Etreby, R. E., W. elakel, M. Said, M. El Kassas, S. Seif, T. Elbaz, M. E. Raziky, S. Abdel Rehim, S. Zaky, R. Fouad, et al., "Real life Egyptian experience of efficacy and safety of Simeprevir/Sofosbuvir therapy in 6211 chronic HCV genotype IV infected patients.", Liver international : official journal of the International Association for the Study of the Liver, vol. 37, issue 4, pp. 534-541, 2017. Abstract

BACKGROUND & AIMS: Major changes have emerged during the last few years in the therapy of chronic HCV. Several direct acting antiviral agents have been developed showing potent activity with higher rates of sustained virological response, even in difficult-to-treat patients. This study explores real life experience concerning efficacy, safety and possible predictors of response for the first cohort of Egyptian patients with chronic HCV genotype IV treated with Sofosbuvir/Simprevir combination therapy.

METHODS: This real life study recruited the first (6211) chronic HCV genotype IV Egyptian patients, who received antiviral therapy in viral hepatitis specialized treatment centres affiliated to the National committee for control of viral hepatitis. All enrolled patients received 12 weeks course of daily combination of sofosbuvir (400 mg) and simeprevir (150 mg). Patients were closely monitored for treatment safety and efficacy.

RESULTS: Overall sustained virological response 12 rate was 94.0% while the end of treatment response rate was 97.6%. sustained virological response 12 rates in easy and difficult-to-treat groups were 96% and 93% respectively. Univariate and multivariate logistic regression analysis revealed significant association of low albumin (<3.5), cirrhosis and Fib-4 score (>3.25) with treatment failure. Fatal adverse events occurred in 23/6211 cases (0.37%) due to liver cell failure adverse events or SAEs leading to treatment discontinuation occurred in 97 patients (1.6%).

CONCLUSION: Sofosbuvir/Simeprevir combination is an effective and well tolerated regimen for patients with chronic HCV genotype IV.

Haleem, H. A., H. G. E. deen, M. M. Nabeel, R. Abdelmoniem, W. elakel, N. Zayed, Z. abdellatif, B. Monir, M. S. AbdelAziz, S. Mogawer, et al., "Evaluation of acoustic radiation force impulse (ARFI) elastography as non-invasive diagnostic tool in living donor liver transplantation.", Abdominal radiology (New York), vol. 44, issue 2, pp. 464-472, 2019. Abstract

BACKGROUND AND AIMS: Role of acoustic radiation force impulse (ARFI) elastography, in transplant setting, is not well established. We aimed to define the normal mean values of the liver stiffness by ARFI Elastography in healthy liver donors and to evaluate ARFI elastography as predictor of graft fibrosis post living donor liver transplant (LDLT) in comparison to other non-invasive methods (transient elastography [TE], APRI and FIB4).

PATIENTS AND METHODS: A total of 100 subjects (70 recipients and 30 donors) were recruited. APRI and FIB4 scores were calculated for all recipients. TE and ARFI elastography (Siemens Acuson S2000 Ultrasound System, Germany) were performed to all subjects. All donors and only 30 recipients had liver biopsy. Significant fibrosis was defined as ≥ F2.

RESULTS: The mean ARFI velocity among the donors was 1.05 ± 0.09 m/s. Regarding the recipients: mean age was 49.5 ± 8.49 years, 85.7% males, fibrosis stages < F2 were the most frequent stages by liver biopsy (86.7%) and TE (67.1%). ARFI median was significantly correlated with TE median, APRI and FIB-4 (r = 0.888, p = 0.000; r = 0.62, p = 0.000, and r = 0.585, p = 0.000, respectively). ARFI performed well in discriminating patients with ≥ F2 (AUROC = 0.93, 95% CI 0.86-0.99, p < 0.01) with best cutoff median value of 1.34 m/s (sensitivity 90%, specificity 82%).

CONCLUSION: ARFI can be used as a reliable method in assessment of significant fibrosis post-LDLT.

Alem, S. A., M. Said, I. Anwar, Z. abdellatif, T. Elbaz, R. E. Etreby, M. Abouelkhair, M. El-Serafy, S. Mogawer, M. E. - Amir, et al., "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, vol. 90, issue 9, pp. 1508-1515, 2018. 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.

Etreby, R. E., M. Said, Z. abdellatif, Y. Saad, M. E. Serafy, H. Dabes, K. Elsaeed, Y. El-Shazly, and W. Doss, "High prevalence of HCV (GT4)-related TSH abnormality among 13402 Egyptian patients treated with direct acting antiviral therapy.", Hepatology international, vol. 12, issue 2, pp. 143-148, 2018. 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.

Attia, D., K. Elsaeed, W. Elakel, T. Elbaz, A. Omar, A. Yosry, M. H. Elsayed, M. Said, M. El Raziky, M. Anees, et al., "The adverse effects of interferon-free regimens in 149 816 chronic hepatitis C treated Egyptian patients.", Alimentary pharmacology & therapeutics, vol. 47, issue 9, pp. 1296-1305, 2018. Abstract

BACKGROUND: Interferon-free regimens are associated with high sustained virological response; however, associated adverse effects have yet to be fully reported.

