Safety, tolerability and efficacy of a novel self-use biodegradable device for management of obesity.

OBJECTIVE: Obesity is a major public health issue with significant impact on quality of life, morbidity and mortality rates. It is estimated that if the current trends continue, 18% of men and 21% of women worldwide will be obese by 2025. All the current therapies are not optimal due to limited efficacy or safety; thus, there is a need for additional devices for the treatment of obesity. This study aimed to examine the safety, tolerability, and efficacy of a biodegradable encapsulated Epitomee device for weight loss. The technology is based on absorbent pharmaceuticals polymers and bonding materials that self-expand in the stomach to create a pH-sensitive super absorbent gel structure for weight loss. METHODS: A prospective, 12-week twice daily use of the encapsulated device in patients with body mass index of 27-40 kg m-2. Efficacy endpoints were the percent total body weight loss (%TBWL), proportion of participants with 5% TBWL and changes in cardio-metabolic markers. Safety analysis included evaluation of adverse events, laboratory and endoscopic findings. RESULTS: Overall, 52 patients completed the study. TBWL per intension-to-treat analysis was 3.68 ± 3.07% (3.23 ± 2.69 kg) and 4.52 ± 2.97% (3.95 ± 2.57 kg) per protocol. No device serious adverse effects reported. The most common adverse events were headache (18.1%), viral infection (11.5%), abdominal discomfort (10.1%), bloating (7.9%), nausea and constipation (5% each) and flatulence (4.3%). Endoscopy in 26 patients revealed mild, asymptomatic gastric/duodenal erythema without erosions in five patients. CONCLUSIONS: Twelve weeks of Epitomee capsules treatment combined with lifestyle counselling resulted in 3.68-4.52% of TBWL. With continued research, the Epitomee capsules have considerable potential to become a non-invasive, safe and effective treatment option for weight loss.

Reduced GLP-1R expression in gastric glands of patients with type 2 diabetes mellitus.

BACKGROUND: The incretin effect is reduced in type 2 diabetes mellitus (T2DM) patients. Whether the impaired function of the enteropancreatic axis in these patients is due to defective GLP-1 receptor (GLP-1R) expression in extrapancreatic target organs is not known. AIMS AND METHODS: To compare the GLP-1R expression and distribution in gastric mucosa biopsies of patients with (n =22) and without (n =22) T2DM referred for routine esophagogastroduodenoscopies. GLP-1R mRNA levels were estimated by real-time PCR. The intensity of GLP-1R immunostaining, frequency, and types of glandular cells bearing GLP-1R and their glandular distribution in different stomach mucosa regions were evaluated by immunohistochemical morphological semiquantitative and quantitative analysis. RESULTS: Mean mRNA GLP-1R levels were significantly reduced in patients with T2DM compared with nondiabetic patients (P < .02). Immunohistochemical analysis revealed that the reduced GLP-1R expression in T2DM patients was due to a decreased intensity of immunostaining (P < .01). The number of glandular GLP-1R-bearing cells in both body and antrum mucosa was decreased in T2DM patients. Most notably, the frequency of GLP-1R immunoreactive acid-secreting parietal cells was reduced in the neck area of the gastric principal glands of T2DM patients (P < .01). No correlation was found between the reduced GLP-1R expression and clinical parameters including body mass index, age, glycosylated hemoglobin, and disease duration. CONCLUSION: This is the first evidence of reduced GLP-1R expression in gastric glands of T2DM patients. These data demonstrate that the defective function of the incretin axis in T2DM may also result from decreased GLP-1R expression in its extrapancreatic target organs.

Comparison of central and intraesophageal factors between gastroesophageal reflux disease (GERD) patients and those with GERD-related noncardiac chest pain.

