Hepatitis: Idilman R

Idilman R. · Department of Gastroenterology, Ankara University School of Medicine, Ibn-i Sina Hospital, Sihhiye, 06100 Ankara, Turkey. · Minerva Gastroenterol Dietol. · Pubmed #16554705 No free full text.

Abstract: Hepatitis B virus reactivation-related hepatitis is a serious cause of liver-related morbidity and mortality in inactive hepatitis B virus carriers with hemato/oncological malignancies who receive chemo/immunosuppressive therapy. It occurs in 14% to 50% of such individuals and the mortality ranges from 3.7% to 60%. The aims of the present review were 1) to determine the effect of lamivudine prophylaxis in inactive hepatitis B virus carriers with hemato/oncological malignancies who receive chemo/immunosuppressive therapy, and 2) to define the safety and duration of lamivudine in such individuals. The data currently available suggest that all individuals with hemato/oncological malignancies who undergo chemo/immunosuppressive therapy should be screened for hepatotropic viruses. Lamivudine prophylaxis in inactive hepatitis B virus carriers with hemato/oncological malignancies who receive chemo/immunosuppressive therapy prevents chemo/immunosuppressive-induced hepatitis B virus reactivation. Lamivudine also prevents interruptions in treatment as a result of hepatitis B virus reactivation. Lamivudine is safe and tolerable in such individuals. The ideal protocol of lamivudine prophylaxis for the prevention of hepatitis B virus reactivation in such individuals is not yet established. However, it would appear prudent to begin lamivudine at the time of the initiation of the chemo/immunosuppressive therapy and to continue it throughout the period of chemo/immunosuppressive administration and for at least one but possibly two years following the therapy discontinuation.

Idilman R, Colantoni A, De Maria N, Harig JM, van Thiel DH. · Loyola University Medical Center, Gastroenterology/Liver Transplantation, Maywood, Ill. 60153, USA. · Scand J Gastroenterol. · Pubmed #11305507 No free full text.

This publication has no abstract.

Bozkaya H, Yurdaydin C, Idilman R, Tüzün A, Cinar K, Erkan O, Bozdayi AM, Erden E, Uzun Y, Cetinkaya H, Uzunalimoglu O. · Department of Gastroenterology, Ankara University School of Medicine, Cebeci, Ankara-Turkey. · Antivir Ther. · Pubmed #15865226 No free full text.

Abstract: BACKGROUND: Our aim was to determine the short-term natural course of viraemia and the response to lamivudine treatment in HBeAg-negative chronic hepatitis B patients with a persistently low hepatitis B virus (HBV)-DNA level. METHODS: A total of 55 patients were included. Group 1 consisted of 37 patients with low-level viraemia and high serum alanine aminotransferase (ALT) levels and further randomized to two groups: group 1a (n=19) patients received 1 year of lamivudine therapy and group 1b (n=18) patients were untreated controls. Group 2 consisted of 18 inactive carriers who were followed as controls of untreated low viraemic chronic hepatitis B patients. HBV DNA was longitudinally determined by real-time polymerase chain reaction assay. RESULTS: A female predominance in group 2 was observed while males were predominant in group 1. Mean age and baseline HBV-DNA levels did not differ between group 1 and 2 patients while group 1 patients had a higher histological score (P<0.01). Of group 1a patients, 44% had complete ALT normalization at end of treatment, whereas 21% untreated group 1b patients had normal ALT at the end of the follow-up. No change in histological activity was observed in group 1a patients at the end of treatment. HBV-DNA levels did not significantly change from baseline to end-of-treatment/observation period in patient groups. The viraemia course was not different across the groups. CONCLUSIONS: Low viraemic HBeAg-negative patients with high ALT present with minimal/mild histological activity. Inactive carriers cannot be differentiated from low viraemic patients with high ALT based on HBV DNA determination. Although lamivudine treatment can be effective in some cases, observation rather than a prompt treatment attempt seems to be more logical because of mild histological changes and low response rate to treatment in these patients.

