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    Mithat Bozdayi

    Thromboembolic events are more common in patients with inflammatory bowel disease than in the normal population; however, the reason for the increased prevalence is not clear. The aim of this study was to evaluate the prevalence of factor... more
    Thromboembolic events are more common in patients with inflammatory bowel disease than in the normal population; however, the reason for the increased prevalence is not clear. The aim of this study was to evaluate the prevalence of factor V Leiden, prothrombin G20210A and methylene tetrahydrofolate reductase (MTHFR) gene mutations in IBD patients followed in our outpatient clinic. Thirty-four patients with ulcerative colitis and 28 patients with Crohn's disease and 80 healthy controls were included in the study. No patient had a history of previous thromboembolism. Factor V Leiden, prothrombin G20210A and MTHFR gene mutations were studied. Heterozygote factor V Leiden mutation was found in five (6.25%) control patients and in two (3.2%) IBD patients. Heterozygote MTHFR mutation was obtained in seven (11.3%) IBD patients and in five (6.25%) controls. Heterozygote prothrombin G20210A mutation was found in two (2.5%) and homozygote MTHFR mutation in one (1.25%) control patient. The...
    A relation between hepatitis C virus (HCV) infection with lichen planus (LP) has been reported in the literature but remains controversial. To find out the prevalence of HVC infection among patients with LP. Forty-one cases of LP... more
    A relation between hepatitis C virus (HCV) infection with lichen planus (LP) has been reported in the literature but remains controversial. To find out the prevalence of HVC infection among patients with LP. Forty-one cases of LP diagnosed at the Dermatology Clinic of our hospital between March 1995 and May 1996 were evaluated (22 men and 19 women; mean age 41.6 years). They were screened for the presence of HBsAg, anti HBs, and anti-HCV by ELISA and HCV-RNA by nested polymerase chain reaction (PCR). Blood donors registered in Ankara University Ibni Sina Hospital Blood Bank were used as a control group. Of the 41 LP patients, 2 (4.8%) had anti-HCV positivity together with HCV-RNA positivity. Twelve patients (29.2%) had anti-HBs and 3 patients (7.3%) had HBsAg positivity. In blood donors, anti-HCV positivity prevalence was 2.5%. The results of this study suggest that no relationship exists between hepatitis C virus infection and lichen planus among Turkish patients.
    A significant association between variations in amino acid sequences resides between 2209-2248 nucleotides of HCV non-structural 5A (NS5A) gene, and response to interferon treatment has been proposed. The aim of this study was to... more
    A significant association between variations in amino acid sequences resides between 2209-2248 nucleotides of HCV non-structural 5A (NS5A) gene, and response to interferon treatment has been proposed. The aim of this study was to determine whether the amino acid sequence changes in ISDR could be correlated to response to alpha interferon treatment in Turkish patients infected with HCV genotypes 1b and 1a. Thirty-nine patients with chronic C virus infection (35 and 4 patients with genotype 1b and 1a, respectively), receiving 3x3-5 MU of interferon a-2b for six months were included in the study. Following PCR amplification of the region from pre-treatment serum samples, the products were directly sequenced. The amino acid sequence of NS5A was compared with the published sequence for HCV-J (AA 2209-2248). Mutant type was defined as three or more amino acid mutations, and intermediate type as 1-3 amino acids in this region. Otherwise, they were defined as the wild type (no amino acid mu...
    Research Interests:
    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),... more
    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 sub...
    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... more
    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 ther...
    Clarithromycin resistance in Helicobacter pylori is a principal cause of failure of eradication therapies, and its prevalence varies geographically. The IceA gene is a virulence factor associated with clinical outcomes. The objective of... more
    Clarithromycin resistance in Helicobacter pylori is a principal cause of failure of eradication therapies, and its prevalence varies geographically. The IceA gene is a virulence factor associated with clinical outcomes. The objective of this study was to determine the current state of clarithromycin resistance prevalence, and to investigate the role of iceA genotypes in 87 Turkish adult patients (65 with functional dyspepsia and 22 with duodenal ulcer). A2143G and A2144G point mutations were tested by PCR-RFLP for clarithromycin resistance. Among the patients in the study, 28 patients were tested by agar dilution as well. Allelic variants of the iceA gene were identified by PCR. A total of 24 (27.6%) strains evidenced one of the mutations, either A2143G or A2144G. IceA1 was found to be positive in 28 of the strains (32.2%), iceA2 was positive in 12 (13.8%) and, both iceA1 and iceA2 were positive in 22 (25.3%) strains. In conclusion, we discovered no relationships between iceA genoty...
