Therapeutic Drug Monitoring of Ganciclovir in Cytomegalovirus-Infected Patients With Solid Organ Transplants and Its Correlation to Efficacy and Toxicity.

Background: Cytomegalovirus causes morbidity and mortality, especially in immunocompromised patients, and is treated with (val)ganciclovir. Therapeutic drug monitoring of ganciclovir is often performed; however, clinically established target trough levels corresponding to efficacy are lacking. In 2021, our clinic increased the target trough level for ganciclovir from 1 to 2 mg/L to 2-4 mg/L.

HCV virology and diagnosis.

Hepatitis C virus (HCV) infection is a major cause of severe liver disease including chronic hepatitis, cirrhosis and hepatocellular carcinoma. The HCV burden in public health is estimated at about 71 million people worldwide by World Health Organization (WHO) with at least 400,000 people that died every year from HCV disease [1]. New hepatitis C treatments with oral direct-acting antivirals (DAAs) showing high rates of response, with short treatment duration [2] have been available.

A Dutch nationwide evaluation of serological assays for detection of Borrelia antibodies in clinically well-defined patients.

Numerous tests for the detection of antibodies against Borrelia burgdorferi are commercially available. Manufacturer-derived data invariably report a high sensitivity and specificity, but comparative studies demonstrate large differences in clinical practice, especially with regard to specificity. We retrospectively collected data from validation studies for B.

Interest of human papillomavirus DNA quantification and genotyping in paired cervical and urine samples to detect cervical lesions.

Background: Cervical cancer is caused by persistent infection with high-risk human papillomavirus (HR-HPV). Conventional human papillomavirus (HPV) testing requires cervical sampling. However, vaginal and urine self-sampling methods are more acceptable for patients and result in increased participation when they are available in screening programs.

Improved fibrosis staging by elastometry and blood test in chronic hepatitis C.

Aims: Our main objective was to improve non-invasive fibrosis staging accuracy by resolving the limits of previous methods via new test combinations. Our secondary objectives were to improve staging precision, by developing a detailed fibrosis classification, and reliability (personalized accuracy) determination.

Methods: All patients (729) included in the derivation population had chronic hepatitis C, liver biopsy, 6 blood tests and Fibroscan.

Distribution of total DNA and cccDNA in serum and PBMCs may reflect the HBV immune status in HBsAg+ and HBsAg- patients coinfected or not with HIV or HCV.

Background: The potential reservoir role of serum and peripheral blood mononuclear cells (PBMCs) for total HBV DNA (tDNA) and cccDNA still remains unknown.

Material And Methods: We analyzed tDNA and cccDNA with a single sensitive and validated standardized real-time PCR method in serum and PBMCs in two populations of chronic HBV infection coinfected or not with HCV and/or HIV viruses: a retrospective cohort of 130 HBsAg-negative (HBsAg-) patients with "anti-HBc alone" or anti-HBc and anti-HBs antibodies (Ab) and a cohort of 70 HBsAg-positive patients, 16 of them being prospectively followed under treatment.

Results: Among HBsAg- patients, HBV DNA was detected in serum or PBMCs in about half of the cases with various distributions of tDNA and cccDNA: in HIV-negative patients with an "antiHBc alone" profile, tDNA was mostly detected in PBMCs suggesting a possible active role of PBMCs; although cccDNA was not detected in PBMCs in HIV-positive patients, tDNA and cccDNA were mostly observed in serum, suggesting a specific pattern of more "persistent" than "occult" infection in this population.

Virological and epidemiological features of hepatitis delta infection among blood donors in Nouakchott, Mauritania.

Background: In Mauritania, some authors have described a possible high prevalence of hepatitis delta virus (HDV) infection in the 1990s in studies of small-size samples.

Objectives: The aims of our study were to assess the prevalence of HDV in HBsAg positive blood donors in Mauritania, to identify the main risk factors for HDV transmission and to analyze genetic diversity of HDV strains.

Study Design: From October 2008 to December 2009, 11,100 consecutive blood donors were considered in this study.

[Viral markers of hepatitis B, C and D and HB vaccination status of a health care team in a rural district of Cameroon].

Unlabelled: Ninety-three health care workers (HCW) in the Tokombere sahelian district volunteered to participate in a trial to investigate viral markers of hepatitis B, C, and D and HB vaccination status.

Methods: . Sera were tested using the Vikia HBsAg kit followed by CMIA for detection of HBsAg, anti-HBs, anti-HBc, and anti-HCV.

