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Papers by Ghada Refat

Sohag Medical Journal, 2017

Sohag Medical Journal, Oct 1, 2018

Esophageal varices are the major complication of portal hypertension. It is detected in about 50%... more Esophageal varices are the major complication of portal hypertension. It is detected in about 50% of cirrhosis patients. Portal hypertensionis associated with both increased portal inflow and increased intrahepatic vascular resistance. Intrahepatic vascular resistance is caused by the architectural distortion of the liver resulting from fibrosis and by increased sinusoidal tone. Portal venous inflow results from a combination of ahyperdynamic circulatory state and increased plasma volume. In response to the increased portal pressure, collateral circulation develops by the opening of preexisting vascular channels. Esophagogastric varices are the most important collateral vessels: they tend to increase in size with the increase of portal pressure and rupture when wall tension exceeds a critical value.

Sohag Medical Journal, Apr 1, 2019

Hepatitis C virus (HCV) is endemic in Egypt. Over 15% of populations of the people in Egypt are i... more Hepatitis C virus (HCV) is endemic in Egypt. Over 15% of populations of the people in Egypt are infected, this is ten times greater than in any other country in the world. To validate a simple, inexpensive, non invasive markers (Fib-4, APRI, syndecan-1 and apolipoprotein A-1(ApoA-1) for detection of liver fibrosis in patients with chronic HCV and thereby reduce the need for liver biopsy. Estimation of serum syndecan-1 and apoA-1 by ELISA were done on 20 normal healthy persons and 57 chronic hepatitis C patients, the patients were staged according to liver biopsies (Metavir fibrosis staging) (stage f1=15, f2=15, f3=14,f4= 13). The area under the receiver operating characteristic (ROC) curve (AUC) of syndecan-1=(0.72), the mean level of plasma syndecan-1 was significantly higher in chronic HCV patients when compared to control subjects (P=0.0008), but the mean level of ApoA-1 was not significantly different from that of controls (p=o.65), and it had significant negative correlation to the stage of fibrosis (AUC=0.57). Moreover the APRI and Fib-4 were proved significantly directly correlated with fibrosis stage of the studied patients. This study not reveals putative biomarkers of liver fibrosis (syndecan-1, ApoA-1 APRI, Fib-4) but also proves the differential expression of those markers in different stages of fibrosis. It is expected that combination of these novel biomarkers could be applied clinically to predict the stage of liver fibrosis without the need of liver biopsy.

Sohag Medical Journal, Oct 1, 2018

Non-invasive markers for assessing liver fibrosis have been developed, and they are frequently us... more Non-invasive markers for assessing liver fibrosis have been developed, and they are frequently used in clinical practice. They have been validated in different studies, and some were found to be highly accurate compared with liver biopsies which have always been used as the standard reference method for evaluating the accuracy of non-invasive methods 1 .The performance of a non-invasive diagnostic method is evaluated by calculation of the area under the receiver operator characteristic curve (AUROC) 2. PDF created with pdfFactory Pro trial version www.pdffactory.com SOHAG MEDICAL JOURNAL Non-invasive methods for diagnosis of hepatic fibrosis in Vol. 22 No.

Sohag Medical Journal, Jul 1, 2018

Background: Chronic liver diseases are characterized by two fundamental aspects, persistent injur... more Background: Chronic liver diseases are characterized by two fundamental aspects, persistent injury and fibrosis, which are cardinal features for the continuous progression towards cirrhosis and end stage liver failure. Objective: To study the expression of platelets derived growth factor receptor ß (PDGFR-β) and tumor necrosis factor (TNF α) in the liver and their relation to the stage and grade of chronic HCV. Patients and Methods: Analytical cross-sectional study was conducted on fifty patients with proven chronic hepatitis C. All patients were referred to Tropical Medicine and Gastroenterology Department, Sohag University Hospital. Patients were categorized into two groups according to the histological stages of chronic hepatitis C as follows, group 1 includes 40 patients in stages 0,1 and 2; whereas group 2 includes 10 patients in stage 3. All patients were then recategorized according to the grades of inflammatory activity into patients with minimal and mild inflammation (G1+G2=32 patients) and those with moderate and severe inflammation (G3 +G4=18 patients). All patients were subjected to full history taking, complete clinical examination, complete blood count, liver function tests. Liver biopsy was evaluated for immunohistochemical expression of PDGFR-β and TNFα. Results: The included patients were 80 % males and 20 % females. Their mean age was 44.42±11.17 years. The mean average weighted scores (AWS) of Imunohisto-chemical expression of PDGFR-β, and TNFα were significantly higher in moderate and severe inflammation versus minimal and mild inflammation (P=0.05; 0.0001respectively). Similarly, the mean AWS of PDGFR-β, and TNFα were significantly higher in patients with stage 3 versus stages 0,1 and 2 (P=0.04; 0.0001 respectively). Conclusion: Expression of PDGFR-β, and TNFα markers were associated with progression of disease activity and fibrosis.

Sohag Medical Journal, Oct 1, 2017

Background Worldwide Egypt had the highest prevalence of hepatitis C virus infection. Angiogenesi... more Background Worldwide Egypt had the highest prevalence of hepatitis C virus infection. Angiogenesis is a complex process that regulated by many factors, including vascular endothelial growth factor (VEGF).in the liver HSCs, Kupffer cells, regenerating hepatocytes and existing endothelial cells are responsible for the process of neo angiogenesis and production of vascular endothelial growth factor (VEGF). Aim of the work: To detect the significance vascular endothelial growth factor and its relation to hepatic neoangiogenesis in hepatitis C associated chronic liver disease. Methods: A total of 70 adult patients with chronic hepatitis C infection in various stages with no evidence of cirrhosis, were recruited for the study. We studied the expression of VEGF and vascular density in liver specimens from chronic HCV infected patients using a computer-based analysis of immunohistochemical staining and confirmed it by Western Blot. Results: Relation between stage of fibrosis and laboratory finding was done there were significant relation between the stage of fibrosis and platelet count, also, the level of liver enzyme (AST and ALT) significantly related to the fibrosis stage, Serum albumin significantly related to fibrosis stage. The most important findings that VEGF level were significantly related to fibrosis stage. Conclusion: Angiogenesis was present in 45.5% cases of chronic liver disease. It was proportional to the increase in stage of fibrosis. Expression of VEGF was commonly found in early stages of fibrosis.

Sohag Medical Journal, Dec 5, 2019

Background: Worldwide use of direct-acting antiviral agents (DAAs) is nowadays the standard metho... more Background: Worldwide use of direct-acting antiviral agents (DAAs) is nowadays the standard method for the treatment of HCV infection. Different researches reported that DAAs have an acceptable safety profile and sustained virological response (SVR) rate compared with previous treatment combinations containing interferon. Therefore, our study aimed to estimate the rate of SVR in patients treated with sofosbuvir-based regimens in Sohag Governate and to assess the adverse events (AEs) and the biochemical response to therapy in the studied population. Patients and Methods: Our study was a prospective one that included 135 patients eligible for treatment with sofosbuvir-based regimens. Patients were categorized into two different groups: Group one received sofosbuvir with daclatasvir combination and group two received sofosbuvir plus daclatasvir with ribavirin. The SVR12 and adverse events of the treatments were evaluated. Liver function tests were assessed at the start of treatment, at 4 weeks, at the end of therapy and at 12-week after completing the therapy. Results: The SVR rate at 12-week after completing the therapy was nearly equal in both groups (98.5%). The most frequently reported side effects were fatigue and headache. Liver function tests were significantly improved at SVR12. Conclusion: Sofosbuvir plus daclatasvir ± ribavirin were highly effective and adequately tolerated.

Egyptian Journal of Medical Microbiology

Background: Hepatocellular carcinoma (HCC) is considered as the primary malignancy of the liver t... more Background: Hepatocellular carcinoma (HCC) is considered as the primary malignancy of the liver that usually occurs on top of chronic viral hepatitis. The TP53 (tumor protein 53) is a tumor suppressor gene which is the key in tumor development and progression and the single nucleotide polymorphism (SNP) of the p53 gene codon 72 (p53Arg/Pro) changes the structure of the protein. Objectives: to determine the association of the TP53 Arg72Pro polymorphism with the risk of HCC development in Hepatitis C virus (HCV) infected Egyptian patients. Methodology: This is a case control study conducted in Sohag University Hospital on 100 participants (20 HCC, 20 CHCV, 40 LC and 20 control). TP53 gene polymorphism was identified by Polymerase chain reaction-Restriction fragment length polymorphism (PCR-RFLP), serum level of TP53 was measured by quantitative ELISA. Results: The GG genotype / G allele has the highest frequency in the controls, while the CC genotype/ C allele was more frequently foun...

Clinical and Experimental Hepatology

Aim of the study: We aimed to investigate the characteristics of acute-on-chronic liver failure (... more Aim of the study: We aimed to investigate the characteristics of acute-on-chronic liver failure (ACLF) and factors associated with 28-day mortality in patients with ACLF. Material and methods: This prospective study included ACLF patients based on the European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) Consortium criteria, admitted between March 2021 and February 2022. We examined variables associated with 28-day mortality using multivariate Cox regression analysis. Results: Of 326 patients admitted with acute decompensation (AD) of cirrhosis, 109 (33.44%) patients were diagnosed with ACLF (mean age 63.61 ±11.15 years, 65.14% males). Of these, 26.61%, 35.78%, and 37.61% of patients were in ACLF grades 1, 2, and 3 respectively. HCV (80.73%) was the main aetiology of cirrhosis. Upper gastrointestinal bleeding (25.69%) was the most common trigger. Kidney failure (73.39%) was the most common organ failure. The 28-day mortality rate was 66.97%. Cox regression analysis revealed that the existence of 2 (HR = 6.99, 95% CI: 2.68-18.25, p < 0.0001) or ≥ 3 (HR = 9.34, 95% CI: 3.6-24.74, p < 0.0001) organ failures, hepatic encephalopathy (HR = 2.96, 95% CI: 1.27-6.94, p = 0.01), and elevated serum bilirubin (HR = 1.03, 95% CI: 1.00-1.06, p = 0.04) were independent predictors for 28-day mortality, while shifting blood pH to the normal range was associated with a decrease in the HR of ACLF mortality (HR = 0.03, 95% CI: 0.002-0.44, p = 0.01). Conclusions: ACLF has a very high 28-day mortality, which is associated with the existence of 2 or more organ failures, hepatic encephalopathy, elevated serum bilirubin, and low blood pH.

BMC Cancer, 2022

Background Hepatocellular carcinoma (HCC) has high incidence and mortality worldwide. Local ablat... more Background Hepatocellular carcinoma (HCC) has high incidence and mortality worldwide. Local ablation using radiofrequency ablation (RFA) or microwave ablation (MWA) is potentially curative for early-stage HCC with outcomes comparable to surgical resection. We explored the influence of demographic, clinical, and laboratory factors on outcomes of HCC patients receiving ablation. Methods This retrospective cohort study included 221 HCC patients receiving local ablation at Mayo Clinic between January 2000 and October 2018, comprising 140 RFA and 81 MWA. Prognostic factors determining overall survival (OS) and disease-free survival (DFS) were identified using multivariate analysis. Results There was no clinically significant difference in OS or DFS between RFA and MWA. In multivariate analysis of OS, pre-ablation lymphocyte-monocyte ratio [Hazard ratio (HR) 0.7, 95% confidence interval (CI) 0.58–0.84, P = 0.0001], MELD score [HR 1.12, 95%CI 1.068–1.17, P < 0.0001], tumor number [HR 1...

Hepatitis B virus (HBV) infection is a major global health problem with over 240 million people c... more Hepatitis B virus (HBV) infection is a major global health problem with over 240 million people chronically infected worldwide [1]. The spectrum of chronic HBV infection is variable, ranging from inactive carrier state to progressive CHB, which can evolve to cirrhosis in up to 20% of the cases, with hepatic insufficiency and portal hypertension being the most serious consequences [2]. Chronically infected subjects also have a 100 times higher risk to develop hepatocellular carcinoma (HCC) than noncarriers [3]. In untreated patients with CHB, the cumulative incidences of cirrhosis, hepatic decompensation and HCC at 5 years were approximately 20%, 15% and 5%, respectively [4]. Liver fibrosis is part of the structural and functional alterations in most chronic liver diseases. It is one of the main prognostic factors as the amount of fibrosis is correlated with the risk of developing cirrhosis and liver-related complications in viral and non viral chronic liver diseases [5]. The current...