Gastroesophageal reflux disease (GERD) causes a wide range of symptoms. Some patients present with typical symptoms such as heartburn and regurgitation and others with atypical symptoms such as chest pain. The mechanism responsible for the varying clinical presentation of GERD is still not fully elucidated. The aim of this study was to prospectively evaluate differences in central and local intraesophageal factors between patients with typical GERD symptoms and those with noncardiac chest pain (NCCP). Patients presenting with typical and atypical symptoms suspicious of GERD underwent upper endoscopy and 24-hour pH monitoring with four sensors, each positioned at a different esophageal level. All patients completed GERD symptom, Hospital Anxiety and Depression Scale, and Symptom Stress Rating questionnaires. From January 2006 to December 2009, 50 patients were recruited, 29 with typical symptoms, and 21 with NCCP. Patients with proven GERD and NCCP had higher proximal extension of acid during reflux episodes than patients with typical symptoms. They were found to be older, had a shorter history of symptom onset, worse anxiety scores, and more endoscopic findings compatible with gastritis. Proximal extension of acid during the reflux episodes in patients with GERD presenting with NCCP may play a role in symptom generation.

Carriage rate of carbapenem-resistant Klebsiella pneumoniae in hospitalised patients during a national outbreak.

During a national outbreak of carbapenem-resistant Klebsiella pneumoniae (CRKP) in Israel, we conducted a point prevalence survey to determine the extent of asymptomatic carriage. Subsequently, a retrospective case-control study was done, comparing carriers of CRKP with non-carriers, in order to detect risk factors for carriage. Oral, perianal and rectal swabs were obtained from all hospitalised eligible and consenting patients. Selective media for carbapenem-resistant Gram-negative bacteria were used and pulsed-field gel electrophoresis (PFGE) helped to determine clonal source. Culture was obtained from 298 patients. Sixteen (5.4%) were carriers of CRKP, with a higher carriage rate in medical and surgical wards. Only 18% of carriers were treated with any carbapenem prior to the survey. Five of the 16 carriers had a positive clinical specimen for CRKP, hence a clinical infection versus asymptomatic carriage ratio of 1:3. The rectum was the most sensitive site sampled, detecting 15/16 carriers, and the overall sensitivity of the method was 94% with a negative predictive value of 99.6%. In a multivariate analysis of risk factors for CRKP carriage, three variables were significantly related to carriage state: diaper use, longer duration of hospital stay and vancomycin use. PFGE demonstrated that all 16 isolates were identical, confirming clonal origin. A point prevalence survey performed at a single medical centre during an outbreak of CRKP demonstrated a carriage rate of 5.4%. The clonal origin of these isolates suggests that strict adherence to isolation procedure may contain this outbreak.

Methotrexate treatment in pediatric Crohn disease patients intolerant or resistant to purine analogues.

BACKGROUND: Immunomodulatory drugs play a major role in maintaining remission and steroid sparing in children with Crohn disease. Although thiopurine agents are commonly used, unresponsiveness or intolerance to these drugs is common. The efficacy of methotrexate in maintenance of remission has been shown in adult Crohn disease; however, pediatric data are limited. Our goal was to evaluate the efficacy and safety of methotrexate in induction and maintenance of clinical remission in children with active Crohn disease who failed thiopurine treatment. PATIENTS AND METHODS: In a retrospective multicenter study, efficacy of methotrexate in inducing and maintaining remission or response was assessed by Harvey-Bradshaw activity index, paediatric Crohn disease activity index and steroid use, in 25 children with Crohn disease, refractory or intolerant to thiopurine analogues. RESULTS: Crohn disease was diagnosed at a mean age of 11.1 +/- 3.1 years and methotrexate was initiated at age 14.5 +/- 3.1 years. The median methotrexate dose was 12.5 mg/m2. Remission was achieved in 16 patients (64%), and response in 6 patients (24%). Out of 18 patients treated for longer than 6 months, 83% were in remission or response after 12 months of treatment. The mean duration of remission and response was 10.8 +/- 8.8 months. Steroid withdrawal was possible in 12/16 patients (75%) receiving steroids at methotrexate introduction. Adverse effects were observed in 6 patients (24%) including nausea and vomiting in 3, elevation of liver enzymes in 2 and pancreatitis in 1 patient. CONCLUSIONS: Methotrexate is beneficial in maintaining remission and steroid-sparing treatment in children with Crohn disease following failure of thiopurine therapy.

