Heba Omar

Circulating microRNA, miR-122 and miR-221 signature in Egyptian patients with chronic hepatitis C related hepatocellular carcinoma

AIM To explore the potential usefulness of serum miR-122 and miR-221 as non-invasive diagnostic markers of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). METHODS This prospective study was conducted on 90 adult patients of both sex with HCV-related chronic liver disease and chronic hepatitis C related HCC. In addition to the 10 healthy control individuals, patients were stratified into; interferon-naïve chronic hepatitis C (CH) (n = 30), post-hepatitis C compensated cirrhosis (LC) (n = 30) and treatment-naïve HCC (n = 30). All patients and controls underwent full clinical assessment and laboratory investigations in addition to the evaluation of the level of serum miRNA expression by RT-PCR. RESULTS There was a significant fold change in serum miRNA expression in the different patient groups when compared to normal controls; miR-122 showed significant fold increasing in both CH and HCC and significant fold decrease in LC. On the other hand, miR-221 showed significant fold elevation in both CH and LC groups and significant fold decrease in HCC group (P = 0.01). Comparing fold changes in miRNAs in HCC group vs non HCC group (CH and Cirrhosis), there was non-significant fold elevation in miR-122 (P = 0.21) and significant fold decreasing in miR-221 in HCC vs non-HCC (P = 0.03). ROC curve analysis for miR-221 yielded 87% sensitivity and 40% specificity for the differentiation of HCC patients from non-HCC at a cutoff 1.82. CONCLUSION Serum miR-221 has a strong potential to serve as one of the novel non-invasive biomarkers of HCC.

Generic daclatasvir plus sofosbuvir, with or without ribavirin, in treatment of chronic hepatitis C: real-world results from 18 378 patients in Egypt

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.

Evaluation of Early Corticosteroid Therapy in Management of Pediatric Septic Shock in Pediatric Intensive Care Patients: A Randomized Clinical Study.

Background: Septic shock is a major healthcare problem. Adrenal insufficiency (AI) in children with septic shock is a recognized complication, yet is controversial regarding its management and effect on mortality. According to the current guidelines, children with risk factors for AI should receive a stress dose of steroids in step 3 of treatment. This study aimed to evaluate and compare early corticosteroid therapy with the traditional use of steroids among pediatric septic shock patients. Methods: This prospective randomized interventional clinical study included 3 groups of patients (32 each) and was conducted in Alexandria University pediatric intensive care unit. By protocol, the first group received steroids in step 3 of the treatment according to the current international guidelines (group A), and the second group was managed as group A and was tested for AI by adrenal stimulation test using intramuscular adrenocorticotropic hormone (cosyntropin) (group B). The third group received steroids at the start of fluid therapy (group C). A fourth group (group D) was created by adding patients from groups A and B who needed corticosteroids in the third stage of therapy according to the international protocol in 1 group. All patients were evaluated for basal serum cortisol and plasma adrenocorticotropic hormone concentrations. Results: The data showed a statistically significant shorter shock reversal time among patients receiving corticosteroids at the start of treatment compared with those who received it at the third step of treatment (P = 0.046); however, mortality was not statistically different among the groups. In addition, there was no superinfection in cases receiving early steroid therapy. Conclusions: Early use of corticosteroid in patients with septic shock might shorten the shock reversal time without increase in mortality or superinfection.

APRI test and hyaluronic acid as non-invasive diagnostic tools for post HCV liver fibrosis: Systematic review and meta-analysis

