Mostafa Sira | National Liver Institute, Menofiya University (original) (raw)

Papers by Mostafa Sira

European journal of gastroenterology & hepatology, 2014

Discrimination of biliary atresia (BA) from other causes of neonatal cholestasis (NC) is challeng... more Discrimination of biliary atresia (BA) from other causes of neonatal cholestasis (NC) is challenging. We aimed to analyze the clinicopathological findings in cholestatic infants who were provisionally diagnosed with BA and then excluded by intraoperative cholangiography compared with those with a definitive diagnosis of BA and to shed light on common misdiagnoses of BA. We retrospectively analyzed the data of infants diagnosed preoperatively with BA and referred to surgery between the years 2009 and 2013. On the basis of intraoperative cholangiography results, infants were divided into those with a definitive diagnosis of BA and those misdiagnosed with BA. Out of 147 infants, there was a misdiagnosis of BA in 10 (6.8%) infants. Alanine transaminase was significantly higher in the non-BA group, whereas other clinical and laboratory findings were comparable in both groups. Hepatomegaly and abnormal gallbladder in ultrasound, and ductular proliferation and advanced grades of portal fibrosis in liver biopsy were significantly higher in infants with BA. However, giant cells were more common in the non-BA infants. Nonetheless, the frequency of clay stool, hepatomegaly, abnormal gallbladder, ductular proliferation, and advanced portal fibrosis was remarkable (100, 70, 40, 70, and 50%, respectively) in the misdiagnosed infants. The misdiagnoses were idiopathic neonatal hepatitis, progressive familial intrahepatic cholestasis type 3, cytomegalovirus hepatitis, Alagille syndrome, and a cholangitic form of congenital hepatic fibrosis. A meticulous preoperative workup should be performed to exclude other causes of NC even if signs of BA are present, especially if features such as giant cells in histopathology are present. This involves completing the NC workup in parallel involving all common causes of NC rather than performing them in series to avoid loss of valuable time and efforts.

AIM: To investigate the safety and efficacy of a Hansenula -derived PEGylated (polyethylene glyco... more AIM: To investigate the safety and efficacy of a Hansenula -derived PEGylated (polyethylene glycol) interferon (IFN)-alpha-2a (Reiferon Retard) plus ribavirin customized regimen in treatment-naïve and previously treated (non-responders and relapsers) Egyptian children with chronic hepatitis C infection.

Molecular signaling of HCV and Antiviral therapy (Poster), Nov 13, 2009

Background and aim The dilemma of early diagnosis of biliary Atresia (BA), particularly distingu... more Background and aim
The dilemma of early diagnosis of biliary Atresia (BA), particularly distinguishing it from other causes of neonatal cholestasis is challenging. The aim was to design and validate a scoring system for early discrimination of BA from other causes of neonatal cholestasis.

Methods
A twelve-point scoring system was proposed according to clinical, laboratory, ultrasonographic, and histopathological parameters. A total of 135 patients with neonatal cholestasis in two sets were recruited to design (n = 60) and validate (n = 75) a scoring system. Parameters with significant statistical difference between BA (n = 30) and non- BA (n = 30) patients in the design set were analyzed by logistic regression to predict the presence or absence of BA then a scoring system was designed and validated.

Results
The total score ranged from 0 to 37.18 and a cutoff value of > 23.927 could discriminate BA from other causes of neonatal cholestasis with sensitivity and specificity of 100% each. By applying this score in the validation set, the accuracy was 98.83% in predicting BA. The diagnosis of BA was proposed correctly in 100% and the diagnosis of non- BA was proposed correctly in 97.67% of patients. By applying this model, unnecessary intraoperative cholangiography would be avoided in non- BA patients.

Conclusions
This scoring system accurately separates infants with BA and those with non- BA, rendering intraoperative cholangiography for confirming or excluding BA unnecessary in a substantial proportion of patients.

