Pegylated interferon α therapy in acute hepatitis C: Relation to hepatitis C virus-specific T cell response kinetics

Kamal, Sanaa M.; Ismail, Alaa; Graham, Camilla S.; He, Qi; Rasenack, J.; Peters, Thomas; Tawil, Ahmed Al; Fehr, Jutta; Khalifa, Khalifa E.; Madwar, Mahmoud M.; Koziel, Margaret James

doi:10.1002/hep.20266

Cited by 149 publications

(147 citation statements)

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“…Kamal et al demonstrated that the high rate of SVR in acute HCV is associated with strong T cell responses [214], although this has not been seen in every study [62]. A rapid drop in viral load on treatment is associated with more vigorous T cell responses, although whether this is cause or effect is not known [215].…”

Section: Role Of Immune Responses In Outcome Following Ifn and Ribavimentioning

confidence: 99%

Immune responses during acute and chronic infection with hepatitis C virus

Ishii

Koziel

2008

Clinical Immunology

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Hepatitis C virus (HCV) induces persistent infection and causes chronic liver disease in most infected patients. Vigorous HCV-specific CD4+ and CD8+ T cell responses against HCV multiple epitopes are necessary for spontaneous viral clearance during the acute phase, but the virus appears to have multiple strategies to evade these defenses. There are relatively few studies on the role of immune responses during the chronic phase of infection. CD4+ T cell responses appear to protect against liver injury and may be important to clearance during interferon and ribavirin based therapy. Classic cytotoxic T cells (CTL) may primarily damage the liver in chronic HCV, but there may be subpopulations of T cells that protect against liver inflammation. Resolution of these outstanding questions is important to the development of a prophylactic vaccine as well as improving therapeutic options for those with chronic infection.

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Section: Role Of Immune Responses In Outcome Following Ifn and Ribavimentioning

confidence: 99%

Immune responses during acute and chronic infection with hepatitis C virus

Ishii

Koziel

2008

Clinical Immunology

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“…For instance, a vigorous HCV-specific type 1 helper T cell CD4 ϩ response, particularly against nonstructural proteins, is associated with viral clearance 65 or a successful response to therapy. 76,[79][80][81][82] In fact, the lack of type 1 helper T effector cells within the first months of acute HCV is a predictor of viral persistence and could thus serve as a criterion for selecting candidates for early antiviral treatment. 65 The cause of dysfunctional CD4 ϩ T cells in chronic HCV infection is not clear.…”

Section: Role Of Cd4 T Cellsmentioning

confidence: 99%

“…Viral clearance was observed in 21 of 26 (81%) treated subjects, leading to SVR. Kamal et al 81 described 54 patients screened after either the first positive HCV RNA or the onset of symptoms. Laboratory studies were performed for 12 weeks, and then HCV RNA-positive subjects were offered interferon-based therapy [either pegylated interferon alpha 2a (180 g/ week) Ϯ RBV (800 mg/day) or pegylated interferon alpha 2b (1.5 g/kg/week) Ϯ weight-based RBV].…”

Section: Treatment Of Acute Hcv Infectionmentioning

confidence: 99%

Acute hepatitis C virus infection: A chronic problem

et al. 2008

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S ince the discovery of the hepatitis C virus (HCV) in the late 1980s, there has been an explosion of information regarding its natural history, treatment, and replication cycle. Nonetheless, there are still relatively few data regarding acute HCV infection. By convention, the term acute hepatitis refers to the presence of clinical signs or symptoms of hepatitis for a period of 6 months or fewer after the presumed time of HCV exposure. Early studies of posttransfusion patients who developed non-A, non-B hepatitis provide a clinical picture of early infection. 1 Following the availability of specific serologic and virologic tests, most such patients were shown to have acute HCV infection. After acute infection, HCV RNA may become detectable in the serum/plasma in as little as 2 weeks ( Fig. 1). Several weeks later, a high percentage of patients experience an increase in serum aminotransferase levels consistent with the development of acute hepatocellular injury. In the majority of cases, patients develop mild constitutional symptoms, including abdominal pain, nausea, vomiting, anorexia, and fatigue. During this acute infection, serum aminotransferases often peak below 1000 IU/mL and may return to normal levels. A minority develops sufficient elevations in bilirubin to lead to overt jaundice or the development of dark urine. Unless the clinical suspicion is high, few patients will be tested for HCV RNA or HCV antibody seroconversion. However, in the majority-but not all-of infected patients, HCV RNA persists, and a chronic disease state develops.The reasons for the general lack of data regarding acute HCV infection are multifactorial and include (1) the relatively high percentage of asymptomatic or unrecognized early infections, (2) the lack of large-scale identification of chronic carriers in the general population who serve as a reservoir for infection, and (3) the decreased number of acute infections that occur in controlled clinical settings such as that of blood transfusions. These factors and the lack of nonprimate animal models necessitate reliance on retrospective studies in chronic carriers, the use of limited historical collections of banked sera, and the extrapolation of outcomes based on small disease outbreaks in unique settings (for example, transmission from a physician to a patient in the operating room setting or following parenteral exposure in healthcare workers). Moreover, there exist only a limited number of population cohorts that continue to experience high rates of HCV transmission (for example, Egypt); nonetheless, there is a growing body of information regarding the clinical presentation, natural history, and treatment outcomes of acute HCV infection.In this article, we review the current information regarding our understanding of the epidemiology, virology, and immunology of HCV with a particular emphasis on acute HCV infection. In addition, we review recent data related to interferon-based treatment intervention and propose an algorithm for the diagnosis and management of acute HCV inf...

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“…The outcome of HCV treatment seems also to depend on the ability of host cellular immune responses to control viral replication. An early Th1 response is key for viral clearance during acute HCV infection (Guidotti & Chisari 2001, Kamal et al 2004, Rehermann & Nascimbeni 2005 and an enhanced HCV-specific T-cell response is also associated with treatment response in chronically infected patients (Nelson et al 1998, Cramp et al 2000, Kamal et al 2002. Therefore, it is reasonable to suppose that pretreatment levels of cytokines, especially those involved in the Th1 response, may predict treatment outcome.…”

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confidence: 99%