Association between hepatitis B and hepatocellular carcinoma recurrence in patients undergoing liver transplantation.

BACKGROUND/AIMS: Hepatitis B virus (HBV) and hepatocellular carcinoma (HCC) recurrences affect both patient and graft survivals post-orthotopic liver transplantation (OLT) in HBV patients with HCC. We analyzed the relationship between HBV and HCC recurrence in a large cohort of HBV-OLT patients with versus without HCC. METHODS: Two hundred eighty-seven HBV patients with OLT (72 also with HCC) were included in the study. Mean follow-up in the post-OLT period was 31.7 +/- 24.7 (range, 3-119) months. RESULTS: Post-OLT HBV recurrence observed in 10.1% of patients was more prevalent among the HCC group; 23.6% versus 5.5% in patients with and without HCC, respectively. The mean interval for the development of HBV recurrence was 39.5 +/- 28.5 (range, 2-99) months. Among 72 HCC patients, 8 patients (11.1%) had recurrent HCC, and 7 of them also had HBV recurrence. The mean interval for the development of HCC recurrence was 11.2 +/- 7.85 (range, 2-23) months after OLT. OLT patients with HCC with tumors exceeding the Milan criteria had worse 1-, 3-, and 5-year survival rates than patients with HCC meeting the Milan criteria. HBV and HCC recurrence-free survivals were significantly lower in patients with HCC and HBV recurrence, respectively. In the 7 patients with both HCC and HBV recurrence, mean HBV recurrence time was 9.42 +/- 6.75 months and mean HCC recurrence time was 9.57 +/- 6.75 months. There was a strong correlation between HBV and HCC recurrence times. Cox proportional hazards regression analysis showed that only HCC recurrence was a significant independent predictor of HBV recurrence (P < .001; hazard ratio [HR] = 26.94; 95% confidence interval [CI] = 10.81-67.11). On the other hand, HBV recurrence (P = .013; HR = 5.80; 95% CI = 1.45-23.17) and nodule count (P = .014; HR = 13.08; 95% CI = 1.70-100.83) were significant predictors of HCC recurrence. CONCLUSIONS: HBV and HCC recurrences demonstrate a close relationship in patients with OLT.

Living donor liver transplantation from hepatitis B core antibody positive donors.

UNLABELLED: Liver allografts from donors previously exposed to hepatitis B virus (HBV) carry the risk of transmission of HBV infection to immunosuppressed recipients. However, exclusion of donor candidates with the serologic evidence of resolved hepatitis B-HBV surface antigen (HbsAg) negative and HBV core antibody (anti-HBc) positive-is not feasible in countries endemic for HBV. AIM: Our aim was to assess the safety of living donor liver transplantation from anti-HBc positive donors. MATERIALS AND METHODS: In our institution, 152 transplants were performed between June 1999 and April 2004. Fifty-six (37%) of the living donors were anti-HBc positive. Twenty of these liver grafts were transplanted to HbsAg-negative recipients. We excluded four HBsAg negative recipients who died because of early complications after transplantation. Lamivudine (100 mg/day) was given for prophylaxis of de novo HBV infection. RESULTS: The mean follow-up time for 16 HBsAg-negative recipients was 21.7 (7-48) months. None of them experienced de novo HBV infection. CONCLUSION: The use of liver allografts from anti-HBc-positive living donors is reasonably safe in HBsAg-negative recipients under lamivudine prophylaxis.

Clinical significance of basal core promoter and precore mutations in chronic hepatitis B.

