Archive for May, 2006

Pegylated interferon and ribavirin treatment for hepatitis C in haemodialysis patients

Journal of Viral Hepatitis May 2006 Vol.13 N.5 P.316

A. Bruchfeld1, K. Lindahl2, O. Reichard2, T. Carlsson2 and R. Schvarcz2

Summary. Standard therapy for chronic hepatitis C (HCV) is pegylated interferon in combination with ribavirin. There is limited experience with either drug in dialysis [end stage renal disease (ESRD)].

Six haemodialysis patients, four with HCV genotype 1, one with genotype 4 and one genotype 2 were treated with pegylated interferon-alfa-2b (n = 4) and pegylated interferon-alfa-2a (n = 2) for 24–48 weeks according to genotype with a dose of 50 or 135 μg/week respectively. All patients were given reduced ribavirin doses, initially 200–400 mg/day.

Ribavirin trough plasma concentrations were measured with a HPLC method previously developed for earlier treatment studies, aiming at a target concentration of 10–15 μmol/L. Interferon related side-effects were common, in one patient peg-alfa-2b was permanently reduced to 50 μg every 9–10 days with improvement in tolerance. Average ribavirin dose was 170–300 mg/day.

Ribavirin-induced anaemia was treated with high doses of erythropoietin and low doses of iron. Blood-transfusions were not needed. All patients became HCV-RNA-PCR negative during treatment which was completed or nearly completed in four patients.

One patient terminated therapy prematurely due to pronounced interferon related side-effects and another died of myocardial infarction probably not related to therapy. Three patients have remained HCV-RNA negative with extended follow-up, two of whom have had a successful kidney transplant.

Pegylated interferons are likely to become a valuable addition for HCV therapy in ESRD and are possible to combine with ribavirin. However the pharmacokinetics and tolerability of both peg-alfa-2a and 2b need to be studied more closely in prospective studies before definite dosing recommendations can be made.

May 28, 2006 at 10:07 pm Leave a comment

Fibrosis progression in initially mild chronic hepatitis C

Journal of Viral Hepatitis May 2006 Vol.13 N.5 P.297 

S. Boccato, R. Pistis, F. Noventa, M. Guido, L. Benvegnù and A. Alberti

Summary. The natural history of chronic hepatitis C presenting with no/minimal liver fibrosis is uncertain with controversies on risk of progression and need for antiviral treatment.

We studied rates and determinants of fibrosis progression in initially mild chronic hepatitis C. One hundred and six patients (mean age 41.65 ± 12.83 years) with chronic hepatitis C virus infection and no/minimal fibrosis in the initial liver biopsy (F0/F1 by METAVIR score) were followed prospectively while untreated with repeated biopsy after 5 or more years (mean interval 7.8 ± 1.51 years).

Patients showing fibrosis progression were compared with nonprogressors for baseline and follow-up parameters. Sixty-four patients (60.4%) showed fibrosis progression including 13 of 27 (49%) with F0 and 51 of 79 (65%) with F1. Progression to F3 or cirrhosis was seen in 36% of those with F1 initially. Fibrosis progression (ΔF/year) was associated with age (P < 0.0001), baseline and follow-up alanine aminotransferase (ALT) (P = 0.005), histological activity (P = 0.004) and steatosis (P = 0.002) in the initial biopsy and use of alcohol (P = 0.008).

Thus liver fibrosis progression occurs in two-thirds of patients with initially mild chronic hepatitis C within 5–10 years and advanced fibrosis/cirrhosis develops in one-third of those with F1 initially. Fibrosis is facilitated by older age and alcohol and associated with inflammatory activity and ALT levels. Antiviral therapy should be considered in mild chronic hepatitis C.

May 28, 2006 at 10:05 pm Leave a comment

Hepatitis C virus carriers with persistently normal ALT levels: biological peculiarities and update of the natural history of liver disease at 10 years

Journal of Viral Hepatitis May 2006 Vol.13 N.5 P.290 

M. Persico1, S. Perrotta2, E. Persico1, L. Terracciano3, A. Folgori4, L. Ruggeri4, A. Nicosia4, R. Vecchione3, V. L. Mura1, M. Masarone1 and R. Torella1

Summary. Some chronic hepatitis C (CHC) patients exhibit persistently normal alanine aminotransferase (ALT) levels (PNAL).

