Search

The aims of the present study were to review biliary complications following liver transplantation in a single-center experience, to identify the factors associated with biliary complications, and to evaluate the success of endoscopic and percutaneous treatment in such patients.Between January 1994 and June 2010, a total of 176 patients with liver disease underwent liver transplantation; 119 recipients were included in this retrospective analysis. Median posttransplant follow-up period was 49 months.Mean age was 43.0±12.7 years. Living donor liver transplantation (LDLT) and deceased-donor liver transplantation (DDLT) were performed in 71 and 48 patients, respectively. Duct-to-duct anastomosis and Roux-en-Y hepaticojejunostomy were performed in 68 and 51 patients, respectively. The overall incidence of posttransplant biliary complications was 36%; anastomotic biliary strictures were the most common biliary complications (42%), followed by biliary leakage (28%). On logistic regression analysis, duct-duct anastomosis was the only risk factor associated with the development of biliary complications (Odds ratio (OR), 3.346; p=0.005). Endoscopic and percutaneous treatment was successful in the majority of patients (81%), and the remaining 19% recipients underwent surgery for biliary repair. Endoscopic retrograde cholangiopancreatography (ERCP) guided drainage and balloon dilatation with stent placement were the most common treatment modalities.Biliary complications were most frequent after liver transplantation; biliary strictures were the most commonly seen. The use of duct-to-duct anastomosis for biliary reconstruction is a risk factor for the development of biliary complications. Endoscopic and percutaneous treatment was successful in the majority of these patients.

Background/aims: Hepatocellular carcinoma is the fifth most common cancer and a major public health problem worldwide. Differences in distribution of hepatocellular carcinoma incidence are probably due to different levels of exposure to hepatocellular carcinoma risk factors: chronic infections with hepatitis B virus (HBV) and aflatoxin exposure in developing countries, and smoking and alcohol abuse in developed countries. Aflatoxin is one of the most important of the environmental toxins that contribute to the pathogenesis of hepatocellular carcinoma, especially in the regions where dietary foodstuff's (peanuts, corn, Brazil nuts, pistachios, spices and figs) are highly contaminated. High aflatoxin levels have been shown in the foodstuffs that are produced in our country. The specific aim of this study was to assess the rate of aflatoxin exposure and to determine some clues about aflatoxin metabolism by measuring and comparing the levels of carcinogenic forms in healthy subjects, in different stages of viral disease, and in different viral hepatitis types. Methods: This was a cross-sectional observational, single-center study. A total of 203 (male 1 female: 119184) viral hepatitis patients who were consecutively admitted to Ankara University, School of Medicine, Gastroenterology Clinic, between January 2006 and June 2007 were enrolled into the study. Sixty-two healthy subjects (male 1 female: 33129) with normal blood chemistry and negative viral serology served as controls. Chemical forms AFB1, AFB2, AFG1, and AFG2 were assessed in plasma of study participants by high-performance liquid chromatography. Results: AFB1, AFB2, AFG1, and AFG2 were detected in 24.6%, 17.2%, 22.7%, 18.2% of the 203 patients, respectively, and were significantly higher than in the control group for all chemical forms. Percentage of AFB1-positive patients was significantly higher than in the control group irrespective of disease stage. There was no significant difference between chronic infected patients, cirrhotic patients and patients with Hepatocellular carcinoma with respect to percentage of aflatoxin-positive individuals. Conclusions: With this study, we have documented that in viral hepatitis patients, aflatoxin exposure is significantly higher than in healthy subjects in Turkey and it may play an important role in the development of hepatocellular carcinoma. Thus, large studies exploring the relation between aflatoxin exposure, viral hepatitis status, and risk of hepatocellular carcinoma development are needed.

Aim/Materials and Methods Between January 2000 and June 2007, 3,548 endoscopic retrograde cholangiopancreatography (ERCP) were performed for extrahepatic cholestasis, cholangitis, and choledocholithiasis. The results of ERCPs were evaluated retrospectively and examined carefully to investigate the management and endoscopic therapy of biliary parasites. Results Of the 3,548 patients who underwent ERCP, 24 (0.66%) were found to have biliary parasitosis. The mean age of the biliary parasitosis patients (16 women) was 48.6 (15–77) years. Of these 24 cases, 16 patients had hydatid cystic disease (eight with partial obstruction of the biliary tract, and eight with ruptured cysts), four patients had Fasciola hepatica, and four patients had Ascaris lumbricoides infestation. Endoscopic sphincterotomy was performed, after which the choledochus was examined carefully by balloon catheter and basket procedure. Conclusion The ERCP procedure is very useful in the therapy of biliary parasitic infestations.

An 11-yr-old boy with familial YNS and FHF and who underwent LRLT is presented. LRLT was performed from his father with YNS. The findings of hepatic failure resolved immediately after LRLT, but severe respiratory complications and chylous ascites were observed during the follow-up. At 12 months after successful LT, the patient has good graft function, but findings of YNS including chronic cough, lymphedema and yellow nails are still present. To the best of our knowledge, this is the first case of YNS who underwent LRLT for FHF.

Background Pegylated interferon α2b (PEG-IFN-α2b) is effective for the treatment of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B, although its mechanism of action remains unclear. HBeAg loss is achieved in 36% of patients after one year of PEG-IFN-α2b treatment and combination therapy with lamivudine is not superior to PEG-IFN-α2b monotherapy. Methods Early pharmacokinetics and viral kinetics were analysed in patients treated for 52 weeks with PEG-IFN-α2b with or without lamivudine. Results After 4 weeks of treatment, there was a median viral decline of 2.94 log10 copies/ml in those treated with PEG-IFN-α2b and lamivudine and only 0.45 log10 copies/ml in the PEG-IFN-α2b monotherapy group. Peak PEG-IFN-α2b levels were reached approximately one day after administration and subsequently declined exponentially, consistent with a viral load rebound near to baseline levels at the end of the dosing period in most patients receiving PEG-IFN-α2b monotherapy. Modelling of pharmacokinetics and viral kinetics data in this group revealed that viral load was minimal 3.6 days after PEG-IFN-α2b administration, the mean maximal and mean antiviral effectiveness was 70% and 48% with a mean infected cell loss rate of 0.07 per day, while no significant biphasic decline was observed. Conclusions PEG-IFN-α2b induces a sustained response in a considerable number of patients despite limited direct antiviral activity during the first weeks of antiviral therapy.