Idilman R, Arat M, Soydan E, Törüner M, Soykan I, Akbulut H, Arslan O, Ozcan M, Türkyilmaz AR, Bozdayi M, Karayalçin S, Van Thiel DH, Ozden A, Beksaç M, Akan H. · Department of Gastroenterology, Ankara University Medical School, Ibn-i Sina Hospital, Ankara, Turkey. · J Viral Hepat. · Pubmed #14996349 No free full text.

Abstract: 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.

Idilman R, Colantoni A, De Maria N, Ustun C, Sam R, Ing TS, Akan H, Koc H, Van Thiel DH. · Loyola University Medical Center, Dept. of Medicine, Division of Gastroenterology and Hepatology, Maywood, IL, USA. · Hepatogastroenterology. · Pubmed #12630026 No free full text.

Abstract: BACKGROUND/AIMS: Because a more rapid and high dose vaccination schedule may be advantageous in immunosuppressed individuals to induce an earlier immunization, the aim of the present study was to assess the response to high dose, short interval hepatitis B virus vaccination in various immunosuppressed-patient populations. METHODOLOGY: A total of one hundred and thirty-eight immunosuppressed patients (86 cirrhotics, 42 dialysis patients, 10 allogeneic hematopoietic cell transplants) and 26 healthy subjects as controls were vaccinated utilizing a high dose vaccine (40 mcg) and a shortened immunization schedule. RESULTS: Ninety-two percent of the controls responded to the high dose, short interval hepatitis B virus vaccination schedule. In contrast, only 48% of the immunosuppressed patients seroconverted to anti-HBs positivity (p < 0.001). No difference in the antibody response rate was seen between the various immunosuppressed populations studied. No significant hepatitis B virus vaccination-related adverse effects were seen in any of the groups vaccinated. CONCLUSIONS: Although a high dose, short interval hepatitis B virus vaccination schedule is safe in immunosuppressed patients, the antibody response is still significantly reduced as compared to healthy subjects and only slightly greater than that achieved with standard vaccination schedules, as reported in literature. The possibility of achieving an earlier immunization, however, may be of some advantage to protect acquired viral infection.

Idilman R, De MN, Colantoni A, Nadir A, Van Thiel DH. · Department of Medicine, Loyola University Medical Center, Maywood, Illinois, USA. · Am J Gastroenterol. · Pubmed #11866284 No free full text.

Abstract: OBJECTIVES: The efficacy of the standard hepatitis B virus (HBV) vaccination schedule in individuals with chronic hepatitis C is reported to be reduced. Our aim was to assess the response rate to high dose, short interval HBV vaccination in such individuals. METHODS: A total of 152 individuals with chronic hepatitis C were vaccinated with 40 microg of vaccine administered monthly for 3 months. Twenty-six individuals with no evidence of liver disease underwent the same vaccination schedule and were considered to be the control group. Hepatitis C virus (HCV)-positive subjects who did not seroconvert to anti-hepatitis B surface positivity after the third dose of the vaccine (nonresponder) were vaccinated with a fourth dose of vaccine (booster dose, 80 microg). RESULTS: One hundred nine of the 152 individuals with chronic hepatitis C (72%) seroconverted to anti-hepatitis B surface positivity (> 10 mIU/ml), as compared to 24 of the 26 controls (92%, p < 0.05). Although individuals with chronic hepatitis C responded less frequently to high dose, short interval HBV vaccination than did the controls, no differences in terms of effective immunity (>100 mIU/ml) were evident among the two groups of responders (51% vs 54%). Also, no difference in response was reported between individuals with chronic active hepatitis C and controls (92% vs 80%). The response rate was significantly lower in cirrhotics than in the noncirrhotic group (54% vs 80%, p < 0.001). Besides cirrhosis, no other demographic or bioclinical factor was found to influence the response to vaccination. After the additional booster dose, the overall response was increased to 74% of the cirrhotics and 88% of the noncirrhotics. No major HBV vaccine-related adverse effects were seen. CONCLUSIONS: A high dose, short interval HBV vaccination schedule is safe in individuals with chronic hepatitis C. From these data, it is suggested that a high dose and a short interval between HBV vaccinations may produce an effective and early antibody response in such patients.

