Hassan H. A-Kader

Nonalcoholic fatty liver disease: A comprehensive review of a growing epidemic

Nonalcoholic fatty liver disease (NAFLD) is quickly becoming one of the most prominent causes of liver disease worldwide. The increasing incidence of NAFLD is tied to the obesity epidemic and the subsequent metabolic derangements brought along with it. Current efforts to elucidate the mechanism and causes of the disease have answered some questions, but much remains unknown about NAFLD. The aim of this article is to discuss the current knowledge regarding the pathogenesis of the disease, as well as the current and future diagnostic, preventative, and therapeutic options available to clinicians for the management of NAFLD.

Complications of percutaneous liver biopsy in children

To determine the frequency and nature of complications after liver biopsy and whether risk factors could be identified to predict these complications, the medical records of all patients (age, 1 week to 28 years) who underwent a percutaneous liver biopsy at Childrens Hospital over a 6-year period (1981-1986) were reviewed. Data were collected from 469 (97%) of 483 eligible charts. Twenty-one patients (4.5%) experienced major complications including bile leak (n = 3, 0.6%), prolonged drainage of ascitic fluid (n = 1, 0.2%), pneumothorax (n = 1, 0.2%), bleeding requiring transfusion (n = 13, 2.8%), and death (n = 3, 0.6%). A subgroup of patients (n = 37) with cancer or bone marrow transplantation was found to be at a nearly fivefold greater risk for transfusion than patients with other diagnoses (P = 0.02). All three deaths in previously stable patients occurred in this same high-risk group of patients with cancer or bone marrow transplantation (P less than 0.001). Two deaths resulted from disseminated intravascular coagulation and one from bleeding. Diagnosis, age, number of percutaneous passes, and prebiopsy coagulation studies were not predictive of subsequent complications. It is concluded that bleeding that requires transfusion is the most common liver biopsy complication and that it occurs more frequently in children than previously reported. Children with cancer or those who have undergone bone marrow transplantation are at a greater risk for bleeding and death following percutaneous liver biopsy.

Prevalence of factor V Leiden mutation and other hereditary thrombophilic factors in Egyptian children with portal vein thrombosis: results of a single-center case-control study

No identifiable cause can be found in more than half of the cases of portal vein thrombosis (PVT). Our aim was to assess the prevalence of factor V Leiden mutation and other thrombophilic factors as risk factors in the development of PVT in the pediatric age group. From March 2001 to January 2002, 40 children with PVT were enrolled in the study, in addition to 20 age-matched and sex-matched controls. Protein C, protein S, antithrombin III, and activated protein C resistance (APCR) were assayed. Molecular study of factor II and factor V mutations was carried out. Of the patients, 25 had detectable hereditary thrombophilia (62.5%), 12 had factor V Leiden mutation (30%), 11 had protein C deficiency (27.5%), 6 had factor II mutation (15%), 1 had antithrombin III deficiency (2.5%), and none had protein S deficiency. Five children had concurrence of more than one defect. Factor V Leiden mutation is the most common hereditary thrombophilia associated with PVT and the relative risk of factor V Leiden mutation, as a cause of PVT, was six times more than in controls (odds ratio=6). Concurrence of more than one hereditary thrombophilic factor was seen in 12.5% of our patients. Circumstantial risk factors (neonatal sepsis, umbilical sepsis, umbilical catheterization) were not more significantly prevalent among patients with hereditary thrombophilia than among those with no detectable abnormalities in anticoagulation.

Foreign body ingestion: children like to put objects in their mouth

BackgroundForeign body ingestion is a common problem in the pediatric age group. Infants and young children explore objects by putting them in the mouth.Data sourcesWe reviewed the most recent literatures regarding the incidence, clinical presentation, as well as the most recent advances in the diagnostic and therapeutic modalities of foreign body ingestion in children.ResultsIn 2007 more than 125 000 foreign body ingestions in patients of 19 years old and younger were reported to American Poison Control Centers in the USA. The majority of ingested foreign bodies pass spontaneously.ConclusionsSome foreign bodies can be harmful and require evaluation and intervention. The challenge in management is to distinguish the patients who require intervention from those who can be safely observed. In this review we suggest an algorithm for evaluation and management of children suspected to ingest a radiopaque foreign body.

