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Papers by nermin adawy

Alexandria Journal of Pediatrics, 2019

Introduction Biliary atresia (BA) is a progressive obliteration of the extrahepatic bile ducts th... more Introduction Biliary atresia (BA) is a progressive obliteration of the extrahepatic bile ducts that affects as many as 1 in 5000 children in certain areas of the world. Aim The aim was to study the expression of integrin β-8 in patients with BA and compare it with patients with non-BA cholestasis. Patients and methods This study was conducted on 30 infants with BA and 30 infants with cholestasis other than BA. Integrin β-8 immunohistochemical (IHC) staining was done to all studied groups. Results In this study, infants with BA had statistically significant more integrin β-8 expression than non-BA patients (P=0.001) with significantly higher expression at IHC score 3 (P<0.0001). While non-BA infants had significantly higher expression at low IHC score 1 (P<0.0001) integrin β-8 IHC score at a cutoff value greater than 2 could discriminate between BA and non-BA groups that had 0.729 area under the receiver-operating characteristic curve with 83.3% sensitivity, 60% specificity, and 71.6% accuracy. Conclusion Integrin β-8 expression is significantly more expressed in patients with BA than non-BA patients and can significantly discriminate BA at an IHC score of greater than 2 from other causes of neonatal cholestasis.

Hepatology International, 2019

Background/purpose of the study Worldwide and national efforts are directed against eradication o... more Background/purpose of the study Worldwide and national efforts are directed against eradication of HCV. The introduction of direct-acting antivirals (DAAs) has changed dramatically the outcome of HCV treatment. In spite of the Food and Drug Administration approval of the oral drugs sofosbuvir (SOF) and ledipasvir (LED) for the treatment of HCV in adolescents more than or equal to 12 years old, sufficient real-world experience is still lacking. The aim of this study was to assess the safety and efficacy of the generic SOF/LED fixed-dose combination 400/90 (400 mg SOF + 90 mg LED) for the treatment of adolescents and children (9-12 years) with chronic hepatitis C (CHC). Methods In this prospective observational study, 100 cases of genotype 4 CHC were recruited consecutively from those fulfilling the inclusion and exclusion criteria. All cases received the generic fixed-dose combination SOF/LED (400/90), one tablet daily for 12 weeks. All clinical, laboratory, and virologic characteristics were evaluated at base line, and week (W) 2, 4, 8, and 12 of therapy and W12 post-treatment (SVR12). Results Recruited children (9-12) and adolescents weighed 28-83 and 31-90 kg, respectively. Eighty cases were naïve and 20 cases were pegylated interferon/ribavirin treatment-experienced. Very rapid virologic response (vRVR) at W2 was 96%, while at W4 response rate was 100% and maintained till the end of treatment and at W12 post-treatment (SVR12). All reported side effects were mild and did not lead to treatment termination and disappeared at W12 post-treatment. Conclusion The generic SOF/LED fixed-dose combination is safe and effective in children, 9-12 years, and adolescents with vRVR rate of 96%, 100% EOT response and SVR12.

Clinical and Experimental Hepatology, 2017

Aim of the study: To assess if elevated serum cystatin C (Cyst-C) is an indicator for renal or he... more Aim of the study: To assess if elevated serum cystatin C (Cyst-C) is an indicator for renal or hepatic dysfunction in presence of liver fibrosis. Material and methods: Data of 50 children with chronic liver diseases (CLDs), out of which 25 were without renal impairment, and 25 with renal impairment were analyzed. Twenty healthy children served as a healthy control group. Routine investigations, creatinine clearance, hepatitis viral markers, abdominal ultrasonography, and liver biopsy were performed for patients with CLDs. Measurement of serum Cyst-C concentration by particle induced immunonephelometry were completed for both patients and control group. Results: Results showed that serum Cyst-C is not correlated with the degree of hepatic impairment (p > 0.05). Cyst-C levels were significantly higher in patients with renal impairment (3.66 ± 0.85) than those without (0.71 ± 0.12), and healthy control group (0.63 ± 0.85). Cystatin-C showed significant elevation in patients with severe fibrosis with renal impairment (3.66 ± 0.85) than those without (0.76 ± 0.04) (p < 0.0001). Cyst-C at cutoff levels of 1.65 mg/l showed 100% accuracy in discrimination between those with and those without renal impairment. Cyst-C > 2.34 mg/l predicting GFR < 40 ml/min with accuracy of 90%. Cyst-C > 2.73 mg/l predicting GFR < 20 ml/min with accuracy of 81.5%. Conclusions: Serum Cyst-C is a promising marker to estimate renal impairment in children with CLDs. Further studies are needed to estimate the accuracy of serum Cyst-C for early detection of renal impairment and close monitoring of the hepatic children.

Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation, 2009

Since brain-death criteria are not accepted in Egypt, only organs acquired from living donors can... more Since brain-death criteria are not accepted in Egypt, only organs acquired from living donors can be used for transplant. Our objective was to highlight the ethical issues raised by living-donor liver transplant. The study was conducted by reviewing publications from centers performing living-donor liver transplant in Egypt and by consulting with a group of experts in the fields of liver transplantation, clinical ethics, and religious scholarship. The first successful living-donor liver transplant in Egypt was performed at the National Liver Institute in 1991; however, this program did not continue because of poor early results. In August 2002, transplants began at Dar-Al-Foaud Hospital; since then, almost 500 cases of living-donor liver transplant have been performed at 9 centers. Although the donor risk is estimated to be low, 2 donors died (0.4%). The ethical principle that best applies to living-donor liver transplant is primum non nocere (first, not to harm), as the donor deriv...

Clinical & Experimental Hepatology, 2021

Aim of the study: To evaluate the role of plasma level of von Willebrand factor antigen (vWF-Ag) ... more Aim of the study: To evaluate the role of plasma level of von Willebrand factor antigen (vWF-Ag) as a possible predictor for the presence of esophageal varices (EVs) in children with chronic liver diseases (CLDs). Material and methods: All patients underwent upper esophagogastroduodenoscopy (EGD) and were categorized as group I (had EVs) and group II (had no EVs). The following patient data were determined: Child-Pugh score (CPS), plasma vWF-Ag, vWF-Ag/thrombocyte ratio (VITRO) score, aspartate transaminase (AST) to platelet ratio index (APRI) score, AST/alanine transaminase (ALT), platelet count/spleen diameter, grading of EVs (small, medium and large) and categorizing the stage of liver fibrosis. Results: The analysis included 50 patients with CLD; 30 (60%) were female. The commonest etiological diagnoses were autoimmune hepatitis (AIH) (20%) and extra-hepatic biliary atresia (EHBA) (12%). 26% of cases were categorized as undiagnosed CLD. The CPS showed CPS-A 34%, CPS-B 44% and CPS-C 22%. The vWF-Ag was found at a high level of 243.52 ±195.97, with a highly statistically significant difference in discriminating the EVs with 74% accuracy at a cutoff value of 108.99 IU/ml, p < 0.0001. Also, ROC analysis was performed for discriminating large esophageal varices with 84% accuracy at a cutoff value of 475.85 mg%. The VITRO score at a cutoff value of 1.72 could detect EVs with 70% sensitivity, 86.7% specificity, and 80% accuracy. Conclusions: High vWF-Ag is a valuable prognostic tool for estimating the presence of EVs, and higher vWF-Ag is associated with increased grade of EVs.