De Maria N, Idilman R, Colantoni A, Van Thiel DH. · Loyola University Medical Center, Department of Medicine, Division of Gastroenterology and Liver Transplantation, Maywood, Illinois 60153, USA. · J Viral Hepat. · Pubmed #11555195 No free full text.

Abstract: Hepatitis B virus (HBV) vaccination is recommended for individuals with chronic liver disease. However, the response to standard doses of hepatitis B vaccines in such individuals has been poor. The aim of the present study was to assess the response to high-dose short-interval HBV vaccination in individuals with chronic liver disease of different aetiologies. A total two hundred and 24 subjects with chronic liver disease (138 chronic active hepatitis and 86 cirrhosis) and 26 healthy controls were vaccinated using a high-dose (40 microg) short-interval (monthly for 3 consecutive months) HBV vaccination schedule. One hundred and thirty-eight of the 224 subjects with chronic liver disease (62%) seroconverted to anti-HBs antibody positivity (>10 mIU/mL) after the third dose of vaccine as compared with 24 of the 26 controls (92%) (P < 0.01). The response rate was reduced in individuals with cirrhosis (36/86, 42%), particularly in alcohol-induced cirrhosis (2/17, 12%), as compared with individuals with chronic hepatitis (102/138, 74%) (P < 0.001). No significant HBV vaccination-related adverse effects were seen in individuals with or without cirrhosis as well as in the controls. High-dose short-interval HBV vaccination is safe and efficacious in individuals with chronic liver disease. The response to HBV vaccination is reduced in cirrhotics, particularly those with alcoholic cirrhosis. These data suggest that HBV vaccination should be accomplished early in an individual cause of chronic liver disease prior to the development of cirrhosis.

Idilman R, Kaymakoglu S, Oguz Onder F, Ahishali E, Bektas M, Cinar K, Pinarbasi B, Karayalcin S, Badur S, Cakaloglu Y, Mithat Bozdayi A, Bozkaya H, Okten A, Yurdaydin C. · Department of Gastroenterology, Faculty of Medicine, Ankara University, Ankara, Turkey. · J Viral Hepat. · Pubmed #19222742 No free full text.

Abstract: 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 (<10(7) copies/mL) was a significant predictor of response to ADV treatment (P<0.01). Cumulative probability of ADV resistance was 1.2%, 15.1% and 37.3% at 12, 24 and 36 months of therapy, respectively. By multivariate analysis, baseline high viral load and primary nonresponse to treatment at week 24 predicted ADV resistance. The data indicate that a time limited add-on strategy does not provide benefit over the switch strategy with respect emergence of ADV resistant mutants in LAM-R CHB patients.

Koytak ES, Mizrak D, Bektaş M, Verdi H, Arslan Ergül A, Idilman R, Cinar K, Yurdaydin C, Ersõz S, Karayalçin K, Uzunalimoğlu O, Bozkaya H. · Departments of Gastroenterology and General Surgery, Ankara University, School of Medicine, Ankara. · Turk J Gastroenterol. · Pubmed #19119483 links to  free full text

