Emergence of the rtA181T/sW172* mutant increased the risk of hepatoma occurrence in patients with lamivudine-resistant chronic hepatitis B

<p>Abstract</p> <p>Background</p> <p>Development of the hepatitis B virus (HBV) rtA181T/sW172* mutant could occur during prolonged lamivudine (LAM) therapy, conferring cross resistance to adefovir. Recent studies demonstrated an increased oncogenic potential of this mutant in NIH3T3 cells. In this study, we aimed to investigate the clinical significance of this finding.</p> <p>Methods</p> <p>Serum samples from 123 LAM-resistant chronic hepatitis B patients were submitted for virological assays. A highly sensitive amplification created restriction enzyme site (ACRES) method was devised to detect small amounts of the rtA181T mutant in the serum. Virological factors including HBV-DNA level, genotype, precore G1896A, BCP A1762T/G1764A, rtM204I/V, rtA181T and pre-S internal deletion mutations as well as clinical variables including subsequent use of rescue drugs were submitted for outcome analysis.</p> <p>Results</p> <p>By use of the highly sensitive ACRES method, the rtA181T mutant was detectable in 10 of the 123 LAM-resistant patients. During the mean follow-up period of 26.2 ± 16.4 months (range 2 to 108 months), 3 of the 10 (30.0%) rtA181T-positive patients and 2 of the 113 (1.8%) rtA181T-negative patients developed hepatocellular carcinoma (HCC). Kaplan-Meier analysis indicated that the presence of rtA181T mutation (P < 0.001), age > 50 years (P = 0.001), and liver cirrhosis (P < 0.001) were significantly associated with subsequent occurrence of HCC. All 5 HCC patients belonged to the older age and cirrhosis groups.</p> <p>Conclusions</p> <p>Emergence of the rtA181T/sW172* mutant in LAM-resistant patients increased the risk of HCC development in the subsequent courses of antiviral therapy.</p

Circulating sCD14 Is Associated with Virological Response to Pegylated-Interferon-Alpha/Ribavirin Treatment in HIV/HCV Co-Infected Patients

Microbial translocation (MT) through the gut accounts for immune activation and CD4+ loss in HIV and may influence HCV disease progression in HIV/HCV co-infection. We asked whether increased MT and immune activation may hamper anti-HCV response in HIV/HCV patients.98 HIV/HCV patients who received pegylated-alpha-interferon (peg-INF-alpha)/ribavirin were retrospectively analyzed. Baseline MT (lipopolysaccharide, LPS), host response to MT (sCD14), CD38+HLA-DR+CD4+/CD8+, HCV genotype, severity of liver disease were assessed according to Early Virological Response (EVR: HCV-RNA <50 IU/mL at week 12 of therapy or ≥2 log(10) reduction from baseline after 12 weeks of therapy) and Sustained Virological Response (SVR: HCV-RNA <50 IU/mL 24 weeks after end of therapy). Mann-Whitney/Chi-square test and Pearson's correlation were used. Multivariable regression was performed to determine factors associated with EVR/SVR.71 patients displayed EVR; 41 SVR. Patients with HCV genotypes 1-4 and cirrhosis presented a trend to higher sCD14, compared to patients with genotypes 2-3 (p = 0.053) and no cirrhosis (p = 0.052). EVR and SVR patients showed lower levels of circulating sCD14 (p = 0.0001, p = 0.026, respectively), but similar T-cell activation compared to Non-EVR (Null Responders, NR) and Non-SVR (N-SVR) subjects. sCD14 resulted the main predictive factor of EVR (0.145 for each sCD14 unit more, 95%CI 0.031-0.688, p = 0.015). SVR was associated only with HCV genotypes 2-3 (AOR 0.022 for genotypes 1-4 vs 2-3, 95%CI 0.001-0.469, p = 0.014).In HIV/HCV patients sCD14 correlates with the severity of liver disease and predicts early response to peg-INF-alpha/ribavirin, suggesting MT-driven immune activation as pathway of HIV/HCV co-infection and response to therapy

Impact of Safety-Related Dose Reductions or Discontinuations on Sustained Virologic Response in HCV-Infected Patients: Results from the GUARD-C Cohort.

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced ≥1 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with ≥1 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not ≥5. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin.This study was sponsored by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Support for third-party writing assistance for this manuscript, furnished by Blair Jarvis MSc, ELS, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

Background: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. Methods: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. Results: SVR24 rates were 46.1 % (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1,2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. Conclusions: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginter-feron alfa-2a/ribavirin

Infection Probability Score: A predictor of Clostridium difficile-associated disease onset in patients with haematological malignancy