Clinical & Experimental Hepatology, 2021

Aim of the study: Azathioprine (AZA) is an important steroid-sparing drug in the management of au... more Aim of the study: Azathioprine (AZA) is an important steroid-sparing drug in the management of autoimmune hepatitis (AIH). Avoidance of its adverse events that could be severe and carry a risk of mortality in a few cases is important, preferably with cheap and easy assessments that could be feasible in developing countries with the unavailability of molecular assays. Assessment of thiopurine methyltransferase (TPMT), the key enzyme for the inactivation of AZA, as a predictor of AZA toxicity had been a matter of conflict. This work aimed to study the role of TPMT serum level assessment and other host-, disease-, and treatment-related factors in predicting AZA toxicity. Material and methods: Sixty-six children with AIH, divided into two groups, were recruited. Group 1 included twelve children with AZA toxicity and group 2 included fifty-four children without AZA toxicities. Both groups were compared for demographic, clinical, laboratory, histopathological, and treatment-related factors, and serum TPMT level, measured by ELISA. Results: TPMT serum level was comparable in both groups (p = 0.363). Duration of treatment until enzyme normalization and duration of AZA therapy were significantly associated with AZA toxicity (p = 0.007 and p = 0.01, respectively). At the first follow-up treatment with AZA, total leucocyte count (TLC) and neutrophil counts were significantly lower in group 1 (p = 0.005 and p = 0.002, respectively). Moreover, the percentage reduction of TLC and neutrophil counts were significantly higher in group 1 (p < 0.001, for both). Conclusions: Monitoring for AZA adverse events in those with the defined predictors of AZA-related adverse events is more important than TPMT assessment.

Global journal of gastroenterology & hepatology, Oct 5, 2017

Background : Biliary atresia (BA) is a progressive disease of infancy. Early diagnosis is particu... more Background : Biliary atresia (BA) is a progressive disease of infancy. Early diagnosis is particularly essential because prognosis is closely related with timing of Kasai portoenterostomy. There is no non-invasive method that clearly identifies the diagnosis. Tumor necrosis factor-α (TNF-α) is a cytokine which is mainly produced by activated macrophages and monocytes. Aim : We aimed to study the performance of serum TNF-α in BA and other neonatal cholestatic disorders. Materials and Methods : The study included 80 infants with neonatal cholestasis divided in two groups; BA group (n=40), non-BA group (n=40) with cholestatic disorders other than BA. Demographic, clinical, laboratory, and histopathological parameters were collected. Serum TNF-α level was measured by enzyme-linked immunosorbent assay. Results : The mean value of TNF-α level was significantly higher in BA group (260.61+155.74 pg/ml) compared to non-BA (126.26+ 64.23 pg/ml) and a cutoff level of 124.4 pg/ml can diagnose BA with 95 % sensitivity and specificity 75 %. TNF-α is correlated with alkaline phosphatase, gamma glutamyle transferase and grade of liver fibrosis (P value 0.019, 0.004 and < 0.0001 respectively). In Conclusion : Serum TNF-α can be used as a non-invasive and sensitive marker for confirming the diagnosis of BA in in suspicious cases.

Egyptian Liver Journal, Jul 1, 2011

Background Nonalcoholic fatty liver disease (NAFLD) is one of the major causes of chronic liver d... more Background Nonalcoholic fatty liver disease (NAFLD) is one of the major causes of chronic liver disease. Unfortunately, accurate noninvasive modalities for diagnosing NAFLD and monitoring its progression are unavailable and liver biopsy is still the mainstay of diagnosis. We aim to highlight the importance of radiologic modalities in detecting hepatic steatosis in overweight and obese children. Patients and Methods One hundred and twenty (age range 2-18 years) children were assigned to two groups. Group 1 (53 girls and 47 boys) consisted of apparently normal children with simple obesity, that is, body mass index (BMI) higher than or equal to 85th centile for age. Group 2 (nine girls and 11 boys) consisted of apparently normal children with normal BMI corresponding for age. All children were thoroughly examined and underwent laboratory tests, ultrasound, computed tomography (CT), and anthropometric measurements. Results Increased BMI was associated with hepatomegaly, especially in older children above or equal to 11 years, and the aspartate aminotransferase/alanine aminotransferase ratio correlates well with the severity of histopathological abnormalities of the liver. Ultrasound echogenicity showed correlation to BMI only in older obese children above or equal to 11 years; ultrasound also correlates well to CT attenuation and liver biopsy steatosis. CT scan attenuation showed correlation to BMI only in older obese children above or equal to 11 years, but it correlates well to ultrasound echogenicity and liver biopsy findings. Conclusion Ultrasound examination when positive is highly accurate in diagnosing NAFLD. A combination of serum biomarkers and radiologic modalities provides a valuable diagnostic approach for patients with nonalcoholic steatosis.

Hepatobiliary & Pancreatic Diseases International, Apr 1, 2019

Background: Serum ferritin (SF) and consequently hepatic iron have long been considered important... more Background: Serum ferritin (SF) and consequently hepatic iron have long been considered important in liver fibrosis progression. They have been studied in different liver diseases with no previous reports in neonatal cholestasis (NC). This study aimed to measure SF in different etiologies of NC and investigate its relation to hepatic iron and fibrosis. Methods: SF was measured in 75 infants, including 50 with NC and 25 with sepsis. SF was compared between these two groups. Biochemical parameters, hepatic iron grades, and liver fibrosis and other histopathological characteristics and correlated with SF were assessed in NC group. Finally, a comparison between intrahepatic cholestasis and obstructive etiology was performed. Results: SF was elevated in NC (1598 ± 2405 ng/mL) with no significant difference from those with sepsis (P = 0.445). NC and sepsis constituted augmenting factors leading to more elevation of SF (2589 ± 3511 ng/mL). SF was significantly correlated with hepatic iron grades (r = 0.536, P < 0.0 0 01) and a cutoff value of 803.5 ng/mL can predict higher grades (≥ grade 3) of iron deposition with sensitivity of 100%, specificity of 70% and accuracy of 85%. Moreover, SF was significantly higher (P < 0.0 0 01) in those with intrahepatic cholestasis (2602 ± 3154 ng/mL) and their prevalent pathological findings of giant cell transformation (P = 0.009) and hepatocyte swelling (P = 0.023) than those with obstructive etiology (672 ± 566 ng/mL) and their prevalent pathological findings of ductular proliferation (P = 0.003) and bile plugs (P = 0.002). SF was unrelated to the grade of liver fibrosis (P = 0.058). Conclusions: SF is non-specifically elevated in NC, with positive correlation to hepatic iron grades. SF ≥ 803.5 ng/mL can predict higher grades (≥ grade 3) of hepatic iron. However, an active role of increased SF and hepatic iron in disease progression remains questionable.

