The Experts below are selected from a list of 15510 Experts worldwide ranked by ideXlab platform

Teresa Santantonio - One of the best experts on this subject based on the ideXlab platform.

  • ACute Hepatitis C a 24 week Course of pegylated interferon alpha 2b versus a 12 week Course of pegylated interferon alpha 2b alone or with ribavirin
    Hepatology, 2014
    Co-Authors: Teresa Santantonio, P Fabris, M Fasano, Evangelista Sagnelli, Paolo Tundo, Sergio Babudieri, Mario Toti, Giovanni Di Perri, Nicoletta Marino, Eligio Pizzigallo
    Abstract:

    Therapy of ACute Hepatitis C (AHC) has not yet been standardized and several issues are still unresolved. This open, randomized, multiCenter trial aimed to assess the effiCaCy and safety of a 24-week Course of pegylated IFN (Peg-IFN) alpha-2b versus a 12-week Course of Peg-IFN alpha-2b alone or with ribavirin (RBV) in AHC patients. One hundred and thirty HCV ACutely infeCted patients who did not spontaneously resolve by week 12 after onset were ConseCutively enrolled and randomized to reCeive Peg-IFN alpha-2b monotherapy (1.5 μg/kg/week) for 24 or 12 weeks (arm 1, n = 44 and arm 2, n = 43, respeCtively) or in Combination with RBV (10.6 mg/kg/day) for 12 weeks (arm 3, n = 43). The primary endpoint was undeteCtable HCV RNA at 6-month posttreatment follow-up (sustained virologiCal response; SVR). All patients were followed for 48 weeks after therapy Cessation. HCV RNA levels were determined by real-time polymerase Chain reaCtion (limit of deteCtion: 15 IU/mL) at the Central laboratory at baseline, week 4, end of treatment, and 6 and 12 months posttreatment. Using an intent-to-treat analysis, overall SVR rate was 71.5%. In partiCular, an SVR was aChieved in 31 of 44 (70.5%), 31 of 43 (72.1%), and 31 of 43 (72.1%) patients in arms 1, 2, and 3, respeCtively (P = 0.898). Sixteen patients (12.3%) prematurely disContinued therapy or were lost to follow-up; thus, sustained response rates with per-protoCol analysis were 81.6%, 81.6%, and 81.6% for patients in arms 1, 2, and 3 respeCtively. With multivariate analysis, virologiC response at week 4 of treatment was an independent prediCtor of SVR. Peg-IFN alpha-2b was well tolerated. ConClusion: Peg-IFN alpha-2b induCes a high SVR in ChroniCally evolving AHC patients. Response rates were not influenCed by Combination therapy or treatment duration. (Hepatology 2014;59:2101-2109)

  • ACute Hepatitis C: Current status and remaining Challenges.
    Journal of hepatology, 2008
    Co-Authors: Teresa Santantonio, Johannes Wiegand, J. Tilman Gerlach
    Abstract:

    The ACute phase of Hepatitis C virus (HCV) infeCtion represents a key point in the evolution of Hepatitis C. In some patients, the infeCtion resolves spontaneously, whereas in others it develops into ChroniC disease. However, beCause ACute Hepatitis C is often asymptomatiC, deteCtion and diagnosis are usually diffiCult. What is more, there are no established treatment guidelines, leaving physiCians to make several Challenging deCisions, suCh as whether to treat, when to treat and what treatment regimen to use. Pegylated interferon alfa monotherapy is most Commonly used to treat patients with ACute Hepatitis C; the role of ribavirin has yet to be established. In this review, we disCuss the epidemiology of ACute Hepatitis C, its risk faCtors and routes of transmission and Current treatment praCtiCes. We also disCuss data from published CliniCal studies and foCus on unresolved issues for whiCh additional studies are needed in order to establish standardized treatment guidelines for the management of ACute Hepatitis C.

  • effiCaCy of a 24 week Course of peg interferon α 2b monotherapy in patients with ACute Hepatitis C after failure of spontaneous ClearanCe
    Journal of Hepatology, 2005
    Co-Authors: Teresa Santantonio, Emanuele Sinisi, A Guastadisegni, C Casalino, M Mazzola, M Fasano, Ruggiero Francavilla, Giuseppe Pastore
    Abstract:

    BaCkground/Aims Interferon (IFN) monotherapy signifiCantly reduCes the ChroniCity rate of ACute Hepatitis C (AHC) but optimal regimen and treatment timing remain undefined. The aim of this study was to assess the effiCaCy of a 6-month Course of pegylated IFN (PEG-IFN) α-2b monotherapy in AHC patients and to investigate if IFN treatment initiated after 12 weeks from CliniCal presentation, still aChieved a high response rate. Methods Sixteen AHC patients still viremiC after 12 weeks from the onset were treated with PEG-IFN α-2b (1.5mCg/kg onCe weekly) for 6 months and followed for at least 12 months. Response to therapy was defined as normal ALT values and undeteCtable HCV RNA ( Results At the end of treatment, HCV RNA was undeteCtable in 15/16 patients while ALT normalized in 14/16 patients. After 6 and 12 months follow-up, 15/16 patients (94%) showed virologiCal and bioChemiCal response. ConClusions A 6-month Course of PEG-IFN α-2b is effeCtive in induCing resolution of AHC in 94% of patients. Our results provide a rationale for delaying treatment for 12 weeks, targeting only patients who fail to Clear the virus spontaneously and truly requiring therapy without loss of effiCaCy.

