The objectives of this application are to plan and conduct pilot research leading to the development of a clinical trial in the treatment of alcoholic fibrosis with dilinoleoyl phosphatidycholine (DLPC) and to develop instruments and methodologies which can support larger scale studies on such treatment. Specifically, we wish to organize and start a double-blind, randomized multicenter pilot study on the effect of DLPC on alcohol-induced liver fibrosis in eight medical centers (Beth Israel Medical Center, NY, NY; Cincinnati University Medical Center, Cincinnati, Ohio; Elmhurst Medical Center, Queens, NY; Miami University Medical Center, Miami, FL; New York Medical College, Valhalla, NY; University of Medicine and Dentistry, Newark, NJ; Mt. Sinai Medical Center, New York, NY and the Veterans Affairs Medical Center, Bronx, NY). DLPC is the key ingredient of polyunsaturated lecithin, a food supplement (extracted from soybeans) recently found to be effective in preventing cirrhosis in the baboon model. It will be administered (or placebo) in a randomized double-blind fashion with informed consent to alcoholics with liver fibrosis varying in severity from early perivenular fibrosis to septal fibrosis. Compliance will be assessed by conventional techniques, including measurement, in urine samples, of riboflavin incorporated in the administered tablets. Alcohol consumption will be verified by interviews of collaterals and several markers of alcohol consumption, including carbohydrate deficient transferrin, measured with a newly developed and validated isoelectric focusing/western blotting technique. Effect of the treatment will be assessed on either progression of liver disease (in those who continue to drink) or regression of preexisting lesions (in those who stop drinking or have a moderate intake). It is estimated that approximately 72 patients may suffice to determine whether DLPC reduces histologic progression in those who continue to drink heavily, and 160 subjects to evaluate the reversal of fibrosis by PUL in subjects who remain sober or drink moderately during the study. In addition to conventional liver function tests, outcome will be evaluated through liver biopsy and blood markers of fibrosis such as radioimmunoassays for procollagen peptides (PIIIP), previously validated in our center. The dose of polyunsaturated lecithin (4.5 gm/day) is commensurate with that which was found to be effective in the baboon model. The same amount has been used previously for a number of other indications in various clinical studies and was shown to be without side effects; it is also available in health food stores in more crude preparations which are being widely consumed as well tolerated food supplements. This small grant is needed to get a pilot project under way. The requested modest support will be used to defray the expenses for the specialized tests (to assess alcohol consumption and the severity of liver fibrosis) and to pay for travel and other costs of the meetings (required to organize a multicenter study); the pilot results will also be used to plan for the final stages of the study and to apply for its support. It is hoped that this investigation will ultimately confirm, in man, the striking beneficial results observed in the baboon and thereby yield an effective way of preventing alcoholic fibrosis and/or promoting its regression.
| Lieber, C S; Robins, S J; Li, J et al. (1994) Phosphatidylcholine protects against fibrosis and cirrhosis in the baboon. Gastroenterology 106:152-9 |
| Lieber, C S (1994) Alcohol and the liver: 1994 update. Gastroenterology 106:1085-105 |
| Lieber, C S; Robins, S J; Leo, M A (1994) Hepatic phosphatidylethanolamine methyltransferase activity is decreased by ethanol and increased by phosphatidylcholine. Alcohol Clin Exp Res 18:592-5 |