Clinical & Experimental Hepatology, 2019

Aim of the study: We aimed to assess oxidative stress factors, glutathione peroxidase (GPX) and m... more Aim of the study: We aimed to assess oxidative stress factors, glutathione peroxidase (GPX) and malondialdehyde (MDA) in children with chronic hepatitis C (CHC) and their relation to treatment response. Material and methods: The study included 50 children with chronic hepatitis C virus (HCV) before treatment (naïve HCV), 25 children responders to HCV treatment, 25 children non-responders to HCV treatment and 25 healthy controls. All patients and controls were subjected to GPX and MDA measurement by enzyme-linked immunosorbent assay. Results: The average GPX activity in erythrocytes of naïve CHC patients was 29.2 ±10.3 mU/ml. It was statistically significantly lower than the average activity of GPX in erythrocytes of the healthy control group (47.3 ±5.2 mU/ml) (p < 0.05). The average GPX activity in erythrocytes of the responder group was 34.93 ±3.17 mU/ml. It was statistically significantly higher than the average activity of GPX in erythrocytes of the non-responder group (11.7 ±4.2 mU/ml) (p < 0.05). Plasma MDA was significantly higher in naïve CHC patients than in healthy controls (9.7 ±3.7 nmol/ml vs. 3 ±1.1 nmol/ml, p < 0.0001). Furthermore, plasma MDA concentration was significantly decreased in the responder group (5.36 ±0.7 nmol/ml) and elevated in the non-responder group (16.05 ±2.9 nmol/ml). Conclusions: Lower pretreatment levels of GPX and higher MDA level might be markers of oxidative stress occurring in HCV patients. Reversal of changes of these levels with completion of the treatment may indicate a correlation between oxidative stress and the viral pathogenesis.

Hepatobiliary & Pancreatic Diseases International, 2021

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Journal of Clinical and Experimental Hepatology, 2021

Background Hyaline globules (HGs) in the cytoplasm of Kupffer cells (KCs) have been appraised for... more Background Hyaline globules (HGs) in the cytoplasm of Kupffer cells (KCs) have been appraised for being a typical feature of autoimmune hepatitis (AIH). This study aimed to determine how useful Kupffer cell hyaline globules (KCHGs) are in diagnosing AIH vs. other causes of pediatric chronic liver diseases (PCLDs). Materials and methods This retrospective study recruited 124 children; 58 with AIH, 50 with chronic hepatitis C virus (HCV) infection, and 16 with Wilson's disease (WD). Two pathologists retrieved paraffin blocks of liver biopsies and prepared new cut sections for Periodic acid-Schiff-Diastase (PAS-D) stain. They independently examined liver biopsies before starting treatment. Two pediatricians reviewed medical records for demographic, clinical, laboratory, and serological findings. Results Females represented 48.6% of the studied children with a median age of 5.8 (4.9) years. Pathologists identified KCHGs in 67.24%, 12.5%, and 6.0% of AIH, WD, and HCV affected children respectively, P < 0.001. A significantly higher proportion of seropositive than seronegative AIH patients had KCHGs (77.5% vs. 50.0%), (P < 0.05). In multivariate analysis, KCHGs and prolonged prothrombin time were the only significant predictors that differentiate between AIH and the other studied PCLDs. The odds ratio of having AIH increased 68 times if KCHGs were seen. Among children with AIH, the presence of KCHGs was associated with higher median levels of direct bilirubin 2.2 (1.3) vs. 1.2 (2.2), and immunoglobulin G 3.2 (1.9) vs. 2.0 (1.7), (P < 0.05), but not to histopathological findings or hepatic fibrosis and activity. Conclusions KCHGs are key indicators that can differentiate between AIH and other PCLDs, and between seropositive and seronegative AIH.

Annals of Hepatology, 2020

Introduction and Objectives: Biliary atresia (BA) is characterized by rapid progression of fibros... more Introduction and Objectives: Biliary atresia (BA) is characterized by rapid progression of fibrosis with no definite causes. Histopathological findings have been extensively described, but very few studies have assessed temporal changes in BA. Understanding these short-term changes and their relationship with fibrosis progression could have an impact on ameliorating rapid fibrogenesis. We aimed to study the relationship between temporal histopathological changes and fibrosis progression in BA within a short time interval. Patients and Methods: Forty-nine infants with BA who underwent Kasai portoenterostomy, a diagnostic liver biopsy, and an intraoperative liver biopsy were recruited. Histopathological characteristics of the two biopsies were examined. Temporal histopathological changes were assessed by comparing the two types of biopsies. Correlation of temporal changes in fibrosis with age, interval between biopsies, laboratory profiles, and temporal histopathological changes were studied. Results: In the univariate analysis, bile ductular proliferation (BDP), portal infiltrate, giant cells, hepatocellular swelling, and fibrosis showed significant temporal changes within a short interval (5-31 days). BDP and fibrosis showed the most frequent increase in their grades (32/49 and 31/49 cases, respectively). In the multivariate analysis, BDP was the only independent pathological feature showing a significant temporal increase (p = 0.021, 95% confidence interval: 1.249-16.017). Fibrosis progression was correlated with temporal changes in BDP (r = 0.456, p = 0.001), but not with age (p = 0.283) or the interval between the biopsies (p = 0.309). Conclusions: Fibrosis in BA progresses rapidly and is significantly correlated with BDP. Assessment of targeting BDP as an adjuvant medical therapy is recommended.

Clinics and Research in Hepatology and Gastroenterology, 2019

Background: Biliary atresia (BA) is a common cause of persistent neonatal cholestasis and liver t... more Background: Biliary atresia (BA) is a common cause of persistent neonatal cholestasis and liver transplantation in the pediatric population. Yes-associated protein (YAP) has also been shown to be necessary for development of bile ducts and adaptive responses within the gastrointestinal tract. We aimed to evaluate the YAP expression in liver tissues of infants with neonatal cholestasis as well as its diagnostic potential in the differential diagnosis of BA. Patients and methods: This prospective study included 100 infants with neonatal cholestasis. After full history taking, thorough clinical examination, routine investigations, and histopathological assessment, the patients were allocated as BA and non-BA; fifty patients in each group. Ten liver biopsies from 10 donors of liver transplant recipients served as controls. Diagnosis of BA was confirmed by operative cholangiography. Hepatic expression of YAP was assessed by immunohistochemical staining. Results: Presence of clay stool, elevated GGT and absence of gall bladder contractility were the main preliminary signs alarming for the possibility of BA. Bile ductular and interlobular biliary epithelium and hepatic lobule expression of YAP in patients with BA was significantly higher than that in Non-BA group (P < 0.05). There was no or weak positive YAP expression in normal liver of transplant donors. Positive YAP immunohistochemical had a sensitivity of 80% and a specificity of 94% with accuracy 87% in discrimination between BA and non-BA group (P-value < 0.0001).

