11.18.2015
Pooled analysis: Improvements in liver histology, but no NASH resolution
by Kristina Fiore
Staff Writer, MedPage Today
SAN FRANCISCO — Vitamin E was associated with improvement in liver histology in non-alcoholic steatohepatitis (NASH) patients whether or not they had diabetes, researchers reported here.
In an analysis that pooled data from two trials, vitamin E supplementation was associated with histologic improvement in both diabetic and non-diabetic patients (OR 4.4 and OR 3.1, respectively), according to Kris Kowdley, MD, of Swedish Medical Center in Seattle, and colleagues.
But it wasn’t tied to NASH resolution in either population, he reported here at the American Association for the Study of Liver Diseases meeting.
NASH is a common liver disease characterized by hepatic steatosis, lobular inflammation, and hepatocellular ballooning, and it can progress to cirrhosis in about 15% of patients.
It’s associated with both insulin resistance and other metabolic issues such as obesity, hypertriglyceridemia, and type 2 diabetes, and oxidative stress has been implicated as a key contributor to hepatic injury in NASH.
Thus, both insulin resistance and oxidative stress have been viewed as potential targets for therapy. The antioxidant vitamin E falls into the later category and some studies have evaluated its potential role as a therapeutic in NASH, a condition for which there are currently no drug therapies.
For their study, Kowdley and colleagues pooled data from two trials: PIVENS and FLINT.
The PIVENS trial, conducted from 2005 to 2009, randomized 247 patients with NASH to either pioglitazone, vitamin E, or placebo for 96 weeks. None of these patients had diabetes.
Ultimately it found that vitamin E was superior to placebo at improving histologic features of NASH, and there was no benefit for pioglitazone over placebo.
The FLINT study, conducted from 2011 to 2014, randomized 283 NASH patients — with or without diabetes — to obeticholic acid or placebo for 72 weeks. The study included a total of 149 patients with diabetes, and 61 patients reported taking vitamin E at baseline.
When Kowdley and colleagues pooled the data from these two studies, they ended up with a total of 15 diabetics and 90 non-diabetics taking vitamin E, and 38 diabetics and 107 non-diabetics not taking vitamin E.
They applied the measures of efficacy from FLINT to the pooled data: histologic improvement defined as at least a two-point improvement in NAS score with no worsening of of fibrosis; NASH resolution; or fibrosis improvement of at least a one-point decrease in fibrosis stage.
Safety measures included the incidence of cardiac events and changes in total cholesterol, HDL and LDL cholesterol, and triglycerides.
Kowdley and colleagues found that vitamin E use was associated with histologic improvement in both diabetic and non-diabetic patients (OR 4.4, 95% CI 1.1 to 18, P=0.04 and OR 3.1, 95% CI 1.7 to 5.8, P<0.001, respectively).
However, the vitamin was not associated with a significantly greater rate of NASH resolution in either population, Kowdley said.
There was a significant improvement in fibrosis with vitamin E in patients without diabetes (OR 2.2, 95% CI 1.2 to 4.2, P=0.01) but not in those with diabetes, he added.
The incidence of cardiac events wasn’t significantly different between those with diabetes taking vitamin E and those with the condition who weren’t taking the vitamin (0% and 12%, P=0.19). Nor were there any differences among non-diabetics whether they took vitamin E or not (12% and 9%, P=0.51).
And there were no significant differences in change from baseline in terms of any lipid parameters, including total cholesterol, HDL or LDL cholesterol, or triglycerides, between any patients.
Kowdley concluded that while these findings are preliminary, they suggest the potential benefit of vitamin E therapy for patients with NASH. He also called for randomized controlled trials to determine whether the safety and efficacy benefits of vitamin E for treating NASH in patients with diabetes are confirmed.
The study was sponsored by the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases
Kowdley disclosed relevant relationships with Evidera, Gilead, Immuron, Intercept, Tobira, AbbVie, Achillion, Bristol-Myers Squibb (BMS), Merck, and Novartis. Some co-authors disclosed multiple relevant relationships with industry including UpToDate, Salix, BMS, Immuron, Gilead, and Genentech.
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American Association for the Study of Liver Diseases