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CROI 2008: Boston, Massachussetts; February 3-6, 2008

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The Body Covers: The 15th Conference on Retroviruses and Opportunistic Infections
Antiretroviral Exposure May Increase Liver Fibrosis Risk; Non-Invasive Tool Simplifies Fibrosis Assessment
An Interview With Francisco Blanco, M.D., Ph.D.

February 5, 2008

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There's nothing like hearing the results of studies directly from those who actually conducted the research. It is these women and men who are transforming HIV treatment and care. In this interview, you'll meet one of these impressive HIV researchers and read an explanation of the study he is presenting at CROI 2008. Accompanying me on this interview is Gerald Pierone, M.D., an HIV clinician/researcher and the founder and executive director of the AIDS Research and Treatment Center of the Treasure Coast in Fort Pierce, Fla.

Francisco Blanco: My name is Francisco Blanco, and I'm an internist. I work in the infectious disease department of the Hospital Carlos III in Madrid.

Francisco Blanco, M.D., Ph.D.
Francisco Blanco, M.D., Ph.D.
My study deals with exposure to antiretrovirals and risk for advanced liver fibrosis.1 [It addresses the question:] Is there a harmful effect of drug-related metabolic alterations? The study includes 681 HIV-positive patients, [some of whom were] monoinfected and [others who were] coinfected with HCV [hepatitis C]. We performed a FibroScan to assess liver fibrosis, and we wanted to assess which factors are associated with advanced liver fibrosis.

We found that, in the multivariate analysis, classical risk factors such as age, alcohol abuse, glucose and elevated ALT values are associated with advanced liver fibrosis. Interestingly, a low CD4+ cell count [was also associated] with advanced liver fibrosis. Also, in the univariate analysis, time on any antiretroviral therapy -- and exposure [specifically] to ddI [didanosine, Videx], d4T [stavudine, Zerit], lopinavir and any PI [protease inhibitor] -- was associated with advanced liver fibrosis. By contrast, nevirapine [NVP, Viramune] associates inversely with advanced liver fibrosis.

We can observe two antagonistic effects: namely, a decrease in liver fibrosis caused by initial immune reconstitution; and an increase in hepatic fibrosis, maybe caused by the toxic effects of antiretroviral therapy -- maybe due to metabolic toxicity, either by mitochondrial toxicity induced by NRTIs or hyperlipidemia induced by PIs.

Gerald Pierone: It looks like a lot of your patient population were intravenous drug users and had infection either with hepatitis C or hepatitis B.

Francisco Blanco: Seventy-seven percent within the advanced liver fibrosis group had infection by hepatitis C, versus 50% within the group that did not have advanced liver fibrosis.

Gerald Pierone: How confident are you in the ability of FibroScan elastometry to predict the degree of liver fibrosis? Has this technique been validated compared with liver biopsies in HIV-infected patients?

Francisco Blanco: In HIV-infected patients, FibroScan is a technique which has demonstrated a good correlation with biopsy in assessing mild and severe degrees of liver fibrosis. To a lesser degree with moderate fibrosis, but there is a very good correlation [in assessing] mild and advanced liver fibrosis.2

Gerald Pierone: Have you tried combining elastometry with some of the blood-based algorithms for determining fibrosis to see if that would improve the receiver-operating characteristics of your curve for determining accuracy?

Francisco Blanco: Not in this study. Obviously, elastometry is a non-aggressive tool that permits us to assess liver fibrosis in a higher number of patients than liver biopsy. That is why we could perform it in more than 600 patients [in this study]. I think it has a very good advantage in comparison with the liver biopsy. This advantage permits us to carry out studies like this, which the liver biopsy would not.

Gerald Pierone: In your center, are you now using elastometry instead of liver biopsy for clinical management of your patients?

Francisco Blanco: Yes. It's nearly a routine tool. We use it in nearly every HIV patient, because we think that HIV itself induces hepatic toxicity. It is very interesting to study the degree of liver fibrosis in every HIV-positive patient. Since we have this very accessible, non-aggressive technique, we use it in nearly every patient. We can follow the evolution of liver fibrosis, mainly in coinfected patients, but also in monoinfected, HIV-positive patients.

Bonnie Goldman: Is this all throughout Spain that this is being used? Or just your clinic?

Francisco Blanco: Our clinic was one of the first clinics in Spain with this technique available. At the moment, this technique is readily available in several hospitals all over Spain.

Bonnie Goldman: Is it available in the United States? Is it commonly used?

Gerald Pierone: Not commonly used. It's available in selected centers, but it's becoming more commonly available.

Francisco Blanco: Yes, in Spain it [has been] the same. It is becoming more available. It's not exceptional now.

Bonnie Goldman: I see, good. Because looking for a non-invasive way is very, very important. Many patients don't want to participate in a liver biopsy.

Francisco Blanco: No, of course. It's the same example in coinfected patients -- take the decision of treating or not treating [HCV], for example. If you have a coinfected patient with a low degree of fibrosis, you can wait to start treatment, but if you have a high degree of fibrosis, you have to start treatment soon. You can make this decision [using elastometry].

Gerald Pierone: I'm curious: Do you see regression of fibrosis in patients that are successfully treated? Can you track regression fibrosis with elastometry in your successfully treated hepatitis C patients?

Francisco Blanco: Yes. We have proven that, in successfully treated patients, fibrosis regresses. This is something that we have proven with elastometry.

Bonnie Goldman: Thank you very much.

This transcript has been edited for clarity.


  1. Blanco F, Barreiro P, Ryan P et al. Exposure to antiretrovirals and risk for advanced liver fibrosis: harmful effect of drug-related metabolic abnormalities? In: Program and abstracts of the 15th Conference on Retroviruses and Opportunistic Infections; February 3-6, 2008; Boston, Mass. Abstract 959.
  2. de Lédinghen V, Barreiro P, Foucher J et al. Liver fibrosis on account of chronic hepatitis C is more severe in HIV-positive than HIV-negative patients despite antiretroviral therapy. J Viral Hepat. June 2008;15(6):427-33.

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