Marek Woynarowski

Endoscopic ligation of esophageal varices for prophylaxis of first bleeding in children and adolescents with portal hypertension: preliminary results of a prospective study

BACKGROUND/PURPOSE Endoscopic variceal ligation (EVL) is effective in controlling rebleeding from esophageal varices in children, but there is no data on the use of EVL to prevent initial bleeding. The objective of this study was to prospectively evaluate the efficacy of EVL in preventing the first hemorrhage from esophageal varices in children. METHODS Thirty-seven children with portal hypertension (22 liver cirrhosis, 15 portal vein thrombosis), aged 4 to 17 years (M = 9.5 +/- 4.4 years) were included in the study. The criteria for inclusion were (1) no previous variceal bleeding; (2) the presence of esophageal varices classified grade II or more, and (3) their enlargement by at least I grade after 6 months of observation without endoscopic treatment or appearance of endoscopic signs of high bleeding risk. A Multi-Band Ligator was used, and 2 to 6 bands were fixed under general anesthesia during one procedure depending on the number and size of varices. Follow-up examinations were performed every 3 months, repeating the procedure if necessary. In total, 75 procedures of EVL were performed, from one to 5 in each patient RESULTS Four patients underwent liver transplantation before eradication of varices. Two others were excluded from the observation because of lack of compliance to the protocol. Of the remaining 31 patients, eradication of varices was achieved in 28 children (90.3%) after 2.0 EVL sessions performed at 3-month intervals. The average time of follow-up after cessation of treatment is 16 months. No bleeding from varices occurred in any child during or after treatment. There were no differences in results between children with liver cirrhosis and portal vein thrombosis. Development of hypertensive gastropathy was observed in 2 children with one episode of bleeding. Recurrence of varices without bleeding occurred in 3 children after 12, 13, and 28 months from eradication. CONCLUSIONS The study results confirmed that endoscopic variceal ligation is a safe and highly effective procedure in children with portal hypertension, regardless of its etiology. Eradication of esophageal varices was followed by 16 months free of bleeding. Prolonged observation is mandatory to conclude if preventive EVL influences the natural history of disease and diminishes the risk of first bleeding onset.

The impact of infliximab induction therapy on mucosal healing and clinical remission in Polish pediatric patients with moderate-to-severe Crohn's disease.

Objective To assess the clinical efficacy and the impact of infliximab (IFX) induction therapy on mucosal healing in Polish children with Crohn’s disease (CD). Methods A total of 66 children (29 boys and 37 girls) aged 14.06±3.59 years with CD diagnosed at the mean age of 8.4±7.3 years were included in the study. Patients received IFX (5 mg/kg) in three repeated infusions at 0, 2, and 6 weeks. The clinical activity of the disease was assessed using the Pediatric Crohn’s Disease Activity Index (PCDAI) and the endoscopic activity was scored using the Simple Endoscopic Score for Crohn’s disease at baseline and at week 10. Results Twenty-two (33%) of the studied patients reached clinical remission (PCDAI⩽10), 26 (39%) showed a clinical response (PCDAI between 15 and 30), and 18 (28%) did not respond to the therapy. When comparing data at baseline and at week 10, significant decreases were observed in the median PCDAI, C-reactive protein, and platelet count. In addition, a significant increase in BMI was noted. A significant decrease in the Simple Endoscopic Score for CD was observed between the initial and the control colonoscopies. Fifteen out of 66 patients (22.7%) had score 0 in the control endoscopy at week 10. No adverse events leading to therapy termination were observed. Conclusion Biological therapy with IFX enables mucosal healing in pediatric patients with CD. Induction therapy with infliximab was found to be clinically effective in 72% of Polish pediatric patients with CD and induced a remission in 33% of them. Induction therapy with infliximab helps to increase BMI.

The IgG subclass profile of anti-HBs response in vaccinated children and children seroconverted after natural infection.

The IgG subclass profiles of anti-HBs antibodies were investigated in 30 children who had recovered from acute hepatitis B and 40 children vaccinated against hepatitis B virus (HBV) with Engerix B. After natural seroconversion the mean geometric value of anti-HBs titres was ca 41-fold lower than at the peak of response in vaccinees, and specific antibodies were highly restricted to IgG1 subclass followed by IgG3 with only a minor contribution of IgG2 and IgG4. Conversely, in children immunized with recombinant HBsAg, IgG1 and IgG3 dominated after two doses of vaccine and 1 month after the third injection but the response was less selective and more variable. One year after vaccination IgG4 anti-HBs antibodies became the second dominating isotype. Significant statistical differences in the profiles of IgG anti-HBs were observed when the age and maturity of humoral response were considered. While children vaccinated below 5 years of age responded mainly with IgG1 and IgG3 subclasses, older children (> 5 years) showed a high individual variability in the specific profiles with a high contribution of IgG4. We concluded that vaccination at a younger age leads to the production of antibody subclasses which are more effective for virus neutralization.