Achalasia is a rare esophageal motility disorder, with dysphagia to solids and liquids being the most common symptom. It can be confused with distal esophageal and gastric cardia malignancies. When this disorder is suspected, the first investigation should be barium esophagography, while the definite diagnosis is made by esophageal manometric measurements and upper gastrointestinal tract endoscopic series. Pneumatic dilation is the most effective and safest medical treatment approach. The present case is reported due to failure to diagnose the condition in spite of a ten year history., Akalazya nadir gözlenen bir özofagus motilite bozukluğudur. Katı ve sıvı gıdalara karşı yutma güçlüğü en sık semptomudur. Özellikle distal özofagus ve mide kardiya tümörleri ile klinik ve radyolojik olarak karışabilmektedir. Klinik olarak akalazyadan şüphenildiği durumlarda ilk yapılması gereken baryumlu özofagogram olup, manometrik çalışmalar ve üst gastrointestinal sistem endoskopik incelemeleri ile kesin tanı konulur. Tedavisinde balon dilatasyonu medikal yaklaşımlardan en etkili ve güvenilir olanıdır. Vakamız uzun süreli disfaji şikayetinin olması fakat tanıyı ancak 10 yıl sonra alabilmesi nedeniyle sunuldu ve literatür gözden geçirildi.

Objectives: Data regarding the long-term treatment of ursodeoxycholic acid (UDCA) in individuals of chronic graft-vs.-host disease (cGVHD) of the liver are limited. The aims of this prospective study were to determine whether, (i) UDCA treatment is useful as a long-term treatment for individuals with limited cGVHD of the liver following allogeneic hematopoietic cell transplantation, and (ii) the tolerability of UDCA treatment in such individuals. Methods: Fifteen consecutive patients with de novo isolated cGVHD of the liver were included. All individuals were treated with UDCA at a dose of 13 mg/kg/d for 1 yr. Clinical evaluation and laboratory testing were assessed at 30-d intervals during UDCA therapy and every 30 d after discontinuation of UDCA for a total of 3 months. Results: At the end of the treatment, 60% of patients with cGVHD of the liver had normal liver tests, the remaining 40% of patients demonstrated improvement in their abnormal liver tests (partial responders), whereas none of the patients had worsening of the liver tests. When compared with baseline, there was a significant decrease in the serum aminotransferases, alkaline phosphatase and gamma-glutamyl transpeptidase levels after completion of the UDCA treatment at 12 months (p

Thrombophilic gene mutations have been reported to be associated with the formation of portal vein thrombosis (PVT). This study aimed to investigate the role of thrombophilic gene mutations in cirrhotic patients with PVT.A total of 74 cirrhotic patients (17 with PVT, 57 without PVT), and 19 non-cirrhotic patients with PVT and 80 healthy controls were included. Factor V Leiden G1691A, prothrombin G20210A and methylenetetrahydrofolate reductase C677T mutations were analysed by restriction fragment length polymorphism.Aetiologies and Child-Pugh distribution of cirrhotic patients with and without PVT were similar. Five of 17 (29%) of cirrhotic patients with PVT but only two of 57 (3.5%) of cirrhotics without PVT, five of 80 (6%) of controls and none of the 19 non-cirrhotic patients with PVT had factor V Leiden G1691A mutation (P0.05). Prothrombin G20210A mutation was found in five (29%) cirrhotic patients with PVT while only two (3.5%) cirrhotic patients without PVT, one (5%) non-cirrhotic patient with PVT and two (2.5%) controls had this mutation (P0.05). The frequency of the homozygote methylenetetrahydrofolate reductase 677C-T mutation was similar in all four groups.Inherited thrombophilic gene mutations appear to increase the risk of PVT formation in cirrhotic patients but not in patients without liver disease in a cohort of Turkish patients.

Background: The aim of this study was to determine the role of hepatitis B virus (HBV) vaccination as defined by the seroconversion to hepatitis B surface antibody (anti-HBs) positivity in peripheral blood stem cell transplants. Methods: A total of 65 recipients and their donors were enrolled in this study. Recipients were divided into four distinct groups. Group 1 consisted of individuals who were vaccinated, group 2 consisted of individuals who were naturally immunized, group 3 consisted of individuals who were HBs-Ag positive, and group 4 consisted of individuals who were HBV naive and not vaccinated. Results: Eighty-eight percent of the HBV-vaccinated recipients (14 of 16), who had vaccinated-donors, seroconverted to anti-HBs positivity. Eighty-three percent of HBV-naive recipients (five of six), who received stem cells from HBV-immune donors, seroconverted to anti-HBs positivity. Two of the four HBs-Ag positive recipients with HBV-immune donors seroconverted to anti-HBs positivity after transplantation. Fifty-seven percent of previously vaccinated-recipients (eight of 14) lost detectable anti-HBs antibody following transplantation. Finally, 31% of HBV-naive recipients with HBV-naive donors acquired a de novo HBV infection. Conclusions: (i) Hepatitis B virus immunization of recipients of allogeneic hematopoietic cell transplantation results in an effective antibody response. (ii) The HBV-immune status of the donor plays an important role in post-transplantation HBs-Ab on seroconversion. (iii) Systematic re-immunization of recipients will be necessary to maintain HBV immunity in long-term serving recipients.