Hepatobiliary & Pancreatic Diseases International, 2019

Background: Serum ferritin (SF) and consequently hepatic iron have long been considered important... more Background: Serum ferritin (SF) and consequently hepatic iron have long been considered important in liver fibrosis progression. They have been studied in different liver diseases with no previous reports in neonatal cholestasis (NC). This study aimed to measure SF in different etiologies of NC and investigate its relation to hepatic iron and fibrosis. Methods: SF was measured in 75 infants, including 50 with NC and 25 with sepsis. SF was compared between these two groups. Biochemical parameters, hepatic iron grades, and liver fibrosis and other histopathological characteristics and correlated with SF were assessed in NC group. Finally, a comparison between intrahepatic cholestasis and obstructive etiology was performed. Results: SF was elevated in NC (1598 ± 2405 ng/mL) with no significant difference from those with sepsis (P = 0.445). NC and sepsis constituted augmenting factors leading to more elevation of SF (2589 ± 3511 ng/mL). SF was significantly correlated with hepatic iron grades (r = 0.536, P < 0.0 0 01) and a cutoff value of 803.5 ng/mL can predict higher grades (≥ grade 3) of iron deposition with sensitivity of 100%, specificity of 70% and accuracy of 85%. Moreover, SF was significantly higher (P < 0.0 0 01) in those with intrahepatic cholestasis (2602 ± 3154 ng/mL) and their prevalent pathological findings of giant cell transformation (P = 0.009) and hepatocyte swelling (P = 0.023) than those with obstructive etiology (672 ± 566 ng/mL) and their prevalent pathological findings of ductular proliferation (P = 0.003) and bile plugs (P = 0.002). SF was unrelated to the grade of liver fibrosis (P = 0.058). Conclusions: SF is non-specifically elevated in NC, with positive correlation to hepatic iron grades. SF ≥ 803.5 ng/mL can predict higher grades (≥ grade 3) of hepatic iron. However, an active role of increased SF and hepatic iron in disease progression remains questionable.

Clinical and experimental hepatology, 2018

We aimed to assess the utility of serum level IL-13Rα2 receptors as a non-invasive marker for ear... more We aimed to assess the utility of serum level IL-13Rα2 receptors as a non-invasive marker for early diagnosis of biliary atresia (BA) and selection of BA patients indicated for Kasai portoenterostomy. The study included 60 infants with neonatal cholestasis in three groups; early BA group ( = 20), delayed BA group ( = 20) and non-BA cholestasis group ( = 20). A fourth group of 20 healthy neonates ( = 20) served as controls. IL-13Rα2 was measured by enzyme-linked immunosorbent assay in all patients and controls. The mean value of IL-13Rα2 was significantly higher in delayed BA group (11.05 ± 10.9 ng/ml) compared to early BA (0.34 ± 0.37 ng/ml), non-BA (0.54 ± 0.85 ng/ml) and control (0.24-0.2 ng/ml) groups. The levels of serum IL-13Rα2 increase with the severity of the degree of fibrosis. IL-13Rα2 at a cutoff level > 0.782 ng/ml could predict late fibrosis with accuracy of 77.55% ( < 0.0001). IL-13Rα2 could differentiate between preserved and disturbed liver architecture at a cu...

Clinical and Experimental Hepatology, 2020

Aim of the study: Liver transplantation remains the only definitive treatment for children with a... more Aim of the study: Liver transplantation remains the only definitive treatment for children with acute liver failure proven to have irreversible liver injury. Many prognostic models have been used for outcome prediction in pediatric acute liver failure to select patients in a real need of liver transplantation, but unfortunately all have shown inconsistent reproducibility and prognostic accuracy. The aim of this study was to evaluate the pediatric chronic liver failure sequential organ failure assessment (pCLIF-SOFA) score as a predictor of pediatric acute liver failure outcome. Material and methods: Clinical and laboratory data of 41 children with acute liver failure admitted to the National Liver Institute-Menoufia University were collected retrospectively and used for calculation of both pCLIF-SOFA and Pediatric End-Stage Liver Disease (PELD)/Model for End-Stage Liver Disease (MELD) scores on the day of admission, then statistical analysis was performed to identify the ability of these scores to predict the outcome. Results: According to the outcome, children enrolled in this study were allocated to survived (n = 16) and died (n = 25) groups, which were age and sex matched. The non-survival group had significantly higher values of both pCLIF-SOFA score (11 [7-13]) and PELD/MELD score (36 [18-42]) than those of the survival group (8 [7-11], 27.5 [15-45]; p < 0.001, p = 0.004) respectively. Both pCLIF-SOFA and PELD/MELD scores at cutoff values > 8 and > 30 respectively on admission could predict death in children with acute liver failure (ALF) with high sensitivity, but with higher specificity, positive and negative predictive values for pCLIF-SOFA. Conclusions: pCLIF-SOFA is a good predictor of death in pediatric acute liver failure.

Journal of Pediatrics & Neonatal Care, 2020

Aim: To assess fulminant hepatic failure (FHF) in children and its interrelating factors. Methods... more Aim: To assess fulminant hepatic failure (FHF) in children and its interrelating factors. Methods and materials: A retrospective review study of 24 patients less than 17 years old who presented to the National Liver Institute with FHF over a period of two years was done. FHF was defined as the presence of acute liver failure with or without encephalopathy without pre-existing liver disease, within 8 weeks of the onset of clinical liver disease. Hepatitis A virus (HAV) IgM antibodies, Hepatitis B virus surface antigen (HBsAg), IgM-anti Hepatitis B core antigen (HBc), Hepatitis E virus (HEV) IgM and Hepatitis C virus (HCV) RNA in nested PCR were done in all patients. Special investigations like alpha fetoprotein, serum copper, blood culture, drug levels and other metabolic studies were carried out whenever indicated. Detailed clinical evaluations and routine hepatic laboratory profile were done. Results: Acute hepatitis-A virus was the commonest cause. Severe coma was significantly pr...

Egyptian Pediatric Association Gazette, 2018

Biliary atresia (BA) is a rare disease characterized by ascending obstruction of bile ducts that ... more Biliary atresia (BA) is a rare disease characterized by ascending obstruction of bile ducts that exclusively affects newborn infants. The etiology of the disease is not known. BA is considered to be a phenotype resulting from several pathogenic processes leading to obstruction of the biliary tree. It usually presents shortly after birth, characterized by persistent jaundice, hepatosplenomegaly, clay-colored stool, and dark urine. It affects both the extra-hepatic biliary ducts (EHBDs) and the intra-hepatic biliary system (IHBDs), but the former is more severely affected. Diagnosis of BA is a great challenge and must be achieved as early as possible to delay progression to cirrhosis. Laboratory tests reveal direct hyperbilirubinemia and, variable levels of transaminases, gamma-glutamyl transpeptidase (GGT), and alkaline phosphatase (ALP), which overlap significantly with other causes of neonatal cholestasis. The intraoperative cholangiogram is considered the gold standard for the diagnosis of BA and is performed routinely in many institutions. BA can be divided into correctable and non-correctable types; the former accounts for (10-15%) of cases, in which the proximal common hepatic duct is patent, allowing primary anastomosis of the EHBDs to the bowel. All patients are subjected to identical surgical and medical treatments; consisting of Kasai portoenterostomy (KPE), which entails removal of the atretic extra-hepatic tissue and a Roux-en-Y jejunal loop anastomosed to the hepatic hilum. Kasai portoenterstomy is considered a transition to liver transplantation, as the pathology may be still ongoing. BA is the most frequent indication for liver transplantation in infants, which is the only treatment that can definitively arrest the natural disease course. In conclusion: BA is a serious liver disease that needs to be further studied, and awareness of BA should be increased among the public and health care workers to prevent the complications of this disease.

