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C Sarrazin

Publications and source records attributed to C Sarrazin.

At least 19 recordsLinked to original sources
PubMed2007

Induction of hepatitis C virus (HCV)-specific T cells by needle stick injury in the absence of HCV-viraemia.

BACKGROUND: The risk of hepatitis C virus (HCV) infection after occupational exposure is low with seroconversion rates between 0 and 5%. However, factors associated with natural resistance against HCV after needle stick injury are poorly defined. HCV-specific T-cell responses have been described in cross-sectional studies of exposed HCV-seronegative individuals. MATERIALS AND METHODS: In this study, we prospectively followed 10 healthcare professionals who experienced an injury with an HCV-contaminated needle. Blood samples were taken on the day or the day after the event and at different time points during follow-up for up to 32 months. HCV-specific T-cell responses were investigated directly ex vivo and in T-cell lines. RESULTS: None of the individuals became positive for HCV-RNA in serum tested with the highly sensitive transcription-mediated amplification (TMA)-assay or in peripheral blood mononuclear cells (PBMC). All of them remained anti-HCV negative throughout follow-up. At the time of injury, HCV-specific CD4+ T-cell responses were already detectable in two individuals and became detectable thereafter in three additional persons. Transient HCV-specific CD8+ T-cell responses developed in two HLA-A2 positive patients, which became negative until the most recent follow-up after 5 and 17 months, respectively. CONCLUSION: We demonstrate the development of HCV-specific T cells in HCV-exposed individuals after needle stick injury indicating subinfectious exposure to HCV. T-cell immunity against HCV may contribute to the low prevalence of HCV in medical healthcare professionals in Western countries.

Adult↗
PubMed2006

Multicenter performance evaluation of a new TaqMan PCR assay for monitoring human immunodeficiency virus RNA load.

A TaqMan real-time PCR assay, the COBAS TaqMan human immunodeficiency virus (HIV) (HPS-CTMHIV) PCR assay, recently developed for the quantification of HIV type 1 RNA in plasma, was evaluated in comparison with the licensed COBAS AMPLICOR HIV-1 MONITOR (CAHIM) assay. In this study, we have analyzed the tests' sensitivities, precisions, and linearities using multiple replicates of a standard panel of HIV RNA covering a 7-logarithm range of concentrations, as well as serial threefold dilutions of high-titer clinical samples. The subtype inclusivity was also investigated, using a panel of subtypes A to H, while a collection of 160 clinical samples was analyzed to assess the tests' specificities and the systems' similarities. The results of these experiments showed that the HPS-CTMHIV assay has a sensitivity of 53 copies/ml (95% hit rate), 100% specificity, and good intra- and interassay precision. The results of the HPS-CTMHIV assay were linear in the 50- to 10(7)-copies/ml range, with a correlation coefficient (R) for expected versus observed results of 0.98. Compared to the CAHIM assay, the HPS-CTMHIV assay showed a high correlation (R=0.99) across the dynamic range of RNA concentrations that, for the CAHIM assay, requires two different sample preparations. Equivalent performances were also observed for the two systems in the detection and quantification of HIV subtypes A to H. These data indicate that the HPS-CTMHIV assay may be one of the tests of choice for monitoring viral load throughout the course of HIV infection and during highly active antiretroviral therapy.

Analysis of Variance↗
PubMed2006

Review article: predicting response in hepatitis C virus therapy.

The introduction of combination therapy with ribavirin and of pegylated interferons has improved treatment results in patients with chronic hepatitis C. However, overall rates of sustained virologic response following antiviral therapy of chronic hepatitis C still do not exceed 54-63%. Because of several virus- and patient-related factors, treatment is even less successful in some patient subpopulations. The major viral factors associated with impaired response are hepatitis C virus genotype 1 infection and a high viral load. Among patient-related factors cirrhosis is of special importance. Baseline predictive factors for sustained virologic response become less important for prediction of treatment outcome when quantifications of hepatitis C virus RNA during early therapy are taken into account. This article provides a summary of virus- and patient-related parameters, which are prognostic for response to antiviral therapy in chronic hepatitis C and focuses on the prediction of treatment response by quantification of hepatitis C virus RNA concentration during therapy.

