Selim Badur

Spread of OXA-48-Positive Carbapenem-Resistant Klebsiella pneumoniae Isolates in Istanbul, Turkey

ABSTRACT The first outbreak of carbapenem-resistant Klebsiella pneumoniae isolates producing the plasmid-encoded carbapenem-hydrolyzing oxacillinase OXA-48 is reported. The 39 isolates belonged to two different clones and were collected at the University Hospital of Istanbul, Turkey, from May 2006 to February 2007, and they coproduced various β-lactamases (SHV-12, OXA-9, and TEM-1 for clone A and CTX-M-15, TEM-1, and OXA-1 for clone B).

Occult HBV infection and YMDD variants in hemodialysis patients with chronic HCV infection.

BACKGROUND/AIMS End-stage renal disease patients on chronic hemodialysis are at risk for both hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Although the prevalence is unknown in hemodialysis patients, occult HBV infection is frequent in subjects with chronic HCV infection. We aimed to investigate (1) the prevalence and clinical impact of occult HBV infection in hemodialysis patients with chronic HCV infection, and (2) the frequency of YMDD variants (tyrosine-methionine-aspartate-aspartate amino acid motif of HBV polymerase) in this setting. METHODS Thirty-three anti-HCV and HCV-RNA-positive, HBsAg-negative hemodialysis patients (mean age 36.9+/-10.4 years, 22 male) were admitted to this study. HBV-DNA (Innogenetics kit) and HCV-RNA (Cobas Amplicor HCV kit) were investigated by polymerase chain reaction technique (PCR). YMDD mutation was studied in all HBV-DNA-positive patients by the BOOM method. RESULTS HBV-DNA was detected in 12 of 33 patients (36.4%) by PCR. Their mean age was 33.0+/-9.0 years. Age, dialysis period (years) and biochemical parameters were not significantly different in patients with and without occult HBV infection. YMDD variants were identified in six of 12 (50%) patients with occult HBV infection. CONCLUSIONS Occult HBV infection is frequent in hemodialysis patients with chronic HCV infection. YMDD variants are common in this setting.

Vaccine Safety Controversies and the Future of Vaccination Programs

In the years following the hepatitis B vaccination/multiple sclerosis controversy, a number of new issues regarding vaccine safety have been raised, in some cases leading to more debate and confusion. Against this background, an international group of experts was convened to review the current points of view concerning the use of thimerosal as a preservative and its potential risks; the suggested link between thimerosal-containing vaccines and acute lymphoblastic leukemia; the alleged association between aluminum-containing vaccines/macrophagic myofasciitis and general systemic complaints; a possible link between vaccination and autoimmune pathology; and a hypothetical link between measles-mumps-rubella vaccination and autism. At present, there are no data to conclude that childhood vaccines, and in particular hepatitis B vaccine, pose a serious health risk or justify a change in current immunization practice. However, vaccine “scares” continue to have an international impact on immunization coverage. Creating a positive environment for immunization can be achieved by repositioning the value of vaccines and vaccination, supported by evidence-based information. The role of international organizations, the media, and the industry in the implementation of communication strategies was discussed and the impact of litigation issues on vaccination was evaluated. The Viral Hepatitis Prevention Board confirms its commitment to current recommendations for universal and risk group hepatitis B vaccination and further encourages the conduct of vaccine safety studies and the dissemination of their results.