    Different methods of diagnosis have been found to be inefficient in terms of screening and early diagnosis of lung cancer. Cancer cells produce proteins whose serum levels may be elevated during the early stages of cancer development.... more
    Different methods of diagnosis have been found to be inefficient in terms of screening and early diagnosis of lung cancer. Cancer cells produce proteins whose serum levels may be elevated during the early stages of cancer development. Therefore, those proteins may be recognized as potential cancer markers. The aim of this study was to differentiate healthy individuals and lung cancer cases by analyzing their serum protein profiles and evaluate the efficacy of this method in the early diagnosis of lung cancer. 170 patients with lung cancer, 53 under high risk of lung cancer, and 47 healthy people were included in our study. Proteomic analysis of the samples was performed with the SELDI-TOF-MS approach. The most discriminatory peak of the high risk group was 8141. When tree classification analysis was performed between lung cancer and the healthy control group, 11547 was determined as the most discriminatory peak, with a sensitivity of 85.5%, a specificity of 89.4%, a positive predict...
    We aimed to compare the efficacy of interferon-alpha2b (IFN) induction treatment in combination with ribavirin to IFN induction alone in chronic hepatitis C. In total, 125 patients (66 male, 59 female, mean age: 48 +/- 9, range: 21-70)... more
    We aimed to compare the efficacy of interferon-alpha2b (IFN) induction treatment in combination with ribavirin to IFN induction alone in chronic hepatitis C. In total, 125 patients (66 male, 59 female, mean age: 48 +/- 9, range: 21-70) were enrolled and randomized into two arms: In the first, patients received 5 MU/day of IFN for 4 weeks followed by 3 MU/day for the next 4 weeks. Treatment was continued with 3 MU three times a week IFN for an additional 40 weeks. Ribavirin was administered 1000-1200 mg/day according to the body weight for the entire 48-week period. In the second arm, patients received placebo in addition to IFN. Fifty-nine patients were placed in the ribavirin arm and 66 in placebo arm. All patients were genotype 1. At week 48, 24/66 (36%) from the placebo and 31/59 (52%) from the ribavirin group responded (P > 0.05). However, during the 24-week untreated follow-up period, 13/24 (54%) from the placebo, and 8/31 (26%) from the ribavirin group relapsed (P = 0.002.)...
    A few series of indole derivatives were screened for antimicrobial, antifungal and anti-HBV activities. The compounds were tested for their in vitro antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli... more
    A few series of indole derivatives were screened for antimicrobial, antifungal and anti-HBV activities. The compounds were tested for their in vitro antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli and for their antifungal activity against Candida albicans using a disc diffusion method, which measures the diameter of the inhibition zone around a paper disc soaked in a solution of the test compounds. The antimicrobial activity results showed that all compounds are as a active as the standard compound ampicillin against Staphylococcus aureus. It was also found that indole carboxamide derivatives, substituted at 3-position with several benzyl groups, showed better inhibition of Bacillus subtilis than their congeners substituted at 2-position. Activity patterns of the compounds against Escherichia coli and Staphylococcus aureus were found slightly different by the same method. In this case, there was no correlation between structure and activity of the compounds. The antifungal activity of carboxamide derivatives was found higher compared to that of the propanamide derivatives. The minimum inhibitory concentration (MIC) values of some indole derivatives were also determined by the tube dilution technique. The MIC values of the compounds were found nearly 20- to 100-fold smaller compared to the standard compounds ciprofloxacin and ampicillin (1.56-3.13 microg/ml and 1.56-12.5 microg/ml, respectively) against Staphylococcus aureus, Bacillus subtilis and Escherichia coli. The MIC values of the tested compounds showed that these are better inhibitors for Candida albicans. Indole derivatives were screened by the anti-HBV susceptibility test. No compound showed good inhibition against the HBV virus.
    Page 1. http://ves.sagepub.com/ Vascular and Endovascular Surgery http://ves.sagepub.com/ content/27/4/264 The online version of this article can be found at: DOI: 10.1177/ 153857449302700403 1993 27: 264 VASC ENDOVASCULAR SURG Kemal... more
    Page 1. http://ves.sagepub.com/ Vascular and Endovascular Surgery http://ves.sagepub.com/ content/27/4/264 The online version of this article can be found at: DOI: 10.1177/ 153857449302700403 1993 27: 264 VASC ENDOVASCULAR SURG Kemal Bayazit ...