Alexandria Journal of Pediatrics, 2019

Introduction Biliary atresia (BA) is a progressive obliteration of the extrahepatic bile ducts th... more Introduction Biliary atresia (BA) is a progressive obliteration of the extrahepatic bile ducts that affects as many as 1 in 5000 children in certain areas of the world. Aim The aim was to study the expression of integrin β-8 in patients with BA and compare it with patients with non-BA cholestasis. Patients and methods This study was conducted on 30 infants with BA and 30 infants with cholestasis other than BA. Integrin β-8 immunohistochemical (IHC) staining was done to all studied groups. Results In this study, infants with BA had statistically significant more integrin β-8 expression than non-BA patients (P=0.001) with significantly higher expression at IHC score 3 (P<0.0001). While non-BA infants had significantly higher expression at low IHC score 1 (P<0.0001) integrin β-8 IHC score at a cutoff value greater than 2 could discriminate between BA and non-BA groups that had 0.729 area under the receiver-operating characteristic curve with 83.3% sensitivity, 60% specificity, and 71.6% accuracy. Conclusion Integrin β-8 expression is significantly more expressed in patients with BA than non-BA patients and can significantly discriminate BA at an IHC score of greater than 2 from other causes of neonatal cholestasis.

Hepatology International, 2019

Background/purpose of the study Worldwide and national efforts are directed against eradication o... more Background/purpose of the study Worldwide and national efforts are directed against eradication of HCV. The introduction of direct-acting antivirals (DAAs) has changed dramatically the outcome of HCV treatment. In spite of the Food and Drug Administration approval of the oral drugs sofosbuvir (SOF) and ledipasvir (LED) for the treatment of HCV in adolescents more than or equal to 12 years old, sufficient real-world experience is still lacking. The aim of this study was to assess the safety and efficacy of the generic SOF/LED fixed-dose combination 400/90 (400 mg SOF + 90 mg LED) for the treatment of adolescents and children (9-12 years) with chronic hepatitis C (CHC). Methods In this prospective observational study, 100 cases of genotype 4 CHC were recruited consecutively from those fulfilling the inclusion and exclusion criteria. All cases received the generic fixed-dose combination SOF/LED (400/90), one tablet daily for 12 weeks. All clinical, laboratory, and virologic characteristics were evaluated at base line, and week (W) 2, 4, 8, and 12 of therapy and W12 post-treatment (SVR12). Results Recruited children (9-12) and adolescents weighed 28-83 and 31-90 kg, respectively. Eighty cases were naïve and 20 cases were pegylated interferon/ribavirin treatment-experienced. Very rapid virologic response (vRVR) at W2 was 96%, while at W4 response rate was 100% and maintained till the end of treatment and at W12 post-treatment (SVR12). All reported side effects were mild and did not lead to treatment termination and disappeared at W12 post-treatment. Conclusion The generic SOF/LED fixed-dose combination is safe and effective in children, 9-12 years, and adolescents with vRVR rate of 96%, 100% EOT response and SVR12.

Clinical and Experimental Hepatology, 2017

Aim of the study: To assess if elevated serum cystatin C (Cyst-C) is an indicator for renal or he... more Aim of the study: To assess if elevated serum cystatin C (Cyst-C) is an indicator for renal or hepatic dysfunction in presence of liver fibrosis. Material and methods: Data of 50 children with chronic liver diseases (CLDs), out of which 25 were without renal impairment, and 25 with renal impairment were analyzed. Twenty healthy children served as a healthy control group. Routine investigations, creatinine clearance, hepatitis viral markers, abdominal ultrasonography, and liver biopsy were performed for patients with CLDs. Measurement of serum Cyst-C concentration by particle induced immunonephelometry were completed for both patients and control group. Results: Results showed that serum Cyst-C is not correlated with the degree of hepatic impairment (p > 0.05). Cyst-C levels were significantly higher in patients with renal impairment (3.66 ± 0.85) than those without (0.71 ± 0.12), and healthy control group (0.63 ± 0.85). Cystatin-C showed significant elevation in patients with severe fibrosis with renal impairment (3.66 ± 0.85) than those without (0.76 ± 0.04) (p < 0.0001). Cyst-C at cutoff levels of 1.65 mg/l showed 100% accuracy in discrimination between those with and those without renal impairment. Cyst-C > 2.34 mg/l predicting GFR < 40 ml/min with accuracy of 90%. Cyst-C > 2.73 mg/l predicting GFR < 20 ml/min with accuracy of 81.5%. Conclusions: Serum Cyst-C is a promising marker to estimate renal impairment in children with CLDs. Further studies are needed to estimate the accuracy of serum Cyst-C for early detection of renal impairment and close monitoring of the hepatic children.

Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation, 2009

Since brain-death criteria are not accepted in Egypt, only organs acquired from living donors can... more Since brain-death criteria are not accepted in Egypt, only organs acquired from living donors can be used for transplant. Our objective was to highlight the ethical issues raised by living-donor liver transplant. The study was conducted by reviewing publications from centers performing living-donor liver transplant in Egypt and by consulting with a group of experts in the fields of liver transplantation, clinical ethics, and religious scholarship. The first successful living-donor liver transplant in Egypt was performed at the National Liver Institute in 1991; however, this program did not continue because of poor early results. In August 2002, transplants began at Dar-Al-Foaud Hospital; since then, almost 500 cases of living-donor liver transplant have been performed at 9 centers. Although the donor risk is estimated to be low, 2 donors died (0.4%). The ethical principle that best applies to living-donor liver transplant is primum non nocere (first, not to harm), as the donor deriv...

Clinical & Experimental Hepatology, 2021

Aim of the study: To evaluate the role of plasma level of von Willebrand factor antigen (vWF-Ag) ... more Aim of the study: To evaluate the role of plasma level of von Willebrand factor antigen (vWF-Ag) as a possible predictor for the presence of esophageal varices (EVs) in children with chronic liver diseases (CLDs). Material and methods: All patients underwent upper esophagogastroduodenoscopy (EGD) and were categorized as group I (had EVs) and group II (had no EVs). The following patient data were determined: Child-Pugh score (CPS), plasma vWF-Ag, vWF-Ag/thrombocyte ratio (VITRO) score, aspartate transaminase (AST) to platelet ratio index (APRI) score, AST/alanine transaminase (ALT), platelet count/spleen diameter, grading of EVs (small, medium and large) and categorizing the stage of liver fibrosis. Results: The analysis included 50 patients with CLD; 30 (60%) were female. The commonest etiological diagnoses were autoimmune hepatitis (AIH) (20%) and extra-hepatic biliary atresia (EHBA) (12%). 26% of cases were categorized as undiagnosed CLD. The CPS showed CPS-A 34%, CPS-B 44% and CPS-C 22%. The vWF-Ag was found at a high level of 243.52 ±195.97, with a highly statistically significant difference in discriminating the EVs with 74% accuracy at a cutoff value of 108.99 IU/ml, p < 0.0001. Also, ROC analysis was performed for discriminating large esophageal varices with 84% accuracy at a cutoff value of 475.85 mg%. The VITRO score at a cutoff value of 1.72 could detect EVs with 70% sensitivity, 86.7% specificity, and 80% accuracy. Conclusions: High vWF-Ag is a valuable prognostic tool for estimating the presence of EVs, and higher vWF-Ag is associated with increased grade of EVs.

