The“Hidden” Liver DiseaseFebruary 2004
By Penelope Hamil
Can NAFLD Be Treated or Prevented?
Phosphatidylcholine (the main component of lecithin) is an integral part of cell membranes, essential for their structural and functional integrity. Cell membranes act like gatekeepers, allowing nutrients into the cells but blocking damaging toxins from gaining entrance. PPC has been shown to enhance cell membrane function throughout the body.
PPC already is approved for the treatment of chronic liver diseases in many European countries and is being investigated for treatment of hepatitis (see sidebar on p. 55, “PPC in Viral Hepatitis”). PPC is listed in the Physician’s Desk Reference (PDR) commonly used by US physicians. An accumulating body of research suggests that PPC’s umbrella of protection may extend from the liver to the stomach, pancreas, and cardiovascular system. PPC is well absorbed in humans and animals when taken orally and has no known contraindications, side effects, or interactions with other drugs, even when consumed in large quantities. In one pilot study, researchers found that daily doses of PPC halted the progression of liver fibrosis,27 and a Czech study showed that taking the supplement every day (along with low doses of fatty acids, B vitamins, and vitamin E) reduced fatty-liver symptoms within six months in more than half of the study participants.28 PPC also appears to increase the breakdown of collagen, the connective-tissue protein that tends to accumulate in liver disease, promoting the scarring behind fibrosis and cirrhosis.29
PPC’s protective effect is believed to be the result of its ability to be incorporated in normal and damaged cell membranes. Animal studies have indicated that PPC, which is a polyunsaturated phosphatidylcholine, becomes incorporated in the membranes of liver cells as a substitute for native saturated phosphatidylcholine molecules.30 This substitution is shown to result in an increase in membrane fluidity and active transport activity across the membrane. Similarly, PPC is incorporated in blood lipoproteins such as cholesterol, leading to lipid-lowering properties. In one Russian clinical trial, the supplement lowered total and LDL (“bad”) cholesterol by about 15%, decreased triglyceride levels by 32%, and raised levels of “good” HDL cholesterol by 10%.31
PPC also appears to have antioxidant properties, which means it may effectively reduce the oxidative stress (cellular changes that generate cell-damaging free radicals) shown to be a contributing factor in the inflammation and scarring of nonalcoholic steatohepatitis.32
Experts point out that simply losing weight often will result in a significant reduction of excess fat in the liver. But they add that it is best to lose weight slowly—at a rate of no more than 1 to 2 pounds a week—because rapid weight loss has been shown to exacerbate a fatty liver condition, causing inflammation and even resulting in liver failure.33-35
Keeping high glucose levels under control also is critical for NAFLD patients, as research has shown that a fatty liver improves as glucose levels are controlled.36 A preliminary study found that a drug called metformin (Glucophage®), which improves insulin sensitivity and is used to treat type II diabetes, also significantly lowered liver enzyme levels and decreased fatty deposits in the liver in people with NAFLD.7 Additional studies are now under way.
Doctors say that NAFLD can probably be largely prevented and even eliminated in the future by encouraging the adoption of healthy eating habits and more-active lifestyles. For those who already have nonalcoholic fatty liver disease, encouraging discoveries show that the use of natural products may potentially alter the course of this serious consequence of aging and unhealthful lifestyles.
1. Clark JM, Brancati FL, Diehl AM. Nonalcoholic fatty liver disease: the most common cause of abnormal liver enzymes in the U.S. population [abstract]. Gastroenterology. 2001;120:A–65.
2. The American Liver Foundation. What is NAFLD/NASH? (Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis). Available at: http://www.liverfoundation. org/db-select/articles/CatNonAlcy/1/1/ ascend/Validated. Accessed November 24, 2003.
3. Ludwig J, Viggiano TR, McGill DB, Oh BJ. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed dis- ease. Mayo Clin Proc. 1980 Jul;55(7):434-8.
4. Sathya P, Martin S, Alvarez F. Nonalcoholic fatty liver disease (NAFLD) in children. Curr Opin Pediatr. 2002 Oct;14(5):593-600.
5. Roberts EA. Nonalcoholic steatohepatitis in children. Curr Gastroenterol Rep. 2003 Jun;5(3):253-9.
6. Kagansky N, Levi S, Keter D. A high preva- lence of NAFL in an octogenarian popula- tion. Gastroenterology. 2003 Apr;Suppl.1 124(4):A-745.
