Alexander Fich

Autoimmune hepatitis in southern Israel: A 15-year multicenter study

In this study we aimed to assess the incidence, prevalence and clinical outcomes of patients with autoimmune hepatitis (AIH) in southern Israel.

Incidence, predictors and outcome of upper gastrointestinal bleeding in patients with acute coronary syndromes.

BACKGROUNDnThe broad utilization of revascularization and antithrombotic therapy in patients with acute coronary syndrome (ACS) is associated with a substantial risk of bleeding primarily related to arterial punctures, which can lead to worse outcome.nnnAIMnTo define the characteristics and outcome of patients who develop upper gastrointestinal bleeding (UGIB) in the setting of ACS.nnnMETHODSnWe identified all patients admitted to the coronary care unit between 10/96 and 11/07 with ACS who developed UGIB. For each case 3 control cases were matched. Multiple baseline characteristics, as well as antithrombotic agents, revascularization strategy and endoscopy reports were assessed. Mortality at 30-day was the primary endpoint of the analysis.nnnRESULTSnOf 7240 ACS patients, 64 (0.9%) developed UGIB. There were no significant differences between groups in the prevalence of diabetes and other risk factors, revascularization strategy, or the use of proton pump inhibitors. Patients with UGIB suffered more from renal impairment and left ventricular dysfunction and were more frequently treated with thienopyridines (89% vs. 68%, p=0.002) and glycoprotein IIb/IIIa inhibitors (39% vs. 24%, p=0.03). The combination of unfractionated heparin (UFH) with glycoprotein IIb/IIIa inhibitors was strongly associated with UGIB (OR: 2.87, 95% CI 1.66-4.97). Patients who developed UGIB had a substantially higher 30-day mortality rate (33% vs. 5%, p<0.001).nnnCONCLUSIONSnUGIB in patients with ACS is associated with a markedly increased mortality. Previous peptic disease and the use of combined anti-platelet therapy, especially in conjunction with heparin, are strong risk factors for this serious complication.

Primary biliary cirrhosis in Southern Israel: a 20 year follow up study.

BACKGROUNDnThe epidemiology of primary biliary cirrhosis (PBC) in Israel is unknown. We aimed to determine the epidemiology, long-term survival and outcomes of PBC in Southern Israel from 1990 to 2010.nnnMETHODSnCase-finding methods and population-based administrative data were used to estimate and evaluate the incidence, prevalence and prognostic factors of outcome in our PBC cohort.nnnRESULTSn138 cases of PBC were identified. The average annual prevalence of PBC was 255 cases per million. The overall age/sex-adjusted annual incidence of PBC was 10 cases per million from 1990 through 1999 and 20 cases per million from 2000 to 2010. Among 138 incident cases with a total follow-up of 960 persons-years from diagnosis, 30 patients (21.7%) died. Survival in PBC patients was significantly lower than that of the age/sex-matched Israeli population. Mortality was significantly increased in patients with an initial MELD score greater than 8 (P<0.001), with portal hypertension (P<0.001), and in non-responders to ursodeoxycholic acid (UDCA) therapy according to Barcelona criteria (P=0.005). Out of 138 patients, 95 patients (68.0%) responded to UDCA therapy according to Barcelona and Paris criteria. None of the responders died during the follow-up period as opposed to 30 out of 43 (69.8%) of non-responders. In multivariate analysis the factors associated with response to UDCA were: albumin levels above 3.5 g/dL (P<0.001) and lower degree of fibrosis per liver biopsy (P=0.003).nnnCONCLUSIONSnThis study addresses the increasing burden of PBC in Israel and confirms the importance of some clinical and therapeutic factors as predictors of long-term prognosis.