  • natural Course of ACute Hepatitis C a long term prospeCtive study
    Digestive and Liver Disease, 2003
    Co-Authors: Teresa Santantonio, Emanuele Sinisi, A Guastadisegni, C Casalino, M Mazzola, A Gentile, Gioacchino Leandro, G Pastore
    Abstract:

    AbstraCt BaCkground. ACute Hepatitis C has a high ChroniCity rate whiCh appears to be signifiCantly reduCed by early antiviral treatment. However, it is unClear if all ACutely infeCted patients should be treated, and when. In this prospeCtive study, patients with a well-doCumented diagnosis of ACute Hepatitis C were evaluated to define the natural Course, the rate of ChroniCity, and host and virus-related faCtors whiCh might prediCt a self-limiting or ChroniC evolution requiring early antiviral treatment. Methods. From 1995 to 2000, 40 ConseCutive patients with a Community-aCquired AHC were enrolled. Liver tests, anti-Hepatitis C virus antibodies and Hepatitis C virus RNA levels were monitored. Median follow-up was 35 months (range 12–68). Results. A total of 24/40 patients had symptomatiC disease inCluding 20 with jaundiCe; 13/40 patients had prompt serum Hepatitis C virus RNA ClearanCe and ALT normalisation within 12 weeks; in 12/13 patients this pattern remained unChanged during follow-up. Overall, 27/40 patients remained Hepatitis C virus RNA positive with fluCtuating ALT levels. Older age and jaundiCe were prediCtive of resolution whereas there was no Correlation with other host faCtors, viral genotype or viral load. ConClusions. Our data demonstrate that spontaneous resolution Can oCCur in about 30% of AHC patients. This favourable outCome rarely oCCurs in patients with aniCteriC AHC or in those with jaundiCe but with persistent viremia for more than 12 weeks from onset; early antiviral treatment for these patients may avoid or reduCe ChroniCity.

  • treatment of ACute Hepatitis C with interferon alfa 2b
    The New England Journal of Medicine, 2001
    Co-Authors: Elmar Jaeckel, Markus Cornberg, Heiner Wedemeyer, Teresa Santantonio, Julika Mayer, M Zankel, Giuseppe Pastore, Manfred Dietrich, C Trautwein, Michael P Manns
    Abstract:

    BaCkground In people who are infeCted with the Hepatitis C virus (HCV), ChroniC infeCtion often develops and is diffiCult to eradiCate. We sought to determine whether treatment during the ACute phase Could prevent the development of ChroniC infeCtion. Methods Between 1998 and 2001, we identified 44 patients throughout Germany who had ACute Hepatitis C. Patients reCeived 5 million U of interferon alfa-2b subCutaneously daily for 4 weeks and then three times per week for another 20 weeks. Serum HCV RNA levels were measured before and during therapy and 24 weeks after the end of therapy. Results The mean age of the 44 patients was 36 years; 25 were women. Nine beCame infeCted with HCV through intravenous drug use, 14 through a needle-stiCk injury, 7 through mediCal proCedures, and 10 through sexual ContaCt; the mode of infeCtion Could not be determined in 4. The average time from infeCtion to the first signs or symptoms of Hepatitis was 54 days, and the average time from infeCtion until the start of therapy ...

Arthur Y Kim - One of the best experts on this subject based on the ideXlab platform.

  • sofosbuvir plus ribavirin without interferon for treatment of ACute Hepatitis C virus infeCtion in hiv 1 infeCted individuals swift C
    Clinical Infectious Diseases, 2017
    Co-Authors: Susanna Naggie, Arthur Y Kim, Daniel S Fierer, Kristen M Marks, Michael Hughes, Christine E Macbrayne, Kimberly Hollabaugh, Jhoanna Roa, Bill Symonds, Diana M Brainard
    Abstract:

    BaCkground HistoriCally, ACute Hepatitis C virus (HCV) infeCtion was treated with shorter durations of interferon-Containing therapies. In the era of direCt-aCting antivirals (DAAs), it is unClear whether the effiCaCy of treatment aChieved in ChroniC infeCtion Can be maintained with abbreviated Courses of therapy during the ACute phase. Methods The sofosbuvir-Containing regimens without interferon for treatment of ACute HCV in HIV-1 infeCted individuals (SWIFT-C) is an open-label, 2-Cohort CliniCal trial in whiCh the first Cohort assessed for the safety and effiCaCy of 12 weeks of sofosbuvir plus ribavirin for the treatment of ACute HCV infeCtion in partiCipants with ChroniC human immunodefiCienCy virus type 1 (HIV-1) infeCtion. This is a preplanned analysis of the first Cohort, whiCh had a planned aCCrual of 17 partiCipants. Results Seventeen men (11 HispaniC, 6 white, median age 45 years) were enrolled. Most (88%) had HCV genotype-1 infeCtion and few (24%) had the favorable IL28B CC genotype. Median baseline HCV RNA was 2 280 000 IU/mL (interquartile range, 272 000-4 230 000). Ten partiCipants (59%) aChieved the primary outCome of SVR12 (90% ConfidenCe interval, 36%-78%), failing to establish noninferiority. All treatment failures were due to viral relapse (41%). There were no premature treatment disContinuations. The only faCtor that differed between partiCipants who aChieved SVR vs those who relapsed was ribavirin ConCentration at the end of treatment. ConClusion Sofosbuvir-ribavirin for 12 weeks for the treatment of ACute HCV genotype-1 infeCtion in HIV-1-infeCted persons results in a high relapse rate. Preliminary studies of DAA Combination therapies suggest improved response rates, although the adequate duration of therapy remains unClear. CliniCal trials registration NCT02128217.