Evidence for aberrant regulation of MAP kinase signal transduction pathway in peripheral blood mononuclear cells in patients with active celiac disease.

BACKGROUND: Aberrant signaling via the p21/mitogen-activated proteins (MAP) kinase pathway has been described in lymphocytes of patients with various autoimmune diseases. There is little published data about the intracellular mediators and signals that regulate expression and activity of transcription factors and their effect on celiac disease induction and progression. AIM: To investigate the possible involvement of MAP kinase pathway in peripheral blood mononuclear cells (PBMC) in celiac disease and its correlation with disease activity. METHODS: Expression of the total and activated forms of two MAP kinases [extracellular response kinase (ERK) and c-Jun amino terminal kinase (JNK)] were studied by Western blots in PBMC of 17 untreated and 19 treated celiac patients, and 17 controls. Seven of these untreated celiac patients were studies before and after 6 months of gluten-free diet. RESULTS: Phosphorylated ERK of active celiac disease patients was significantly lower compared with controls (P < 0.01) and was increased towards normal after 6 month of gluten-free diet (P < 0.01). Phosphorylated JNK was increased significantly in the untreated celiac group (P < 0.01) and normalized towards the control level after 6 months of gluten-free diet (P < 0.04). CONCLUSIONS: Aberrant MAP-kinase pathway activity is associated with active celiac disease (CD). Further studies should examine the potential role of this aberration in pathogenesis of CD.

Antiplatelet therapy and the risk of bleeding induced by gastrointestinal endoscopic procedures. A systematic review of the literature and recommendations.

Antiplatelet drugs may increase the risk of bleeding induced by gastrointestinal endoscopic procedures. The antiplatelet effect of cyclooxygenase-1 inhibitors lasts less than 4 h. Skin and colonic bleeding times are prolonged for 3 and 5 days after aspirin and ticlopidine withdrawal respectively. Major bleeding from endoscopic biopsies is extremely rare. In the four recent largest series, the general incidence of polypectomy-induced major bleeding was 0.11-0.42%. In more than half of the cases the bleeding was delayed, usually up to 2 weeks after the endoscopy. Although three retrospective studies suggested that aspirin does not increase the risk of polypectomy-induced bleeding, the power of these studies is limited. Similarly, it is difficult to draw conclusions from the two studies that assessed the risk of aspirin use during sphincterotomy. Aspirin withdrawal may be harmful in susceptible patients, mainly if it is for more than 7 days. There is no indication to stop aspirin before esophagogastroduodenoscopy, which may reveal aspirin-induced lesions. We recommend discontinuation of aspirin 4-7 days (according to the cardiovascular risk) before other endoscopic procedures. When aspirin is indicated for primary prevention, it can be resumed 14 and 10 days after polypectomy and sphincterotomy respectively. In cases of secondary prevention, it should be resumed after 1 week.

Chronic hepatitis C infection in children.

Hepatitis C virus infection may differ in the pediatric age group with respect to transmission, natural history and response to treatment. Most infected children develop chronic hepatitis but with a relatively mild course of the disease. The most efficient transmission of hepatitis C virus is through direct percutaneous exposure to infected blood or blood products. However, the major risk factor for acquisition of hepatitis C virus in children at present is maternal-infant transmission. The rate of progression to advanced liver disease seems to be more rapid in post transfusional and vertically acquired hepatitis C virus infection than in sporadic hepatitis C virus infection acquired postnatally, or in those without known risk factors. There is a wide variety of histopathological expression, depending on the geographical distribution of the different countries. Treatment for hepatitis C virus in children has not yet been approved. However, combination treatment with peginterferon-alpha-2b with ribavirin shows encouraging results and is generally well tolerated. More randomized controlled trials are needed in the future to optimize the approach to hepatitis C virus infection in children.

