U.S. Department of Health and Human Services

Treatments for Fatty Liver Disease (NASH) Study: PIVENS

Purpose

NIDDK funded the Pioglitazone versus Vitamin E versus Placebo for the Treatment of Non-Diabetic Patients with Nonalcoholic Steatohepatitis (PIVENS) study to research effective treatments for nonalcoholic steatohepatitis (NASH) in adults. This study is part of NIDDK’s NASH Clinical Research Network, which also conducted a similar study in children. At the time, this study was the largest clinical trial of treatments ever conducted in people with NASH.

NASH is a serious disease that involves a buildup of fat in the liver, inflammation, and liver damage. This fat buildup is not caused by heavy alcohol use. Over time, NASH may lead to cirrhosis–a condition in which the liver slowly weakens and is unable to function normally–liver cancer, or liver failure. Currently, there are no approved treatments for NASH.

NASH affects approximately 3 to 12 percent of the U.S. population, but exact numbers are difficult to obtain without performing a liver biopsy on large numbers of people. Some racial/ethnic groups are prone to developing NASH—such as Hispanics/Latinos, American Indians, and people of South Asian descent—and would benefit even more from effective treatments.

Results

Researchers found that a daily dose of a certain form of vitamin E improved NASH in study participants overall. The medicine pioglitazone, another study treatment, also improved some features of NASH although researchers couldn’t prove that they were statistically significant (did not occur randomly).

Despite these positive outcomes, many study participants taking pioglitazone gained weight, and many participants did not improve from either treatment. Researchers also found that changes in quality of life did not differ much between the treatment groups. Additional studies are needed to explore whether treatment with vitamin E or pioglitizone causes long-term risks, and whether either improve NASH in patients who have diabetes.

Some ongoing studies are helping to refine methods and tests to better measure if individuals respond to treatment. For example, researchers who studied participants’ blood alanine transaminase (ALT) levels, a liver enzyme, found that liver damage is usually improved when blood ALT levels decrease to normal. Participants in the PIVENS study who received vitamin E had lower blood ALT levels compared to those receiving placebo. As a result, researchers suggest that ALT levels can be used as a fairly reliable test to detect improvements in liver function in NASH.

Study Size, Participant Demographics, and Study Design

The PIVENS study took place from 2005 to 2009 and involved 247 adults who had NASH and did not have cirrhosis or diabetes at the start of the study. Participants were assigned to one of three treatment groups for 96 weeks.

  • One group received a pill with a form of vitamin E (800 international units)
  • The second group received a pill with pioglitazone (30 mg)
  • and a third group received a placebo, or a pill that contains no medicine.

Before the study began, all participants had a liver biopsy. All participants also had a liver biopsy at the end of the study to see if the treatments in the study had an effect on the liver. Blood tests for liver function, blood glucose or blood sugar, fat, and insulin (a hormone that helps to control blood glucose levels) were done throughout the study. Measurements such as body weight, height, waist and hip size, and body fat percentage were also taken. Questionnaires were given to participants throughout the study to assess their lifestyle and quality of life.

PIVENS was conducted by researchers at the following centers:

  • Case Western Reserve University and the Cleveland Clinic, Cleveland, Ohio
  • Duke University, Raleigh-Durham, North Carolina
  • Indiana University, Indianapolis, Indiana
  • Johns Hopkins University, Baltimore, Maryland
  • Saint Louis University and Washington University, St. Louis, Missouri
  • University of California San Diego, San Diego, California
  • University of California San Francisco, San Francisco, California
  • Virginia Commonwealth University, Richmond, Virginia
  • Virginia Mason Medical Center and the University of Washington, Seattle, Washington

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