Ahmed El-Hennawy

Predictive accuracy of serum hyaluronic acid as a non-invasive marker of fibrosis in a cohort of multi-transfused Egyptian children with β-thalassaemia major

BACKGROUND AND STUDY AIM Liver disease remains a major cause of morbidity and mortality in patients with β-thalassaemia major (β-TM); therefore, its identification at an early stage is of great significance. Serum hyaluronic acid (HA) is considered as a non-invasive marker that appears early before pathological changes occur. We aim to determine the predictive accuracy of HA in detecting and staging hepatic fibrosis in β-TM patients. PATIENTS AND METHODS 30 Egyptian children with β-TM, and 15 age and sex-matched controls were studied. All had abdominal ultrasonography (US), measurement of serum amino-transferases (ALT, AST); hepatitis C, B and human immunodeficiency viruses (HCV, HBV, HIV) sero-markers, serum ferritin and HA. Liver biopsy was done for patients and fibrosis was scaled using Metavir scoring system and liver iron concentration (LIC) was measured. RESULTS Twenty patients (67.7%) had sero-markers of HCV, none had HBV or HIV. Serum HA was significantly higher in patients (90.78±28.79 ng/ml) compared to controls (21.1±13.24 ng/ml) with p<0.05. No difference between HCV infected and non-infected patients was detected. Positive significant correlation was detected between serum HA and stages of fibrosis by histopathology and US. No correlation was found between serum HA and age, sex, weight, height, haemoglobin level, platelet count, AST, serum ferritin, necro-inflammatory grade, and LIC. CONCLUSIONS Serum HA is a valuable non-invasive marker that may contribute to the assessment of liver fibrosis in multi-transfused children and adolescents with β-TM, irrespective of concomitant HCV infection.

Safety and efficacy of Hansenula-derived PEGylated-interferon alpha-2a and ribavirin combination in chronic hepatitis C Egyptian children

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. METHODS Forty-six children with chronic hepatitis C virus (HCV) infection were selected from three tertiary pediatric hepatology centers. Clinical and laboratory evaluations were undertaken. Quantitative polymerase chain reaction (PCR) for HCV-RNA was performed before starting treatment, and again at 4, 12, 24, 48, 72 wk during treatment and 6 mo after treatment cessation. All patients were assigned to receive a weekly subcutaneous injection of PEG-IFN-alpha-2a plus daily oral ribavirin for 12 wk. Thirty-four patients were treatment-naïve and 12 had a previous treatment trial. Patients were then divided according to PCR results into two groups. Group I included patients who continued treatment on a weekly basis (7-d schedule), while group II included patients who continued treatment on a 5-d schedule. Patients from either group who were PCR-negative at week 48, but had at least one PCR-positive test during therapy, were assigned to have an extended treatment course up to 72 wk. The occurrence of adverse effects was assessed during treatment and follow up. The study was registered at www.ClinicalTrials.gov (NCT02027493). RESULTS Only 11 out of 46 (23.9%) patients showed a sustained virological response (SVR), two patients were responders at the end of treatment; however, they were lost to follow up at 6 mo post treatment. Breakthrough was seen in 18 (39.1%) patients, one patient (2.17%) showed relapse and 14 (30.4%) were non-responders. Male gender, short duration of infection, low viral load, mild activity, and mild fibrosis were the factors related to a better response. On the other hand, patients with high viral load and absence of fibrosis failed to respond to treatment. Before treatment, liver transaminases were elevated. After commencing treatment, they were normalized in all patients at week 4 and were maintained normal in responders till the end of treatment, while they increased again significantly in non-responders (P = 0.007 and 0.003 at week 24 and 72 respectively). The 5-d schedule did not affect the response rate (1/17 had SVR). Treatment duration (whether 48 wk or extended course to 72 wk) gave similar response rates (9/36 vs 2/8 respectively; P = 0.49). Type of previous treatment (short acting IFN vs PEG-IFN) did not affect the response to retreatment. On the other hand, SVR was significantly higher in previous relapsers than in previous non-responders (P = 0.039). Only mild reversible adverse effects were observed and children tolerated the treatment well. CONCLUSION Reiferon Retard plus ribavirin combined therapy was safe. Our customized regimen did not influence SVR rates. Further trials on larger numbers of patients are warranted.