Antiviral Agents↗
PubMed2006

[Effectiveness of antiviral therapy in patients with chronic hepatitis C treated by private practice gastroenterologists].

The standard treatment for patients with chronic hepatitis C consists of pegylated interferon (PegIFN) alpha in combination with ribavirin. Information on treatment effectiveness outside clinical trials is sparse. To study community-based health care, a regional network supported by the German network of competence for hepatitis (Hep-Net) was created between gastroenterologists in private practice and a tertiary referral centre. A treatment register containing evidence-based guidelines was established and 212 consecutive patients who were treated with either PegIF Nalpha 2a/ribavirin (n = 126) or PegIFNalpha2b/ribavirin (n = 86) for 24 weeks (HCV genotype 2, 3) and 48 weeks (HCV genotype 1, 4, 5), respectively, were included and followed prospectively. Twenty-four weeks after cessation of antiviral treatment a sustained virological response was achieved in 54 % of the patients. By univariate analyses, infection with HCV genotypes 2 or 3 (p < 0.0001), younger age (p < 0.0001), normal gamma-glutamyltransferase levels before initiation of treatment (p = 0.003), and absence of language communication problems (p = 0.023) were associated with a sustained virological response. The presence of liver cirrhosis in patients with HCV genotype 1, 4, 5 infection was associated with lower sustained response rates (p = 0.025). Patients infected with HCV genotype 1 in whom the PegIFNalpha dose was reduced had higher virological relapse rates (p = 0.049). With regard to the treating physician, sustained virological response rates ranged from 26 - 67 % in patients infected with HCV genotype 1. Our study shows that virological response rates similar to those in international randomised clinical trials can be achieved by private practice gastroenterologists. The presented network allows characterization of the treatment outcome in chronic hepatitis C not only with regard to virus- and host-related factors but also on an individual physician basis.

Adult↗
PubMed2006

Impaired health-related quality of life in patients with chronic hepatitis C and persistently normal aminotransferase levels.

A significant impact of hepatitis C virus (HCV) infection on health-related quality of life (HRQOL) has been previously described. However, comprehensive data on the quality of life in patients with chronic hepatitis C and persistently normal aminotransferase levels (PNAL) are currently not available. One hundred fifteen patients with chronic hepatitis C (45 with persistently normal aminotransferases and 70 with elevated aminotransferases) and 50 healthy subjects were enrolled. Emotional and psychological states were assessed by Profile of Mood States (POMS) scale and HRQOL was assessed by the 'Everyday Life' questionnaire (EDLQ), a validated questionnaire related to the SF-36 Health Survey. An impairment in HRQOL was observed in patients with chronic hepatitis C showing PNAL compared with healthy subjects with significant differences for the factor scores depression and anger in the POMS scale as well as for the items body, relationship to partner, self-confidence and zest of life in the EDLQ. No differences in any questionnaire were observed between patients with chronic hepatitis C showing PNAL or elevated aminotransferase levels except of a worse mean level for factor score anger in POMS scale in patients with persistently normal aminotransferases. No association of quality of life with severity of liver disease was found. Impairment of HRQOL by chronic infection with HCV is similar in patients with PNAL and those with elevated aminotransferase levels.

Adult↗
PubMed2005

13C-methacetin breath test as liver function test in patients with chronic hepatitis C virus infection.

