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Sanaa M Kamal - One of the best experts on this subject based on the ideXlab platform.
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Acute Hepatitis c a systematic review
The American Journal of Gastroenterology, 2008Co-Authors: Sanaa M KamalAbstract: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
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peginterferon alfa 2b therapy in Acute Hepatitis c impact of onset of therapy on sustained virologic response
Gastroenterology, 2006Co-Authors: Sanaa M Kamal, Amr El Fouly, Refaat Kamel, Bridgette Hockenjos, Ahmed Al Tawil, Khalifa E Khalifa, Margaret James Koziel, Khairy El M NaggarAbstract: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.
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Duration of peginterferon therapy in Acute Hepatitis C: A randomized trial†
Hepatology (Baltimore Md.), 2006Co-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 RasenackAbstract: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.
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pegylated interferon α therapy in Acute Hepatitis c relation to Hepatitis c virus specific t cell response kinetics
Hepatology, 2004Co-Authors: Sanaa M Kamal, Ahmed Al Tawil, Khalifa E Khalifa, Jutta Fehr, Jens Rasenack, Alaa Ismail, Camilla S Graham, Thomas Peters, Mohamed A. MadwarAbstract: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.
Raymond T Chung - One of the best experts on this subject based on the ideXlab platform.
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early treatment improves outcomes in Acute Hepatitis c virus infection a meta analysis
Journal of Viral Hepatitis, 2010Co-Authors: Kathleen E Corey, J Mendeznavarro, Emmanuel C Gorospe, Hui Zheng, Raymond T ChungAbstract:Acute Hepatitis C virus infection is associated with high rates of spontaneous clearance and variable rates of treatment-induced clearance. The benefit of early treatment versus awaiting spontaneous clearance is unknown, as is the optimal timing of treatment.We performed a MEDLINE and EMBASE search for the time period 1950 to October 2008. All English language abstracts using the search terms Acute Hepatitis C, Hepatitis C and Acute and Hepatitis C and Acute disease or Acute infection were reviewed. Bibliographies were reviewed.Twenty-two studies including 1075 patients met the inclusion criteria. The sustained virologic response (SVR) rate for treated patients was 78%, significantly higher than 55.1% in untreated patients (OR = 3.08, 95% CI: 1.8-4.8 P value <0.0001). Mean time from diagnosis to spontaneous clearance was 9.7 weeks (SD 6.5). SVR rates varied inversely with time from Acute HCV diagnosis. SVR rates for treatment within 12 weeks was 82.5% (95% CI: 75.6-89.3), significantly better than the clearance rates in untreated patients (P < 0.001). Response rates fell to 66.9% for treatment between 12 and 24 weeks, and decreased further to 62.5% for treatment beyond 24 weeks. Rates of viral clearance in treated patients with Acute Hepatitis C virus infection were significantly higher than that in untreated patients. Treatment rates were highest when treatment was initiated within 12 weeks of diagnosis. Based on these findings, we would advocate a 12 week period of observation for spontaneous clearance before treatment initiation. If no clearance has occurred by 12 weeks, treatment should be initiated.