Laparoscopically monitored percutaneous endoscopic gastrostomy (PEG) in children: a safer procedure.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) has now become the preferred technique for facilitating enteral nutrition in children with inadequate caloric intake. Because many problems related to PEG insertion have recently been reported, we were motivated to reassess this established technique. We have therefore added a new step--laparoscopic monitoring--to the classic PEG procedure. METHODS: Fifteen children who required PEG during the previous year were studied. Their ages ranged from 2 months to 18 years. Six children were < 1 year old at the time of operation. In 11 patients, the PEG was performed at the end of a laparoscopic Nissen fundoplication. In the others, it was done as a single procedure. RESULTS: In all 15 children, the PEG was performed safely and quickly, without complications. CONCLUSION: The addition of 'laparoscopic monitoring' to the classic PEG procedure introduced by Gauderer et al. changes the first and last parts of the procedure from an almost 'blind' undertaking to a well-controlled and safer procedure.

Diagnosing small bowel Crohn's disease with wireless capsule endoscopy.

BACKGROUND: The small bowel is the most commonly affected site of Crohn's disease (CD) although it may involve any part of the gastrointestinal tract. The current methodologies for examining the small bowel are x ray and endoscopy. AIMS: To evaluate, for the first time, the effectiveness of wireless capsule endoscopy in patients with suspected CD of the small bowel undetected by conventional modalities, and to determine the diagnostic yield of the M2A Given Capsule. PATIENTS: Seventeen patients (eight males, mean age 40 (15) years) with suspected CD fulfilled study entry criteria: nine had iron deficiency anaemia (mean haemoglobin 10.5 (SD 1.8) g%), eight had abdominal pain, seven had diarrhoea, and three had weight loss. Small bowel x ray and upper and lower gastrointestinal endoscopic findings were normal. Mean duration of symptoms before diagnosis was 6.3 (SD 2.2) years. METHODS: Each subject swallowed an M2A Given Capsule containing a miniature video camera, batteries, a transmitter, and an antenna. Recording time was approximately eight hours. The capsule was excreted naturally in the patient's bowel movement, and the data it contained were retrieved and interpreted the next day. RESULTS: Of the 17 study participants, 12 (70.6%, six males, mean age 34.5 (12) years) were diagnosed as having CD of the small bowel according to the findings of the M2A Given Capsule. CONCLUSIONS: Wireless capsule endoscopy diagnosed CD of the small bowel (diagnostic yield of 71%). It was demonstrated as being an effective modality for diagnosing patients with suspected CD undetected by conventional diagnostic methodologies.

Lack of correlation between disease activity and decreased stimulated secretion of IL-10 in lymphocytes from patients with celiac disease.

BACKGROUND: Celiac disease (CD) is commonly believed to be a predominantly Th1 disease. However, the exact balance between the Th1 and Th2 arms, as well as the correlation to clinical parameters, remains unclear. The aim was to assess the Th1/Th2 cytokine profile and its correlation to clinical parameters in active and non-active CD patients. METHODS: Peak, total secretion and secretory pattern of the Th1 cytokines (IFN-gamma and IL-2) and Th2 cytokines (IL-4 and IL-10) were determined in resting and stimulated peripheral blood mononuclear cells (PBMC) from 19 CD patients with active and non-active disease and 20 normal controls. RESULTS: Peak and total secretion of IL-10 were significantly reduced in CD patients compared with normal controls. This was due to a persistently flat secretory pattern of IL-10 over time in CD patients. In addition, IFN-gamma/IL-10 and the IL-2/IL-10 ratios of peak and total secretion were higher in patients than in controls. In contrast, peak, total secretion and secretory pattern of IL-2, IFN-gamma and IL-4 were comparable in patients and controls as well as the IL-2/IL-4 and IFN-gamma/IL-4 ratios. No difference in the cytokine secretion or Th1/Th2 ratio was found between active and non-active patients or between pediatric and adult patients. CONCLUSIONS: These data indicate that the Thl/Th2 balance in CD is shifted towards Th1 cytokines because of a down-regulated IL-10 secretion. The aberrant profile of cytokine secretion of these patients is not associated with clinical parameters and suggests an inherent defect in IL-10 secretion in CD.

