Pegylated interferon α/ribavirin therapy enhances bone mineral density in children with chronic genotype 4 HCV infection.

BACKGROUND: The impact of chronic hepatitis C (CHC) on bone mineral density (BMD) has been well studied in adults with a relative paucity of data in children, especially concerning effect of treatment with pegylated interferon (PEG-IFN) plus ribavirin (RV). In the current work, we assessed prospectively changes in BMD in children with CHC before, during, and after treatment. METHODS: Forty-six consecutive children with noncirrhotic genotype 4 CHC were subjected to dual-energy X-ray absorptiometry at baseline, 24 weeks, 48 weeks of therapy and 24 weeks after treatment. BMD, bone mineral content (BMC), and Z score of lumbar spine (L2-L4) were reported. Tanner pubertal stage, viral load, liver function tests, serum calcium, phosphorus, alkaline phosphatase, parathyroid hormone, and liver histopathology were assessed in all included children. RESULTS: Thirty (65.2%) patients had normal BMD, 10 (21.7%) were at risk for low BMD, and 6 (13.1%) had low BMD for chronological age. Patients with low BMD were significantly older (P=0.001), with higher frequency of delayed puberty than other groups (P=0.002). Baseline densitometric parameters (BMD & BMC) were significantly positively correlated with patients' age, weight, height, body mass index and hemoglobin level; while they were insignificantly correlated with basal viral load, histopathology activity index and fibrosis score. Densitometric parameters improved significantly on PEG-IFN plus RV treatment, this improvement was found to be sustainable 24 weeks after therapy. CONCLUSIONS: Low BMD is detectable in a proportion of CHC children. Antiviral therapy leads to a sustainable increase in BMD.

Morphometric assessment of liver fibrosis may enhance early diagnosis of biliary atresia.

BACKGROUND: Neonatal cholestasis syndrome is considered as a major challenge in pediatric practice. This study was undertaken to investigate the value of morphometric assessment of hepatic fibrosis in early diagnosis of biliary atresia. METHODS: We studied liver biopsy specimens from 53 patients with neonatal cholestasis. The patients were assigned to two groups: group 1 (25 patients with biliary atresia) and group 2 (28 patients with non-obstructive cholestasis). Morphometric assessment of fibrosis was performed for all biopsies; in addition, another twelve histological parameters were estimated and scored on a scale of 0 to 4. Biopsies of infants aged 60 days or younger were characterized and analyzed separately. RESULTS: Morphometric value of fibrosis was significantly higher in group 1 than in group 2 (16.8 ± 8.4% vs. 5.9 ± 2.3%, respectively; P<0.001). By multiple regression analysis, bile ductular plugs, morphometric assessment of fibrosis, rosetting, portal tract inflammation and pattern of cholestasis were found to be significant in discriminating the two groups. In infants aged 60 days or younger, a cutoff value for morphometric assessment of fibrosis of 7.5% was the discriminating point between the two groups with a sensitivity of 80% and a specificity of 84%. CONCLUSION: Morphometric assessment of hepatic fibrosis could enhance the value of liver biopsy in early diagnosis of biliary atresia.

Anorectal functional abnormalities in Egyptian children with chronic functional constipation.

BACKGROUND AND STUDY AIMS: Chronic functional constipation represents 95% of the cases of paediatric constipation. Epidemiologic data, pathophysiology and anorectal functional abnormalities vary greatly among different reports across different populations. The aim of this study was to evaluate these data in Egyptian children with chronic functional constipation. PATIENTS AND METHODS: This study included 150 children with chronic functional constipation (101 males, 49 females; mean age 6 ± 3.1 years); a control group of 50 age- and sex-matched healthy children were enrolled for standardisation of the manometry technique. A structured symptom questionnaire and clinical examination including digital rectal examination in addition to anorectal manometry were done for all included children. Defaecation dynamics were assessed in all children 5 years or older using anorectal manometry with integrated electromyogram of the external anal sphincter and the puborectalis muscle. RESULTS: The maximal tolerable volume was significantly higher in the constipated children than in the control group (p=0.03). No significant differences existed between constipated and control children regarding other anorectal manometric parameters. Abnormal defaecation dynamics were detected in 35 out of 95 tested patients (36.8%). CONCLUSION: Increased maximal tolerable volume is the most striking manometric feature in Egyptian children with chronic functional constipation. Abnormal defaecation dynamics were detected in about one-third of the tested patients. Standardisation of the measurement techniques and obtaining normal ranges for anorectal manometric parameters for each laboratory are recommended.