Biliary atresia (BA) constitutes about one third of all neonatal cholestasis (NC) and the most co... more Biliary atresia (BA) constitutes about one third of all neonatal cholestasis (NC) and the most common indication (up to 50%) of liver transplantation (LTx) in children. Despite extensive studies, its etiopathogenesis has not been clearly revealed. Treatment is primarily surgical based on reinstitution of bile flow by Kasai portoenterostomy, the success of which is largely dependent on the early diagnosis before 60 days of age. If portoenterostomy is not successful or not performed, LTx is the only life-saving alternative. Accurate diagnosis of BA, particularly distinguishing it from other causes of liver injury in the neonatal period, is challenging as there is a high degree of overlap in clinical, biochemical, imaging, and histological characteristics. There is no single preoperative investigation that enables the diagnosis of BA to be made with certainty. Liver biochemistry assessment, biliary radionuclide excretion scanning, magnetic resonance cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP), percutaneous needle liver biopsy, and laparoscopy can all be helpful, but their results are not individually diagnostic. The current review presents an overview of BA with emphasis on the recent diagnostic modalities.

The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology, 2013

World journal of hepatology, 2013

AIM: To evaluate serum complement C4a and its relation to liver fibrosis in children with chronic... more AIM: To evaluate serum complement C4a and its relation to liver fibrosis in children with chronic hepatitis C virus (HCV) infection.

Nature Reviews Gastroenterology and Hepatology, 2011

Journal of pediatric …, 2012

Objectives: Hepatitis C virus (HCV) infection is a serious health problem that causes chronic inf... more Objectives: Hepatitis C virus (HCV) infection is a serious health problem that causes chronic infection in up to 85% of cases. HCV nonstructural (NS) cysteine protease, NS2/3, is required for viral replication in vivo. Cystatin C is a naturally occurring cysteine protease inhibitor in human cells. We aimed to investigate the relation between serum levels of cystatin C and HCV viremia in treatment-naïve children with chronic hepatitis C. Methods: Serum cystatin C levels were measured in 27 children with chronic hepatitis C and determined their relation with liver functions, histopathological parameters, and hepatitis C viral load. Serum cystatin C was compared with that of 25 age-and sex-matched healthy controls.

European journal of …, 2012

The diagnosis of biliary atresia (BA) can be challenging as its histopathologic features overlap ... more The diagnosis of biliary atresia (BA) can be challenging as its histopathologic features overlap with those of other pediatric cholestatic liver diseases. We aimed to study the diagnostic value of hepatic CD56 immunostaining in the differentiation of BA from other causes of neonatal cholestasis. Hepatic CD56 immunostaining was investigated in 30 infants with BA and compared with that in 30 infants with non-BA cholestatic disorders. The expression of positive cells was interpreted semiquantitatively on the basis of the extent (percentage or number) of positive cells on a scale of 0-3. The occurrence of CD56-positive biliary epithelial cells was significantly higher in the BA (83.3%) than in the non-BA group (6.7%), whereas the occurrence of CD56 natural killer cells in hepatic parenchyma was significantly higher in the non-BA group (76.7%) than in the BA group (6.7%; P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001 for both). In contrast, there was no significant difference between both groups in CD56 natural killer cells in portal tracts (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;0.05). Using this differential expression as a discriminative tool between the BA and the non-BA group, positive biliary epithelial cell staining had high specificity, whereas negative parenchymal staining had high sensitivity (93.3% for both) with an accuracy of 88.3 and 84.65%, respectively. The combination of both parameters improved the accuracy up to 91.65%, with 100% specificity in the diagnosis of BA. CD56 immunostaining of the liver had a diagnostic value; it can be used to differentiate BA from other neonatal cholestatic disorders and might be useful as an additional stain when investigating infants with neonatal cholestasis.