AIM: To evaluate the adverse effects associated with the different direct-acting antiviral drug (DAA) regimens in Egyptian patients.

METHODS: This multicenter retrospective study included all adverse effects during and after treatment with DAA regimens of 149 816 chronic hepatitis C treated Egyptian patients. Patients received sofosbuvir (SOF)/ribavirin (RBV) (n = 21 835), SOF/simeprevir (n = 24 215) SOF/daclatasvir (DCV) (n = 58 477), SOF/DCV/RBV (n = 45 188) and paritaprevir/ombitasvir/ritonavir/RBV (n = 101). The duration of treatment varied between 12 and 24 weeks. All changes in the treatment regimens, discontinuation, mortality, and serious side effects were reported.

RESULTS: Adverse effects developed in 2475 (1.7%) (mean age [54 ± 9], male gender [53%]) patients. Serious side effects developed in 68% of these patients, and SOF/RBV was the most common causing regimen (73%, P < 0.001). Anaemia and hyperbilirubinemia were the most common side effects (731/149816, 0.5% and 463/149816, 0.3%, respectively) and SOF/RBV (588/21835, 3% and 353/21835, 1.6%, respectively) showed the highest incidence in the treated patients. Hepatocellular carcinoma and mortality were reported in 0.02% and 0.06% of all treated patients, respectively. Patients with liver cirrhosis showed higher incidence of serious side effects (Log rank P = 0.045) and mortality (Log rank P = 0.025) than patients without liver cirrhosis. Male gender (P = 0.012), lower haemoglobin (P < 0.001), platelets (P < 0.001) and albumin (P = 0.001), higher bilirubin (P = 0.002) and cirrhosis (P < 0.001) were factors associated with serious side effects development.

CONCLUSION: Adverse effects associated with DAAs are few, anaemia being the most common. SOF/RBV regimen showed the highest rate of side effects while SOF/DCV showed the least.

Said, M., Z. Soliman, H. Daebes, S. M. El-Nahaas, and M. El-Serafy, "Real life application of FIB-4 & APRI during mass treatment of HCV genotype 4 with directly acting anti-viral agents in Egyptian patients, an observational study.", Expert review of gastroenterology & hepatology, pp. 1-7, 2019. Abstract

: Non-invasive prediction of significant liver fibrosis and gastro-esophageal varices during mass treatment for HCV is crucial.The aim is to validate the accuracy of FIB-4 & APRI for predicting significant fibrosis in chronic HCV patients during mass treatment with directly acting anti-viral agents (DAAs) & their validity for predicting varices.: We did a search in a database of 21,617 patients with chronic HCV infection recruited to one of the national HCV treatment centers to find out those with fibrosis assessment by recent liver biopsies &/or liver stiffness to serve as a gold standard. The diagnostic accuracy of FIB-4 and APRI values were assessed against the gold standard. Demographics and relevant laboratory data of 3144 patients (14.5%) were retrieved.: Significant fibrosis (F3-F4) was detected in 1585 (50.4%). AUROCs for detecting significant fibrosis (F3-F4) were 0.76 (0.75-0.78) for FIB-4 and 0.72 (0.72-0.75) for APRI. To diagnose liver cirrhosis, AUROCs were higher; 0.82 (0.80-0.83) for FIB-4 and 0.78 (0.76-0.79) for APRI, p < 0.001. Prediction of gastro-oesophageal varices; AUROC for FIB-4 and APRI, were 0.65 and 0.62 respectively.: FIB-4 and APRI are reliable methods in predicting cirrhosis during mass HCV treatment. Their role in predicting gastro-oesophageal varices is less remarkable.

Said, M., H. Omar, Z. Soliman, Y. Saad, H. Dabes, S. Hamed, K. ElSaeed, Y. ElShazly, and M. ElSerafy, "Ritonavir-boosted paritaprevir, ombitasvir plus ribavirin could improve eGFR in patients with renal impairment and HCV: an Egyptian cohort.", Expert review of gastroenterology & hepatology, vol. 13, issue 1, pp. 89-93, 2019. Abstract

BACKGROUND: The present study aimed at evaluation of changes in estimated glomerular filtration rate (eGFR) among chronic Hepatitis C virus (HCV) patients with chronic kidney disease (CKD) Stages 3-5 who were treated with 12 weeks of ritonavir-boosted paritaprevir, ombitasvir plus ribavirin.

METHODS: Changes in renal functions were compared across follow up time points (baseline, SVR4, and SVR8). Data on on-treatment adverse events (AEs), serious AEs, laboratory abnormalities, treatment discontinuation were collected.