Nonalcoholic Fatty Liver Disease in Children: A Single Center Experience

BACKGROUND & AIMS Nonalcoholic fatty liver disease (NAFLD) is the most common disorder seen in pediatric hepatology practice. However, little is known about the clinical, biochemical, and histologic features of the disorder. In addition, there have been no reports of the natural history of NAFLD in the pediatric age group. METHODS Therefore, we retrospectively reviewed the charts of children diagnosed with NAFLD in our institution between January 2000 and March 2007. RESULTS One hundred six children (82 male and 24 female) were diagnosed with NAFLD. Mean age at diagnosis was 13.4 years (range, 4-18 years). Liver biopsy was done in all patients. Fibrosis was noticed in 6 of 15 patients with normal liver enzymes. Eighteen children had a follow-up liver biopsy during an average period of 28 months. In 8 patients there was no change in fibrosis. Seven patients had progression of fibrosis, whereas 3 patients had regression or disappearance of fibrosis after losing weight. CONCLUSIONS The entire spectrum of histologic features of NAFLD can be seen in children with normal liver enzymes. Rapid progression might be seen in a large proportion of patients and can happen during a short period of time. Larger studies with long duration follow-up are needed to better understand the pathogenesis and the natural history of the disease in the pediatric age group.

Caustic ingestion in children

Caustic ingestion continues to be a significant problem worldwide especially in developing countries. In 2008 over 200,000 exposures to caustic substances were reported to the National Poison Data System. The presence or absence of symptoms or oral lesions does not predict the existence or severity of lesions. The best predictor of morbidity and mortality is the extent of injury as assessed during initial evaluation. Upper endoscopy remains the mainstay diagnostic modality for the evaluation of patients with caustic ingestion. There is a pressing need for noninvasive diagnostic modalities and effective therapeutic options to evaluate and treat the complications associated with caustic ingestion.

Nonalcoholic fatty liver disease in children living in the obeseogenic society

BackgroundThe problem of obesity in children has grown considerably in recent years in the United States as well as the rest of the world. This has resulted in a marked increase in the prevalence of nonalcoholic liver disease in the pediatric age group. Nonalcoholic fatty liver disease (NAFLD) is currently the most common hepatic disorder seen in pediatric hepatology practice.Data sourcesWe have reviewed the most recent literature regarding the prevalence, pathogenesis as well as the most recent advances in the diagnostic and therapeutic modalities of NAFLD in children.ResultsNAFLD affects a substantial portion of the population including children.ConclusionsThe rising incidence of NAFLD, nonalcoholic steatohepatitis (NASH) and cirrhosis emphasizes the need for effective treatment options. The lack of complete understanding of the pathogenesis of NAFLD still limits our ability to develop novel therapeutic modalities that can target the metabolic derangements implicated in the development of the disorder.

Altered Regulation of Hepatic Efflux Transporters Disrupts Acetaminophen Disposition in Pediatric Nonalcoholic Steatohepatitis

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, representing a spectrum of liver pathologies that include simple hepatic steatosis and the more advanced nonalcoholic steatohepatitis (NASH). The current study was conducted to determine whether pediatric NASH also results in altered disposition of acetaminophen (APAP) and its two primary metabolites, APAP-sulfate and APAP-glucuronide. Pediatric patients with hepatic steatosis (n = 9) or NASH (n = 3) and healthy patients (n = 12) were recruited in a small pilot study design. All patients received a single 1000-mg dose of APAP. Blood and urine samples were collected at 1, 2, and 4 hours postdose, and APAP and APAP metabolites were determined by high-performance liquid chromatography. Moreover, human liver tissues from patients diagnosed with various stages of NAFLD were acquired from the Liver Tissue Cell Distribution System to investigate the regulation of the membrane transporters, multidrug resistance–associated protein 2 and 3 (MRP2 and MRP3, respectively). Patients with the more severe disease (i.e., NASH) had increased serum and urinary levels of APAP-glucuronide along with decreased serum levels of APAP-sulfate. Moreover, an induction of hepatic MRP3 and altered canalicular localization of the biliary efflux transporter, MRP2, describes the likely mechanism for the observed increase in plasma retention of APAP-glucuronide, whereas altered regulation of sulfur activation genes may explain decreased sulfonation activity in NASH. APAP-glucuronide and APAP-sulfate disposition is altered in NASH and is likely due to hepatic membrane transporter dysregulation as well as altered intracellular sulfur activation.