Journal of …, 2013

Diagnosis of biliary atresia (BA), particularly distinguishing it from other causes of neonatal c... more Diagnosis of biliary atresia (BA), particularly distinguishing it from other causes of neonatal cholestasis (NC), is challenging. Ultrasonography is a helpful investigation when evaluating NC. The aim was to determine the value of color Doppler ultrasound, particularly hepatic subcapsular flow, as a possible tool in early discrimination of BA from other causes of NC. Ultrasonographic and color Doppler findings of 27 BA patients were compared with that in 27 non-BA cholestasis patients and a control group of 22 non-hepatic neonates. Hepatic artery diameter was significantly higher in BA (2.48 ± 0.55 mm) than that in non-BA group (1.91 ± 0.63 mm) (P = 0.001) and the control group (1.6 ± 0.47 mm) (P &amp;amp;amp;lt; 0.0001), while there were no statistically significant difference between BA and non-BA groups as regards portal vein diameter and flow, hepatic vein flow, and hepatic artery resistance index. The frequency of hepatic subcapsular flow was significantly higher in BA than that in non-BA group (96.3% vs 3.7%; P &amp;amp;amp;lt; 0.0001), while it was not detected in any of the non-hepatic control group. The presence of hepatic subcapsular flow had 96.3% sensitivity and specificity in predicting BA. Color Doppler ultrasound findings could help significantly in discriminating BA from other causes of NC, among which hepatic subcapsular flow had the best performance. Considering the young age of BA patients (61.8 ± 15.1 days), hepatic subcapsular flow can help in early diagnosis of BA and prevent the delay in surgical correction.

Journal of Pediatric …, 2010

Chronic hepatitis C has been described as a mild disease in children, but fibrosis progression an... more Chronic hepatitis C has been described as a mild disease in children, but fibrosis progression and end stage liver disease have been documented. Thus, the problem of therapy has become a challenging issue. Our preliminary results using the standard treatment regimen of alternate day interferon (IFN) plus ribavirin yielded 21.4% sustained virological response (SVR). In this study, we evaluate the efficacy and safety of daily IFN alpha-2a induction regimen plus ribavirin in treatment of children with chronic hepatitis C genotype 4. The study included 40 children with chronic hepatitis C. Thirty patients were naive hepatitis C and 10 were previously non-responders to the standard treatment regimen. All children were assigned to receive daily IFN plus ribavirin for 1 month, then alternate day IFN plus ribavirin for 11 months. The mean age of children was 11.7 ± 0.35 years and 27 (67.5%) were males. Twenty-nine (72.5%) had low, three (7.5%) moderate and eight (20%) high viremia. Thirty-four (85%) had rapid virological response and 33 (82.5%) had SVR. One patient had a breakthrough at 6 months duration of therapy. Adverse effects were mild, and were not treatment limiting. Low viral load was significantly associated with higher rate of SVR. Rapid virological response had 90% positive predictive value for subsequent SVR with 100% sensitivity. Daily IFN induction regimen showed a high efficacy and safety for treatment of children with chronic hepatitis C virus genotype 4.

In this chapter, we want to highlight the etiology, pathophysiology, clinical presentation and th... more In this chapter, we want to highlight the etiology, pathophysiology, clinical presentation and the role of surgery in the management of this disease category, especially that medical therapy is of limited value in a magnitude of cases. Moreover, liver transplant is not without significant side effects. So, raising the orientation about this not uncommon condition will help in timely surgical intervention and improving patients' outcome.