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early treatment improves outcomes in Acute Hepatitis c virus infection a meta analysis
Journal of Viral Hepatitis, 2010Co-Authors: Kathleen E Corey, J Mendeznavarro, Emmanuel C Gorospe, Hui Zheng, Raymond T ChungAbstract:Chronic Hepatitis C virus infection infects more than 170 million people worldwide and more than 4 million Americans.(1) The incidence of new Hepatitis C virus infections in the United States is estimated to be 100-200 cases per 100,000 people each year, with 28,000 new cases globally.(2) Unfortunately, 75-80% of patients who acquire Hepatitis C virus are asymptomatic, delaying diagnosis and preventing early treatment.(3) However, symptomatic patients who present with Acute Hepatitis C virus may have higher rates of spontaneous clearance, with some studies noting spontaneous clearance rates as high as 66%.(4-7) Treatment studies of patients with symptomatic Acute HCV have yielded varying rates of treatment-induced SVR from as low as 21% to as high as 98%.(8-10) Trials have been limited by small patient numbers, the lack of randomized controls, and variability in enrollment criteria, including the definition of Acute Hepatitis C virus infection and of sustained virologic response.(11, 12) Additionally, in several of these studies, early treatment (12-35 days after diagnosis) was initiated.(13, 14) Early initiation of treatment most likely includes a proportion of patients who would have spontaneously cleared HCV which may overestimate the treatment response. Recommendations for the timing of treatment initiation vary widely from 35 days after diagnosis to 120 days, with some studies suggesting that earlier treatment is associated with higher rates of SVR.(8, 14-18) With high rates of spontaneous clearance and varying rates of treatment-induced clearance in symptomatic patients with Acute Hepatitis C virus infection, it is unknown whether treatment in the Acute phase is clearly superior to watchful waiting. Furthermore, if treatment is chosen, the optimal timing of initial therapy remains unknown. Premature initiation of treatment in the Acute phase may subject patients who would otherwise spontaneously clear HCV to unnecessary and costly treatment. However, delay in treatment initiation may lower rates of treatment-induced clearance. This meta-analysis sought to more definitively establish the rate of spontaneous and treatment-induced clearance in patients with Acute Hepatitis C virus infection, and further sought to evaluate whether treatment outcomes vary based on the timing of treatment initiation.
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outcomes and treatment of Acute Hepatitis c virus infection in a united states population
Clinical Gastroenterology and Hepatology, 2006Co-Authors: Kathleen E Corey, Julian Schulze Zur Wiesch, Andrew Slavin Ross, Alysse G Wurcel, Arthur Y Kim, Georg M Lauer, Raymond T ChungAbstract: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.
Teresa Santantonio - One of the best experts on this subject based on the ideXlab platform.
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Acute Hepatitis C: current status and remaining challenges.
Journal of hepatology, 2008Co-Authors: Teresa Santantonio, Johannes Wiegand, J. Tilman GerlachAbstract: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.
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natural course of Acute Hepatitis c a long term prospective study
Digestive and Liver Disease, 2003Co-Authors: Teresa Santantonio, Emanuele Sinisi, A Guastadisegni, C Casalino, M Mazzola, A Gentile, Gioacchino Leandro, G PastoreAbstract: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.
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association of Hepatitis c virus specific cd8 t cells with viral clearance in Acute Hepatitis c
The Journal of Infectious Diseases, 2000Co-Authors: N Grune, Reinhart Zachoval, M C Jung, Teresa Santantonio, Tilma Gerlach, Helmu M Diepolde, Carl Albrech Schirre, W Schrau, Robe Hoffma, M CucchiariniAbstract:++ T cell response with the outcome of infection. Eighteen patients with Acute Hepatitis C and 19 normal donors were studied. Hepatitis C virus (HCV)‐specific CD8 + T cells were identified in the enzyme-linked immunospot assay by their interferon-g (IFN-g) production after specific stimulation. The highest numbers of IFN-g‐producing HCV-specific CD8 + T cells were found in patients with Acute Hepatitis C and a self-limited course of disease during the first 6 months after onset of disease, but these numbers dropped thereafter to undetectable levels. The differences in responsiveness between patients with self-limited disease versus patients with a chronic course were statistically significant ( ). Our data show that the number of IFN-g‐producing P ! .001 HCV-specific CD8 + T cells during the first 6 months after onset of disease is associated with eradication of the HCV infection. A better knowledge of the role of Hepatitis C virus (HCV)‐ specific CD8 1 T lymphocytes is of great importance for the understanding of the pathogenesis of HCV and the development of new therapeutic strategies for chronic HCV infection. In contrast to other viral infections, such as Hepatitis B, in which clearance of the virus during the Acute phase of disease has been shown to be associated with a strong polyclonal and multispecific cytotoxic T cell response [1, 2], the frequency and significance of HCV-specific CD8 1 T cells for viral clearance in Acute Hepatitis C (aHCV) is unknown. A comparison of the virus-specific CD8 1 T cell response in patients with Acute selflimited disease versus that in patients with chronic Hepatitis C infection may lead to a better understanding of the role of CD8 1
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possible mechanism involving t lymphocyte response to non structural protein 3 in viral clearance in Acute Hepatitis c virus infection
The Lancet, 1995Co-Authors: Helmut Diepolder, Eddy A Wierenga, Reinhart Zachoval, M C Jung, Teresa Santantonio, Robert Hoffmann, G R Pape, Dieter EichenlaubAbstract:In Acute Hepatitis C virus (HCV) infection only 20-50% of patients spontaneously clear the virus. To characterise the immune reaction during that phase we studied the response of peripheral blood mononuclear cells (PBMC) to the recombinant HCV proteins core, non-structural protein 3 (NS3), NS4, and NS5 in 14 patients with Acute Hepatitis C. All eight patients with self-limited disease compared with two of six with evolving chronic infection showed an NS3- specific PBMC response (p = 0.015). Of 65 patients with established chronic Hepatitis C, five showed a PBMC response to NS3. NS3-specific CD4 T-cell clones from patients with self-limited infection predominantly produced interferon-gamma and may thus support cytotoxic effector mechanisms important for viral clearance.