Background and Aim: Anemia is a major clinical multifactorial problem in hemodialysis (HD) patien... more Background and Aim: Anemia is a major clinical multifactorial problem in hemodialysis (HD) patients. Iron metabolism is frequently impaired and may complicate the management of anemia. Hepcidin is synthesized in the liver. It is thought to be a key regulator of iron homeostasis. Therefore, we thought to assess prohepcidin level and iron indices in patients on regular HD with and without associated viral hepatitis. Patients and Methods: Sixty patients (38 males and 22 females) with chronic renal failure (CRF) undergoing regular HD and twenty age and sex matched healthy controls were included. Peripheral hemogram, liver function tests, kidney function tests, lipogram, C-reactive protein, iron indices, serum prohepcidin, HBsAg, HBcIgM and anti-HCV antibody were tested for both patients and controls. Results: 22 Patients were positive for anti-HCV, 16 were HBsAg positive and 22 were negative for both markers. Mean serum prohepcidin and ferritin levels in HD patients were significantly h...

Infection and Drug Resistance, 2021

Background: Tumor necrosis factor (TNF) family includes lymphotoxin-alpha (LTA) which is a pro-in... more Background: Tumor necrosis factor (TNF) family includes lymphotoxin-alpha (LTA) which is a pro-inflammatory cytokine which plays a role in hepatic fibrogenesis. LTA gene polymorphism plays a role in different inflammatory and immunomodulatory diseases. This polymorphism is also suggested to affect chronic hepatitis C (CHC) infection course. Aim: To study the contribution of LTA gene polymorphism in different chronic hepatitis C stages and hepatocellular carcinoma risk. Patients and Methods: Our study included 108 chronic HCV patients grouped according to the disease stage. Group (A): CHC, group (B): liver cirrhosis (LC), group (C): LC with HCC, and group (D): healthy controls. Routine laboratory investigations, polymerase chain reaction (PCR) for quantification of HCV, abdominal ultrasonography, and Liver stiffness measurement (LSM) were done. Child-Turcotte-Pugh, Model for end-stage liver disease (MELD), and Fibrosis index based on 4 (FIB-4) scores were calculated. We used the PCRrestriction fragment length polymorphism technique for lymphotoxin-α genotyping. Results: The A/G genotype was predominant in all groups. In HCC patients, G/G genotype was more frequent (31.8%) than in the LC group (19.4%), CHC group (17.8%), and controls (4.17%). A significant association was found between LTA genotypes and the child classes in HCC (P<0.01) but not in LC patients (P>0.05). HCC patients carrying A/G genotype had higher MELD scores than other genotypes. Multivariate binary logistic regression analysis confirmed that LTA G/G genotype and low platelet count were independent predictors for HCC development in patients with HCV-related LC. Conclusion: Detection of LTA G/G genotype in chronic HCV patients could help to recognize high-risk patients for disease progression and HCC development.

Sohag Medical Journal, 2019

Liver fibrosis is a chronic condition that originates as a result of prolonged hepatic injury. Li... more Liver fibrosis is a chronic condition that originates as a result of prolonged hepatic injury. Liver fibrosis is caused mainly by Schistosomiasis, chronic hepatitis C and B viral infections, non-alcoholic fatty liver disease, alcoholic liver disease, cholestatic and autoimmune liver diseases. Hepatic stellate cells are the master cells in the fibrosis process regardless of the cause. HSCs activation involves two separate stages: the initiation stage and the perpetuation stage. The activated HSCs up-regulate gene expression of extracellular matrix elements, matrix-degrading enzymes, and their inhibitors. The components of fibrotic ECM or inflammatory mediators implicated in either the process of fibrosis or degradation of scar tissue could be used as direct markers of fibrosis. Direct indices of fibrosis are classified into direct markers associated with matrix deposition such as HA and laminin, direct markers associated with matrix degradation such as MMPs and TIMPs, and Cytokines and chemokines linked to hepatic fibrosis such as TGF-1 and PDGF. The validation of these markers for use in clinical practice instead of liver biopsy should be balanced against the possibility of misleading results of these markers as they are affected by factors other than fibrosis.

Sohag Medical Journal, 2019

Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world and the fourth most c... more Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world and the fourth most common cause of cancer death.The development of HCC is a complex and multifactorial process, in which both environmental and genetic features interfere and contribute to malignant transformation. Numerous genetic studies have reported associations between single nucleotide polymorphisms (SNPs) and the presence of HCC.The purpose of thisreview is to describethe structure ofvitamin D receptor (VDR) gene and common polymorphisms involving it, and to address the associationsbetween VDR SNPs and cancer including HCC.

Sohag Medical Journal, 2018

Background and aim: Thrombocytopenia is a common complication of chronic liver diseases and is du... more Background and aim: Thrombocytopenia is a common complication of chronic liver diseases and is due to various causes.The effect of thrombocytopenia on liver damage and the exact mechanisms that lead to thrombocytopenia in chronic liver disease and cirrhosis are still unclear. As Platelets Derived Growth Factor ß (PDGF-ß) is released from platelets (PLTs) upon activation. We tried to identify PLTs and PDGFR-ß in the liver to shed some light on the pathophysiology of thrombocytopenia and liver fibrosis in chronic hepatic C patients. Patients and Methods: Analytical cross-sectional study was conducted on fifty patients with proven chronic hepatitis C. All patients were referred to Tropical Medicine and Gastroenterology Department, Sohag University Hospital. Patients were categorized into two groups. Group 1 includes patients with PLT count less than 150000/µL (thrombocytopenia). Group 2 includes patients with normal PLT count (150000-450000/µL). All patients were subjected to full history taking, complete clinical examination, complete blood count, liver function tests. Liver biopsy was obtained for histological staging and grading. Immunohistochemical study of PLTs and PDGFR-ß were done using monoclonal antibodies against PLT's surface marker CD41 and PDGFR-ß. Results: The included patients were 80 % males and 20 % females. Their mean age was 44.42± 11.17 years. The mean average weighted score (AWS) of Imunohisto-chemical expression of CD41was significantly higher in thrombocytopenic group compared to normal PLTs group (5.8±2.86 vs 3.43±3.03; P<0.001). There was a significant negative correlation between CD41 expression and peripheral PLT count (r=-0.4; P=0.007). PDGFR-ß expression was significantly stronger in thrombocytopenic patients than patients with normal PLT count (6.9±3.6 vs 5.27±3.92; P=0.001). It showed also a significant negative correlation with peripheral PLT count (r=-0.34, P=0.045). Both CD41 and PDGFR-ß expression were significantly elevated in patients with advanced stage of fibrosis than in those with earlier stages (7.26±5.23 vs 5.88±3.24; P=0.04 &9.2±2.7 vs 6.7±3.6; P<0.01 respectively). Conclusion: The accumulation of PLTs in the liver in patients with chronic hepatitis C may be involved in thrombocytopenia and liver fibrosis.