Journal of Hepatology, 1998

LKM a&antibodies -all positive in indirect immunofluorescence -were characterized in 41 pat!& wit... more LKM a&antibodies -all positive in indirect immunofluorescence -were characterized in 41 pat!& with autoimmune hepatitis type 2 (AIH-2) 7 patients with hepatitls in the Autoimmune Polyglandular Syndrome Type 1 (APSl) and in 45 patients with chronic hepatitis C. A new sensitive assay was established using immunoprecipitation of cytochrome P4502D6 (CYP2D6) produced by in vitro transcription/translation and used for the quantitation of antXYPZD6 autoantibodies. LKM tiers in CYP2D6 positive sera as determined by indirect immunofluorescence correlate well with the titers obtained by immunoprecipitation of "S-labeled protein in AIH-2 and LKM positive hepatitis C. In chronic hepatitis C 42/45 LKM positive sera were found to contain autoantibodies directed against CYP2D6, while 40141 sera with AIH-2 recognized CYP2D6. Titers of LKM autoantibodies were found to be comparable in patients with AIH-2 and chronic hepatitis C. Sera from patients with AIH-1 (30), AIH-3 (30) hepatitis D (20) and healthy controls (50) did not contain anti-CYP2D6 antibodies detectable with the new assay system, which also detects conformational epitopes. 2/3 anti-CYP2D6 negative HCV sets with LKM autoantibodies contained recognized a 59 kDa pmtein and 1 serum in AIH-2 detected UGTI only. In spite of the high frequency of antiCYP2D6 autoantibodies in AIH-2 and LKM positive HCV sera, the spectrum of target proteins diieres in patients with chronic hepatitis C and AIH-2. In chronic hepatitis C antiCYPZD6 is frequently associated with a protein of 70 kDa or a protein of 59 kDa, while in 10% of patients with AIH-2 antiCYP2D6 is associated with anti-UGT1. Recently CYPlA2 was identifNd as a target protein in hepatitis as disease component in APSI. 68 patients with APSI were tested for CYP2D6, however none of the APSI patients -7 of whom were affe&d by hepatitiswere CYP2D6 positive. 417 sera of these hepatitis patients recognized CYPlA2, which isn't detected by 40 sera from AIH-2 patients.

Gastroenterology …, 2011

The need for repetition of liver biopsy, especially in assessing the degree of fibrosis and follo... more The need for repetition of liver biopsy, especially in assessing the degree of fibrosis and follow-up of treatment protocols, justifies an intensive search for non-invasive alternatives. We attempted to investigate the clinical usefulness of serum fibrogenesis markers in pediatric chronic liver diseases.

Hepatology …, 2011

The diagnosis of biliary atresia (BA) is challenging as no single preoperative test is 100% acc... more The diagnosis of biliary atresia (BA) is challenging as no single preoperative test is 100% accurate, especially for distinguishing it from other causes of neonatal cholestasis (NC). Intercellular adhesion molecule (ICAM) elevation was reported in BA as a part of the immune-mediated inflammatory process. The use of ICAM-1 as a discriminative tool between BA and other causes of NC has never been addressed before. This study was to evaluate the diagnostic potentials of ICAM-1 in BA versus other forms of NC. For this purpose, serum ICAM-1 (sICAM-1) and ICAM-1 expression, in liver biopsy using immunohistochemistry, were estimated in 30 patients with BA and compared to that in 20 patients with other forms of NC. sICAM-1 levels were compared to that in 20 healthy controls. sICAM-1 levels were significantly higher in BA (1055.9 ± 230.2 ng/mL) than that in cholestasis (604.8 ± 194.8 ng/mL) and the control groups (158.9 ± 78.7 ng/mL) (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). A cut-off value of 793.8 ng/mL had 86.7% sensitivity and 95% specificity in discriminating the BA from the cholestasis group. The biliary expression score of ICAM-1 at a cut-off value of 110 could discriminate between BA and other causes of NC with 100% sensitivity and specificity. Neither serum levels nor liver expression of ICAM-1 scores correlated with disease severity or with fibrosis stage. These results suggest that ICAM-1 has a diagnostic value in patients with BA and would be a promising helpful tool when investigating patients with NC.

