Tomer Adar

Adalimumab-induced autoimmune hepatitis.

Antitumor necrosis factor antibodies are widely used in the treatment of autoimmune diseases. We describe the occurrence of autoimmune hepatitis in a patient treated with adalimumab, a fully human IgG antibody against tumor necrosis factor, for psoriatic arthritis. The patient made a full recovery after discontinuation of adalimumab and treatment with steroids. This is the first reported case of adalimumab-induced autoimmune hepatitis.

Radiofrequency ablation for the treatment of gastric antral vascular ectasia

BACKGROUND AND STUDY AIMS The traditional endoscopic treatment for gastric antral vascular ectasia (GAVE) is argon plasma coagulation, but results are not always positive. Radiofrequency ablation (RFA) is a new endoscopic therapy that may be an attractive option for the treatment of GAVE. The aim of this study was to assess the efficacy and safety of RFA for the treatment of GAVE. PATIENTS AND METHODS This was an open-label, retrospective, case series study. The main outcome measures were number of red blood cell (RBC) packs transfused (transfusion requirement) and hemoglobin concentrations (g/dL) in the 6 months prior to and after RFA. Success was defined as a decrease in transfusion requirement in the 6 months after RFA compared with before treatment. RESULTS A total of 24 patients underwent a mean of 1.8 ± 0.8 RFA sessions. No complications were reported. One patient was referred for additional argon plasma coagulation during follow-up. The mean number of RBC packs decreased in all 23 transfusion-dependent patients, from a mean of 10.6 ± 12.1 during the 6 months prior to RFA, to a mean of 2.5 ± 5.9 during the 6 months after RFA treatment (P < 0.001), and 15 patients (65.2 %) were weaned off transfusions completely. An increase in the hemoglobin concentration was reported in all patients after RFA (from 6.8 ± 1.4 g/dL to 9.8 ± 1.8 g/dL; P < 0.001). CONCLUSION RFA for the treatment of GAVE seems feasible and safe, and significantly reduced the need for RBC transfusion and increased the hemoglobin level in this retrospective case series.

Oral administration of immunoglobulin G-enhanced colostrum alleviates insulin resistance and liver injury and is associated with alterations in natural killer T cells

Insulin resistance and metabolic syndrome are chronic inflammatory conditions that lead to hepatic injury and non‐alcoholic steatohepatitis (NASH). Bovine colostrum has therapeutic effects in a variety of chronic infections. However its effectiveness in NASH was never studied. Natural killer T (NKT) cells have been shown to be associated with some of the pathological and metabolic abnormalities accompanying NASH in leptin‐deficient (ob/ob) mice. In the present study, we used hyperimmune bovine colostrum to treat hepatic injury and insulin resistance and we also assessed the effects on NKT cells. We used ob/ob mice that were fed for 6 weeks with either 0·1 mg bovine colostrum prepared from non‐immunized cows, 0·1 mg hyperimmune colostrum raised against a bacterial lipopolysaccharide (LPS) extract or 0·001, 0·1 or 1 mg of immunoglobulin (Ig)G purified from hyperimmune colostrum (IgG–LPS). NKT cells were phenotyped by flow cytometry, and hepatic injury and insulin resistance were assessed by measuring fasting glucose levels, glucose tolerance tests and liver enzymes. Fat accumulation was measured in the liver and plasma. Oral administration of hyperimmune colostrums decreased alanine aminotransferase (ALT) serum levels and serum triglycerides compared to controls. Glucose intolerance was also improved by the hyperimmune colostrum preparations. These results were accompanied by a decrease in serum tumour necrosis factor (TNF)‐α levels following oral treatment with 0·1 or 1 mg of IgG–LPS. The beneficial effects of hyperimmune colostrums were associated with an increase in the number of splenic NKT cells. These data suggest that oral administration of hyperimmune colostrum preparations can alleviate chronic inflammation, liver injury and insulin resistance associated with NASH.

