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Liver Cirrhosis (Holistic)

Liver Cirrhosis (Holistic)

About This Condition

Get added support for this serious disease by taking care of your nutritional needs. According to research or other evidence, the following self-care steps may be helpful.
  • Stop drinking

    Head off additional liver damage by avoiding alcohol

  • Balance protein and amino acids

    Work with a knowledgeable health professional to determine that amount of protein or specific amino acids that will meet your daily needs without overtaxing your liver

  • Discover SAMe

    Taking 1,200 mg a day of this nutritional supplement can improve liver function, bile flow, and survival

  • Try milk thistle

    Protect liver cells and improve function by taking a daily herbal supplement delivering 420 to 600 mg of silymarin

  • Get to know phosphatidylcholine

    Take 900 mg a day of this nutritional supplement to improve liver function

About

About This Condition

Cirrhosis is a condition of severe damage to the liver that impairs its ability to function normally.

In the United States, the most common cause of liver cirrhosis is chronic alcoholism . Liver cirrhosis may also result from chronic viral infection of the liver ( hepatitis types B, C, and D) and a number of inherited diseases, such as cystic fibrosis , hemochromatosis, and Wilson’s disease . If severe, liver cirrhosis may lead to liver failure and death. In the Western world, liver cirrhosis is the third leading cause of death in people from ages 45 to 65 (after cardiovascular disease and cancer).1 Liver cirrhosis may also cause a dangerous brain abnormality called portal-systemic encephalopathy (PSE), which may lead to coma. Another form of cirrhosis, primary biliary cirrhosis (PBC), damages the bile ducts in the liver, and occurs primarily in women over 35 years of age. The cause of PBC is not known.

Symptoms

Many people with cirrhosis have no symptoms for years. Others may have weakness, loss of appetite, malaise, and weight loss. With blocked bile flow, it is common for people with cirrhosis to have jaundice, itching, and fatty yellow skin nodules. Later in the disease, there may be massive bleeding inside the throat, brain abnormalities due to accumulation of ammonia in the blood, liver failure, and death.

Healthy Lifestyle Tips

Alcoholism is the leading cause of liver cirrhosis in the Western world. Drinking too much alcohol also impairs the absorption and accelerates loss of several nutrients.2 , 3 , 4 Therefore, avoidance of alcohol is strongly recommended for people with liver cirrhosis. Alcohol is directly toxic to the liver. In people with alcohol-induced liver cirrhosis, even moderate alcohol consumption increases the risk of portal hypertension, a dangerous blood pressure abnormality in the liver’s circulation.5

Eating Right

The right diet is the key to managing many diseases and to improving general quality of life. For this condition, scientific research has found benefit in the following healthy eating tips.

Recommendation Why
Get enough protein, but not too much
Getting adequate protein is essential, but because of the danger of ammonia toxicity, a doctor should closely supervise any changes in protein intake.

Adequate protein intake is essential for people with alcoholic liver cirrhosis, because this condition often results in significant protein, as well as calorie, deficiency.6 However, people with liver cirrhosis may be unable to tolerate normal amounts of dietary protein because the cirrhotic liver is less able to detoxify ammonia, a major product of protein digestion. Ammonia toxicity contributes to PSE. The amount of protein that can be tolerated by people with cirrhosis varies considerably.7 In these people, there is only a small margin of safety when treating protein deficiency. Extreme caution must be exercised when changing their protein intake. A doctor familiar with this disease should closely supervise any changes in dietary protein intake by people with cirrhosis.

Watch the copper
Some people with cirrhosis may have an excess of copper in the liver. If this is the case, avoid foods rich in copper, such as chocolate, shellfish, and liver.

Some people with cirrhosis and impaired bile flow (such as in Wilson’s disease or PBC) may have an excess amount of copper accumulate in the liver.8 , 9 If laboratory tests confirm copper excess, most doctors would recommend avoiding foods rich in copper (such as chocolate, shellfish, and liver) along with medical treatment to reduce copper stores.10

Supplements

What Are Star Ratings?

