Articles

Liver Disorders

Introduction

What should I know about Liver Disorders?

The liver is our largest organ. Located in the upper right portion abdominal cavity, the liver weighs approximately three to five pounds. The liver’s primary function is to filter toxins out of the blood and break them down into harmless substances that can be eliminated from the body. At any given time, the liver contains about 300 milliliters of blood, which amounts to just under one and a half cups. The liver has many other important jobs in addition to its role as the body’s blood filter. The liver metabolizes nutrients, stores blood glucose in the form of glycogen, and aids in the digestion of fat by producing bile, to name a few of its duties.

The liver is divided into four sections called "lobes." The right lobe is the largest, followed by the left lobe. The two remaining sections, the "caudate" and "quadrate" lobes, are smaller by comparison. The right and left lobes are partitioned into compartments called "lobules." A lobule is a cluster of liver cells surrounding a central vein. A network of blood vessels called a "sinusoid" nourishes the cells inside a lobule and separates the lobules from each other. The sinusoids are lined with specialized cells called "Kupffer cells." These cells perform the liver’s filtration functions. Kupffer cells belong to a category of cells called "phagocytes," which literally means "big eaters." And indeed, Kupffer cells have a voracious appetite for foreign substances in the blood. Acting as garbage collectors for the body, Kupffer cells remove dead cells, bacteria, toxins, metabolic wastes, and any other unwanted material that may be circulating through the sinusoids.

When the liver is diseased, a number of important regulatory, metabolic, and storage functions are compromised. Because of the important and extensive roles of the liver, a diseased liver results in serious illness. Among its major functions, the liver:

    Produces bile salts Metabolizes hormones Metabolizes drugs Synthesizes glucose Forms lipoproteins Converts carbohydrates and proteins to fat Manufactures cholesterol Forms ketones from fatty acids Converts ammonia to urea Synthesizes plasma proteins Synthesizes clotting factors Stores glycogen Stores vitamins and minerals Filters and detoxifies blood Eliminates bilirubin- a waste byproduct produced when worn-out red blood cells are broken down.

Cirrhosis is one of the most serious of all liver diseases. Cirrhosis is a chronic degenerative condition characterized by progressive scarring and buildup of fibrous tissue in the liver. Liver function declines as the disease progresses. Cirrhosis is a leading cause of death among people aged 45-74 years. There are three types of cirrhosis: post-necrotic, biliary, and portal (alcoholic). Approximately 80 percent of cirrhosis cases are portal. (1) Although the major cause of portal cirrhosis is alcoholism, it can sometimes occur in non-alcohol drinkers. Since the majority of alcoholics do not develop cirrhosis, other factors clearly play a role in the development of the disease.

The liver undergoes several important alterations as cirrhosis worsens. At the beginning, fatty deposits begin to form. Alcohol displaces fat as an energy source. Fat that would normally be used as fuel then begins to accumulate. This fat buildup in the liver causes it to enlarge. This enlargement leads to alcoholic hepatitis, with inflammation and destruction of liver cells. Areas of damaged tissues called "lesions" develop in patches throughout the liver. Eventually, the liver becomes scarred and distorted by bands of fibrous tissue. Liver function is destroyed and blood flow to the liver is obstructed.

Hepatitis is inflammation of the liver. Hepatitis can result from chronic alcohol abuse, certain medications, trauma, or viral infection. Viral hepatitis is caused by infection from one or more viruses, including hepatitis A, B, C, D, and E. All forms of viral hepatitis can cause acute illness; some may lead to cirrhosis or liver cancer.

Viral hepatitis is highly contagious. People can be chronically infected and yet remain free of symptoms, unknowingly passing the virus to others. Some may become non-symptomatic carriers, never realizing they have been exposed. Those at greatest risk for contracting viral hepatitis include health care workers and students, dentists, dental hygienists, and anyone regularly exposed to infectious diseases. Other than strict adherence to universal precautions and proper sanitation, vaccinations offer the greatest protection against certain strains of the viruses.

