Gonca Tatar

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.

Interferon Therapy for Acute Hepatitis C during Pregnancy

OBJECTIVE: Due to their antiproliferative activity, the probable effects of interferons on a fetus are a concern. We report on a pregnant patient who developed acute hepatitis C during pregnancy and was treated with a short course of interferon alfa therapy with a successful outcome. CASE SUMMARY: A 26-year-old woman was diagnosed with acute hepatitis C at the 16th week of pregnancy. She received a total dose of 72 million units of interferon alfa-2b during a 2 1/2 month period. Although the therapy was discontinued due to adverse effects, a complete biochemical and virologic response was obtained. Premature labor occurred and healthy, but growth-restricted, twin infants were born transvaginally. At 18 months of age, they had normal development, with a negative hepatitis C serology. DISCUSSION: The rate of transmission of hepatitis C virus from mother to infant is within the range of 1–5%. Although acute hepatitis C during pregnancy is a very rare occurrence, the mother is at a great risk for chronic infection. There is scarce literature about the probable effects of interferon use during pregnancy due to a lack of controlled studies in this special population. A total of 8 infants, including ours, exposed to interferon alfa and/or ribavirin during pregnancy showed no congenital anomalies or malformations. CONCLUSIONS: Patients with chronic hepatitis whose therapy can be delayed should not be treated with interferon due to a lack of controlled studies. However, women exposed to interferon inadvertently during pregnancy may be encouraged to continue pregnancy. In patients with acute hepatitis C during pregnancy, the use of interferon therapy should be considered with close monitoring.

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.

Diagnostic difficulties, therapeutic strategies, and performance of scoring systems in patients with autoimmune hepatitis and concurrent hepatitis B/C.

Abstract Background. The diagnosis of autoimmune hepatitis (AIH) is already difficult, and that of AIH with chronic viral hepatitis including hepatitis B (HBV) or hepatitis C (HCV) is even more challenging. To date, only a few case-based studies have described this association. Aim. The aim was to retrospectively assess diagnostic difficulties, therapeutic approaches, and performance of the scoring systems in AIH patients with concurrent HBV and HCV. Methods. A total of 25 patients from United States, Sweden, Italy, and Turkey were retrospectively evaluated. Both revised and simplified criteria suggested by the International Autoimmune Hepatitis Group were applied for each patient. All study data were obtained from medical records. Results. Of the 25 patients, 20 (80%) had concomitant HCV and 5 (20%) had HBV. Based on the revised scoring system and simplified criteria, 18 (72%) and 12 (48%) patients were diagnosed as “probable” AIH. None of the patients were diagnosed as “definite” AIH according to both scoring systems. Patients with HCV initially were treated with immunosuppressive agents, and antiviral therapy was commenced when biochemical remission occurred. AIH patients with HBV were first treated with antiviral and thereafter, immunosuppressive therapy was started. Conclusions. This large case series describes concurrent AIH and chronic viral hepatitis. The revised scoring system for AIH had a better performance than the simplified scoring system. However, neither scoring system is optimal for diagnosing AIH alone. In these patients, a definitive diagnosis of AIH should be based on a combination of serological profiles, histological findings, scoring systems, treatment response, and outcomes.

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.

Elevated serum soluble fas levels in the various stages of hepatitis C virus-induced liver disease

We aimed to determine serum soluble Fas antigen (sFas) levels at various stages of hepatitis C virus (HCV)-induced liver disease, and investigate correlations between serum sFas levels and clinical, biochemical and pathologic features. Sixty-five patients were categorized into five groups: 1, chronic active hepatitis C, elevated alanine aminotransferase (ALT), HCV-polymerase chain reaction (PCR) positive;2, responders to interferon + ribavirin therapy; 3, cirrhosis; 4, chronic hepatitis C, normal ALT, HVC-PCR positive;and 5, sustained responders. Group 6 comprised 15 control individuals. Serum sFas levels were measured by enzyme-linked immunosorbent assay. Significant differences in serum sFas levels were found between the following groups: 1 and 2; 1 and 3; 1 and 4; 1 and 6; and 3 and 6. Serum sFas levels did not correlate with ALT, histological activity or HCV-PCR positivity within group 1. Serum sFas levels appear to increase in advanced stages of HCV-induced liver disease, as a result of host-related immunological factors.

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.

Impaired lipopolysaccharide-induced interleukin-1-Beta production in patients with anti-hepatitis C virus antibody-positive chronic liver disease

The aim of our study was to determine the role of cytokine interleukin-1-beta (IL-1-beta) in patients with chronic hepatitis C virus (HCV) infection. Twenty-eight patients with chronic HCV infection were studied and compared with 18 healthy subjects. IL-1-beta levels were measured with an enzyme-linked immunosorbent assay in plasma and in supernatants of peripheral blood mononuclear cells (PBMC) incubated alone or in the presence of lipopolysaccharide (LPS). No IL-1-beta was found in plasma or unstimulated PBMC supernatants. The mean LPS-induced IL-1-beta production was 20.0 +/- 4.0 ng/ml in patients with chronic HCV infection and 29.4 +/- 3.7 ng/ml in the control group. The patients had significantly lower levels of LPS-induced IL-1-beta than the control group (p < 0.00001). No difference in LPS-induced IL-1-beta production was found in patients in relation to the histologic diagnosis (p > 0.05). There was no correlation between LPS-induced IL-1-beta production and serum alanine aminotransferase levels in patients with chronic HCV infection (r = 0.37, p > 0.05). Although limited to a small number of cases, our results suggest that LPS-induced IL-1-beta production by PBMC is impaired in patients with chronic HCV infection.