Alagille syndrome: clinical and ocular pathognomonic features

Purpose This study was carried out to determine the frequency of clinical diagnostic criteria in patients with Alagille syndrome (AGS) in comparison to a group of children with cholestasis and histologically proven neonatal hepatitis (NH). The type and frequency of ocular manifestations are highlighted. Methods According to histologic findings on liver biopsy, the 32 patients included in the study were classified into 2 groups: group 1 had paucity of interlobular bile ducts (PILBD) (n=13) and at least 3 of 5 characteristics of AGS and group 2 had NH on liver biopsy (n=19). Results The mean age of patients with AGS was higher than in group 2 (3.9 vs 1.6 years) (p<0.05). Pruritus was a significant symptom in the AGS group (p<0.05). Characteristic fades was detected in 61.5% of the AGS group. None of our patients with AGS had vertebral anomalies. Although cardiac murmurs were heard in 5 patients with AGS, cardiac anomalies were detected in only 3 by echocardiography: pulmonary stenosis in 2 patients and patent foramen ovale in 1. Posterior embryotoxon (PE) was detected in 69.2% of patients with AGS as compared to 10.5% of the NH group. Optic nerve drusen was detected in 91% of patients with AGS as compared to 5.3% of patients with NH. Conclusions Optic nerve drusen was the most common finding in AGS, followed by PE and facial features. Ocular ultrasound needs to be performed in all cholestatic infants with PILBD.

Predictors of non-alcoholic fatty liver disease in obese and overweight Egyptian children: single center study.

Background/Aim: Pediatric non-alcoholic fatty liver disease (NAFLD) is a global problem which has been increasingly recognized with the dramatic rise in pediatric obesity. The aim of the present study was to identify the clinical, sonographic, and biochemical predictors for NAFLD in obese children. Materials and Methods: Seventy-six children (2-15 years) were included after an informed consent. All were subjected to full anthropometric assessment (including height, weight, body mass index, subscapular skin fold thickness, waist and hip circumference and calculation of waist: hip ratio), biochemical assessment of liver function tests, lipid profile and insulin resistance and sonographic assessment of hepatic echogenicity. Liver biopsy when indicated, was done in 33 patients. Results: Sixteen patients (21%) had elevated ALT and 6 (7.9%) had elevated AST. Significant dyslipidemia (low HDL-c, high total cholesterol, high LDL-c and triglycerides) and higher insulin resistance were found in obese patients (P<0.01). The main sonographic findings were hepatomegaly in 20 patients (26.3%) and echogenic liver in 41 patients (53.9%). Liver biopsy showed simple steatosis in eight cases (24.2%) and non-alcoholic steatohepatitis (NASH) in seven cases (21.2%). Anthropometric measurements, increased hepatic echogenicty by ultrasound, insulin resistance and lipid profile were good predictors of NAFLD in obese children if assessed together. However, LDL-c was the only sensitive predictor (independent variable) for NAFLD in both uni- and multivariate logistic regression analyses. Conclusion: Dyslipidemia per se is a strong predictor of NAFLD among obese Egyptian children.

Patterns of hepatitis B infection in Egyptian children in the era of obligatory hepatitis B vaccination

BACKGROUND AND STUDY AIMS Mass compulsory HBV vaccination was applied in Egypt in 1992. The first dose of vaccine is administered at 2 months of age and routine screening of pregnant women for HBsAg is not applied. We aimed to evaluate the pattern of HBV infections after the implementation of HBV vaccination in Egyptian children. PATIENTS AND METHODS Fifty-six children with HBV infection presented to the Paediatric Hepatology Unit, Cairo University Childrens Hospital, over the period from 1992 to 2006. Their data were reviewed for risk factors, clinical, serological and histopathological profiles. These cases were followed-up for 6.3 ± 3.4 years. The data of those born before 1993 (did not receive HBV vaccine) (group I) was compared to those who received the vaccine (group II). RESULTS Sixty percent of HBV infected cases were born before 1993. Comparison of data of both groups revealed: (1) A significant younger age of onset in group II (3.34 ± 3.31 years vs. 9.84 + 2.95 years; p ≤ 0.01). (2) Vertical transmission was a significant risk factor in group II. (3) Chronic hepatitis developed in almost half of cases in both groups but cirrhosis was diagnosed only in 4 cases (all from group I) (p=0.04). CONCLUSION Vertically transmitted HBV infection is becoming an important risk factor for acquisition of HBV among children born after the era of mass vaccination in Egypt. Mass screening for HBsAg of pregnant Egyptian women and/or giving a birth dose of HBV vaccine is becoming mandatory with the increased incidence of vertical transmission.