Journal of Hepatology, 2014

Background and Aims: Telaprevir (TVR)-based triple therapy is effective for hepatitis C patients.... more Background and Aims: Telaprevir (TVR)-based triple therapy is effective for hepatitis C patients. However, we have reported that TVR causes a reduction in renal function, with a reduction in the excretion of ribavirin (RBV), and the serum RBV concentration rises and the increased RBV concentration leads to hemolytic anemia (Y. Karino et al. J viral hepat. 2013). In this study, we retrospectively investigated the effects and adverse events of simeprevir (SMV)based triple therapy in comparison with TVR-based triple therapy and PEG-IFN/RBV therapy. Methods: Twenty seven patients were assigned to SMV for 12 weeks along with PEG-IFN/RBV for 24 weeks (Group A), while 65 patients were assigned to TVR for 12 weeks along with PEG-IFN/ RBV for 24 weeks (Group B) and 190 patients were assigned to PEG-IFN/RBV for 48 weeks (Group C). SMV was administered at a dose of 100 mg (or 50 mg) per day for 12 weeks (or 24weeks) and TVR was administered at a dose of 1500 mg or 2250 mg per day for 12 weeks. Results: SVR24 rate was 85.2% in Group A, 84.5% in Group B, and 45.3% in Group C. Adherence to RBV was significantly lower in Group B (63.3%) than Group A (93.5%) and Group C (94.3%). Average hemoglobin level (g/dl) at weeks 0/1/2/4/8/12 was 14.

Sohag Medical Journal, 2019

Vitamin D through the vitamin D receptor (VDR) is involved in the control of bone and calcium hom... more Vitamin D through the vitamin D receptor (VDR) is involved in the control of bone and calcium homeostasis, immunoregulation, cellular differentiation,and antiinflammatoryactions.The liver is central in vitamin D synthesis, however the direct involvement ofthe vitamin D with chronic liver disease, chronic hepatitis C (CHC) infection, and hepatocellular carcinoma (HCC) remains to be evaluated.The purpose of thisreview is to describevitamin D metabolism, the mechanisms of homeostatic control, and to address the associationsbetween vitamin D and HCV-related liver disease.

The Egyptian Journal of Hospital Medicine

Background: With the advent of direct-acting antivirals (DAAs) for hepatitis C virus (HCV), there... more Background: With the advent of direct-acting antivirals (DAAs) for hepatitis C virus (HCV), there has been a marked increase in the number of patients who achieve sustained virological response (SVR). Several factors mediate the response to therapy as immunologic and genetic factors. Objective: We aimed to assess the pattern of response to sofosbuvir and daclatasvir +/-ribavirin regimen in chronic hepatitis C (CHC) patients and to study the predictors of non SVR (relapse). Patients and methods: This prospective study was conducted on 506 consecutive HCV-infected patients. Abdominal ultrasonography, liver function tests, alpha-fetoprotein (AFP), HCV polymerase chain reaction (PCR), complete blood count (CBC), random blood glucose, C-X-C motif chemokine ligand 10 (CXCL10), Child-Pugh score, and some serum fibrosis indices were performed. After completion of the course of treatment, all patients were followed up for 6 months and then categorized into sustained virological responders and non-sustained virological responders (relapsers). Results: Out of the 506 HCV-infected patients, 497 (98.2%) achieved SVR, and 9 (1.8%) experienced relapse. Response rates to sofosbuvir and daclatasvir +/-ribavirin in cirrhotic patients were lower than those without cirrhosis. The presence of liver cirrhosis (LC) and the need for receiving triple therapy were the main factors that predicted relapse in univariate analysis. CXCL10 levels showed statistically insignificant differences between responders and relapsers, between cirrhotic and non-cirrhotic patients, and between pretreatment and post-treatment levels. Conclusions: Response rate of CHC patients to sofosbuvir and daclatasvir +/-ribavirin is excellent and relapse only occurred in a minority of patients (1.8%). Cirrhotic patients showed higher relapse rate than non-cirrhotic (55.65% vs 44.4%).

The Egyptian Journal of Hospital Medicine, 2022

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease involving ... more Background: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease involving about 25% of the world's population. Several studies investigated the role of the different anthropometric measures in NAFLD diagnosis. Objective: This study aimed to evaluate the diagnostic performance of the different anthropometric measures as noninvasive predictors for the presence of steatosis in a series of NAFLD patients. Patients and methods: A cross-sectional study was conducted in a series of adult asymptomatic subjects. NAFLD was diagnosed in 100 cases by ultrasonography for whom controlled attenuation parameters (CAP) examination was done. Body mass index (BMI), waist circumference (WCir), waist to height ratio (WHtR), lipid accumulation product (LAP) were measured. Also, subcutaneous and preperitoneal fat were measured using abdominal ultrasound. Roc curve analysis was used to detect the optimal cutoff of different models that predict steatosis. Results: BMI, WCir, WHtR, LAP, subcutaneous and preperitoneal fat had good diagnostic performance for predicting hepatic steatosis (AUROC for LAP=1 and approaching 1 in all other anthropometric measures). Conclusion: The clinical anthropometric measures are easy applicable and non-costly promising tools for the prediction of NAFLD in Egyptian patients.

