Renal profile of chronic hepatitis C patients with sofosbuvir-based therapy.

PURPOSE: The impact of SOF-based therapy on renal functions is quite controversial in clinical practice. Therefore, we aimed to evaluate the serial changes of renal indices during SOF-based therapy in CHC patients with normal kidney function or mild renal impairment. METHODS: We retrospectively reviewed all CHC patients who received different SOF-based regimens from January 2015 until December 2017, and presented with a baseline eGFR ≥ 30 ml/min/1.73m2. Patients who didn't achieve SVR, with missing creatinine or eGFR data, and patients with eGFR less than 30 ml/min/1.73m2 at baseline were excluded. eGFR was calculated for each time of evaluation using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. RESULTS: A total of 1004 patients were finally included. The mean serum creatinine and eGFR levels varied between 0.84 mg/dl and 106.53 ml/min/1.73m2 for baseline and 0.87 mg/dl and 104.24 ml/min/1.73m2 for SVR12, respectively. The maximum increase of creatinine was 3.69 mg/dl and the maximum decrease of eGFR level was 83.30 ml/min/1.73m2 during treatment. Moreover, 74.4% of treated patients stayed in the same eGFR category, 14.3% progressed to a higher eGFR category, and 11.3% had an improvement eGFR category at EOT and continued to SVR12. Age > 65 years, baseline eGFR, and ribavirin-containing regimens were independent risk factors of eGFR decline during and after SOF-based treatment. CONCLUSION: SOF-based therapies seem to be safe in CHC patients with baseline normal or slightly impaired renal function.

Epigallocatechin gallate (EGCG) and miR-548m reduce HCV entry through repression of CD81 receptor in HCV cell models.

Epigallocatechin gallate (EGCG) is the most abundant component in green tea extract, that has powerful antioxidant and antiviral effects. It has been previously reported to inhibit HCV entry via several mechanisms. Hence, this study aimed at further investigating the potential impact of EGCG on HCV entry through regulation of the expression of tetraspanin receptor CD81 by the novel predicted miR-548m. Liver biopsies were obtained from 29 HCV patients and 10 healthy controls for expression profiling. Huh7 cells were stimulated with EGCG and subsequently miR-548m expression was assessed. Naïve, HCV- ED43/JFH-1 and HCV-JFH-1 infected Huh7 cells were transfected by miR-548m mimics and inhibitors. Consequently, CD81 protein and mRNA levels were assessed using flow cytometry and qRT-PCR, respectively. Additionally, these cells were used to investigate HCV permissiveness into Huh7 cells using qRT-PCR for viral quantification. Direct binding confirmation of miR-548m to CD81 was done using luciferase reporter assay. In-silico analysis revealed miR-548m to have two potential binding sites in the 3'UTR of CD81 mRNA. EGCG boosted miR-548m expression in Huh7 cells. Additionally, miR-548m caused a downregulation of CD81 protein and mRNA levels as well as reduction in HCV infectivity of Huh7 cells. Luciferase binding assay confirmed the binding of miR-548m to CD81 mRNA at the two predicted binding sites. Intriguingly, miR-548m expression was not detected in healthy liver biopsies but was found in liver biopsies of HCV patients. This study shows that EGCG might act as an anti-HCV agent that reduces cellular infectivity via enhancing miR-548m expression and repressing CD81 receptor.

Novel scores combining AFP with non-invasive markers for prediction of liver fibrosis in chronic hepatitis C patients.