Background/Aim: Hepatitis C virus (HCV) populations in vivo consist of genetically different heterogeneous mixtures defined as ‘quasispecies’, which vary in the hypervariable region 1 (HVR1) mostly. To further address the role of quasispecies diversity in hepatitis C infection, this study aimed to evaluate the influence of ALT, viral load and genotypes on quasispecies heterogeneity in patients with HCV infection. Methods: Thirty-six chronic hepatitis C patients with high levels of alanine aminotransferase (ALT) were studied. None of them received any antiviral therapy. HCV RNA serum levels, genotype and genetic heterogeneity were determined by branched-chain DNA assay, restriction fragment length patterns and RT-PCR single-strand conformational polymorphism analysis of HVR1, respectively. Results: Twenty-eight patients had genotype 1b (28/36; 78%), 6 patients had genotype 1a (6/36; 17%), 1 patient was 2a (1/36; 3%) and genotype could not be determined in 1 patient. The patients were categorized into two groups according to the number of bands representing the dominant strains in the circulation: group A with 2 bands having 1 strain (14/36 patients; 39%) and group B with more than 2 bands indicating more than 1 strain (22/36 patients; 61%). The serum viremia and ALT levels for these groups were 11 ± 8.8 and 5.3 ± 4.6 mEq/ml (p < 0.05), and 79 ± 20, and 127 ± 80 IU/l (p < 0.05), respectively. Conclusion: The results of this study suggest that hepatitis C patients having 1 dominant strain in the circulation may show a relatively weaker immune response resulting in lower ALT and higher viremia levels, whereas patients with high degrees of virus quasispecies diversity have higher ALT levels and a more active immune response causing the selection of new genome variants and depressing viral replication partly.

Background and goals The aim of this cohort study was to determine the characteristics and clinical outcome of 170 patients with drug-induced liver injury (DILI) in a single center. Study Between January 2001 and June 2007, a total of 170 individuals who were diagnosed with DILI were retrospectively analyzed. The median follow-up period was 110.0 days. Results During the study period, a total of 5471 new patients were assessed for liver test abnormalities. Of those, 170 patients (3.1%) fulfilled the criteria of DILI. A total of 83 different drugs were considered to be related to the hepatotoxicity; a single drug was suspected in 57.6% of individuals. The median interval between the suspicious drug intake and DILI recognition was 15.0 days. Hepatocellular pattern was observed in 50.0% of patients with a mean alanine aminotransferase level of 952.2+/-907.0 U/L. The main causative group of drugs was antibiotics. Sixty-two patients required hospitalization; acute liver failure developed in 14 (8.2%), chronicity was observed in 19 (11.2%), and 7 died (4.1%). Overall, complete recovery occurred in 82% of patients. The presence of jaundice on admission and shorter interval period between drug intake and DILI recognition were identified as risk factors for the development of acute liver failure. Conclusions DILI is an important cause of liver test abnormalities in outpatient clinics, and antibiotics represent the most common drug group. Overall, complete recovery after the withdrawal of the suspicious drug occurred in the majority of patients, but DILI may progress to acute liver failure, chronicity, and death.

SUMMARY. The aims of the study were to investigate the efficacy of rescue therapy with lamivudine (LAM) and adefovir (ADV) combination for 6 months followed by ADV monotherapy in lamivudine-resistant chronic hepatitis B (LAM-R CHB) patients, and to analyze the frequency of ADV resistance mutant development in such patients. A total of 170 consecutive LAM-R CHB patients (male/female: 130/ 40, mean age: 42.9 ± 13.4 years) with viral breakthrough under LAM therapy were analyzed. A total of 68 had HBeAg-positive. Patients received rescue therapy with LAM [100 mg (qd)]+ADV [10 mg (qd)] for 6 months after which LAM was discontinued. HBV-DNA was assessed with the HBV-DNA 3.0 bDNA assay. ADV-resistant mutations were identified by sequencing the reverse transcriptase region. The median duration of rescue therapy was 24 months. Cumulative probability of becoming HBV-DNA undetectable was 33.8%, 59.6% and 68.2% after 24, 48 and 96 weeks of treatment, respectively. These figures were 43.2%, 58.0% and 73.1% for ALT normalization. Among 68 HBeAg-positive CHB patients, 10 patients had an e-antigen seroconversion. Low baseline HBV-DNA level (

Pegylated interferon alpha2b (PEG-IFN-alpha(2b) is effective for the treatment of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B, although its mechanism of action remains unclear. HBeAg loss is achieved in 36% of patients after one year of PEG-IFN-alpha2b treatment and combination therapy with lamivudine is not superior to PEG-IFN-alpha2b monotherapy.Early pharmacokinetics and viral kinetics were analysed in patients treated for 52 weeks with PEG-IFN-alpha2b with or without lamivudine.After 4 weeks of treatment, there was a median viral decline of 2.94 log10 copies/ml in those treated with PEG-IFN-alpha2b and lamivudine and only 0.45 log10 copies/ml in the PEG-IFN-alpha2b monotherapy group. Peak PEG-IFN-alpha2b levels were reached approximately one day after administration and subsequently declined exponentially, consistent with a viral load rebound near to baseline levels at the end of the dosing period in most patients receiving PEG-IFN-alpha2b monotherapy. Modelling of pharmacokinetics and viral kinetics data in this group revealed that viral load was minimal 3.6 days after PEG-IFN-alpha2b administration, the mean maximal and mean antiviral effectiveness was 70% and 48% with a mean infected cell loss rate of 0.07 per day, while no significant biphasic decline was observed.PEG-IFN-alpha2b induces a sustained response in a considerable number of patients despite limited direct antiviral activity during the first weeks of antiviral therapy.