7. Mendler M, Schoenfield LJ. Fatty liver: non- alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Available at: http://www.medicinenet.com/ Fatty_Liver/article.htm. Accessed November 24, 2003.
8. Angulo P. Nonalcoholic fatty liver disease. N Engl J Med. 2002 Apr 18;346(16):1221-31.
9. Clark JM, Solga SS, Horska A, et al. Prevalence of fatty liver in overweight adults with type 2 diabetes. Gastroenterology. 2003 Apr;Suppl. 1 124(4):A-702.
10. Shaffer EA. Nonalcoholic steatohepatitis: more than just being fat. Can J Gastroenterol. 2002 May;16(5):318-21.
11. Kral JG, Schaffner F, Pierson RN Jr, Wang J. Body fat topography as an independent pre- dictor of fatty liver. Metabolism. 1993 May;42(5):548-51.
12. Brady LM, Fox ES, Fimmel CJ. Polyenylphosphatidylcholine inhibits PDGF- induced proliferation in rat hepatic stellate cells. Biochem Biophys Res Commun. 1998 Jul 9;248(1):174-9.
13. Reid AE. Nonalcoholic steatohepatitis. Gastroenterology. 2001 Sep;121(3):710-23.
14. Lombardi B. Considerations on the patho- genesis of fatty liver. Lab Invest. 1966 Jan;15(1 Pt 1):1-20.
15. Chitturi S, Farrell GC. Etiopathogenesis of nonalcoholic steatohepatitis. Semin Liver Dis. 2001;21(1):27-41.
16. McCullough AJ. Update on nonalcoholic fatty liver disease. J Clin Gastroenterol. 2002 Mar;34(3):255-62.
17. Chiemprabha A, Smith R, Vieira J, et al. Prevalence and characterization of nonalco- holic fatty liver disease in patients with hypertriglyceridemia. Gastroenterology. 2003 Apr; Suppl.1 124(4):A-744.
18. Born T, Ong JP, Schlauch K, et al. Insulin resistance, serum leptin and fibrosis in non- alcoholic fatty liver disease (NAFL). Gastroenterology. 2003 Apr; Suppl.1 124(4):A-748.
19. Dixon JB, Bhathal PS, O’Brien PE. Nonalcoholic fatty liver disease: predictors of nonalcoholic steatohepatitis and liver fibrosis in the severely obese. Gastroenterology. 2001 Jul;121(1):91-100.
20. Keeffe EB. Nonalcoholic fatty liver disease: simple steatosis versus nonalcoholic steato- hepatitis with fibrosis. Gastroenterol Disord. 2002;2(2):91-3.
21. Sheth SG, Gordon FD, Chopra S. Nonalcoholic steatohepatitis. Ann Intern Med.1997 Jan 15;126(2):137-45.
22. Clark JM, Diehl AM. Nonalcoholic fatty liver disease: an underrecognized cause of cryptogenic cirrhosis. JAMA. 2003 Jun 11;289(22):3000-4.
23. Matteoni CA, Younossi ZM, Gramlich T, Boparai N, Liu YC, McCullough AJ. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology. 1999 Jun;116(6):1413-9.
24. Marrero JA, Fontana RJ, Su GL, Conjeevaram HS, Emick DM, Lok AS. NAFLD may be a common underlying liver disease in patients with hepatocellular carci- noma in the United States. Hepatology. 2002 Dec;36(6):1349-54.
25. Kitada T, Seki S, Sakaguchi H, et al. Hepatocyte proliferative activity in non-alco- holic steatohepatitis. Gastroenterology 2003 Apr; Suppl.1 124(4):A-747.
26. Ma X, Zhao J, Lieber CS. Polyenylphosphatidylcholine attenuates non- alcoholic hepatic fibrosis and accelerates its regression. J Hepatol.1996 May;24(5):604-13.
27. Lieber CS. Role of oxidative stress and antioxidant therapy in alcoholic and nonal- coholic liver diseases. Adv Pharmacol. 1997;38:601-28.
28. Horejsova M, Urban J. The effect of polyene- phosphatidylcholine (Essentiale forte) in the treatment of liver steatosis and ultrasound findings—preliminary study. Cas Lek Cesk. 1994 Jun 13;133(12):366-9.