Serum levels of alpha-fetoprotein (AFP) were reported to increase in patients with significant or advanced hepatic fibrosis. Combination of non-invasive tests decreases the use of liver biopsy in large proportion of chronic HCV patients. The aim of the study was to compare and combine AFP with commonly used non-invasive fibrosis tests in novel scores for prediction of different stages of hepatic fibrosis. Six hundred and fifty two treatment naïve chronic hepatitis C patients were enrolled. Demographic data, basic pre-treatment laboratory tests including complete blood count (CBC), liver biochemical profile and renal functions test, international normalized ratio (INR) in addition to AFP, liver stiffness measurement (LSM) by Fibroscan and liver biopsies were retrospectively analyzed. AST to Platelet Ratio Index (APRI) and FIB-4 scores were calculated. Different predictive models using multivariate logistic regression analysis were generated and presented in equations (scores) composed of a combination of AFP, LSM plus FIB-4/APRI scores. AFP was correlating significantly with LSM, FIB-4, and APRI scores. Areas under receiver operating characteristic curves (AUROCs) for predicting significant hepatic fibrosis, advanced hepatic fibrosis, and cirrhosis were 0.897, 0.931, and 0.955, respectively, for equations (scores) containing AFP, LSM, and FIB-4. AUROCs for predicting significant hepatic fibrosis, advanced hepatic fibrosis and cirrhosis were 0.897, 0.929, and 0.959, respectively, for equations (scores) containing AFP, LSM, and APRI. The study shows that combining AFP to serum biomarkers and LSM increases their diagnostic performance for prediction of different stages of liver fibrosis.

MiRNAs as molecular biomarkers in stage II egyptian colorectal cancer patients.

AIM: To assess the role of aberrant miRNAs expressions in stage II CRC patients from Egypt. METHODS: Tumor tissue samples were obtained from 124 CRC stage II patients compared to 100 healthy controls for assessing miRNAs expression using; 1) a cataloged 84-miRNAs PCR array panel, and 2) another five miRNAs (miR-21, miR-137, miR-145, miR-320 and miR-498) that have been reported in previous studies to have a role in CRC, by quantitative real time PCR (qPCR). The results were correlated to patients' characteristics, response to treatment and survival. RESULTS: There were 17 out of 84 miRNAs differentially expressed in the CRC patients. Twenty six miRNAs were significantly differentially expressed in the female CRC patients, while 16 miRNAs were significantly differentially expressed in the male CRC patients. Only, five miRNAs (miR-21, Let-7a-5p, miR-100-5p, miR-200c-3p and miR-23b-3p) were significantly common deregulated in CRC patients regardless gender. miR-21 was overexpressed in 48.4% of the patients and it was significantly downregulated in females and over expressed in males. In univariate analysis; performance status, over-expression of miR-21 and miR-498 and reduced miR-137, miR-145, and miR-320 associated significantly with reduced DFS and OS whereas in multivariate analysis; miR-498 and miR-320 were independent prognostic factors for DFS and miR-21 was independent prognostic factors for OS. CONCLUSION: miRNAs expression differs significantly between male and female stage II CRC patients, miR-21, Let-7a-5p, miR-100-5p, miR-200c-3p and miR-23b-3p could be used as common diagnostic biomarkers for CRC. On the other hand, a three miRNAs panel (miR-21, miR-498 and miR-320) can predict recurrence and survival in those patients.

Is expert opinion reliable when estimating transition probabilities? The case of HCV-related cirrhosis in Egypt.

BACKGROUND: Data on HCV-related cirrhosis progression are scarce in developing countries in general, and in Egypt in particular. The objective of this study was to estimate the probability of death and transition between different health stages of HCV (compensated cirrhosis, decompensated cirrhosis and hepatocellular carcinoma) for an Egyptian population of patients with HCV-related cirrhosis. METHODS: We used the "elicitation of expert opinions" method to obtain collective knowledge from a panel of 23 Egyptian experts (among whom 17 were hepatologists or gastroenterologists and 2 were infectiologists). The questionnaire was based on virtual medical cases and asked the experts to assess probability of death or probability of various cirrhosis complications. The design was a Delphi study: we attempted to obtain a consensus between experts via a series of questionnaires interspersed with group response feedback. RESULTS: We found substantial disparity between experts' answers, and no consensus was reached at the end of the process. Moreover, we obtained high death probability and high risk of hepatocellular carcinoma. The annual transition probability to death was estimated at between 10.1% and 61.5% and the annual probability of occurrence of hepatocellular carcinoma was estimated at between 16.8% and 58.9% (depending on age, gender, time spent in cirrhosis and cirrhosis severity). CONCLUSIONS: Our results show that eliciting expert opinions is not suited for determining the natural history of diseases due to practitioners' difficulties in evaluating quantities. Cognitive bias occurring during this type of study might explain our results.

