Sofosbuvir plus simeprevir for the treatment of HCV genotype 4 patients with advanced fibrosis or compensated cirrhosis is highly efficacious in real life.

Chronic hepatitis C virus (HCV) infection is a major cause of chronic liver disease and liver-related death. Recently, multiple regimens of different direct-acting antiviral agents (DAAs) have been registered. Although treatment with sofosbuvir (SOF) and simeprevir (SMV) is registered for the treatment of genotype 4 patients in some countries, data on efficacy of this combination are lacking. We aimed to assess the efficacy of SOF and SMV with or without RBV during 12 weeks in a real-life cohort of genotype 4 HCV patients. A retrospective multicentre observational study was conducted in 4 hospitals in Amsterdam, the Netherlands, including patients with advanced liver fibrosis or liver cirrhosis treated with SOF plus SMV with or without RBV during 12 weeks for a genotype 4 chronic HCV infection from 1 January 2015 to 1 August 2015. Sustained viral response (SVR) was established at week 12 after end of treatment. A total of 53 patients with genotype 4 HCV infection, treatment naïve and experienced, were included. SVR was achieved in 49 of 53 patients (92%). The four failures all had a virological relapse and did not receive ribavirin. Three were nonresponder to earlier interferon-based treatment, and one was treatment naive. In this real-life cohort of patients with HCV genotype 4 infection and advanced liver fibrosis/cirrhosis, we show that treatment with SOF and SMV is effective. The addition of RBV could be considered in treatment-experienced patients as recommended in guidelines.

Tuberculids: cutaneous indicator diseases of Mycobacterium tuberculosis infection in young patients.

BACKGROUND: In the past years the incidence of tuberculosis has dropped significantly in most parts of Europe and the presentation of symptomatic tuberculosis cases have become increasingly rare. With the recent influx of refugees in Europe coming from tuberculosis endemic areas like the Middle East and Africa, it is expected that the incidence of tuberculosis will increase. OBJECTIVES: Cutaneous symptoms are important hallmarks that can be of aid for the correct diagnosis of an underlying disease, like tuberculosis. METHODS: We describe 2 young patients with tuberculids, respectively lichen scrofulosorum and papulonecrotic tuberculids, caused by a systemic Mycobacterium tuberculosis infection. RESULTS: Tuberculids are cutaneous immunological reactions triggered by a Mycobacterium tuberculosis infection elsewhere in the body. The three main manifestations of cutaneous tuberculids are: lichen scrofulosorum, papulonecrotic tuberculids and erythema induratum of Bazin. Whereas the latter is more common, the first two presentations are rare. CONCLUSION: It is of importance that clinicians, including dermatologists, are aware of the spectrum of clinical presentations of tuberculosis to halt this destructive and highly contagious disease early in its course.

The impact of laboratory closing times on delay of adequate therapy in blood stream infections.

BACKGROUND: Patients with bloodstream infections need early adequate antimicrobial treatment to reduce mortality. This raises the question of timing and logistics. How important is the time of day when a culture is flagged positive to the processing of blood cultures and optimisation of antimicrobial therapy? METHODS: We performed a retrospective study assessing the time delay of a positive blood culture result during and after office hours and its impact on adequate antimicrobial therapy. Process duration from the moment of culture positivity to Gram stain completion was compared at different timepoints during the day in a medium-sized hospital with an offsite microbiological laboratory. RESULTS: Ninety-four patients with positive, noncontaminated blood cultures were included. Sixty-six patients (70%) received adequate empirical therapy; this increased to 76 cases (82%) and to 88 cases (95%) after analysis of Gram stain results and complete determination, respectively (p < 0.05 for all comparisons). Median duration from culture positivity to Gram stain completion (including offsite culture transport) increased from a median of four to 12 hours if time of cultures turned positive after office hours (p < 0.05), irrespective of the adequacy of empirical coverage. This also resulted in a median 12-hour delay for the complete process from time of culture positivity to administration of the antimicrobial drug (p < 0.05). CONCLUSION: Processing blood cultures after office hours is often deferred, which can lead to a delay in adequate antimicrobial therapy for patients with bloodstream infections.

Acute hepatitis C in the Netherlands: characteristics of the epidemic in 2014.