29. Li J, Kim CI, Leo MA, Mak KM, Rojkind M, Lieber CS. Polyunsaturated lecithin prevents acetaldehyde-mediated hepatic collagen accumulation by stimulating collagenase activity in cultured lipocytes. Hepatology. 1992 Mar;15(3):373-81.
30. Stoffel W, Darr W, Assmann G. Pleomorphic functions of highly unsaturated phospho lipids in biological membranes and serum lipoproteins. Med Welt. 1978 Jan 27;29(4):124-31.
31. Klimov AN, Konstantinov VO, Lipovetsky BM, et al. “Essential” phospholipids versus nicotinic acid in the treatment of patients with type IIb hyperlipoproteinemia and ischemic heart disease. Cardiovasc Drugs Ther. 1995 Dec;9(6):779-84.
32. Aleynik SI, Leo MA, Takeshige U, Aleynik MK, Lieber CS. Dilinoleoylphospha- tidylcholine is the active antioxidant of polyenylphosphatidylcholine. J Investig Med. 1999 Nov;47(9):507-12.
33. American Gastroenterological Association medical position statement: nonalcoholic fatty liver disease. Gastroenterology. 2002 Nov;123(5):1702-4.
34. Capron JP, Delamarre J, Dupas JL, Braillon A, Degott C, Quenum C. Fasting in obesity: another cause of liver injury with alcoholic hyaline? Dig Dis Sci. 1982 Mar;27(3):265-8.
35. Keeffe EB, Adesman PW, Stenzel P, Palmer RM. Steatosis and cirrhosis in an obese dia- betic. Resolution of fatty liver by fasting. Dig Dis Sci. 1987 Apr;32(4):441-5.
36. Poordad FF. Fatty liver disease: the new epi- demic. Audio-Digest Gastroenterology. 17:01(Feb 1),2003.
37. Patton HM, Patel K, Vallee M. Steatosis influences the early virologic response rate in patients with chronic hepatitis C infection. Gastroenterology. 2003 Apr;Suppl.1 124(4):A703.
38. Patel K, Patton HM, Vallee M, et al. Steatosis influences the relapse rate in chronic hepatitis C genotype-1 infection. Gastroenterology. 2003 Apr;Suppl. 1 124(4):A782-3.
39. Antunez I, Aponte N, Fernandez A, et al. Steatosis as a predictive factor for treatment response in patients with chronic hepatitis C. Gastroenterology. 2003 Apr; Suppl.1 124(4):A779.
40. Hill D, Diehl AM, Tsukamoto H, Shedlofsky S, McClain CJ. Cytokines and liver disease. In Cytokines in Health and Disease. 2nd ed. New York, NY: Marcel Dekker, Inc.;1997.
41. Marchesini G, Brizi M, Bianchi G, et al. Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes. 2001 Aug;50(8):1844-50.
42. Marchesini G, Bugianesi E, Forlani G, et al. Nonalcoholic fatty liver, steatohepati- tis, and the metabolic syndrome. Hepatology. 2003Apr;37(4):917-23.43. Bhandari R. Understanding nonalcoholic fatty liver disease. Available at: http://www.drbhandari.com
44. Canbakan B, Ozgulle S, Hatemi I, et al. Biochemical, radiological, and histological correlates in patients with non-alcoholic fatty liver disease with or without ALT elevation. J Hepatol. 2003;38 (suppl 2):A3764.
45. Mofrad P, Contos MJ, Haque M, et al. Clinical and histologic spectrum of nonalco- holic fatty liver disease associated with nor- mal ALT values. Hepatology. 2003 Jun;37(6):1286-92.
46. Lonardo A, Bellini M, Tondelli E, et al. Nonalcoholic steatohepatitis and the “bright liver syndrome”: should a recently expanded clinical entity be further expanded? Am J Gastroenterol.1995 Nov;90(11):2072-4.
47. Rofsky NM, Fleishaker H. CT and MRI of diffuse liver disease. Semin Ultrasound CT MR. 1995 Feb;16(1):16-33.
48. Saadeh S, Younossi ZM, Remer EM, et al. The utility of radiological imaging in nonal- coholic fatty liver disease. Gastroenterology. 2002 Sep;123(3):745-50.
49. Laurin J. Motion - all patients with NASH need to have a liver biopsy: arguments against the motion. Can J Gastroenterol. 2002 Oct;16(10):722-6.