Yasemin H. Balaban

Screening of tissue transglutaminase antibody in healthy blood donors for celiac disease screening in the Turkish population.

Celiac disease (CD) is a disease having the characteristic pathology of the mucosa of the small intestine. The prevalence of CD in the Turkish population has not been investigated previously. The present study was designed to determine the prevalence of CD in healthy blood donors. Serum samples of 2000 healthy blood donors presenting to Hacettepe University Faculty of Medicine Hospital Blood Bank were tested for tissue transglutaminase (tTG) IgA and IgG antibodies with enzyme-linked immunosorbent assay (ELISA; Euroimmune, Germany). The histopathological findings for the cases with positive serology were evaluated. The distribution of sex was 95.7% male, and 4.3% female. The mean age was 33±9. Among 2000 donors, 23 (1.15%) were positive for tTG IgA antibody and 3 (0.15%) were positive for tTG IgG antibody. None of the samples was positive for both antibodies. Serum total IgA was measured in two cases with only tTG IgG positivity and was found to be low in one case. Twelve subjects positive for tTG agreed to endoscopy and biopsy. Histopathological examination revealed changes classified as Marsh III–II in one, Marsh II in two, Marsh I in seven, and Marsh 0 in two donors. This was the first study conducted to determine the prevalence of tTG positivity in the Turkish population. The tTG antibody positivity prevalence in healthy blood donors was as high as 1.3%. This study shows that the prevalence of CD in the Turkish population is relatively high in comparison to that in the Western world.

Diagnostic and therapeutic ERCP in hepatic hydatid disease

BACKGROUND This retrospective study evaluated the use of diagnostic and therapeutic ERCP in pre- and postoperative patients with hepatic hydatid disease. METHODS For 8 years, ERCP was performed in 39 patients with hepatic echinococcal disease. Indications in the preoperative group of patients (n = 19) included a cholestatic enzyme profile in all cases; jaundice or acute cholangitis also was present in, respectively, 14 and 7 cases. In the postoperative group (n = 20), indications for ERCP included persistent external biliary fistula after surgery in 10 patients, jaundice in 8, acute cholangitis in 7, and right upper quadrant pain in 2 patients. RESULTS ERCP findings in the preoperative group included cystobiliary fistula (9 patients), external compression of the hepatic biliary system (5), hydatid vesicles and/or membranes within the biliary tract (3), intrahepatic duct stricture (1), and a normal cholangiogram (4). The most common ERCP finding in the postoperative group was external biliary fistula (10 patients); other findings consisted of hydatid cyst material within the bile duct (4), bile duct stenosis (2), cystobiliary fistula and hydatid cyst material in the bile duct (1), cystobiliary fistula (1), hydatid membranes in the gallbladder (1), extrinsic compression to bile ducts (1), and a normal cholangiogram (1). In the preoperative group, endoscopic sphincterotomy was performed in 11 patients, with balloon catheter extraction in 2; complete resolution of findings was achieved in 10 cases. In the postoperative group, sphincterotomy (with balloon or basket extraction as needed) was performed in 19 patients, stents were placed in 2 patients, 1 patient underwent balloon dilatation, and 1 had nasobiliary drainage; there was complete resolution of the findings in 14 of the 20 patients. CONCLUSIONS ERCP and related therapeutic maneuvers are safe and valuable in the pre- and postoperative management of patients with hepatic hydatid disease.

Frequency of HFE mutations among Turkish blood donors according to transferrin saturation: genotype screening for hereditary hemochromatosis among voluntary blood donors in Turkey.