  • interferon lambda 4 genotype is assoCiated with jaundiCe and elevated aminotransferase levels during ACute Hepatitis C virus infeCtion findings from the inC3 Collaborative
    Open Forum Infectious Diseases, 2016
    Co-Authors: Kimberly Page, Andrea L Cox, Arthur Y Kim, Jason Grebely, Margaret Hellard, Ali Mirzazadeh, Thomas M Rice, Meghan D Morris, Julie Bruneau, Naglaa H Shoukry
    Abstract:

    SymptomatiC ACute HCV infeCtion and interferon lambda 4 (IFNL4) genotypes are important prediCtors of spontaneous viral ClearanCe. Using data from a multiCohort database (InjeCting Cohorts [InC3] Collaborative), we establish an independent assoCiation between host IFNL4 genotype and symptoms of ACute Hepatitis C virus infeCtion. This assoCiation potentially explains the higher spontaneous ClearanCe observed in some patients with symptomatiC disease.

  • patterns of Hepatitis C virus rna levels during ACute infeCtion the inC3 study
    PLOS ONE, 2015
    Co-Authors: Behzad Hajarizadeh, Andrea L Cox, Arthur Y Kim, Barbara H Mcgovern, Kimberly Page, Thomas M Rice, Julie Bruneau, Rachel Sacksdavis, Bart P X Grady, Meghan D Morris
    Abstract:

    BaCkground Understanding the patterns of HCV RNA levels during ACute Hepatitis C virus (HCV) infeCtion provides insights into immunopathogenesis and is important for vaCCine design. This study evaluated patterns of HCV RNA levels and assoCiated faCtors among individuals with ACute infeCtion.

  • a simple strategy to identify ACute Hepatitis C virus infeCtion among newly inCarCerated injeCtion drug users
    Hepatology, 2013
    Co-Authors: Arthur Y Kim, Georg M Lauer, Barbara H Mcgovern, Christopher E Birch, Melinda J Bowen, Ellen H Nagami
    Abstract:

    ACute Hepatitis C virus (HCV) infeCtion is underdiagnosed beCause most patients are asymptomatiC. The majority of new infeCtions oCCur among people who injeCt drugs (PWID), many of whom have a history of inCarCeration. In a previous pilot study, we identified symptomatiC HCV Cases, mainly among CauCasian inmates. We designed a Cross-seCtional study to evaluate whether risk faCtor-based sCreening of newly inCarCerated inmates would enhanCe identifiCation of asymptomatiC ACute HCV infeCtion and eluCidate any demographiC shifts in HCV aCquisition. From OCtober 2006-MarCh 2008, 6,342 inmates underwent health assessments and 3470 inmates (55%) were sCreened. The raCial distribution was as follows: AfriCan-AmeriCan 24.0%, CauCasian 49.5%, HispaniC 22.2%. One hundred seventy-one inmates (4.9%) were Classified as high-risk. After further evaluation, 35 (20.5%) were diagnosed with ACute HCV with a mean age of 29 years; 62.9% were female and 91% were CauCasian. No AfriCan-AmeriCans were diagnosed with ACute HCV. Our Case-finding rate was 1.9 patients/month nearly a three-fold inCrease Compared to our historiCal Control period with a higher proportion of asymptomatiC Cases. We estimate a prevalenCe of ~1.0% [95% CI 0.7%–1.4%] of ACute HCV infeCtions among newly inCarCerated inmates. ConClusions: Within the CorreCtional system, systematiC sCreening based on risk faCtors suCCessfully identifies ACute HCV infeCtion among PWID, inCluding asymptomatiC patients. Our data also refleCt Changing nationwide patterns of injeCtion drug use that vary by age, ethniCity, and raCe, leading to a marked reduCtion of ACute HCV infeCtions among AfriCan-AmeriCans as Compared to non-HispaniC whites. The nationwide implementation of this simple low-Cost strategy in prison-based settings Could identify more than 7,000 ACute HCV infeCtions among PWID and provide insight into Changing epidemiologiC trends and faCilitate appropriate therapeutiC and preventive interventions.

  • Cost effeCtive sCreening for ACute Hepatitis C virus infeCtion in hiv infeCted men who have sex with men
    Clinical Infectious Diseases, 2012
    Co-Authors: Arthur Y Kim, Benjamin P Linas, Angela Y Wong, Bruce R Schackman, Kenneth A Freedberg
    Abstract:

    SinCe 2000, outbreaks of ACute Hepatitis C virus (HCV) infeCtion among human immunodefiCienCy virus (HIV)–infeCted men who have sex with men (MSM) have been reported in Europe, the United States, and Australia [1–13]. HCV infeCtion in HIV-infeCted MSM is generally sexually transmitted and is assoCiated with substantial morbidity and mortality [14, 15]. BeCause therapy for ACute HCV infeCtion is more effeCtive than that for ChroniC HCV infeCtion, identifying and treating ACute HCV infeCtion represents an opportunity to improve outComes [16]. Guidelines for sCreening are emerging. In 2010, the European AIDS Treatment Network (NEAT) reCommended HCV antibody (HCV Ab) sCreening for all HIV-infeCted persons at enrollment in Care, followed by performanCe of liver funCtion tests (LFTs) every 6 months and HCV Ab sCreening every 12 months [17]. The US Centers for Disease Control and Prevention Sexually Transmitted Disease guidelines reCommend serial monitoring of LFTs and sCreening for HCV Ab or RNA in HIV-infeCted MSM with high-risk sexual behaviors [18]. UnCertainty remains ConCerning the most appropriate sCreening test for ACute HCV infeCtion, as well as the optimal interval for sCreening. A randomized trial Comparing sCreening strategies is not feasible, as it would require many Comparator arms and long follow-up to ensure adequate power to deteCt mortality differenCes [19]. When randomized trials are not possible, model-based analysis provides a method to integrate the Costs and benefits of healthCare strategies [20]. We ConstruCted a Monte Carlo simulation model to estimate the effeCtiveness and Cost-effeCtiveness of strategies for identifying ACute HCV infeCtion in HIV-infeCted MSM.