International …, 2009

Human colostrum contains many bioactive factors that must promote the development of intestinal m... more Human colostrum contains many bioactive factors that must promote the development of intestinal mucosal immunity in infants. Especially, the presence of certain cytokines such as transforming growth factor (TGF)-b or IL-10 has been of great interest for IgA production as a function of mucosal immune response. In the present study, we attempted to investigate whether unidentified factors inducing generation of IgA-producing cells from naive B cells might exist in colostrum. For this purpose, colostrum samples were directly added to a culture consisting of naive B cells and dendritic cells from cord blood and CD40 ligand-transfected L cells, comparing with recombinant IL-10 (rIL-10) and/or rTGF-b. It was noted that most colostrum samples alone were able to induce IgA-secreting cells at higher levels than rIL-10 and/or rTGF-b. IgA-inducing activity of colostrum was abolished by neither anti-neutralizing mAbs against IL-10 nor TGF-b, though partially by anti-IL-6 mAb. We prepared partially purified fractions from both pooled colostrums with and without IgA-inducing activity and comparatively performed quantitative proteomic analysis by two-dimensional difference gel electrophoresis followed by liquid chromatography-mass spectrometry. As a result, syntenin-1 was identified as a candidate for IgA-inducing protein in colostrum. Western blot analysis indicated that levels of syntenin-1 in colostrum samples were correlated with their IgA-inducing activities. Moreover, we demonstrated that recombinant syntenin-1 could induce preferentially IgA production from naive B cells. These results suggest that syntenin-1 serves as one of IgA-inducing factors for B cells.

Early human …, 2004

Background: Transforming growth factor (TGF)-β has a crucial effect on IgA production, which is t... more Background: Transforming growth factor (TGF)-β has a crucial effect on IgA production, which is the major humoral effector of mucosal immunity. Breast milk contains the abundant amount of TGF-β in the early period of lactation. Aim–study design: To verify the notion that TGF-β in breast milk might contribute to the development of IgA production in newborns, we investigated the association of TGF-β in maternal colostrum with an increase of serum IgA in newborns during the first month of life. Subjects and methods: The concentrations of TGF-β1 and TGF-β2, including IL-6 and IL-10, in colostrum samples from 55 healthy mothers were determined by ELISA. The levels of IgA and IgM in serum samples collected from corresponding newborn babies at birth and at 1 month of age were measured by ELISA. Results: TGF-β1 and TGF-β2 were detected in substantial quantities in all colostrum samples, but IL-6 and IL-10 were present only in a proportion of samples. An increase of serum IgA in newborn during the first month of life was significantly higher than that of serum IgM (p<0.001). Notably, an increase of serum IgA in newborns during 1 month of life was well correlated with levels of both TGF-β1 (r=0.38, p=0.005) and TGF-β2 (r=0.45, p=0.0005) in colostrum, while that of IgM was marginally correlated with colostral TGF-β2 (r=0.28, p=0.04). The association of increase of serum IgA in newborns with IL-6 and IL-10 in colostrum was not evident. Conclusion: Our findings suggest that TGF-β in colostrum might serve as the starter of IgA production in newborn infants.

Genes and Immunity, 2007

Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized by recurrent ba... more Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized by recurrent bacterial infections, hypogammaglobulinemia and low to normal numbers of circulating B cells. Mutations in the ICOS, TACI and CD19 genes have recently been identified in o10% of CVID patients. We, herein, describe two novel CD19 gene disruptions in an 8-year-old Japanese boy, who had been clinically diagnosed as having CVID at the age of 5 years. Flow-cytometric analysis demonstrated absence of CD19 and reduced CD21 expression on CD20-postive peripheral blood B cells. Mutation analysis of CD19 revealed a mutation in the splice acceptor site of intron 5 (IVS5-1G4T) of the maternal allele, resulting in skipping of exon 6, and a truncated protein product. The paternal allele was disrupted by a gross deletion encompassing at least the ATP2A1, CD19 and NFATC2IP genes. The patient had a small number of IgD À CD27 þ memory B cells, in which somatic mutation were detected. His B cells showed substantial proliferation upon stimulation, but reduced IgG and IgA production in vitro. These findings extend the mutation spectrum of the CD19 deficiency to four, and confirm the homogeneity of the CD19 deficiency as a unique type of CVID.