M C Jung - One of the best experts on this subject based on the ideXlab platform.
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Acute Hepatitis c high rate of both spontaneous and treatment induced viral clearance
Gastroenterology, 2003Co-Authors: Tilman J Gerlach, Helmut Diepolder, Reinhart Zachoval, Norbert H Gruener, M C Jung, Axel Ulsenheimer, W Schraut, Albrecht C Schirren, M Waechtler, Markus BackmundAbstract:Abstract Background & Aims: Acute Hepatitis C virus infection accounts for approximately 20% of cases of Acute Hepatitis today. The aim of this study was to define the natural course of the disease and to contribute to the development of treatment strategies for Acute Hepatitis C virus. Methods: The diagnosis of Acute Hepatitis C virus in 60 patients was based on seroconversion to anti-Hepatitis C virus antibodies or clinical and biochemical criteria and on the presence of Hepatitis C virus RNA in the first serum sample. Results: Fifty-one of 60 (85%) patients presented with symptomatic Acute Hepatitis C virus. In the natural (untreated) course of Acute symptomatic Hepatitis C (n = 46), spontaneous clearance was observed in 24 patients (52%), usually within 12 weeks after the onset of symptoms, whereas all asymptomatic patients (n = 9) developed chronic Hepatitis C. The start of antiviral therapy (interferon-α with or without ribavirin) beyond 3 months after the onset of Acute Hepatitis induced sustained viral clearance in 80% of treated patients. Conclusions: The management of Acute Hepatitis C has to take into account the high rate of spontaneous viral clearance within 12 weeks after the onset of symptomatic disease. Treatment of only those patients who remain Hepatitis C virus RNA positive for more than 3 months after the onset of disease led to an overall viral clearance (self-limited and treatment induced) in 91% of patients, and unnecessary treatment was avoided in those with spontaneous viral clearance. Patients with asymptomatic Acute Hepatitis C virus infection are unlikely to clear the infection spontaneously and should be treated as early as possible.