Age-specific seroepidemiology of hepatitis A, B, and E infections among children in Istanbul, Turkey

This study was performed for evaluation of seroprevalence of hepatitis A, B, and E among children in Istanbul, Turkey. The study group included 909 children who were 6 months–15 years of age. The children were separated to three age groups: Group 1 (6 months–4.9 years; n = 321), Group 2 (5.0–9.9 years; n = 318), and Group 3 (10.0–15.0 years; n = 270). Group 1 was divided to two subgroups for evaluation of the maternal antibody sera (6 months–2 years and over 2 years). Serum IgG anti-HAV, anti-HBc, and anti-HEV were tested by commercial ELISA kits. The data were studied by multivariant analysis. In all subjects, seroprevalence of hepatitis A, B, and E were determined as 29, 15.9, and 2.1% respectively. The prevalence of hepatitis A increased with age (p < 0.05; Group 1 15.1% and Group 3 49.6%). Anti-HBc IgG level did not significantly change with age (Group 1 18.6% and Group 3 15.4%; p > 0.05). The seroprevalence of hepatitis E virus infection was higher in Group 1 (3.7%) than Group 3 (0.3%; p < 0.05). In Group 1 first subgroup, between 6 month and 2 year, antibody levels were 12.2, 17.3, and 4.8% respectively, for anti-HAV IgG, anti-HBc IgG and anti-HEV IgG. Hepatitis A and B infection is a community health problem, but hepatitis E infection is low in children in Istanbul, Turkey. The high positive rate in Group 1 for IgG anti-HEV may be due to maternal antibodies.

Is severe cryptogenic chronic hepatitis similar to autoimmune hepatitis

BACKGROUND/AIMS It has been reported that severe cryptogenic chronic hepatitis may be a subgroup of autoimmune hepatitis. The aims of this study were to investigate the clinical features, liver function tests, human leukocyte antigens and response to immunosuppressive therapy in severe cryptogenic chronic hepatitis, and to compare the findings in such patients with those in patients with autoimmune hepatitis. METHODS History of alcohol and hepatotoxic drug intake, markers of metabolic liver disease, autoantibodies (antinuclear antibody, smooth muscle antibody, antibody to liver/kidney microsome type 1), and viral markers (HBsAg, HBV DNA, anti-HCV, HCV RNA) were negative in all severe cryptogenic chronic hepatitis patients (histological activity index > 9 and alanine aminotransferase level > 2 x normal). Fifteen cryptogenic patients (13 women; mean age, 33 +/- 16 years) and seven autoimmune patients (seven women; mean age, 28 +/- 3.9 years; five type 1; two type 2a) received prednisolone and azathioprine for at least 2 years. RESULTS Cryptogenic chronic hepatitis patients were similar to patients with autoimmune hepatitis with respect to age, sex, clinical presentation, liver function tests and Knodell scores at admission. HLA phenotype frequencies were comparable between cryptogenic and autoimmune groups: BW6 (77% vs. 100%), DR4 (62% vs. 57%), and HLA B8 (15% vs. 43%). The rates of complete and partial remissions achieved during therapy were 87% vs. 57% and 13% vs. 29%, respectively (p > 0.05). CONCLUSIONS The clinical, biochemical and HLA phenotypic features, and the responsiveness to immunosuppressive therapy in severe cryptogenic chronic hepatitis support the idea that it may be an autoimmune liver disease similar to autoimmune hepatitis.

Immunization of renal transplant recipients with pneumococcal polysaccharide vaccine

Background: Streptococcus pneumoniae, a common pathogen leading to pneumonia, is a cause of morbidity and mortality in immunosuppressed patients. Vaccination against this agent can be recommended for immunosuppressed patients, including those with chronic renal failure, nephrotic syndrome and renal transplant recipients; however, a diminished immune response and loss of protective antibodies have been observed.Patients and methods: In our prospective study, the efficacy and side effects of polyvalent pneumococcal vaccination were investigated in renal transplant recipients. A total of 21 patients (6 female, 15 male) with well‐functioning renal allografts, who had transplant surgery at least 2 months before, were included in the study. The patients were stratified according to the immunosuppressive protocol and 8 received double, while 13 received triple, immunosuppresive agents. After obtaining basal serum samples, all cases were vaccinated with the 0.5 mL intramuscular administration of polyvalent polysaccharide pneumococcal vaccine (Pneumo 23 Pasteur–Merieux, lot No: K 1131).Results: Following a mean of 6 wk in all patients and also a mean of 12 wk in 12 patients, serum samples were again obtained to measure pneumococcal antibodies. Antibody titers following 6 and 12 wk of vaccination were significantly higher, as compared with basal values in all patients, except one. These titers did not show any statistically significant difference between double and triple therapies. There was no significant difference between the 12th and 6th wk postvaccination antibody titers. No systemic or local adverse effects were observed.Conclusion: Pneumococcal vaccination is safe and effective in patients with well‐functioning renal allografts, at least in the short term. This vaccination policy may be useful for preventing invasive pneumococcal disease in immunosuppressed patients.

