Hi. I'm Dr. Henry Black, Immediate Past President of the American Society of Hypertension and a Clinical Professor of Internal Medicine at the New York University School of Medicine and a member of the Center for the Prevention of Cardiovascular Disease.
I think that we're all aware that there's an obesity epidemic in the United States, and that one of the things that seems to be happening is an increase in deposition of fat in the liver. We used to call this "fatty liver"; now it's got a fancier name -- it's "nonalcoholic steatohepatitis." It's a serious problem because about 15% of the people who have this condition end up with cirrhosis, and the question is whether we can treat it and how. There have been some small studies about using glitazones, others using antioxidants, because both insulin resistance and oxidative stress are thought to be related to fatty liver. These are 2 therapies that are considered useful.
The National Institutes of Diabetes and Kidney Disease underwent a study that directly looked at this problem. They compared pioglitazone (a glitazone) and vitamin E (an antioxidant) with placebo in individuals with biopsy-proven steatohepatitis (nonalcoholic steatohepatitis) and planned to enroll about 80 people per group, and they actually achieved their goal. The follow-up was planned to be 96 weeks with an additional 24 weeks afterward to monitor as the therapy was withdrawn. These individuals were about 45 years of age, and they were not diabetic -- because this could change the answer a little bit -- so the investigators were very careful. I'm actually quite impressed with how they did this. Participants had to undergo a biopsy within 6 months, and the biopsy specimens were judged on ballooning, steatohepatitis, and lobular inflammation; these were looked at by local pathologists and then reviewed later by one of the central pathologists. So this was carefully done and very rarely was the diagnosis changed. Points were assigned as has been tradition in this field, and everybody got a point score based on how much steatosis they had, how much lobular inflammation, and how much ballooning.
It's interesting that because it's a small study by our current standards, only about 80 per group, there were some differences in the 3 groups in how many people actually had a biopsy that showed steatosis. There were many fewer in the pioglitazone group who had ballooning. So ballooning, of course, couldn't improve in that group. At the end of 96 weeks, the participants had a biopsy. Everybody had one, just about across the board, and these were analyzed in a blinded fashion by the pathologist to see which medication worked better. It turned out that both active groups were better than placebo, but because of the need to compare each to the placebo, the P value was set at less than .025 to be significant. It turned out that only the Vitamin E group managed to reach that level of significance. There was a P value of less than 0.04 for the pioglitazone group but because of the additional need to compare to placebo, that wasn't significant. It turned out, though, if you looked at other endpoints like how often the condition resolved, both active groups did better than placebo, but the pioglitazone group was the only one that was significant.
If you looked at the various histological changes between those 2 active groups there really wasn't anything different. Remember that there was less ballooning in the pioglitazone group by chance and that this couldn't improve, of course, since it wasn't there. When you looked at the biochemical findings for both the antioxidant (vitamin E) and for the glitazone (pioglitazone), there was an improvement in transaminases, but insulin resistance got better only with pioglitazone as we would anticipate. But curiously, the pioglitazone group gained about 5 kg over the year, and that didn't go away when they stopped the medicine. The transaminase improvement did go away in both groups.
So it looks like now that we actually have a way to address this problem because exercise and diet, which we'd all like to do, are not necessarily going to help. We may eventually reduce the amount of cirrhosis from this problem, which would be a good thing. It's interesting, too, that this is one of the first studies where vitamin E has actually worked. Most of the time that vitamin E has been looked, at it has failed.
Medscape Cardiology © 2010
Cite this: Henry R. Black. Finally, Vitamin E May Work -- And It's in the Liver - Medscape - Jul 06, 2010.