BACKGROUND: The 13C-methacetin breath test enables the quantitative evaluation of the cytochrome P450-dependent liver function. AIM: To find out whether this breath test is sensitive in noncirrhotic patients also with chronic hepatitis C in early stages of fibrosis. METHODS: Sixty-one healthy controls and 81 patients with chronic hepatitis C underwent a 13C-methacetin breath test. In all patients, a liver biopsy was performed. The liver histology was classified according to the histology activity index-Knodell score. RESULTS: Delta over baseline values of the patients at 15 min significantly differed from controls (19.2 +/- 9.2 per thousand vs. 24.1 +/- 5.7 per thousand; P < 0.003). The cumulative recovery after 30 min in patients was 11.4 +/- 4.8% and in healthy controls 13.8 +/- 2.8% (P < 0.002). However, patients with early fibrosis (histology activity index IVB) did not differ in delta over baseline values of the patients at 15 min (23.2 +/- 7.9 per thousand vs. 22.6 +/- 7.2 per thousand; P = 0.61) or cumulative recovery (13.6 +/- 3.7% vs. 13.2 +/- 3.8%; P = 0.45) from patients with more advanced fibrosis (histology activity index IVC). Patients with clinically nonsymptomatic cirrhosis (histology activity index IVD; Child A) metabolized 13C-methacetin to a significantly lesser extent (delta over baseline values of the patients at 15 min: 8.3 +/- 4.9 per thousand; P < 0.005 and cumulative recovery after 30 min: 5.6 +/- 3.2%; P < 0.003). The 13C-methacetin breath test identified cirrhotic patients with 95.0% sensitivity and 96.7% specificity. CONCLUSION: The non-invasive 13C-methacetin breath test reliably distinguishes between early cirrhotic (Child A) and noncirrhotic patients, but fails to detect early stages of fibrosis in patients with chronic hepatitis C.

Acetamides↗
PubMed2005

Apoptotic cytokeratin 18 neoepitopes in serum of patients with chronic hepatitis C.

In patients with chronic hepatitis C, alanine aminotransferase (ALT) levels do not accurately reflect the extent of liver inflammation. The discrepancy between ALT level and liver damage could be related to the mode of cell death. In the present study, we quantified serum levels of apoptotic cytokeratin 18 (CK-18) neoepitopes that are generated by activated caspases during apoptosis. Apoptotic CK-18 neoepitopes were quantified by enzyme linked immunosorbent assay in sera from patients with chronic hepatitis C and elevated ALT levels (n = 72), patients with chronic hepatitis C and persistently normal ALT levels (n = 27) and healthy controls (n = 19). Serum CK-18 neoepitope levels were strongly correlated with ALT (r = 0.659, P < 0.0001) and the histology activity index (r = 0.374, P < 0.001). Patients with chronic hepatitis C and persistently normal ALT levels had higher apoptotic CK-18 neoepitope levels than healthy controls (P = 0.03) but lower levels than patients with chronic hepatitis C and elevated ALT levels (P < 0.001). Highest serum CK-18 neoepitope levels were observed in patients with cirrhosis (P = 0.002). Hence apoptotic CK-18 neoepitopes in serum of patients with chronic hepatitis C are associated with ALT level and histological liver damage. Serum apoptotic CK-18 neoepitope levels are elevated both in patients with chronic hepatitis C and elevated ALT levels as well as in patients with normal ALT levels indicating that also patients with chronic hepatitis C and normal ALT have an increased hepatocyte loss by apoptosis.

Adult↗
PubMed2004

[Postexposure prevention after occupational exposure to HBV, HCV and HIV].

After occupational exposure to HBV, HCV, and HIV, the patient from whom the potentially infectious material originates (index patient) as well as the exposed person should undergo serological and, if needed, molecular screening. Active and passive immunoprophylaxis after exposure to HBV is an effective tool against infection with hepatitis B virus in unvaccinated persons. The post-exposure prophylaxis (PEP) should be given within 24 h after exposure of an unprotected person to HBV-positive material. Once acute hepatitis B infection is diagnosed, therapy is not recommended for immunocompetent persons. At present, PEP against HCV infection is not available. Monotherapy with interferon-alpha avoids chronification in most patients suffering from acute hepatitis C. After exposure with an increased risk for transmission of HIV (percutaneous needle stick injury, cut), PEP should be recommended and can also be offered for further indications. PEP should be started as early as possible and carried out for 28 days. The recommended PEP consists of two inhibitors of the reverse transcriptase and one inhibitor of the protease.

Drug Therapy, Combination↗
PubMed2004

[Postexposure prophylaxis after occupational exposure to HBV, HCV and HIV].

After occupational exposure to HBV, HCV, and HIV, the patient from whom the potentially infectious material originates (index patient) as well as the exposed person should undergo serological and, if needed, molecular screening. Active and passive immunoprophylaxis after exposure to HBV is an effective tool against infection with hepatitis B virus in unvaccinated persons. The post-exposure prophylaxis (PEP) should be given within 24 h after exposure of an unprotected person to HBV-positive material. Once acute hepatitis B infection is diagnosed, therapy is not recommended for immunocompetent persons. At present, PEP against HCV infection is not available. Monotherapy with interferon-alpha avoids chronification in most patients suffering from acute hepatitis C. After exposure with an increased risk for transmission of HIV (percutaneous needle stick injury, cut), PEP should be recommended and can also be offered for further indications. PEP should be started as early as possible and carried out for 28 days. The recommended PEP consists of two inhibitors of the reverse transcriptase and one inhibitor of the protease.

Acute Disease↗
PubMed2004

[Post-exposure prevention after occupational exposure to HBV, HCV and HIV].

After occupational exposure to HBV, HCV, and HIV, the patient from whom the potentially infectious material originates (index patient) as well as the exposed person should undergo serological and, if needed, molecular screening. Active and passive immunoprophylaxis after exposure to HBV is an effective tool against infection with hepatitis B virus in unvaccinated persons. The post-exposure prophylaxis (PEP) should be given within 24 h after exposure of an unprotected person to HBV-positive material. Once acute hepatitis B infection is diagnosed, therapy is not recommended for immunocompetent persons. At present, PEP against HCV infection is not available. Monotherapy with interferon-alpha avoids chronification in most patients suffering from acute hepatitis C. After exposure with an increased risk for transmission of HIV (percutaneous needle stick injury, cut), PEP should be recommended and can also be offered for further indications. PEP should be started as early as possible and carried out for 28 days. The recommended PEP consists of two inhibitors of the reverse transcriptase and one inhibitor of the protease.

HIV Infections↗
PubMed2004

[Hepatitis C-virus --virus kinetics and resistance mechanisms].

Typically, a biphasic decay of viremia can be observed during the first few weeks of interferon-based treatment in patients with chronic hepatitis C. The mathematical and statistical analysis of viral kinetics enables the estimation of individual kinetic parameters. Especially, the infected cell loss, the degradation rate of free virus, and an efficiency factor on blocking viral production can be estimated. Furthermore, mathematical models of viral kinetics have the potential to reveal mechanisms of antiviral therapy. The lower sustained virologic response rates in several patient populations are reflected by impaired kinetic parameters. Besides host-specific and treatment-related differences, especially hepatitis C virus genotype strongly correlates with initial and long-term virologic responses. Reasons for virologic response or non-response to interferon-based therapy for individual patients are unknown. Beside host- and treatment-related causes it is assumed that HCV is able to specifically evade the antiviral actions of interferon. So far, three HCV proteins [envelope (E)2, non-structural (NS) protein 3/4A, and NS5A protein] have been associated with interferon resistance mechanisms. However, within the E2 (HVR2, CD81 binding domains, PePHD) and NS3/4A proteins no specific mutations in correlation with virologic response to interferon-based antiviral therapy were observed. For the NS5A protein, mutations within the interferon sensitivity determining region (ISDR) and the complete NS5A protein may be of importance for virologic treatment response in patients infected with genotype HCV-1a/b isolates.

Animals↗
PubMed2004

Mutations in the putative HCV-E2 CD81 binding regions and correlation with cell surface CD81 expression.

The hepatitis C virus (HCV) envelope (E)2 protein interacts with the cellular receptor CD81 leading to modulation of B and T cell function. Recently, a higher binding affinity of subtype 1a in comparison with 1b derived E2 proteins for CD81 in vitro was described. The importance of mutations within the putative CD81 binding regions of different HCV geno-/subtypes in correlation with CD81 expression is unknown. In the present study, CD81 expression on blood lymphocytes of patients with chronic hepatitis C infected with different HCV geno-/subtypes were analysed by fluorescence activated cell sorter analyses. In addition, the putative CD81 binding regions on the E2 gene comprising the hypervariable region (HVR)2 were analysed by direct sequencing. CD81 expression on CD8(+) T-lymphocytes from patients infected with subtype 1a (n = 6) was significantly higher in comparison with subtype 1b (n = 12) and 3 (n = 5) infected patients before and during antiviral therapy (P = 0.006; P = 0.021, respectively). Sequencing of the putative CD81 binding regions in the E2 protein comprising the HVR2 (codon 474-495 and 522-552 according to the HCV-1a prototype HCV-H) showed a highly conserved motif within HVR2 for subtype 1a isolates and an overall low number of mutations within the putative CD81 binding regions, whereas numerous mutations were detected for subtype 1b isolates (12.0 vs 23.6%). HCV-3 isolates showed an intermediate number of mutations within the putative binding sites (19.2%; P = 0.022). In conclusion, the highly conserved sequence within HVR2 and putative CD81 binding sites of subtype 1a isolates previously associated with a high CD81 binding affinity in vitro is correlated with high CD81 expression on CD8(+) T-lymphocytes in vivo.

