibrosis scores after DAA treatment in LT recipients with hepatitis C virus recurrence. A single-center, prospective study including 58 LT recipients with hepatitis C recurrence who received different sofosbuvir-based treatment regimens. Transient elastography and ARFI elastography values were recorded as well as fibrosis 4 score (FIB-4) and aspartate aminotransferase-to-platelet ratio index were calculated at baseline and SVR at week 24 (SVR24). The outcome was improvement in LSM and at least a 20% decrease in LSM at SVR24 compared with baseline. The sustained virological response was 98.1%. There was improvement of platelet counts, alanine aminotransferase, and aspartate aminotransferase, which in turn caused improvement in fibrosis scores at SVR24. LSM by TE and ARFI elastography decreased from the baseline median value of 6.3 kPa (interquartile range [IQR]; 4.6 to 8.8 kPa) and 1.28 m/s (IQR; 1.07 to 1.53 m/s) to an SVR24 median value of 6.2 kPa (IQR; 4.85 to 8.9 kPa) and 1.12 (IQR; 0.97 to 1.30 m/s), respectively. Logistic regression analysis showed that baseline viral load was the only significant predictor of improvement in LS after DAA therapy at SVR24. Sofosbuvir-based treatment resulted in an early improvement in parameters of liver fibrosis in post-LT patients with hepatitis C recurrence.

El-Nahaas, S. M., Fouad R., Elsharkawy A., Khairy M., Elhossary W., Anwar I., et al. (2018).  High sustained virologic response rate using generic directly acting antivirals in the treatment of chronic hepatitis C virus Egyptian patients: single-center experience.. European journal of gastroenterology & hepatology. 30(10), 1194-1199. Abstract

BACKGROUND: Hepatitis C virus (HCV) is a major health problem in Egypt, with a high prevalence of genotype 4.

AIM: This study aimed to evaluate the safety and efficacy of generic sofosbuvir (SOF) plus generic daclatasvir (DAC) with or without ribavirin in the treatment of Egyptian chronic HCV patients compared with the use of brand drugs.

MATERIALS AND METHODS: An observational study that included 234 Egyptian chronic HCV patients was carried out. Patients were classified into two groups: group A (101 patients) received brand SOF 400 mg plus brand DAC 60 mg and group B (134 patients) received generic SOF 400 mg plus generic DAC 60 mg with or without ribavirin for 12 weeks. The end point was a sustained virological response at 12 weeks after treatment.

RESULTS: Thirty-eight (37.2%) patients in group A were treatment experienced compared with 12 (9.02%) patients in group B; there were 39 (38%) cirrhotic patients in group A and 22 (16.5%) cirrhotic patients in group B. In group A, 50% of patients received ribavirin, while in group B, 42.1% of patients received ribavirin. All patients were followed up; all of them attended their week 12 post-treatment visit with negative HCV RNA, with achievement of sustained virological response at 12 in 100% of patients receiving generic drugs (group B) and 99% of patients receiving brand drugs (group A). Generic SOF and DAC were well tolerated, with mild adverse events including fatigue and headache.

CONCLUSION: Use of generic SOF and DAC with or without ribavirin is an extremely effective and a well-tolerated treatment for Egyptian chronic HCV patients.

Abdelaziz, A. O., Shousha H. I., Said E. M., Soliman Z. A., Shehata A. A., Nabil M. M., et al. (2018).  Evaluation of liver steatosis, measured by controlled attenuation parameter, in patients with hepatitis C-induced advanced liver fibrosis and hepatocellular carcinoma.. European journal of gastroenterology & hepatology. 30(11), 1384-1388. Abstract

INTRODUCTION: Steatosis is a documented feature of chronic hepatitis C (CHC). There is an association between steatosis decrease and fibrosis progression. The association between steatosis and advanced fibrosis versus hepatocellular carcinoma (HCC) development has not been precisely evaluated. The controlled attenuation parameter (CAP) was applied as an immediate and efficient process to detect and quantify hepatic steatosis with adequate accuracy.

AIMS: The aim of this study was to assess the difference in liver steatosis between patients with hepatitis C virus-related advanced hepatic fibrosis versus HCC.

PATIENTS AND METHODS: This cross-sectional study included 130 patients with HCC, attending the multidisciplinary HCC clinic, Cairo University, and 54 patients with CHC between October 2015 and June 2016. Clinical and laboratory characteristics were recorded. Liver stiffness and CAP were obtained by using the FibroScan 502, touch.

RESULTS: All included patients had genotype 4. The mean CAP value was significantly lower in HCC (209.5±57.1 dB/m) versus CHC (259.9±54.9 dB/m). Receiver operating characteristic curve revealed an area under the curve of 0.75 for the differentiation between groups. At a cutoff value of 237 dB/m, sensitivity was 72.3%, specificity was 70.7%, positive likelihood ratio was 2.5, and negative likelihood ratio was 0.4 in the differentiation between CHC versus HCC. Logistic regression analysis revealed an odds ratio of 6.4 for the diagnosis of HCC with CAP of less than 237 dB/m. Multivariate analysis, controlling for age, sex, BMI, triglycerides, and cholesterol levels, revealed a significantly increased odds for HCC diagnosis (odds ratio: 4.3, P=0.006).

CONCLUSION: The progression of CHC is associated with a decrease in steatosis, particularly toward advanced fibrosis and HCC. Steatosis reduction less than 237 dB/m is likely to be associated with HCC.