Sohag Medical Journal, 2017

Sohag Medical Journal, Oct 1, 2018

Esophageal varices are the major complication of portal hypertension. It is detected in about 50%... more Esophageal varices are the major complication of portal hypertension. It is detected in about 50% of cirrhosis patients. Portal hypertensionis associated with both increased portal inflow and increased intrahepatic vascular resistance. Intrahepatic vascular resistance is caused by the architectural distortion of the liver resulting from fibrosis and by increased sinusoidal tone. Portal venous inflow results from a combination of ahyperdynamic circulatory state and increased plasma volume. In response to the increased portal pressure, collateral circulation develops by the opening of preexisting vascular channels. Esophagogastric varices are the most important collateral vessels: they tend to increase in size with the increase of portal pressure and rupture when wall tension exceeds a critical value.

Sohag Medical Journal, Apr 1, 2019

Hepatitis C virus (HCV) is endemic in Egypt. Over 15% of populations of the people in Egypt are i... more Hepatitis C virus (HCV) is endemic in Egypt. Over 15% of populations of the people in Egypt are infected, this is ten times greater than in any other country in the world. To validate a simple, inexpensive, non invasive markers (Fib-4, APRI, syndecan-1 and apolipoprotein A-1(ApoA-1) for detection of liver fibrosis in patients with chronic HCV and thereby reduce the need for liver biopsy. Estimation of serum syndecan-1 and apoA-1 by ELISA were done on 20 normal healthy persons and 57 chronic hepatitis C patients, the patients were staged according to liver biopsies (Metavir fibrosis staging) (stage f1=15, f2=15, f3=14,f4= 13). The area under the receiver operating characteristic (ROC) curve (AUC) of syndecan-1=(0.72), the mean level of plasma syndecan-1 was significantly higher in chronic HCV patients when compared to control subjects (P=0.0008), but the mean level of ApoA-1 was not significantly different from that of controls (p=o.65), and it had significant negative correlation to the stage of fibrosis (AUC=0.57). Moreover the APRI and Fib-4 were proved significantly directly correlated with fibrosis stage of the studied patients. This study not reveals putative biomarkers of liver fibrosis (syndecan-1, ApoA-1 APRI, Fib-4) but also proves the differential expression of those markers in different stages of fibrosis. It is expected that combination of these novel biomarkers could be applied clinically to predict the stage of liver fibrosis without the need of liver biopsy.

Sohag Medical Journal, Oct 1, 2018

Non-invasive markers for assessing liver fibrosis have been developed, and they are frequently us... more Non-invasive markers for assessing liver fibrosis have been developed, and they are frequently used in clinical practice. They have been validated in different studies, and some were found to be highly accurate compared with liver biopsies which have always been used as the standard reference method for evaluating the accuracy of non-invasive methods 1 .The performance of a non-invasive diagnostic method is evaluated by calculation of the area under the receiver operator characteristic curve (AUROC) 2. PDF created with pdfFactory Pro trial version www.pdffactory.com SOHAG MEDICAL JOURNAL Non-invasive methods for diagnosis of hepatic fibrosis in Vol. 22 No.

Sohag Medical Journal, Jul 1, 2018

Background: Chronic liver diseases are characterized by two fundamental aspects, persistent injur... more Background: Chronic liver diseases are characterized by two fundamental aspects, persistent injury and fibrosis, which are cardinal features for the continuous progression towards cirrhosis and end stage liver failure. Objective: To study the expression of platelets derived growth factor receptor ß (PDGFR-β) and tumor necrosis factor (TNF α) in the liver and their relation to the stage and grade of chronic HCV. Patients and Methods: Analytical cross-sectional study was conducted on fifty patients with proven chronic hepatitis C. All patients were referred to Tropical Medicine and Gastroenterology Department, Sohag University Hospital. Patients were categorized into two groups according to the histological stages of chronic hepatitis C as follows, group 1 includes 40 patients in stages 0,1 and 2; whereas group 2 includes 10 patients in stage 3. All patients were then recategorized according to the grades of inflammatory activity into patients with minimal and mild inflammation (G1+G2=32 patients) and those with moderate and severe inflammation (G3 +G4=18 patients). All patients were subjected to full history taking, complete clinical examination, complete blood count, liver function tests. Liver biopsy was evaluated for immunohistochemical expression of PDGFR-β and TNFα. Results: The included patients were 80 % males and 20 % females. Their mean age was 44.42±11.17 years. The mean average weighted scores (AWS) of Imunohisto-chemical expression of PDGFR-β, and TNFα were significantly higher in moderate and severe inflammation versus minimal and mild inflammation (P=0.05; 0.0001respectively). Similarly, the mean AWS of PDGFR-β, and TNFα were significantly higher in patients with stage 3 versus stages 0,1 and 2 (P=0.04; 0.0001 respectively). Conclusion: Expression of PDGFR-β, and TNFα markers were associated with progression of disease activity and fibrosis.

Sohag Medical Journal, Oct 1, 2017

Background Worldwide Egypt had the highest prevalence of hepatitis C virus infection. Angiogenesi... more Background Worldwide Egypt had the highest prevalence of hepatitis C virus infection. Angiogenesis is a complex process that regulated by many factors, including vascular endothelial growth factor (VEGF).in the liver HSCs, Kupffer cells, regenerating hepatocytes and existing endothelial cells are responsible for the process of neo angiogenesis and production of vascular endothelial growth factor (VEGF). Aim of the work: To detect the significance vascular endothelial growth factor and its relation to hepatic neoangiogenesis in hepatitis C associated chronic liver disease. Methods: A total of 70 adult patients with chronic hepatitis C infection in various stages with no evidence of cirrhosis, were recruited for the study. We studied the expression of VEGF and vascular density in liver specimens from chronic HCV infected patients using a computer-based analysis of immunohistochemical staining and confirmed it by Western Blot. Results: Relation between stage of fibrosis and laboratory finding was done there were significant relation between the stage of fibrosis and platelet count, also, the level of liver enzyme (AST and ALT) significantly related to the fibrosis stage, Serum albumin significantly related to fibrosis stage. The most important findings that VEGF level were significantly related to fibrosis stage. Conclusion: Angiogenesis was present in 45.5% cases of chronic liver disease. It was proportional to the increase in stage of fibrosis. Expression of VEGF was commonly found in early stages of fibrosis.