BACKGROUND/AIMS: The mutations in the basal core promoter and precore region of hepatitis B virus genome in hepatitis B e antigen-positive and -negative chronic hepatitis B patients have been described. The reports about their prevalence and clinical significance in the Mediterranean region where D is the predominant genotype, are very limited. METHODOLOGY: The serum samples were collected from 44 naive chronic hepatitis B patients. For detection of the mutations basal core promoter and precore regions of HBV genome were amplified and sequenced. RESULTS: All samples were determined as genotype D. Before initiation of treatment basal core promoter mutations were found as 55% (11/20) and 46% (11/24) in HBeAg-positive and -negative patients, respectively (p > 0.5). HBeAg-negative samples were associated with precore mutations (G1896A and G1899A). Three of 20 (15%) patients of HBeAg-positive and seven of 24 (29%) of HBeAg-negative populations showed sustained response to therapy at the 24th month of initiation. CONCLUSIONS: The presence of precore stop codon mutant in those with sustained response was 89%, overall at the end of therapy. At initiation of therapy basal core promoter mutations were more common in non-responders than responders (65% vs. 20%; p < 0.001). While 23% of cases totally showing sustained response, absence of mutations in the basal core promoter region of hepatitis B virus genotype D may be related to sustained response in patients with chronic hepatitis B.

Comparison of sequence analysis and INNO-LiPA HBV DR line probe assay in patients with chronic hepatitis B.

The aim of this study was to compare direct sequence analysis of partial HBV pol gene and Inno-LiPA HBV DR in serum samples of 120 chronic hepatitis B patients sent to the Clinical Microbiology Laboratory of Ege University Hospital because of lamivudine resistance. Sequence analysis was performed on ABI Prism 310 Genetic Analyzer. Comparison of Inno-LiPA and sequence results obtained by double-blind evaluation showed full agreement (both at rt180 and rt204) in 58.8% of samples. Visually rechecking of the electropherograms increased this rate to 68.3% Codon based rates are 81.7% and 75.8% at rt180 and rt204 respectively. LiPA detected variants in additional 12 (10%) samples, but missed one variant sample (both rt180 and rt204) and one sample was indeterminate due to poor probe binding. LiPA allows determination of mixed variants and seems to be more sensitive and simple for routine testing even though sequence analysis is still the gold standard for detecting new variants.

Rubella seroprevalence in an unvaccinated population in Izmir: recommendations for rubella vaccination in Turkey.

BACKGROUND: The European Advisory Group on the Expanded Program on Immunization of WHO has recommended that by 2010 or earlier congenital rubella should be well-controlled or eliminated in all countries in Europe. Debate on the introduction of rubella vaccine into national immunization schedules continues to occur, and data on rubella and congenital rubella syndrome in Turkey are insufficient. OBJECTIVE: To determine age-specific rubella seroprevalence in the 1- to 29-year-old unvaccinated population in Izmir, Turkey. METHODS: A total of 600 unvaccinated persons 1 to 29 years old were selected for the study with cluster sampling in Izmir, Turkey. The information on sociodemographic characteristics and disease history was gathered for each participant, and in 580 of them rubella-specific IgG antibodies were assayed quantitatively by the micro-enzyme immunoassay. RESULTS: Of the 580 participants tested for rubella antibodies, 135 (23.3%) were seronegative. The proportions of susceptible individuals were 61.7, 29.5, 12.4, 10.3 and 8.4% in the age groups of 1 to 4, 5 to 9, 10 to 14, 15 to 19 and 20 to 29 years, respectively. Of the young women 15 to 19 years of age, 13.5% were susceptible to rubella infection. CONCLUSIONS: Because a substantial proportion of women in their childbearing years are susceptible to rubella, immunization efforts should be directed at infants or prepubertal children.

Nosocomial hepatitis C virus infection in a renal transplantation center.