Hepatitis A virus (HAV) is contracted by mouth, primarily through food and water that contains fecal matter. HAV infection is common in regions with poor sanitation and waste disposal, where drinking water is contaminated with sewage that contains the virus. HAV is also spread by contamination of food by infected persons. In 90 percent of all cases, people infected with the Hepatitis A virus have no symptoms. Exposure and subsequent recovery result in lifelong immunity. Persons at high risk include international travelers, household members or sexual contacts of infected persons, and those residing in facilities with poor sanitation or high rates of infection. Children are particularly vulnerable to HAV infection. The hepatitis A vaccine is a highly effective prevention tool. Good hygiene and sanitation practices are other primary preventative measures.

Hepatitis B virus (HBV) is transmitted through contact with infected blood or body fluids. In the majority of infected individuals, symptoms are mild or absent. Approximately 15 to 20 percent experience joint pain and 10 percent develop jaundice. Ten percent of those infected develop chronic HBV infection. Active chronic HBV infection is associated with high risk of cirrhosis. Those at highest risk of becoming infected include sexually active heterosexuals, homosexual men, infants born to infected mothers, health care workers, and IV drug users. Incidence of hepatitis B has decreased since the introduction of the HBV vaccine, but has increased since 1993 among the sexually active and IV drug users. Prevention is aimed at vaccinations, screening of blood, organ, and tissue donors, and universal precautions among health care workers.

Hepatitis C (HCV) is the most common form of chronic viral hepatitis. (2) Seventy percent of people with HCV infection become permanent carriers of the virus. Many develop cirrhosis within 5 to 30 years. (3) HCV is transmitted in the same manner as HBV, through contact with blood and body fluids, most often in the same risk groups. Prevention is targeted at high-risk behavior modification, screening of donors, and universal precautions. NO vaccine is available for HCV.

The most serious type of viral hepatitis, hepatitis D, is caused by infection of the hepatitis delta virus (HDV). Although hepatitis D accounts for less than 5 percent of chronic viral hepatitis infections, it leads to cirrhosis in 70 percent of cases. (4) HDV can only occur among patients with HBV who are positive for the HBs-antigen. The HBV vaccine provides protection against HDV. Other identified strains of viral hepatitis include hepatitis E and G, although the symptoms and outcomes of infection by these viruses are not well understood at this time.

Statistic

World Health Organization, 2000.

  • The majority of the worldwide hepatitis burden, with subsequent chronic hepatitis, cirrhosis and liver cancer is due to hepatitis virus B (HBV), about 1.2 million people worldwide each year.

National Center for Health Statistics and the American Liver Foundation, 1998.

    One in every 250 persons is a carrier of the hepatitis B virus. About 150,000 people are infected with hepatitis C each year. Cirrhosis is the 7th leading disease related cause of death in the US. 22,000 pregnant women are carriers of hepatitis B each year.

Signs and Symptoms

[span class=alert]The following list does not insure the presence of this health condition. Please see the text and your healthcare professional for more information.[/span]

Cirrhosis causes a variety of symptoms that manifest gradually. Many patients are symptom-free until the late stages of the disease. Early symptoms include weight loss, fatigue, nausea, and abdominal pain. "Ascites," or fluid buildup in the abdominal cavity, commonly occurs in the final stages of cirrhosis. Ascites can enlarge the abdomen to twice its normal size. New "collateral" veins are formed to bypass the liver and return blood from the GI tract to the heart. Collateral veins in the esophagus and stomach may rupture, leading to massive, often fatal, hemorrhage. The spleen may enlarge and the abdomen may be tender.

Failure of the liver to carry out its many important functions leads to a variety of serious problems. Jaundice is common. Mental confusion and coma can occur from a build up of toxins (particularly ammonia) normally metabolized by the liver. The kidneys may be unable to keep up with their heightened metabolic load, leading to renal failure. Other complications associated with liver failure include skin disorders, endocrine malfunction (including sterility, impotence, and menstrual abnormalities), and anemia.

