II. Veterans Affairs Cooperative Study of Polyenylphosphatidylcholine in Alcoholic Liver Disease

Authors

  • Charles S. Lieber,

    Corresponding author
    1. Bronx Veterans Affairs Medical Center and the Mount Sinai School of Medicine (CSL, FP), Bronx, New York; Perry Point Veterans Affairs Medical Center, University of Maryland School of Medicine (DGW), Perry Point, Maryland; West Haven Veterans Affairs Medical Center and Yale University School of Medicine (RG), New Haven, Connecticut; and San Antonio Veterans Affairs Medical Center and University of Texas Health and Science Center (SS), San Antonio, Texas.
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  • David G. Weiss,

    1. Bronx Veterans Affairs Medical Center and the Mount Sinai School of Medicine (CSL, FP), Bronx, New York; Perry Point Veterans Affairs Medical Center, University of Maryland School of Medicine (DGW), Perry Point, Maryland; West Haven Veterans Affairs Medical Center and Yale University School of Medicine (RG), New Haven, Connecticut; and San Antonio Veterans Affairs Medical Center and University of Texas Health and Science Center (SS), San Antonio, Texas.
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  • Roberto Groszmann,

    1. Bronx Veterans Affairs Medical Center and the Mount Sinai School of Medicine (CSL, FP), Bronx, New York; Perry Point Veterans Affairs Medical Center, University of Maryland School of Medicine (DGW), Perry Point, Maryland; West Haven Veterans Affairs Medical Center and Yale University School of Medicine (RG), New Haven, Connecticut; and San Antonio Veterans Affairs Medical Center and University of Texas Health and Science Center (SS), San Antonio, Texas.
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  • Fiorenzo Paronetto,

    1. Bronx Veterans Affairs Medical Center and the Mount Sinai School of Medicine (CSL, FP), Bronx, New York; Perry Point Veterans Affairs Medical Center, University of Maryland School of Medicine (DGW), Perry Point, Maryland; West Haven Veterans Affairs Medical Center and Yale University School of Medicine (RG), New Haven, Connecticut; and San Antonio Veterans Affairs Medical Center and University of Texas Health and Science Center (SS), San Antonio, Texas.
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  • Steven Schenker,

    1. Bronx Veterans Affairs Medical Center and the Mount Sinai School of Medicine (CSL, FP), Bronx, New York; Perry Point Veterans Affairs Medical Center, University of Maryland School of Medicine (DGW), Perry Point, Maryland; West Haven Veterans Affairs Medical Center and Yale University School of Medicine (RG), New Haven, Connecticut; and San Antonio Veterans Affairs Medical Center and University of Texas Health and Science Center (SS), San Antonio, Texas.
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  • for the Veterans Affairs Cooperative Study 391 Group

    1. Bronx Veterans Affairs Medical Center and the Mount Sinai School of Medicine (CSL, FP), Bronx, New York; Perry Point Veterans Affairs Medical Center, University of Maryland School of Medicine (DGW), Perry Point, Maryland; West Haven Veterans Affairs Medical Center and Yale University School of Medicine (RG), New Haven, Connecticut; and San Antonio Veterans Affairs Medical Center and University of Texas Health and Science Center (SS), San Antonio, Texas.
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  • Supported by the Cooperative Studies Program, Department of Veterans Affairs, and the Kingsbridge Research Foundation.

  • Presented at the Annual Meeting of the American Association for the Study of Liver Diseases, November 2002, Boston, Massachusetts.

  • *

    Study group members are listed in Appendix 1.

Charles S. Lieber, MD, MACP, Alcohol Research Center and Section of Liver Disease & Nutrition (151-2), VA Medical Center, 130 W. Kingsbridge Rd., Bronx, NY 10468; Fax: 718-733-6257; E-mail: liebercs@aol.com.

Abstract

Background: Polyenylphosphatidylcholine (PPC) has been shown to prevent alcoholic cirrhosis in animals. Our aims were to determine the effectiveness of PPC in preventing or reversing liver fibrosis in heavy drinkers and to assess the extent of liver injury associated with the reduced drinking achieved in these patients.

Methods: This randomized, prospective, double-blind, placebo-controlled clinical trial was conducted in 20 Veterans Affairs Medical Centers with 789 patients (97% male; mean age, 48.8 years) averaging 16 drinks per day (1 drink = 14 g of alcohol) for 19 years. A baseline liver biopsy confirmed the presence of perivenular or septal fibrosis or incomplete cirrhosis. They were randomly assigned either PPC or placebo. Liver biopsy was repeated at 24 months, and the main outcome measure was the stage of fibrosis compared with baseline. Progression was defined as advancing to a more severe stage.

Results: The 2-year biopsy was completed in 412 patients. PPC did not differ significantly from placebo in its effect on the main outcome. Alcohol intake was unexpectedly reduced in both groups to approximately 2.5 drinks per day. With this intake, 21.4% advanced at least one stage (22.8% of PPC patients and 20.0% of placebo patients). The hepatitis C virus–positive subgroup exhibited accelerated progression. Improvement in transaminases and bilirubin favoring PPC was seen at some time points in other subgroups (hepatitis C virus–positive drinkers or heavy drinkers).

Conclusions: PPC treatment for 2 years did not affect progression of liver fibrosis. A trend in favor of PPC was seen for transaminases and bilirubin (in subgroups). One of five patients progressed even at moderate levels of drinking, and thus health benefits commonly associated with moderate drinking do not necessarily extend to individuals in the early stages of alcoholic liver disease.

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