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Biomedical subjects

R Idilman

Publications and source records attributed to R Idilman.

At least 19 recordsLinked to original sources

Evaluation of the effect of transplant-related factors and tissue injury on donor-derived hepatocyte and gastrointestinal epithelial cell repopulation following hematopoietic cell transplantation.

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.

Adolescent↗

Anti-viral prophylaxis in inactive hepatitis B virus carriers with hemato-oncological malignancies who receive chemotherapy.

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.

Antiviral Agents↗

Lamivudine prophylaxis for prevention of chemotherapy-induced hepatitis B virus reactivation in hepatitis B virus carriers with malignancies.

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.

Adult↗

Lymphoproliferative disorders in chronic hepatitis C.

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.

Adult↗

Increased effective immunogenicity to high-dose and short-interval hepatitis B virus vaccination in individuals with chronic hepatitis without cirrhosis.

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.

Female↗

The impact of previous HBV infection on the course of chronic hepatitis C.

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.

Adult↗

Cirrhosis in Turner's syndrome: case report and literature review.

A case of cryptogenic cirrhosis in a patient with Turner's syndrome is presented. The individual was admitted for upper gastrointestinal bleeding due to oesophageal varices. After failure of medical treatment, a transjugular intra-hepatic portal systemic shunt was used to control the bleeding. A liver biopsy revealed cirrhosis with minimal necro-inflammatory activity and no steatosis. Immunohistochemical staining for HCV, HBsAg and HBcAg was negative. No other risk factor for liver disease was recognized and none of the known causes of chronic liver disease was identified after a thorough evaluation for such. Turner's syndrome is a genetic disorder due to X chromosome monosomy in which a wide range of congenital anomalies can occur. Cardiac, renal and skeletal anomalies are all well recognized. The possible association of Turner's syndrome with cirrhosis is herein discussed along with a review of the published literature.

Adult↗

Influence of sex hormonal status on alcohol-induced oxidative injury in male and female rat liver.

BACKGROUND: Oxidative stress contributes to the development of liver injury after chronic alcohol intake. Women exhibit greater sensitivity to alcohol-induced liver disease than do men. The aim of the study was to determine the relationship between the sex hormone status of male and female rats and the degree of alcohol-induced oxidative stress in the liver. METHODS: Male and female rats were pair-fed a liquid diet that contained 36% of their total daily calories as ethanol (EtOH group) or maltose (control group). Blood and liver samples were collected at the end of 8 weeks of diet. RESULTS: Male EtOH rats experienced a reduction in plasma testosterone (T) and an increase in estradiol (E2) levels, with an increase in their calculated E2/T ratio with respect to their controls. Malonaldehyde (MDA) levels, an index of lipid peroxidation, and protein carbonyl content, an index of protein oxidation, in the liver were greater among the EtOH groups in females than in males. In males, an inverse correlation was found between hepatic MDA and circulating T levels, and a direct correlation was disclosed between MDA and estradiol levels. In addition, the hepatic histopathological score correlated inversely with the plasma T levels and directly with the calculated E2/T ratio, an index of feminization. CONCLUSIONS: Alcohol-induced oxidative injury, which contributes to hepatic injury in both male and female rats, is enhanced in females compared with males. A role for plasma T levels in protecting male rat liver from ethanol-induced oxidative injury can be hypothesized.

Animals↗

Hematopoietic stem cell transplantation from non-replicative hepatitis B virus carriers is safe.

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.

Adolescent↗

Pathogenesis of hepatitis B and C-induced hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is estimated to have an annual worldwide incidence of 0.25 to 1.2 million new cases per year. Both the prevalence and incidence of HCC vary markedly as a function of geography and the local prevalence of chronic viral hepatitis. Both chronic hepatitis B and chronic hepatitis C are recognized as risk factors for HCC. The prevalence of cirrhosis in individuals with HCC and chronic hepatitis B or C is reported to be 80.9% and 75.8%, respectively. HCC occurs at a lower rate in chronic viral hepatitis in the absence of cirrhosis. Moreover, hepatitis C virus (HCV) rather than hepatitis B virus (HBV) is associated with the majority of non-cirrhotic cases of HCC. It is probable that the ongoing process of hepatocyte necrosis and liver cell renewal coupled with inflammation, which is characteristic of chronic viral hepatitis, causes not only nodular regeneration and cirrhosis but also progressive genomic errors in hepatocytes as well as unregulated growth and repair mechanisms leading to hepatocyte dysplasia and, in some cases, hepatic carcinoma. Current concepts concerning virus-induced HCC are reported and discussed in the following review.

Carcinoma, Hepatocellular↗

Immunosuppressive drug-induced leukoencephalopathy in patients with liver transplant.

Organ transplantation has become a practical and effective option for patients with acute and/or chronic irreversible organ disease. However, solid organ transplantation is associated with many different complications which depend upon the specific surgical procedure and/or confounding medical problems (e.g. rejection, infection, adverse effect of immunosuppressive agents) experienced by a given patient. Tacrolimus and cyclosporin A are immunosuppressive drugs used to prevent rejection following allogeneic solid organ transplantation. Adverse events are common with both drugs and include long-term organ dysfunction, opportunistic infections, haematopoietic alterations, nephrotoxicity and neurotoxicity. Neurological complications, both central and peripheral, occur in 10-42% of transplant recipients using either of these two immunosuppressive agents. Two cases of reversible posterior leukoencephalopathy manifested by headache, nausea and seizures associated with the use of immunosuppressive drugs following liver transplantation are reported.

Adolescent↗