Abstract: BACKGROUND/AIMS: Several lines of evidence suggest that peroxisome proliferator-activated receptor alpha may be involved in hepatocarcinogenesis. L162V polymorphism of the peroxisome proliferator-activated receptor alpha gene enhances the transactivation activity of this transcription factor. The aim of this study was to determine the frequency and clinical correlates of peroxisome proliferator-activated receptor alpha L162V polymorphism in hepatitis virus-induced hepatocellular carcinoma. METHODS: 90 hepatocellular carcinoma patients diagnosed at Ankara University Gastroenterology Clinic between January 2002 and July 2003 and 80 healthy controls with normal body mass index, blood chemistry and with negative viral serology were included. peroxisome proliferator-activated receptor alpha L162V polymorphism was determined by PCR-RFLP. RESULTS: hepatocellular carcinoma etiologies were as follows: 56 HBV, 12 HBV+HDV, 22 HCV. Eighty-seven patients (97%) were cirrhotic, and 60 patients (67.5%) had advanced tumors. In 83 (92%) of 90 hepatocellular carcinoma patients, gene segment including polymorphic region could be amplified by PCR (50 HBV, 12 HBV+HDV, 21 HCV) and 6 of them (7.2%, all infected with HBV) had L162V polymorphism, while 2 (2.5%) of 80 controls had this polymorphism (p=0.162). This trend became more remarkable when only HBV (HBV+HDV)-infected patients were compared with controls (6/62, 9.7% vs. 2/80, 2.5%, respectively, p=0.071). Five of 6 patients with L162V had advanced disease. CONCLUSIONS: Peroxisome proliferator-activated receptor alpha L162V polymorphism tends to occur in HBV-induced hepatocellular carcinoma and is absent in HCV-related hepatocellular carcinoma. These findings may show clues for the existence of different carcinogenesis mechanisms in these two common etiologies. Frequent occurrence of advanced disease in patients with L162V polymorphism suggests a role for this polymorphism in tumor progression.

Uzun Y, Bozkaya H, Erden E, Cinar K, Idilman R, Yurdaydin C, Uzunalimoglu O. · Department of Gastroenterology, Faculty of Medicine, Karadeniz Technical University, Blok 30 Daire 11, 61080 Trabzon, Turkey. · J Gastroenterol Hepatol. · Pubmed #16724981 No free full text.

Abstract: BACKGROUND: In hepatitis B early antigen (HBeAg)-negative patients, response predictors to current treatment regimens are not well known. Hepatocyte cell cycle may influence hepatitis B virus (HBV) replication and hepatitis B core antigen (HBcAg) expression, which is a major target for antiviral immune response. The aim of the present paper was to evaluate the role of HBcAg expression in liver tissue and the rate of hepatocyte proliferation in response to antiviral treatment in chronic hepatitis B. METHODS: A total of 33 chronic hepatitis B patients (nine HBeAg positive, 24 HBeAg negative) treated with either lamivudine and interferon combined or lamivudine alone were included. Liver expressions of proliferating cell nuclear antigen (PCNA) and HBcAg were immunohistochemically determined. The HBV-DNA levels were measured by a hybrid capture assay. Complete response was defined as alanine aminotransferase (ALT) normalization and HBV-DNA negativity. RESULTS: At the end of treatment, 23 patients (67.7%) were responders (12 of 23 were sustained responders), while 10 (33.3%) were non-responders. Age, sex, ALT, HBV-DNA levels, HBeAg status, histological activity, fibrosis scores and PCNA labeling index were similar in responders versus non-responders at baseline. The number of patients with positive HBcAg staining was lower in responders compared to non-responders at the end of treatment (17.4% vs 80%, respectively, P < 0.001), although a similar number of sustained responders and non-responders had positive HBcAg staining. CONCLUSION: Absence or a low level of HBcAg expression may predict the end of treatment response to current therapies, especially in HBeAg (-) patients. The PCNA determination does not predict treatment response.

Coban S, Palabiyikoğlu M, Ensari A, Idilman R, Köklü S, Yolcu OF, Ormeci N. · Department of Gastroenterology, Ankara University Medical School, Ankara, Turkey. · Dig Dis Sci. · Pubmed #16416190 No free full text.

This publication has no abstract.

Verdi H, Koytak ES, Onder O, Ergül AA, Cinar K, Idilman R, Erden E, Bozdayi AM, Yurdaydin C, Uzunalimoglu O, Bozkaya H. · Institute of Hepatology, Ankara University, Turkey. · J Investig Med. · Pubmed #16297361 No free full text.