Sohag Medical Journal, Dec 5, 2019

Background: Worldwide use of direct-acting antiviral agents (DAAs) is nowadays the standard metho... more Background: Worldwide use of direct-acting antiviral agents (DAAs) is nowadays the standard method for the treatment of HCV infection. Different researches reported that DAAs have an acceptable safety profile and sustained virological response (SVR) rate compared with previous treatment combinations containing interferon. Therefore, our study aimed to estimate the rate of SVR in patients treated with sofosbuvir-based regimens in Sohag Governate and to assess the adverse events (AEs) and the biochemical response to therapy in the studied population. Patients and Methods: Our study was a prospective one that included 135 patients eligible for treatment with sofosbuvir-based regimens. Patients were categorized into two different groups: Group one received sofosbuvir with daclatasvir combination and group two received sofosbuvir plus daclatasvir with ribavirin. The SVR12 and adverse events of the treatments were evaluated. Liver function tests were assessed at the start of treatment, at 4 weeks, at the end of therapy and at 12-week after completing the therapy. Results: The SVR rate at 12-week after completing the therapy was nearly equal in both groups (98.5%). The most frequently reported side effects were fatigue and headache. Liver function tests were significantly improved at SVR12. Conclusion: Sofosbuvir plus daclatasvir ± ribavirin were highly effective and adequately tolerated.

Egyptian Journal of Medical Microbiology

Background: Hepatocellular carcinoma (HCC) is considered as the primary malignancy of the liver t... more Background: Hepatocellular carcinoma (HCC) is considered as the primary malignancy of the liver that usually occurs on top of chronic viral hepatitis. The TP53 (tumor protein 53) is a tumor suppressor gene which is the key in tumor development and progression and the single nucleotide polymorphism (SNP) of the p53 gene codon 72 (p53Arg/Pro) changes the structure of the protein. Objectives: to determine the association of the TP53 Arg72Pro polymorphism with the risk of HCC development in Hepatitis C virus (HCV) infected Egyptian patients. Methodology: This is a case control study conducted in Sohag University Hospital on 100 participants (20 HCC, 20 CHCV, 40 LC and 20 control). TP53 gene polymorphism was identified by Polymerase chain reaction-Restriction fragment length polymorphism (PCR-RFLP), serum level of TP53 was measured by quantitative ELISA. Results: The GG genotype / G allele has the highest frequency in the controls, while the CC genotype/ C allele was more frequently foun...

Clinical and Experimental Hepatology

Aim of the study: We aimed to investigate the characteristics of acute-on-chronic liver failure (... more Aim of the study: We aimed to investigate the characteristics of acute-on-chronic liver failure (ACLF) and factors associated with 28-day mortality in patients with ACLF. Material and methods: This prospective study included ACLF patients based on the European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) Consortium criteria, admitted between March 2021 and February 2022. We examined variables associated with 28-day mortality using multivariate Cox regression analysis. Results: Of 326 patients admitted with acute decompensation (AD) of cirrhosis, 109 (33.44%) patients were diagnosed with ACLF (mean age 63.61 ±11.15 years, 65.14% males). Of these, 26.61%, 35.78%, and 37.61% of patients were in ACLF grades 1, 2, and 3 respectively. HCV (80.73%) was the main aetiology of cirrhosis. Upper gastrointestinal bleeding (25.69%) was the most common trigger. Kidney failure (73.39%) was the most common organ failure. The 28-day mortality rate was 66.97%. Cox regression analysis revealed that the existence of 2 (HR = 6.99, 95% CI: 2.68-18.25, p < 0.0001) or ≥ 3 (HR = 9.34, 95% CI: 3.6-24.74, p < 0.0001) organ failures, hepatic encephalopathy (HR = 2.96, 95% CI: 1.27-6.94, p = 0.01), and elevated serum bilirubin (HR = 1.03, 95% CI: 1.00-1.06, p = 0.04) were independent predictors for 28-day mortality, while shifting blood pH to the normal range was associated with a decrease in the HR of ACLF mortality (HR = 0.03, 95% CI: 0.002-0.44, p = 0.01). Conclusions: ACLF has a very high 28-day mortality, which is associated with the existence of 2 or more organ failures, hepatic encephalopathy, elevated serum bilirubin, and low blood pH.

BMC Cancer, 2022

Background Hepatocellular carcinoma (HCC) has high incidence and mortality worldwide. Local ablat... more Background Hepatocellular carcinoma (HCC) has high incidence and mortality worldwide. Local ablation using radiofrequency ablation (RFA) or microwave ablation (MWA) is potentially curative for early-stage HCC with outcomes comparable to surgical resection. We explored the influence of demographic, clinical, and laboratory factors on outcomes of HCC patients receiving ablation. Methods This retrospective cohort study included 221 HCC patients receiving local ablation at Mayo Clinic between January 2000 and October 2018, comprising 140 RFA and 81 MWA. Prognostic factors determining overall survival (OS) and disease-free survival (DFS) were identified using multivariate analysis. Results There was no clinically significant difference in OS or DFS between RFA and MWA. In multivariate analysis of OS, pre-ablation lymphocyte-monocyte ratio [Hazard ratio (HR) 0.7, 95% confidence interval (CI) 0.58–0.84, P = 0.0001], MELD score [HR 1.12, 95%CI 1.068–1.17, P < 0.0001], tumor number [HR 1...

Hepatitis B virus (HBV) infection is a major global health problem with over 240 million people c... more Hepatitis B virus (HBV) infection is a major global health problem with over 240 million people chronically infected worldwide [1]. The spectrum of chronic HBV infection is variable, ranging from inactive carrier state to progressive CHB, which can evolve to cirrhosis in up to 20% of the cases, with hepatic insufficiency and portal hypertension being the most serious consequences [2]. Chronically infected subjects also have a 100 times higher risk to develop hepatocellular carcinoma (HCC) than noncarriers [3]. In untreated patients with CHB, the cumulative incidences of cirrhosis, hepatic decompensation and HCC at 5 years were approximately 20%, 15% and 5%, respectively [4]. Liver fibrosis is part of the structural and functional alterations in most chronic liver diseases. It is one of the main prognostic factors as the amount of fibrosis is correlated with the risk of developing cirrhosis and liver-related complications in viral and non viral chronic liver diseases [5]. The current...

