Mona Isa

99mTechnetium-macroaggregated albumin perfusion lung scan versus contrast enhanced echocardiography in the diagnosis of the hepatopulmonary syndrome in children with chronic liver disease.

Background and aims The hepatopulmonary syndrome (HPS) is a triad of advanced chronic liver disease (CLD), arterial hypoxemia and intrapulmonary arteriovenous shunting in the absence of a primary cardiopulmonary disease. HPS has been more frequently reported in adults than in children with no data on its prevalence in children with CLD. The aim of this study was to detect the prevalence of the HPS in a cohort of children with CLD because of chronic hepatitis B and/or C virus infection, schistosomiasis as well as inborn metabolic errors. We also aimed to evaluate the role of 99mTechnetium labeled macroaggregated albumin (99mTc--MAA) perfusion lung scan versus contrast enhanced echocardiography (CEE) with intravenous injection of agitated saline in the diagnosis and quantification of intrapulmonary shunts and their relationship to important clinical and laboratory findings. Methods Forty Egyptian children (22 males) were investigated. Their ages ranged from 5 to 12 years (with a mean of 9.5 years). Twenty individuals proved to have cirrhosis. Results Blood gas determination revealed more significant arterial hypoxemia in cirrhotics than noncirrhotics both under room air and after breathing 100% oxygen for 15 mins. CEE showed comparable cardiac measurements in cirrhotic and noncirrhotic patients, and diagnosed intrapulmonary shunts in three hypoxemic cirrhotic patients; whereas 99mTc--MAAperfusion lung scan diagnosed shunts in seven patients (five of them cirrhotic). The presence of shunts was significantly correlated with the duration of CLD, clinical findings, presence of cirrhosis and porto-systemic collaterals. We calculated for each patient a shunt index (SI) by the formula: (activity outside thorax/activity outside plus inside thorax) 100; and an SI value of 0.278 was found to be a cutoff value for shunt detection. All patients with SI above this value had shunting associated with hypoxemia and all patients with SI below this value had no hypoxemia (specificity 100%). Conclusion Arterial hypoxemia and intrapulmonary shunts were diagnosed in 17.5% of this cohort of children with cirrhotic or noncirrhotic CLD representing the classic HPS. 99mTc--MAA perfusion lung scan was more sensitive than CEE in detection of intrapulmonary shunts. SI cutoff value of 0.278 was found to be highly specific for shunt detection and we recommend its validation in further studies.

Celiac Disease in Children and Adolescents with Autoimmune Hepatitis: a Single-centre Experience

OBJECTIVES Celiac disease (CD) is increasingly reported from North Africa, including Egypt. Autoimmune hepatitis (AIH) is considered a high risk factor for CD. We aimed to investigate the frequency of CD diagnosis in AIH. METHODS We prospectively enrolled 26 AIH patients aged 3.5-21 (mean 9.98 ± 3.94) years and 20 healthy age- and sex-matched controls. Serodiagnosis of CD was based on the most sensitive tests namely immunoglobulin A (IgA) human tissue transglutaminase antibody (IgA-tTGA) by enzyme-linked immunosorbent assay and/or IgA endomysial antibody (IgA-EMA) by immunofluoresence and confirmed the diagnosis by upper gastrointestinal endoscopy and histo-pathological findings in jejunal biopsy. RESULTS IgA-EMA was positive in four patients (15.4%), whereas IgA-tTGA was positive in two of them (7.7%). Histopathology was confirmatory in three (11.5%) seropositive patients. CONCLUSION The high prevalence (11.5%) of CD among Egyptian children with AIH indicates that CD exists in high-risk groups in our region and must be carefully looked into.