Monoethylglycinexylide formation in assessing pediatric donor liver function.

Lidocaine metabolism to monoethylglycinexylide (MEGX) has been described as a novel method to assess liver function in adult transplant donors and recipients. While this assay appears to offer a number of advantages over existing liver function tests, limited work has been done to evaluate its potential in the pediatric population. This study evaluated MEGX formation in potential pediatric liver donors (n = 35) and a control group of children (n = 16). The mean MEGX formation was significantly higher in pediatric donors than in the control group (156 ± 62 vs 106 ± 33 ng/ml, p < 0.05). No correlation with age, total bilirubin, liver transaminases, or alkaline phosphatase could be made within each group. Significant differences in MEGX levels were noted when each group was compared to its adult counterpart. Both pediatric donors and controls had greater mean MEGX formation than has been reported for adult donors and controls (156 ± 62 vs 127 ± 61 ng/ml, p < 0.05 and 106 ± 33 vs 72 ± 36 ng/ml, p < 0.05, respectively). Drugs that alter lidocaine pharmacokinetics and their potential influence on MEGX formation were evaluated in the pediatric donor group. Donors exposed to hepatic enzyme-inducing drugs had a higher mean MEGX formation (187 ± 60 vs 146 ± 63 ng/ml). No significant differences were noted between donors receiving and not receiving va-sopressors. In conclusion, the significant differences between pediatric and adult MEGX formation should be noted when establishing reference or normal ranges for this diagnostic test. Furthermore, concomitant drug therapy may significantly alter MEGX formation.

Serum intercellular adhesion molecule-I in children with chronic liver disease: Relationship to disease activity

Intercellular adhesion molecule-I (ICAM-I) is a member of the immunoglobulin supergene family. It is expressed on the surface membrane of cells of multiple lineages at sites of inflammation. A soluble form of ICAM (sICAM-I) comprising the five extracellular Ig-like domains of ICAM-I has been detected in human serum and has been found to be increased in a variety of acute and chronic liver disorders. However, little is known about sICAM-I levels in children with chronic liver disease. Therefore, we measured sICAM-I in 23 children with chronic hepatitis, 14 children with cirrhosis, and 10 age- and sex-matched normal children by commercially available ELISA. We also correlated the sICAM-I levels with the histological activity index (HAI) score as determined from liver biopsies. Patients with chronic hepatitis had higher sICAM-I levels compared to controls (723 ± 272 ng/ml vs 282 ± 43 ng/ml, mean ± sd; P < 0.05). sICAM-I levels were also higher in patients with cirrhosis compared to controls (630 ± 218 ng, mean ± sd; P < 0.05). However, there was no significant difference between sICAM levels in patients with chronic hepatitis and cirrhosis. A significant correlation was found between the ICAM-I level and the histological activity index score in patients with chronic hepatitis (r = 0.58; P < 0.001) and in patients with cirrhosis (r = 0.7; P < 0.001). We also found that by using the cutoff level of 346 ng/ml, sICAM-I can be used as a screening test with high specificity (100%) and sensitivity (94%) to differentiate children with chronic liver disease from normal children. We conclude that sICAM is increased in children with chronic hepatitis and cirrhosis compared to controls. The degree of elevation correlates with the HAI score. sICAM may be used as a marker of the disease activity and may provide diagnostic and prognostic information in children with chronic liver disease. However, this needs to be further studied.