Dual treatment of acute HCV infection in HIV co-infection: influence of HCV genotype upon treatment outcome.

PURPOSE: With DAAs still only being licensed for chronic HCV infection, the ongoing epidemic of acute hepatitis C (AHC) infection among MSM highlights the need to identify factors allowing for optimal HCV treatment outcome. METHODS: 303 HIV-infected patients from 4 European countries with diagnosed acute HCV infection were treated early with pegylated interferon (pegIFN) and ribavirin (RBV) (n = 273) or pegylated interferon alone (n = 30). RESULTS: All patients were male, median age was 39 years. Main routes of transmission were MSM (95%) and IVDU (3%). 69% of patients were infected with HCV GT 1, 4.3% with GT 2, 10.6% with GT 3, 16.1% with GT 4. Overall SVR rate was 69.3% (210/303). RVR (p ≤ 0.001), 48-w treatment duration (p ≤ 0.001) and GT 2/3 (p = 0.024) were significantly associated with SVR. SVR rates were significantly higher in HCV GT 2/3 receiving pegIFN and RBV (33/35) when compared with pegIFN mono-therapy (6/10) (94% vs. 60 % respectively; p = 0.016). In multivariate analysis, pegIFN/RBV combination therapy (p = 0.017) and rapid virological response (RVR) (p = 0.022) were significantly associated with SVR in HCV GT 2/3. In HCV GT 1/4, RVR (p ≤ 0.001) and 48-w treatment duration (p ≤ 0.001) were significantly associated with SVR. CONCLUSIONS: Treatment of AHC GT 2 and 3 infections with pegIFN/RBV is associated with higher SVR rates suggesting different cure rates depending on HCV genotype similar to the genotype effects seen previously in chronic HCV under pegIFN/RBV. With pegIFN/RBV still being the gold standard of AHC treatment and in light of cost issues around DAAs and very limited licensed interferon-free DAA treatment options for chronic HCV GT 3 infection AHC GT 3 patients might benefit most from early interferon-containing treatment.

Identification and quantification of ethylene oxide in sterilized medical devices using multiple headspace GC/MS measurement.

This manuscript, based on the ISO 10993-7 approach, describes a multiple HS-GC measurement of residual EO present in sterilized plastic samples. The quantification of EO is done, according to the ISO standard, by addition of EO amounts extracted for each repeated extraction. During the method development, the specificity of the detection of EO regarding acetaldehyde (structural isomer of EO) which may be formed from EO has been ensured and different tests were performed to check a possible influence of the sample preparation. Assays to maximize EO extraction were performed for different materials (Cyclo-olefine Copolymer (COC), Cyclo-olefine Polymer (COP), Silicon, Polyurethane (PUR)) changing extraction temperatures and times for the headspace and the pre-thermal treatment. Results highlight that depending on the material, EO can be more or less retained and thus thermal extraction conditions to maximize the amount of extractible EO from plastics may change accordingly. For COC syringes a validation according to ICH guidelines and an inter-laboratories study were performed. The method has been used for a market survey of EO sterilized medical devices, results obtained are reported in this manuscript.

Antiviral therapy for hepatitis C virus recurrence after liver transplantation in HIV-infected patients: outcome in the Bonn cohort.

Recurrent hepatitis C is a major cause of mortality in HIV/hepatitis C virus (HCV)-co-infected patients after orthotopic liver transplantation. We report sustained viral clearance in all four transplanted HIV/HCV-positive patients treated with pegylated interferon/ribavirin. Early therapy after HCV recurrence, tailoring treatment duration to the individual decline in HCV-RNA and the management of side effects are key factors for improved efficacy. At experienced centres interferon treatment is a valuable option for recurrent hepatitis C in HIV-positive patients.

Pegylated interferon-alpha for the treatment of sexually transmitted acute hepatitis C in HIV-infected individuals.

BACKGROUND: Sexually transmitted acute hepatitis C among HIV-positive homosexual men has been noted as an emerging epidemic. METHODS: Forty-seven patients with mainly sexually acquired, acute hepatitis C were enrolled in this prospective, multicentre trial, and 36 of these patients were treated within the acute phase of hepatitis C infection with pegylated interferon (peg-IFN) therapy. RESULTS: Early treatment resulted in sustained virological response in 61% of patients. Peg-IFN alone showed similar treatment response rates and lower incidence of anaemia compared with peg-IFN+ribavirin combination therapy. Higher treatment response rates were observed in patients treated over 48 weeks compared with 24 weeks. CONCLUSIONS: Treatment of hepatitis C in HIV-positive individuals in the acute phase of infection leads to high rates of sustained virological response. Optimal time and mode of therapy have yet to be defined.

Development of multinuclear giant cells during the degradation of Bioglass particles in rabbits.

Bioglass particles of the compositions 45s5, 52s, and 55s were implanted in the distal femoral epiphysis of rabbits. Animals were sacrificed at 7, 28, and 84 days postoperatively and specimens investigated using electron microscopy and electron dispersive X-ray analysis. The intention was to correlate the finding of different types of multinuclear giant cells (MNGC) in the center of the implantation bed with earlier hypothesized accumulated particle eluates and changed particle compositions. The distribution of Si, Na, Ca, P, O, S, and Cl throughout the implantation bed was analyzed. Bioglass particles degraded either in Si-rich remnants or in CaP-shells. MNGC of foreign body giant cell type in high numbers as well as of osteoclast-like type at later time intervals in small numbers were found on the surface of Si-rich as well as on Ca- and P-rich particle remnants. Osteoclast-like cells were detected on the particles after transformation in CaP-shells. It is concluded that the formation of different types of MNGC is determined by the composition of the substrate, that is, osteoclast-like cells develop exclusively on resorbable substrates. The absolute number of MNGC depended on the time after implantation and the solubility of the implant. Bone bonding, however, only occurred on Ca- and P-rich surfaces.

HIV and hepatitis C co-infection: acute HCV therapy.

PURPOSE OF REVIEW: Almost 10 years ago clinicians started to note first cases of an outbreak of acute hepatitis C (AHC) infections among HIV-positive men who have sex with men (MSM) in Europe, soon followed by similar reports from the USA and Australia. To date, no randomized controlled treatment trials in AHC co-infection have been conducted. However, to give clinicians guidance in best clinical management of these patients expert consensus recommendations based upon published data from uncontrolled clinical and cohort studies have recently been published. RECENT FINDINGS: The early course of hepatitis C virus (HCV) RNA in the first 4 weeks after diagnosis is considered to be a helpful predictor of spontaneous clearance of AHC in HIV-infected individuals. Additionally, single-nucleotide polymorphisms near the IL28B gene further augment chances of spontaneous clearance. Pegylated interferon in combination with weight-adapted ribavirin is still recommended as treatment of choice for all HCV genotypes. For patients developing a rapid virological response (RVR), defined as a negative HCV-RNA in an ultrasensitive assay, treatment duration of 24 weeks is recommended. If antiviral therapy was initiated within 24 weeks after diagnosis high sustained virological response (SVR) rates of 60-80% have been observed. SUMMARY: Prevention and screening efforts along with early anti-HCV therapy have to be intensified to allow control of viral dissemination as the current epidemic of AHC particularly among MSM is still ongoing. Concise recommendations for best clinical management of AHC in HIV infection on the basis of published observational data have been published.

Treatment of acute HCV infection in HIV-positive patients: experience from a multicentre European cohort.

BACKGROUND: Early treatment of acute HCV infection has been shown to improve virological response rates in HIV-positive patients; however, details on when and how to best treat acute HCV infection remain unclear at present. METHODS: In this European multicentre cohort study, HIV-positive patients with acute HCV infection were offered immediate or delayed anti-HCV therapy, pegylated interferon or pegylated interferon plus ribavirin combination therapy for 24 or 48 weeks, depending on the local protocol. The main outcome measure was the rate of sustained virological response (SVR). RESULTS: A total of 150 HIV-infected men with acute HCV were enrolled between 2001 and 2006, 111 of whom received anti-HCV therapy. The predominant HCV genotype was type 1 and was present in 71 (64%) patients. Patients were treated with pegylated interferon (n=14) or pegylated interferon plus ribavirin (n=97), with a median duration of treatment of 25 weeks. SVR was obtained in 62% (95% confidence interval 52-71) of patients. There was no difference in SVR by genotype, CD4(+) T-cell count, HIV RNA, HCV RNA, alanine aminotransferase levels or use of ribavirin. Negative HCV RNA at weeks 4 and 12 were strong predictors of SVR. CONCLUSIONS: High rates of SVR (62%) were obtained in HIV-coinfected patients with acute HCV infection undergoing early anti-HCV treatment using pegylated interferon alone or in combination with ribavirin. Treatment response at weeks 4 and 12 might be of help to further guide treatment duration. Urgent prospective studies are needed to further determine the optimal treatment regimen and the duration of therapy.

Effect of the interleukin-6 C174G gene polymorphism on treatment of acute and chronic hepatitis C in human immunodeficiency virus coinfected patients.

UNLABELLED: Hepatitis C virus (HCV)/human immunodeficiency virus (HIV) coinfection poses a difficult therapeutic problem. Response to HCV-specific therapy is variable but might be influenced by host genetic factors, including polymorphisms of cytokine genes. Here, we studied whether interleukin-6 (IL-6) C174G gene polymorphism affects the response to antiviral treatment in HCV-infected HIV-positive subjects. We determined IL-6 genotypes in HIV-positive patients with acute (n = 52) and chronic (n = 60) hepatitis C treated with pegylated interferon-alpha. Two hundred ten HCV monoinfected, 197 HIV monoinfected, and 100 healthy individuals were studied as controls. Patients were classified into high and low producers according to IL-6 genotypes. Rates of sustained virological responses (SVRs) were compared between the IL-6 genotypes. Signal transducer and activator of transcription three phosphorylation was analyzed by Western blot in HCV core-transfected human hepatoma cell line (HUH7) cells. Distribution of IL-6 genotypes did not differ significantly between the study groups. SVR was achieved in 63% of HIV/HCV coinfected patients. Carriers of the IL-6 high producer (HP) genotype had significantly higher SVR rates than patients with an IL-6 low producer genotype (70.1% versus 52%; P < 0.002). This effect was seen in both HIV-positive patients with acute (74% versus 33%; P < 0.05) and chronic (66% versus 33%; P < 0.05) hepatitis C. Multivariate analysis confirmed IL-6 HP carriage as an independent positive predictor for SVR (Odd's ratio 6.1; P = 0.004). This effect corresponds to the in vitro observation that in HCV core-transfected HUH7 cells, IL-6 overcomes the HCV core-mediated inhibition of STAT3 activation. CONCLUSION: Response rates to HCV-specific treatment are higher in HCV/HIV-positive patients carrying the IL-6 HP genotype, which might be because of IL-6 mediated STAT3 activation.

Effects of humidity and filter material on diffusive sampling of isocyanates using reagent-coated filters.

Diffusive sampling of methyl isocyanate (MIC) on 4-nitro-7-piperazinobenzo-2-oxa-1,3-diazole (NBDPZ)-coated glass fibre (GF) filters is strongly affected by high relative humidity (RH) conditions. It is shown that the humidity interference is a physical phenomenon, based on displacement of reagent from the filter surface. In this paper, this drawback has been overcome by changing the filter material to the less polar polystyrene divinyl benzene (SDB). A series of experiments was performed to compare the analyte uptake on the two filter materials for different sampling periods and analyte concentrations at both low and high RH conditions. Additionally, the materials were investigated as well for passive sampling of ethyl (EIC) and phenyl isocyanate (PhIC) with NBDPZ and 1-(2-methoxyphenyl) piperazine (2-MP) as an alternative derivatising agent. Using 2-MP, the mean GF/SDB response ratios were determined to be 1.02 for MIC (RSD: 6.1%) and 1.03 for EIC (RSD: 6.8%), whereas PhIC could only be determined on SDB filters. Using NBDPZ as reagent, the negative influence of high humidity disappeared when SDB filters were used instead of GF filters. Even at low RH conditions, sampling with SDB material generally resulted in a higher analyte uptake than with GF filters. The GF/SDB response ratios were independent of sampling time or analyte concentration and were determined to be 0.70 (RSD: 4.7%) for MIC, 0.84 (RSD: 4.5%) for EIC and 0.95 (RSD 5.4%) for PhIC, meaning that the NBDPZ diffusive sampler based on SDB can be used at all humidity conditions without any restrictions.