The changes in short circuit current (electrogenic Cl- secretion) of rat colon brought about by xanthine/xanthine oxidase in the Ussing chamber were inhibited by catalase and diethyldithiocarbamate, but not by superoxide dismutase. These results, the reproduction of the response with glucose/glucose oxidase and with exogenous H2O2, and the lack of effect of preincubation with deferoxamine or thiourea implicate H2O2, and not O2- or OH., as the important reactive oxygen metabolite altering intestinal electrolyte transport. 1 mM H2O2 stimulated colonic PGE2 and PGI2 production 8- and 15-fold, respectively, inhibited neutral NaCl absorption, and stimulated biphasic electrogenic Cl secretion with little effect on enterocyte lactic dehydrogenase release, epithelial conductance, or histology. Cl- secretion was reduced by cyclooxygenase inhibition. Also, the Cl- secretion, but not the increase in prostaglandin production, was reduced by enteric nervous system blockade with tetrodotoxin, hexamethonium, or atropine. Thus, H2O2 appears to alter electrolyte transport by releasing prostaglandins that activate the enteric nervous system. The change in short circuit current in response to Iloprost, but not PGE2, was blocked by tetrodotoxin. Therefore, PGI2 may be the mediator of the H2O2 response. H2O2 produced in nontoxic concentrations in the inflamed gut could have significant physiologic effects on intestinal water and electrolyte transport.

AimsThis study was conducted to clarify the resistance profile of a novel mutation pattern emerging during lamivudine (3TC) therapy and showing cross-resistance to adefovir dipivoxil (ADV) in a patient with chronic hepatitis B.Methods and resultsSuccessful suppression of hepatitis B virus (HBV) replication by sequential therapy of 9 MU thrice weekly interferon (IFN) and 3TC was followed by genotypical resistance detected at month 28 of therapy (month 19 of lamivudine treatment). ADV was added to 3TC therapy on month 44 of antiviral treatment. Neither alanine aminotransferase normalization nor a stable decrease in HBV viral load was observed, although ADV was used for more than 40 months. The HBV pol region was amplified from serum samples obtained before and after ADV treatment. The complete genome was cloned into a TA vector. PCR products and 7–10 clones from each cloned vector were sequenced. A novel mutation, A181S, in the reverse transcriptase gene leading to a conversion of W172C in the overlapping surface antigen gene was detected along with a M204I mutation. The complete genome comprising the A181S+M204I pattern was cloned into an expression vector and its in vitro susceptibility to 3TC, ADV, tenofovir (PMPA), clevudine (l-FMAU) and emtricitabine (FTC) were determined in transiently transfected Huh7 cells. This mutation pattern displayed more than 1,000-fold resistance to the nucleoside analogues 3TC and FTC and approximately sixfold resistance to l-FMAU, while it confers 28.23- and 5.57-fold resistance for the nucleotide analogues ADV and PMPA, respectively.ConclusionA new mutation pattern, A181S+M204I, arising under lamivudine treatment confers cross-resistance to ADV both in vivo and in vitro.

Background: ‘‘Bone marrow-derived stem cells’’ have attracted great attention as potential candidates for liver-directed gene therapy and as a tool for regenerative medicine. However, the fate of these cells is not well-known. The aim of this present study was to investigate the fate of ‘‘recipient-derived repopulated hepatocytes’’ in sex-mismatched liver allografts in individuals following liver transplantation during systematic longitudinally performed liver biopsies. Methods: Paraffin-embedded sex-mismatched liver biopsy samples of nine recipients (male/female ratio 5/4; mean age: 39.7 yr) were reviewed. Double labeling with immunohistochemistry for hepatocytes and recipient-specific bone marrow-derived cells and fluorescence in-situ hybridization for visualizing X and Y chromosomes were performed. These slides were examined systematically using an image analyzer system (Olympus microscope; Cyto-Vision, Applied Imaging, Biosciences Centre, Newcastle, UK). Only cells with two nuclear spots were considered for interpretation. Results: The mean times from transplantation to first biopsy and between the first and the second biopsies were 5.9 and 20.9 months respectively. The proportion of recipient-derived repopulated hepatocytes was significantly decreased in the late biopsies when compared with the early biopsies (p = 0.001). All nine samples of the first biopsies had demonstrated recipient-derived hepatocyte repopulation, with a mean of 2.0%, whereas only seven of nine samples of the second biopsies had demonstrated recipient-derived hepatocyte repopulation with a low mean of 0.5% (p = 0.001). Conclusion: Based on these results, we suggest that ‘‘recipient-specific bone marrow-derived hepatocyte repopulation’’ in liver allograft during tissue injury is a relatively early event.