Choroidal thickness and retinal vascular changes in patients with lichen planus: an inflammatory disease beyond the skin.

BACKGROUND: Lichen planus (LP) is a common inflammatory condition of unknown etiology that commonly affects the skin and mucous membranes. Optical coherence tomography angiography (OCTA) is a noninvasive technique for identifying early retinal vascular impairment in systemic disease without clinical damage by imaging deep and superficial capillary networks. AIMS: To assess the impacts of LP on the choroid and assess vascular changes in retinal capillary density using OCTA. METHODS: This single-center prospective case-control study included 30 therapeutic-naïve LP patients and 30 age and sex-matched healthy individuals. All study subjects underwent a complete ophthalmological examination, including best-corrected visual acuity (BCVA) measurement using a Snellen chart, slit-lamp biomicroscopy, intraocular pressure (IOP) measurement, and fundus examination. They were then examined using spectral domain OCT and choroidal thickness was measured. The vessel density of the superficial and deep capillary networks was measured and assessed using OCTA. RESULTS: Patients had significantly thicker choroidal and retinal thickness than controls, with subfoveal, nasal, and temporal areas showing a significant difference. A significantly higher vascular density in the superficial capillary plexus, particularly in the nasal perifoveal area, was found compared to the control group. Significantly, higher vascular density in the deep capillary plexus in the parafoveal area compared to controls was reported. Significant correlations were found between visual acuity and IOP, and age, duration of disease, and severity of disease. CONCLUSIONS: This study is the first to reveal that LP patients exhibit choroidal changes and retinal vascular alterations compared to healthy controls.

Efficacy and safety of ombitasvir/paritaprevir/ritonavir-based therapy in HCV patients with chronic kidney disease.

BACKGROUND AND STUDY AIMS: Hepatitis C virus (HCV) prevalence inchronic kidney disease (CKD) patients is significantly higher than in the general population. This study evaluated the efficacy and safety of combined ombitasvir/paritaprevir/ritonavir-based therapy in HCV patients with renal impairment. PATIENTS AND METHODS: Our study included 829 patients with normal kidney functions (group 1) and 829 patients with CKD (group 2),which were subdivided into patients not requiring dialysis (group 2a) and those on hemodialysis (group2b). Patients received regimens of ombitasvir/paritaprevir/ritonavir with or without ribavirin or sofosbuvir/ombitasvir/paritaprevir/ritonavir with or without ribavirin for 12 weeks. Clinical and laboratory assessment was done before treatment, and patients were followed up for12 weeks after treatment. RESULTS: The sustained virological response (SVR) at week 12 was significantly higher in group 1 than in the other three groups/subgroups, being 94.2% vs 90.2%, 90%, and 90.7%, respectively. The regimen with the highest SVR was ombitasvir/paritaprevir/ritonavir with ribavirin. The most common adverse event was anemia, which was more common in group 2. CONCLUSION: Ombitasvir/paritaprevir/ritonavir-based therapy in chronic HCV patients with CKD is highly effective, with minimal side effects despite ribavirin-induced anemia.

Vitamins and minerals: A means for surviving the COVID-19 pandemic or just a myth?

A novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) that was initially reported from Wuhan, China in December 2019, was declared a pandemic by the WHO in March 2020. Considering the current COVID-19 pandemic, where there are no specific effective preventive or therapeutic drugs available, a healthy immune system is one of the most important tools that should be considered. Vitamins and minerals supplements have been well known to help the immune system in battling viral infections in general. Physicians worldwide are largely interested in vitamin and mineral supplements to help them battle COVID-19 whether through protection or treatment. Dietary supplementations especially vitamin D, vitamin C, and Zinc offer good prophylactic and therapeutic support to the currently available treatment regimens. They are relatively safe and were proven to aid recovery in other respiratory infections. Further studies should be encouraged especially those examining their role in prophylaxis from COVID-19 while maintaining current recommendations for social distancing and proper protective gear.

Hepatitis B Reactivation Following Eradication of HCV with Direct-Acting Antiviral Drugs (DAAs) in a Cohort of Patients from Different Institutions in Egypt.

Background: Concerns about HBV reactivation (HBVr) have been raised with the introduction of DAA for HCV treatment. The aim of the study was to assess the risk of HBVr in chronic HCV patients during or after DAA. Methods: A cohort of 166 chronic HCV patients who were treated with SOF-based DAA regimens and initially positive for HBcAb total were evaluated; 10 HBsAg-positive, 156 had past HBV exposure (HBsAg-negative/HBcAb-positive). Laboratory investigations, including liver functions tests, HBV-DNA, LSM by Transient elastography, and ARFI together with serum markers of fibrosis; APRI and FIB-4 were done at baseline and after 12 weeks of DAAs therapy. HBV-DNA levels and liver functions were monitored for assessment of HBVr. Results: Virological HBVr was diagnosed by ≥ 1 log10 IU/ml HBV-DNA levels in 2/166 patients (1.2%) among the whole HCV cohort, who were initially positive for HBsAg; 20%. Clinical HBVr (>3 folds liver enzyme elevation) was detected in one patient with virological HBVr. Conversely, none of past HBV-infected patients experienced HBVr. All patients achieved SVR12 and had a significant decline in serum transaminases, bilirubin, APRI, and LSM measurements after HCV eradication. Conclusion: HBVr might be considered after successful eradication of HCV following DAAs therapy, especially among patients who are positive for HBsAg, while past HBV infection does not seem to be a predisposing condition to HBVr.

Hepatitis C viral RNA in blood mononuclear cells of patients treated with directly acting antivirals.

BACKGROUND AND STUDY AIMS: Occult hepatitis C viral infection (OCI) may have serious complications, such as relapse, ongoing histological impairment, hepatic decompensation, hepatocellular carcinoma, and the possible risk of transmission. This study was conducted to assess the occurrence and prevalence of secondary OCI in patients with chronic hepatitis C viral infection (HCV) who received a complete course of directly acting antivirals (DAAs). PATIENTS AND METHODS: Antiviral therapy consisted of sofosbuvir + daclatasvir ± ribavirin for 12 weeks to 90 treatment-naive, compensated, chronic HCV patients. Plasma and peripheral blood mononuclear cells (PBMCs) were tested for HCV RNA viral load by quantitative, reverse transcription, real-time PCR at 8, 12 (Group I, n = 45), and 24 (Group II, n = 45) weeks after treatment initiation. RESULTS: By week 8, only 2 and 7 patients were positive for HCV RNA in plasma and PBMCs, respectively. No HCV RNA was detected by weeks 12 or 24 in the PBMCs of Groups I and II, respectively. Older age was significantly associated with HCV RNA positivity in plasma and PBMCs (n = 8) at week 8 compared with HCV RNA negativity (n = 82). No other significant differences were observed for any other variables. CONCLUSION: The development of secondary OCI among easy-to-treat patients following a full course of DAA treatment doesn't exist, hence, we do not recommend testing the HCV RNA in the PBMCs after complete course of treatment in this patient category. The detection of HCV RNA in PBMCs is recommended as a confirmatory test of cure following a shortened DAA treatment regimen.

Effect of disease stage and treatment outcomes on the dynamics of liver functions during and after treatment of hepatitis C with directly acting antivirals.