Measles is more prevalent in Crohn's disease patients. A multicentre Israeli study.

The question whether there is a transmissible pathogenetic agent as a cause for Crohn's disease, remains unanswered. Measles virus has been the subject of many intensive studies, in the attempt to find a role for it in the pathogenesis of inflammatory bowel disease. Whether an early infection with measles virus may predispose to Crohn's disease in later life is still not clear. We conducted a large scale multicentre study, in order to obtain sufficient data to answer this question. To do so, we compared inflammatory bowel disease patients, with Crohn's disease or ulcerative colitis, with two matched control groups: clinical controls, and community controls. A total of 531 patients, 271 with ulcerative colitis and 260 with Crohn's disease were interviewed, as well as 903 matched controls. Blood from 104 inflammatory bowel disease patients and 50 controls was tested for antibodies to measles virus. We did not find any differences related to measles vaccination, either in Crohn's disease or in ulcerative colitis. Exposure to measles in childhood was more frequent in Crohn's disease patients than in their controls, the difference being statistically significant (p < 0.05) in relation to community controls. The presence of IgG antibodies to measles virus was higher in patients with Crohn's disease than in patients with ulcerative colitis or controls (p = 0.084). Another observation of interest was the finding that Crohn's disease patients who had measles in childhood, more frequently had large bowel disease than those who had not had measles. These data lead us to postulate that there may be a role for measles infection in Crohn's disease, even if, at present, this role remains unclear.

Effects of current cigarette smoking on clinical course of Crohn's disease and ulcerative colitis.

Cigarette smoking worsens Crohn's disease (CD) but ameliorates ulcerative colitis (UC). In Israel, where there is no epidemiological association of smoking with CD, we examined the effects of current smoking on the course of CD and UC. Patients at nine public hospitals completed a questionnaire detailing their smoking history, disease course and treatments; subjects altering their smoking habit after the onset of disease were excluded. Sixty-four smokers and 144 nonsmokers had CD, and 34 smokers and 158 nonsmokers had UC. No differences were found between CD smokers and nonsmokers for hospitalizations, operations, and requirement for corticosteroid and immunosuppressive treatment. By contrast, UC smokers had less extensive disease than nonsmokers (P < 0.02) and fewer hospitalizations (P = 0.01) and operations (P = 0.025). Our results agree with a minority of studies showing no adverse effect of smoking on the course of CD, and confirm the protective effect of smoking in UC.

Effectiveness of acupuncture for treatment of childhood constipation.

The aim of the present study was to examine the influence of acupuncture on chronic constipation in children and to investigate their basal plasma panopioid level and the changes of this treatment. Seventeen children constipated for at least six months were treated by five weekly placebo acupuncture sessions, followed by 10 weekly true acupuncture sessions. Their parents filled a bowel habit questionnaire. Panopioid activity was measured at time 0 and after 5, 10, and 15 acupuncture sessions. The frequency of bowel movements in males increased more gradually compared to females and reached a maximal improvement only after 10 true acupuncture sessions, from 1.4 +/- 0.6/week to 4.4 +/- 0.6/week and females from 1.4 +/- 0.3/week up to 5.6 +/- 1.2/week. The basal panopioid activity was lower in constipated children as compared to the control population and increased gradually up to control level after 10 true acupuncture sessions. This study is the first to describe a successful treatment by acupuncture of constipated children.

Appendectomy is more frequent but not a risk factor in Crohn's disease while being protective in ulcerative colitis: a comparison of surgical procedures in inflammatory bowel disease.

