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Are you one of the few that respond to treatment for hepatitis C? (07/2003)

In some patients resistance to treatment for hepatitis C can be detected as early as the first three days of treatment, according to a team of scientists in a recent article published in Hepatology1.  This knowledge should help clinicians predict the effectiveness of individual treatments and consequently decide who should go through such a regimen.

Jennifer Layden-Almer, leading the clinical study at the Department of Medicine, University of Illinois, Chicago and Ruy Ribeiro (Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, USA), responsible for the mathematical modeling, show that in African-Americans, a group usually associated with poor response to treatment, resistance results from an impaired response to the drug of choice, IFN-alpha. The other group studied, Caucasians, do not suffer from this inability and consequently exhibit a better disease outcome after being treated.

Using a mathematical model to study the disease viral kinetics, Ribeiro, a Portuguese investigator, shows that the impaired response to IFN-alpha, seen in African-Americans, results from deficient viral inhibition, induced by the drug during the first twenty-four hours of treatment.

The scientists also show that this inability to respond to IFN-alpha during the first day of treatment relates directly with the success of the treatment by the end of the one-year drug protocol. In fact, patients who, in the first twenty-four hours, were incapable of clearing at least 90% of total virus load were unable to combat hepatitis

The team of scientists write: “Results indicate that IFN-alpha-based treatment in African Americans has significantly lower effectiveness in blocking viral production than in Caucasians. This impaired effectiveness blunts the ability of treatment to drive the virus to undetectable levels early in treatment…no patient cleared virus regardless of race at week 48 without an effectiveness of >90%…”  

Hepatitis C is a major reason for liver transplants throughout the world. However, the disease can present a wide range of symptoms and severities in different individuals, from mild, barely noticeable alterations to extreme cases where liver collapse occurs and transplants are necessary.

The treatment of hepatitis C with exogenous IFN-alpha (a natural protein produced by the body and that, among other functions, fights viral infections) is associated with a very low percentage of recovery, never higher than 60%. This is a major problem because, not only is IFN-alpha extremely expensive, but also, and more importantly, it can induce very unpleasant side effects.

Because not all patients have acute disease that demands immediate treatment, it is of extreme importance to be able to predict which patient will have the best chance of responding to treatment before deciding whether to put them through the unpleasant and long (one year) treatment course. The work of Layden-Almer and Ribeiro, although done in a very specific and small population, the African-Americans, can help with this aspect of patient care.

Their work also try to understand the exact mechanism why patients may or may not respond to hepatitis C treatment. Mathematical models of biological systems, in this case studying the viral kinetics during IFN-alpha therapy, provide new knowledge of the disease and can help optimize treatments.

Layden-Almer’ and Ribeiro’s results for example, seem to indicate that increasing the dosage of IFN-alpha will make no difference in overcoming the inability to fight hepatitis in African-Americans. Based on their results the alternative for this group of patients will have to be a new drug

 hep c response

1 Hepatology (2003) Jun; 37(6): 1343-50.

Authors’ contact

Dr. Ruy Ribeiro – ruy.ribeiro@zoology.ox.ac.uk

In collaboration with the Observatório da Ciência e do Ensino Superior (OCES)
Financed by the Fundação para a Ciência e Tecnologia (FCT)