    Abstract This study was planned to show the beneficial effects of prostacyclin (PGI 2) utilization on adverse effects of protamine. PGI 2 was administered at a rate of 5 ng/kg/min. Twenty patients entered this study. Half of them received... more
    Abstract This study was planned to show the beneficial effects of prostacyclin (PGI 2) utilization on adverse effects of protamine. PGI 2 was administered at a rate of 5 ng/kg/min. Twenty patients entered this study. Half of them received PGI 2 whereas the others did not.
    A total of 20 patients with coronary artery disease were studied in order to assess the benefits of prostacyclin administration on reperfusion of the ischaemic myocardium after cardiopulmonary bypass. Ten received prostacyclin (25 ng/kg... more
    A total of 20 patients with coronary artery disease were studied in order to assess the benefits of prostacyclin administration on reperfusion of the ischaemic myocardium after cardiopulmonary bypass. Ten received prostacyclin (25 ng/kg per min) while ten were untreated controls. There was no difference between groups with regard to age, preoperative ejection fraction and aortic cross-clamping times. There were no in-hospital deaths in either group. The administration of prostacyclin significantly altered the metabolic side effects of reperfusion followed by hypothermic cardioplegic arrest. Myocardial oxygen consumption after cardiopulmonary bypass was significantly higher in the prostacyclin-treated group than in controls (18.5 ml versus 13 ml; P < 0.01). Prostacyclin treatment significantly reduced the leucocyte activity: leukotriene B4 concentrations were 58 pmol/l in prostacyclin-treated patients compared with 93 pmol/l in controls (P < 0.01). Such recovery of metabolic status during reperfusion resulted in better haemodynamic function in patients receiving prostacyclin.
    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... more
    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 (P<0.0001 and P<0.05, respectively). No significant difference in terms of positive TFF3 stained BECs between GVHD and PBC samples was observed (P>0.05). 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 (P<0.0001). 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.
    The aim of this study was to demonstrate the beneficial effects of aminophylline on protamine cardiotoxicity. Thirty-four patients were examined, 17 of whom received aminophylline 3 mg/kg before protamine administration, being the study... more
    The aim of this study was to demonstrate the beneficial effects of aminophylline on protamine cardiotoxicity. Thirty-four patients were examined, 17 of whom received aminophylline 3 mg/kg before protamine administration, being the study group, while the other 17, being the control group, did not. All cardiac output and biochemical measurements were evaluated 5 min following protamine administration. The cAMP level was 43.4 +/- 3.51 pmol/ml in the study group and 18.7 +/- 2.98 in the control group (P < 0.0001) before protamine administration, while the oxygen extraction rate decreased from 49% to 44 +/- 2% in the control group, and from 51.2% to 47 +/- 3% in the study group (P < 0.03). The N-acetyl glucosaminidase value was 16.9 +/- 13.9 pmol/ml in the study group and 27.8 +/- 1.47 pmol/ml in the control group (P < 0.01), and myocardial lactate extraction was -0.20 +/- 0.03 in the control group and -0.07 +/- 0.07 in the study group (P < 0.001). The left ventricular stroke work index was 28.6 +/- 3.14 gm/m2 in the control group and 37 +/- 6.77 gm/m2 in the study group (P < 0.002). The findings of this study led us to conclude that the adverse effects of heparin neutralization using protamine can be relieved by aminophylline.
    The aims of this study were to assess hepatitis B surface antigen (HBsAg) seroconversion and to determine its impact on the natural course of the disease in patients with HBeAg-negative chronic hepatitis B (CHB) during lamivudine (LMV)... more
    The aims of this study were to assess hepatitis B surface antigen (HBsAg) seroconversion and to determine its impact on the natural course of the disease in patients with HBeAg-negative chronic hepatitis B (CHB) during lamivudine (LMV) treatment. A total of 183 consecutive patients with HBeAg-negative CHB who were treated with LMV were included in the study. Data were retrospectively collected from outpatient visit charts. The primary endpoint was HBsAg seroconversion to anti-HBs. The secondary endpoint was to determine the development of cirrhosis. Loss of HBsAg was confirmed in 10 patients and seroconversion to anti-HBs in nine patients during LMV treatment or after its discontinuation. HBsAg seroconversion was achieved on-treatment in four patients after a median treatment duration of 30 months and off-treatment in the remaining five patients in a median 61 months after LMV discontinuation. The cumulative probability of HBsAg seroconversion increased from 0.6% at 1 year and 1.9% at 5 years to 21.5% at 10 years of LMV during and after LMV treatment. HBsAg clearance was preceded by undetectable serum hepatitis B virus (HBV) DNA. The majority of the patients responding to treatment had undetectable HBV DNA levels at 24 weeks of treatment. The cumulative probability of LMV resistance increased from 2.2% at 1 year to 37.3% at 5 years. No baseline parameter predicting either HBsAg seroconversion or the emergence of LMV resistance was identified. None of the patients with HBsAg seroconversion experienced virological breakthrough or disease progression during the follow-up period. These results indicate that HBsAg seroclearance can occur in patients with HBeAg-negative CHB under LMV therapy and predicts better clinical outcome.