Regression of fibrosis in paediatric autoimmune hepatitis: morphometric assessment of fibrosis versus semiquantiatative methods.

BACKGROUND: Regression of hepatic fibrosis in patients with autoimmune hepatitis (AIH) has been described in response to immunosuppressive therapy. These studies, however, besides being few in number, were conducted on adult populations. Our aim was to assess the regression of hepatic fibrosis, using morphometric assessment of fibrosis versus semi-quantitative methods, in children with AIH who achieved clinical and biochemical remission. Thirteen patients who achieved clinical and biochemical remission were included in the study, out of 62 children with AIH. Repeat biopsy was performed after 6 to 12 months of clinical and biochemical remission. Morphometric assessment of fibrosis was performed and correlated with METAVIR and Ishak semi-quantitative scores. RESULTS: The study group included eight male and five female patients. The median age at presentation was 4 years (range 2 to 12 years). The mean duration of treatment was 22 +/- 7.3 months, and the mean interval between biopsies was 26.2 +/- 6.5 months. Following therapy, there was significant reduction in aspartate aminotransferase, ALT and IgG levels as well as improvement of necroinflammation. The mean fibrosis scores were significantly decreased from 4.5 +/- 1.19 and 2.9 +/- 0.7 before therapy to 2.7 +/- 1.16 and 2 +/- 0.8 after treatment as assessed by Ishak and METAVIR scores, respectively (P = 0.001 and 0.004). The mean morphometric assessment of fibrosis before treatment was 20% +/- 9.7 and following therapy it decreased to 5.6% +/- 3.9 (P = 0.000). CONCLUSION: Significant regression of fibrosis in paediatric AIH could occur with current therapeutic regimens. Morphometric assessment of fibrosis is more sensitive than semi-quantitative methods to identify changes in fibrosis.

Pepsin assay: a marker for reflux in pediatric glue ear.

OBJECTIVE: To evaluate if analysis of pepsin/pepsinogen in middle ear effusions can be considered a diagnostic marker for laryngopharyngeal reflux (LPR) in children with otitis media with effusion (OME). MATERIAL AND METHODS: Ambulatory 24-hour dual-probe pH monitoring was carried out on 31 children with OME. Middle ear effusions were collected from 17 children during myringotomy. Total pepsin/pepsinogen concentrations in effusions were measured by ELISA using antipepsin antibody. RESULTS: Dual-probe pH monitoring showed that 22/31 (71%) of the studied children had significant LPR. The concentrations of pepsin/pepsinogen in middle ear effusions, ranged from 0.085 to 5.02 microg/ml, were found to be up to 4.5 to 231.44 times higher than the serum levels. There was a significant positive correlation between the level of pepsin/pepsinogen assayed in the effusions of the 17 children and the number of pharyngeal reflux episodes measured by pH monitoring. CONCLUSIONS: Control of LPR may be an essential component in the successful management of OME in pediatric patients. Pepsin/pepsinogen analysis in effusions of children, using ELISA, can be considered a reliable marker for assessment of reflux in children with OME.

Immunohistochemical identification of HCV target antigen in paraffin-embedded liver tissue: reproducibility and staining patterns.

BACKGROUND: Immunohistochemical staining has been applied successfully to detect hepatitis C virus (HCV) antigen in fresh frozen tissue. In paraffin-embedded tissues, however, minimal trials with conflicting results have been reported. AIMS: The present study is a trial to evaluate the identification of HCV antigen in paraffin-embedded liver biopsies using the anti-HCV monoclonal antibody (MAb) TORDJI-22. METHODS: We applied immunohistochemical staining for HCV in 56 paraffin-embedded liver biopsy specimens, 46 from patients seropositive for HCV-RNA and 10 control liver biopsy specimens. The TORDJI-22 MAb was applied in dilution 1:40, with overnight incubation. RESULTS: Reproducible staining patterns of HCV antigen in tissues were identified among the majority (42/46-91%) of HCV RNA seropositive cases. The staining pattern was cytoplasmic of hepatocytes, with occasional nuclear hue. It is mainly coarse granular with microvesicular pattern. Three staining patterns were identified: A, diffuse or membranous; B, patchy; and C, occasional paranuclear. None of the control samples showed a similar staining pattern. CONCLUSION: Immunohistochemical identification of HCV antigen is easy to apply in paraffin-embedded liver biopsy specimens when the optimal detection techniques are applied. The staining pattern is reproducible, being mainly coarse granular cytoplasmic. Cross reactivity with hepatitis B virus antigens was not detected.