Purpose: to assess the predictive power of three systems: Infection Probability Score, APACHE II and KARNOFSKY score for the onset of Clostridium difficile-associated disease (CDAD) in hematology-oncology patients. Methods and sample: A retrospective pilot surveillance survey was conducted in the hematology unit of a general hospital in Greece. Data were collected by using an anonymous standardised case-record form. The sample consisted of 102 hospitalized patients. Results: The majority of the patients (33.3%) suffered from acute myeloid leukemia. The cumulative incidence of CDAD was 10.8% and the incidence rate of C difficile associated diarrhea was 5 per 1000 patient-days (14.2 per 1000 patient-days at risk). Patients with CDAD had twofold higher time of mean length of hospital stay compared with patients without CDAD (38.82 ± 23.88 vs 19.45 ± 14.56 days). Additionally patients with CDAD had received a greater number of different antibiotics compared to those without CDAD (5.18 ± 1.99 vs 2.54 ± 2.13), suffered from diabetes, from non Hodgkin&apos;s lymphoma, had a statistically significant higher duration of neutropenia ≥3 days and had received antifungal treatment. The best cutoff value of IPS for the prediction of CDAD was 13 with a sensitivity of 45.5% and a specificity of 82.4%. Conclusions: IPS is an early diagnostic test for CDAD detection. © 2010 Elsevier Ltd

Infection Probability Score, APACHE II and KARNOFSKY scoring systems as predictors of bloodstream infection onset in hematology-oncology patients

Background: Bloodstream Infections (BSIs) in neutropenic patients often cause considerable morbidity and mortality. Therefore, the surveillance and early identification of patients at high risk for developing BSIs might be useful for the development of preventive measures. The aim of the current study was to assess the predictive power of three scoring systems: Infection Probability Score (IPS), APACHE II and KARNOFSKY score for the onset of Bloodstream Infections in hematology-oncology patients.Methods: A total of 102 patients who were hospitalized for more than 48 hours in a hematology-oncology department in Athens, Greece between April 1stand October 31st2007 were included in the study. Data were collected by using an anonymous standardized recording form. Source materials included medical records, temperature charts, information from nursing and medical staff, and results on microbiological testing. Patients were followed daily until hospital discharge or death.Results: Among the 102 patients, Bloodstream Infections occurred in 17 (16.6%) patients. The incidence density of Bloodstream Infections was 7.74 per 1,000 patient-days or 21.99 per 1,000 patient-days at risk. The patients who developed a Bloodstream Infection were mainly females (p = 0.004), with twofold time mean length of hospital stay (p &amp;lt; 0.001), with fourfold time mean length of neutropenia (p &amp;lt; 0.001), with neutropenia &amp;lt; 500 (p &amp;lt; 0.001), suffered mainly from acute myeloid leukemia (p &amp;lt; 0.001), had been exposed to antibiotics (p = 0.045) and chemotherapy (p = 0.023), had a surgery (p = 0.048) and a Hickman catheter (p = 0.025) as compared to the patients without Bloodstream Infection. The best cut-off value of IPS for the prediction of a Bloodstream Infection was 10 with a sensitivity of 75% and specificity of 70.9%. Conclusion: Between the three different prognostic scoring systems, Infection Probability Score had the best sensitivity in predicting Bloodstream Infections. © 2010 Apostolopoulou et al; licensee BioMed Central Ltd

Prevalence of hepatitis b in haemodialysis nursing staff in athens

Background: Healthcare workers are at high risk of acquiring hepatitis B and particularly haemodialysis staff. The aim of the study was to examine the prevalence of hepatitis B markers in haemodialysis nurses and to explore the determinants of the infection. Patients and methods: Two hundred and sixteen haemodialysis nurses from 20haemodialysis units in Athens completed an anonymous questionnaire, their blood samples were taken and tested for hepatitis B virus (HBV) markers. Results: The prevalence of positive HBsAg among nurses was 0.5%. Anti-HBc positivity due to past exposure to HBV was 12.5%. A total of 87.5% of the participants had immunity to HBV. Multivariate analysis demonstrated that previous exposure to HBV was related positively with the age of the haemodialysis nursing staff [odd ratios (OR): 1.115, 95% CI: 1.014-1.226, P = 0.025]. Conclusion: The prevalence of HBV in the haemodialysis nursing staff in Athens is low, the vaccination coverage and the immunity to HBV are high in comparison to previous reports. © 2012 European Dialysis and Transplant Nurses Association/European Renal Care Association

Spontaneous preterm birth in women with chronic hepatitis B virus infection

Objective: To determine whether chronic hepatitis B virus (HBV) infection, as evidenced by serum levels of HBsAg and HBV DNA, is a risk factor for spontaneous preterm birth (SPB). Method: The prevalence of HBV infection and the SPB rate were prospectively investigated among 1826 pregnant women, 30.89% Albanian and the remainder of other European origins. Results: Overall, 70 (3.8%) of the women were chronically infected with HBV. HBsAg status was strongly linked to SPB, which incurred to 5 (7.3%) of 64 women with circulating HBsAg compared with 28 (1.6%) of 1703 without current HBV infection (odds ratio, 5.2; P = 0.007). SPB, however, was linked neither to HBsAg levels, nor to HBV DNA levels, nor to the presence or absence of viremia. Conclusion: Pregnant women were found to be at higher risk for SPB if they had circulating HBsAg, and the risk did not seem to be influenced by the levels of HBsAg or HBV DNA. © 2010 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved