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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
Non-Alcoholic Fatty Liver Disease Is Common in HAART-Experienced Patients; Several HIV- and Antiretroviral-Related Factors May Play Role
An Interview With Giovanni Guaraldi, M.D.

February 6, 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.

Giovanni Guaraldi: My name is Giovanni Guaraldi. I work in Modena University [in Italy], where I run a metabolic clinic. It's a place where people with lipodystrophy come from all over Italy to have a metabolic risk profile [taken]. The study I'm presenting here is entitled, "Evolution of Non-Alcoholic Fatty Liver Disease [NAFLD] in HIV-Infected Patients: Incidence, Characteristics, and Predictors."1

Giovanni Guaraldi, M.D.
Giovanni Guaraldi, M.D.
These are the prospective results of a cross-sectional analysis that was presented at the EACS [European AIDS Clinical Society] meeting in Madrid [Spain] last October, in which we presented 2,025 HIV-infected patients negative to HCV [hepatitis C virus] and HBV [hepatitis B virus] in which we were able to identify liver disease [by] looking at the liver-to-spleen ratio by CT [computed tomography] examination. The reason why we did that is that, as soon as you look to liver steatosis with ultrasound, there is a big variability in diagnosis, while if you use a CT scan, the reproducibility of the data is very good.

Of course, for NAFLD, a liver biopsy should be used, but it's very difficult to offer liver biopsy to HIV patients that have no coinfection [with hepatitis C]. We decided to study this disease looking at people with a liver-to-spleen ratio less than 1.1. This cutoff has been established for liver donor transplant patients; we know that people having a liver-to-spleen ratio less than 1.1 have at least a 30% steatosis of the liver. In the cross-sectional study, we were able to identify a risk factor for NAFLD. We found that transaminase level, male sex, waist circumference and cumulative NRTI [nucleoside reverse transcriptase inhibitor] exposure were all predictors of prevalence of NAFLD.

What we wanted to do here was to understand not only the prevalence, which is nearly 30% in HIV-infected patients, but the incidence of this disease. We had 52 patients that had two CT scans done one year apart. We found that NAFLD incidence is 10 per 100 person-years. We have an incidence in the general HIV-negative population [of] 10 per 1,000 person-years.2 We can say that in HIV-infected [people], the probability of developing NAFLD is ten times what is found in the general population.

We were able to find the predictors of developing NAFLD. Actually, what we found -- by dividing the population into three different groups, according to quartile of delta liver-to-spleen ratio -- was that some metabolic parameters, like HDL [high-density lipoprotein] and apolipoprotein, were related to the probability of improving or worsening NAFLD.

What is striking is that, even if cumulative NRTI exposure is not statistically significant, there's a clear trend [based] on the fact that people [who had] improving NAFLD had less than 50% exposure [to] NRTI drugs [compared to] the people [who had] worsening NAFLD. Of course, this is an observational study, not a clinical trial. We have no proof of the concept that NRTIs are involved in this phenomenon. But we believe that there may be, apart from classical metabolic risk factors for NAFLD, other HIV- or drug-related factors that may explain such a high incidence of this disease.

Gerald Pierone: As a clinician, it sounds like you're making your diagnosis of fatty infiltration based on CAT scans in your referral center throughout Italy. How do you manage these patients? When you have an HIV patient that you find, you make this diagnosis non-invasively. What sort of interventions do you do?

Giovanni Guaraldi: I think that we have to understand that NAFLD is a metabolic condition, and it's a metabolic condition very often strictly related to metabolic syndrome. What we were able to find is that, in the cross-sectional analysis, HOMA [homeostatic model assessment] was the leitmotif [recurring theme] of [patients] developing NAFLD. I think the first issue that we needed to address is, "What is the metabolic condition that is underneath the NAFLD?"

Of course, as soon as you find a high insulin level or high lipids, you should address that with appropriate intervention. In our metabolic clinic, for instance, we have diet counseling for all the patients. We have a physical trainer that prescribes exercise to HIV patients and gives a specific physical activity as therapy. As soon as there's the possibility of using the best lipid-friendly drugs, we offer switching, if it is feasible and if it's possible to have the same virological results. As soon as needed, we offer lipid-lowering agents -- in particular, our experience is with rosuvastatin. What is not yet clear is [whether] we need to introduce thiazolidinediones -- for instance, rosiglitazone or pioglitazone -- just to treat the fat infiltration of the liver.

What we stress is the need to follow up, with HOMA-IR [homeostasis model assessment of insulin resistance], the evolution of these patients, considering that HOMA-IR may predict the metabolic syndrome, and that NAFLD may be an equivalent of the metabolic syndrome in the liver.

Gerald Pierone: You mentioned switching antiretrovirals. Give me an example.

Giovanni Guaraldi: What we do, for instance, is consider the possibility of deboosting protease inhibitors [PI] [using a protease inhibitor without ritonavir (RTV, Norvir)] and using TDM [therapeutic drug monitoring] in order to monitor the trough level of an unboosted PI. If we believe that [there is] some PI with a higher metabolic risk profile -- like, for instance, Kaletra [lopinavir/ritonavir, LPV/r] -- [compared] to other, more lipid-friendly [drugs], we offer the [option of] switching either [from] PI to NRTI, or [from] PI to unboosted PI. It's individualized according to the patient history, according to both the metabolic and the cardiovascular risk.

What is new is that it's not sufficient to look at the Framingham risk. We must also look at some disease equivalent of the metabolic syndrome, and NAFLD may be one of these. Of course, what we don't know is the proportion of [patients with] NAFLD that will actually develop NASH [non-alcoholic steatohepatitis] -- that is, liver fibrosis -- and the proportion of NASH that will develop into cirrhosis. This is not known, and it's not known whether some metabolic intervention, like lipid-lowering agents or glitazone, will be able to change the natural history of this disease.

Bonnie Goldman: Thank you very much.

This transcript has been lightly edited for clarity.


Footnotes

  1. Guaraldi G, Squillace N, Stentarelli C, et al. Evolution of non-alcoholic fatty liver disease in HIV-infected patients: Incidence, characteristics, and predictors. In: Program and abstracts of the 15th Conference on Retroviruses and Opportunistic Infections; February 3-6, 2008; Boston, Mass. Abstract 958.
    View poster: Download PDF
  2. El-Serag HB, Tran T, Everhart JE. Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma. Gastroenterology. 2004 Feb;126(2):460-468.

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Please note: Knowledge about HIV changes rapidly. Note the date of this summary's publication, and before treating patients or employing any therapies described in these materials, verify all information independently. If you are a patient, please consult a doctor or other medical professional before acting on any of the information presented in this summary. For a complete listing of our most recent conference coverage, click here.

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