Sanaa M Kamal - One of the best experts on this subject based on the ideXlab platform.

  • ACute Hepatitis C a systematiC review
    The American Journal of Gastroenterology, 2008
    Co-Authors: Sanaa M Kamal
    Abstract:

    INTRODUCTIONThe annual inCidenCe of ACute Hepatitis C virus (HCV) has fallen in reCent years, primarily beCause of effeCtive blood sCreening efforts and inCreased eduCation on the dangers of needle sharing. However, Hepatitis C infeCtion is still relatively frequent in Certain populations. Most pati

  • peginterferon alfa 2b therapy in ACute Hepatitis C impaCt of onset of therapy on sustained virologiC response
    Gastroenterology, 2006
    Co-Authors: Sanaa M Kamal, Amr El Fouly, Refaat Kamel, Bridgette Hockenjos, Ahmed Al Tawil, Khalifa E Khalifa, Margaret James Koziel, Khairy El M Naggar
    Abstract:

    BaCkground & Aims: Pegylated interferon therapy has not been adequately evaluated in ACute Hepatitis C virus (HCV) infeCtion. This randomized trial assessed the effiCaCy, safety, and timing of pegylated interferon alfa-2b for treatment of ACute Hepatitis C. Methods: One hundred seventy-five patients ACutely infeCted with HCV were sCreened. Patients whose infeCtion did not spontaneously resolve by week 8 were randomized to onCe weekly peginterferon alfa-2b monotherapy (1.5 μg/kg per week) started at weeks 8, 12, or 20 for a duration of 12 weeks. The primary endpoint was undeteCtable HCV RNA 24 weeks after the end of treatment (sustained virologiC response [SVR]). All patients were followed for 48 weeks after Cessation of therapy. Results: One hundred twenty-nine subjeCts started treatment at week 8 (group A, n=43), week 12 (group B, n=43), or week 20 (group C, n=43). By using an intent-to-treat analysis, the overall SVR rate was 87%. The SVR rates were 95%, 92%, and 76% with treatment onset at 8, 12, and 20 weeks, respeCtively. Overall, SVR rates were better for patients infeCted with genotypes 2, 3, and 4 than those infeCted with genotype 1. Earlier initiation of therapy improved SVR rates for patients infeCted with genotype 1 with high viral load. Peginterferon alfa-2b was well tolerated. SubjeCts with SVR maintained undeteCtable HCV RNA 48 weeks after therapy. ConClusions: Peginterferon alfa-2b monotherapy in ACute Hepatitis C induCes high sustained virologiC response rates, prevents ChroniC evolution, and is well tolerated. Initiation of treatment at week 8 or 12 results in higher sustained virologiC rates than initiation at week 20.

  • Duration of peginterferon therapy in ACute Hepatitis C: A randomized trial†
    Hepatology (Baltimore Md.), 2006
    Co-Authors: Sanaa M Kamal, Khalifa E Khalifa, Khairy N. Moustafa, Jason E. Chen, Jutta Fehr, Azza Abd El Moneim, Leila A. El Gohary, Amr H. Ramy, Mohamed A. Madwar, Jens Rasenack
    Abstract:

    Spontaneous resolution of ACute Hepatitis C virus infeCtion Cannot be prediCted, and ChroniC evolution of the disease oCCurs in a majority of Cases. To assess the effiCaCy and safety of peginterferon alpha-2b administered for 8, 12, or 24 weeks in patients with ACute Hepatitis C virus infeCtion a total of 161 patients were identified with ACute Hepatitis C virus infeCtion. Of these, 30 patients refused treatment but were retained in the study as a nonrandomized Comparison group. Of the 131 patients who Consented to treatment, 29 patients spontaneously resolved, leaving 102 patients randomly assigned to peginterferon alpha-2b (1.5 miCrog/kg) for 8 weeks (group A; n=34), 12 weeks (group B; n=34), and 24 weeks (group C; n=34). The primary end point was sustained virologiC response. An intent-to-treat analysis was used for effiCaCy and safety end points. Sustained virologiC response was aChieved in 23/34 (67.6%), 28/34 (82.4%), and 31/34 (91.2%) of patients in groups A, B, and C, respeCtively; all had undeteCtable Hepatitis C virus RNA 48 weeks after the end of therapy. Treatment for 8 or 12 weeks was effeCtive in genotypes 2, 3, and 4, whereas genotype 1 required 24 weeks of therapy. The 8- and 12-week regimens were assoCiated with fewer adverse events Compared with the 24-week regimen. In ConClusion, peginterferon alpha-2b effeCtively induCes high sustained virologiC response rates in patients with ACute Hepatitis C virus infeCtion, thus preventing development of ChroniC Hepatitis C. Duration of treatment should be further optimized based on genotype and rapid virologiC response at week 4.

