NASH

WHAT IS LATEST RESEARCH ON NASH

[mikesimon]

"Management of Nonalcoholic Steatohepatitis With Vitamin E
Bruce R. Bacon, MD
Posting Date: August 16, 2010

James F. King, MD, Endowed Chair in Gastroenterology
Professor of Internal Medicine
Division of Gastroenterology and Hepatology
Saint Louis University Liver Center
Saint Louis University School of Medicine
St Louis, Missouri

Nonalcoholic steatohepatitis (NASH) is a hepatic disorder associated with the metabolic syndrome and insulin resistance. It is a very common problem for which no therapy, short of diet/weight loss and exercise, has shown benefit. Extreme measures of weight loss include bariatric surgery, which has not been well studied, but may be beneficial.[1] Accordingly, there is considerable interest in developing pharmacologic therapies directed toward addressing the presence of insulin resistance. There is also interest in exploring the effectiveness of antioxidant therapy because of the role oxidant stress plays in the development of NASH.

The current study by Sanyal and colleagues[2] was designed to determine if either an insulin-sensitizing agent (pioglitazone) or an antioxidant (vitamin E) is effective for improving the histologic features of NASH in nondiabetic individuals (Capsule Summary). The study was carefully conducted through a number of expert academic medical centers that comprise the Nonalcoholic SteatoHepatitis Clinical Research Network (NASH CRN) and was supported by the National Institutes of Health (NIH). A major strength of the study is its design; it was a randomized, controlled, multicenter trial conducted under the direction of the NIH using expert clinical trial centers from around the United States. Therefore, it is clear that the study protocol was designed by experts and that the research was carefully performed. The protocol randomly divided 247 patients with NASH but no diabetes into 3 treatment groups: 1 group received pioglitazone 30 mg/day, 1 group received vitamin E 800 IU/day, and 1 group received placebo. Patients were treated for 2 years (96 weeks), at which time they underwent liver biopsy.

The results showed that use of vitamin E was beneficial in ameliorating several parameters of disease progression. Improvement in NASH, as measured by using a composite of standardized scores for steatosis, lobular inflammation, hepatocellular ballooning, and fibrosis, was observed in 43% of patients receiving vitamin E compared with 19% of patients receiving placebo (P = .001). Specific improvements conferred by vitamin E in comparison with placebo included significant reductions in serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) (P < .001), hepatic steatosis (P = .005), lobular inflammation (P = .02), and hepatocellular ballooning (P = .01). No significant improvements in fibrosis scores were observed with use of vitamin E. It should also be noted that although pioglitazone also yielded significant reductions in individual parameters, such as serum ALT/AST (P < .001), hepatic steatosis (P < .001), and lobular inflammation (P = .004), the difference in the proportion of patients achieving NASH improvement as measured by the composite score was not significantly different between pioglitazone and placebo (34% vs 19%; P = .04; P ≤ .025 level of significance needed for the primary outcome according to the study protocol).

The clinical implications of this study are that vitamin E, which is felt to be relatively harmless and safe, can be used for the treatment of patients with NASH. Although the findings were unanticipated, the study was carefully performed and clinicians can be confident of the findings. Other small pilot studies have been performed showing vitamin E benefits in NASH,[3-5] and there are also small studies showing benefits of either pioglitazone or rosiglitazone in the treatment of NASH.[5-8] However, none of the previous studies was of the scope or the scientific rigor of the present clinical trial. Undoubtedly, additional clinical trials will be performed using the strength of the NASH CRN.

The findings of Sanyal and colleagues add weight to the recommendation to use antioxidants (vitamin E) in the treatment of NASH. Although some benefit was observed with pioglitazone, I do not feel that NASH patients should receive this therapy on a chronic basis at the present time due to small body of data. The exclusion of diabetics may have reduced the benefit of pioglitazone and more studies including diabetics should be performed. Despite the encouraging findings with the use of vitamin E in NASH, clinicians still must counsel their overweight patients with fatty liver disease to work toward attaining an ideal body weight through diet and regular exercise, not only for liver health but also for other general health benefits that will ensue."

See: http://tinyurl.com/24kny9j

Mike