Alleviation of insulin resistance and liver damage by oral administration of Imm124-E is mediated by increased Tregs and associated with increased serum GLP-1 and adiponectin: results of a phase I/II clinical trial in NASH

Background Nonalcoholic steatohepatitis (NASH) is considered to be part of the nonalcoholic fatty liver disorders and its incidence is increasing. Imm124-E (Immuron Ltd, Melbourne, Australia), containing hyperimmune bovine colostrum, has been shown to exert an immunomodulatory effect and to alleviate target organ damage in animal models of NASH. The aim of our study was to determine the safety and efficacy of oral administration of Imm124-E to patients with insulin resistance and NASH. Methods In an open-label trial, ten patients with biopsy-proven NASH and insulin resistance were orally treated with Imm124-E for 30 days. Results Oral administration of Imm124-E was safe, and no side effects were noted. Alleviation of insulin resistance was reflected by significantly improved hemoglobin A1c (HbA1c) values in all ten treated patients. For between five and eight responders, the following effects were noted: a decrease in fasting glucose levels; improved oral glucose tolerance test (OGGT) and homeostatic model assessment insulin resistance (HOMA) scores; and alleviation in lipid profile. These effects were accompanied by increased serum levels of glucagon-like peptide 1 (GLP-1), adiponectin and T regulatory cells. Conclusion Hyperimmune colostrum alleviates NASH.

Assessment of insulin resistance by a 13C glucose breath test: a new tool for early diagnosis and follow-up of high-risk patients.

Background/AimsInsulin resistance (IR) plays an important role in the pathogenesis of diabetes and non-alcoholic fatty liver disease (NAFLD). Current methods for insulin resistance detection are cumbersome, or not sensitive enough for early detection and follow-up. The BreathID® system can continuously analyse breath samples in real-time at the point-of-care. Here we determined the efficacy of the BreathID® using the 13C-Glucose breath test (GBT) for evaluation of insulin resistance.MethodsTwenty healthy volunteers were orally administered 75 mg of 13C-glucose 1-13C. An oral glucose tolerance test (OGTT) was performed immediately; followed by serum glucose and insulin level determinations using GBT. GBT and OGTT were repeated following exercise, which alters insulin resistance levels.ResultsWithin-subject correlations of GBT parameters with serum glucose and serum insulin levels were high. Before and after exercise, between-subjects correlations were high between the relative insulin levels and the % dose recoveries at 90 min (PDR 90), and the cumulative PDRs at 60 min (CPDR 60). Pairwise correlations were identified between pre-exercise Homeostasis Model Assessment (HOMA) IR at 90 min and PDR 90; HOMA B (for beta cell function) 120 and CPDR 30; HOMA IR 60 and peak time post-exercise; and HOMA B 150 with PDR 150.ConclusionsThe non-invasive real-time BreathID® GBT reliably assesses changes in liver glucose metabolism, and the degree of insulin resistance. It may serve as a non-invasive tool for early diagnosis and follow up of patients in high-risk groups.

From airway inflammation to inflammatory bowel disease: eotaxin-1, a key regulator of intestinal inflammation.

Eotaxin-1 (CCL-11) is a potent eosinophil chemoattractant that is considered a major contributor to tissue eosinophilia. Elevated eotaxin-1 levels have been described in various pathologic conditions, ranging from airway inflammation, to Hodgkin lymphoma, obesity and coronary artery disease. The main receptor for eotaxin-1 is CCR3; however, recent evidence indicates that eotaxin-1 may also bind to other receptors expressed by various cell types, suggesting a more widespread regulatory role for eotaxin-1 beyond the recruitment of eosinophils. Eotaxin-1 is also strongly associated with various gastrointestinal (GI) disorders. Although the etiology of inflammatory bowel disease (IBD) is still unknown, eotaxin-1 may play a key role in the development of mucosal inflammation. In this review, we summarize the biological context and effects of eotaxin-1, as well as its potential role as a therapeutic target, with a special focus on gastrointestinal inflammation.

Aggregation of red blood cells in patients with Gaucher disease

Gaucher disease is associated with increased red blood cell (RBC) aggregation, but the pathophysiological significance of this phenomenon and its correlation with disease manifestations are unclear. RBC aggregation was evaluated in 43 patients with Gaucher disease and 53 healthy controls. Dynamic RBC aggregation was examined in a narrow‐gap flow chamber at varying shear stress. Compared with the controls, RBC aggregation in Gaucher disease was increased by 25%. Comparison of RBC aggregation in autologous plasma and in dextran (500 kDa) showed an increase both in plasma‐dependent (extrinsic) and ‐independent (intrinsic) RBC aggregation. Subgroup analysis revealed that increased RBC aggregation was limited to patients with an intact spleen. RBC aggregation in patients did not correlate with plasma fibrinogen concentration, disease severity, enzyme replacement therapy or genotype. We conclude that RBC aggregation is increased in patients with Gaucher disease and an intact spleen, possibly reflecting the accumulation of glucocerebroside and other substances in the plasma and RBC membranes of these patients. Our results do not support a role for RBC aggregation in the pathogenesis of vascular complications of Gaucher disease.