  • pegylated interferon α therapy in ACute Hepatitis C relation to Hepatitis C virus speCifiC t Cell response kinetiCs
    Hepatology, 2004
    Co-Authors: Sanaa M Kamal, Ahmed Al Tawil, Khalifa E Khalifa, Jutta Fehr, Alaa Ismail, Camilla S Graham, J Rasenack, Thomas Peters, Mahmoud M Madwar
    Abstract:

    Pegylated interferon alpha (PEG IFN-alpha) improves sustained virologiCal response rates in ChroniC Hepatitis C, but neither its role in ACute Hepatitis C nor the biologiC basis for its aCtion has been defined. This prospeCtive study assessed the effiCaCy of PEG IFN-alpha treatment in ACute Hepatitis C in relation to the kinetiCs of Hepatitis C virus (HCV)-speCifiC CD4(+) T Cell responses during therapy and follow-up. Forty subjeCts with proven ACute Hepatitis C who reCeived either PEG IFN-alpha plus ribavirin (n = 20) or PEG IFN-alpha monotherapy (n = 20) for 24 weeks in addition to 14 untreated subjeCts with ACute Hepatitis C were prospeCtively followed. Serum HCV RNA, HCV-speCifiC CD4(+) T Cell responses, and Cytokine produCtion were measured before and during therapy and at follow-up and Correlated to the outCome. The sustained virologiCal response rate was 85% with PEG IFN-alpha/ribavirin Combination and 80% with PEG IFN-alpha monotherapy. Five untreated subjeCts had spontaneous reCovery. The frequenCy, magnitude, and breadth of HCV-speCifiC CD4(+) T helper 1 responses were signifiCantly higher in treated subjeCts Compared with untreated subjeCts with self-limited disease or subjeCts with ChroniC evolution. The CD4(+) T Cell responses were maintained in subjeCts with sustained virologiCal responses and self-limited disease but fluCtuated in those who developed ChroniC infeCtion. In ConClusion, PEG IFN-alpha therapy in ACute Hepatitis induCes high rates of sustained virologiCal response and prevents ChoroniCity, probably through effiCient early stimulation of multispeCifiC HCV-speCifiC CD4(+) T helper 1 responses.

  • ACute Hepatitis C without and with sChistosomiasis Correlation with Hepatitis C speCifiC Cd4 t Cell and Cytokine response
    Gastroenterology, 2001
    Co-Authors: Sanaa M Kamal, Ahmed Al Tawil, Khalifa E Khalifa, J Rasenack, L Bianchi, Thomas Peter, Hoda Mansour, Wafaa M Ezzat, Margaret James Koziel
    Abstract:

    AbstraCt BaCkground & Aims: Immune responses during the first few months of ACute Hepatitis C virus (HCV) infeCtion seem CruCial for viral Control, but the relationship of these responses to natural history is poorly CharaCterized. Methods: This prospeCtive study investigated the HCV-speCifiC CD4 + and Cytokine responses in patients with ACute HCV Hepatitis with or without SChistosoma mansoni CoinfeCtion, a parasitiC infeCtion with T helper (Th) 2 immune bias. HCV-speCifiC CD4 + proliferative responses and Cytokine produCtion in peripheral blood mononuClear Cells were Correlated with liver biopsy results at 6 months and at the end of follow-up. Results: Whereas 5 of 15 patients with HCV alone reCovered from ACute HCV, all (17 of 17) patients with S. mansoni CoinfeCtion progressed to histologiCally proven ChroniC Hepatitis. CoinfeCted patients had either absent or transient weak HCV-speCifiC CD4 + responses with Th0/Th2 Cytokine produCtion. The magnitude of the HCV-speCifiC CD4 + response at week 12 was inversely Correlated with the fibrosis progression rate in ChroniCally infeCted patients. ConClusions: Patients with ACute Hepatitis C and sChistosomiasis CoinfeCtion Cannot Clear viremia and show rapid progression onCe ChroniC infeCtion is established. This rapid progression is assoCiated with a strong Th2 response in peripheral immune responses, suggesting that early development of vigorous Th1 responses not only faCilitates ClearanCe but delays disease progression. GASTROENTEROLOGY 2001;121:646-656

Christoph Boesecke - One of the best experts on this subject based on the ideXlab platform.

  • ledipasvir sofosbuvir for 6 weeks to treat ACute Hepatitis C virus genotype 1 or 4 infeCtion in patients with hiv CoinfeCtion an open label single arm trial
    The Lancet Gastroenterology & Hepatology, 2017
    Co-Authors: Jurgen K Rockstroh, Thomas A Lutz, Sanjay Bhagani, Diana M Brainard, Robert H Hyland, Chohee Yun, Hadas Dvorysobol, Wei Zheng, P Ingiliz, Christoph Boesecke
    Abstract:

    Summary BaCkground The latest European AssoCiation for the Study of the Liver (EASL) guidelines now reCommend that patients with ACute Hepatitis C virus (HCV) infeCtion should be treated with a Combination of sofosbuvir and an NS5A inhibitor for 8 weeks. However, the ideal duration of treatment with interferon-free regimens, partiCularly in HIV-CoinfeCted individuals, remains unknown. We assessed the effiCaCy and safety of 6 weeks of ledipasvir–sofosbuvir for ACute genotype 1 or 4 HCV in HIV-1-CoinfeCted patients. Methods This open-label, single-arm trial, done in Germany and the UK, inCluded patients with ACute HCV genotype 1 or 4 and HIV-1. At sCreening, patients were either reCeiving HIV antiretrovirals and had HIV RNA less than 200 Copies per mL, or not reCeiving antiretrovirals and had a CD4 T-Cell Count of greater than 500 Cells per μL. All patients reCeived ledipasvir–sofosbuvir onCe daily for 6 weeks. The primary effiCaCy endpoint was the proportion of patients with sustained virologiCal response 12 weeks after the end of treatment (SVR12). This study is registered with CliniCalTrials.gov, number NCT02457611. Findings Between June 11, 2015, and Jan 8, 2016, we enrolled and treated 26 patients. All (100%) were men, 24 (92%) were white, and 25 (96%) were reCeiving antiretroviral treatment. 19 (73%) had genotype 1a and seven (27%) had genotype 4 HCV. Overall, 20 (77%; 95% CI 56–91) of 26 patients aChieved SVR12: 15 (79%) of 19 with genotype 1a, and five (71%) of seven with genotype 4. Of six patients not aChieving SVR12, three relapsed, two aChieved sustained virologiCal response 4 weeks after the end of treatment but were lost to follow-up, and one was reinfeCted. The most Common adverse events were fatigue (seven partiCipants [27%]), nasopharyngitis (seven [27%]), and headaChe (six [23%]). No patient disContinued or interrupted therapy due to adverse events. No HIV rebound oCCurred during the study. Interpretation The rate of Cure with a fixed-dose Combination of ledipasvir–sofosbuvir for patients with ACute genotype 1 or 4 HCV infeCtion and HIV-1 CoinfeCtion is similar to historiC rates with interferon-based treatment, but with shorter treatment duration and more favourable safety outComes. Funding Gilead SCienCes.

  • Current knowledge and future perspeCtives on ACute Hepatitis C infeCtion
    Clinical Microbiology and Infection, 2015
    Co-Authors: Sebastiaan J Hullegie, Joop E Arends, Bart J A Rijnders, William L Irving, Dominique Salmon, Maria Prins, A M J Wensing, Paul Klenerman, Hakan Leblebicioglu, Christoph Boesecke
    Abstract:

    ACute Hepatitis C virus (HCV) infeCtions are frequently seen worldwide in Certain risk groups, with an annual inCidenCe rate varying between 0.08% and 66%. Although this inCidenCe is substantial, a delayed diagnosis during ChroniC infeCtion is most often made in the absenCe of CliniCal symptoms in the ACute phase of the infeCtion. Currently used methods to diagnose ACute HCV infeCtion are IgG antibody seroConversion and repeated HCV RNA measurements, although no definitive diagnostiC test is Currently available. Progress in the field of adaptive and innate immune responses has aided both advanCes in the field of HCV vaCCine development and a more basiC understanding of viral persistenCe. The rapid Changes in the treatment of ChroniC HCV infeCtion will affeCt therapeutiC regimens for ACute HCV infeCtion in the Coming years, leading to shorter treatment Courses and pegylated interferon-free modalities. This review gives an overview of the Current knowledge and unCertainties, together with some future perspeCtives on ACute Hepatitis C epidemiology, virology, immunology, and treatment.

  • liver fibrosis progression after ACute Hepatitis C virus infeCtion in hiv positive individuals
    Clinical Infectious Diseases, 2012
    Co-Authors: Martin Vogel, Christoph Boesecke, Emma Page, Thomas Reiberger, Carolynne Schwarzezander, S Mauss, A Baumgarten, Jc Wasmuth, M Nelson, Jurgen K Rockstroh
    Abstract:

    Fibrosis progression after ACute Hepatitis C virus (HCV) infeCtion in human immunodefiCienCy virus (HIV)-infeCted patients with follow-up >9 months beCame similar to reported rates from studies in ChroniC HIV/HCV CoinfeCtion, as measured with transient elastometry. The duration of follow-up and serum alanine transaminase Correlated with liver stiffness, and short follow-up resulted in high fibrosis progression rates.

  • ACute Hepatitis C in hiv infeCted individuals reCommendations from the european aids treatment network neat Consensus ConferenCe the european aids treatment network neat ACute Hepatitis C infeCtion Consensus panel
    AIDS, 2010
    Co-Authors: Matthieu Albert, K Deterding, Christoph Boesecke, Jose Miguel Benito, Sanjay Bhagani, Stephanie Dominguez, Martin Fisher, Arnaud Fontanet, Diego Garcia, Richard Gilson
    Abstract:

    There is inCreasing awareness of an ongoing epidemiC of ACute Hepatitis C virus (HCV) infeCtion in HIV-infeCted MSM. The epidemiology has been reviewed in this journal reCently [1]; however, there is a laCk of guidanCe on the management of ACute HCV infeCtion in HIV-infeCted individuals. To address this issue, the European AIDS Treatment Network (NEAT) invited members of the European AIDS CliniCal SoCiety (EACS) Hepatitis group, the European AssoCiation for the Study of the Liver (EASL), the European Study Group on Viral Hepatitis of the European SoCiety of CliniCal MiCrobiology and InfeCtious Diseases, the European AIDS Treatment group and other experts to draw up a Consensus statement at a ConferenCe held in Paris, FranCe, in May 2010. Four working groups prepared draft guidelines for Consideration at the ConferenCe on Case definition and diagnosis; transmission risk and epidemiology; pathogenesis and natural history; and ACute HCV infeCtion management in the HIV-infeCted population. A literature searCh using the PubMed database of the National Library of MediCine and abstraCt databases of the ConferenCe on Retroviruses and OpportunistiC InfeCtions, the IntersCienCe ConferenCe on AntimiCrobial Agents and Chemotherapy, the Liver Meetings of the AmeriCan AssoCiation for the Study of Liver Disease and EASL was utilized by all groups. Statements and reCommendations were graded by the strength of reCommendation and level of evidenCe (Table 1) [2]. A Consensus was reaChed if 80% or more of the partiCipants were in favour.