Abstract: BACKGROUND: Peroxisome proliferator-activated receptor alpha (PPARalpha) plays important roles in lipid metabolism. A recently discovered L162V polymorphism of the PPARalpha gene is associated with enhanced transcriptional activity. In this study, the frequency of L162V was investigated in nonalcoholic steatohepatitis (NASH) and genotype 1 hepatitis C virus (HCV)-related liver steatosis. METHODS: Seventy-two NASH and 141 HCV-infected patients (54 with steatosis, 87 without steatosis) and 119 healthy controls were included. L162V polymorphism of the PPARalpha gene was analyzed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). RESULTS: PCR and RFLP analysis of the related gene segment was successful in 93%, 96%, and 100% of NASH and HCV-infected patients and controls, respectively. The frequency of the L162V polymorphism was similar in the NASH and HCV-infected patients and controls (5.9%, 3.6%, and 2.5%, respectively). No difference in the frequency of this polymorphism was observed in HCV-infected patients with or without significant liver steatosis. L162V was not associated with obesity, type 2 diabetes mellitus, hypercholesterolemia, or hypertriglyceridemia. CONCLUSIONS: Neither NASH nor genotype 1 HCV-related liver steatosis seems to be associated with the PPARalpha L162V polymorphism. This polymorphism may have no association with the presence of type 2 diabetes mellitus, obesity, or various blood lipid alterations in NASH and HCV-infected patients.

Idilman R, Erden E, Arat M, Soydan E, Erkan O, Kuzu I, Sahin Y, Coban S, Bozdayi M, Giraud A, Akan H, Karayalcin S, Ozden A. · Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey. · Transplantation. · Pubmed #16278592 No free full text.

Abstract: BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Bozdayi G, Türkyilmaz AR, Idilman R, Karatayli E, Rota S, Yurdaydin C, Bozdayi AM. · Department of Microbiology, School of Medicine, Gazi University, Ankara, Turkey. · J Med Virol. · Pubmed #15977237 No free full text.

Abstract: Hepatitis viruses are the leading causes of chronic liver disease resulting in chronic hepatitis, cirrhosis, and hepatocellular carcinoma in the world and also in Turkey. Although Turkey has an intermediate rate of hepatitis B virus (HBV) infection with a prevalence reported as 5%, a complete HBV genome sequence has not been published. In this study, the molecular characterization and phylogenetic analysis are described of 11 complete HBV genomes isolated from 11 naïve patients (5 male, 6 female; ages: 18--54 years old, median 35 years old) with chronic HBV infection. Of 11 patients, 7 and 4 were HBeAg positive/anti-HBe negative and HBeAg negative/anti-HBe positive, respectively. All patients had no co-infection with HCV, HDV, or HIV. HBV DNA was extracted from the sera of the patients. The complete genome was amplified by PCR and cloned into a TA vector. The PCR products were sequenced directly and the complete HBV genome sequences were determined. Ten HBV genomes were 3182 base pairs in length. There was a 183 bp deletion (between nucleotides 2987--3169) in pre-S region in one HBeAg positive patient. There were two pre-core stop codons (G1896A) in two HBeAg negative and three core promoter dual mutations (T1762/A1764) in one HBeAg positive and two HBeAg negative patients' HBV genomes. Phylogenetic analysis of all complete genomes yielded that all Turkish sequences were clustered in genotype D branch (ten in subgenotype D1 and one in subgenotype D2). The analysis of S gene amino acid sequences revealed that surface gene subtypes of one and ten HBV strains were subtype ayw3 and ayw2, respectively. This study indicates that Turkish patients with chronic hepatitis B infection show very little genotypic heterogeneity. Genotype D of HBV DNA and subtype ayw2 of surface gene represent almost the whole Turkish patient population infected with HBV.