Background and Aims: Gastroesophageal reflux is the most frequent disease affecting the esophagus. The purpose of this study was to determine if there has been any change in esophagitis detection rates in recent years. Materials and Methods: All 63,854 upper gastrointestinal endoscopies performed at Ankara University, Gastroenterology Department, Ibn-i Sina and Cebeci Endoscopy Centers, between 1990 – 2008 were analyzed retrospectively. Grading for esophagitis was done using Savary – Miller Classification until 1999, after which the Los Angeles Classification was used. Age, sex, and other endoscopic findings like hiatal hernia, duodenal ulcer, bulbar deformity, gastric ulcer, pyloric stenosis, apical stenosis, gastric operations, gastritis, and alkaline reflux were recorded. Results: Of these 63,854 cases, 52.9% were women. The mean age was 46.75 (15-98). Esophagitis was detected in 10,275 (16.1%) cases. Severity was grade I in 61.9%, II in 26.5%, III in 8.1%, and IV in 3.4%. Esophagitis frequency and severity increased with age ( Giris Mide iceriginin ozofagusa gecmesi fizyolojik bir olaydir. Ozofagusa gecen mide iceriginin rahatsizlik yaratmasi veya ozofagus hasarina neden olmasina Gastroozofageal Reflu Hastaligi (GORH) denir. Gelisimindeki en onemli unsur reflu onleyici mekanizmalarin bozulmus olmasidir. Gastroozofageal Reflu Hastaligi toplumda sik gorulen, hayat kalitesini olumsuz etkileyen ve saglik sistemine giderek daha fazla yuk olan pahali bir hastaliktir (1, 2). Hastaligin seyrinde, Barret ozofagusu, hemoraji, striktur, perforasyon ve kanser gelisimi gibi ciddi komplikasyonlar gelistigi bilinmektedir. Yetiskinlerin %15-44'unde ayda bir, %20'sinde haftada bir, %7'sinde gunde bir kez reflu semptomlari goruldugu bildirilmistir. Bati toplumunda ust sindirim sistemi endoskopisi yapilan hastalarin %15-25'inde ozofajit bulundugu raporlanmistir. Asya'dan yapilan calismalarda ise bu sikligin %0.8-16.3 gibi cok daha az siklikta goruldugu bildirilmekte ve batililasmayla beraber sikligin giderek arttigi iddia edilmektedir (3). Son yillarda hem hekim ve hastalarin farkindaliginin artmasi ile daha fazla tani konmasi, hem de prevalansinda gercek bir artis oldugu bildirilmektedir. Gastroenterolojistlerin %90'i ve aile hekimlerinin %67'sinin gorusunun prevalansin arttigi yonunde oldugu bildirilmistir (4). Bu calismanin amaci ulkemizde yillar icinde ozofajit sikliginda degisiklik olup olmadigini degerlendirmektir. Gerec ve Yontem Ankara Universitesi Gastroenteroloji Bilim Dali Ibni Sina Hastanesi ve Cebeci Klinigi Endoskopi merkezlerinde 1990 – 2008 yillarinda yapilan 63854 ust gastrointestinal sistem endoskopisi sonucu retrospektif olarak degerlendirildi. Calismaya alinan vakalar, islem endikasyonu ve tekrar endoskopi olup olmamasi gozetilmeden alindi. Ozofajit derecelendirmesi 1999'a kadar Savary-Miller ve 1999`dan itibaren Los Angeles siniflamalarina gore yapilmisti (Tablo 1). Hastalarin yaslari, cinsiyeti ve ozofajite yandas endoskopik bulgulari (hiatus hernisi, duodenal ulser, bulbus deformitesi, gastrik ulser, pilor stenozu, apikal darlik, mide operasyonu, gastrit, safra gastriti, ozofagus ve mide kanseri) kaydedildi. Istatistik analizler icin SPSS 13.0 paket programi kullanildi. Anlamlilik degeri p

The aim of this study was to detect donor-derived hepatocytes and gastrointestinal epithelial cells in recipients of sex-mismatched allogeneic hematopoietic cell transplants, and to assess the effect of tissue injury on the extent of the repopulation. A total of 29 paraffin-embedded biopsy samples were reviewed. Double labeling by immunohistochemistry and fluorescence in situ hybridization was performed. Eighty-nine percent of sex-mismatched samples with histologic evidence of injury demonstrated the presence of donor-derived hepatocytes and gastrointestinal epithelial cells (mean 2.4%). None of the hepatocytes and gastrointestinal epithelial cells in samples obtained from female recipients with female donors showed a Y chromosome signal. The proportion of donor-derived hepatocyte and gastrointestinal epithelial cells in samples with severe graft-versus-host disease was greater than that of samples with mild/moderate graft-versus-host disease (P = 0.09). No relationship between the source of stem cells and the population rate was detected (P > 0.05). We conclude that some recipient hepatocytes and gastrointestinal tract epithelial cells are replaced by donor-derived cells during tissue injury. The severity of tissue injury seems to influence on the extent of this repopulation.

Antiviral therapy leads to HBeAg seroconversion in 10-40% of the patients with HBeAg-positive chronic hepatitis B. Nonresponse may result in progression of liver disease and increased risk of hepatocellular carcinoma. As part of a global randomized controlled trial we investigated the efficacy (i.e., loss of HBeAg at the end of follow-up) of peginterferon alfa-2b (Peg-IFN alpha2b) in patients who failed to respond to previous courses of standard interferon (IFN) or lamivudine.We analyzed a total of 76 previous nonresponders: 37 were nonresponders to standard IFN, 17 were nonresponders to lamivudine, and 22 were nonresponders to both therapies. All patients received a 52-wks course of 100 microg Peg-IFN alpha2b weekly combined with either 100 mg lamivudine daily or a placebo. After therapy patients were followed for 26 wks.Thirteen (35%) nonresponders to previous IFN, five (29%) nonresponders to previous lamivudine, and four (22%) nonresponders to both IFN and lamivudine responded to treatment with Peg-IFN alpha2b. No difference in response was found for those treated with Peg-IFN alpha2b alone or in combination with lamivudine. Nonresponders to prior IFN therapy with baseline ALT (alanine aminotransferase)4 x ULN (upper limit of normal) responded better to Peg-IFN alpha2b than those with ALT levelsor= 4 x ULN (53%vs 20%, respectively, p= 0.036).Peg-IFN alpha2b is effective in approximately one-third of patients who failed to respond to previous treatment with standard IFN or lamivudine. High serum ALT level at baseline of Peg-IFN alpha2b therapy was the best predictor for response in these patients.

