Skip to main content
Back to Research Library
A
High Confidence
Randomized Controlled TrialPMC Full Text2010

Pioglitazone, Vitamin E, or Placebo for Nonalcoholic Steatohepatitis

Sanyal AJ, Chalasani N, Kowdley KV, et al. • N Engl J Med

Key Finding

Vitamin E improved NASH in 43% vs 19% placebo (P=0.001, NNT 4.2); NASH resolution 36% vitamin E vs 21% placebo; neither treatment improved fibrosis

Key Findings

  • 1Vitamin E improved NASH in 43% vs 19% placebo (P=0.001, NNT 4.2)
  • 2NASH resolution: vitamin E 36%, pioglitazone 47%, placebo 21%
  • 3ALT reduction: vitamin E −37 U/L, pioglitazone −41 U/L vs placebo −20 U/L
  • 4Neither vitamin E nor pioglitazone improved fibrosis scores

Original title: “Pioglitazone, Vitamin E, or Placebo for Nonalcoholic Steatohepatitis”

Plain English Summary

PIVENS trial: multicenter RCT of 247 non-diabetic adults with biopsy-confirmed NASH. 96 weeks treatment comparing vitamin E 800 IU, pioglitazone 30 mg, or placebo.

In-Depth Analysis

Study Details

Lead Author: Arun J Sanyal, MD, Virginia Commonwealth University
Journal: NEJM, 2010 Apr 28; 362(18):1675-1685
PMCID: PMC2928471

Study Design

  • •N = 247 adults without diabetes
  • •Biopsy-confirmed NASH
  • •Multicenter RCT, double-blind, placebo-controlled
  • •96 weeks treatment
Treatment Groups
  • •Placebo: n=83
  • •Vitamin E: n=84 (800 IU daily, natural form)
  • •Pioglitazone: n=80 (30 mg daily)

Primary Outcome: Histological Improvement

TreatmentImprovement RateP vs PlaceboNNT
Vitamin E43%0.0014.2
Pioglitazone34%0.04*6.9
Placebo19%——

*Did not reach prespecified 0.025 threshold

Secondary Outcomes (96 weeks)

ALT Reduction
  • •Vitamin E: −37.0 U/L (P=0.001)
  • •Pioglitazone: −40.8 U/L (P<0.001)
  • •Placebo: −20.1 U/L
NASH Resolution
  • •Vitamin E: 36%
  • •Pioglitazone: 47%
  • •Placebo: 21%
Steatosis Improvement
  • •Vitamin E: 54%
  • •Pioglitazone: 69%
  • •Placebo: 31%
Fibrosis
  • •Neither active drug significantly improved fibrosis scores

Adverse Effects

  • •Pioglitazone: +4.7 kg weight gain (P<0.001)
  • •Vitamin E: +0.4 kg

Source: PMC full text (PMC2928471)

Paradigm Relevance

How this study applies to different clinical perspectives:

Standard Medical

Relevant

Conventional clinical guidelines used by most doctors

Why it matters:

Supports vitamin E 800 IU daily as treatment option for biopsy-confirmed NASH. Requires discussion of potential risks with healthcare provider.

Research Consensus

Relevant

Current scientific understanding, often ahead of guidelines

Why it matters:

Provides high-quality evidence for vitamin E in NASH. Importantly, did not improve fibrosis — early intervention before scarring is key.

Metabolic Optimization

Relevant

Proactive targets for optimal health, not just disease absence

Why it matters:

Validates antioxidant approach to liver health. Consider vitamin E supplementation for elevated ALT with suspected NASH, alongside lifestyle optimization.

Study Details

Type
Randomized Controlled Trial
Methodology
N = 247 non-diabetic adults with biopsy-confirmed NASH. Multicenter RCT, double-blind. 96-week treatment. Primary outcome: histological improvement.

Evidence Quality

Grade A - RCT. PMC2928471. PIVENS trial established vitamin E as NASH treatment in non-diabetics.

Topic

Liver HealthInflammation

Related Biomarkers

ALTASTLIVER ENZYMESNAFLD

Calculate & Evaluate on Metabolicum

🫀

ALT

Evaluator

Liver enzyme with optimal range guidance

Original Source

View on PubMedView DOIFull Text (Open Access)

DOI (Digital Object Identifier) is a permanent link to this publication. Unlike website URLs that can change, a DOI always resolves to the correct source.

Related Studies