Idilman R. · Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey. · J Antimicrob Chemother. · Pubmed #15849263 links to  free full text

Abstract: Reactivation of hepatitis B virus (HBV) is a well-recognized complication of chemo/immunosuppressive therapy in individuals who are HBV surface antigen-positive inactive carriers and in individuals with chronic HBV infection. Although it is well established that chemo/immunosuppressive therapy enhances HBV replication with a resultant increase in the viral load and disease activation, the role of prophylactic lamivudine therapy to prevent chemo/immunosuppressive therapy-induced HBV activation in HBV-positive individuals who are to receive chemo/immunosuppressive therapy remains controversial. The aims of the present article are: (i) to determine the effect of lamivudine prophylaxis in HBV carriers with haemato-oncological malignancies who require chemotherapy; (ii) to define the duration and safety of lamivudine in such individuals; and (iii) to identify the effect of lamivudine prophylaxis on the outcome of chemotherapy administered for the primary disease. The data currently available suggest that lamivudine prophylaxis prevents chemotherapy-induced HBV reactivation in HBV carriers with haemato-oncological malignancies who receive chemotherapy. Lamivudine is safe and tolerable in such individuals. The duration of lamivudine prophylaxis is not yet known; however, it would appear prudent to begin lamivudine at the time of the initiation of the chemotherapy and to continue it throughout the period of chemotherapy administration and for at least 1 and possibly 2 years following the discontinuation of the chemotherapy. Finally, the prophylactic use of lamivudine in inactive HBV carriers with haemato-oncological malignancy prevents interruptions in their treatment for primary disease as a result of HBV reactivation.

Soykan A, Boztaş H, Idilman R, Ozel ET, Tüzün AE, Ozden A, Ozden A, Kumbasar H. · Division of Consultation Liaison Psychiatry, Department of Psychiatry, Ankara University, School of Medicine, Ankara, Turkey. · Int J Impot Res. · Pubmed #15510190 No free full text.

Abstract: The frequency of sexual dysfunction (SD) is not very well known in patients with chronic hepatitis C. In this study, the prevalence of SD and its correlations with psychological and biological variables was assessed in 46 HCV positive patients. The mean age of patients was 46.4+/-9.4 y; the mean duration of HCV infection was 43.4+/-34.0 months; 52% were male; 89% were living with a spouse. SD was assessed using the Arizona Sexual Experiences Scale (ASEX), the level of anxiety and depression measured with the Hospital Anxiety and Depression Scale (HADS). Biochemical parameters were also assessed. Overall, as indicated by ASEX criteria, SD was observed in 35% of our patients. Of 24 males, 21% described SD; problems with drive (25%), arousal (17%) and erection (17%) were the most frequent complaints. Of 22 female patients, 50% described SD; problems with drive (55%) arousal (50%), and reaching orgasm (59%) were the most frequent complaints. Total ASEX scores were correlated with age (P<0.07, significant at trend level), education (P<0.001), and was higher in female patients (P<0.02). After controlling for the effects of age, sex, education, duration of HCV and marital status, depression levels could still significantly predict the SD (P<0.05). Moreover, even after controlling the effects of all other variables, gamma glutamyl transpeptidase (GGT) levels could predict the SD status of the patients (P<0.05). Our results indicate that the prevalence of SD was 35% in HCV-infected patients and the level of depression and GGT levels were predictive of patients SD status.

Idilman R, Colantoni A, De Maria N, Alkan S, Nand S, Van Thiel DH. · Department of Medicine, Division of Gastroenterology and Liver Transplantation, Loyola University Medical Center, Maywood, IL, USA. · J Viral Hepat. · Pubmed #15230852 No free full text.