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association of Hepatitis c virus specific cd8 t cells with viral clearance in Acute Hepatitis c
The Journal of Infectious Diseases, 2000Co-Authors: N Grune, Reinhart Zachoval, M C Jung, Teresa Santantonio, Tilma Gerlach, Helmu M Diepolde, Carl Albrech Schirre, W Schrau, Robe Hoffma, M CucchiariniAbstract:++ T cell response with the outcome of infection. Eighteen patients with Acute Hepatitis C and 19 normal donors were studied. Hepatitis C virus (HCV)‐specific CD8 + T cells were identified in the enzyme-linked immunospot assay by their interferon-g (IFN-g) production after specific stimulation. The highest numbers of IFN-g‐producing HCV-specific CD8 + T cells were found in patients with Acute Hepatitis C and a self-limited course of disease during the first 6 months after onset of disease, but these numbers dropped thereafter to undetectable levels. The differences in responsiveness between patients with self-limited disease versus patients with a chronic course were statistically significant ( ). Our data show that the number of IFN-g‐producing P ! .001 HCV-specific CD8 + T cells during the first 6 months after onset of disease is associated with eradication of the HCV infection. A better knowledge of the role of Hepatitis C virus (HCV)‐ specific CD8 1 T lymphocytes is of great importance for the understanding of the pathogenesis of HCV and the development of new therapeutic strategies for chronic HCV infection. In contrast to other viral infections, such as Hepatitis B, in which clearance of the virus during the Acute phase of disease has been shown to be associated with a strong polyclonal and multispecific cytotoxic T cell response [1, 2], the frequency and significance of HCV-specific CD8 1 T cells for viral clearance in Acute Hepatitis C (aHCV) is unknown. A comparison of the virus-specific CD8 1 T cell response in patients with Acute selflimited disease versus that in patients with chronic Hepatitis C infection may lead to a better understanding of the role of CD8 1
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immunodominant cd4 t cell epitope within nonstructural protein 3 in Acute Hepatitis c virus infection
Journal of Virology, 1997Co-Authors: Helmut Diepolder, J T Gerlach, T Santantonio, Eddy A Wierenga, S. Scholz, Michael Houghton, Reinhart Zachoval, M C Jung, Reinhard Hoffmann, Scott SouthwoodAbstract:In Acute Hepatitis C virus infection, 50 to 70% of patients develop chronic disease. Considering the low rate of spontaneous viral clearance during chronic Hepatitis C infection, the first few months of interaction between the patient’s immune system and the viral population seem to be crucial in determining the outcome of infection. We previously reported the association between a strong and sustained CD4 1 T-cell response to nonstructural protein 3 (NS3) of the Hepatitis C virus and a self-limited course of Acute Hepatitis C infection. In this study, we identify an immunodominant CD4 1 T-cell epitope (amino acids 1248 to 1261) that was recognized by the majority (14 of 23) of NS3-specific CD4 1 T-cell clones from four of five patients with Acute Hepatitis C infection. This epitope can be presented to CD4 1 T cells by HLA-DR4, -DR11, -DR12, -DR13, and -DR16. HLA-binding studies revealed a high binding affinity for 10 of 13 common HLA-DR alleles. Two additional CD4 1 T-cell epitopes, amino acids 1388 to 1407 and amino acids 1450 to 1469, showed a very narrow pattern of binding to individual HLA-DR alleles. Our data suggest that the NS3-specific CD4 1 T-cell response in Acute Hepatitis C infection is dominated by a single, promiscuous peptide epitope which could become a promising candidate for the development of a CD4 1 T-cell vaccine. Hepatitis C virus (HCV) infection has an estimated worldwide prevalence of 0.3 to 1.5% and is a leading cause of chronic Hepatitis, cirrhosis, and hepatocellular carcinoma (1, 15). More than 50% of Acute infections lead to chronic disease (2), and once chronic infection is established, spontaneous recovery is exceptional. Therefore, characterization of the antiviral immune response during the first few weeks of Acute Hepatitis C infection in patients with self-limited disease as opposed to those developing chronic Hepatitis C may allow the identification of successful antiviral immune strategies. In two recent studies of patients with Acute Hepatitis C infection, a strong association between a vigorous and sustained HCVspecific CD4 1 T-cell response and a self-limited course of Acute Hepatitis C infection could be demonstrated (5, 16). Although the CD4 1 T-cell response was directed against several HCV antigens (core, E2, nonstructural protein 3 [NS3], NS4, and NS5), in the majority of patients with self-limited disease, the response to NS3 was frequently strongest and was detected most consistently. In this study, we identify one immunodominant CD4 1 T-cell epitope within the NS3 protein that is recognized by the majority of patients with self-limited Acute Hepatitis C infection and which binds promiscuously to the most common HLA-DR alleles.
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possible mechanism involving t lymphocyte response to non structural protein 3 in viral clearance in Acute Hepatitis c virus infection
The Lancet, 1995Co-Authors: Helmut Diepolder, Eddy A Wierenga, Reinhart Zachoval, M C Jung, Teresa Santantonio, Robert Hoffmann, G R Pape, Dieter EichenlaubAbstract:In Acute Hepatitis C virus (HCV) infection only 20-50% of patients spontaneously clear the virus. To characterise the immune reaction during that phase we studied the response of peripheral blood mononuclear cells (PBMC) to the recombinant HCV proteins core, non-structural protein 3 (NS3), NS4, and NS5 in 14 patients with Acute Hepatitis C. All eight patients with self-limited disease compared with two of six with evolving chronic infection showed an NS3- specific PBMC response (p = 0.015). Of 65 patients with established chronic Hepatitis C, five showed a PBMC response to NS3. NS3-specific CD4 T-cell clones from patients with self-limited infection predominantly produced interferon-gamma and may thus support cytotoxic effector mechanisms important for viral clearance.