Our proprietary “Star-Rating” system was developed to help you easily understand the amount of scientific support behind each supplement in relation to a specific health condition. While there is no way to predict whether a vitamin, mineral, or herb will successfully treat or prevent associated health conditions, our unique ratings tell you how well these supplements are understood by some in the medical community, and whether studies have found them to be effective for other people.

For over a decade, our team has combed through thousands of research articles published in reputable journals. To help you make educated decisions, and to better understand controversial or confusing supplements, our medical experts have digested the science into these three easy-to-follow ratings. We hope this provides you with a helpful resource to make informed decisions towards your health and well-being.

3 Stars Reliable and relatively consistent scientific data showing a substantial health benefit.

2 Stars Contradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit.

1 Star For an herb, supported by traditional use but minimal or no scientific evidence. For a supplement, little scientific support.

Supplement Why
3 Stars
SAMe
1,200 mg daily
Taking SAMe may improve liver function, bile flow, and survival.

Large amounts of SAMe (S-adenosylmethionine) may improve survival and liver function in alcoholic liver cirrhosis. A double-blind trial found that 1,200 mg of SAMe per day for two years significantly decreased the overall death rate and the need for liver transplantation in people with alcoholic liver cirrhosis, particularly in those with less advanced liver disease.11 Preliminary trials suggest that lower amounts of SAMe (180 mg per day in one trial12 and 800 mg per day in another13) may improve liver function in people with liver cirrhosis. SAMe supplementation has been shown to reverse the depletion of glutathione , an important antioxidant required for liver function.14It has also been shown to aid in the resolution of blocked bile flow (cholestasis), a common complication of liver cirrhosis.15 , 16

2 Stars
Acetyl-L-Carnitine
2 grams twice a day for 3 months
A double-blind trial suggests that supplementing with acety-l-carnitine may improve mental and neurological function in people whose cirrhosis has impaired function.
In double-blind trials, supplementing with acety-L-carnitine (2 grams twice a day for three months) improved fatigue and various measures of mental and neurological function in people with impaired function (minimal hepatic encephalopathy) due to cirrhosis.17 , 18
2 Stars
Beta-Glucan, Inulin, Pectin, and Resistant Starch
10 grams total fermentable fiber daily
In a study of people with cirrhosis, supplementing with fermentable fiber (containing equal parts of beta-glucan, inulin, pectin, and resistant starch) improved liver and brain function.

In a study of people with cirrhosis, supplementing with 10 grams of fermentable fiber per day (containing equal parts of beta-glucan, inulin, pectin, and resistant starch) for 30 days resulted in an improvement in liver function.19 The impaired brain function that often accompanies cirrhosis of the liver (hepatic encephalopathy) also improved.

2 Stars
Branched-Chain Amino Acids
At least 5 grams daily, up to 0.24 grams per 2.2 lbs (1 kg) body weight per day
Under a doctor’s supervision, supplementing with branched-chain amino acids may correct an imbalance of amino acids and improve cirrhosis symptoms.

In addition to protein deficiency, liver cirrhosis is characterized by low blood levels of branched-chain amino acids (BCAAs) in relation to other amino acids .20 This imbalance may contribute to the development of PSE.21 BCAA supplementation could be a way to correct this problem, as well as to provide a source of needed protein, but its effectiveness is unclear.22 BCAAs (isoleucine, leucine, and valine) represent a good protein source for people with cirrhosis because they are less likely to induce PSE. A controlled study of protein-intolerant people with cirrhosis showed that BCAA supplementation corrected abnormal protein metabolism about as well as an equivalent amount of dietary protein without inducing PSE as frequently.23 In a small double-blind trial, people with liver cirrhosis taking 5 grams per day of BCAAs had significant improvement in their ability to process protein.24

However, treatment trials using BCAAs alone or in solutions containing other amino acids in people with cirrhosis and PSE have reported conflicting results.25 , 26 , 27 , 28 It may be that certain people with liver cirrhosis can benefit from supplementation with BCAAs while others cannot, for reasons that are unclear.29 In a double-blind trial, people with liver cirrhosis and PSE received 0.24 grams per 2.2 pounds body weight (approximately 16–17 grams per day) of BCAAs for 15 days, after which most experienced significant improvement in brain function, mental status, and protein metabolism. Those who continued taking BCAAs for three months also had mild improvement in liver function tests.30

Therapeutic effects of oral BCAAs have also been shown in children with liver failure31 and in adults with cirrhosis of the liver without PSE.32 Overall, it appears that BCAA supplementation does not always help in cirrhosis, but some people with and without PSE may benefit. A qualified doctor must closely supervise such BCAA supplementation.

2 Stars
L-Ornithine-L-Aspartate
18 grams daily of L-ornithine-L-aspartate
As both a supplement and injection, L-ornithine-L-aspartate has been shown to significantly improve liver function, mental status, and brain function.

L-ornithine-L-aspartate (OA) is a nutritional supplement that has been investigated as a treatment for cirrhosis and hepatic encephalopathy. In a double-blind trial, participants taking 18 grams of OA for 14 days had significant improvements in liver function, mental status, and brain function.33 Similar benefits have also been demonstrated using injections of OA.34 , 35

2 Stars
Milk Thistle
420 mg of silymarin daily
Supplementing with milk thistle may protect liver cells and improve function.

An extract of milk thistle  (Silybum marianum) that is high in a flavonoid compound known as silymarin may improve liver function and increase survival in people with cirrhosis. Clinical trials have shown that silymarin (420–600 mg per day) improves liver function tests and protects liver cells against oxidative damage in people with alcohol-related liver disease.36 , 37 , 38 , 39 However, evidence is conflicting regarding the ability of silymarin to prolong survival of people with liver cirrhosis. In one double-blind trial, a significant increase in survival was found in people with cirrhosis who were given 140 mg of silymarin three times a day for approximately two years.40 Positive results were also found in a 12-month controlled study of adults with diabetes and alcoholic liver cirrhosis taking the same daily amount of silymarin.41 However, another double-blind trial found that 150 mg of silymarin three times a day for two years had no significant effect on survival among alcoholics with liver cirrhosis.42

For people with chronic liver disease, milk thistle extract may be taken long-term. Milk thistle extracts containing 80% silymarin are commercially available and may be taken in amounts that deliver 420 mg of silymarin per day.

2 Stars
Peony
Under medical supervision: take the Chinese herbal formula shakuyaku-kanzo-to
One trial showed that the Chinese formula shakuyaku-kanzo-to (containing white peony and licorice roots) relieved muscle cramps due to liver cirrhosis.

One double-blind trial showed that the Chinese formula shakuyaku-kanzo-to (containing white peony and licorice roots) effectively relieved muscle cramps due to cirrhosis of the liver.43 This formula is approved by the Japanese Ministry of Health and Welfare for cirrhosis-induced muscle cramps.

2 Stars
Phosphatidyl Choline
900 mg phosphatidyl choline per day
Phosphatidylcholine breaks down scar tissue in the liver and may be able to reverse tissue changes that cause cirrhosis.

Phosphatidylcholine (PC) breaks down scar tissue in the liver and may be able to reverse tissue changes that cause cirrhosis.44 In animal studies, PC has been repeatedly shown to prevent or reverse the progression of alcohol-induced cirrhosis,45 , 46 , 47 but this has not yet been demonstrated in humans. In a controlled trial, Czech researchers found that PC supplementation (900 mg per day for four months) improved liver function in people with cirrhosis.48

2 Stars
Sea Buckthorn
15 grams three times daily of sea buckthorn extract
Preliminary research suggests that sea buckthorn may improve indicators of liver damage.
Sea buckthorn has been shown to protect the liver from damage in animal studies,49 and to reduce blood indicators of liver damage in preliminary human studies.50. In a controlled trial,51 80% of people with cirrhosis who took 15 grams three times daily of sea buckthorn extract (potency or standardization not stated) had blood indicators of liver damage return to normal within six months, compared to 56% of a group taking a B-complex vitamin.
2 Stars
Sho-Saiko-To (Bupleurum, Peony, Pinellia, Cassia, Ginger, Jujube, Asian Ginseng, Asian Scullcap, and Licorice)
2.5 grams of the Chinese herbal formula sho-saiko-to three times daily
The Chinese herb bupleurum is a component of the formula sho-saiko-to, which was shown in one preliminary trial to liver cancer risk in people with liver cirrhosis.

The Chinese herb bupleurum is an important component of the formula known as sho-saiko-to. Sho-saiko-to was shown in one preliminary trial to reduce the risk of liver cancer in people with liver cirrhosis.52 The amount of this formula used was 2.5 grams three times daily.

2 Stars
Zinc
Take under medical supervision: 135 to 215 mg daily
Supplementing with zinc may correct the deficiency common in alcoholic liver cirrhosis and may correct the impaired taste function that people with cirrhosis often experience.

Alcoholic liver cirrhosis is associated with zinc deficiency.53 , 54 In a double-blind trial, zinc acetate supplementation (200 mg three times daily, providing a total of 215 mg of elemental zinc per day), given to cirrhosis patients for seven days, significantly improved portal-systemic encephalopathy (PSE).55 A second trial achieved similar results after three months of treatment 56 and a third trial found a beneficial effect from 6 months of treatment with 51 mg per day of zinc in the form of zinc L-carnosine complex.57 People with cirrhosis sometimes have impaired taste function, and it has been suggested that zinc deficiency may be the cause of this abnormality. Although one study demonstrated that taste problems in cirrhosis are due to the disease process itself and not to zinc deficiency,58 a double-blind trial showed that 200 mg three times per day of zinc sulfate (providing 135 mg of elemental zinc per day) for six weeks significantly improved taste function in people with alcoholic liver cirrhosis.59 A doctor should supervise long-term supplementation of zinc in these amounts.

1 Star
Bile Acids (Primary Biliary Cirrhosis)
Refer to label instructions
People with cirrhosis have decreased secretion of bile acids. Supplementing with bile acids may improve bile composition and delay disease progression in primary biliary cirrhosis.

People with cirrhosis have decreased secretion of bile acids.60 Supplementation with bile acids (such as ursodeoxycholic acid and tauroursodeoxycholic acid) may improve the composition of bile and delay disease progression in primary biliary cirrhosis (PBC). In one trial, people with PBC were followed for five to nine years. Those who took 13–15 mg per 2.2 pounds body weight of ursodeoxycholic acid (about 900–1200 mg) per day had improved liver function tests and significantly delayed progression to cirrhosis.61 Several other trials have confirmed that bile acids improve liver function in people with PBC.62 , 63 , 64 , 65 , 66 Commercial supplements of bile acids are available as ox bile concentrates. However, these ox bile preparations contain other types of bile acids than those used in PBC research. The effectiveness and appropriate amount of ox bile concentrates in the treatment of PBC is unknown.

1 Star
L-Carnitine
Refer to label instructions
L-carnitine injections have been used to improve circulation to the liver in people with cirrhosis.

L-carnitine injections have been used to improve circulation to the liver in people with cirrhosis,67 but trials of the oral supplement are lacking.

1 Star
Selenium
Refer to label instructions
People with liver cirrhosis often have low selenium levels and a greater need for antioxidants. In one study, selenium improved liver function in people with alcoholic cirrhosis.

Selenium levels have been found to be low in people with liver cirrhosis68 and the need for antioxidants has been found to be increased.69 A small, preliminary trial suggested that 100 mcg per day of selenium may improve liver function in people with alcoholic cirrhosis.70 Larger, double-blind trials of selenium in people with liver cirrhosis are needed.

1 Star
Vitamin E
Refer to label instructions
Vitamin E has been shown to decrease damage in cirrhotic livers and may reduce immune abnormalities that contribute to the development of the disease.

Vitamin E has been shown to decrease damage in cirrhotic livers and may reduce immune abnormalities that contribute to the development of the disease.71 However, a study reported that supplementation of 500 IU per day of vitamin E for one year failed to influence laboratory tests, liver function, survival or hospitalization rates in people with alcoholic cirrhosis.72 Further clinical trials are needed to determine if any benefits may be expected from vitamin E supplementation in people with liver cirrhosis.

References

1. Beers MH, Berkow R (eds). The Merck Manual, 17th ed. Whitehouse Station, NJ: Merck and Co., Inc., 1999, 372-4.

2. Halsted CH. Alcohol: medical and nutritional effects. In Ziegler EE, Filer LJ (eds). Present Knowledge in Nutrition, 7th ed. ILSI Press, Washington, DC, 1996, 553.

3. Roggin GM, Iber FL, Kater RM, Tabon F. Malabsorption in the chronic alcoholic. Johns Hopkins Med J 1969;125:321-30.

4. Roggin GM, Iber FL, Linscheer WG. Intraluminal fat digestion in the chronic alcoholic. Gut 1972;13:107-11.

5. Luca A, Garcia-Pagan JC, Bosch J, et al. Effects of ethanol consumption on hepatic hemodynamics in patients with alcoholic cirrhosis. Gastroenterology 1997;112:1284-9.

6. Lochs H, Plauth M. Liver cirrhosis: rationale and modalities for nutritional support—the European Society of Parenteral and Enteral Nutrition consensus and beyond. Curr Opin Clin Nutr Metab Care 1999;2:345-9.

7. Lieber CS. Nutrition in liver disorders. In: Shils ME, Olson JA, Shike M, Ross AC (eds). Modern Nutrition in Health and Disease, 9th ed. Baltimore, MD: Williams and Wilkins, 1999, 1179-80.

8. Rodriguez-Moreno F, Gonzalez-Reimers E, Santolaria-Fernandez F, et al. Zinc, copper, manganese, and iron in chronic alcoholic liver disease. Alcohol 1997;14:39-44.

9. Gibbs K, Walshe JM. Studies with radioactive copper (64 Cu and 67 Cu); the incorporation of radioactive copper into caeruloplasmin in Wilson's disease and in primary biliary cirrhosis. Clin Sci 1971;41:189-202.

10. Lieber CS. Nutrition in liver disorders. In: Shils ME, Olson JA, Shike M, Ross AC (eds). Modern Nutrition in Health and Disease, 9th ed. Baltimore, MD: Williams and Wilkins, 1999, 1179-80.

11. Mato JM, Camara J, Fernandez de Paz J, et al. S-adenosylmethionine in alcoholic liver cirrhosis: a randomized, placebo-controlled, double-blind, multicenter clinical trial. J Hepatol 1999;30:1081-9.

12. Miglio F, Stefanini GF, Corazza GR, et al. Double-blind studies of the therapeutic action of S-Adenosylmethionine (SAMe) in oral administration, in liver cirrhosis and other chronic hepatitides. Minerva Med 1975;66:1595-9 [In Italian].

13. Gorbakov VV, Galik VP, Kirillov SM. Experience in heptral treatment of diffuse liver diseases. Ter Arkh 1998;70:82-6 [in Russian].

14. Loguercio C, Nardi G, Argenzio F, et al. Effect of S-adenosyl-L-methionine administration on red blood cell cysteine and glutathione levels in alcoholic patients with and without liver disease. Alcohol Alcohol 1994;29:597-604.

15. Frezza M, Centini G, Cammareri G, et al. S-adenosylmethionine for the treatment of intrahepatic cholestasis of pregnancy. Results of a controlled clinical trial. Hepatogastroenterology 1990;37 Suppl 2:122-5.

16. Frezza M, Surrenti C, Manzillo G, et al. Oral S-adenosylmethionine in the symptomatic treatment of intrahepatic cholestasis. A double-blind, placebo-controlled study. Gastroenterology 1990;99:211-5.

17. Malaguarnera M, Gargante MP, Cristaldi E, et al. Acetyl-L-carnitine treatment in minimal hepatic encephalopathy. Dig Dis Sci 2008;53:3018-25.

18. Malaguarnera M, Vacante M, Giordano M, et al. Oral acetyl-L-carnitine therapy reduces fatigue in overt hepatic encephalopathy: a randomized, double-blind, placebo-controlled study. Am J Clin Nutr. 2011;93:799-808

19. Liu Q, Duan ZP, Ha DK, et al. Synbiotic modulation of gut flora: effect on minimal hepatic encephalopathy in patients with cirrhosis. Hepatology 2004;39:1441-9.

20. Lieber CS. Nutrition in liver disorders. In: Shils ME, Olson JA, Shike M, Ross AC (eds). Modern Nutrition in Health and Disease, 9th ed. Baltimore, MD: Williams and Wilkins, 1999, 1179-80.

21. Beers MH, Berkow R (eds). The Merck Manual, 17th ed. Whitehouse Station, NJ: Merck and Co., Inc., 1999, 362-4.

22. Nompleggi DJ, Bonkovsky HL. Nutritional supplementation in chronic liver disease: an analytical review. Hepatology 1994;19:518-33 [review].

23. Horst D, Grace ND, Conn HO, et al. Comparison of dietary protein with an oral, branched chain-enriched amino acid supplement in chronic portal-systemic encephalopathy: a randomized controlled trial. Hepatology 1984;4:279-87.

24. Okita M, Watanabe A, Nagashima H. Treatment of liver cirrhosis with branched chain amino acid-supplemented diet. Gastroenterol Jpn 1981;16:389-92.

25. Maddrey WC. Branched chain amino acid therapy in liver disease. J Am Coll Nutr 1985;4:639-50 [review].

26. Wahren J, Denis J, Desurmont P, et al. Is intravenous administration of branched chain amino acids effective in the treatment of hepatic encephalopathy? A multicenter study. Hepatology 1983;3:475-80.

27. Egberts E-H, Schomerus H, Hamster W, Jürgens P. Branched chain amino acids in the treatment of latent portosystemic encephalopathy. A doublel-blind placebo-controlled crossover study. Gastroenterology 1985;88:887-95.

28. Muto Y, Sato S, Watanabe A, et al. Effects of oral branched-chain amino acid granules on event-free survival in patients with liver cirrhosis. Clin Gastroenterol Hepatol 2005;3:705-13.

29. Dioguardi FS, Brigatti M, Dell'Oca M, et al. Effects of chronic oral branched-chain amino acid supplementation in a subpopulation of cirrhotics. Clin Physiol Biochem 1990;8:101-7.

30. Marchesini G, Dioguardi FS, Bianchi GP, et al. Long-term oral branched-chain amino acid treatment in chronic hepatic encephalopathy. A randomized double-blind casein-controlled trial. The Italian Multicenter Study Group. J Hepatol 1990;11:92-101.

31. Chin SE, Shepherd RW, Thomas BJ, et al. Nutritional support in children with end-stage liver disease: a randomized crossover trial of a branched-chain amino acid supplement. Am J Clin Nutr 1992;56:158-63.

32. Kato M, Miwa Y, Tajika M, et al. Preferential use of branched-chain amino acids as an energy substrate in patients with liver cirrhosis. Internal Med 1998;37:429-34.

33. Stauch S, Kircheis G, Adler G, et al. Oral L-ornithine-L-aspartate therapy of chronic hepatic encephalopathy: results of a placebo-controlled double-blind study. J Hepatol 1998;28:856-64.

34. Kircheis G, Nilius R, Held C, et al. Therapeutic efficacy of L-ornithine-L-aspartate infusions in patients with cirrhosis and hepatic encephalopathy: results of a placebo-controlled, double-blind study. Hepatology 1997;25:1351-60.

35. Staedt U, Leweling H, Gladisch R, et al. Effects of ornithine aspartate on plasma ammonia and plasma amino acids in patients with cirrhosis. A double-blind, randomized study using a four-fold crossover design. J Hepatol 1993;19:424-30.

36. Salmi HA, Sarna S. Effect of silymarin on chemical, functional and morphological alterations of the liver. A double-blind controlled study. Scand J Gastroenterol 1982;17:517-21.

37. Feher J, Deak G, Muzes G, et al. Liver-protective action of silymarin therapy in chronic alcoholic liver diseases. Orv Hetil 1989;130:2723-7 [in Hungarian].

38. Muzes G, Deak G, Lang I, et al. Effect of silymarin (Legalon) therapy on the antioxidant defense mechanism and lipid peroxidation in alcoholic liver disease (double blind protocol.) Orv Hetil 1990:131:863-6 [in Hungarian].

39. Velussi M, Cernogoi AM, De Monte A, et al. Long-term (12 months) treatment with an antioxidant drug (silymarin) is effective on hyperinsulinemia, exogenous insulin need and malondialdehyde levels in cirrhotic diabetic patients. J Hepatology 1997;26:871-9.

40. Ferenci P, Dragosics B, Dittrich H, et al. Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. J Hepatol 1989;9:105-13.

41. Velussi M, Cernogoi AM, De Monte A, et al. Long-term (12 months) treatment with an antioxidant drug (silymarin) is effective on hyperinsulinemia, exogenous insulin need and malondialdehyde levels in cirrhotic diabetic patients. J Hepatology 1997;26:871-9.

42. Pares A, Planas R, Torres M, et al. Effects of silymarin in alcoholic patients with cirrhosis of the liver: results of a double-blind, randomized and multicenter trial. J Hepatol 1998;28:731-3.

43. Kumada T, et al. Effect of shakuyaku-kanzo-to (Tsumura TJ-68) on muscle cramps accompanying cirrhosis in a placebo-controlled double-blind parallel study. J Clin Ther Med 1999;15:499-523.

44. Ma X, Zhao J, Lieber CS. Polyenylphosphatidylcholine attenuates non-alcoholic hepatic fibrosis and accelerates its regression. J Hepatol 1996;24:604-13.

45. Lieber CS, Robins SJ, Leo MA. Hepatic phosphatidylethanolamine methyltransferase activity is decreased by ethanol and increased by phosphatidylcholine. Alcohol Clin Exp Res 1994;18:592-5.

46. Lieber CS, Robins SJ, Li J, et al. Phosphatidylcholine protects against fibrosis and cirrhosis in the baboon. Gastroenterology 1994;106:152-9.

47. Lieber CS, DeCarli LM, Mak KM, et al. Attenuation of alcohol-induced hepatic fibrosis by polyunsaturated lecithin. Hepatology 1990;12:1390-8.

48. Fassati P, Horejsi J, Fassati M, et al. Essential choline phospholipids and their effect on HBsAg and selected biochemical tests in cirrhosis of the liver. Cas Lek Cesk 1981 22;120:56-60 [in Czech].

49. Suryakumar G, Gupta A. Medicinal and therapeutic potential of Sea buckthorn (Hippophaerhamnoides L.). J Ethnopharmacol 2011;138:268-78.

50. Huang DL, Chang XZ, Gui HN, et al. Analysis of 156 cases of chronic hepatitis treated with sea buckthorn. ZhongxiyiJieheZazhi 1991;11:697-6980 [in Chinese].

51. Gao ZL, Gu XH, Cheng FT, Jiang FH. Effect of sea buckthorn on liver fibrosis: a clinical study. World J Gastroenterol 2003;9:1615-7.

52. Yamamoto S, Oka H, Kanno T, et al. Controlled prospective trial to evaluate Shosaiko-to in preventing hepatocellular carcinoma in patients with cirrhosis of the liver. Gan To Kagaku Ryoho (Jpn J Cancer Chemother) 1989;16:1519-24 [in Japanese].

