Treatment extension benefits HCV genotype 1 patients without rapid virological response: a systematic review.

BACKGROUND: Current guidelines recommend 48 weeks of treatment with pegylated interferon and ribavirin for patients infected with chronic hepatitis C virus (HCV) genotype 1. Several clinical trials have investigated the efficacy of treatment duration longer than 48 weeks, but yielded discordant results. METHODS: We performed a structured search of PubMed, Web of Science and the Cochrane library to identify randomised clinical trials in HCV genotype 1 patients who were treated either for 48 or 72 weeks. Sustained viral response (SVR) data were pooled and a sample size weighted pooled proportion was calculated. RESULTS: We identified five studies matching our criteria. Studies randomised at baseline (n=1), at absence of rapid virological response (RVR) at week 4 (n=1), at early virological response at week 12 (EVR) (n=1) or at slow response at week 24 (n=2). In the RCT that randomised at absence of RVR, SVR was significantly higher in the extended treatment arm (57 vs 42%, p=0.02) with an RR of 1.35 (95% CI 1.04 to 1.75). This tendency was also observed in the studies that randomised at slow response (44 vs 35%), although no longer statistically significantly different. CONCLUSION: Prolonged 72-week treatment should be considered in HCV genotype 1 patients without RVR at week 4, as this increased SVR.

Current clinical care compared with new Dutch guidelines for hepatitis C treatment.

BACKGROUND: Recently, the Dutch Association of Gastroenterology and Hepatology issued new guidelines for the treatment of chronic hepatitis C virus (HCV). These guidelines reflect the current standard of care. Before these guidelines were published and implemented we (1) studied the current clinical care of HCV patients among Dutch physicians, and (2) identified areas for future refinement in the current treatment. METHODS: We conducted a non-targeted survey among Dutch medical specialists in Gastroenterology, Hepatology and Internal Medicine who actively treat HCV patients. The questionnaire contained items about facility, duration and dosing of treatment, and side effect management using clinical vignettes followed by short questions. RESULTS: We received 49 questionnaires from treating HCV specialists. The majority (65%) of respondents treat HCV patients during regular outpatient clinics, while 35% treat these patients in a separate setting dedicated to the care of HCV patients. The majority of physicians follow the stipulated dosage regimens of pegylated interferon (88%) and ribavirin (83%). A minority (13%) exceed the advised dosage of ribavirin. Side effects such as neutropenia are mostly managed by decreasing the interferon dosage (42%). Some 35% of physicians reduce ribavirin if haemoglobin levels drop below 5.4 mmol/l, and 41% initiate erythropoietin treatment. CONCLUSION: Dutch clinical practice reflects the recently issued HCV guidelines. An important area of refinement in treatment of HCV is the management of side effects.

Prevalence of hepatitis C in the general population in the Netherlands.

BACKGROUND: Chronic hepatitis C virus (HCV) is transmitted by blood-blood contact and this leads to high HCV prevalence in risk populations such as haemophilia patients and intravenous drug users. The prevalence in the general Dutch population is unknown, although it appears to be very low in screened blood donors (0.0169%). AIM: The objective of this study is to estimate the prevalence of HCV in a general population sample living in an urbanized region in the Netherlands. METHODS: We randomly selected 2200 EDTA blood samples that had been submitted for analysis of biochemical parameters to a regional servicing laboratory for general practitioners (SHO, Arnhem/Nijmegen, the Netherlands). HCV antibody testing was performed using a three-step approach. For initial screening, an enzyme immunoassay (Bioelisa HCV 4.0, Biokit, Spain) was used. Positive samples were subjected to a second, microparticle enzyme-linked immunoassay (AxSYM HCV version 3.0, Abbott laboratories, IL , USA). Genotypes were determined by Line Probe Assay. RESULTS: A total of four persons (two females, two males) (0.2%) tested positive for HCV antibodies. The average OD/cut-off ratio of the screening assay was 2.9 (range 1.0 to 7.3) and serological findings were confirmed using a specific second immunoassay. HCV RNA (genotype 1b) was found in the sera of two persons. CONCLUSION: The HCV prevalence in our sample of the Dutch population was 0.2% which accords with earlier estimates from prevalence studies in the Netherlands.

Which drugs cause preventable admissions to hospital? A systematic review.

AIMS: Previous systematic reviews have found that drug-related morbidity accounts for 4.3% of preventable hospital admissions. None, however, has identified the drugs most commonly responsible for preventable hospital admissions. The aims of this study were to estimate the percentage of preventable drug-related hospital admissions, the most common drug causes of preventable hospital admissions and the most common underlying causes of preventable drug-related admissions. METHODS: Bibliographic databases and reference lists from eligible articles and study authors were the sources for data. Seventeen prospective observational studies reporting the proportion of preventable drug-related hospital admissions, causative drugs and/or the underlying causes of hospital admissions were selected. Included studies used multiple reviewers and/or explicit criteria to assess causality and preventability of hospital admissions. Two investigators abstracted data from all included studies using a purpose-made data extraction form. RESULTS: From 13 papers the median percentage of preventable drug-related admissions to hospital was 3.7% (range 1.4-15.4). From nine papers the majority (51%) of preventable drug-related admissions involved either antiplatelets (16%), diuretics (16%), nonsteroidal anti-inflammatory drugs (11%) or anticoagulants (8%). From five studies the median proportion of preventable drug-related admissions associated with prescribing problems was 30.6% (range 11.1-41.8), with adherence problems 33.3% (range 20.9-41.7) and with monitoring problems 22.2% (range 0-31.3). CONCLUSIONS: Four groups of drugs account for more than 50% of the drug groups associated with preventable drug-related hospital admissions. Concentrating interventions on these drug groups could reduce appreciably the number of preventable drug-related admissions to hospital from primary care.