Reinhart Zachoval - One of the best experts on this subject based on the ideXlab platform.
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Acute Hepatitis c high rate of both spontaneous and treatment induced viral clearance
Gastroenterology, 2003Co-Authors: Tilman J Gerlach, Helmut Diepolder, Reinhart Zachoval, Norbert H Gruener, M C Jung, Axel Ulsenheimer, W Schraut, Albrecht C Schirren, M Waechtler, Markus BackmundAbstract:Abstract Background & Aims: Acute Hepatitis C virus infection accounts for approximately 20% of cases of Acute Hepatitis today. The aim of this study was to define the natural course of the disease and to contribute to the development of treatment strategies for Acute Hepatitis C virus. Methods: The diagnosis of Acute Hepatitis C virus in 60 patients was based on seroconversion to anti-Hepatitis C virus antibodies or clinical and biochemical criteria and on the presence of Hepatitis C virus RNA in the first serum sample. Results: Fifty-one of 60 (85%) patients presented with symptomatic Acute Hepatitis C virus. In the natural (untreated) course of Acute symptomatic Hepatitis C (n = 46), spontaneous clearance was observed in 24 patients (52%), usually within 12 weeks after the onset of symptoms, whereas all asymptomatic patients (n = 9) developed chronic Hepatitis C. The start of antiviral therapy (interferon-α with or without ribavirin) beyond 3 months after the onset of Acute Hepatitis induced sustained viral clearance in 80% of treated patients. Conclusions: The management of Acute Hepatitis C has to take into account the high rate of spontaneous viral clearance within 12 weeks after the onset of symptomatic disease. Treatment of only those patients who remain Hepatitis C virus RNA positive for more than 3 months after the onset of disease led to an overall viral clearance (self-limited and treatment induced) in 91% of patients, and unnecessary treatment was avoided in those with spontaneous viral clearance. Patients with asymptomatic Acute Hepatitis C virus infection are unlikely to clear the infection spontaneously and should be treated as early as possible.
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association of Hepatitis c virus specific cd8 t cells with viral clearance in Acute Hepatitis c
The Journal of Infectious Diseases, 2000Co-Authors: N Grune, Reinhart Zachoval, M C Jung, Teresa Santantonio, Tilma Gerlach, Helmu M Diepolde, Carl Albrech Schirre, W Schrau, Robe Hoffma, M CucchiariniAbstract:++ T cell response with the outcome of infection. Eighteen patients with Acute Hepatitis C and 19 normal donors were studied. Hepatitis C virus (HCV)‐specific CD8 + T cells were identified in the enzyme-linked immunospot assay by their interferon-g (IFN-g) production after specific stimulation. The highest numbers of IFN-g‐producing HCV-specific CD8 + T cells were found in patients with Acute Hepatitis C and a self-limited course of disease during the first 6 months after onset of disease, but these numbers dropped thereafter to undetectable levels. The differences in responsiveness between patients with self-limited disease versus patients with a chronic course were statistically significant ( ). Our data show that the number of IFN-g‐producing P ! .001 HCV-specific CD8 + T cells during the first 6 months after onset of disease is associated with eradication of the HCV infection. A better knowledge of the role of Hepatitis C virus (HCV)‐ specific CD8 1 T lymphocytes is of great importance for the understanding of the pathogenesis of HCV and the development of new therapeutic strategies for chronic HCV infection. In contrast to other viral infections, such as Hepatitis B, in which clearance of the virus during the Acute phase of disease has been shown to be associated with a strong polyclonal and multispecific cytotoxic T cell response [1, 2], the frequency and significance of HCV-specific CD8 1 T cells for viral clearance in Acute Hepatitis C (aHCV) is unknown. A comparison of the virus-specific CD8 1 T cell response in patients with Acute selflimited disease versus that in patients with chronic Hepatitis C infection may lead to a better understanding of the role of CD8 1