    CD4+ T cells are thought to contribute to antiviral immune responses by secretion of cytokines thereby providing help to CD8+ T and B cells. However, perforin-positive cytotoxic CD4+ T cells have been described in human immunodeficiency... more
    CD4+ T cells are thought to contribute to antiviral immune responses by secretion of cytokines thereby providing help to CD8+ T and B cells. However, perforin-positive cytotoxic CD4+ T cells have been described in human immunodeficiency virus-positive patients suggesting a role not only of CD8+ but also of CD4+ T cells for killing virus-infected cells. We investigated 76 patients with viral hepatitis [15 hepatitis B virus (HBV), 22 HBV/hepatitis D virus and 17 hepatitis C virus (HCV)] for cytotoxic CD4+ T cells. The frequency of perforin-positive CD4+ T cells in viral hepatitis was highly variable ranging from < 1% to more than 25%. Perforin-positive CD4+ T cells displayed the phenotype of terminally differentiated effector cells (CD28-, CD27-). The highest frequencies of CD4+ cytotoxic T lymphocytes (CTLs) were found in patients with delta hepatitis (P = 0.04 vs HBV and HCV patients), and the presence of CD4+ CTLs was associated with elevated aspartate aminotransferase levels (P = 0.01) and decreased platelet counts (P = 0.03). Perforin-positive CD4+ T cells decreased in two individuals during spontaneous clearance of acute hepatitis C. Significant associations were found between the frequency of perforin-expressing CD4+ cells and age (P = 0.04), perforin-positive CD8+ cells (P < 0.001) and perforin-positive CD4-/CD8- lymphoid cells (P = 0.002). Differentiated CD27- effector CD4+ CTLs can be detected in patients with viral hepatitis. In particular in patients with more advanced liver disease, the accumulation of perforin-positive T cells with age could be one correlate for the more severe course of viral hepatitis in elderly individuals.
    A number of disorders for which an association with hepatitis C virus infection exist. These disorders include essential mixed cryoglobulinemia, membranoproliferative glomerulonephritis, and idiopathic pulmonary fibrosis. This study was... more
    A number of disorders for which an association with hepatitis C virus infection exist. These disorders include essential mixed cryoglobulinemia, membranoproliferative glomerulonephritis, and idiopathic pulmonary fibrosis. This study was initiated to investigate the cellular content and lymphocyte subpopulations of bronchoalveolar lavage fluid obtained from individuals with chronic hepatitis C and to compare the results to those of controls. Eighteen patients with chronic hepatitis C (male/female, 6/12) and 14 healthy volunteers (male/female, 6/8), were studied. Bronchoalveolar lavage fluid was obtained from each; and the lymphocyte subtypes and the presence of HCV-RNA in the bronchoalveolar lavage fluid were determined. All anti-HCV positive subjects were HCV-RNA positive in serum. One (5.6%) had a HCV-RNA positive bronchoalveolar lavage. The total cell and neutrophil counts of the bronchoalveolar lavage fluid were significantly greater in patients with chronic hepatitis C as compared to controls (5,799.6 +/- 957.4 x 10(3)/ml vs. 1,835.7 +/- 447.8 x 10(3)/ml, P = 0.001; 1,175.8 +/- 634.7 x 10(3)/ml vs. 53.1 +/- 28.1 x 10(3)/ml, P = 0.029). In contrast, the lymphocyte, macrophage and eosinophil counts did not differ. No difference in the percentage, median or range of individual T cell subsets or B cell numbers in the bronchoalveolar lavage fluid existed between the groups. It is concluded that hepatitis C virus infection may be associated with an occult pulmonary inflammatory reaction manifested by an increased number of polymorphonuclear neutrophils in bronchoalveolar lavage fluid. This finding may contribute to the process that leads to idiopathic pulmonary fibrosis seen in a minority of cases of chronic hepatitis C.
