Download Article PDF/SlidesThis is also true during the acute stage of infection. While symptoms such as fatigue, lethargy, myalgia, low-grade fever, nausea and vomiting do occur in patients with acute HCV infection, they are virtually indistinguishable from more common and benign viral infections and, as a result, usually go unchecked. Even one of HCV's hallmark features-jaundice-develops in fewer than half of all individuals during acute infection, even though HCV-RNA and liver enzyme levels are usually at their highest.
The clinical silence of HCV during the earliest weeks of infection is frustrating, as there is now reason to believe that the identification, diagnosis, and treatment of acute HCV may be associated with truly remarkable results. Without more telltale signs of infection-especially when a patient's risk of infection is not entirely known or appreciated by his or her clinician-it is likely that few patients will benefit from what has come to be recognized as a breakthrough in the treatment of hepatitis C: the use of interferon to reduce the likelihood of acute HCV infection progressing into a life-long and life-threatening disease.
| Treatment of Acute HCV Infection: The Rationale | Top of page |
In murine models of lymphocytic choriomeningitis virus (LCMV) infection—a non-cytopathic RNA virus associated with high levels of replication, much like HCV—early control of viral load allows for the host immune response to clear the virus and effectively prevent the development of chronic infection: virus-specific CD4+ and CD8+ cells remain, whereas the virus does not (Moskophidis, 1993; Oxenius, 1998). Conversely, mice maintaining high concentrations of LCMV generally experience depletion in their virus-specific CD4+ and CD8+ cell responses, leading to chronic infection in the vast majority of cases. “If viral replication is not controlled,” Dr. Jaeckel added, “the initial immune response simply becomes overwhelmed and virus-specific CD4+ cell responses are either deleted or are rendered anergic.”
Even more relevant, perhaps, is the recent experience with treating acute HIV infection. As has been reviewed in several past issues of The PRN Notebook—most recently in a special edition of the Notebook focusing specifically on the diagnosis and treatment of primary HIV infection, published in February 2002—data coming out of studies conducted at Massachusetts General Hospital and other groups indicate that early treatment may be associated with the long-term control of HIV replication (Rosenberg, 2000). These groups have shown that, if antiretroviral therapy is initiated during the acute stage of HIV infection, virus-specific CD4+ cell responses are permitted to proliferate and to continue orchestrating the much-needed activity of cytotoxic T-lymphocytes. “Using antiretroviral therapy appropriately during acute HIV infection appears to be the key in maintaining these necessary responses,” Dr. Jaeckel said. “We don’t see the same proliferation of virus-specific immune responses in patients treated with antiretroviral therapy during the chronic stage of infection.
With respect to the treatment of acute HCV infection, there have actually been a number of studies conducted over the past ten years evaluating the safety and effectiveness of early intervention strategies. During his lecture, Dr. Jaeckel made reference to 14 clinical trials that have evaluated interferon therapy during acute HCV infection, the majority of which demonstrated a benefit associated with the treatment. Only one study, conducted at the Amedeo di Savoia Hospital in Torino, Italy, failed to show a statistically significant difference in the incidence of chronic HCV infection among acutely infected patients receiving interferon or placebo (Calleri, 1998). Among the studies that did associate interferon with a beneficial effect, Dr. Jaeckel suggested that they were either too small, too brief in duration, or did not use HCV-RNA levels as an endpoint. Some studies also used interferon-beta—including the failed Torino study—a compound that has been shown to be less effective in the treatment of hepatitis C than interferon-alpha.
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