Clinical & Experimental Hepatology, 2021

Aim of the study: Azathioprine (AZA) is an important steroid-sparing drug in the management of au... more Aim of the study: Azathioprine (AZA) is an important steroid-sparing drug in the management of autoimmune hepatitis (AIH). Avoidance of its adverse events that could be severe and carry a risk of mortality in a few cases is important, preferably with cheap and easy assessments that could be feasible in developing countries with the unavailability of molecular assays. Assessment of thiopurine methyltransferase (TPMT), the key enzyme for the inactivation of AZA, as a predictor of AZA toxicity had been a matter of conflict. This work aimed to study the role of TPMT serum level assessment and other host-, disease-, and treatment-related factors in predicting AZA toxicity. Material and methods: Sixty-six children with AIH, divided into two groups, were recruited. Group 1 included twelve children with AZA toxicity and group 2 included fifty-four children without AZA toxicities. Both groups were compared for demographic, clinical, laboratory, histopathological, and treatment-related factors, and serum TPMT level, measured by ELISA. Results: TPMT serum level was comparable in both groups (p = 0.363). Duration of treatment until enzyme normalization and duration of AZA therapy were significantly associated with AZA toxicity (p = 0.007 and p = 0.01, respectively). At the first follow-up treatment with AZA, total leucocyte count (TLC) and neutrophil counts were significantly lower in group 1 (p = 0.005 and p = 0.002, respectively). Moreover, the percentage reduction of TLC and neutrophil counts were significantly higher in group 1 (p < 0.001, for both). Conclusions: Monitoring for AZA adverse events in those with the defined predictors of AZA-related adverse events is more important than TPMT assessment.

Global journal of gastroenterology & hepatology, Oct 5, 2017

Background : Biliary atresia (BA) is a progressive disease of infancy. Early diagnosis is particu... more Background : Biliary atresia (BA) is a progressive disease of infancy. Early diagnosis is particularly essential because prognosis is closely related with timing of Kasai portoenterostomy. There is no non-invasive method that clearly identifies the diagnosis. Tumor necrosis factor-α (TNF-α) is a cytokine which is mainly produced by activated macrophages and monocytes. Aim : We aimed to study the performance of serum TNF-α in BA and other neonatal cholestatic disorders. Materials and Methods : The study included 80 infants with neonatal cholestasis divided in two groups; BA group (n=40), non-BA group (n=40) with cholestatic disorders other than BA. Demographic, clinical, laboratory, and histopathological parameters were collected. Serum TNF-α level was measured by enzyme-linked immunosorbent assay. Results : The mean value of TNF-α level was significantly higher in BA group (260.61+155.74 pg/ml) compared to non-BA (126.26+ 64.23 pg/ml) and a cutoff level of 124.4 pg/ml can diagnose BA with 95 % sensitivity and specificity 75 %. TNF-α is correlated with alkaline phosphatase, gamma glutamyle transferase and grade of liver fibrosis (P value 0.019, 0.004 and < 0.0001 respectively). In Conclusion : Serum TNF-α can be used as a non-invasive and sensitive marker for confirming the diagnosis of BA in in suspicious cases.

Egyptian Liver Journal, Jul 1, 2011

Background Nonalcoholic fatty liver disease (NAFLD) is one of the major causes of chronic liver d... more Background Nonalcoholic fatty liver disease (NAFLD) is one of the major causes of chronic liver disease. Unfortunately, accurate noninvasive modalities for diagnosing NAFLD and monitoring its progression are unavailable and liver biopsy is still the mainstay of diagnosis. We aim to highlight the importance of radiologic modalities in detecting hepatic steatosis in overweight and obese children. Patients and Methods One hundred and twenty (age range 2-18 years) children were assigned to two groups. Group 1 (53 girls and 47 boys) consisted of apparently normal children with simple obesity, that is, body mass index (BMI) higher than or equal to 85th centile for age. Group 2 (nine girls and 11 boys) consisted of apparently normal children with normal BMI corresponding for age. All children were thoroughly examined and underwent laboratory tests, ultrasound, computed tomography (CT), and anthropometric measurements. Results Increased BMI was associated with hepatomegaly, especially in older children above or equal to 11 years, and the aspartate aminotransferase/alanine aminotransferase ratio correlates well with the severity of histopathological abnormalities of the liver. Ultrasound echogenicity showed correlation to BMI only in older obese children above or equal to 11 years; ultrasound also correlates well to CT attenuation and liver biopsy steatosis. CT scan attenuation showed correlation to BMI only in older obese children above or equal to 11 years, but it correlates well to ultrasound echogenicity and liver biopsy findings. Conclusion Ultrasound examination when positive is highly accurate in diagnosing NAFLD. A combination of serum biomarkers and radiologic modalities provides a valuable diagnostic approach for patients with nonalcoholic steatosis.

Hepatobiliary & Pancreatic Diseases International, Apr 1, 2019

Background: Serum ferritin (SF) and consequently hepatic iron have long been considered important... more Background: Serum ferritin (SF) and consequently hepatic iron have long been considered important in liver fibrosis progression. They have been studied in different liver diseases with no previous reports in neonatal cholestasis (NC). This study aimed to measure SF in different etiologies of NC and investigate its relation to hepatic iron and fibrosis. Methods: SF was measured in 75 infants, including 50 with NC and 25 with sepsis. SF was compared between these two groups. Biochemical parameters, hepatic iron grades, and liver fibrosis and other histopathological characteristics and correlated with SF were assessed in NC group. Finally, a comparison between intrahepatic cholestasis and obstructive etiology was performed. Results: SF was elevated in NC (1598 ± 2405 ng/mL) with no significant difference from those with sepsis (P = 0.445). NC and sepsis constituted augmenting factors leading to more elevation of SF (2589 ± 3511 ng/mL). SF was significantly correlated with hepatic iron grades (r = 0.536, P < 0.0 0 01) and a cutoff value of 803.5 ng/mL can predict higher grades (≥ grade 3) of iron deposition with sensitivity of 100%, specificity of 70% and accuracy of 85%. Moreover, SF was significantly higher (P < 0.0 0 01) in those with intrahepatic cholestasis (2602 ± 3154 ng/mL) and their prevalent pathological findings of giant cell transformation (P = 0.009) and hepatocyte swelling (P = 0.023) than those with obstructive etiology (672 ± 566 ng/mL) and their prevalent pathological findings of ductular proliferation (P = 0.003) and bile plugs (P = 0.002). SF was unrelated to the grade of liver fibrosis (P = 0.058). Conclusions: SF is non-specifically elevated in NC, with positive correlation to hepatic iron grades. SF ≥ 803.5 ng/mL can predict higher grades (≥ grade 3) of hepatic iron. However, an active role of increased SF and hepatic iron in disease progression remains questionable.