BACKGROUND AND STUDY AIMS Hepatitis C virus (HCV) accounts for a sizable proportion of chronic liver disease cases and represents the most common indication for liver transplantation. Precise diagnosis of hepatic fibrosis stage is considered a funnel-neck in proper management and follow-up of HCV-infected patients. Given the possible complications of liver biopsy, a non-invasive method for assessing hepatic fibrosis is needed. This study aimed to evaluate the diagnostic accuracy of APRI and hyaluronic acid as non-invasive diagnostic assessment tools for post HCV liver fibrosis. PATIENTS AND METHODS Systematic literature searching identified studies performed on Egyptian territory to evaluate APRI and hyaluronic acid as non-invasive tests of fibrosis and using liver biopsy as the reference standard. Meta-analysis was performed for areas with an adequate number of publications. Validation of meta- analysis on APRI was done on a subset of 150 treatment-naïve post-hepatitis C patients. RESULTS Both APRI and hyaluronic acid have superior predictive power for hepatic cirrhosis (F4) than for significant fibrosis (F2-F3). The pooled estimate for sensitivities and specificities of APRI and hyaluronic acid to diagnose F4 were (84% and 82%) and (83% and 89%) respectively. In the subgroup of treatment naïve post-hepatitis C patients, APRI had higher diagnostic performance to diagnose liver cirrhosis with 93.8% sensitivity and 72.4% specificity (AUC; 0.908, 95%CI; 0.851-0.965, p-value; <0.001) compared to its accuracy to diagnose significant hepatic fibrosis with 65.1% sensitivity and 77.8% (AUC; 0.685, 95% CI; 0.59-0.78, p-value; 0.001). CONCLUSION APRI score and hyaluronic acid levels are simple and reliable non-invasive markers to detect advanced fibrosis among post-hepatitis C patients.

Circulating adipokines in children with nonalcoholic fatty liver disease: possible noninvasive diagnostic markers

Background The growing obesity pandemic is the leading cause for increasing prevalence of nonalcoholic fatty liver disease (NAFLD) in children. Histopathological evaluation of the liver remains the gold standard for NAFLD diagnosis, but it is an invasive procedure with a low but real risk of morbidity and mortality. The current study evaluated circulating chemerin and adiponectin as possible noninvasive diagnostic markers for NAFLD in obese non-diabetic children. Methods A prospective case-control study was conducted, which included 101 obese children with biopsy-proven NAFLD and 57 age- and sex-matched controls. The overall mean age of the children was 10.08±3.12 years. All underwent a full clinical assessment, routine laboratory investigation, and abdominal ultrasound. Homeostatic model assessment-insulin resistance was calculated and circulating chemerin and adiponectin were evaluated using ELISA. Results Elevated serum chemerin and decreased serum adiponectin were significantly associated with an increased likelihood of exhibiting NAFLD. Receiver operator characteristic curve analysis for differentiation of NAFLD patients from those in the control group demonstrated that chemerin, at a cutoff value of 186.7 ng/mL, yielded a sensitivity and specificity of 56.44% and 87.72% respectively (P<0.001), whereas adiponectin, at a cutoff value of 2.4 µg/mL, had a sensitivity and specificity of 74.26% and 3.51% respectively (P<0.001). Furthermore, body mass index, aspartate transaminase, alanine transaminase, triglycerides, and gamma-glutamyl transferase had significant positive correlations with chemerin and significant negative correlations with adiponectin (P≤0.001). Conclusion Circulating chemerin and adiponectin could serve as simple noninvasive diagnostic markers for NAFLD in non-diabetic obese children.

An account of the real-life hepatitis C management in a single specialized viral hepatitis treatment centre in Egypt: results of treating 7042 patients with 7 different direct acting antiviral regimens

ABSTRACT Background: A large Egyptian treatment program for HCV was launched in2014 after the introduction of direct-acting antiviral agents (DAAs). This program depended mainly on establishing specialized independent centres for HCV treatment. These centres represent the major strengths in the Egyptian model of care, as they provide integrated care for HCV patients and have enabled Egypt to treat more than one million patients in 3 years. The New Cairo Viral Hepatitis Treatment Center (NCVHTC) is an example of these specialized centres. Methods: The Egyptian experience in the management of HCV was evaluated by analysing the data of real-life HCV management in the NCVHTC from 2014 to 2017. Results of different treatment regimens in addition to their strengths, limitations and areas for improvement are discussed in this report. Results: A total of 7042 HCV patients have been evaluated for treatment in the NCVHTC. Among them, 5517 patients received treatment by seven different DAA regimens with excellent results. Conclusions: All regimens were highly effective at treating HCV in a real-life setting, apart from SOF/RBV, which was the least effective. A nationwide screening program and enhancing the follow-up of treated patients are the main missing pillars in the Egyptian model.

HCV in Egypt, prevention, treatment and key barriers to elimination

ABSTRACT Introduction: Currently, direct-acting antivirals (DAAs) are considered the ideal choice for the treatment of chronic HCV patients due to their proven efficacy (SVR> 90%), and minimal adverse effects. Egypt launched a large treatment program aimed at providing treatment coverage for Egyptian HCV- infected patients. Areas covered: This review covers the treatment and prevention efforts made by the Egyptian National Committee for the Control of Viral Hepatitis (NCCVH) with the available model of care for HCV patients in Egypt, in addition to the barriers that prevent elimination of HCV from Egypt. Expert commentary: Egypt could provide a model for establishing the largest HCV management system aimed at eliminating HCV from the country with the highest worldwide prevalence. Despite the huge efforts and achieved results in combating the HCV epidemic in Egypt, certain improvements are needed in order to attain HCV elimination, such as the development of an enhanced screening program working in parallel to the present treatment options.

Efficacy and safety of sofosbuvir and daclatasvir with or without ribavirin in elderly patients with chronic hepatitis C virus infection: ELBAZ et al.

Hepatitis C virus (HCV) infection is considered as a major public health problem that, worldwide, chronically affects 170 million people. Elderly patients are more likely than younger patients to have increased duration of infection, increased rate of disease progression, and subsequently increased incidence of advanced liver disease. Natural history models predicted that the prevalence of HCV infection and its chronic sequelae as well as extrahepatic manifestations will eventually increase through the next decade and will mostly affect those who are greater than 60 years of age. Moreover, polytherapy and polypharmacy are frequent in elderly patients due to associated comorbidities. As advanced age is associated with increasing risk of development of cirrhosis and hepatocellular carcinoma, elderly patients are in special need of safe and effective antiviral therapies. Achievement of sustained viral responses (SVR) is associated with reduced liver‐related complications and overall mortality in such patients with the advanced liver disease. With the recent introduction of interferon‐free direct‐acting antivirals, successful treatment for chronic HCV infection had dramatically improved, with overall cure rates that exceed 90% SVR. In our study, we aimed to study the efficacy and safety of combined sofosbuvir and daclatasvir, with or without ribavirin, in management of chronically infected HCV elderly patients who are more than 60 years old.

Utility of point shear wave elastography in characterisation of focal liver lesions

ABSTRACT Background: The present study aimed at evaluation of the usefulness of point shear wave elastography (pSWE) in characterization of FLL(s) by quantifying their stiffness. Methods: In total, 197 patients (mean age was 56.57 years) with FLL(s) on conventional ultrasound were included. Final diagnoses, confirmed by imaging and/or biopsy whenever possible, included hepatocellular carcinoma (HCC) (n = 143), metastasis (n = 36), hemangioma (n = 16), and focal nodular hyperplasia (n = 2). Stiffness evaluation was performed by pSWE. Stiffness ratio (lesion to background liver) was calculated. ROC analysis was performed to evaluate the diagnostic accuracy of the stiffness value and stiffness ratio and to extract the optimal cutoff values for characterisation of FLL(s). Results: HCC was significantly softer than its surrounding liver parenchyma [5.43 (3.03) vs. 17.05 (8.53) kPa, p <0.001]. However, the stiffness values for the other examined FLLs were comparable to their surrounding liver parenchyma. No significant difference was detected across different types of metastases or between metastases and surrounding liver (p>0.05). Stiffness ratio was superior to stiffness value in discrimination of HCC from metastasis (AUROC, 0.91 vs. 0.51 respectively). Conclusion: pSWE could provide a complementary information about FLLs especially in differentiation between HCCs from metastases.

Longitudinal assessment of hepatic fibrosis in responders to direct-acting antivirals for recurrent hepatitis C after liver transplantation using noninvasive methods

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.