Nosocomial hepatitis C virus (HCV) infections were recorded in the renal transplantation unit of the university hospital. There were cases of acute HCV infection with aggressive clinical courses diagnosed from a positive HCV RNA test in the early post-transplantation period and which remained anti-HCV negative. Their anti-HCV seronegativity was attributed to them having acquired HCV under intense immunosuppressive therapy and suggested that the aggressive clinical course could be due to the deficient immune response resulting in an inability to limit viral replication. There were also donors diagnosed as having acute HCV infection in the early post-operative period. Genotyping and sequence analysis for HCV were performed on the isolates of eight of these patients who were consecutively transplanted and of three donors whose recipients were infected with HCV prior to transplantation, and who acquired acute HCV infection after transplantation. Of the eight recipients in the first group three were genotype 1a, three were genotype 1b, one was genotype 3a, and the last one was genotype 4 according to Simmond's classification. Of the three donor-recipient couples both the HCV isolates from one couple were genotyped as 1b and the phylogenetic analysis indicated that the patients were infected with a common variant of HCV, but the genotypes of HCV isolates from the other couples were different. Recipients were genotype 1b and the donors were genotype 1a in these couples. Genotype results of the first group and donor-recipient couples, and sequence analysis of genotype 1b and 1a isolates, showed that the source of infection was not a unique strain and there were multiple breaks in universal precautions while managing these patients.

Is 201Tl a reliable agent in tumour imaging?

Thallium-201 (201Tl) imaging has been widely used to differentiate post-therapy reactions from residual viable tumour or local recurrence. However, the ability of 201Tl to discriminate between tumour and post-therapy changes with superimposed infection/inflammation is unclear. This experimental study investigated the localization of 201Tl in infected/inflamed tissues. Twenty-four rats infected with Staphylococcus aureus and 10 rats injected with a standard volume of saline solution (SS) into the thigh muscles were studied. Twenty-four ours after microorganism or SS administration, 18 MBq 201Tl was injected intravenously. Images were recorded at 20 min and 3 h post-injection. The increased tracer uptake was evaluated qualitatively and quantitatively by calculating the ratios (L/C) derived from regions of interest drawn over the lesion and the contralateral thigh muscle. After the imaging procedure, histopathological examination was also performed. Whereas the control group showed no abnormal accumulation of activity, the infected rats demonstrated markedly increased activity, especially on the 20 min images. The mean L/C ratios for the 20 min and 3 h images for the infected rats were 2.18 +/- 0.20 and 1.52 +/- 0.04, respectively (P < 0.0005). In conclusion, positive uptake due to an infective process may limit the use of 201Tl in studies monitoring response to tumour therapy. Although delayed imaging may help to overcome this limitation, further investigations among a large series of patients are required in order to improve the reliability of 201Tl imaging in oncology.

Accumulation of 99Tcm-polyclonal immunoglobulin in different stages of infection: an experimental study.

In this experimental study, the utility of 99Tc(m)-polyclonal human immunoglobulin (99Tcm-HIG) for localizing acute and chronic phases of inflammatory lesions was investigated. Three groups of rats were inoculated with Staphylococcus aureus in the right thigh. Then, 24 h (group I, n = 12), 48 h (group II, n = 12) and 72 h (group III, n = 12) post-inoculation, the rats received 40 MBq 99Tcm-HIG into the jugular vein. In addition, two control rats were studied at 24 h after inoculation of sterile saline. Both visual and quantitative evaluations were undertaken. The acute and chronic stages of inflammation were determined by pathological examination. The mean ( +/- S.D.) lesion/contralateral uptake ratios at 4 and 24 h after 99Tcm-HIG injection were: group I, 1.22 +/- 0.1 and 2.12 +/- 0.16; group II, 1.15 +/- 0.08 and 2.25 +/- 0.16; group III, 1.06 +/- 0.09 and 2.08 +/- 0.14. In conclusion, the acute and chronic phases of infection showed non-significant differences in 99Tcm-HIG uptake ratios.

The prevalence of human papilloma virus DNA in women with mucopurulent endocervicitis.