Clinical & Experimental Hepatology, 2019

Aim of the study: We aimed to assess oxidative stress factors, glutathione peroxidase (GPX) and m... more Aim of the study: We aimed to assess oxidative stress factors, glutathione peroxidase (GPX) and malondialdehyde (MDA) in children with chronic hepatitis C (CHC) and their relation to treatment response. Material and methods: The study included 50 children with chronic hepatitis C virus (HCV) before treatment (naïve HCV), 25 children responders to HCV treatment, 25 children non-responders to HCV treatment and 25 healthy controls. All patients and controls were subjected to GPX and MDA measurement by enzyme-linked immunosorbent assay. Results: The average GPX activity in erythrocytes of naïve CHC patients was 29.2 ±10.3 mU/ml. It was statistically significantly lower than the average activity of GPX in erythrocytes of the healthy control group (47.3 ±5.2 mU/ml) (p < 0.05). The average GPX activity in erythrocytes of the responder group was 34.93 ±3.17 mU/ml. It was statistically significantly higher than the average activity of GPX in erythrocytes of the non-responder group (11.7 ±4.2 mU/ml) (p < 0.05). Plasma MDA was significantly higher in naïve CHC patients than in healthy controls (9.7 ±3.7 nmol/ml vs. 3 ±1.1 nmol/ml, p < 0.0001). Furthermore, plasma MDA concentration was significantly decreased in the responder group (5.36 ±0.7 nmol/ml) and elevated in the non-responder group (16.05 ±2.9 nmol/ml). Conclusions: Lower pretreatment levels of GPX and higher MDA level might be markers of oxidative stress occurring in HCV patients. Reversal of changes of these levels with completion of the treatment may indicate a correlation between oxidative stress and the viral pathogenesis.

Hepatobiliary & Pancreatic Diseases International, 2021

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Journal of Clinical and Experimental Hepatology, 2021

Background Hyaline globules (HGs) in the cytoplasm of Kupffer cells (KCs) have been appraised for... more Background Hyaline globules (HGs) in the cytoplasm of Kupffer cells (KCs) have been appraised for being a typical feature of autoimmune hepatitis (AIH). This study aimed to determine how useful Kupffer cell hyaline globules (KCHGs) are in diagnosing AIH vs. other causes of pediatric chronic liver diseases (PCLDs). Materials and methods This retrospective study recruited 124 children; 58 with AIH, 50 with chronic hepatitis C virus (HCV) infection, and 16 with Wilson's disease (WD). Two pathologists retrieved paraffin blocks of liver biopsies and prepared new cut sections for Periodic acid-Schiff-Diastase (PAS-D) stain. They independently examined liver biopsies before starting treatment. Two pediatricians reviewed medical records for demographic, clinical, laboratory, and serological findings. Results Females represented 48.6% of the studied children with a median age of 5.8 (4.9) years. Pathologists identified KCHGs in 67.24%, 12.5%, and 6.0% of AIH, WD, and HCV affected children respectively, P < 0.001. A significantly higher proportion of seropositive than seronegative AIH patients had KCHGs (77.5% vs. 50.0%), (P < 0.05). In multivariate analysis, KCHGs and prolonged prothrombin time were the only significant predictors that differentiate between AIH and the other studied PCLDs. The odds ratio of having AIH increased 68 times if KCHGs were seen. Among children with AIH, the presence of KCHGs was associated with higher median levels of direct bilirubin 2.2 (1.3) vs. 1.2 (2.2), and immunoglobulin G 3.2 (1.9) vs. 2.0 (1.7), (P < 0.05), but not to histopathological findings or hepatic fibrosis and activity. Conclusions KCHGs are key indicators that can differentiate between AIH and other PCLDs, and between seropositive and seronegative AIH.

Annals of Hepatology, 2020

Introduction and Objectives: Biliary atresia (BA) is characterized by rapid progression of fibros... more Introduction and Objectives: Biliary atresia (BA) is characterized by rapid progression of fibrosis with no definite causes. Histopathological findings have been extensively described, but very few studies have assessed temporal changes in BA. Understanding these short-term changes and their relationship with fibrosis progression could have an impact on ameliorating rapid fibrogenesis. We aimed to study the relationship between temporal histopathological changes and fibrosis progression in BA within a short time interval. Patients and Methods: Forty-nine infants with BA who underwent Kasai portoenterostomy, a diagnostic liver biopsy, and an intraoperative liver biopsy were recruited. Histopathological characteristics of the two biopsies were examined. Temporal histopathological changes were assessed by comparing the two types of biopsies. Correlation of temporal changes in fibrosis with age, interval between biopsies, laboratory profiles, and temporal histopathological changes were studied. Results: In the univariate analysis, bile ductular proliferation (BDP), portal infiltrate, giant cells, hepatocellular swelling, and fibrosis showed significant temporal changes within a short interval (5-31 days). BDP and fibrosis showed the most frequent increase in their grades (32/49 and 31/49 cases, respectively). In the multivariate analysis, BDP was the only independent pathological feature showing a significant temporal increase (p = 0.021, 95% confidence interval: 1.249-16.017). Fibrosis progression was correlated with temporal changes in BDP (r = 0.456, p = 0.001), but not with age (p = 0.283) or the interval between the biopsies (p = 0.309). Conclusions: Fibrosis in BA progresses rapidly and is significantly correlated with BDP. Assessment of targeting BDP as an adjuvant medical therapy is recommended.

Clinics and Research in Hepatology and Gastroenterology, 2019

Background: Biliary atresia (BA) is a common cause of persistent neonatal cholestasis and liver t... more Background: Biliary atresia (BA) is a common cause of persistent neonatal cholestasis and liver transplantation in the pediatric population. Yes-associated protein (YAP) has also been shown to be necessary for development of bile ducts and adaptive responses within the gastrointestinal tract. We aimed to evaluate the YAP expression in liver tissues of infants with neonatal cholestasis as well as its diagnostic potential in the differential diagnosis of BA. Patients and methods: This prospective study included 100 infants with neonatal cholestasis. After full history taking, thorough clinical examination, routine investigations, and histopathological assessment, the patients were allocated as BA and non-BA; fifty patients in each group. Ten liver biopsies from 10 donors of liver transplant recipients served as controls. Diagnosis of BA was confirmed by operative cholangiography. Hepatic expression of YAP was assessed by immunohistochemical staining. Results: Presence of clay stool, elevated GGT and absence of gall bladder contractility were the main preliminary signs alarming for the possibility of BA. Bile ductular and interlobular biliary epithelium and hepatic lobule expression of YAP in patients with BA was significantly higher than that in Non-BA group (P < 0.05). There was no or weak positive YAP expression in normal liver of transplant donors. Positive YAP immunohistochemical had a sensitivity of 80% and a specificity of 94% with accuracy 87% in discrimination between BA and non-BA group (P-value < 0.0001).