The aims of this study were to determine the presence of trefoil factor family-3 (TFF3) expression in biliary epithelial cells (BECs) of chronic graft-versus-host disease (cGVHD) of the liver after allogeneic hematopoietic cell transplantation, to compare such expression in chronic liver diseases (CLD) with/without predominantly biliary disease, and to assess the effect of bile duct injury on the degree of TFF3 expression in BECs of cGVHD.A total of 82 paraffin-embedded liver biopsy samples were reviewed. These samples were basically divided into two distinct groups according to the presence of ductal injury: group 1 with CLD and predominantly biliary disease (n=26: 17 cGVHD and 9 primary biliary cirrhosis [PBC]) and group 2 with CLD and predominantly parenchymal liver disease (n=56: 20 steatohepatitis and 36 chronic viral hepatitis). Group 2 was used as the controls. Immunohistochemistry was performed using a polyclonal anti-TFF3 antibody. Real-time quantitative PCR was used for the detection of TFF3 mRNA expression.Positive TFF3 immunohistochemical staining and the presence of TFF3 messenger RNA gene expression was demonstrably higher in group 1 than that in group 2 (P0.0001 and P0.05, respectively). No significant difference in terms of positive TFF3 stained BECs between GVHD and PBC samples was observed (P0.05). The extent of TFF3 expression in GVHD samples with severe ductal injury were significantly more common than that of GVHD samples with mild/moderate ductal injury (P0.0001).The expression of TFF3 in cGVHD of the liver is increased in response to bile duct damage and repair. Such expression seems to be related the severity of ductal injury.

Interferon alpha (IFN-alpha) is an immunomodulator that is used as an antiviral agent in active chronic viral hepatitis C. IFN therapy can cause an induction or exacerbation of sarcoidosis. Although several reports in the gastroenterology literature have suggested an association between IFN therapy and sarcoidosis, this association has rarely been described elsewhere. A 47-year-old woman developed sarcoidosis after cessation of treatment with IFN and ribavirin for chronic hepatitis C. Her sarcoidosis showed liver, pulmonary and skin involvement. She continues to be monitored regularly in the Department of Pulmonary Diseases without steroid therapy. Her sarcoidosis improved spontaneously. We conclude that patients should be monitored for sarcoidosis during and after IFN therapy.

Although hepatitis B virus (HBV) reactivation in HBV carriers undergoing immunosuppressive therapy is clearly documented, the role of antiviral prophylaxis in such individuals is still controversial. The aim of this study was to determine the efficacy of lamivudine prophylaxis in HBV carriers with haemato/oncological malignancies, who receive chemotherapy. Eighteen HBV carriers with malignancy, who were candidates for chemotherapy, were enrolled. Eight subjects (three with leukaemia, four with lymphoma and one with multiple myeloma) were enrolled for prophylactic lamivudine therapy. The remaining 10 patients (six with leukaemia, three with lymphoma and one with breast cancer) were not treated with lamivudine and were used as a control. Lamivudine was administered beginning on the same day as the chemotherapy and was maintained for a year after chemotherapy was discontinued. No HBV-related mortality was observed in either group. In the lamivudine-treated group, none of the subjects had clinical, biochemical or serological evidence of HBV reactivation during the time they were receiving chemotherapy and after their chemotherapy was discontinued. In contrast, five of the 10 HBV carriers not receiving lamivudine therapy experienced a reactivation of HBV infection. This reactivation of HBV was observed during the chemotherapy in four with one individual experiencing a HBV activation 12 months after chemotherapy was discontinued. No lamivudine-related major adverse effects were observed. Hence prophylactic lamivudine treatment in HBV carriers with haemato/oncological malignancy receiving chemotherapy prevents chemotherapy-induced HBV reactivation.

Different genotypes of the hepatitis viruses may influence the clinical outcome of the disease. The distribution of genotypes may vary according to geographical regions. The aim of this study was to evaluate hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus (HDV) genotypes in Turkish patients with chronic hepatitis in a large cohort of patients. Genotyping was performed in 41, 59 and 365 patients with chronic hepatitis B, D and C, respectively, and 36 hemodialysis patients with chronic hepatitis C. Genotypes were determined by direct sequencing in hepatitis B and by polymerase chain reaction-restriction fragment length polymorphism in hepatitis C and D patients. In addition, HBV subtyping by multiplex PCR and subtype specific ELISA were performed in 83 and 71 HBsAg (+) blood donors, respectively. All hepatitis B (100%) and hepatitis D (100%) patients had genotype D and type I, respectively. HBsAg subtyping by two methods yielded that 99% of the patients were subtype ayw. S gene amino acid sequence in the 41 patients included for HBV genotyping revealed the ayw2 subtype. Genotype distribution of 365 patients with chronic C hepatitis were as follows: 306 (84%) patients genotype 1b, 43 (11%) patients genotype 1a, 10 (3%) patients genotype 2, 3 (1%) patients genotype 3, 3 (1%) patients genotype 4. Among 36 patients receiving hemodialysis, 28 (78%) patients had genotype 1b and 8 (22%) patients had genotype 1a. The study indicates that Turkish patients with chronic viral hepatitis show very little genotypic heterogeneity. Subtype ayw and the genotype D of HBV DNA, and the type I of HDV RNA represent almost 100% of related infections. The genotype 1b of HCV RNA was found to be significantly dominant in Turkish patients.