    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... more
    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. 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. 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. 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<0.05). The number of T/A and A1896 stop codon mutations did not yield a statistically significant difference between ALT normal and elevated groups. It was also found that 1762-1764 T/A and precore A 1896 mutation existed in five and six out of 29 HBeAg positive patients, respectively. In 38 anti-HBe positive patients, 1762-1764 T/A and precore A1896 mutation were detected in three and 16 patients respectively, and coexisted in 10 patients. Precore A 1896 stop codon mutation seems to play an essential role in the loss of HBeAg in Turkish patients. Serum viremia levels of HBV in patients having precore stop codon and/or T/A mutation were not significantly different from the other patients carrying wild type strains. Nucleotide variability in the core promoter region may be one of the factors linked to hepatitis B disease activity.
    Prolonged antiviral treatment results in selection and accumulation of resistant strains in quasispecies pool in hepatitis B virus (HBV) infection. The aim of this study was to characterise a novel HBV pattern which shows resistance to... more
    Prolonged antiviral treatment results in selection and accumulation of resistant strains in quasispecies pool in hepatitis B virus (HBV) infection. The aim of this study was to characterise a novel HBV pattern which shows resistance to lamivudine, adefovir dipivoxil and entecavir using in vitro phenoyping assay. A male 36 years old patient diagnosed with anti HBe-positive chronic hepatitis B (CHB) had received lamivudine treatment for 7 years following an initial unsuccessfull interferon treatment. The therapy had been switched to adefovir and then to entecavir when breakthrough occcured during each treatment. This led only to a temporary HBV DNA decline which soon was followed by viral breakthrough despite the lack of known entecavir resistance mutations. Patient died after 9 months of entecavir treatment from liver failure. A total of 434 clones from 6 different serum samples were analysed retrospectively. HBV genomes bearing mutation patterns suggestive of antiviral resistance were analysed by in vitro phenotyping assay. Dominance of a clone carrying L80LV, L91I, M204I, S219A, N238D, Y245H changes was detected in the last serum sample of the patient just before his death. This pattern displayed 30.4 fold resistance to entecavir when compared with the wild type HBV by in vitro phenotyping assay. A novel mutation pattern showing a high degree of resistance to entecavir was documented. In this pattern, the S219A and Y245H mutations mainly seem to contribute to the emergence of ETV resistance.
    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... more
    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. 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. 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. 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.
    Gastroenterology, Volume 120, Issue 5, Pages A568, April 2001, Authors:Hakan Senturk; Galip Ersoz; Resat Ozaras; Sabahattin Kaymakoglu; Hakan Bozkaya; Ali Mert; Selim Karayalcin; Mithat Bozdayi; Yucel Batur. Gastroenterology ...
    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... more
    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 (P<0.05). 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 (P<0.05). 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.
    We report a severe flare-up in a chronic hepatitis patient due to dual infection with hepatitis B and D viruses during alpha-interferon therapy. Pre-treatment, the patient had detectable levels of both viruses. After 9 months of therapy,... more
    We report a severe flare-up in a chronic hepatitis patient due to dual infection with hepatitis B and D viruses during alpha-interferon therapy. Pre-treatment, the patient had detectable levels of both viruses. After 9 months of therapy, an alanine aminotransferase flare with acute hepatic decompensation was detected. Alpha-interferon was discontinued and lamivudine (100 mg once daily) was started, after which the patient reversed slowly. Hepatitis B early antigen (HBeAg) seroconversion with hepatitis B virus-DNA clearance was observed 1 month after the flare; 15 months later, the patient had persistently normal alanine aminotransferase levels with negative results for both serum hepatitis B virus-DNA and hepatitis D virus-RNA. In conclusion, liver disease may be exacerbated during interferon therapy in patients with chronic hepatitis D who are also positive for hepatitis B surface antigen (HBsAg) and HBeAg. Therefore, extra care in monitoring should be considered and strict follow-up is recommended, since clearance of hepatitis D may occur after HBeAg seroconversion in coinfected patients. Lamivudine may be administered early in hepatitis D-RNA/HBsAg-positive patients at high risk of liver failure once a severe flare-up occurs during interferon therapy.

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