Performance of the new Platelia Candida Plus assays for the diagnosis of invasive Candida infection in patients undergoing myeloablative therapy.

The performance of the new Platelia Candida Antigen Plus (Ag Plus) and Antibody Plus (Ab Plus) assays (Biorad Laboratories, France) was evaluated using a collection of serum samples obtained from 21 patients with microbiologically proven invasive candidiasis and 30 control patients who were being treated with myeloablative chemotherapy, and the data compared with that obtained with the earlier version of the Platelia Candida assays (Ag and Ab), and 1,3-ß-D-glucan (BG) detection systems. The sensitivity of the Ag Plus and Ab Plus assays in the per patient analysis ranged from 55-70% and from 30-64% for patients with less than 15 days of neutropenia and more than 15 days of neutropenia, respectively. Sensitivity and time to detection of these new assays was not significantly better than of the conventional Platelia Candida tests.

Interpretation of real-time PCR results for hepatitis C virus RNA when viral load is below quantification limits.

Hepatitis C virus RNA quantification results obtained in 18 laboratories using real-time PCR methods with 10 negative samples and 22 sample dilutions (viral loads of 0.5 to 500 IU/ml) showed a score of correct results of up to 93.5%.

A Q fever outbreak in a psychiatric care institution in The Netherlands.

In May 2008 the Nijmegen Municipal Health Service (MHS) was informed about an outbreak of atypical pneumonia in three in-patients of a long-term psychiatric institution. The patients had been hospitalized and had laboratory confirmation of acute Q fever infection. The MHS started active case finding among in-patients, employees of and visitors to the institution.

Resolution of chronic hepatitis Delta after 1 year of combined therapy with pegylated interferon, tenofovir and emtricitabine.

Background: Hepatitis Delta virus (HDV) Infection has a worldwide distribution, with approximately 20 millions infected persons. Interferon (IFN) is the only approved drug for the treatment of HDV infection which is still a difficult to treat disease.

Objectives: To report a successful treatment of a patient with a chronic severe hepatitis Delta using combination therapy with Pegylated interferon (PegIFN), Tenofovir disoproxil fumarate (TDF) and Emtricitabine (FTC).

Value of Candida serum markers in patients with invasive candidiasis after myeloablative chemotherapy.

Invasive Candida infections are associated with a significant morbidity and mortality. Detection of circulating biomarkers has been shown to precede conventional diagnostic methods, which is important in improving outcome. We investigated the performance of multiple biomarkers using Candida antigen and anti-Candida antibody detection systems of Platelia and Serion and beta-d-glucan detection in serial serum samples from patients, treated for leukemia, with invasive candidiasis.

FibroMeters: a family of blood tests for liver fibrosis.

FibroMeters are blood tests for liver fibrosis with several specificities: two main diagnostic targets (fibrosis stage and area of fibrosis); adaptation to specific causes; and results confirmed by an expert system. Thus, FibroMeters comprise six different tests: one for staging and one for quantitation of liver fibrosis in each of the three main causes of chronic liver disease-chronic viral hepatitis, alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). FibroMeters display a high overall diagnostic accuracy and are the only tests to correctly classify 100% of HCV patients without fibrosis or with cirrhosis.

Evaluation and improvement of a reliable diagnosis of cirrhosis by blood tests.

Objective: To evaluate the rates of reliable diagnosis of cirrhosis by two usual blood tests.

Methods: Reliable diagnosis was mainly evaluated by comparing rates of positive (PPV) and negative (NPV) predictive values with FibroTest and FibroMeters, as either standard test or specifically designed for cirrhosis, in 1056 patients with chronic hepatitis C.

Results: Using the diagnostic limits provided by fibrosis stage scales, the PPV for cirrhosis was: standard FibroMeters: 68.

Comparison of blood tests for liver fibrosis specific or not to NAFLD.

Background/aims: To compare blood tests of liver fibrosis specific for NAFLD: the FibroMeter NAFLD and the NAFLD fibrosis score (NFSA) with a non-specific test, APRI.

Methods: Two hundred and thirty-five NAFLD patients with liver Metavir staging and blood markers from two independent centres were randomly assigned to a test (n=121) or a validation population (n=114).

Results: The highest accuracy--91%--for significant fibrosis was obtained with the FibroMeter whose (i) AUROC (0.

A revised method for estimating hepatitis B virus transfusion residual risk based on antibody to hepatitis B core antigen incident cases.