OBJECTIVE: The aim of the study was to determine the prevalence of human papillomavirus (HPV) infection in a group of patients with mucopurulent endocervicitis. MATERIALS AND METHODS: One hundred and forty-eight patients who came for their routine medical screening and were diagnosed with mucopurulent endocervicitis were enrolled in the study. HPV DNA was sought in cervical swab specimens placed in digene transport medium by use of the Digene Hybrid Capture assay. RESULTS: HPV infection was detected in 5.4% (8/148) of the patients with mucopurulent endocervicitis. The mean age of the patients was 36.4+/-8.2 (18-54) years. Approximately 40% (59/148) of the patients used intrauterine devices currently or in the past, while 16.2% (24/148) used combined oral contraceptives as the contraceptive method. HPV DNA was detected in eight patients: five had infections with low-risk subtypes, one with high/intermediate risk subtypes and one with the combination of high- and low-risk subtypes. The mean age of the HPV infected patients was significantly lower than the HPV negative patients (28.2+/-6.3 versus 36.9+/-8.1 years, p = 0.003). Risk factors for HPV infection did not differ between the infected and uninfected groups. CONCLUSION: HPV infection should be sought in patients with clinical evidence of mucopurulent endocervicitis even without risk factors for cervical neoplasia.

Evaluation of the risk of cervical intraepithelial neoplasia and human papilloma virus infection in renal transplant patients receiving immunosuppressive therapy.

OBJECTIVE: To investigate the risk of cervical intraepithelial neoplasia and the coexistence of human papilloma virus (HPV) infection in renal transplant patients receiving immunosuppressive therapy. MATERIALS AND METHODS: Cervical Papanicolaou (Pap) smear and colposcopic examinations were performed in 48 renal transplant patients receiving immunosuppressive therapy. Microbiological and histopathologic findings were discussed. RESULTS: The patients were evaluated as to cervical neoplasia risk factors and the results were found to be statistically insignificant (p>0.05). Genital neoplasia was encountered in 20 of the 48 renal transplant patients. Koilocytosis developed in 6 out of 8 (75%) patients who were receiving high dose immunosuppressive therapy due to transplant rejection. HPV was found in 2 out of 48 patients; these 2 patients had koilocytosis in their cervical biopsies. The difference between the positive predictive value of colposcopic evaluation and the Pap smear was found to be insignificant (p>0.05). However, if colposcopy had not been performed in two cases of cervical intraepithelial neoplasia class I (CIN-I) and in one case of cervical microinvasive carcinoma, the cases would have been incorrectly diagnosed as normal by the false-negative results of the Pap smear. CONCLUSION: Renal transplant patients who were undergoing immunosuppressive therapy were found to be at increased risk of developing cervical intraepithelial neoplasia. All the patients using immunosuppressive agents should be followed-up by Pap smears every six months and by colposcopic evaluation every year. Avoiding high-risk sexual acts will decrease the risk of HPV transmission and the risk of genital neoplasia as well.

Seroprevalence of Helicobacter pylori in a pediatric population.

Helicobacter pylori (H. pylori) is one of the common bacterial infections in humans. In this study, seroprevalence of H. pylori infection in a pediatric population in Izmir and its relationship with different variables were investigated. Two hundred twenty-six children (115 boys, 111 girls, age range: 1-18) were tested for anti-H. pylori IgG. Socioeconomic conditions, living area (urban or rural), and number of people living in the same house were noted for each subject. H. pylori antibodies were determined by an enzyme immunoassay. Overall, 120 (53%) subjects were seropositive for H. pylori. The seroprevalence of H. pylori increased significantly with age and poor socioeconomic conditions. Seroprevalence did not differ according to sex, number of people living in the same house or living area.

HBV vaccination in liver transplant recipients: not an effective strategy in the prophylaxis of HBV recurrence.

