The trial design and rationale for the PIVENS trial have been described previously.16 (link) This trial focused on adults without diabetes who had nonalcoholic steatohepatitis. Adults with diabetes were excluded because it was unclear whether they would have the same responses to therapy as would adults without diabetes and because it was possible that changes in antidiabetic therapy might confound the analysis of data both from subjects with diabetes and from those without diabetes. All subjects underwent a liver biopsy within 6 months before randomization.
Steatohepatitis was categorized as absent, possible, or definite.17 (link) Disease activity was assessed with the use of the nonalcoholic fatty liver disease activity score, which is based on a standardized grading system for steatosis (on a scale of 0 to 3), lobular inflammation (on a scale of 0 to 3), and hepatocellular ballooning (on a scale of 0 to 2), with higher scores indicating increasing severity).17 (link) The specific inclusion criteria were definite or possible steatohepatitis with an activity score of 5 or more, or definite steatohepatitis (confirmed by two pathologists) with an activity score of 4. A score of at least 1 for hepatocellular ballooning was required in all cases. Although eligibility was determined by the pathologist at each site from an assessment of tissue sections prepared locally, the final analysis was based on review by a pathology committee of deeper cuts, prepared centrally, from the biopsy specimens obtained at baseline and at the end of treatment. Members of the pathology committee who performed the final analysis were unaware of the study-group assignments.
Exclusion criteria were alcohol consumption of more than 20 g per day in the case of women and more than 30 g per day in the case of men for at least 3 consecutive months during the previous 5 years, as assessed with the use of the Lifetime Drinking History questionnaire of Skinner et al.18 (link) and the self-administered Alcohol Use and Disorders Identification Test (AUDIT).19 (link) Subjects were also excluded if they had cirrhosis, hepatitis C or other liver diseases, or heart failure (New York Heart Association class II to IV), or if they were receiving drugs known to cause steatohepatitis.
Both at the initial evaluation and at the completion of treatment 96 weeks later, subjects underwent an assessment of body weight, height, and waist and hip circumferences, and blood samples were obtained for routine biochemical tests and assessment of fasting levels of lipids, glucose, and insulin. Body composition was assessed with the use of dual-energy x-ray absorptiometry. The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) was administered for the assessment of quality of life.
Steatohepatitis was categorized as absent, possible, or definite.17 (link) Disease activity was assessed with the use of the nonalcoholic fatty liver disease activity score, which is based on a standardized grading system for steatosis (on a scale of 0 to 3), lobular inflammation (on a scale of 0 to 3), and hepatocellular ballooning (on a scale of 0 to 2), with higher scores indicating increasing severity).17 (link) The specific inclusion criteria were definite or possible steatohepatitis with an activity score of 5 or more, or definite steatohepatitis (confirmed by two pathologists) with an activity score of 4. A score of at least 1 for hepatocellular ballooning was required in all cases. Although eligibility was determined by the pathologist at each site from an assessment of tissue sections prepared locally, the final analysis was based on review by a pathology committee of deeper cuts, prepared centrally, from the biopsy specimens obtained at baseline and at the end of treatment. Members of the pathology committee who performed the final analysis were unaware of the study-group assignments.
Exclusion criteria were alcohol consumption of more than 20 g per day in the case of women and more than 30 g per day in the case of men for at least 3 consecutive months during the previous 5 years, as assessed with the use of the Lifetime Drinking History questionnaire of Skinner et al.18 (link) and the self-administered Alcohol Use and Disorders Identification Test (AUDIT).19 (link) Subjects were also excluded if they had cirrhosis, hepatitis C or other liver diseases, or heart failure (New York Heart Association class II to IV), or if they were receiving drugs known to cause steatohepatitis.
Both at the initial evaluation and at the completion of treatment 96 weeks later, subjects underwent an assessment of body weight, height, and waist and hip circumferences, and blood samples were obtained for routine biochemical tests and assessment of fasting levels of lipids, glucose, and insulin. Body composition was assessed with the use of dual-energy x-ray absorptiometry. The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) was administered for the assessment of quality of life.