OBJECTIVE: Appendectomy was shown to be protective in patients with ulcerative colitis (UC). There are fewer data in Crohn's disease (CD). Other operations were less studied. The aim of this study was to investigate the prevalence of appendectomy, cholecystectomy, and tonsillectomy, including their timing, in patients with inflammatory bowel disease in comparison to controls. METHODS: Two hundred seventy-one patients with UC and 260 with CD, 475 clinic controls, and 428 community controls were interviewed. RESULTS: Appendectomy was found in 5.5% patients with UC, in 11% of clinic controls (p < 0.05), and 7.7% of community controls (p = not significant). The differences were more significant for appendectomy before onset of disease. Appendectomy was performed in 19.2% of patients with CD, in 10.9% of clinic controls, and in 10.1% of community controls (p < 0.01). However, there were no significant differences when only appendectomy before onset of disease was considered. Cholecystectomy was found in 1.5% of patients with UC, in 6.1% of clinic controls (p < 0.01), and in 4.5% of community controls (p = not significant). The difference remained significant when confined to operations performed before disease onset. No such difference was found in patients with CD. No significant difference was found in the prevalence of tonsillectomy between patients and controls. CONCLUSIONS: Appendectomy is protective in UC; it is more frequent, but not a risk factor in CD. The role of cholecystectomy should be investigated further.

Passive smoking in patients with inflammatory bowel disease: an Israeli multicentre case-control study.

BACKGROUND: The association between smoking and inflammatory bowel disease (IBD) is well established. There are, however, no large scale studies of passive smoking in inflammatory bowel disease and this has never been surveyed in the Jewish population of Israel. AIM: To study the passive smoking exposure of Jewish IBD patients in Israel in a large scale multicentre study. METHODS: Patients with established IBD, aged 18-70 years, were interviewed regarding smoking and other habits. Two controls, one clinic and one neighbourhood, matched by age, sex, community group, and education, were sought for each subject. RESULTS: Five hundred and thirty-four patients (273 ulcerative colitis (UC) and 261 Crohn's disease (CD)), 478 clinic controls and 430 community controls were interviewed. There were no significant differences in the passive smoking habits between IBD patients and their controls. Fifty-one percent of UC patients, 50% of the clinic controls and 58% of the community controls were exposed to passive smoking at home (NS); similar results were found among CD patients (50%, 55% and 56%, respectively). When a quantitative exposure index was used UC patients were significantly less exposed to passive smoking than were their community controls (7.46 +/- 8.40 vs 9.36 +/- 9.46, n = 229, P< 0.031). There was no difference in the exposure to passive smoking among CD patients and their controls. No differences in exposure to passive smoking were found when UC patients who had never smoked were compared with their controls. When the quantitative index was used 'never-smoked' CD patients tended to be less exposed to passive smoking at home than their community controls (5.40 +/- 7.60 vs 8.04 +/- 8.72, P < 0.05). CONCLUSION: There is a lack of association between passive smoking and IBD in Jewish patients in Israel. When a quantitative exposure index was used UC patients were found to be less exposed to passive smoking than their community controls.

Serum transferrin receptor in children and adolescents with inflammatory bowel disease.