Background and Aim: Anemia is a major clinical multifactorial problem in hemodialysis (HD) patien... more Background and Aim: Anemia is a major clinical multifactorial problem in hemodialysis (HD) patients. Iron metabolism is frequently impaired and may complicate the management of anemia. Hepcidin is synthesized in the liver. It is thought to be a key regulator of iron homeostasis. Therefore, we thought to assess prohepcidin level and iron indices in patients on regular HD with and without associated viral hepatitis. Patients and Methods: Sixty patients (38 males and 22 females) with chronic renal failure (CRF) undergoing regular HD and twenty age and sex matched healthy controls were included. Peripheral hemogram, liver function tests, kidney function tests, lipogram, C-reactive protein, iron indices, serum prohepcidin, HBsAg, HBcIgM and anti-HCV antibody were tested for both patients and controls. Results: 22 Patients were positive for anti-HCV, 16 were HBsAg positive and 22 were negative for both markers. Mean serum prohepcidin and ferritin levels in HD patients were significantly h...

Infection and Drug Resistance, 2021

Background: Tumor necrosis factor (TNF) family includes lymphotoxin-alpha (LTA) which is a pro-in... more Background: Tumor necrosis factor (TNF) family includes lymphotoxin-alpha (LTA) which is a pro-inflammatory cytokine which plays a role in hepatic fibrogenesis. LTA gene polymorphism plays a role in different inflammatory and immunomodulatory diseases. This polymorphism is also suggested to affect chronic hepatitis C (CHC) infection course. Aim: To study the contribution of LTA gene polymorphism in different chronic hepatitis C stages and hepatocellular carcinoma risk. Patients and Methods: Our study included 108 chronic HCV patients grouped according to the disease stage. Group (A): CHC, group (B): liver cirrhosis (LC), group (C): LC with HCC, and group (D): healthy controls. Routine laboratory investigations, polymerase chain reaction (PCR) for quantification of HCV, abdominal ultrasonography, and Liver stiffness measurement (LSM) were done. Child-Turcotte-Pugh, Model for end-stage liver disease (MELD), and Fibrosis index based on 4 (FIB-4) scores were calculated. We used the PCRrestriction fragment length polymorphism technique for lymphotoxin-α genotyping. Results: The A/G genotype was predominant in all groups. In HCC patients, G/G genotype was more frequent (31.8%) than in the LC group (19.4%), CHC group (17.8%), and controls (4.17%). A significant association was found between LTA genotypes and the child classes in HCC (P<0.01) but not in LC patients (P>0.05). HCC patients carrying A/G genotype had higher MELD scores than other genotypes. Multivariate binary logistic regression analysis confirmed that LTA G/G genotype and low platelet count were independent predictors for HCC development in patients with HCV-related LC. Conclusion: Detection of LTA G/G genotype in chronic HCV patients could help to recognize high-risk patients for disease progression and HCC development.

Sohag Medical Journal, 2019

Liver fibrosis is a chronic condition that originates as a result of prolonged hepatic injury. Li... more Liver fibrosis is a chronic condition that originates as a result of prolonged hepatic injury. Liver fibrosis is caused mainly by Schistosomiasis, chronic hepatitis C and B viral infections, non-alcoholic fatty liver disease, alcoholic liver disease, cholestatic and autoimmune liver diseases. Hepatic stellate cells are the master cells in the fibrosis process regardless of the cause. HSCs activation involves two separate stages: the initiation stage and the perpetuation stage. The activated HSCs up-regulate gene expression of extracellular matrix elements, matrix-degrading enzymes, and their inhibitors. The components of fibrotic ECM or inflammatory mediators implicated in either the process of fibrosis or degradation of scar tissue could be used as direct markers of fibrosis. Direct indices of fibrosis are classified into direct markers associated with matrix deposition such as HA and laminin, direct markers associated with matrix degradation such as MMPs and TIMPs, and Cytokines and chemokines linked to hepatic fibrosis such as TGF-1 and PDGF. The validation of these markers for use in clinical practice instead of liver biopsy should be balanced against the possibility of misleading results of these markers as they are affected by factors other than fibrosis.

Sohag Medical Journal, 2019

Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world and the fourth most c... more Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world and the fourth most common cause of cancer death.The development of HCC is a complex and multifactorial process, in which both environmental and genetic features interfere and contribute to malignant transformation. Numerous genetic studies have reported associations between single nucleotide polymorphisms (SNPs) and the presence of HCC.The purpose of thisreview is to describethe structure ofvitamin D receptor (VDR) gene and common polymorphisms involving it, and to address the associationsbetween VDR SNPs and cancer including HCC.

Sohag Medical Journal, 2018

Background and aim: Thrombocytopenia is a common complication of chronic liver diseases and is du... more Background and aim: Thrombocytopenia is a common complication of chronic liver diseases and is due to various causes.The effect of thrombocytopenia on liver damage and the exact mechanisms that lead to thrombocytopenia in chronic liver disease and cirrhosis are still unclear. As Platelets Derived Growth Factor ß (PDGF-ß) is released from platelets (PLTs) upon activation. We tried to identify PLTs and PDGFR-ß in the liver to shed some light on the pathophysiology of thrombocytopenia and liver fibrosis in chronic hepatic C patients. Patients and Methods: Analytical cross-sectional study was conducted on fifty patients with proven chronic hepatitis C. All patients were referred to Tropical Medicine and Gastroenterology Department, Sohag University Hospital. Patients were categorized into two groups. Group 1 includes patients with PLT count less than 150000/µL (thrombocytopenia). Group 2 includes patients with normal PLT count (150000-450000/µL). All patients were subjected to full history taking, complete clinical examination, complete blood count, liver function tests. Liver biopsy was obtained for histological staging and grading. Immunohistochemical study of PLTs and PDGFR-ß were done using monoclonal antibodies against PLT's surface marker CD41 and PDGFR-ß. Results: The included patients were 80 % males and 20 % females. Their mean age was 44.42± 11.17 years. The mean average weighted score (AWS) of Imunohisto-chemical expression of CD41was significantly higher in thrombocytopenic group compared to normal PLTs group (5.8±2.86 vs 3.43±3.03; P<0.001). There was a significant negative correlation between CD41 expression and peripheral PLT count (r=-0.4; P=0.007). PDGFR-ß expression was significantly stronger in thrombocytopenic patients than patients with normal PLT count (6.9±3.6 vs 5.27±3.92; P=0.001). It showed also a significant negative correlation with peripheral PLT count (r=-0.34, P=0.045). Both CD41 and PDGFR-ß expression were significantly elevated in patients with advanced stage of fibrosis than in those with earlier stages (7.26±5.23 vs 5.88±3.24; P=0.04 &9.2±2.7 vs 6.7±3.6; P<0.01 respectively). Conclusion: The accumulation of PLTs in the liver in patients with chronic hepatitis C may be involved in thrombocytopenia and liver fibrosis.