Hepatobiliary & Pancreatic Diseases International, 2019

Background: Serum ferritin (SF) and consequently hepatic iron have long been considered important... more Background: Serum ferritin (SF) and consequently hepatic iron have long been considered important in liver fibrosis progression. They have been studied in different liver diseases with no previous reports in neonatal cholestasis (NC). This study aimed to measure SF in different etiologies of NC and investigate its relation to hepatic iron and fibrosis. Methods: SF was measured in 75 infants, including 50 with NC and 25 with sepsis. SF was compared between these two groups. Biochemical parameters, hepatic iron grades, and liver fibrosis and other histopathological characteristics and correlated with SF were assessed in NC group. Finally, a comparison between intrahepatic cholestasis and obstructive etiology was performed. Results: SF was elevated in NC (1598 ± 2405 ng/mL) with no significant difference from those with sepsis (P = 0.445). NC and sepsis constituted augmenting factors leading to more elevation of SF (2589 ± 3511 ng/mL). SF was significantly correlated with hepatic iron grades (r = 0.536, P < 0.0 0 01) and a cutoff value of 803.5 ng/mL can predict higher grades (≥ grade 3) of iron deposition with sensitivity of 100%, specificity of 70% and accuracy of 85%. Moreover, SF was significantly higher (P < 0.0 0 01) in those with intrahepatic cholestasis (2602 ± 3154 ng/mL) and their prevalent pathological findings of giant cell transformation (P = 0.009) and hepatocyte swelling (P = 0.023) than those with obstructive etiology (672 ± 566 ng/mL) and their prevalent pathological findings of ductular proliferation (P = 0.003) and bile plugs (P = 0.002). SF was unrelated to the grade of liver fibrosis (P = 0.058). Conclusions: SF is non-specifically elevated in NC, with positive correlation to hepatic iron grades. SF ≥ 803.5 ng/mL can predict higher grades (≥ grade 3) of hepatic iron. However, an active role of increased SF and hepatic iron in disease progression remains questionable.

Clinical and experimental hepatology, 2018

We aimed to assess the utility of serum level IL-13Rα2 receptors as a non-invasive marker for ear... more We aimed to assess the utility of serum level IL-13Rα2 receptors as a non-invasive marker for early diagnosis of biliary atresia (BA) and selection of BA patients indicated for Kasai portoenterostomy. The study included 60 infants with neonatal cholestasis in three groups; early BA group ( = 20), delayed BA group ( = 20) and non-BA cholestasis group ( = 20). A fourth group of 20 healthy neonates ( = 20) served as controls. IL-13Rα2 was measured by enzyme-linked immunosorbent assay in all patients and controls. The mean value of IL-13Rα2 was significantly higher in delayed BA group (11.05 ± 10.9 ng/ml) compared to early BA (0.34 ± 0.37 ng/ml), non-BA (0.54 ± 0.85 ng/ml) and control (0.24-0.2 ng/ml) groups. The levels of serum IL-13Rα2 increase with the severity of the degree of fibrosis. IL-13Rα2 at a cutoff level > 0.782 ng/ml could predict late fibrosis with accuracy of 77.55% ( < 0.0001). IL-13Rα2 could differentiate between preserved and disturbed liver architecture at a cu...

Clinical and Experimental Hepatology, 2020

Aim of the study: Liver transplantation remains the only definitive treatment for children with a... more Aim of the study: Liver transplantation remains the only definitive treatment for children with acute liver failure proven to have irreversible liver injury. Many prognostic models have been used for outcome prediction in pediatric acute liver failure to select patients in a real need of liver transplantation, but unfortunately all have shown inconsistent reproducibility and prognostic accuracy. The aim of this study was to evaluate the pediatric chronic liver failure sequential organ failure assessment (pCLIF-SOFA) score as a predictor of pediatric acute liver failure outcome. Material and methods: Clinical and laboratory data of 41 children with acute liver failure admitted to the National Liver Institute-Menoufia University were collected retrospectively and used for calculation of both pCLIF-SOFA and Pediatric End-Stage Liver Disease (PELD)/Model for End-Stage Liver Disease (MELD) scores on the day of admission, then statistical analysis was performed to identify the ability of these scores to predict the outcome. Results: According to the outcome, children enrolled in this study were allocated to survived (n = 16) and died (n = 25) groups, which were age and sex matched. The non-survival group had significantly higher values of both pCLIF-SOFA score (11 [7-13]) and PELD/MELD score (36 [18-42]) than those of the survival group (8 [7-11], 27.5 [15-45]; p < 0.001, p = 0.004) respectively. Both pCLIF-SOFA and PELD/MELD scores at cutoff values > 8 and > 30 respectively on admission could predict death in children with acute liver failure (ALF) with high sensitivity, but with higher specificity, positive and negative predictive values for pCLIF-SOFA. Conclusions: pCLIF-SOFA is a good predictor of death in pediatric acute liver failure.

Journal of Pediatrics & Neonatal Care, 2020

Aim: To assess fulminant hepatic failure (FHF) in children and its interrelating factors. Methods... more Aim: To assess fulminant hepatic failure (FHF) in children and its interrelating factors. Methods and materials: A retrospective review study of 24 patients less than 17 years old who presented to the National Liver Institute with FHF over a period of two years was done. FHF was defined as the presence of acute liver failure with or without encephalopathy without pre-existing liver disease, within 8 weeks of the onset of clinical liver disease. Hepatitis A virus (HAV) IgM antibodies, Hepatitis B virus surface antigen (HBsAg), IgM-anti Hepatitis B core antigen (HBc), Hepatitis E virus (HEV) IgM and Hepatitis C virus (HCV) RNA in nested PCR were done in all patients. Special investigations like alpha fetoprotein, serum copper, blood culture, drug levels and other metabolic studies were carried out whenever indicated. Detailed clinical evaluations and routine hepatic laboratory profile were done. Results: Acute hepatitis-A virus was the commonest cause. Severe coma was significantly pr...

Egyptian Pediatric Association Gazette, 2018

Biliary atresia (BA) is a rare disease characterized by ascending obstruction of bile ducts that ... more Biliary atresia (BA) is a rare disease characterized by ascending obstruction of bile ducts that exclusively affects newborn infants. The etiology of the disease is not known. BA is considered to be a phenotype resulting from several pathogenic processes leading to obstruction of the biliary tree. It usually presents shortly after birth, characterized by persistent jaundice, hepatosplenomegaly, clay-colored stool, and dark urine. It affects both the extra-hepatic biliary ducts (EHBDs) and the intra-hepatic biliary system (IHBDs), but the former is more severely affected. Diagnosis of BA is a great challenge and must be achieved as early as possible to delay progression to cirrhosis. Laboratory tests reveal direct hyperbilirubinemia and, variable levels of transaminases, gamma-glutamyl transpeptidase (GGT), and alkaline phosphatase (ALP), which overlap significantly with other causes of neonatal cholestasis. The intraoperative cholangiogram is considered the gold standard for the diagnosis of BA and is performed routinely in many institutions. BA can be divided into correctable and non-correctable types; the former accounts for (10-15%) of cases, in which the proximal common hepatic duct is patent, allowing primary anastomosis of the EHBDs to the bowel. All patients are subjected to identical surgical and medical treatments; consisting of Kasai portoenterostomy (KPE), which entails removal of the atretic extra-hepatic tissue and a Roux-en-Y jejunal loop anastomosed to the hepatic hilum. Kasai portoenterstomy is considered a transition to liver transplantation, as the pathology may be still ongoing. BA is the most frequent indication for liver transplantation in infants, which is the only treatment that can definitively arrest the natural disease course. In conclusion: BA is a serious liver disease that needs to be further studied, and awareness of BA should be increased among the public and health care workers to prevent the complications of this disease.