Abstract: Chronic hepatitis C virus (HCV) infection is associated with the development of lymphoproliferative disorders (LPDs). The aim of this investigation was to determine the prevalence and characterization of monoclonal gammopathy and benign and malignant LPDs in individuals with chronic hepatitis C. A total of 233 subjects diagnosed with chronic hepatitis C (male/female ratio: 131/102, median age; 49 years) were studied. Serum and urine were examined for the presence of a monoclonal gammopathy. A bone marrow aspirate and biopsy was obtained in individuals with a monoclonal gammopathy. Thirty-two patients (13.7%, 32 of 233) had a monoclonal gammopathy; 75% of them were benign and were not associated with malignant disorders (24 of 32) while 25% were associated with malignant LPDs or a plasma cell disorder (eight of 32). Two additional subjects without monoclonal gammopathy were diagnosed as having a malignant LPDs. The prevalence of malignant LPDs/plasma cell disorder in individuals with HCV-induced chronic liver disease was 4.3%. No difference was found in terms of disease duration, HCV genotype, viral load, alanine aminotransferase level or histopathologic score between the subjects with or without a monoclonal gammopathy. The presence of mixed cryoglobulinaemia was strongly associated with the presence of an underlying malignant disorder. Hence a monoclonal gammopathy is found in 14% of patients with chronic hepatitis C and is associated with malignant B-cell LPD in more than a quarter of such patients. The prevalence of LPDs in individuals with HCV-induced chronic liver disease is greater than that of the normal healthy population.

Idilman R, Ustün C, Karayalçin S, Aktemel A, Turkyilmaz AR, Ozcan M, Arslan O, Bozdayi AM, Van Thiel DH, Akan H. · Department of Gastroenterology, Ankara University Medical School, Ibn'i Sina Hospital, Sihhiye, Ankara, Turkey. · Clin Transplant. · Pubmed #14703927 No free full text.

Abstract: 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 naïve 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-naïve 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-naïve recipients with HBV-naïve 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.

De Maria N, Colantoni A, Idilman R, Friedlander L, Harig J, Van Thiel DH. · Department of Internal Medicine, Division of Gastroenterology, Hepatology and Nutrition, Loyola University Medical Center, Building 114, Room 48, 2160 South 1st Ave, Maywood, IL 60153, USA. · Hepatogastroenterology. · Pubmed #12063991 No free full text.

Abstract: BACKGROUND/AIMS: The prevalence of hepatitis C virus infection in the USA is higher among African-Americans than among Caucasians. Despite this, little information is available on the course of hepatitis C virus infection in Blacks and in other minority groups. The aim of this retrospective case-control study was to determine the response rate to high dose interferon-alpha treatment in two racial groups with chronic hepatitis C virus infection. METHODOLOGY: Thirty-one African-Americans and 62 Caucasians with chronic hepatitis C were considered in the study. The subjects were matched for gender, age, presence/absence of cirrhosis, histologic score, and viral genotype. All were treated with interferon-alpha (5 mU/day for 12 months). Three end-points (on-therapy, after 6 months of interferon-alpha, end-of-therapy, at the end of the 12 months of treatment, and off-therapy, 6 months after treatment) were chosen to describe the response to interferon-alpha treatment. RESULTS: African-Americans had a significantly reduced response to interferon-alpha as compared to Caucasians at all end-points. At the on-therapy end-point, 26% of African-Americans were HCV-RNA negative and had normal transaminases level as compared to 60% of the Caucasians (P < 0.01); at the end-of-therapy end-point the rates were, respectively, 10% and 53% (P < 0.0001). No differences were detected in terms of pretreatment serum ALT, HCV-RNA, iron and ferritin levels or hepatic iron contents between the two groups. CONCLUSIONS: African-Americans have a reduced response to high-dose interferon-alpha treatment as compared to Caucasians. Both environmental and genetic factors may be implicated in this impaired ability to clear hepatitis C virus infection.

Idilman R, Cetinkaya H, Savaş I, Aslan N, Sak SD, Baştemir M, Sarioğlu M, Soykan I, Bozdayi M, Colantoni A, Aydintuğ O, Bahar K, Uzunalimoğlu O, Van Thiel DH, Numanoğlu N, Dökmeci A. · Department of Gastroenterology, University of Ankara, Medical School, Ankara, Turkey. · J Med Virol. · Pubmed #11748656 No free full text.

Abstract: 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.

