[Double-blind study in patients with alcoholic toxic fatty liver. Effect of essential phospholipids on enzyme behavior and lipid composition of the serum].

Die Medizinische Welt 04/1979; 30(11):411-6.
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    ABSTRACT: Characteristic features of alcoholic liver injury include fibrosis and striking membrane alterations, with associated phospholipid changes. To offset some of these abnormalities, a 10-yr study was conducted in baboons: 12 animals (eight females, four males) were fed a liquid diet supplemented with polyunsaturated lecithin (4.1 mg/kcal) for up to 8 yr, with either ethanol (50% of total energy) or isocaloric carbohydrate. They were compared with another group of 18 baboons fed an equivalent amount of the same diet (with or without ethanol), but devoid of lecithin. In the two groups, comparable increases in lipids developed in the ethanol-fed animals, but striking differences in the degree of fibrosis were seen. Whereas at least septal fibrosis (with cirrhosis in two) and transformation of their lipocytes into transitional cells developed in seven of the nine baboons fed the regular diet with ethanol, septal fibrosis did not develop in any animals fed lecithin (p less than 0.005). They did not progress beyond the stage of perivenular fibrosis (sometimes associated with pericellular and perisinusoidal fibrosis) and had a significantly lesser activation of lipocytes to transitional cells. Furthermore, when three of these animals were taken off lecithin, but continued on the same amount of the ethanol-containing diet, they rapidly (within 18 to 21 mo) progressed to cirrhosis, accompanied by an increased transformation of their lipocytes to transitional cells. These results indicate that some component of lecithin exerts a protective action against the fibrogenic effects of ethanol. Because we had previously found that choline, in amounts present in lecithin, has no comparable action, the polyunsaturated phospholipids themselves might be responsible for the protective effect.
    Hepatology 12/1990; 12(6):1390-8. DOI:10.1002/hep.1840120621 · 11.19 Impact Factor
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    ABSTRACT: Essential phospholipids (EPL) contain a highly purified extract of polyenylphosphatidylcholine (PPC) molecules from soybean. The main active ingredient is 1,2-dilinoleoylphosphatidylcholine (DLPC), which differentiates it from other phospholipids, lecithins, or extracts from other sources. Although EPLis widely used in liver diseases of various origins, its mode of action and pharmacological and clinical evidence of its efficacy have not yet been concisely reviewed. This paper critically summarizes experimental and clinical results. With regard to in-vitro and animal tests, EPL influenced membrane-dependent cellular functions and showed anti-oxidant, anti-inflammatory, anti-fibrotic, apoptosis-modulating, regenerative, membrane-repairing and -protective, cell-signaling and receptor-influencing, as well as lipid-regulating effects in intoxication models with chemicals or drugs. Clinical studies, primarily from European and Asian countries, have shown improvement in subjective symptoms; clinical, biochemical and imaging findings; and histology in liver indications such as fatty liver of different origin, drug hepatotoxicity, and adjuvant in chronic viral hepatitis and hepatic coma. The available studies characterize EPL as evidence-based medicine, although further long-term controlled clinical trials are required to precisely determine its benefit for alleviating symptoms, improving well-being, inducing histological changes and slowing the progression of liver disease. EPL-related relevant side effects were not observed.
    Pharmacological reports: PR 05/2011; 63(3):643-59. DOI:10.1016/S1734-1140(11)70576-X · 2.17 Impact Factor
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    ABSTRACT: Much progress has been made in the understanding of the pathogenesis of alcoholic liver disease, resulting in improvement of prevention and therapy, with promising prospects for even more effective treatments. The most successful approaches that one can expect to evolve are those that deal with the fundamental cellular disturbances resulting from excessive alcohol consumption. Two pathologic concepts are emerging as particularly useful therapeutically. Whereas it continues to be important to replenish nutritional deficiencies, when present, it is crucial to recognize that because of the alcohol-induced disease process, some of the nutritional requirements change. This is exemplified by methionine, which normally is one of the essential amino acids for humans, but needs to be activated to S-adenosylmethionine (SAMe), a process impaired by the disease. Thus, SAMe rather than methionine is the compound that must be supplemented in the presence of significant liver disease. Indeed, SAMe was found to attenuate mitochondrial lesions in baboons, replenish glutathione, and significantly reduce mortality in patients with Child A or B cirrhosis. Similarly, polyenylphosphatidylcholine (PPC) corrects the ethanol-induced hepatic phospholipid depletion as well as the decreased phosphatidylethanolamine methyltransferase activity and opposes oxidative stress. It also deactivates hepatic stellate cells, whereas its dilinoleoyl species (DLPC) increases collagenase activity, resulting in prevention of ethanol-induced septal fibrosis and cirrhosis in the baboon. Clinical trials with PPC are ongoing in patients with alcoholic liver disease. Furthermore, enzymes useful for detoxification, such as CYP2E1, when excessively induced, become harmful and should be downregulated. PPC is one of the substances with anti-CYP2E1 properties that is now emerging. Another important aspect is the association of alcoholic liver disease with hepatitis C: a quarter of all patients with alcoholic liver disease also have markers of HCV infection, with an even higher incidence in some urban areas but, at present, no specific therapy is available since interferon is contraindicated in that population. However, in addition to antiviral medications, agents that oppose oxidative stress and fibrosis should also be tested for hepatitis C treatment since these two processes contribute much to the pathology and mortality associated with the virus. In addition to antioxidants (such as PPC, silymarin, alpha-tocopherol and selenium), anti-inflammatory medications (corticosteroids, colchicine, anticytokines) are also being tested as antifibrotics. Transplantation is now accepted treatment in alcoholics who have brought their alcoholism under control and who benefit from adequate social support but organ availability is still the major limiting factor and should be expanded more aggressively. Finally, abstinence from excessive drinking is always indicated; it is difficult to achieve but agents that oppose alcohol craving are becoming available and they should be used more extensively.
    Journal of Hepatology 02/2000; 32(1 Suppl):113-28. DOI:10.1016/S0168-8278(00)80420-1 · 10.40 Impact Factor