Clinical Predictors of Liver Fibrosis Presence and Progression in HIV-Associated NAFLD

In this video, Lindsay T. Fourman, MD, talks about the predictors of liver fibrosis and progression among patients with HIV-associated nonalcoholic fatty liver disease. Read the transcript here.

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Lindsey T. Fourman: In nonalcoholic fatty liver disease, liver fibrosis is the number one predictor of liver‑specific and total mortality. Understanding what predicts who will develop fibrosis is particularly important, so that we can target those individuals for more aggressive monitoring, and for treatment once treatments do become available.

We recently completed a randomized placebo‑controlled trial of a medication called tesamorelin to treat fatty liver in HIV. Tesamorelin is a growth hormone, releasing hormone analog that's FDA approved to treat visceral fat. We also wanted to know whether or not it can reduce liver fat in HIV.

This previous study provided us with a framework to look at the long‑term natural history of NAFLD in HIV, particularly, should we go on to develop fibrosis, since we had serial liver biopsies on all of our patients, and in particular, on the placebo‑treated arm.

There's very limited data in HIV about what the natural history of NAFLD is, especially very limited biopsy data. This study afforded us a nice window to be able to do that.

Overall, the presence of fibrosis was seen in about 40% of individuals, so a very high percent, consistent with previous reports in HIV that have shown that NAFLD does tend to be more severe in this population.

In terms of the predictors that we did find, we saw that at baseline, the presence of fibrosis among our overall sample was associated with increased NAS score or NAFLD Activity Score, which is a composite of the amount of fat and inflammation in the liver.

We also found that fibrosis at baseline was associated with higher liver enzymes, ALT and AST. We did not find that it was associated with any body composition parameters.

Then we went on to look at the presence of progression in the placebo‑treated arm of our study. We wanted to know what percentage of people would go on to develop a more severe disease. These findings were very interesting and, as I said, have never been shown before.

What we saw was that about almost 40% of individuals had progression of fibrosis over the one‑year period, which is a very strikingly high number. At baseline, over half of these individuals had no fibrosis at baseline. The presence of having no fibrosis at baseline is not that reassuring in terms of someone's ability to have more-severe disease and progress rapidly.

In terms of what we saw, in terms of clinical correlates that predicted this fibrosis progression, the only one that came out positive in our study was visceral adipose tissue. Having higher visceral fat at baseline conferred an increased odds of going on to have fibrosis progression over the study period.

We found this fascinating, especially since we did not find other liver‑specific parameters to be associated with progression. Having fibrosis at baseline or having more liver fat at baseline was not associated with more aggressive disease. That baseline liver biopsy wasn't that predictive of who would go on to progress.

Lindsay T. Fourman, MD, is a physician at Massachusetts General Hospital in Boston, Massachusetts.



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