The cancer cells-of-origin in the gastrointestinal tract: progenitors revisited

A prominent model of tumor progression posits that normal self-renewing and multipotent stem cells(SCs) are the initial target of transformation. This view has been robustly challenged by the recurring observation that transit-amplifying cells and differentiated progenitors can initiate neoplasia outside the SC zone thus qualifying as cancer cells-of-origin. The emerging concept is that a cancer SC and a cancer cell-of-origin are not necessarily the same cell. Importantly, progenitor cells were shown to possess remarkable plasticity and to revert, on demand, to a SC-like state. The present review revisits our early hypothesis that colonic progenitors acquiring a mutant adenomatous polyposis coli gene after exiting the stem zone may serve as genuine cancer cells-of-origin. New findings consonant with this view are examined, and tenable molecular and cellular mechanisms underpinning the plasticity of progenitor cells in the gastrointestinal tract and in other tissues are discussed. The translational impact of cell plasticity is addressed, and recommendations for future research are advanced.

Controlled release of TGF-β1 impedes rat colon carcinogenesisin vivo

Transforming growth factor β1 (TGF‐β1) is a cytokine known to play a key role in the control of cell growth. TGF‐β1 potently inhibits the proliferation of human and rodent‐derived epithelial cells. Colonic precancerous and moderately differentiated cancer cells are responsive to TGF‐β1, whereas malignant colon cancer cells are resistant to the inhibitory action of the cytokine. These observations have been derived exclusively from in vitro studies. Therefore, the main aim of our study was to determine whether TGF‐β1 exerts a growth‐restraining action on colon carcinogenesis in vivo. TGF‐β1 was sequestered into ethylene acetate copolymer matrices and “loaded” preparations were implanted intraperitoneally (i.p.) in rats. One week later, the animals were treated with dimethylhydrazine (DMH), a colon procarcinogen. Empty matrices devoid of TGF‐β1 but containing bovine serum albumin (BSA) carrier served as the appropriate control preparations. The number of aberrant crypt foci (ACF), considered to be preneoplastic lesions of the colon, was scored. Tumor formation and size were assessed at the appropriate times. TGF‐β1 released in a sustained manner from copolymer matrices: (i) markedly inhibited colonic ACF formation and the number of aberrant crypts and (ii) significantly reduced colonic tumor formation and size. Int. J. Cancer 78:618–623, 1998.

Efficacy of combined pegylated interferon and ribavirin therapy in Jewish patients of Israel suffering from chronic hepatitis C

Background and purposeThe efficacy and safety of pegylated interferon and ribavirin treatment for chronic hepatitis C (CHC) in the Jewish population has not been previously ascertained. The aims of our study were to determine the efficacy of pegylated interferon and ribavirin therapy in an Israeli outpatient practice.MethodsThe medical records of 331 consecutive naïve patients with CHC infection treated with pegylated interferon and ribavirin between 2003 and 2010 were reviewed in order to document the virological response to the combination therapy. We used logistic regression to identify predictors for the sustained virological response (SVR). Variable selection in multivariable modeling was based on clinical and statistical significance and performed in a hierarchical fashion. First demographic characteristics, then patient clinical characteristics, viral characteristics, and finally adherence to the therapy were introduced into the model.ResultsThe overall SVR was 57.1% (42.5% in genotype 1, 87.5% in genotype 2, 81.6% in genotype 3, and 100% in genotype 4). SVR was significantly associated with genotype 2 (OR 3.77, 95% CI 1.04–13.60, Pxa0=xa00.04), genotype 3 (OR 9.72, 95% CI 4.07–23.20, Pxa0<xa00.001), baseline viral load lower than 400,000xa0IU/mL (OR 23.1, 95% CI 8.23–64.98, Pxa0<xa00.001), and adherence to the 80/80/80 rule (OR 36.22, 95% CI 11.14–117.72, Pxa0<xa00.001).ConclusionsCombined pegylated interferon and ribavirin therapy was of similar or even higher efficacy in the Israeli population as compared to that reported by international trials in Caucasian, Hispanic, and African American populations.

Small Intestinal Cancer: Why the Rarity?

The small intestine (SI) is unique in being highly resistant to cancer. This resistance is remarkable in view of the high frequency of cancer in the neighboring stomach and large intestine (LI). Possible protective mechanisms have been proposed, including the reduced intensity of exposure of SI to oral carcinogens owing to rapid transit time, the low density of microflora compared with LI, or regional differences in luminal pH and in immune cells [1]. In addition to extrinsic factors, much evidence indicates that key molecular and phenotypic differences between SI and LI stem cells also account for the markedly decreased incidence of cancer in SI.