De Maria N, Colantoni A, Friedlander L, Leandro G, Idilman R, Harig J, Van Thiel DH. · Department of Internal Medicine, Loyola University at Chicago, Maywood, Illinois 60153, USA. · Am J Gastroenterol. · Pubmed #11151889 No free full text.

Abstract: OBJECTIVE: Individuals with chronic hepatitis C who are anti-HBc positive may carry an occult hepatitis B virus (HBV) infection that can affect their response to antiviral therapy. METHODS: In this study the prevalence of anti-HBc and HBV-DNA positivity was assessed in the serum and liver of 285 HCV-RNA-positive subjects treated with interferon-alpha at 5 mU/day for 12 months. The response to interferon (normal ALT and undetectable serum HCV-RNA) was evaluated at three different endpoints: 1) after 6 months; 2) at the end of treatment; and 3) 6 months after interferon discontinuation. RESULTS: Ninety individuals were anti-HBc positive (32%), 2 of these were HBV-DNA positive in serum and 7 in liver (8%). None of the anti-HBc-negative individuals was HBV-DNA positive in serum or liver. The prevalence of cirrhosis was greater in the anti-HBc-positive group than in the anti-HBc-negative group (p < 0.05), whereas HCV-RNA levels were lower. Anti-HBc-positive individuals had a lower response rate to interferon at 6 months and at the end of treatment as compared to anti-HBc-negative subjects (respectively 42% vs 66%, p < 0.01; and 32% vs 57%, p < 0.01). No difference between the two groups in terms of sustained response was detected 6 months after interferon discontinuation. CONCLUSIONS: The prevalence of anti-HBc is high among HCV-positive individuals. HCV-positive individuals who are anti-HBc positive have: 1) a higher prevalence of cirrhosis; 2) lower HCV-RNA levels; and 3) an impaired ability to respond to interferon treatment.

Ustün C, Idilman R, Gürman G, Ozcan M, Akyol G, Akan H, Ilhan O, Beksaç M, Uysal A, Konuk N, Karayalçin S, Poyraz A, Van Thiel D, Koç H. · University of Ankara, Medical School, Department of Hematology-Oncology, Turkey. · J Hepatol. · Pubmed #10453930 No free full text.

Abstract: BACKGROUND/AIMS: Hepatitis B virus can cause serious problems in individuals undergoing organ transplantation. The aim of this study was to evaluate the hepatic events among HBs-Ag positive recipients and HBs-Ag negative recipients who received products from hepatitis B virus carriers. METHODS: A total of 151 patients received an allogeneic hematopoietic stem cell transplantation at the Department of Hematology-Oncology, University of Ankara, between June 1989 and June 1998. Among these, eight HBs-Ag positive and four HBs-Ag negative recipients received a product from a hepatitis B virus positive donor. The median follow-up period for these 12 patients was 13.2 months. RESULTS: Three of the eight HBs-Ag positive recipients died (one from hepatic failure); of the remainder, two are HBs-Ag negative, two HBs-Ag positive with normal liver injury tests and one HBs-Ag positive with elevated ALT levels. Of the four HBs-Ag negative recipients who received stem cells from a hepatitis B positive donor, two died; none of the patients in this group became HBs-Ag positive after transplantation. CONCLUSION: Hepatitis B virus infection is a common problem in patients being considered for allogeneic hematopoetic stem cell transplantation, especially in areas where hepatitis B virus infection is endemic. We believe that the presence of HBs-Ag positivity is not an absolute contraindication for allogeneic hematopoetic stem cell transplantation unless the hepatitis B virus is in a replication phase.

Idilman R. · No affiliation provided · Gut. · Pubmed #16849352 links to  free full text

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Soykan I, Toruner M, Sarioglu M, Idilman R. · No affiliation provided · J Clin Gastroenterol. · Pubmed #12080240 No free full text.

This publication has no abstract.

De Maria N, Colantoni A, Idilman R, Harig J, Van Thiel DH. · No affiliation provided · J Hepatol. · Pubmed #11131445 No free full text.

This publication has no abstract.