Background: To take into account the transient nature of hepatitis B virus (HBV) antigenemia, the calculation of HBV residual risk (RR), based on the incidence/window period model, is adjusted by a correction factor that adds uncertainty to the RR estimates.

Study Design And Methods: This new method to estimate the RR for HBV is a weighted sum of the RR derived from hepatitis B surface antigen (HBsAg) incident cases and the one derived from antibody hepatitis B core antigen (HBc) incident cases. An anti-HBc incident case was defined as a donation from a blood donor who had made at least one anti-HBc-negative donation followed by a donation that was found positive with two different assays within a 3-year period and positive for at least one of the following markers: 1) antibody to hepatitis B e antigen or hepatitis B e antigen, 2) anti-HBc immunoglobulin M, 3) HBV DNA, 4) hepatitis B surface antibody without HBV vaccination history, or 5) HBV DNA retrospectively found in the previous donation.

Ribavirin exposure after the first dose is predictive of sustained virological response in chronic hepatitis C.

Unlabelled: The impact of ribavirin exposure on sustained virological response (SVR) in patients with chronic hepatitis C is unknown. Preliminary studies showed marked inter-individual variability of ribavirin concentrations despite dose adjustment for body weight (BW) and suggested there was a correlation between single time point concentrations and SVR. None of them evaluated the global exposure to ribavirin.

Multicenter trials need to use the same assay for hepatitis C virus viral load determination.

This study, involving 20 laboratories and using currently available assays for hepatitis C virus RNA quantification, demonstrated that differences in viral load values are due not to interlaboratory variations but rather to the nature of the assay itself. This underlines the importance of using the same assay in multicenter studies or when monitoring antiviral therapy.

Therapeutic drug monitoring of the HIV protease inhibitor atazanavir in clinical practice.

Background: Therapeutic drug monitoring (TDM) is being applied for a number of antiretroviral agents. Little is known about the use of TDM for atazanavir.

Methods: This is a retrospective cohort analysis on the use of TDM of atazanavir at three clinical sites in The Netherlands.

High hepatitis C virus viral load in HIV/hepatitis C virus-co-infected patients: a different influence of protease inhibitor and non-protease inhibitor-based HAART?

We examined the possible relationships between hepatitis C virus (HCV) viral load and host factors, viral factors, and anti-HIV therapy in 379 HIV/HCV-co-infected patients. Multiple linear regression analysis identified two independent factors associated with higher HCV viral load, HCV genotype 1 or 4 infection and protease inhibitor-based antiretroviral therapy. Antiretroviral therapy in general was independently associated with lower HCV viral load.

Quasispecies evolution in NS5A region of hepatitis C virus genotype 1b during interferon or combined interferon-ribavirin therapy.

Aim: To evaluate the implication of substitutions in the hepatitis C virus (HCV) non-structural 5A (NS5A) protein in the resistance of HCV during mono-interferon (IFN) or combined IFN-ribavirin (IFN-R) therapy. Although NS5A has been reported to interact with the HCV RNA-dependent RNA polymerase, NS5B, as well as with many cellular proteins, the function of NS5A in the life cycle of HCV remains unclear.

Methods: HCV quasispecies were studied by cloning and sequencing of sequential isolates from patients infected by HCV genotype 1b.

Rapid and early virological response to chronic hepatitis C treatment with IFN alpha2b or PEG-IFN alpha2b plus ribavirin in HIV/HCV co-infected patients.

Background And Aims: An algorithm based on a 2 log(10) decline in hepatitis C virus (HCV) RNA at week (W) 12 has been proposed in US and European recommendations for the management of patients with chronic hepatitis C treated with pegylated-interferon and ribavirin.

Methods: We examined rapid virological response (RVR; at W2 and W4 after the initiation of therapy) in HIV/HCV co-infected patients. Using HCV RNA measurements (Versant HCV RNA 3.

Human papillomavirus quantification in urine and cervical samples by using the Mx4000 and LightCycler general real-time PCR systems.

During the last decade, growing efforts have focused on human papillomavirus (HPV) detection using liquid hybridization, conventional PCR, and real-time PCR-based methods to increase the overall proportion of patients participating in cervical cancer screening procedures. We proposed a new general HPV DNA real-time PCR on the Mx4000 (Stratagene) and LightCycler (Roche Diagnostics) systems usable for both cervical scrape specimens and urine samples. A linear range was obtained from 5 DNA copies to 8 log(10) DNA copies/ml, and intra- and interassay variations were between 1.