Rabab Fouad

Sofosbuvir plus ribavirin for treating Egyptian patients with hepatitis C genotype 4

BACKGROUND & AIMS Egypt has the highest prevalence of chronic hepatitis C virus (HCV) infection in the world, and more than 90% of patients are infected with genotype 4 virus. We evaluated the efficacy and safety of the HCV polymerase inhibitor sofosbuvir in combination with ribavirin in HCV genotype 4 patients in Egypt. METHODS Treatment-naïve or treatment-experienced patients with genotype 4 HCV infection (n=103) were randomly assigned to receive either 12 or 24 weeks of sofosbuvir 400 mg and ribavirin 1000-1200 mg daily. Randomization was stratified by prior treatment experience and by presence or absence of cirrhosis. The primary endpoint was the percentage of patients with HCV RNA <25 IU/ml 12 weeks after therapy (SVR12). RESULTS Among all patients, 52% had received prior HCV treatment and 17% had cirrhosis at baseline. SVR12 rates were 90% (46/51) with 24 weeks and 77% (40/52) with 12 weeks of sofosbuvir and ribavirin therapy. Patients with cirrhosis at baseline had lower rates of SVR12 (63% 12 weeks, 78% 24 weeks) than those without cirrhosis (80% 12 weeks, 93% 24 weeks). The most common adverse events were fatigue, headache, insomnia, and anemia. Two patients experienced serious adverse events (cerebral ischemia, dyspnea). No adverse events resulted in treatment discontinuation. CONCLUSION Sofosbuvir plus ribavirin for 12 or 24 weeks is effective in treating both treatment-naïve and treatment-experienced Egyptian patients with genotype 4 HCV.

Schistosoma haematobium infection in Egyptian schoolchildren: Demonstration of both hepatic and urinary tract morbidity by ultrasonography

Parasitological, clinical and ultrasonographical studies were performed upon 422 schoolchildren aged 12-16 years living in a village in the Fayoum where Schistosoma haematobium, but not S. mansoni, was transmitted. Over half of the children gave a history of receiving praziquantel therapy during the preceding 2 years. Symptoms (e.g., haematuria, burning micturition), signs (e.g., hepatomegaly, splenomegaly) and urinary findings (e.g., haematuria, proteinuria) correlated better with the presence and intensity of S. haematobium infection after correcting for this variable. Renal obstructive lesions detected by ultrasound were 2 and 3 times as common in those with moderate and heavy infections as in those with no or light infections, and urinary bladder wall lesions were far more frequent in those with moderate and heavy infections. A mild grade of periportal fibrosis, hepatomegaly and splenomegaly were present in some children in all groups. However, the prevalence of splenomegaly correlated directly with the intensity of infection; liver lesions occurred much more frequently in children with infection or a history of treated infection than in non-infected children denying recent treatment; and no child had hepatomegaly or splenomegaly in the absence of periportal fibrosis.

Sofosbuvir‐based treatment regimens: real life results of 14 409 chronic HCV genotype 4 patients in Egypt

Chronic hepatitis C virus infection is one of the most important health problems in Egypt. The Ministry of Healths National Treatment Programme introduced sofosbuvir‐based therapy in October 2014.

Changes in liver stiffness measurements and fibrosis scores following sofosbuvir based treatment regimens without interferon

Accurate evaluation of the degree of liver fibrosis in patients with chronic liver diseases is crucial, as liver fibrosis is important in order to make therapeutic decisions, determine prognosis of liver disease and to follow‐up disease progression. Multiple non‐invasive methods have been used successfully in the prediction of fibrosis; however, early changes in non‐invasive biomarkers of hepatic fibrosis under effective antiviral therapy are widely unknown. The aim of this study is to evaluate changes of transient elastography values as well as FIB‐4 and AST to platelet ratio index (APRI) in patients treated with Sofosbuvir‐based treatment regimen.

THE IMPACT OF INTERLEUKIN 28B GENE POLYMORPHISM ON THE VIROLOGICAL RESPONSE TO COMBINED PEGYLATED INTERFERON AND RIBAVIRIN THERAPY IN CHRONIC HCV GENOTYPE 4 INFECTED EGYPTIAN PATIENTS USING DATA MINING ANALYSIS