RESULTS: 171 patients were included (females 35%, mean age 53 years). 29 patients had liver cirrhosis. The most common etiologies of CKD were diabetes and/or hypertension (n = 67). All included patient reached the end of treatment (EOT) with no treatment discontinuations. The overall EOT response was 100%. 122/122 (100%) patients who reached 4 weeks post-treatment have achieved SVR4, and 80/80 (100%) have achieved SVR12. No reported SAEs. Ribavirin therapy was interrupted in 25% (43/171) of patients due to anemia; 16 patients required blood transfusions. The median eGFR improved from 33.5 (15) mL/min/1.73 m at baseline to 35 (36) mL/min/1.73 m2 at SVR8 (p = 0.0003).

CONCLUSIONS: The use of ombitasvir, paritaprevir, and ritonavir for treatment of HCV-infected patients with advanced renal disease was safe and effective, moreover, it was associated with significantly improved eGFR.

Omar, H., M. Said, R. E. Etreby, M. Mehrez, M. Bassam, Z. abdellatif, A. Hosny, S. Megawer, M. Elamir, and A. Yosry, "Longitudinal assessment of hepatic fibrosis in responders to direct-acting antivirals for recurrent hepatitis C after liver transplantation using noninvasive methods.", Clinical transplantation, vol. 32, issue 8, pp. e13334, 2018. 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.

Omar, H., W. Elakel, T. Elbaz, M. El Kassas, K. Elsaeed, H. El Shazly, M. Said, M. Yousif, A. A. Gomaa, A. Nasr, et al., "Generic daclatasvir plus sofosbuvir, with or without ribavirin, in treatment of chronic hepatitis C: real-world results from 18 378 patients in Egypt.", Alimentary pharmacology & therapeutics, vol. 47, issue 3, pp. 421-431, 2018. Abstract

BACKGROUND: Treatment of chronic hepatitis C using combination of sofosbuvir (SOF) and daclatasvir (DCV) was used in several clinical trials and multicentre studies, which were somewhat limited to genotypes 1-3. The national program in Egypt is using SOF-DCV combination for large scale treatment.

AIM: To assess the efficacy and safety of combined SOF-DCV in treating patients with HCV-G4 in a real-world setting.

METHODS: Data and outcome of chronic HCV patients who were treated for 12 weeks with generic medications: DCV 60 mg plus SOF 400 mg ± ribavirin (RBV) within the national hepatitis C treatment program in Egypt are presented. Treatment-naïve patients without cirrhosis were treated without RBV, and those who had cirrhosis or were treatment-experienced (interferon experienced or SOF experienced) received RBV. Efficacy and safety were assessed, and baseline factors associated with sustained virological response at post-treatment week 12 (SVR12) were explored.

RESULTS: During the first 2 months of the programme, 18 378 patients with HCV-G4 started treatment with SOF-DCV with or without RBV. Overall, 95.1% achieved SVR12 (95.4% among patients treated without RBV and 94.7% for patients treated with RBV, P = .32). Treatment was prematurely discontinued in only 1.5% of patients. The most common events leading to discontinuation were patient withdrawal (n = 76) and pregnancy (n = 5). Five deaths occurred within this group.

CONCLUSIONS: Real-world experience of generic SOF-DCV in patients with chronic HCV-G4 proved to be safe and associated with a high SVR12 rate, in patients with different stages of fibrosis.

Shahin, A. A., H. S. Zayed, M. Said, and S. A. Amer, "Efficacy and safety of sofosbuvir-based, interferon-free therapy : The Management of rheumatologic extrahepatic manifestations associated with chronic hepatitis C virus infection.", Zeitschrift fur Rheumatologie, vol. 77, issue 7, pp. 621-628, 2018. Abstract

BACKGROUND: The use of pegylated interferon alpha (IFN) has been of concern in chronic hepatitis C virus (HCV) patients with rheumatologic extrahepatic manifestations (EHM) due to the immunostimulatory effects of IFN.

AIM: To study the efficacy and safety of sofosbuvir-based, IFN-free antiviral therapy in chronic HCV patients with rheumatologic EHM.

MATERIAL AND METHODS: Group A included 24 patients with arthropathy (arthralgia or arthritis, n = 15) or vasculitis (n = 9) who received sofosbuvir and ribavirin (n = 17) or sofosbuvir and simeprevir (n = 7). Group B comprised 15 historical controls suffering from arthropathy who had received IFN and ribavirin. All patients were clinically evaluated and by detection of HCV viremia at baseline (V0), at the end of treatment (V1), 12 weeks after end of treatment (V2) and 24 weeks after end of treatment (V3).

RESULTS: Sustained viral response was obtained in all patients of group A (100%) versus 12 out of 15 of group B (80%). In group A, the tender joint count (TJC) and visual analogue scale for pain (VAS) improved (p = 0.001 for both) while the swollen joint count (SJC) decreased at V1 (p = 0.001) but returned to baseline values at V3. All vasculitis patients improved. Purpura, arthralgia and leg ulcers disappeared, but peripheral neuropathy persisted. In group B, TJC, SJC and VAS increased from baseline values (p = 0.034, 0.03 and 0.001, respectively). Side effects in group A were generally mild, but one patient developed deterioration of arthralgia.

CONCLUSION: The use of IFN-free regimens is safe and effective in the treatment of most HCV-related rheumatologic EHM.

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