53. Taniguchi S, Kaneto K, Hamada T. Acquired zinc deficiency associated with alcoholic liver cirrhosis. Int J Dermatol 1995;34:651-2.

54. Scholmerich J, Lohle E, Kottgen E, Gerok W. Zinc and vitamin A deficiency in liver cirrhosis. Hepatogastroenterology 1983;30:119-25.

55. Reding P, Duchateau J, Bataille C. Oral zinc supplementation improves hepatic encephalopathy. Results of a randomised controlled trial. Lancet 1984;2(8401):493-5.

56. Marchesini G, Fabbri A, Bianchi G, et al. Zinc supplementation and amino acid-nitrogen metabolism in patients with advanced cirrhosis. Hepatology 1996;23:1084-92.

57. Takuma Y, Nouso K, Makino Y, et al. Clinical trial: oral zinc in hepatic encephalopathy. Aliment Pharmacol Ther 2010;32:1080-90

58. Sturniolo GC, D'Inca R, Parisi G, et al. Taste alterations in liver cirrhosis: are they related to zinc deficiency? J Trace Elem Electrolytes Health Dis 1992;6:15-9.

59. Weismann K, Christensen E, Dreyer V. Zinc supplementation in alcoholic cirrhosis. A double-blind clinical trial. Acta Med Scand 1979;205(5):361-6.

60. Vlahcevic ZR, Miller JR, Farrar JT, Swell L. Kinetics and pool size of primary bile acids in man. Gastroenterology 1971;61:85-90.

61. Angulo P, Batts KP, Therneau TM, et al. Long-term ursodeoxycholic acid delays histological progression in primary biliary cirrhosis. Hepatology 1999;29:644-7.

62. Larghi A, Crosignani A, Battezzati PM, et al. Ursodeoxycholic and tauro-ursodeoxycholic acids for the treatment of primary biliary cirrhosis: a pilot crossover study. Aliment Pharmacol Ther. 1997;11:409-14.

63. Crosignani A, Battezzati PM, Setchell KD, et al. Tauroursodeoxycholic acid for treatment of primary biliary cirrhosis. A dose-response study. Dig Dis Sci 1996;41:809-15.

64. Setchell KD, Rodrigues CM, Podda M, Crosignani A. Metabolism of orally administered tauroursodeoxycholic acid in patients with primary biliary cirrhosis. Gut 1996;38:439-46.

65. Ferri F, Bernocchi P, Fedeli S. Taurodeoxycholic acid in the treatment of primary biliary cirrhosis. A controlled study in comparison to ursodeoxycholic acid. Clin Ter 1993;143:321-6 [in Italian].

66. Pares A, Caballeria L, Rodes J, et al. Long-term effects of ursodeoxycholic acid in primary biliary cirrhosis: results of a double-blind controlled multicentric trial. UDCA-Cooperative Group from the Spanish Association for the Study of the Liver. J Hepatol 2000;32:561-6.

67. Pugliese D, Sabba C, Ettorre G et al. Acute systemic and splanchnic haemodynamic effects of l-carnitine in patients with cirrhosis. Drugs Exp Clin Res 1992;18:147-53.

68. Burk RF, Early DS, Hill KE, et al. Plasma selenium in patients with cirrhosis. Hepatology 1998;27:794-8.

69. Feher J, Lengyel G, Blazovics A. Oxidative stress in the liver and biliary tract diseases. Scand J Gastroenterol Suppl 1998;228:38-46.

70. Van Gossum A, Neve J. Low selenium status in alcoholic cirrhosis is correlated with aminopyrine breath test. Preliminary effects of selenium supplementation. Biol Trace Elem Res 1995;47:201-7.

71. Ferro D, Basili S, Practico D, et al. Vitamin E reduces monocyte tissue factor expression in cirrhotic patients. Blood 1999;93:2945-50.

72. de la Maza MP, Petermann M, Bunout D, Hirsch S. Effects of long-term vitamin E supplementation in alcoholic cirrhotics. J Am Coll Nutr 1995;14:192-6.

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