Background: Chronic HCV represents one of the common causes of chronic liver disease worldwide with Egypt having the highest prevalence, namely genotype 4. Interleukin IL-28B gene polymorphism has been shown to relate to HCV treatment response, mainly in genotype1. Objectives: We aim to evaluate the predictive power of the rs12979860 IL28B SNP and its protein for treatment response in genotype 4 Egyptian patients by regression analysis and decision tree analysis. Patients and Methods: The study included 263 chronic HCV Egyptian patients receiving peg-interferon and ribavirin therapy. Patients were classified into 3 groups; non responders (83patients), relapsers (76patients) and sustained virological responders (104 patients). Serum IL 28 B was performed, DNA was extracted and analyzed by direct sequencing of the SNP rs 12979860 of IL28B gene. Results: CT, CC and TT represented 56 %, 25 % and 19% of the patients, respectively. Absence of C allele (TT genotype) was significantly correlated with the early failure of response while CC was associated with sustained virological response. The decision tree showed that baseline alpha fetoprotein (AFP ≤ 2.68 ng/ml) was the variable of initial split (the strongest predictor of response) confirmed by regression analysis. Patients with TT genotype had the highest probability of failure of response. Conclusions: Absence of the C allele was significantly associated with failure of response. The presence of C allele was associated with a favorable outcome. AFP is a strong baseline predictor of HCV treatment response. A decision tree model is useful for predicting the probability of response to therapy.

Role of Clinical Presentations and Routine CSF Analysis in the Rapid Diagnosis of Acute Bacterial Meningitis in Cases of Negative Gram Stained Smears

Background and Aim. Bacterial meningitis is a lethal, disabling endemic disease needing prompt antibiotic management. Gram stained smears is rapid accurate method for diagnosis of bacterial meningitis. In cases of negative gram stained smears diagnosis is delayed till culture results. We aim to assess the role of clinical presentations and routine CSF analysis in the cost-effective rapid diagnosis of negative gram stained smears bacterial meningitis. Methods. Cross sectional study including 623 acute meningitis patients divided into two groups: bacterial meningitis and nonbacterial meningitis groups. The clinical presentations, systemic inflammatory parameters, and CSF analysis were evaluated and compared in both groups. Results. Altered conscious level, localizing neurological signs, Kernigs and Brudzinskis signs together with peripheral leucocytosis (>10.000/mm3), high CRP (>6) together with high CSF protein (>50 gl/dL), CSF neutrophilic count (≥50% of total CSF leucocytic count), and low CSF glucose level (<45 gm/dL) and CSF/serum glucose ≤0.6 were significantly diagnostic in bacterial meningitis patients. From the significant CSF analysis variables CSF protein carried the higher accuracy of diagnosis 78% with sensitivity 88% and specificity 72%. Conclusions. High CSF protein (>50 mg/dL) together with plasma inflammatory markers and CSF cytochemical parameters can diagnose bacterial meningitis in gram stain negative smear till culture results.

Impact of different sofosbuvir based treatment regimens on the biochemical profile of chronic hepatitis C genotype 4 patients

ABSTRACT Background: Huge efforts have been made to control chronic HCV in Egypt with introduction of Direct-Acting Antivirals (DAAs). Current study aims at evaluating effect of various DAA regimens on liver biochemical profile and haematological indices during treatment. Methods: 272 patients with chronic HCV genotype 4 treated by different DAA regimens (SOF/RBV, SOF/DAC ± RBV, SOF/SIM) for a duration of 12 or 24 weeks in Kasr Alainy Viral Hepatitis Center, Cairo University were followed up for serum bilirubin (BIL), albumin (ALB), alanine transaminase (ALT), aspartate aminotransferase (AST), prothrombin concentration, international normalized ratio (INR), and CBC at baseline, week-4 and end of treatment. Results: Mean age was 54 years. Males comprised 64.7%, 72.4% were treatment-naïve, 39% were cirrhotic. Overall SVR12 rate was (93.4%). With all regimens, ALT and AST declined after treatment. In cirrhotics, there was a rise in BIL and INR; with no change in ALB and a decrease in White blood cells. Drop in Hemoglobin and platelets in cirrhotic patients were noted with SOF/RBV, while SOF/SIM showed rise in BIL. Conclusion: DAAs are safe and effective in genotype 4 chronic HCV patients. It improves liver necro-inflammatory markers in cirrhotics and non-cirrhotics. Cirrhotic patients require careful observation being more vulnerable for treatment related complications.