Adult↗
PubMed2003

[44-year-old patient with fulminant liver failure].

The 44-year old female patient was admitted with acute hepatic failure and extensive haemolysis under the preliminary diagnosis of Wilson's disease. General characteristic criteria of Wilson's disease as Kayser-Fleischer ring, low serum copper and low ceruloplasmin levels were not observed. The preliminary diagnosis of acute Wilson's disease was established on the basis of the characteristic laboratory values with an AP/bilirubin ratio <2, an AST/ALT ratio >4, accompanying hemolysis and a highly elevated cupruresis. The definitive diagnosis of Wilson's disease was verified after orthotopic liver transplantation by quantitative copper evaluation in the explanted liver. The case represents the yet oldest patient reported with an acute manifestation of Wilson's disease.

Adult↗
PubMed2003

Dynamics of hepatitis C virus quasispecies turnover during interferon-alpha treatment.

Interferon-alpha (IFN) has been shown to accelerate the evolution of hepatitis C virus (HCV) variants (quasispecies) in nonresponder patients. Different sensitivities of HCV variants to IFN are discussed as a possible mechanism. In the present study, quasispecies were investigated in detail by a newly established and validated direct solid-phase sequencing of the hypervariable region 1 (HVR1), during the initial 3 months of IFN therapy. According to single strand conformation polymorphism (SSCP) analysis, 14 of 26 (54%) virologic nonresponders with quasispecies evolution were identified. Six representative patients with SSCP changes were selected for frequent HVR1 sequencing. Pre-existing variants were identified by cloning and sequencing of the pretreatment serum HCV sample. In one patient the major type was substituted by a minor variant within 3 days of treatment while in the majority of patients the pretreatment major type did not decline before days 26-57 of treatment. Total serum HCV RNA levels remained constant in all patients. In conclusion, although quasispecies evolution during IFN therapy is common, it occurs after a wide range of time intervals after initiation of therapy. Thus, nonresponse to IFN cannot exclusively be explained by changes in the quasispecies.

Adult↗
PubMed2003

Response predictors and results of a long-term treatment with lamivudine in patients with chronic hepatitis B.

INTRODUCTION: European data on outcome and follow-up of long-term lamivudine treatment are sparse. Moreover, little is known about predictors for sustained virologic response and for development of drug resistance in patients with lamivudine monotherapy. Patients and methods : 39 patients (17 HBeAg+, 22 HBeAg-) were treated with lamivudine for a median duration of 2.5 years (range: 0.5-4). Outcome to therapy and predictors for response and drug resistance were analyzed retrospectively. RESULTS: None of the patients lost HBsAg. In 14 of 17 initially HBeAg positive patients the HBeAg status was available at the end of treatment. Loss of HBeAg was observed in 8 patients and 7 of these 8 patients seroconverted to anti-HBe. Five of 6 patients with HBeAg seroconversion and a post-treatment follow-up period showed sustained HBeAg seroconversion. In HBeAg negative patients virologic response (serum HBV DNA< or =1 x 10(5) copies/ml) was observed in 12 of 22 patients after a median treatment period of 2.5 years. Post-treatment follow-up data were available in only 2 patients, one of which remained below 1 x 10(5) HBV DNA copies/ml for one year. Resistance emerged in 15 of 36 patients with available serum HBV DNA data after a median treatment period of 2 years. CONCLUSION: The present retrospective study confirms international data for lamivudine treatment in a central European setting. Lamivudine therapy achieved disease control in more than 50 % of patients treated for chronic hepatitis B. Baseline predictors could neither be identified for sustained virologic response nor for the development of drug resistance.