Background and Goals The C282Y and H63D mutations of HFE gene are associated with hereditary hemochomatosis (HH), the most common autosomal recessive disorder in European population. This is the first Turkish population study of, the prevalence of these mutations. Study 2677 healthy volunteer blood donors were screened by means of transferrin saturation (TS) with the cutoff value of 45. As study group, 86 donors with a TS 45 or higher and as control group 57 donors with TS less than 45 were tested for these mutations, ferritin, and alanin aminotransferase (ALT) levels. Results The mean age of donors were 33 ± 9 and 94.1% of them were male. The number of donors with TS 45 or higher was 265 (9.9%). C282Y mutation was not detected. The frequency of H63D mutation in the study, control and general groups were 27.32%, 21.05%, and 24.83%, respectively. As a result, the H63D mutation was present in 60 out of 143 participants in whom 49 were heterozygote (frequency of heterozygote allel 49/286 = 17.13%), 11 were homozygote (frequency of homozygote allel 22/286 = 7.69%). Serum ALT and TS were not affected from the type of H63D mutation. There was no difference in ferritin levels according to type of H63D mutations among 143 blood donors. Conclusion This study revealed the absence of C282Y mutation in our population. Although the frequency of H63D heterozygosity seems to be higher than the other population, the genetic screening for the HFE gene mutation is inadequate and the phenotypic screening with TS and ferritin seems to be preferable in Turkish population.

Celiac Disease in the Turkish Population

Celiac disease (CD) is characterized by malabsorption of nutrients in the small intestine. The availability of highly specific and sensitive serologic tests has facilitated its diagnosis, increasing the disease prevalence. The aim of this study was to determine the clinical, laboratory, and histopathological features of CD in Turkish adults. Between 1968 and 2002, CD patients presenting to the Gastroenterology Unit were evaluated retrospectively. From 2002, newly diagnosed patients were prospectively followed up. Sixty patients (39 female, 21 male) were included in the study. Mean body mass index was 22.2 ± 5.4 kg/m2. The most common symptoms were diarrhea, weight loss, and flatulence. Most common comorbidities were anemia, osteoporosis, type 1 diabetes mellitus, and steatohepatitis. Six (10.0%) patients had a family history of diabetes mellitus; one (1.7%) patient had a family history of CD. Plasma glucose and serum γ-glutamyltransferase levels were significantly higher in females than males. Most common histopathological findings were increased lymphocytes in the lamina propria (76.2%) and villus epithelium (59.5%). Over the years, the cumulative frequency of CD increased more in females than males. This is the first study in the literature showing the characteristics of CD in Turkish adults. In our previous recent study, the prevalence of tissue transglutaminase antibody positivity in Turkish healthy blood donors was 1.3%, indicating a high prevalence of CD in our population. In this study, the cumulative frequency of CD increased more in females than males. With the better understanding and increased suspicion of the disease, more patients are being diagnosed in our population.

Coincidence or Causality: Celiac and Crohn Diseases in a Case of Turner Syndrome

We describe a 29-year-old woman presenting with chronic diarrhea, growth retardation, and primary amenorrhea who was diagnosed as having celiac disease coexisting with Crohn disease and Turner syndrome. The association of Turner syndrome, inflammatory bowel disease, and celiac disease is reviewed with insights into the genetics of immunologic disorders and possible chromosomal derangements leading to inflammatory bowel disease. To our knowledge, this is the first case of Crohn disease associated with celiac disease and Turner syndrome.

Mutations of the HFE gene among Turkish hereditary hemochromatosis patients

Since the discovery of the HFE gene, C282Y and H63D mutations have been reported as significantly correlated with clinically manifested hereditary hemochromatosis (HH). As the other genes involved in iron metabolism have been described, non-HFE cases of HH have been identified. Since in the general Turkish population, the C282Y mutation is not found and the H63D mutation is of high frequency, we aimed to determine mutations in the HFE genes in our patients with HH. The HFE gene of the five patients with HH were sequenced. C282Y mutation was absent, and all HH patients were heterozygote for H63D mutation. No other mutation was found in HFE gene by sequencing. Although the higher allele frequency of the H63D mutation in Turkish HH patients than in the general population implies a role of the H63D mutation in iron overload, there is a strong possibility that Turkish HH patients have non-HFE hemochromatosis.