BACKGROUND: Virus C infection is recently treated successfully with plenty of direct antiviral agents (DAAs). We aimed to evaluate the effect of disease stage and treatment outcome on the dynamics of liver functions during treatment of hepatitis C with DAAs. METHODS: We reported the liver function in 2354 subjects diagnosed as chronic hepatitis C before, during and after treatment with different DAAs regimens. Patients were classified into two groups according to treatment response with further subclassification according to the presence or absence of cirrhosis, and changes in liver functions were compared in each group and subgroup. RESULTS: Totally 2213 (94%) achieved sustained virological response (SVR) to DAAs therapy with significant improvement in all liver biochemistry. Also, there was an improvement in the non-SVR group's liver enzymes in relapsers during and after treatment; however, there was no improvement in serum albumin. We noticed a slight increase in serum bilirubin at weeks 4 and 8 for both groups. CONCLUSION: DAAs therapy is associated with improvement of the liver biochemical profile and improved outcome in the majority of chronic hepatitis C virus patients due to suppression of viral replication. However, the long-term impact of DAAs therapy needs to be further evaluated.

Smart stability-indicating spectrophotometric methods for determination of binary mixtures without prior separation.

Ratio subtraction and isosbestic point methods are 2 innovating spectrophotometric methods used to determine vincamine in the presence of its acid degradation product and a mixture of cinnarizine (CN) and nicergoline (NIC). Linear correlations were obtained in the concentration range from 8-40 microg/mL for vincamine (I), 6-22 microg/mL for CN (II), and 6-36 microg/mL for NIC (III), with mean accuracies 99.72 +/- 0.917% for I, 99.91 +/- 0.703% for II, and 99.58 +/- 0.847 and 99.83 +/- 1.039% for III. The ratio subtraction method was utilized for the analysis of laboratory-prepared mixtures containing different ratios of vincamine and its degradation product, and it was valid in the presence of up to 80% degradation product. CN and NIC in synthetic mixtures were analyzed by the 2 proposed methods with the total content of the mixture determined at their respective isosbestic points of 270.2 and 235.8 nm, and the content of CN was determined by the ratio subtraction method. The proposed method was validated and found to be suitable as a stability-indicating assay method for vincamine in pharmaceutical formulations. The standard addition technique was applied to validate the results and to ensure the specificity of the proposed methods.

Kinetic study on the degradation of meclophenoxate hydrochloride in alkaline aqueous solutions by high performance liquid chromatography.

A high performance liquid chromatographic method was developed and validated for determination of meclophenoxate hydrochloride (I) in the presence of its degradation product (p-chlorophenoxy acetic acid) (II). Separation of (I) from (II) was performed using a ZORBAX ODS column with a mobile phase consisting of 0.2% triethylamine in 0.01 M ammonium carbonate: acetonitrile (70:30 v/v). The method showed high sensitivity with good linearity over the concentration range of 50 to 400 mug/ml. The method was successfully applied to the analysis of a pharmaceutical formulation containing (I) with excellent recovery. A kinetics investigation of the alkaline hydrolysis of (I) was carried out in sodium hydroxide solutions of 1, 1.5 and 2 N by monitoring the parent compound itself. The reaction order of (I) followed pseudo-first order kinetics. The activation energy could be estimated from the Arrhenius plot and it was found to be 12.331 kcal/mole.

Stability-indicating electrochemical methods for the determination of meclophenoxate hydrochloride and pyritinol dihydrochloride using ion-selective membrane electrodes.

The construction and electrochemical response characteristics of polyvinyl chloride (PVC) membrane sensors for the determination of meclophenoxate hydrochloride (I) and pyritinol dihydrochloride (II) in presence of their degradation products are described. The sensors are based on the use of the ion-association complexes of (I) and (II) cation with sodium tetraphenyl borate and ammonium reineckate counteranions as ion-exchange sites in the PVC matrix. In addition beta-cyclodextrin (beta-CD) membranes were used in the determination of I and II. These ion pairs and beta-CD were then incorporated as electroactive species with ortho nitrophenyl octyl ether (oNPOE) as a plasticizer. Three PVC sensors were fabricated for each drug, i.e. meclophenoxate tetraphenyl borate (meclo-TPB), meclophenoxate reineckate (meclo-RNC) and meclophenoxate beta-cyclodextrin (meclo-beta-CD), and the same was done for pyritinol (pyrit-TPB), (pyrit-RNC) and (pyrit-beta-CD). They showed near Nernestian responses for meclophenoxate over the concentration range 10(-5)-10(-2) with slopes of 52.73, 51.64 and 54.05 per concentration decade with average recoveries of 99.92+/-1.077, 99.96+/-0.502 and 100.03+/-0.763 for meclo-TPB, meclo-RNC and meclo-beta-CD respectively. Pyritinol also showed near Nernestian responses over the concentration range of 3.162 x 10(-6) - 3.162 x 10(-4) for pyrit-TPB and pyrit-RNC, and 10(-6) - 3.162 x 10(-4) for pyrit-beta-CD with slopes of 30.60, 31.10 and 32.89 per concentration decade and average recoveries of 99.99+/-0.827, 100.00+/-0.775 and 99.99+/-0.680 for pyrit-TPB, pyrit-RNC and pyrit-beta-CD respectively. The sensors were used successfully for the determination of I and II in laboratory prepared mixtures with their degradation products, in pharmaceutical dosage forms and in plasma.

Impact of old Schistosomiasis infection on the use of transient elastography (Fibroscan) for staging of fibrosis in chronic HCV patients.

BACKGROUND AND AIM: In tropical regions, Hepatitis C virus (HCV) - Schistosomiasis coinfection remains one of the health problems. With the new era of HCV treatment and the variety of methods of assessment of liver fibrosis so we aimed to evaluate the effectiveness of FibroScan for staging hepatic fibrosis in HCV-Schistosomiasis coinfected patients. METHODOLOGY: Three groups of patients were enrolled. Group 1: chronic HCV with out antischistosomal antibody (122 patients), Group 2: chronic HCV with positive antischistosomal antibodies and without periportal tract thickening (122 patients), Group 3: chronic HCV with positive antischistosomal antibodies and ultrasonographic picture of periportal tract thickening (108 patients). Routine laboratory workup, serum Antischistosomal antibody, and Schistosomal antigen in serum were performed. Ultrasound guided liver biopsy with histopathological examination; abdominal ultrasound and fibroscan examination were done for all patients. RESULTS: The agreement between results of liver biopsy and results of fibroscan in the staging of fibrosis was the best in group 1 (55.7%), Although the agreement was higher among those with no periportal tract thickening (70.7%) and the disagreement was higher among those with positive schistosomal serology (66.5%), yet this relation was not statistically significant. Multivariate logistic regression analysis showed that disagreement is significantly associated with older age, higher BMI (≥30), and increase in anti Schistosomal antibody titer. CONCLUSION: Fibroscan is a reliable, non-invasive tool for staging hepatic fibrosis among HCV-schistosomiasis co-infected patients with no effect of the induced periportal tract thickening on the readings. Only higher antischistosomal antibody titres may cause disagreement between liver biopsy and fibroscan.

A multicenter, open-label, phase III study of Abcertin in Gaucher disease.

BACKGROUND: Gaucher disease (GD) is caused by a deficiency in the lysosomal enzyme glucocerebrosidase. Enzyme replacement therapy (ERT) is recommended for clinical improvement. METHODS: The efficacy and safety of a new imiglucerase, Abcertin, were assessed in 7 Egyptian patients with treatment-naïve type 1 GD. Each patient was administered a biweekly 60 U/kg dose of Abcertin for 6 months. The primary endpoint was the change in hemoglobin concentration. The secondary endpoints were changes from baseline in platelet counts, spleen and liver volumes, biomarker levels, skeletal parameters, and bone mineral density. RESULTS: The hemoglobin concentration increased by a mean of 1.96 ±â€Š0.91 g/dL (range 1.11-2.80 g/dL) or 20.6% (P = .001). Statistically significant increases in the platelet count and decreases in the spleen volume and biomarker levels were also observed. There were no severe drug-related adverse events. One patient developed anti-imiglucerase antibodies without neutralizing activity. CONCLUSION: Our study results demonstrate the efficacy and safety of Abcertin in patients with type 1 GD. This suggests that Abcertin can be an alternative ERT option for type 1 GD.

