Is HCV Viral Load a Predictor of Progression of Chronic Hepatitis C?  

Following are excerpts from an editorial by Heller and Seeff of the NIH that accompanies the study findings by Hisada et al published in the December 2005 issue of Hepatology :

“So, what accounts for the findings by the present authors [Hisada et al] of a strong association between HCV RNA levels and ESLD, given that the weight of evidence seems to contradict this relationship? Indeed, if their findings are valid it would suggest, as the authors note, that lowering viral load with antiviral treatment may decrease advancement to ESLD, even if virus cannot be eliminated.”

“Possible explanations for these discrepancies are that either the conclusions of previous studies or those of the present study are erroneous, or that both are correct and the variation is accounted for by diverse study populations. Alternatively, disagreement among the differing studies might stem from utilization of serological assays of differing sensitivities or from faulty data interpretation.”

“All subjects in the present study were injection drug users; some were immunocompromised by co-infection with HIV and HTLV II and others possibly by factors peculiar to this population, such as additional infections, co-morbidities, or nutritional deficits. In contrast, most previous studies involved patients with a lesser likelihood of immune compromise.”

“Conceivably, the higher HCV RNA levels might result from the induced immune deficiency, which itself accounts for the liver disease progression. Indeed, as is widely accepted and even referred to by the authors, HCV is not considered a cytopathic agent, further supporting the likelihood that it is the immune compromise rather than the viral load that is responsible for inducing progression of chronic liver disease.

“Additional evidence for this view is that other HCV-infected groups who are immunosuppressed, such as those co-infected with HIV, those who have received kidney or liver transplants, or those with agammaglobulinemia, display a high HCV viral load and a high likelihood of progressing to ESLD. Thus, the immune dysregulation itself could account for both the raised viral load and the liver disease progression. The issue thus becomes the difference between cause and effect….”

“Another issue to consider is the report by the authors that HIV was not associated with ESLD when adjusted for HCV viral level in multivariate analyses, and that death from AIDS was not associated with HCV RNA. This must be viewed in the context of the time of the study, which occurred prior to the introduction of highly active antiretroviral therapy (HAART). At that time, most deaths resulted from the HIV infection, an outcome that has changed with the advent of HAART; currently, most deaths are due to ESLD. Since progression to cirrhosis generally requires the passage of 20 to 30 years, and the present study began approximately 8 years ago, it is feasible that many study participants already had severe underlying chronic liver disease at study initiation. This raises the issue of lead-time bias.”

“Nevertheless, the findings of these authors cannot be dismissed and are clearly of importance regarding the question of therapy. However, it seems premature to recommend therapy with the implied aim of reducing viral load in order to prevent or reduce ESLD until further studies are undertaken using a prospective approach with serial viral level measurements and probably repeat liver biopsies….Relevant studies are in progress.”

[Note: emphasis in bold added by editor—RB]

12/13/05

Reference
T Heller and L B Seeff. Viral load as a predictor of progression of chronic hepatitis C? (editorial) Hepatology 42(6): 1261-1263. December 2005.

http://www.hivandhepatitis.com/hep_c/news/2005/ad/121305_c.html