Key Learning Objectives
At the end of the session, the participants will be able to:
- identify those host factors that influence HCV progression
- consider the mechanisms whereby host factors can be modulated to beneficially alter the course of HCV
- apply the presence or absence of certain host factors to decisions regarding whether to initiate and/or maintain anti-viral therapy
- apply the presence or absence of certain host factors to counseling patients regarding their chronic HCV infections
- use host factors to provide insights regarding the pathogenesis of HCV progression.
The progression of any form of chronic viral hepatitis to cirrhosis is thought to depend on a combination of the virulence of the virus and so-called “host factors” that determine the threshold for hepatocyte injury and response to that injury. The viral levels of HCV in the liver do not correlate with histologic findings suggests that host factors may play a more important role in determining the rate of progression to cirrhosis. Host factors themselves can be divided into two broad categories; intrinsic and extrinsic. Of the former, the results of the largest clinical studies carried out to date suggest that age at the time of infection (beyond the age of 50 years), gender (males) and the immune competence of the host (immune-compromised) are the most important predictor variables of more rapid progression to cirrhosis. Of the extrinsic factors, alcohol has emerged as the most important and consistent determinant of progression to cirrhosis.
It should be noted, however, that the role, if any, of light or “social” alcohol consumption in HCV progression has yet to be determined. Although some data exist to implicate the presence or absence of other host factors (both intrinsic and extrinsic) such as HLA phenotypes, hemophilia, diabetes, hemochromatosis, smoking, environmental and geographic factors, for the most part, these data are limited or have been associated with conflicting reports. With the more established predictor variables in mind (age, gender, immune status and alcohol), it might be of therapeutic benefit to consider whether one specific component of the progressive process might serve as the target for non-antiviral therapy, particularly in individuals who fail to respond to antiviral agents.
For example, if older age, male gender, an immune-compromised state, and alcohol consumption all have a negative impact on the hepatic regenerative activity then theoretically, agents that enhance hepatic regeneration might be useful in preventing the progression of HCV infections to cirrhosis. On the other hand, if none of these factors have an adverse effect on hepatic regenerative activity then presumably, enhancing hepatic regeneration is unlikely to be of benefit in this condition. The same considerations would apply to the effects of host factors on hepatocyte necrosis and hepatic fibrinogenesis. These and other aspects of the host response to HCV will be discussed in detail.
Gerald Minuk, MD
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