Anti-HBs immunoglobulins (HBIG) and lamivudine are main options to prevent hepatitis B virus (HBV) reinfection after liver transplantation. Although they are very effective, development of mutant viruses and high cost of treatment are main limitations for their application. Additionally there is an uncertainity for the duration of that prophylaxis regimen and its mostly applied indefinitely. Recently, post-transplant HBV vaccination is reported to be a cheaper alternative prophylaksis strategy, that enables discontinuation of HBIG. To investigate the efficacy of HBV vaccination in patients transplanted for HBV cirrhosis, we administered double course of double dose recombinant HBV vaccine (Genhavac B; containing HBV pre-S1, pre-S2, and S gene products). Vaccination has been started 1 month after HBIg discontinuation, and lamivudine (100 mg/day) was given throughout the study. The first cycle consisted of 0, 1- and 6-month schedule, and, in nonresponders, second cycle 0, 1-, 2-month schedule. Fourteen patients included into the study. Only one patient seroconverted (an anti-HBs titre of 37 IU/L) after the first cycle. No other patient responded to second cycle. HBV vaccination in the post-transplantation setting does not seems like an effective strategy in the prophylaxis of HBV recurrence.

Immunity to diphtheria in Izmir, Turkey.

In order to assess immunity to diphtheria in Izmir, Turkey, a total of 743 persons 1-70 years of age were selected with cluster sampling. The information on socio-demographic characteristics, vaccination status and diphtheria history was gathered for each participant. Diphtheria antitoxin levels were measured qualitatively by using micro-enzyme immune assay. Of studied population, 79.1% had fully protective antitoxin levels (> or = 0.1 IU/ml). Diphtheria protection rates showed a gradual age-related decrease, reaching minimum in the 30-44 age group, in which 40.2% of these subjects had antibody titre below the full protective level. The diphtheria antitoxin geometric mean titer was highest in the 5-9 year age group (1.05 IU/ml). Then, geometric mean titer decreased with increasing age, and reached the minimum level in the 30-44 age group (0.19 IU/ml). These results suggest that in Izmir, Turkey, full serological protection against diphtheria is only detectable in 60% of the adult population. The enhancement of diphtheria immunity by booster vaccinations in adolescents and adults should be considered in Turkey.

Measles seroprevalence in Izmir with special emphasis on measles vaccination policy for Turkey.

BACKGROUND: Measles outbreaks seem to occur every 2- to 3-year intervals in Turkey. However, sero-epidemiological studies are limited. Knowing the prevalence of measles susceptibility as measured either by serologic markers of immunity or surveys of vaccination coverage is an important tool to assess the risk for measles outbreaks. METHODS: In order to determine the seroprevalence of measles antibodies among a 1 to 29-year-old population in Izmir (Turkey) and to develop the best vaccination policy for measles, a total of 600 people aged from 1 to 29 were selected for the study with cluster sampling. The information on sociodemographic characteristics, vaccination status and measles history was gathered for each participant. Measles-specific IgG antibodies were screened qualitatively by using microenzyme immune assay for 595 subjects. RESULTS: Of the 595 participants screened for the measles antibodies, 56 (9.4%) were seronegative. The proportion of the susceptible individuals in the age groups of 1-4, 5-9, 10-14, 15-19 and 20-29 was 20.0, 10.4, 6.0, 10.3 and 3.0%, respectively. The logistic regression analysis showed that none of the independent characteristics (sex, socioeconomic status, past measles history, vaccination status) with the exception of age group, was significantly associated with measles seronegativity. CONCLUSION: The optimal measles vaccination policy for Turkey may be to increase vaccination coverage above 90%, to conduct a catch-up campaign covering persons aged 1-19, regardless of previous vaccination status. Another factor to consider is to adopt a routine two-dose vaccination, giving the first dose at 12-15 months of age and the second dose at school entry.

DNA insitu hybridization in the diagnosis of human papillomavirus infection.