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immunodominant cd4 t cell epitope within nonstructural protein 3 in Acute Hepatitis c virus infection
Journal of Virology, 1997Co-Authors: Helmut Diepolder, J T Gerlach, T Santantonio, Eddy A Wierenga, S. Scholz, Michael Houghton, Reinhart Zachoval, M C Jung, Reinhard Hoffmann, Scott SouthwoodAbstract:In Acute Hepatitis C virus infection, 50 to 70% of patients develop chronic disease. Considering the low rate of spontaneous viral clearance during chronic Hepatitis C infection, the first few months of interaction between the patient’s immune system and the viral population seem to be crucial in determining the outcome of infection. We previously reported the association between a strong and sustained CD4 1 T-cell response to nonstructural protein 3 (NS3) of the Hepatitis C virus and a self-limited course of Acute Hepatitis C infection. In this study, we identify an immunodominant CD4 1 T-cell epitope (amino acids 1248 to 1261) that was recognized by the majority (14 of 23) of NS3-specific CD4 1 T-cell clones from four of five patients with Acute Hepatitis C infection. This epitope can be presented to CD4 1 T cells by HLA-DR4, -DR11, -DR12, -DR13, and -DR16. HLA-binding studies revealed a high binding affinity for 10 of 13 common HLA-DR alleles. Two additional CD4 1 T-cell epitopes, amino acids 1388 to 1407 and amino acids 1450 to 1469, showed a very narrow pattern of binding to individual HLA-DR alleles. Our data suggest that the NS3-specific CD4 1 T-cell response in Acute Hepatitis C infection is dominated by a single, promiscuous peptide epitope which could become a promising candidate for the development of a CD4 1 T-cell vaccine. Hepatitis C virus (HCV) infection has an estimated worldwide prevalence of 0.3 to 1.5% and is a leading cause of chronic Hepatitis, cirrhosis, and hepatocellular carcinoma (1, 15). More than 50% of Acute infections lead to chronic disease (2), and once chronic infection is established, spontaneous recovery is exceptional. Therefore, characterization of the antiviral immune response during the first few weeks of Acute Hepatitis C infection in patients with self-limited disease as opposed to those developing chronic Hepatitis C may allow the identification of successful antiviral immune strategies. In two recent studies of patients with Acute Hepatitis C infection, a strong association between a vigorous and sustained HCVspecific CD4 1 T-cell response and a self-limited course of Acute Hepatitis C infection could be demonstrated (5, 16). Although the CD4 1 T-cell response was directed against several HCV antigens (core, E2, nonstructural protein 3 [NS3], NS4, and NS5), in the majority of patients with self-limited disease, the response to NS3 was frequently strongest and was detected most consistently. In this study, we identify one immunodominant CD4 1 T-cell epitope within the NS3 protein that is recognized by the majority of patients with self-limited Acute Hepatitis C infection and which binds promiscuously to the most common HLA-DR alleles.
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possible mechanism involving t lymphocyte response to non structural protein 3 in viral clearance in Acute Hepatitis c virus infection
The Lancet, 1995Co-Authors: Helmut Diepolder, Eddy A Wierenga, Reinhart Zachoval, M C Jung, Teresa Santantonio, Robert Hoffmann, G R Pape, Dieter EichenlaubAbstract:In Acute Hepatitis C virus (HCV) infection only 20-50% of patients spontaneously clear the virus. To characterise the immune reaction during that phase we studied the response of peripheral blood mononuclear cells (PBMC) to the recombinant HCV proteins core, non-structural protein 3 (NS3), NS4, and NS5 in 14 patients with Acute Hepatitis C. All eight patients with self-limited disease compared with two of six with evolving chronic infection showed an NS3- specific PBMC response (p = 0.015). Of 65 patients with established chronic Hepatitis C, five showed a PBMC response to NS3. NS3-specific CD4 T-cell clones from patients with self-limited infection predominantly produced interferon-gamma and may thus support cytotoxic effector mechanisms important for viral clearance.