Signs and symptoms for all forms of hepatitis are similar, although symptoms of HBV are usually the most severe. Initially, many of those infected are symptom-free. Early symptoms include headache, fatigue, appetite loss, fever, and weakness. Nausea, indigestion, gas, and intolerance of chemical odors occur as the disease worsens. Jaundice, caused by an accumulation of bilirubin in the blood, is the classic sign of hepatitis. The excess bilirubin, a waste product from the breakdown of old red blood cells normally eliminated by the liver via bile, produces the yellowing of the skin, eyes, and mucous membranes. Jaundice is often accompanied by light, clay colored stool and dark urine. The liver and spleen may become enlarged.

Many patients are asymptomatic until the late stages of the disease

General

  • Yellowing of the skin, eyes, and linings of the nose and mouth
  • Mental confusion
  • Kidney disorders
  • Skin disorders
  • Sterility
  • Impotence
  • Menstrual abnormalities

Cirrhosis

  • Weight loss
  • Fatigue
  • Nausea
  • Vague abdominal pain
  • Fluid buildup in the abdominal cavity
  • Enlarged spleen

Hepatitis

  • Headache
  • Fatigue
  • Loss of appetite
  • Fever
  • Weakness
  • Nausea
  • Indigestion
  • Gas
  • Intolerance of chemical odors
  • Jaundice

Treatment Options

Conventional

Treatment for cirrhosis works on three fronts: 1) Halting liver damage, 2) Reducing symptoms and 3) Providing the needed nutritional support.

    Alcohol and drugs, especially those metabolized by the liver should be eliminated. Sodium intake is restricted and potassium-sparing diuretics are prescribed to reduce the fluid buildup associated with ascites. Antacids are prescribed to reduce gastric acid and prevent GI bleeding. Antibiotics are given to reduce the ammonia-producing bacteria in the GI tract. Lactulose may be given to help lower the bowel pH and convert ammonia to ammonium ions. (5) The blood does not absorb ammonium ions. The anti-inflammatory drug colchicine, traditionally used in the treatment of gout, has been shown to improve symptoms and increase length of survival in some patients. (6)

There is no cure for hepatitis. The acute illness can take two to six months to resolve, and leaves the patient with varying risk for developing chronic liver disease and liver cancer. Acetaminophen and other agents metabolized by the liver should not be taken during acute illness. Alcoholic beverages should be strictly avoided. Antiviral drugs are the only course of treatment for chronic hepatitis. The goal of therapy is to normalize liver function and prevent the virus from multiplying.

    Alpha-interferon: Although it is effective in only a small group of patients with chronic hepatitis B, alpha-interferon is the antiviral agent mostly widely prescribed for the disease. (7) Interferon is a protein-based substance the body produces to fight viral infections. Synthetic alpha-interferon for use as a drug is made by recombinant DNA technology. Its effectiveness is limited, however, because it does not provide long-term protection. Lamivudine is one of a new class of antiviral drugs. It appears to be very effective and well tolerated by those with hepatitis B infection. Lamivudine often works when alpha-interferon has failed. It also appears to be extremely safe.

Nutritional Suplementation

Additional minerals: The development of abnormal fibrous tissue in cirrhosis may be linked to the levels of zinc, copper, iron, and manganese in the liver. One study found that low liver zinc and high liver copper favors fibrous tissue growth. The severity of chronic alcoholic liver disease may correlate with the liver’s elevated copper content and excretion of zinc, copper, and iron in the urine. An elevated manganese level in the liver, along with reduced urinary excretion of manganese also appears to be a factor. (8)


N-Acetyl Cysteine (NAC), S-Adenosylmethionine (SAMe)

N-acetylcysteine (NAC) is a cousin of the amino acid cysteine. NAC helps protect the liver against the damaging effects of toxins. It also promotes detoxification and regeneration of the liver once it has been damaged. NAC helps replenish liver stores of an important detoxifying compound called "glutathione." As part of the liver’s antioxidant defenses against free radicals, glutathione is an essential for the breakdown and elimination of toxins from the body. NAC also supplies sulfur, an essential dietary mineral needed for detoxification.