The emergence of drug-resistant virus in hepatitis B virus (HBV) patients treated with lamivudine is well documented. In this study, we determined the mutations occurring in the tyrosine-methionine-aspartate-aspartate (YMDD) amino acid motif of the HBV DNA polymerase gene, as well as upstream and downstream of this region, in patients with breakthrough virus during lamivudine therapy. Thirty-one Turkish patients (20 patients HBeAg positive, 11 patients HBeAg negative and anti-HBe positive) with chronic HBV infection who completed at least 104 weeks of lamivudine treatment were investigated. All patients received lamivudine, (150 mg/day), for 104 weeks, with or without 4 months of interferon (IFN) combination. HBV-specific sequences were amplified by polymerase chain reaction (PCR) from sera of patients with breakthrough virus, and the PCR products were directly analysed by sequencing. Breakthrough virus was detected in seven of the 31 patients (22.6%) between 9 and 18 months of therapy. Of the seven patients, six were HBeAg positive at baseline, and four had a double mutation consisting of rtM204V and rtL180M, while two had an rtM204I change. In one patient, two base substitutions at rt204 (ATG --> AGT; T to G and G to T) lead to a methionine to serine change (YMDD --> YSDD). This novel DNA pol mutation was detected at month 18 of lamivudine treatment. In addition, this new variant had the rtL180M mutation and a 12 base pair deletion in the pre-S1 region between nucleotides 43-54. The YSDD mutation was still present 6 months after lamivudine discontinuation. In vitro transfection studies also confirmed that the YSDD strain is resistant to lamivudine. In conclusion, the results indicate that, in addition to a Met --> Val and Met --> Ile change in YMDD, a Met --> Ser change at rt204 (YMDD --> YSDD) associated with the rtL180M change can also emerge during lamivudine treatment, which confers lamivudine resistance in vivo and in vitro, leading to virological breakthrough and ALT increases.

Forty subjects with chronic hepatitis B and hepatitis B e antigen (HBeAg) seroconversion following lamivudine therapy in previous trials were monitored after treatment to assess the durability of serologic responses. Patient follow-up began a median of 4.3 months after completion of therapy in previous trials. At months 2, 4, 6, 9, and 12 of year 1, and every 6 months thereafter, we tested for HBeAg and hepatitis B surface antigen (HBsAg), hepatitis B virus (HBV) DNA, and alanine aminotransferase (ALT). After a median (range) of 36.6 (4.8-45.6) months of follow-up monitoring, HBeAg seroconversion was demonstrated at the last visit by 77% (30 of 39) of patients. In a post hoc analysis of a slightly different population of all 65 patients with HBeAg seroconversion in previous trials, the 3-year durability of HBeAg seroconversion measured from the time immediately after discontinuing lamivudine therapy was 64%. Nine (9 of 40, 23%) patients were HBsAg negative at the last assessment. Seventy-four percent (17 of 23) of patients with baseline undetectable HBV DNA and normal ALT maintained these responses at the last visit. Eight patients (8 of 40, 20%) initiated retreatment for reappearance of HBV markers, and 7 showed biochemical and/or virologic improvement (including regained HBeAg seroconversion in 2). No safety issues of concern emerged. In conclusion, most HBeAg responses achieved during lamivudine therapy were durable, and most responders experienced prolonged clinical benefit after HBeAg seroconversion and subsequent discontinuation of lamivudine. Lamivudine retreatment for reappearance of hepatitis B markers can achieve resumption of viral suppression. (Hepatology 2003;37:748-755.)

The purpose of this study is to compare contrast-enhanced three-dimensional (3D) magnetic resonance (MR) portograms to Doppler sonography in detection of portal venous abnormalities. Thirty-five consecutive patients, who were suspected of having portal venous system abnormalities, were examined with MR portography and Doppler sonography. Vascular abnormalities were identified in 27 of 35 patients. There was statistically significant agreement between the results of MR portography and Doppler sonography. The major limitation of contrast-enhanced 3D MR portography was its inability to provide objective hemodynamic data regarding flow direction and flow pattern.

Background/Aims: Lamivudine is effective in treatment-naive patients with chronic hepatitis B, but its role in interferon nonresponders has not been described. We assessed lamivudine treatment, with or without added interferon, in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B who had failed interferon therapy previously. Methods: Patients were randomized to lamivudine (100 mg) or placebo for 52 weeks or to a 24-week regimen of lamivudine plus interferon. Primary treatment comparisons were at week 52, with a 16-week posttreatment follow-up period. Measurements included histology (primary endpoint), HBeAg response, normalization of alanine aminotransferase, reduction of hepatitis B virus (HBV) DNA, and safety. Results: Among 238 patients, histologic response was significantly more common in patients treated with lamivudine (52 versus placebo 25%, P = 0.002) or the combination regimen (32%, P = 0.01). HBeAg loss was also more common with lamivudine (33 versus 13 versus 21%), as were virologic and alanine aminotransferase responses. Among 28 subjects with HBeAg loss/seroconversion, 71% had durable responses 16 weeks posttreatment. Conclusions: Lamivudine for 52 weeks is as effective in interferon nonresponders as in previously reported treatment-naive patients; however, a combination of lamivudine for 24 weeks and interferon for 16 weeks was not effective in this population.

Although liver disease seems to be stable in most patients who are infected with lamivudine-resistant mutant hepatitis B virus (HBV) in the short term, it may progress to more-advanced disease in some patients. In our pilot study, we investigated the efficacy of oral ganciclovir for the treatment of lamivudine-resistant HBV infection. Six patients infected with lamivudine-resistant HBV (3 patients had decompensated cirrhosis and 3 had chronic active hepatitis without cirrhosis) were included. Ganciclovir was administered at a dosage of 3 g daily for 6 months. Four of 6 patients completed the 6-month treatment period. Two patients with cirrhosis completed only 2 months of ganciclovir treatment because they died of cirrhosis complications. None of the patients had a > or =2-log(10) reduction of HBV DNA and complete alanine aminotransferase normalization at the end of their treatment regimens. In conclusion, 6 months of ganciclovir treatment is not effective for suppression of lamivudine-resistant HBV infection.