L-Carnitine Improves the Asthma Control in Children with Moderate Persistent Asthma

The objective. was to investigate L-Carnitine level and the effects of its supplementation in children with moderate persistent Asthma. Methods. Free and total serum carnitine levels were measured in 50 children having moderate persistent asthma and 50 healthy control children. The patients group was randomly divided into two subgroups. Subgroup A was supplemented with L-carnitine for 6 months while subgroup B was used as a placebo controls. Both subgroups were assessed by pulmonary function tests (PFT) and childhood-asthma control test (C-ACT) before and 6 months after carnitine supplementation. Results. Total and free carnitine levels were significantly lower in patient group than in control group. PFT and C-ACT showed significant improvements in asthmatic children supplemented with L-carnitine than in those who were not supplemented. Conclusion. L-carnitine levels were initially lower in moderate persistent asthmatic children as compared to healthy control children. Asthmatic children who received L-carnitine supplementation showed statistically significant improvement of C-ACT and PFT.

Diagnosis of spontaneous bacterial peritonitis in infants and children with chronic liver disease: A cohort study

BackgroundSpontaneous bacterial peritonitis (SBP) is a serious complication in infants and children with chronic liver disease (CLD); however its diagnosis might be difficult. We aimed to study the feasibility of diagnosing SBP by routine ascitic fluid tapping in infants and children with CLD.MethodsWe enrolled thirty infants and children with biopsy-proven CLD and ascites. Ascitic fluid was examined for biochemical indices, cytology and cell count. Aerobic and anaerobic bacteriological cultures of ascitic fluid were preformed. Direct smears were prepared from ascitic fluid deposit for Gram and Zheil-Nelson staining.ResultsPatients were divided into three groups: Group I included five patients with SBP in which the cell count was ≥ 250/mm3 and culture was positive (16.7%), Group II, eight patients with culture negative neutrocytic ascites (CNNA) with cells ≥ 250/mm3 and negative culture (26.7%) and Group III, seventeen negative patients (56.6%) in which cells were <250/mm3 and culture was negative. None of our patients had bacteriascites (i.e. culture positive with cells <250/mm3). Presence of fever was significantly higher in SBP and CNNA. The mean lactate dehydrogenase (LDH) level was significantly higher in ascitic fluid in the infected versus sterile cases (p < 0.002). A ratio of ascitic/serum LDH ≥ 0.5 gave a sensitivity of 80%, specificity of 88%, positive predictive value (PPV) of 66.7%, negative predictive value (NPV) of 93.7% and accuracy of 63.3%. The mean pH gradient (arterial - ascitic) was significantly higher in SBP and CNNA cases when compared to the negative cases (p < 0.001). Ascitic fluid protein level of ≤ 1 gm/dl was found in 13/30 (43.3%) of studied cases with a sensitivity of 100%, specificity of 64.7%, PPV of 45.5%, NPV of 100% and diagnostic accuracy of 53.3% (p = 0.0001).ConclusionsSBP is a rather common complication in children with CLD. Culture of the ascitic fluid is not always diagnostic of infection. Biochemical parameters of the ascitic fluid definitely add to the diagnostic accuracy. LDH ascitic/serum ratio ≥ 0.5, an arterial-ascitic pH gradient ≥ 0.1 and total ascitic fluid protein ≤ 1 gm/dl are the most significant parameters suggesting infection.

Colorectal polyps: a frequently-missed cause of rectal bleeding in Egyptian children

Abstract Objectives: Colorectal polyps are important causes of rectal bleeding but they have been infrequently reported in Egyptian children. The prevalence and characteristics of colorectal polyps in a consecutive cohort of Egyptian children with rectal bleeding are presented. Methods: A total of 174 children aged 2–12 years [mean (SD) 6·4 (3·7)] with fresh rectal bleeding were enrolled prospectively. Rectal examination, laboratory investigations and fibre-optic colonoscopy were performed in all patients. Results: The source of bleeding was diagnosed as colorectal polyps in 100 patients (57·4%) and was owing to other causes in 74. The interval between onset of symptoms and presentation ranged from 2 to 48 months [mean (SD) 18·3 (16)]. In patients with other causes, rectal bleeding was attributed to intestinal amoebiasis (42), diarrhoea/dysentery (18), severe constipation (2) and intestinal schistosomiasis (2). Polyps were solitary in 56 children (56%) and ranged from 2 to 5 in 34 (34%) and >5 in 10 (10%). Polyps were confined to the rectum in 68 children, were rectosigmoid in 20, in the descending colon in 8, and splenic flexure in 4. Polyps were juvenile in 84 children (84%), inflammatory in 10 (10%) and hyperplastic, schistosomal or adenomatous in 2 each (6%). Colonoscopic polypectomy was successful and arrested the bleeding in all cases. Conclusion: In Egyptian children, colorectal polyps are relatively common and an easily treatable cause of fresh rectal bleeding. They should be high on the list of differential diagnoses.