The value of quantitative measurement of HBeAg and HBsAg before interferon-α treatment of chronic hepatitis B in children

Serum concentrations of HBsAg, HBeAg and hepatitis B virus DNA were measured quantitatively before interferon treatment in 23 children (17 boys, 6 girls) suffering from chronic hepatitis B, and correlated to the outcome of the treatment. Five children remained HBsAg- and HBeAg-positive throughout the treatment and 6 months after the end of the treatment (non-responders), 12 children eliminated HBeAg but not HBsAg (partial responders) and six eliminated HBeAg and HBsAg (complete responders). The five non-responders had significantly higher initial HBsAg and HBeAg concentrations and significantly lower alanine aminotransferase levels than the partial or complete responders. The six complete responders had significantly lower HBsAg concentrations than the partial or non-responders, and seemed to be younger. No significant difference in HBV DNA levels was found in the three response groups. These data suggest that quantitative assays of HBsAg and HBeAg are particularly useful in selecting patients with chronic hepatitis B for interferon therapy.

Essential fatty acid depletion in children with inflammatory bowel disease

Objective Children with inflammatory bowel disease (IBD) suffer from malabsorption and malnutrition and therefore may be at risk of developing polyunsaturated fatty acid (PUFA) deficiency. The aim of this study was to investigate PUFA status in children with IBD and the possible relationship to disease activity and nutritional status. Material and methods We assessed the fatty acid composition of plasma phospholipids (%wt/wt) of 21 children aged 5.5–18 years with IBD (ulcerative colitis, 15; Crohns disease, 6) with mild or moderate disease activity. The clinical symptoms and biochemical indices of disease activity and nutritional status (lean and fat body mass, Hb, albumin serum conc.) were also determined. Results The patients had lower phospholipid PUFAs than 13 healthy, aged-matched controls (25.8±5.2 versus 34.2±5.7, M±SD, p<0.001), mainly due to lower values of linoleic acid (18:2n−6, 14.0±3.8 versus 18.3±4.3, p<0.01) and its major metabolite arachidonic acid (20:4n−6, 5.3±2.0 versus 9.3±1.9, p<0.0001). There were also higher values of α-linolenic acid (18:3n−3, 0.3±0.4 versus 0.2±0.1, p<0.01) while the long-chain n−3 PUFA-eicosapentaenoic and docosahexaenoic acids were normal. Total n−6 PUFA correlated inversely to erythrocyte sedimentation rate (p<0.01), seromucoid (p<0.05) and positively to Hb concentration (p<0.01). Conclusions Children with inflammatory bowel disease have a high risk of n−6 PUFA depletion, which is related to disease activity.

IgG Subclass Distribution of Hepatitis B Surface Antigen Antibodies Induced in Children with Chronic Hepatitis B Infection after Interferon-α Therapy

The IgG subclass distribution of antibody to hepatitis B surface antigen (anti-HBs) was investigated in 19 children with chronic active hepatitis B infection who showed a complete serological seroconversion after interferon-alpha therapy. Determinations were done 6 and 12 months after treatment. Our results showed no selectivity in anti-HBs synthesis among IgG subclasses. All 4 IgG isotypes were involved in the response, with similar percentage contributions, on average, of IgG1 (35%), IgG3 (27%), and IgG4 (28%), followed by IgG2 (10%). IgG4 became the second most dominant isotype at the end of observation. These results are in contrast to those found after natural seroconversion, in which anti-HBs was highly restricted to neutralizing IgG1 and IgG3, with only a minor contribution from IgG2 and IgG4. It is postulated that analysis of the specific profiles of IgG subclasses may be of value for the estimation of the therapeutic efficacy of recombinant interferon-alpha used and may be helpful in choosing more-effective treatment.

High- versus low-volume polyethylene glycol plus laxative versus sennosides for colonoscopy preparation in children.

Objective: Many protocols of bowel preparation are available for use in children; however, none of them is commonly accepted. The aim of the study was to evaluate the efficacy and acceptability of high-volume polyethylene glycol (PEG) versus low-volume PEG combined with bisacodyl (BPEG) versus sennosides for colonoscopy preparation in children. Methods: Participants ages 10 to 18 years were randomly assigned to receive either PEG 60 or PEG 30 mL kg−1 day−1 plus oral bisacodyl 10 to 15 mg/day or sennosides 2 mg kg−1 day−1 for 2 days. A blinded assessment of bowel cleansing was made by the endoscopist according to the Aronchick and Ottawa scales. Patient acceptability was evaluated with the visual-analog scale. Analysis was done on an available case analysis basis. Results: Of 240 patients enrolled in the study 234 patients were available for analysis of the efficacy of colon cleansing. There were no significant differences found among the 3 groups for the proportions of participants with excellent/good (PEG: 35/79, BPEG: 26/79, sennosides 25/76) and poor/inadequate (PEG: 20/79, BPEG: 28/79, sennosides 28/76) bowel preparation evaluated with the Aronchick scale and for the mean Ottawa total score (PEG: 5.47 ± 3.63, BPEG: 6.22 ± 3.3, sennosides: 6.18 ± 3.53). Acceptability of bowel cleansing protocol was similar in all of the groups (P = 0.8). Conclusions: All 3 cleansing methods showed similar efficacy and tolerability; however, none of them was satisfactory.