Thyroid Dysfunction in Chronic Hepatitis C Patients Treated with the Combined Pegylated Interferon-Ribavirin Therapy.

Hepatitis C virus (HCV) is an Egyptian serious national health problem. The combination of pegylated interferon (PEG-IFN) with ribavirin (RIB) was considered the established therapy for chronic hepatitis C (CHC), and it was associated with several adverse effects, including thyroid dysfunction (TD). The aim of this work was to study TD in CHC patients receiving PEG-IFN+ RIB therapy. This retrospective study included 100 adult patients attending the outpatient clinics at AL-Kahera Al-Fatemya hospital and were eligible candidates for PEG-IFN+ RIB therapy. Thyroid hormonal profile (thyroid-stimulating hormone, free triiodothyronine, and free thyroxine) was done before initiation of treatment (week 0) and at weeks 12, 24, 48, and 72. The incidence of TD was more evident by the end of treatment (week 48); it was found to be 35%, mostly in the form of hypothyroidism, while the least incidence was detected by week 12 (2%), all in the form of hyperthyroidism. Generally, hypothyroidism was higher than hyperthyroidism in multiple folds. Thyroid profile was not significantly related to viral load.

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.

Stability-indicating methods for determination of vincamine in presence of its degradation product.

Three different stability indicating assay methods are developed and validated for determination of vincamine in the presence of its degradation product (vincaminic acid). The first method is based on the derivative ratio zero crossing spectrophotometric technique using 0.1 N hydrochloric acid as a solvent. In the second method, measurements are based on spectro-densitometric technique using high performance thin-layer chromatography (HPTLC) plates with a developing system consisting of methanol-chloroform-ethyl acetate (2:1:1, v/v/v). The third method depends on high-performance liquid chromatography (HPLC). Separation of vincamine from vincaminic acid using Lichrocart RP-18 column (250 mm x 4.6 mm i.d.) with a mobile phase consisting of acetonitrile-ammonium carbonate (0.01 M) (7:3, v/v) is achieved. The methods showed high sensitivity with good linearity over the concentration ranges of 12 to 48 microg ml-1, 3 to 17 microg/spot, and 2 to 20 microg ml-1 for derivative spectrophotometry, spectro-densitometry and HPLC methods, respectively. The developed methods were successfully applied to the analysis of pharmaceutical formulations containing vincamine with excellent recoveries.

Stability-indicating methods for determination of pyritinol dihydrochloride in the presence of its precursor and degradation product by derivative spectrophotometry.

A first-derivative spectrophotometric (1D) method and a derivative-ratio zero-crossing spectrophotometric (1DD) method were used to determine pyritinol dihydrochloride (I) in the presence of its precursor (II) and its degradation product (III) with 0.1N hydrochloric acid as a solvent. Linear relationships were obtained in the ranges of 6-22 microg/mL for the (1D) method and 6-20 microg/mL for the (1DD) method. By applying the proposed methods, it was possible to determine pyritinol dihydrochloride in its pure powdered form with an accuracy of 100.36 +/- 1.497% (n = 9) for the (1D) method and an accuracy of 99.92 +/- 1.172% (n = 8) for the (1DD) method. Laboratory-prepared mixtures containing different ratios of (I), (II), and (III) were analyzed, and the proposed methods were valid for concentrations of < or = 10% (II) and < or = 50% (III). The proposed methods were validated and found to be suitable as stability-indicating assay methods for pyritinol in pharmaceutical formulations.