Commentary on: The optimal Dose of Ribavirin for Chronic Hepatitis C: From Literature Evidence to Clinical Practice.

Dear Editor, We enjoyed reading the excellent article by Abenavoli and colleagues on the clinical role of Ribavirin (RBV), and particularly the selection and maintenance of the optimal RBV dosing strategy that are required to achieve sustained viral suppression in patients with chronic hepatitis C (CHC) infection. They concluded that contemporary therapy for CHC infection is to deliver doses of both RBV and pegylated interferon-alpha (PEG-IFN) that confer optimal antiviral efficacy for a sufficient time to minimize viral relapse. At the same time, it is important to minimize the impact of side effects that might erode the effectiveness of therapy due to dose reductions below the level of therapeutic efficacy, or because the patient is unable to complete an optimal treatment course (1). The early diagnosis and treatment of CHC infection is still a great worldwide healthcare problem. The prevalence of CHC ranges from 0.1% to 6% in different countries. There are an estimated five million chronic hepatitis C virus (HCV) carriers in Western Europe and four million in the United States (2). The incidence of new symptomatic infection has been estimated to be 1-3 cases per1,000,000 annually, with the actual incidence of new infections clearly being much higher, because the majority of cases are asymptomatic (3). A milestone in CHC therapy was the introduction of the guanosine-analogue RBV which has a broad antiviral spectrum, not yet fully elucidated. RBV can cause a decrease in alanine aminotransferase (ALT) levels, but it has a few effects on the HCV RNA levels. RBV is known as an immunomodulator, inhibiting the viral RNA-polymerase, balancing T-helper (Th) 1 and 2 cell responses, and acting by direct cytoprotection (3). We know also from the data of Weber et al. that RBV acts via the signal transduction pathway like other cytostatic agents (4). Over the past decade, significant improvements have been made in the treatment of CHC, especially with the introduction of combined therapy using both interferon and RBV. The optimal dose and duration of treatment is still a matter of debate and importantly the efficacy of this combined treatment varies with the viral genotype responsible for infection. In general, patients infected with HCV genotypes 2 or 3 more readily achieve a sustained viral response (SVR) than those infected with genotype 1. The introduction of the pegylated version of interferon in the past decade has produced better clinical outcomes in patients infected with viral genotype 1. However, the published literature shows no significant improvement in clinical outcomes in patients infected with genotypes 2 or 3 when they are treated with PEG-IFN as opposed to the non-pegylated, when both were given in combination with RBV (5). Conversely, Zeuzem et al. (6) compared the SVR to treatment with PEG-IFN alpha-2b plus RBV for 24 weeks and found a lower rate of response in genotype 3 than in genotype 2 patients: in this multicentre study, the lower SVR in patients with genotype 3 was attributed to the high levels of steatosis in those patients. In the study by Bressler et al., (7) steatosis was not an independent negative predictor of response to CHC treatment, whereas in other studies, the presence of steatosis was negatively associated with SVR in patients with genotype 1 (8-10). Based on the results by Abenavoli et al. (1), weight-based doses of RBV are advantageous for genotype 1-infected patients, but its success in genotype 2- and 3-infected patients is unknown, particularly for shorter treatment durations. Typically, patients are treated by subcutaneous injection of IFN three times per week in conjunction with a daily oral dose of RBV (15mg/kg/day) for 24 to 48 wk. The therapeutic efficacy is typically measured by the following end points: [1] an SVR defined as no detectable levels of the viral RNA in serum at least 24 wk after the end of treatment; [2] a decrease in ALT to within the normal reference range; and [3] signs of histological improvement as demonstrated typically by a paired liver biopsy performed prior to the initiation of therapy and at 24 wk after the end of therapy. Correlations between serum virus levels, serum ALT levels, and liver pathology, while generally acceptable (11, 12), and have not been definitly established. The primary measure of current therapy virtually shows no detectable levels of HCV in serum at least 24 wk following the end of therapy, defined as the SVR. The SVR correlates well in clinical practice with patient recovery and wellbeing (5). The efficacy of the combination therapy with PEG-IFN-α-2b and RBV in children with HCV infection is comparable to and even higher than that reported in adults. This possibly better viral response in children may be associated with shorter duration of HCV infection, lower frequency of liver fibrosis, and iron overload, lower rate of risky behavior (intravenous drug usage and/or alcohol consumption), and lesser co-morbidities (13-15). Treatment with PEG-IFN-α-2b and RBV is associated with several, and sometimes severe, adverse effects, which may affect the treatment efficacy and the patient’s adherence to the treatment regimen. Side effects of such a combination therapy mainly include fever, headache, fatigue, flu-like syndrome, and hematological disorders such as leucopenia, thrombocytopenia, and anemia. Depression, weight loss, thyroiditis, and other autoimmune diseases such as decreasing in height growth, especially in children, have also been reported to be the side effects of the combination therapy (15, 16). In conclusion, successful antiviral treatment has important results as it reduces the number of infected patients, diminishing the spread of the pathogen, inhibiting hepatitis C progression to cirrhosis and perhaps lowering the risk of hepatocellular carcinoma (3). The combination therapy, RBV (more anti-inflammatory, immunomodulant, immunosuppressive) plus PEG-INF (more antiviral), is the standard of care for patients with CHC and/or extrahepatic manifestations of HCV. We still need more effective antiviral modalities with multiple drug combinations for the treatment of CHC. RBV was the first milestone along this road of multiple therapies and to date it is cornerstone of this therapy.