Efficacy of Tenofovir in Patients with Lamivudine Failure Is Not Different from That in Nucleoside/Nucleotide Analogue-Naïve Patients with Chronic Hepatitis B

ABSTRACT We evaluated the efficacy of tenofovir disoproxil fumarate (TDF) in patients with lamivudine failure (LAM-F) in comparison with that in nucleoside/nucleotide analogue (NA)-naïve patients with chronic hepatitis B (CHB). The criteria for inclusion were being NA naïve or having previous LAM-F and receiving TDF therapy for at least 6 months. Biochemical and virological tests were performed at the baseline, at 3-month intervals in the first year, and every 6 months thereafter. The primary outcome measure for efficacy was a complete virological response (CVR), defined as an HBV DNA level of <20 IU/ml. CVR rates were calculated by Kaplan-Meier analysis, and a multivariate Cox proportional-hazard model was generated in order to find predictive factors independently associated with the time to a CVR. We included 197 patients in the study (136 males; mean age, 43 ± 12 years; 105 patients were NA naïve). Sixty-five patients had hepatitis B e antigen (HBeAg)-positive CHB. The median duration of TDF treatment was 29 (range, 6 to 52) months. Seventy-one patients (77%) in the LAM-F group were treated with TDF add-on therapy. The CVR rates of the NA-naïve and LAM-F groups were comparable in HBeAg-negative (94% versus 96% at month 36, P = 0.10) and HBeAg-positive patients (67% versus 83% at month 36, P = 0.48). According to the multivariate Cox regression model, only HBeAg positivity (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.26 to 0.59; P < 0.001) and a high baseline HBV DNA level (HR, 0.44; 95% CI, 0.29 to 0.67; P < 0.001) had a significant influence on the time to a CVR. The similar cumulative CVR rates during the follow-up show that TDF has comparable efficacy in lamivudine-experienced and NA-naïve patients, and the presence of resistance mutations did not alter the response rates.

Alpha Interferon and Ribavirin Combination Therapy of Chronic Hepatitis D

ABSTRACT The success of alpha interferon (IFN-α) monotherapy for the treatment of chronic hepatitis D is very limited. In this study, the efficacy of IFN-α and ribavirin combination therapy for chronic hepatitis D was investigated. Nineteen patients (15 males; mean age ± standard deviation, 36.8 ± 12.8 years) with chronic hepatitis D who were treated with IFN-α2b (10 million U, three times/week, subcutaneously) and ribavirin (1,000 to 1,200 mg/day, orally) for 24 months were studied. All patients had compensated liver disease (15 were precirrhotic), elevated transaminase levels, and hepatitis D virus RNA positivity at baseline. Genotypic analyses revealed hepatitis D virus genotype I and hepatitis B virus genotype D. All patients completed the 24 months of treatment and at least 6 months (7 to 19 months) of a follow-up period. Biochemical responses were observed in eight patients (42.1%) at the end of treatment and in seven patients (36.8%) at the end of follow-up. Eight patients (42.1%) at the end of treatment and four patients (21%) at the end of follow-up had virological responses. In conclusion, combination treatment of IFN-α and ribavirin for chronic hepatitis D is not able to induce virological responses at a sufficient rate, despite its partial effectiveness in improving biochemical responses, and is not superior to IFN-α monotherapy.