Adolescent↗
PubMed2002

Role of ultrasonography in the detection of small adrenal masses.

AIM: Computed tomography (CT) scanning is commonly used for evaluation of adrenal masses in adults. In this prospective study we evaluated whether adrenal gland masses of less or equal than 20 mm in diameter could be detected by modern abdominal ultrasonography (US). METHOD: Between July 1999 and June 2000, 44 consecutive patients with 50 adrenal masses documented by contrast-enhanced CT (left adrenal gland, n = 31; right adrenal gland, n = 19; bilateral, n = 6; median size, 15 [5 +/- 80] mm) and, additionally, 50 patients without CT findings of an adrenal mass were prospectively evaluated by high-resolution US performed by physicians. Based upon CT measurement, 34 adrenal masses were </= 20 mm and 16 were > 20 mm in diameter. RESULTS: The overall sensitivity of US for the detection of adrenal masses was 96 % (48/50) (94 % [29/31] for left and 100 % [19/19] for right adrenal masses, respectively). The overall specificity of US for the detection of adrenal masses was 92 % (92/100) (90 % [45/50] for left and 94 % [47/50] for right adrenal masses, respectively). Thus, the diagnostic accuracy of US for the detection of adrenal masses is 93 % (140/150). Sensitivity and specificity of US for the detection of adrenal masses </= 20 mm (n = 34) did not differ significantly from those > 20 mm (n = 16). CONCLUSION: US is effective for detecting small adrenal masses. In rare cases small masses of the left adrenal gland might be missed and nodular adrenal hyperplasia or retroperitoneal lymph nodes might be misinterpreted as adrenal masses.

Adrenal Gland Neoplasms↗
PubMed2001

Quasispecies heterogeneity of the carboxy-terminal part of the E2 gene including the PePHD and sensitivity of hepatitis C virus 1b isolates to antiviral therapy.

Two regions within the HCV genome, hypervariable region 1 (HVR1) within the envelope (E)2 region and the PKR-binding domain (PKRbD) comprising the interferon sensitivity determining region (ISDR) within the nonstructural (NS)5A protein, have been reported to correlate with the outcome of antiviral treatment. Recently, a PKR/eIF2alpha phosphorylation homology domain (PePHD) within the E2 protein of HCV-1 isolates was described to inhibit PKR in vitro. PePHD deleted HCV-1 mutants remain capable of binding PKR to some extent while inhibition of PKR was found to be abolished by carboxy-terminal truncated E2 protein. The importance of mutations and quasispecies heterogeneity within the carboxy-terminal part of the E2 protein comprising the PePHD of HCV-1b is unknown. Therefore, the carboxy-terminal part of the HCV E2 gene (codons 618-746) including the PePHD was analyzed by sequencing of PCR products and individual clones of 41 HCV-1b-infected patients with sustained (SR, n = 12), end-of-treatment (ETR, n = 10), or no virological (NR, n = 19) response to antiviral therapy. Two highly conserved regions (codons 658-673 comprising the PePHD and codons 675-704) and one variable region (codons 705-720) were detected within the carboxy-terminal part of E2. No significant correlation of specific mutations or number of mutations with treatment response was observed for the PePHD and the carboxy-terminal part of the E2 protein. Phylogenetic and conformational analyses showed no specific clusters related to treatment outcome. Calculation of genetic complexity and diversity based on nucleotide sequence analyses of 20 individual clones per patient showed no differences between matched SR, ETR, and NR patients. However, calculation of genetic complexity and diversity on the basis of amino acid sequences showed significantly lower normalized Shannon entropy as well as mean Hamming distances for SR patients than in ETR and NR patients (P = 0.029 and P = 0.027, respectively). This indicates that patients achieving a sustained virological response to interferon-alpha-based antiviral therapy may elicit more effective immunological pressure, resulting in continuous clearing of individual variants of HCV quasispecies.

Adult↗