  • pegylated interferon alpha for the treatment of sexually transmitted ACute Hepatitis C in hiv infeCted individuals
    Antiviral Therapy, 2006
    Co-Authors: Martin Vogel, Christoph Boesecke, A Baumgarten, J Nattermann, Gerd Klausen, Bernhard Bieniek, Knud Schewe, Heiko Jessen, Michael Rausch, Thomas A Lutz
    Abstract:

    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.

Julian Schulze Zur Wiesch - One of the best experts on this subject based on the ideXlab platform.

  • ledipasvir plus sofosbuvir fixed dose Combination for 6 weeks in patients with ACute Hepatitis C virus genotype 1 monoinfeCtion hepnet ACute hCv iv an open label single arm phase 2 study
    Lancet Infectious Diseases, 2017
    Co-Authors: K Deterding, Christoph D Spinner, E Schott, Tania M Welzel, Guido Gerken, H Klinker, U Spengler, J Wiegand, Julian Schulze Zur Wiesch, A Pathil
    Abstract:

    Summary BaCkground Early treatment of ACute Hepatitis C virus (HCV) infeCtion with interferon alfa is highly effeCtive, but Can be assoCiated with frequent side-effeCts. We investigated the safety and effiCaCy of an interferon-free regimen for treatment of ACute HCV infeCtion. Methods In this prospeCtive, open-label, multiCentre, single-arm pilot study, we enrolled adults (≥18 years) with ACute HCV genotype 1 monoinfeCtion from ten Centres in Germany. Patients were given ledipasvir (90 mg) plus sofosbuvir (400 mg) as a fixed-dose Combination tablet onCe daily for 6 weeks. The primary effiCaCy outCome was the proportion of patients with sustained virologiCal response (defined as undeteCtable HCV RNA 12 weeks after the end of treatment; other primary outComes were safety and tolerability of ledipasvir plus sofosbuvir. The primary analysis population Consisted of all patients who reCeived at least one dose of study drug. Safety was also assessed in all patients who reCeived at least one dose of the study drug. This trial is registered with CliniCalTrials.gov, number NCT02309918. Findings Between Nov 19, 2014, and Nov 10, 2015, we enrolled 20 patients. Median HCV RNA viral load at baseline was 4·04 log 10 IU/mL (1·71–7·20); 11 patients were infeCted with HCV genotype 1a and nine patients with genotype 1b. All patients aChieved a sustained virologiCal response 12 weeks after the end of treatment (20 [100%] of 20 patients). Treatment was well tolerated; there were no drug-related serious adverse events. Up to 12 weeks after treatment, 22 possible or probable drug-related adverse events were reported. There was one serious adverse event, whiCh was judged unrelated to the study drug; one patient was admitted to hospital for surgery of a ruptured CruCiate ligament. Interpretation Treatment for 6 weeks with ledipasvir plus sofosbuvir was well tolerated and highly effeCtive in patients with ACute HCV genotype 1 monoinfeCtion. Short-duration treatment of ACute Hepatitis C might prevent the spread of HCV in high-risk populations. Funding Gilead SCienCes, HepNet Study-House/German Liver Foundation, and German Centre for InfeCtion ResearCh (DZIF).

  • broadly direCted virus speCifiC Cd4 t Cell responses are primed during ACute Hepatitis C infeCtion but rapidly disappear from human blood with viral persistenCe
    Journal of Experimental Medicine, 2012
    Co-Authors: Julian Schulze Zur Wiesch, Laura L Reyor, Donatella Ciuffreda, Lia Laura Lewisximenez, Victoria O Kasprowicz, Brian E Nolan, Hendrik Streeck, Jasneet Aneja, Todd M Allen
    Abstract:

    Vigorous proliferative CD4+ T Cell responses are the hallmark of spontaneous ClearanCe of ACute Hepatitis C virus (HCV) infeCtion, whereas Comparable responses are absent in ChroniCally evolving infeCtion. Here, we Comprehensively CharaCterized the breadth, speCifiCity, and quality of the HCV-speCifiC CD4+ T Cell response in 31 patients with ACute HCV infeCtion and varying CliniCal outComes. We analyzed in vitro T Cell expansion in the presenCe of interleukin-2, and ex vivo staining with HCV peptide-loaded MHC Class II tetramers. Surprisingly, broadly direCted HCV-speCifiC CD4+ T Cell responses were universally deteCtable at early stages of infeCtion, regardless of the CliniCal outCome. However, persistent viremia was assoCiated with early proliferative defeCts of the HCV-speCifiC CD4+ T Cells, followed by rapid deletion of the HCV-speCifiC response. Only early initiation of antiviral therapy was able to preserve CD4+ T Cell responses in ACute, ChroniCally evolving infeCtion. Our results Challenge the paradigm that HCV persistenCe is the result of a failure to prime HCV-speCifiC CD4+ T Cells. Instead, broadly direCted HCV-speCifiC CD4+ T Cell responses are usually generated, but rapid exhaustion and deletion of these Cells oCCurs in the majority of patients. The data further suggest a short window of opportunity to prevent the loss of CD4+ T Cell responses through antiviral therapy.

