Israel Medical Association Journal

Background: The Fibrotest-Actitest™ is a six-parameter scoring system that allows quantification of liver fibrosis and inflammation. This test has been validated by several studies in hepatitis B and C viruses and alcoholic liver disease, with a high correlation between the liver biopsy and the results of the FT-AT[1] (AUROC between 0.78 and 0.95).The FT-AT was introduced in Israel (Rambam Laboratory) in March 2005.

Objectives: To assess the results of HCV[2] patients who underwent the test during the period March 2005 to February 2006.

Methods: Serum was taken and brought to the central laboratory performing the tests within 4 hours. Six parameters were evaluated using commercial kits approved by the designer of the test (Biopredictive): total bilirubin, gamma-glutamyltransferase, alpha-2 macroglobulin, haptoglobin, alanine aminotransferase, and apolipoprotein-A1. The results were sent to the website of Biopredictive (France), which provided the FT-AT score online using a patented formula.

Results: Of the 325 patients tested, only 4 were not interpretable because of hemolysis. Patients' age ranged from 7 to 72 years (median 42); 54% were female. Liver biopsy was performed in 81 patients and was compared with the results of the Fibrotest. Findings were as follows: 27% of the patients were F0, 19% F1, 20% F2, 17% F3 and 17% F4; 18% were A0, 32% A1, 28% A2 and 22% A3. The AUROC curve comparing the Fibrotest with liver biopsy with a cutoff point at F2 and A2 for significant fibrosis and inflammation was 0.85 and 0.79 respectively.

Conclusion: Fibrotest is a simple and effective method to assess liver fibrosis and inflammation and can be considered an alternative to liver biopsy in most patients with HCV.

Background: Screening for celiac disease is based on the sequential evaluation of serologic tests and intestinal biopsy; an optimal screening protocol is still under investigation. The screening policy of one of the main healthcare providers in Israel (Maccabi) consists of measuring total immunoglobulin A and tissue transglutaminase IgA[1] antibodies and confirming positive results by endomysial antibodies. For IgA-deficient patients antigliadin IgG is measured.

Objectives: To evaluate the use of tTGA[2] as a first-level screening test in patients suspected of having celiac disease

Methods: The results of tTGA and EMA[3] tests over a 3 month period were obtained from the laboratory computer. Letters were sent to the referring physicians of patients with positive tests, requesting clinical information and small intestinal biopsy results. tTGA was performed using an anti-guinea pig tTG-IgA enzyme-linked immunosorbent assay kit.

Results: Overall, 2,505 tTGA tests were performed: 216 (8.6%) were tTGA-positive of which 162 (75%) were EMA-negative (group 1) and 54 (25%) EMA-positive (group 2). Clinical information was obtained for 91 patients in group 1 and 32 in group 2. Small intestinal biopsy was performed in 33 (36%) and 27 patients (84%) in groups 1 and 2, respectively. Celiac disease was diagnosed in 4 biopsies (12%) in group 1 and 23 (85%) in group 2 (P < 0.0001). The positive predictive value was 45% for tTGA and 85% for EMA.

Conclusions: Symptomatic patients with positive tTGA and negative EMA have a low rate of celiac disease compared to those who are tTGA-positive and EMA-positive. Confirmation with EMA is advised when tTGA is performed as a first-level screening for suspected celiac disease.

Background: About one-third of patients with severe ulcerative colitis do not respond to conventional therapy and require urgent colectomy. It was recently shown that cyclosporin is effective in some of these patients.

Objectives: To review the current experience of six hospitals in central Israel that used cyc-losporin in patients with severe ulcerative colitis.

Methods: The files of all 32 patients treated with cyclosporin for corticosteroid-resistant ulcerative colitis were reviewed. Activity of disease was measured by a clinical activity, index colonoscopy and laboratory tests.

Results: The average duration of treatment with intravenous cyclosporin was 12.7 days (range 9–28) after which the disease activity index dropped from an average of 14.22 to 4.74. The mean time for response was 7.5 days (4–14). Twelve patients (40%) required surgery within 6 months and another 6 patients (18.8%) were operated on after more than 6 months. Twelve patients (37%) maintained remission for at least 6 months and did not require surgery. In one patient treatment was stopped because of non-compliance and one was lost to follow-up. There were numerous side effects, but in only one case with neurotoxicity was treatment withdrawn.

Conclusions: Cyclosporin is a relatively safe and effective treatment for severe ulcerative colitis. It induced long-term remission in 37% of the patients, and in those who required surgery the treatment resulted in an improved clinical condition before the operation.

Background: Anti-endomysial antibodies are sensitive and specific markers for celiac disease. This antibody has recently been identified as an antibody to tissue transglutaminase, an enzyme that cross-links and stabilizes extracellular matrix proteins.

Objectives: To evaluate the clinical usefulness of an enzyme-linked immunoassay for anti-transglutaminase antibodies, and to compare the results with those of AEA, the current gold standard serological test for celiac disease.

Methods: Serum samples were collected from 33 patients with biopsy-proven celiac disease and AEA tests were performed. Control samples for anti-transglutaminase were obtained from 155 patients. An ELISA test for immunoglobulin A anti-transglutaminase utilizing guinea pig liver transglutaminase was developed and performed on all sera.  Cutoff values for the test were performed using logistic regression and receiver operating curves analysis.

Results: An optical density cutoff value of 0.34 was established for the assay. The mean value was 0.18±0.19 optical density for controls, and 1.65±1.14 for patients with celiac disease (P<0.001). Sensitivity and specificity of the assay were both 90%, while AEA had a sensitivity and specificity of 100% and 94%, respectively.

Conclusions: A tissue transglutaminase-based ELISA test is both sensitive and specific for  detection of celiac disease.

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AEA = anti-endomysial antibody

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. 

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HBV = hepatitis B virus

IFN = interferon

HBeAg = hepatitis B e antigen