Risk factors for the transmission of hepatitis C virus infection in the Turkish population.

The risk factors for the transmission of hepatitis C virus (HCV) infection varies substantially between countries and geographic regions. The aim of this investigation was to determine the risk factors which may be involved in the transmission of HCV infection in the Turkish population. This study included patients who were admitted to the Department of Gastroenterohepatology, Istanbul Medical Faculty, Istanbul University, between 1996 and 2002 and found to be anti-HCV positive during hospitalization or during follow-up as outpatients. All patients were asked about risk factors for HCV transmission including transfusion, history of operation, hospitalization, hemodialysis, intravenous drug use, suspected sexual contact, tattooing, acupuncture, dental procedures, manicure and pedicure, blood brotherhood rituals, perinatal risk factors, common circumcision rituals, and history of abortion. In our study, total of 320 patients with anti-HCV seropositivity were involved. The numbers and percentages of male and female patients were 139 (43.4%) and 181 (56.6%), respectively. The mean age of the patients was 49.7± 12.4 years (range: 18–73 years). HCV-RNA was found to be positive in 297 (92.8%) patients. The most common risk factor was a history of surgery (305; 98%), and the second most common was blood transfusion (123; 39.7%). The numbers and percentages of patients for the other risk factors were as follows: dental procedure, 86 (27.5%); abortion, 66 (21.2%); long-term hospitalization, 37 (11.6%); hemodialysis, 31 (10%); history of jaundice, 15 (4.6%); history of intravenous drug abuse, 10 (3.1%); history of suspected sexual contact, 5 (1.5%); history of manicure and pedicure, 4 (1.2%); history of occupational transmission, 3 (0.9%); history of tattooing, 2 (0.6%); history of acupuncture, 2 (0.6%); circumcision in a common circumcision ritual, 1 (0.3%); and percutaneous needle puncture, 1 (0.3%). None of the patients had a history of blood brotherhood ritual or perinatal transmission. Only one risk factor was detected in 73 (22.8%) patients, two risk factors were detected in 122 (38.2%) patients, three risk factors were detected in 78 (24.5%) patients, and four risk factors were detected in 39 (12.2%) patients, however, in 8 (1.6%) patients no risk factors could be found. In Turkey, the most common risk factor for the transmission of HCV infection is surgery, which can be preventable.

Anti-CCP and antikeratin antibodies in rheumatoid arthritis, primary Sjogren's syndrome, and Wegener's granulomatosis

The objective of this study was to investigate the frequency of antibodies against cyclic citrullinated peptides (anti-CCP) and keratin (AKA) in patients with rheumatoid arthritis (RA) as well as in patients with primary Sjögren’s syndrome (pSS) and Wegener’s granulomatosis (WG), who may present with rheumatoid factor (RF)-positive arthritis. The study group consisted of 46 patients with RA (26 patients were negative for RF), 32 with pSS, 22 with WG, and 40 healthy controls. The RF, anti-CCP, and AKA were detected in serum using the latex agglutination test, enzyme-linked immunosorbent assay, and indirect immunofluorescence, respectively. The agreement between those tests was evaluated by kappa test. No positive result for AKA was detected in pSS and WG patients, and anti-CCP was found in only one patient with pSS. The results of kappa tests were low, varying between 0.25 (RF-anti-CCP) and 0.02 (RF-AKA). The sensitivity and specificity values were 43 and 44% for RF, 65 and 98% for anti-CCP, and 58 and 100% for AKA, respectively, in RA patients. In the RF-negative RA group, AKA was found to have a high frequency (55%) in comparison to anti-CCP (38%). Seropositivity was found to be 87% for any one of the three autoantibodies tested in RA patients. With a higher specificity, values for RA, anti-CCP, and AKA seem to be helpful for the differential diagnosis of patients with RF-positive arthritis, which may include patients with WG and pSS, and screening of all three antibodies may increase the diagnostic performance.