Sustained Viral Response and Hematological Adverse Events During Chronic Hepatitis C Infection Treatment

Dear Editor, Hepatitis C virus (HCV), as a causative agent of chronic liver disease, has infected approximately 175 million people (almost 3%) of the worlds population; and 3 to 4 million new cases are added to this figure annually [1]. Chronic HCV infection may progress to severe outcomes in the form of cirrhosis and hepatocellular carcinoma (HCC) [2]. Currently, there is no effective HCV vaccine on the horizon due to a lack of a susceptible small animal model, an absence of neutralizing antibodies, and a high degree of viral genomic diversity and mutagenicity; therefore, successful treatment of HCV infection is very much needed. A few years ago, the standard of care (SOC) for chronic HCV infection consisted of subcutaneous injection of conventional Interferon (IFN)-α-2, 3 times per week, plus an oral, daily dose of Ribavirin (RBV) for 24 to 48 weeks [2][3]. This therapy is not ideal because of a very low sustained virologic response [(SVR) i.e., HCV RNA undetectable 6 months after the end of treatment]. The current SOC consists of pegylated INF-α-2 once a week plus daily RBV for 24 to 72 weeks [4]. This treatment aims to achieve a high SVR [5]; however, different people respond differently to this SOC regimen depending on many factors, particularly the age, sex, and ethnicity of the patient; the duration of infection; adiposity; the degree of aminotransferase elevation; HCV genotype; pretreatment viral load; and single nucleotide polymorphisms of interleukin-28B gene [6]. Recently, oral protease inhibitors ( e.g., telaprevir or boceprevir) have been added as direct-acting antivirals to the SOC treatment as a triple therapy, particularly in patients with HCV genotype 1 [7]. We were interested in Pawlowska et al.s study, which examined correlations between the hematological adverse events and the SVR in children undergoing therapy for chronic HCV infection [8]. Specifically, Pawlowska et al. assessed the interdependence of the SVR and the hematological characteristics (leukocyte count, platelet count, and hemoglobin levels) in patients with chronic HCV infection during treatment with IFN and RBV. They divided their sample of children into two groups: patients in Group I were treated with conventional IFN-α-2b plus RBV, and patients in Group II were treated with pegylated IFN-α-2b plus RBV. They concluded that mild decreases in hemoglobin levels, leukocyte counts, and platelet counts during treatment with IFN and RBV in children with chronic HCV infection may be factors associated with SVR induction. Hemoglobin levels decreased significantly in patients who achieved SVR compared to the nonresponders in both groups. In a similar study by Sievert et al. [9] the virologic responses were also higher in anemic patients than in patients who did not develop anemia. After 12 weeks of therapy, the leukocyte and platelet counts were significantly lower in children treated with pegylated IFN-α-2b plus RBV than in those treated with conventional IFN plus RBV [8]. The hematological toxicity that occurs during therapy can result in modifications in dosage or even, in the worst-case scenario, withdrawing INF therapy, which decreases the chances of successful therapy and increases the risk of impaired liver function with cirrhosis and HCC as potential consequences [10]. Two studies have suggested that pegylated INF therapy combined with Danazol could be used to effectively treat patients suffering from HCV-related thrombocytopenia; this combined therapy avoids temporarily reducing or definitively stopping pegylated INF treatment and increases platelet levels [10][11]. The literature has clearly established that the rate of SVR with pegylated INF and RBV is comparatively higher in patients with genotypes 2 and 3 (80%) than in patients with genotypes 1 or 4 (40-50%) [4] . Despite achieving a higher SVR rate, one of the drawbacks of pegylated INF is that it is least 25 times more expensive than conventional interferon, making it unaffordable for many poor people in developing countries [5]. Suwantarat et al. found that chronic HCV-infected patients with SVR had significantly lower white blood cell and platelet counts at the end of treatment compared to those without SVR. These findings suggest that patients who develop leucopenia or thrombocytopenia during interferon treatment respond well to the therapy, and these side effects, if not severe, may not be reasons to withhold or reduce the dose of the treatment. They hypothesized that the greater cytopenia might be an indication of greater tumor necrosis factor activity in a specific treatment recipient, which translates into a higher SVR [12].