Within the Dutch Acute HCV in HIV Study, a surveillance system was initiated to estimate the incidence of hepatitis C virus (HCV) infections in 2014. Following the Dutch HIV treatment guidelines, HIV-positive men having sex with men (MSM) in 19 participating centers were screened. Ninety-nine acute HCV infections were reported, which resulted in a mean incidence of 11 per 1000 patient-years of follow-up. Unfortunately, the HCV epidemic among Dutch HIV-positive MSM is not coming to a halt.

Abnormal radiological findings and a decreased carbon monoxide transfer factor can persist long after the acute phase of Legionella pneumophila pneumonia.

Pulmonary abnormalities may persist long after the acute phase of legionnaires disease (LD). In a cohort of 122 survivors of an outbreak of LD, 57% were still experiencing an increased number of symptoms associated with dyspnea at a mean of 16 months after recovery from acute-phase LD. For 86 of these patients, additional evaluation involving high-resolution computed tomography (HRCT) of the lung revealed pulmonary abnormalities in 21 (24%); abnormal HRCT findings generally presented as discrete and multiple radiodensities. Residual pulmonary abnormalities were associated with a mean reduction of 20% in the gas transport capacity of the lung. This latter sign could not be used to explain the increased symptoms of dyspnea reported by patients. Receipt of mechanical ventilation during the acute phase of LD, delayed initiation of adequate antibiotic therapy, and chronic obstructive pulmonary disease were identified as risk factors for the persistence of lung abnormalities.

Early effects of high doses of retinol (vitamin A) on the in situ cellular metabolism in rat liver.

Understanding of the possible toxicity associated with hypervitaminosis A becomes increasingly important in view of the popularity of vitamin A supplementation. Hypervitaminosis A for many years may eventually lead to hepatocellular damage. In the present study, rats were treated for 7 days with high doses of retinol to study the early effects on the metabolism of different types of liver cells using (enzyme) histochemistry, immunohistochemistry and electron microscopy. Excessive intake of vitamin A activates Kupffer cells and induces accumulation of lipid droplets in fat-storing cells as well as proliferation of these cells. Moreover, it affects the metabolic heterogeneity in the liver lobules, but does not lead to apparent cell damage. Based on the changes in marker enzymes for different metabolic processes, it is concluded that the capacity for breakdown of purines, the antioxidant capacity, the potential for phagocytosis and the regulation of ammonia levels were largely decreased. Increased alkaline phosphatase activity in hepatocytes pointed to an activated process of transport of retinol esters over the bile canalicular membrane. The possible causes of these metabolic changes have been described in the discussion.

Reduced interferon-gamma release in patients recovered from Legionnaires' disease.

BACKGROUND: Legionella pneumophila, a Gram negative intracellular pathogen, causes Legionnaires' disease (LD). Interferon (IFN)-gamma is important for host defence against L pneumophila so reduced IFN-gamma production capacity and/or responsiveness might render humans more susceptible to infection with L pneumophila. METHODS: Seventy seven patients who suffered from LD after a point source outbreak one year earlier participated in the study. Whole blood was incubated with non-specific stimuli (lipopolysaccharide (LPS) or interleukin (IL)-12) or specific stimuli (viable or heat killed L pneumophila) to evaluate IFN-gamma production, and with IFN-gamma to evaluate IFN-gamma responsiveness. Expression of complement receptor 3 on monocytes was determined by flow cytometry. Thirty seven companions who were also exposed but had not developed LD served as controls. RESULTS: Patients released less IFN-gamma than controls in response to stimulation with LPS (mean (SE) 393 (58) pg/ml v 914 (178) pg/ml; p=0.001) and IL-12 (96 (14) pg/ml v 177 (41) pg/ml; p=0.058). IFN-gamma responsiveness, measured by release of IFN-gamma inducible protein (IP)-10, tumour necrosis factor alpha, IL-12 production capacity, and monocyte expression of complement receptor 3, did not differ between patients and controls. IFN-gamma release after stimulation with LPS and IP-10 release after stimulation with IFN-gamma were weakly associated with severity of LD in the former patient group (rho=-0.3, p=0.011 and rho=-0.3, p=0.037, respectively). CONCLUSION: These results suggest that impaired IFN-gamma production may contribute to susceptibility to L pneumophila infection.