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

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

Skin Iron Concentration: a Simple, Highly Sensitive Method for Iron Stores Evaluation in Thalassemia Patients

Iron overload is a potentially fatal complication in thalassemia patients. Accurate assessment of body iron is of utmost importance for these patients. The available methods for iron stores evaluation have limitations. We assessed biochemically the skin iron concentration (SIC) and determined the relation between the hepatic and skin iron level in thalassemia major patients to develop a simple, sensitive, quantitative measure of the body iron stores. Thirty-one cases with thalassemia major were assessed for iron overload. Liver and skin biopsies were performed for the patients and skin biopsies were taken from the 31 controls. The biopsies were subjected to biochemical assay of iron and histologic sections were examined. The SIC of the studied cases was significantly higher than that of the control group with a mean of 2.705 ± 1.14 and 0.275 ± 0.13 mg/g dry skin weight, respectively, p < 0.001. There was significant correlation between the SIC and the liver iron concentration (LIC) (r = 0.43, p = 0.01). The amount of liver iron is equivalent to [(3.5 × SIC) + 12.9]. With the use of this equation, we could reliably estimate an LIC value as high as 21.2 mg/g dry liver weight with a standard error of 4.07. Biochemical assay of the skin iron concentration is a reliable quantitative indicator of the body iron stores in patients with thalassemia major.

Hypermanganesemia with dystonia, polycythemia and cirrhosis in 10 patients: Six novel SLC30A10 mutations and further phenotype delineation

Biallelic mutations in the SLC30A10 gene cause an inborn error of Mn metabolism characterized by hypermanganesemia, polycythemia, early‐onset dystonia, and liver cirrhosis (HMDPC). To date, only 14 families from various ethnic groups have been reported. Here, we describe 10 patients from 7 unrelated Egyptian families with HMDPC. Markedly elevated blood Mn levels, the characteristic basal ganglia hyperintensity on T1‐weighted images, and variable degrees of extrapyramidal manifestations with or without liver disease were cardinal features in all patients. Eight patients presented with striking early diseased onset (≤2 years). Unexpectedly, early hepatic involvement before the neurological regression was noted in 3 patients. Mutational analysis of SLC30A10 gene revealed 6 novel homozygous mutations (c.77T > C (p.Leu26Pro), c.90C > G (p.Tyr30*), c.119A > C (p.Asp40Ala), c.122_124delCCT (p.Ser41del), c.780_782delCAT (p.Iso260del) and c.957 + 1G > C). Treatment using 2,3 dimercaptosuccinic acid as a manganese chelating agent showed satisfactory results with improvement of biochemical markers, hepatic manifestations and relative amelioration of the neurological symptoms. Our findings present a large cohort of patients with HMDPC from same ethnic group. The majority of our patients showed severe and early presentation with clear phenotypic variability among sibship. Moreover, we extend the phenotypic and mutational spectrum and emphasize the importance of early diagnosis and treatment of this potentially fatal disorder.

Glycogen storage disease type III in Egyptian children: A single centre clinico-laboratory study

BACKGROUND AND STUDY AIMS Glycogen storage disease type III (GSD III) is an autosomal recessive disorder caused by deficiency of glycogen debrancher enzyme and is characterised by clinical variability. PATIENTS AND METHODS We herein describe the clinical and laboratory findings in 31 Egyptian patients with GSD III presenting to the Paediatric Hepatology Unit, Cairo University, Egypt. RESULTS Eighteen patients (58%) were males. Their ages ranged between 6 months to 12 years. The main presenting complaint was progressive abdominal distention in 55%. Twelve patients (38.7%) had a history of recurrent attacks of convulsions; four had an erroneous diagnosis of hypocalcaemia and epilepsy. Doll-like facies was noted in 90%. Abdominal examination of all cases revealed abdominal distention and soft hepatomegaly which had bright echogenicity by ultrasound. Hypertriglyceridaemia was present in 93.6%, hyperlactacidaemia in 51.6% and hyperuricaemia in 19.4%. Liver biopsy showed markedly distended hepatocytes with well distinct cytoplasmic boundaries and 32% had macrovesicular fatty changes. Serum creatine kinase was elevated in 64.6% of patients and correlated positively and significantly with age (r=0.7 and P=<0.001), while serum triglycerides correlated negatively with age (r=-0.4 and P=0.05). CONCLUSION Blood glucose assessment and search for hepatomegaly in an infant with recurrent seizures may prevent delay in the diagnosis. A huge soft liver reaching the left midclavicular line that appears echogenic on ultrasonography is characteristic of GSD III. A distended hepatocyte with rarified cytoplasm is pathognomonic but not diagnostic. Hypertriglyceridaemia correlates negatively with age, in contrary to CK level.