Journal of Hepatology, 2014

Background and Aims: Telaprevir (TVR)-based triple therapy is effective for hepatitis C patients.... more Background and Aims: Telaprevir (TVR)-based triple therapy is effective for hepatitis C patients. However, we have reported that TVR causes a reduction in renal function, with a reduction in the excretion of ribavirin (RBV), and the serum RBV concentration rises and the increased RBV concentration leads to hemolytic anemia (Y. Karino et al. J viral hepat. 2013). In this study, we retrospectively investigated the effects and adverse events of simeprevir (SMV)based triple therapy in comparison with TVR-based triple therapy and PEG-IFN/RBV therapy. Methods: Twenty seven patients were assigned to SMV for 12 weeks along with PEG-IFN/RBV for 24 weeks (Group A), while 65 patients were assigned to TVR for 12 weeks along with PEG-IFN/ RBV for 24 weeks (Group B) and 190 patients were assigned to PEG-IFN/RBV for 48 weeks (Group C). SMV was administered at a dose of 100 mg (or 50 mg) per day for 12 weeks (or 24weeks) and TVR was administered at a dose of 1500 mg or 2250 mg per day for 12 weeks. Results: SVR24 rate was 85.2% in Group A, 84.5% in Group B, and 45.3% in Group C. Adherence to RBV was significantly lower in Group B (63.3%) than Group A (93.5%) and Group C (94.3%). Average hemoglobin level (g/dl) at weeks 0/1/2/4/8/12 was 14.

Sohag Medical Journal, 2019

Vitamin D through the vitamin D receptor (VDR) is involved in the control of bone and calcium hom... more Vitamin D through the vitamin D receptor (VDR) is involved in the control of bone and calcium homeostasis, immunoregulation, cellular differentiation,and antiinflammatoryactions.The liver is central in vitamin D synthesis, however the direct involvement ofthe vitamin D with chronic liver disease, chronic hepatitis C (CHC) infection, and hepatocellular carcinoma (HCC) remains to be evaluated.The purpose of thisreview is to describevitamin D metabolism, the mechanisms of homeostatic control, and to address the associationsbetween vitamin D and HCV-related liver disease.

The Egyptian Journal of Hospital Medicine

Background: With the advent of direct-acting antivirals (DAAs) for hepatitis C virus (HCV), there... more Background: With the advent of direct-acting antivirals (DAAs) for hepatitis C virus (HCV), there has been a marked increase in the number of patients who achieve sustained virological response (SVR). Several factors mediate the response to therapy as immunologic and genetic factors. Objective: We aimed to assess the pattern of response to sofosbuvir and daclatasvir +/-ribavirin regimen in chronic hepatitis C (CHC) patients and to study the predictors of non SVR (relapse). Patients and methods: This prospective study was conducted on 506 consecutive HCV-infected patients. Abdominal ultrasonography, liver function tests, alpha-fetoprotein (AFP), HCV polymerase chain reaction (PCR), complete blood count (CBC), random blood glucose, C-X-C motif chemokine ligand 10 (CXCL10), Child-Pugh score, and some serum fibrosis indices were performed. After completion of the course of treatment, all patients were followed up for 6 months and then categorized into sustained virological responders and non-sustained virological responders (relapsers). Results: Out of the 506 HCV-infected patients, 497 (98.2%) achieved SVR, and 9 (1.8%) experienced relapse. Response rates to sofosbuvir and daclatasvir +/-ribavirin in cirrhotic patients were lower than those without cirrhosis. The presence of liver cirrhosis (LC) and the need for receiving triple therapy were the main factors that predicted relapse in univariate analysis. CXCL10 levels showed statistically insignificant differences between responders and relapsers, between cirrhotic and non-cirrhotic patients, and between pretreatment and post-treatment levels. Conclusions: Response rate of CHC patients to sofosbuvir and daclatasvir +/-ribavirin is excellent and relapse only occurred in a minority of patients (1.8%). Cirrhotic patients showed higher relapse rate than non-cirrhotic (55.65% vs 44.4%).

The Egyptian Journal of Hospital Medicine, 2022

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease involving ... more Background: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease involving about 25% of the world's population. Several studies investigated the role of the different anthropometric measures in NAFLD diagnosis. Objective: This study aimed to evaluate the diagnostic performance of the different anthropometric measures as noninvasive predictors for the presence of steatosis in a series of NAFLD patients. Patients and methods: A cross-sectional study was conducted in a series of adult asymptomatic subjects. NAFLD was diagnosed in 100 cases by ultrasonography for whom controlled attenuation parameters (CAP) examination was done. Body mass index (BMI), waist circumference (WCir), waist to height ratio (WHtR), lipid accumulation product (LAP) were measured. Also, subcutaneous and preperitoneal fat were measured using abdominal ultrasound. Roc curve analysis was used to detect the optimal cutoff of different models that predict steatosis. Results: BMI, WCir, WHtR, LAP, subcutaneous and preperitoneal fat had good diagnostic performance for predicting hepatic steatosis (AUROC for LAP=1 and approaching 1 in all other anthropometric measures). Conclusion: The clinical anthropometric measures are easy applicable and non-costly promising tools for the prediction of NAFLD in Egyptian patients.