Our purpose was to present the enhancement patterns of the liver on MR angiography in patients with hepatic outflow obstruction. Twenty-three patients with Budd-Chiari syndrome (4 in acute stage and 19 in chronic stage of the disease) were examined with 3D contrast-enhanced MR angiography. During early and late portal venous phase of MR angiography the pattern of parenchymal enhancement was assessed on source images. The enhancement patterns were evaluated under 4 groups as following: (a) central (b) peripheral (c) patchy and (d) homogeneous enhancement. The morphologic changes in the liver (lobar hypertrophy or atrophy, hepatic surface irregularities) were also recorded. In the acute stage global liver enlargement (75%) with caudate hypertrophy (100%) and central enhancement of the liver (75%) were suggestive findings of the hepatic outflow obstruction. The left lobe hypertrophy (53%) associated with the caudate lobe hypertrophy (72%) and irregular surface (26%) were predominant in the chronic stage of the disease. The enhancement patterns seen in chronic disease were variable and reflected the persistent stasis of the portal blood flow (patchy enhancement in 32% of the patients) or the altered hemodynamics of the liver due to the development of subcapsular collaterals (peripheral enhancement in 21% of the patients). Homogeneous enhancement of the liver in Budd-Chiari syndrome may indicate the chronicity of the outflow obstruction (37%) and shows a more stable hepatic perfusion that occurs after the formation of intra and extrahepatic collateral veins. The morphological and perfusional features on multiphase contrast-enhanced MR angiography are valuable in understanding the effects of the hepatic outflow obstruction on the liver parenchyma.

Background: Mutation in the hepatitis B virus precore codon 28, creating a translational stop codon and double 1762–1764 T/A mutations in the core promoter region, controlling the transcription of the precore RNA and the core RNA have been suggested to correlate with the HBeAg status of patients with HBV infection. Objectives: The aim of the study was to further investigate the association of nucleotide divergences in both core promoter and precore regions with liver cell injury (reflected by ALT levels) in patients with chronic HBV infection. Study Design: The sequences of the core promoter and the precore region of HBV isolated from 67 patients, all having genotype D and subtype ayw were analyzed. The patients were divided into two groups and four subgroups according to their HBeAg and Anti-HBe status, and ALT profile. Results: It was found that the nucleotide divergences in the core promoter but not in the precore region were higher in patients having persistently elevated serum ALT than in serum ALT normal patients in both HBeAg positive and Anti-HBe positive groups (P

PubMedID: 11073139 Background: The importance of circulating immunoregulatory cytokines in response to IFN treatment and the change of in vivo production of these cytokines during interferon (IFN) treatment are not well known. We aimed to determine whether pretreatment serum levels of IL-2 and IL-10 are predictive of the response to IFN treatment and to investigate if treatment response or nonresponse has any effect on the circulating levels of these cytokines. Patients and Methods: 37 patients (18 responders and 19 non-responders) with chronic hepatitis C virus (HCV) infection who received IFN-?2b for 6 months were studied. Responders were defined by complete alanine aminotransferase (ALT) normalization and loss of HCV RNA as detected by bDNA assay while patients who had elevated ALT levels and positive HCV RNA after 6 months were considered as nonresponders. Results: Genotype distribution, ALT and HCV RNA levels were similar in responders and nonresponders. A significant number of patients with chronic hepatitis C (20/37 = 54%) had elevated IL-2 levels while IL-10 levels were not different from controls. No difference in baseline cytokine levels was observed between responders and non-responders. In the posttreatment serum samples some patients lost their detectable IL-2 or IL-10; some patients developed detectable cytokine levels after treatment irrespective of the treatment response. Conclusion: These results suggest that active liver injury in chronic hepatitis C is associated with increased circulating Th1 cytokine IL-2 but not with Th2 cytokine IL-10 and that circulating levels of these cytokines do not predict the response to I FN treatment. There is no constant and regular change in circulating levels of these cytokines under IFN treatment with respect to treatment response.

The ultrastructure of intestinal mucosa in two geophagia patients with growth retardation, hypogonadism, hepatosplenomegaly, zinc deficiency, iron deficiency, and anemia was studied with an electron microscope. Alterations in the ultrastructure of intestinal mucosa, especially in Paneth's cells, possibly due to zinc deficiency were observed.

Fourty-four patients who underwent allogeneic bone marrow transplantation (alloBMT) were studied for hepatitis B virus (HBV)-related complications. The mean follow-up period was 15.3 months. Positivity for HBV surface antigen (HBsAg) was observed in 10 patients (22.7%) throughout the study. Four of the 10 patients were HBsAg carriers before alloBMT, while the remaining six became HBsAg(+) after alloBMT. During the follow-up period (from 6 months to 45 months), an elevation in serum ALT activity was observed in the four carriers when immunosuppression was reduced or withdrawn. All of the four HBsAg carriers developed hepatitis, but none of them died of liver failure due to HBV. Only one death due to GVHD and diabetic ketoacidosis was observed in this group. Two of the four carriers received marrow from anti-HBs positive donors and one of them cleared HBsAg from his serum via adoptive immunity 8 months after transplantation. The remaining six patients acquired HBV after alloBMT, but we were unable to demonstrate the source of HBV. Five of them had a moderate increase in serum ALT activity while the other patient had a normal ALT. Two patients seroconverted to anti-HBs spontaneously. Two patients died during the follow-up, one due to intracranial hemorrhage and the other due to GVHD and accompanying pulmonary infection. The rest of the study group (34 patients) remained HBsAg(-) throughout the study. Two of them had an HBsAg(+) donor, but neither developed HBV infection in their follow-up period. The acquisition rate of HBV infection was relatively low in recipients who were positive for anti-HBs compared to those who were negative for anti-HBs (8 vs 19%). Anti-HBs positivity remained for a longer period in recipients who received marrow from anti-HBs positive donors compared to those recipients who had anti-HBs negative donors (median 12 vs 3 months). We think that HBV is a frequent cause of liver dysfunction in alloBMT patients where HBV infection is endemic. Whether the disease is in the form of reactivation of HBsAg-positive recipients, or is acquired from unknown sources in recipients who never had contact with the virus, the course of the disease is not fatal. Silent serologic changes can be demonstrated if viral serologic markers are sought serially. Among them, the disappearance of serum anti-HBs may be important as it increases the risk of HBV contamination in recipients.