UNLABELLED: Iron studies are difficult to interpret in patients with chronic inflammatory states such as inflammatory bowel disease (IBD). Serum transferrin receptor (TfR) has been reported to be a reliable tool for the diagnosis of iron deficiency in adults. Our aim was to evaluate the role of serum TfR in diagnosing iron deficiency in children and adolescents with IBD. A total of 63 consecutive patients with IBD, aged 9 to 22 years (median 15 years), were tested for serum haemoglobin level, mean corpuscular volume (MCV), and serum iron, transferrin, ferritin and serum TfR levels. Those found to be anaemic were compared with seven age-matched subjects with iron deficiency anaemia (IDA) and 24 age-matched children without signs of anaemia or inflammation. Of the 63 patients with IBD, 26 had anaemia. Based on ferritin levels and MCV indices, anaemia was classified as IDA in 11 patients and as anaemia of chronic disease (ACD) in 15 patients. Mean serum TfR level in normal controls was 3.5 mg/l (range 1.2-8.2 mg/l). Mean (+/-SD) serum TfR levels were significantly lower in the IBD patients with ACD (5.3 +/- 2.3 mg/l) than in the IBD patients with IDA (8.2 +/- 3.1 mg/l) (P < 0.05). Serum TfR levels above 5 mg/l identified 10/11 IBD patients with IDA. The calculated TfR/ferritin ratio was 84 (range 17-367) for controls and 133 (range 6.4-1840) for IBD patients. A cut-off level of 350 (91% sensitivity, 100% specificity, 100% positive predictive value, 98% negative predictive value) was established for the diagnosis of IDA in IBD. CONCLUSION: The results suggest that serum transferrin receptor is a useful parameter for the diagnosis of iron deficiency in inflammatory bowel disease, in particular, the transferrin receptor/ferritin ratio with a cut-off level > or = 350.

Prevalence of celiac antibodies in children with neurologic disorders.

Neurologic complications are a recognized but unusual manifestation of celiac disease (CD) in adults and children. The use of antigliadin and antiendomysial antibodies in screening has revealed the frequency of CD among symptom-free individuals to be high. Recently, a high frequency (57%) of antigliadin antibodies was demonstrated in adult patients with neurologic dysfunctions of unknown cause. We investigated the yield of screening for CD in children with common neurologic disorders. One hundred sixty-seven children, 1-16 years of age, were included in the study: 41 with migraine headaches, 39 with attention-deficit disorder with or without hyperactivity, 36 with epileptic disorders, and 51 with hypotonia and motor abnormalities. Positive IgG antigliadin antibodies were evident in 22 children (13%) in the study group compared with three children (9%) in the control group. However, in all children, negative IgA and endomysial antibodies were observed; thus duodenal biopsies were not performed. Contrary to studies performed in adults, these results did not demonstrate any relationship between common neurologic disorders without a specific diagnosis during childhood and CD. Thus screening for CD does not need to be routinely included in the diagnostic evaluation of children with these disorders.

Chronic hepatitis B virus in children in Israel: clinical and epidemiological characteristics and response to interferon therapy.

OBJECTIVE: To describe the clinical and epidemiological features of hepatitis B virus infection in Israeli children, and to evaluate their response and compliance to therapy. METHODS: We retrospectively studied 51 patients (34 males, 17 females), aged 2-18 years, from several medical centers in Israel. RESULTS: Of the 51 patients, 38 with elevated transaminase, positive hepatitis B e antigen and/or HBV DNA, and histologic evidence of liver inflammation were treated. Interferon was administered by subcutaneous injections three times a week for 3-12 months (dosage range 3-6 MU/m2). Only 16% were native Israelis, while 78% of the children were of USSR origin. A family history of HBV infection was recorded in 25 of the 51 patients (9 mothers, 16 fathers or siblings). Five children had a history of blood transfusion. The histological findings were normal in 3 patients, 24 had chronic persistent hepatitis, 14 had chronic active hepatitis and 2 had chronic lobular hepatitis. Five children also had anti-hepatitis D virus antibodies. Twelve of the 38 treated patients (31.5%) responded to IFN completely, with normalization of the transaminase levels and disappearance of HBeAg and HBV DNA. In no patient was there a loss of hepatitis B surface antigen. The main side effects of IFN were fever in 20 children, weakness in 10, headaches in 9, and anorexia in 6; nausea, abdominal pain, and leukopenia were present in 3 cases each. The response rate was not affected by age, country of origin, alanine/aspartate aminotransferase levels, or histological findings. However, a history of blood transfusion was a predictor of good response, 60% vs 27% (P < 0.05). CONCLUSIONS: We found IFN to be a safe and adequate mode of treatment in children with chronic HBV infection, regardless of their liver histology and transaminase levels. Therefore, in view of the transient side effects associated with this drug, we recommend considering its use in all children with chronic hepatitis B.