Cutoff level to detect heterozygous alpha 1 antitrypsin deficiency in Turkish population

Background: Alpha 1 antitrypsin (AT) deficiency is a hereditary disorder leading to the defective defence system against neutrophil elastasis in lung and accumulation of insoluble heterodimer AT molecules in hepatocytes. Knowledge of the prevalence of AT deficiency in each country is important to organize the public health policy. The aim of this study is to determine the prevalence of AT deficiency in Turkish population and to define the cutoff value of AT level in serum to detect heterozygous AT deficient subjects. Materials and Methods: Serum samples from 1,203 healthy blood donors were used, attending the Blood Bank of Hacettepe Medical Faculty. Isoelectric focusing method for determining PIM, PIS, and PIZ alleles and rate immune nephelometry for measuring the level of AT in serum were used. Results: Out of 1,203 healthy blood donors enrolled, 1,164 (%96.8) had normal variant PI MM allelee, 9 (%0.7) PI MZ, 7 (%0.6) PI MS, 6 (%0.5) MF, and 17 (%1.4) PI M? (unidentified variants with existing standards). Most individuals (89.6%) with low AT level (cutoff <100 mg/dl) in serum were positive for PI MM allele. The cutoff value to investigate PI MZ was 100.5 mg/dl, which had PPV and NPV of 5.0 and 99.9%, respectively. AT deficiency is a rare hereditary disorder in asymptomatic healthy Turkish blood donors. Although the cutoff value of 100.5 mg/dl for AT level in serum was able to detect heterozygous AT deficiency in the healthy population, this finding should be conformed to case‐control studies. J. Clin. Lab. Anal. 25:296–299, 2011.

HFE mutations analysis of Turkish patients with nonalcoholic steatohepatitis.

To the Editor: Chronic liver disease is a well-known cause of secondary iron overloading. Iron overloading of liver is associated with severity of fibrosis and increased risk for hepatocellular carcinoma as well as resistance to antiviral treatment. Iron content of liver in nonalcoholic steatohepatitis (NASH) patients is important because NASH causes chronic hepatitis, and there is also a debate on the role of iron for the pathogenesis of NASH. Uraz et al. [1] report that Turkish patients with NASH do not have iron overload of hepatic parenchyma and the disease activity at liver biopsy is not related with hepatic iron overload both in NASH and chronic viral hepatitis. Because they did not investigate HFE mutation in their study, we would like to discuss the current

Causes of Hypouricemia Among Outpatients

Background The aim of this study was to examine the ratio and underlying causes of hypouricemia in patients visiting our outpatient clinics. The association between hypouricemia and uricosuria and other renal tubular defects was also studied. Methods Serum uric acid levels were determined by uricase methods in 18,330 serum samples. Hypouricemia was defined as a serum uric acid level less than 2.0 mg/dL. Fractional excretion of uric acid (FEUA) higher than 10% was considered as pathological uricosuria. Results The frequency of hypouricemia in our patient population was 0.51% (94/18,330). Moreover, using univariate analysis, hypouricemia was associated with age, gender, diet, drugs, and tea and coffee consumption. Multivariate analysis revealed that FEUA, drugs, and tea consumption were associated with hypouricemia. Conclusion Hypouricemia is a relatively uncommon finding among our outpatients and when it occurs, it is frequently caused by inappropriate uricosuria.

Liver immunology and herbal treatment

Beyond the metabolic functions, the liver recently has been defined as an organ of immune system (IS), which have central regulatory role for innate and adaptive immunity. The liver keeps a delicate balance between hepatic screening of pathogenic antigens and immune tolerance to self-antigens. Herbal treatments with immunological effects have potential to alter this hepatic immune balance towards either therapeutic side or diseases side by inducing liver injury via hepatotoxicity or initiation of autoimmune diseases. Most commonly known herbal treatments, which have therapeutic effect on liver and IS, have proven via in vitro, in vivo, and/or clinical studies were summarized in this review.