Improvement of glycemic state among responders to Sofosbuvir - based treatment regimens: Single center experience†

Chronic HCV infection has emerged as a complex multifaceted disease with manifestations extending beyond the liver. HCV plays a direct role in glucose metabolism leading to both insulin resistance and type 2 diabetes. To evaluate the changes in the glycemic state following Sofosbuvir‐based treatment regimens in diabetic HCV patients. Four hundred chronic hepatitis C patients who underwent Sofosbuvir‐based treatment regimens were retrospectively screened. Sixty‐five diabetic HCV patients only enrolled in our analysis. Baseline demographic and laboratory data were recorded. Pretreatment Transient elastography was performed. At 24‐week post EOT (SVR24), Fasting Plasma glucose, and Hemoglobin A1c were re‐evaluated and compared with baseline. All enrolled diabetic patients were responders. They showed statistically significant decline in Fasting Plasma glucose and Hemoglobin A1c values at SVR24. Whatever the degree of hepatic fibrosis, the level of Fasting Plasma glucose and Hemoglobin A1c decreased at SVR24 in comparison to baseline level. Fifty‐one patients showed improvement in their Hemoglobin A1c values at SVR24 and this improvement was more likely to occur among patients with low Body mass index. The reduction in Fasting Plasma glucose >20 mg/dL (>1.1 mmol/L) and Hemoglobin A1c ≥0.5% was not associated with age, gender or hepatic fibrosis stage. Sofosbuvir‐based regimens are a highly efficient antiviral therapy for diabetic chronic HCV patients resulted in improvement in Fasting Plasma glucose and Hemoglobin A1c.

FibroScan, APRI, FIB4, and GUCI: Role in prediction of fibrosis and response to therapy in Egyptian patients with HCV infection.

BACKGROUND AND STUDY AIMS Multiple noninvasive methods have been used successfully in the prediction of fibrosis. However, their role in the prediction of response to hepatitis C virus (HCV) antiviral therapy is debatable. The aim of this study was to validate and compare the diagnostic performance of FibroScan, APRI (aspartate aminotransferase (AST)-to-platelet ratio index), FIB4, and GUCI (Göteborg University Cirrhosis Index) for the prediction of hepatic fibrosis and treatment outcome in HCV-infected patients receiving pegylated interferon and ribavirin (PEG-IFN/ribavirin). PATIENTS AND METHODS This study included 182 Egyptian patients with chronic HCV infection. They were classified into two groups based on the stages of fibrosis: mild to significant fibrosis (F1-F2) and advanced fibrosis (F3-F4). The APRI, FIB4, and GUCI scores were calculated before the antiviral treatment. The FibroScan was performed for all patients before treatment. RESULTS Stiffness and FIB4 have greater sensitivity and specificity in detecting advanced fibrosis of 80%, 77% and 88%, 84%, respectively. Based on multivariate regression analysis, FIB4, body mass index (BMI), and alpha-fetoprotein (AFP) level were found to be statistically significant predictors of advanced fibrosis (p-value: 0.000, 0.011, and 0.001, respectively) with odds ratio (OR: 3.184, 1.170, and 1.241, respectively). With respect to virological response, the stiffness, APRI, FIB4, and GUCI were significantly lower in sustained virological responders. However, these are not good predictors of response to PEG-IFN/ribavirin therapy. AFP was the only statistically significant predictor of response (p=0.002) with OR of 1.141 in multivariate regression analysis. CONCLUSION FibroScan and noninvasive scores such as APRI, FIB4, and GUCI can be used as good predictors of liver fibrosis in chronic hepatitis C. However, they are not good predictors of response to PEG-IFN/ribavirin therapy.

The association of HLA class II DR B1 alleles with HCV infection in Egyptian children.

BACKGROUND AND STUDY AIMS Human leucocyte antigens (HLA) class II appear to play an important role in the individuals immune response to viral infection. The aim of this study is to assess the relationship between HLA class II antigens with the clinical, laboratory and histopathological state of the liver in Egyptian children and adolescents with chronic hepatitis C virus (HCV) infection. PATIENTS AND METHODS The study included 46 chronically infected HCV children and adolescents without - hepatitis B virus (HBV) nor human immunodeficiency virus - (HIV). Their mean age was 10.4±4.23years (3-17). HLA-DRB typing was done by polymerase chain reaction (PCR) for the patients and 20 control subjects. Biochemical and haematological parameters were assessed as well as a liver biopsy was taken from the included patients. RESULTS The most frequent alleles demonstrated among patients were DRB1∗03, DRB1∗04 and DRB1∗13 (45.6%, 39.1% and 26.1%), respectively. Analysis of DRB1 frequencies between patients and control revealed that DRB1*15 is significantly reduced among patients when compared with the control group (p<0.01). Patients possessing the allele DRB1*03 had significantly reduced platelet count (p=0.03), and this allele was presented to a greater extent in patients with minimal grade of inflammation. Patients with DRB1*04 had significantly low serum albumin (p=0.04) and patients with DRB1*13 had significantly high serum aspartate aminotransferase (AST) levels (p=0.05). CONCLUSION In Egyptian HCV-infected children, special HLA patterns were found; HLA DRB1*03 was present in nearly half of the patients, while the frequency of HLA DRB1*15 was significantly reduced among the cases in comparison to the control subjects.