Endotipsitis-persistent infection of transjugular intrahepatic portosystemic shunt: pathogenesis, clinical features and management.

Transjugular intrahepatic portosystemic shunt (TIPS) is in widespread use for the decompression of portal pressure. The entity of persistent TIPS infection, also known as ‘endotipsitis’ is a rare but serious complication of TIPS insertion. The exact definition of ‘endotipsitis’ is still debated, but involves persistent bacteremia and fever together with either shunt occlusion, or vegetation, or bacteremia in the presence of a patent shunt, when other sources of bacteremia have been ruled out. To date, approximately 40 cases of ‘endotipsitis’ have been described, with predominance for male and alcoholic hepatitis patients. The clinical course is variable, but fever and chills are a constant feature. Bacteremia, can either occur early (<120 days) or late (>120 days) after stent insertion, with some cases occurring many years after the procedure. Although no predominant bacterial species have been described in ‘endotipsitis’, staphylococci and other Gram‐positive bacteria are more commonly seen in early infection. The diagnosis of ‘endotipsitis’ is difficult and requires a high index of suspicion. A rigorous imaging work‐up to rule out other sources of endovascular infection is usually required including ultrasonography, computed tomography and echocardiography. Because removal of the infected stent is impractical, treatment is empirical and based on a prolonged course of antibiotics. If eligible, some patients may be referred for liver transplantation. The use of prophylactic antibiotics during the initial TIPS procedure is controversial, and despite the lack of evidence, prophylaxis is the common practice. The aim of this review was to describe the definition, clinical course, diagnosis, pathogenesis, microbiology, treatment and outcome of endotipsitis.

Radiofrequency ablation for the treatment of radiation proctitis.

BACKGROUND AND STUDY AIMS The main endoscopic therapy for radiation proctitis is argon plasma coagulation (APC); however treatment is not always successful. Radiofrequency ablation (RFA) is a possible treatment for radiation proctitis but data are scarce. The aim of this study was to report on the safety and efficacy of RFA in the treatment of radiation proctitis. PATIENTS AND METHODS This study was an open-label, retrospective, multicenter study of patients with chronic hemorrhagic radiation proctitis who were treated with RFA. Data included a three-item symptom score, the number of packed red blood cell transfusions, the lowest hemoglobin concentration, and complications, during the 6 months prior to and after RFA. Clinical success was defined as a decrease in the symptom score. Biological success was defined as an increase in the hemoglobin rate with equal or decreased number of transfusions required. RESULTS A total of 17 patients underwent a median of 2 RFA sessions (range 1 - 4), without perioperative complications. Symptom scores decreased in 16 patients (clinical success 94 %), from a mean score of 3.6 (median 4) to 1.4 (median 1) (P < 0.01). Two patients developed rectal ulceration, with no local symptoms. During the 6 months after RFA, hemoglobin concentration increased in all 17 patients (from mean 8.3 ± 2.8 g/dL [median 7.5] to 11.3 ± 2.2 g/dL [median 11.0]; P < 0.01). Among 13 patients who were transfusion dependent prior to RFA (mean 7.2 ± 7.7 transfusions [median 4]), 9 patients (69 %) were weaned off transfusions after RFA. A significant increase in the hemoglobin level was observed in this subgroup of patients (from mean 7.2 ± 1.4 g/dL [median 7.3] to 10.7 ± 1.5 g/dL [median 10.5]; P < 0.001). Biological success was 100 %. CONCLUSIONS RFA seems to significantly decrease clinical symptoms and increase the hemoglobin concentration, thus reducing the need for transfusions.

Pregnancy and the Immune System: General Overview and the Gastroenterological Perspective.

Pregnancy represents a unique immune tolerant condition that cannot be attributed merely to generalized immunosuppression. A variety of mechanisms have been described, ranging from the non-self recognition, immunomodulation of specific inflammatory cell populations and a Th2-directed shift of the immune response, which are mediated by both localized and systemic mediators. Furthermore, an inflammatory response directed toward the conceptus is no longer considered an obligatory deleterious response; instead, it is considered an important factor that is necessary for normal growth and development. These immunomodulatory changes during pregnancy may also affect concurrent conditions and alter the course of inflammatory diseases. Herein, we review the main immunomodulatory changes that occur during pregnancy and their effect on coexisting inflammatory conditions, with a specific focus on gastrointestinal disorders.