Hepatitis B virus genotypes in children with chronic hepatitis B in Poland.

Objectives To analyse the distribution of HBV genotypes in Polish children with chronic hepatitis B, and to assess the relation between the viral genotype and the severity of liver damage. Methods Serum samples from children with chronic hepatitis B were used for biochemical and serological testing, and for determination of HBV genotypes by a nested-multiplex-polymerase chain reaction. Liver biopsies were obtained for histological assessment, which was performed according to the Batts and Ludwig scoring system of chronic hepatitis. Results Of 78 children with chronic hepatitis B, 74 had an identifiable HBV genotype: 86.5% were infected with genotype A, and 13.5% were carriers of genotype D. The frequency of HBeAg clearance and the levels of alanine aminotransferase and serum aspartate transaminase were comparable in both genotype groups. There was no correlation between the HBV genotype and either activity of liver inflammation or liver fibrosis. Conclusions This study shows that the distribution of HBV genotypes in Polish children with chronic HBV infection reflects the general prevalence of HBV genotypes in Europe. The course of chronic hepatitis B in children is not significantly influenced by viral genotypes A or D.

Efficacy and Safety of Lactobacillus plantarum DSM 9843 (LP299V) in the Prevention of Antibiotic-Associated Gastrointestinal Symptoms in Children—Randomized, Double-Blind, Placebo-Controlled Study

Objectives To determine if Lactobacillus plantarum DSM9843 (LP299V) reduces the frequency of antibiotic‐associated loose/watery stools and gastrointestinal symptoms, and can be administered safely to children who are prescribed antibiotics. Study design We performed a prospective, double‐blind, randomized, placebo‐controlled, multicenter, parallel‐group study in children receiving outpatient antibiotic therapy in primary healthcare settings. The children were given LP299V/placebo during the antibiotic therapy and for 1 week after the end of treatment. The primary outcome measure was the incidence of at least 1 loose/watery stool (type 6 or 7 according to the Bristol Stool Form Scale). Gastrointestinal symptoms (abdominal pain, abdominal distention, vomiting, and flatulence) were followed up until 1 week after the last intake of the study product. Results A total of 438 children (male: 235, female: 203) aged 1‐11 years (mean ± SD: 5.2 ± 2.7) were randomized to receive LP299V (N = 218) or placebo (N = 220). The incidence of loose/watery stools in the 2 study groups (LP299V and placebo) was similar, 39% vs 44.5% respectively (P = .26) as was the mean number of loose/watery stools (3.9 ± 3.5 vs 4.7 ± 6.3; P = .9). Antibiotic‐associated diarrhea (defined as ≥3 loose/watery stools/24 hours starting from 2 hours after initiation of antibiotic treatment until the end of the study) occurred in 2.8% of the subjects receiving LP299V compared with 4.1% in the placebo arm (P = .4). The number of children with abdominal symptoms did not differ between the groups. Conclusions No beneficial effect of LP299V compared with placebo was observed for the incidence of loose/watery stools, mean number of loose/watery stools, or the incidence of abdominal symptoms. LP299V had a satisfactory safety profile. Trial registration ClinicalTrials.gov: NCT01940913.

Nasogastric tube as protection for recurrent oesophageal stricture: A case report

This report presents the case of an 8.5-year-old boy with Down syndrome after experiencing extensive caustic injury to the oesophagus and stomach resulting from the accidental ingestion of concentrated sulphuric acid. The patient had undergone 32 unsuccessful endoscopic oesophageal stricture dilatations and stenting procedures performed over a period of 15 mo following the accident. Surgical reconstruction of the oesophagus was not possible due to previous gastric and cardiac surgeries for congenital conditions. Before referring the patient for salivary fistula surgery, the patient received a nasogastric tube with perforations located above the upper margin of the oesophageal stenosis for the passage of saliva and fluid. The tube was well tolerated and improved swallowing; however the backflow of gastric contents caused recurrent infections of the respiratory tract. To overcome these problems, we developed a double lumen, varying diameter, perforated tube for protection of the oesophageal closure. This nasogastric tube was found to be safe and decreased the need for hospitalization and further endoscopic procedures. This newly developed tube can thus be considered as a treatment option for patients with recurrent oesophageal stenosis and contraindications for surgical oesophageal reconstruction.