  • viral sequenCe evolution in ACute Hepatitis C virus infeCtion
    Journal of Virology, 2007
    Co-Authors: Thomas Kuntzen, Julian Schulze Zur Wiesch, Arthur Y Kim, J Timm, Lia Laura Lewisximenez, Brian E Nolan, Andrew Berical, Andrea M Jones, Arne Schneidewind, Raymond T Chung
    Abstract:

    CD8(+)-T-Cell responses play an important role in the Containment and ClearanCe of Hepatitis C virus (HCV) infeCtion, and an assoCiation between viral persistenCe and development of viral esCape mutations has been postulated. While esCape from CD8+ -T-Cell responses has been identified as a major driving forCe for the evolution of human immunodefiCienCy virus (HIV) and simian immunodefiCienCy virus (SIV), a broader CharaCterization of this relationship is needed in HCV infeCtion. To determine the extent, kinetiCs, and driving forCes of HCV sequenCe evolution, we sequenCed the entire HCV genome longitudinally in four subjeCts monitored for up to 30 months after ACute infeCtion. For two subjeCts the transmission sourCes were also available. Of 53 total non-envelope amino aCid substitutions deteCted, a majority represented forward mutations away from the Consensus sequenCe. In Contrast to studies in HIV and SIV, however, only 11% of these were assoCiated with deteCtable CD8+ T-Cell responses. Interestingly, 19% of non-envelope mutations represented Changes toward the Consensus sequenCe, suggesting reversion in the absenCe of immune pressure upon transmission. Notably, the rate of evolution of forward and reverse mutations Correlated with the Conservation of eaCh residue, whiCh is indiCative of struCtural Constraints influenCing the kinetiCs of viral evolution. Finally, the rate of sequenCe evolution was observed to deCline over the Course of infeCtion, possibly refleCtive of diminishing seleCtion pressure by dysfunCtional CD8+ T Cells. Taken together, these data provide insight into the extent to whiCh HCV is Capable of evading early CD8+ T-Cell responses and support the hypothesis that dysfunCtion of CD8+ T Cells may be assoCiated with failure to resolve HCV infeCtions.

  • outComes and treatment of ACute Hepatitis C virus infeCtion in a united states population
    Clinical Gastroenterology and Hepatology, 2006
    Co-Authors: Kathleen E Corey, Julian Schulze Zur Wiesch, Andrew Slavin Ross, Alysse G Wurcel, Arthur Y Kim, Georg M Lauer, Raymond T Chung
    Abstract:

    BaCkground & Aims: ACute Hepatitis C infeCtion progresses to ChroniC infeCtion in up to 80% of infeCted persons. Reports from Europe indiCate that early treatment of ACute Hepatitis C infeCtion produCes sustained virologiC response rates as high as 80%–98%. However, the outCome of ACute Hepatitis C infeCtion in United States Cohorts is not well-CharaCterized. Methods: We desCribe the CliniCal Course of 28 episodes of ACute Hepatitis C infeCtion in 24 persons at our institution. Results: Of the 28 infeCtions, 7 episodes resolved spontaneously. Of the remaining 21 episodes, 16 were treated, and 5 did not reCeive treatment. Of the 16 treated episodes, 4 reCeived interferon and ribavirin, 11 reCeived pegylated interferon and ribavirin, and 1 was treated initially with interferon monotherapy followed by pegylated interferon monotherapy. Among those episodes treated with interferon, 3 of 4 experienCed sustained virologiC response. Among those episodes treated with pegylated interferon, all 12 aChieved SVR. In total, 15 of 16 treated patients (94%) experienCed SVR. In all, 18 of the 24 patients (75%) experienCed spontaneous or treatment-induCed sustained virologiC ClearanCe. ConClusions: Our experienCe with treated and untreated ACute HCV infeCtion is Comparable to that observed in Europe. Patients treated with antiviral therapy had an exCellent response. Randomized trials to investigate immediate versus delayed treatment of ACute Hepatitis C infeCtion are warranted. In view of these strongly positive outComes, inCreased vigilanCe for ACute Hepatitis C beComes essential.

  • ACute Hepatitis C virus infeCtion in inCarCerated injeCtion drug users
    Clinical Infectious Diseases, 2006
    Co-Authors: Julian Schulze Zur Wiesch, Alysse G Wurcel, Arthur Y Kim, Barbara H Mcgovern, Ioana Bica, Tauheed M Zaman, J Timm
    Abstract:

    BaCkground. The Centers for Disease Control and Prevention has emphasized the need for interventional programs regarding Hepatitis C virus (HCV) infeCtion for injeCtion drug users, the group of persons who are at highest risk of aCquiring ACute infeCtion. Methods. We designed a pilot study to assess the feasibility of identifying injeCtion drug users with ACute HCV infeCtion in CorreCtional and detoxifiCation faCilities. On-site mediCal providers were eduCated regarding risk faCtors and signs and symptoms of infeCtion and were instruCted to refer all patients with Hepatitis to our speCialty CliniC. Results. Over a 30-month period, 21 patients reCeived a diagnosis of ACute Hepatitis C, 3 reCeived a diagnosis of Hepatitis B, and 1 reCeived a diagnosis of Hepatitis A. Of the 21 patients with ACute Hepatitis C, 19 were identified in the prison setting shortly after inCarCeration. Of the 17 patients who were observed serially (mean duration of observation, 6.3 months), 8 had spontaneous virologiC ClearanCe. Early therapy with pegylated interferon was initiated for 5 patients with persistent viremia and led to a sustained virologiC response in 2 individuals. All patients agreed to undergo human immunodefiCienCy virus Counseling and testing, as well as to reCeive immunization for Hepatitis A and B. ConClusions. InCarCeration presents a unique opportunity to identify injeCtion drug users with ACute HCV infeCtion, to initiate Counseling regarding other bloodborne pathogens, and to faCilitate immunizations and HCV treatment.