BACKGROUND: Certain types of human papillomavirus (HPV) are shown to be associated with the development of genital lesions. DNA hybridization methods are used for the diagnosis of HPV infections. OBJECTIVE: To use a nonradioactive DNA in situ hybridization system for the investigation of HPV infections responsible for the development of genital lesions in women. STUDY DESIGN: Sections from archival paraffin embedded biopsy specimens of 59 cases were screened for the presence of HPV DNA sequences by using digoxigenin labeled DNA probe which is specific for all types of HPVs and digoxigenin detection system. The study group consisted of samples diagnosed as squamous hyperplasia of the vulva (group 1), koilocytosis (group 2), condyloma acuminatum/koilocytotic atypy (group 3), cervical intraepithelial neoplasia (CIN), and epidermoid carcinoma (group 4). RESULTS: No HPV DNA was detected in groups 1 and 2 which consisted of 3 and 13 specimens respectively. Seven of 11 (63.6%) specimens in group 3 and 7 of 32 (21.9%) in group 4 were found to be positive for in situ HPV DNA. Seven positive samples in group 3 and one positive sample in group 4 were typed as HPV 6/11. Five samples of the remaining positives in group 4 were typed as HPV 16/18. One case was found to be positive with both 16/18 and 31/33. CONCLUSION: Nonradioactive DNA in situ hybridization is an easy and efficient method to be performed for the diagnosis of HPV infections. Koilocytosis with atypy is directly correlated with HPV infection and it is suggested to monitor the CIN cases with HPV type 16/18 infection since the pathology can be progressive.

TT virus infection and genotype distribution in blood donors and a group of patients from Turkey.

BACKGROUND: TT virus (TTV) DNA has been found in a large proportion of patients with different forms of non-A-G hepatitis, however the clinical importance is unclear. We aimed to determine the genotypes of TTV isolates found in blood donors and different patient groups from the western part of Turkey. MATERIALS AND METHODS: TT DNA was investigated in serum samples of 91 volunteer blood donors (BD), 105 thalassemia (TH) patients, ten patients with fulminant hepatitis (FH) and 16 hemodialysis (HD) patients by heminested PCR using primers NG059, NG061 and NG063 from the ORF1 region. 39 isolates were genotyped by analyzing the partial sequence of ORF1. RESULTS: TTV DNA was found in 75% of HD, 80% of FH, 61% of TH patients and in 51.6% of BD. Among the sequenced isolates, 14 (35.9%) belonged to genotype 1 (G1) and 25 (64.1%) belonged to genotype 2 (G2). Among the G2 sequences, 22 were grouped as G2c. CONCLUSION: TTV infection was common in the population studied, even with moderately sensitive primers. G2 was the major genotype of the studied population without any significant differences in distribution between various patient groups and BD.

alpha-Interferon-2b treatment for chronic hepatitis-B infection in children with cancer.

We have evaluated the efficacy of treatment with recombinant Interferon-2b (IFN-2b) in 12 children with cancer who developed chronic hepatitis-B infection. Seven of them had lymphoblastic leukaemia and others had solid tumours. Seven cases were male. Mean age was 10.5 years with a range of 5-16 years. Chronic Hepatitis B was diagnosed biochemically, serologically and histopathologically. They were HBsAg(+), HBV-DNA(+), and HCV(-), HIV(-). Seven cases were HBeAg(+) and two of them were anti-Delta IgG(+). Liver biopsy revealed chronic active hepatitis in six cases and persistent hepatitis in three cases. IFN was given at the dose of 5 MU/m2 three times a week, subcutaneously for 6 months. It was well tolerated. After IFN therapy, ALT levels returned to normal in seven cases. All cases were still HBsAg(+). Four of them seroconverted to anti-HBe antibody. Loss of serum HBV-DNA in three cases, but 11 cases showed a marked decrease after IFN. The control liver biopsies showed that histopathological activity index was diminished in five cases. Other 16 patients, serving as control, received no therapy. Five of them were leukaemia and others were solid tumours. Twelve cases were male. Mean age was 9.3 years with a range of 4-19 years. After 6 months, only one patient lost HBV-DNA and three of them seroconverted to anti-HBe with normalization of ALT values. In our study, IFN treatment favourably influenced the progress of chronic hepatitis B in children with cancer.