Noninvasive methods to evaluate liver fibrosis in chronic HCV infection.

Sirli et al.s (1) effort to compare several noninvasive methods of fibrosis assessment in chronic hepatitis C virus (HCV) infection is commendable. Their study evaluated several simple serological tests for the prediction of fibrosis in chronic HCV infection: number of platelets, the aspartate aminotransferase–platelet ratio index (APRI test), the Forns score, the Lok score, and the FIB-4 score. They also compared these tests to liver stiffness measurement (LSM) by transient elastography (TE) and to the current “gold standard”: liver biopsy (LB). They concluded that LSM was the best method for predicting cirrhosis, but all the evaluated tests had excellent predictive value (1). We have to keep in mind that LSM failure can occur in 2%-10% of patients, and this is generally related to obesity, especially with the use of the M probe. For almost all causes of chronic liver disease, assessment of fibrosis is important in estimating the prognosis of and determining the surveillance strategy for liver cancer. In addition, for chronic viral hepatitis, the degree of liver fibrosis is one important parameter for decisions of antiviral therapy. LB is still the standard and most commonly used procedure in the assessment of liver fibrosis. However, it is an invasive method associated with patient discomfort and in rare cases with serious complications. LBs are generally not performed in HCV patients with bleeding disorders because of increased bleeding risk and high costs. Antiviral treatment is only effective in 50% of these patients and is often accompanied by serious side effects. Consequently, careful selection of patients for treatment is warranted, and. assessment of liver fibrosis and cirrhosis noninvasively using LSM is an adequate alternative to LB (2). The importance of using a combination of noninvasive tests for proper assessment of fibrosis in HCV patients has always been stressed. Recently, a series of algorithms based on sequential combination of noninvasive serum markers showed 93%-95% accuracy in the detection or exclusion of significant liver fibrosis and a reduction of 50% of liver biopsies in this subset of patients with HCV infection (3). Par A and Par G concluded that both APRI and LSM results correlated with the METAVIR score, but LSM identified fibrosis better than APRI (4). Likewise, Corradi and colleagues showed that LSM provides good accuracy in identifying patients with significant fibrosis and performs better than noninvasive indexes (5). Similarly, Sirli et al. found that LSM by means of TE seems to be more sensitive than other noninvasive tests, Archive of SID