Patients with PNAL experience significantly milder disease. In order to understand the differences between CHC patients with elevated ALT levels compared with those with PNAL better, we compared epidemiological, immunological and histological findings, in particular, the value of proliferating hepatocyte activity (PCNA) between the two groups of patients.

We studied 40 chronic hepatitis C virus (HCV) carriers with increased ALT who underwent liver biopsy for histological diagnosis and determination of clinical prognosis, and 24 PNAL patients under follow-up for 10 years. Immunological response to different HCV genomic epitopes was tested in both the control group and in PNAL subjects. PCNA values from liver specimens of all patients as well as liver biopsies of PNAL patients at time points 0 and 5 years were calculated according to Hall et al.Age, sex and body mass index (BMI) were not significantly different between the two groups. The median liver histology stage was significantly higher in HCV carriers vs the PNAL group (2.5, range = 2–6 vs 1.5, range = 1–2; P < 0.01).

Among PNAL patients, histological stage was not statistically different at the three time points considered. Interferon (IFN)-gamma production was comparable in the two groups. PCNA was significantly higher in the group with elevated ALT levels vs the PNAL group (8%, range = 4–15%vs 5% range = 3–8%; P < 0.05) and no statistically significant differences were found in PNAL patients at time points 0, 5 and 10 years.

This study confirms that progression to cirrhosis is slow or absent in PNAL patients after 10 years of follow-up. Accordingly, the hepatic proliferative activity index is low and seems to be stable over time.

May 28, 2006 at 10:04 pm Leave a comment

Single-Dose Safety and Pharmacokinetics of Brecanavir, a Novel Human Immunodeficiency Virus Protease Inhibitor

Agents and Chemotherapy 1 Jun 2006 Vol.50 N.6 p.2201-2206

Susan L. Ford,1* Y. Sunila Reddy,1 Maggie T. Anderson,1 Sharon C. Murray,1 Pedro Fernandez,1 Daniel S. Stein,2 and Mark A. Johnson1

GlaxoSmithKline, Research Triangle Park, North Carolina,1 Sanofi-Aventis Pharmaceuticals, Bridgewater, New Jersey2

Clic ver abstract:

May 28, 2006 at 9:34 pm Leave a comment

Fluoroquinolone-Resistant Urinary Isolates of Escherichia coli from Outpatients Are Frequently Multidrug Resistant: Results from the North American Urinary Tract Infection Collaborative Alliance-Quinolone Resistance Study

Agents and Chemotherapy 1 Jun 2006 Vol.50 N.6 p.2251-2254

James A. Karlowsky,1,2* Daryl J. Hoban,1,2 Melanie R. DeCorby,2 Nancy M. Laing,2 and George G. Zhanel2

Department of Clinical Microbiology, Health Sciences Centre/Diagnostic Services of Manitoba,1 Department of Medical Microbiology and Infectious Diseases, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada2

Clic ver abstract:

May 28, 2006 at 9:33 pm Leave a comment

Antimicrobial Susceptibility of Invasive Streptococcus pneumoniae Isolates in Portugal over an 11-Year Period

Agents and Chemotherapy 1 Jun 2006 Vol.50 N.6 p.2098-2105

Ricardo Dias, Deolinda Louro, the Antimicrobial Resistance Surveillance Program in Portugal, and Manuela Caniça*

Antibiotic Resistance Unit, Centre of Bacteriology, National Institute of Health Dr. Ricardo Jorge, Lisbon, Portugal

Clic ver abstract:

May 28, 2006 at 9:32 pm Leave a comment

Activities of Ceftobiprole, a Novel Broad-Spectrum Cephalosporin, against Haemophilus influenzae and Moraxella catarrhalis

Agents and Chemotherapy 1 Jun 2006 Vol.50 N.6 p.2050-2057

Tatiana Bogdanovich,1 Catherine Clark,1 Lois Ednie,1 Gengrong Lin,1 Kathy Smith,1 Stuart Shapiro,2 and Peter C. Appelbaum1*

Department of Pathology, Hershey Medical Center, Hershey, Pennsylvania 17033,1 Basilea Pharmaceutica AG, Basel, Switzerland2

Clic ver abstract:

May 28, 2006 at 9:31 pm Leave a comment

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