NAC breaks up mucous, and for this reason has been used clinically in a variety of respiratory illnesses. NAC is also beneficial in conditions that increase the amount of free radicals in the body such as HIV infection, cancer, heart disease, and cigarette smoking. An 18-dose oral course of NAC is currently the mainstay of treatment for liver toxicity caused by an overdose of the drug acetaminophen. N-acetylcysteine also appears to be useful in treating acute heavy metal poisoning. NAC is a metal "chelator," an agent that binds to heavy metals like lead and mercury, helping to eliminate them from the body. NAC protects both the liver and kidney against heavy metal damage. (9)

N-acetylcysteine has proven to be a life-saving therapy in the protection of the liver and kidneys against Amanita mushroom poisoning. (10) It helps detoxify the liver and neutralize other life-threatening challenges such as acetaminophen poisoning (11) and mercury toxicity. (12) S-adenosyl-L-methionine (SAMe), a form of the amino acid methionine, is another dietary supplement that functions in a variety of ways to support liver health. S-adenosyl-L-methionine has a broad range of effects that are currently being explored for use in liver disease.

SAMe appears to work in several different ways. For example, liver cirrhosis impairs activity of a key enzyme that helps produce SAMe. Supplemental SAMe can help make up for the loss. SAMe replenishes liver stores of glutathione and sulfur-containing amino acids, which are needed to protect the liver from toxins and free radicals.

SAMe also may help make cell membranes more "fluid," thus allowing various enzymes and other key molecules that operate within these membranes to work more efficiently. Because chronic liver disease alters the structure of cell membranes in a way that makes them less fluid, SAMe may be a key therapeutic nutrient.

In fact, very few therapeutic agents are effective for treatment of chronic liver disease. Preliminary evidence for SAMe is promising. In pilot studies, SAMe has restored obstructed bile flow and improved liver function tests. Although SAMe is known to protect the liver in various ways, long-term controlled clinical trials are needed to determine how well it can reverse the symptoms and progression of liver disease. (13)


Selenium

Selenium is an essential trace mineral that supports the immune system and fights free radicals. The body requires selenium as a mineral co-factor for a key anti-free radical enzyme called "glutathione peroxidase."

In an evaluation of 19 hospitalized patients with alcoholic cirrhosis, blood selenium levels were found to be significantly lower in the alcoholic cirrhosis patients than in healthy controls. Among 10 patients who took 100mc of selenium a day, selenium levels were significantly increased and liver function improved. (14)


Vitamin C, Vitamin E

Vitamin C and vitamin E are antioxidants that can also help protect the liver. This was demonstrated in animal experiments where laboratory rats were administered toxic doses of carbon tetrachloride. The livers in the animals that were pretreated with either vitamin C (15) or vitamin E (16) were substantially protected from tissue injury that normally produces this toxic substance.


Zinc

Zinc depletion is a common occurrence in patients with various forms of liver disease such as hepatitis, alcoholic liver disease, hepatic encephalopathy, and cirrhosis. (17) , (18) In view of zinc’s importance, taking a zinc supplements is a good idea for people with liver disease. Whether or not zinc supplements have any effect on the symptoms and progression of liver disease has not been studied in clinical trials.


L-Glutamine

Glutamine is an amino acid that boosts immune function and supports the body’s defenses against free radicals. Glutamine is used to manufacture a protein called "glutathione" that serves as a key antioxidant, protecting tissues from free radical injury. In one study, animals subjected to acetaminophen poisoning were fed a glutamine-fortified diet. Glutamine protected the liver, preserved liver glutathione stores, and prolonged survival time in these animals. Glutamine enhances immunity by boosting antioxidant protection. (19)

One particularly eye-opening study suggests that glutamine may have untapped potential for restoring liver health. In this experiment, animals that had undergone partial surgical removal of the liver were given glutamine intravenously. Within 24 hours, their livers began to regenerate. While this has yet to be demonstrated in humans, glutamine could prove to be a valuable supplemental treatment in liver surgery. (20)


Alpha-Lipoic Acid (ALA)

Alpha lipoic acid is another nutrient that benefits the liver. Alpha lipoic acid is now recognized as one of the most effective treatments for mushroom poisoning. It is an excellent antioxidant that destroys free radicals in both fat and water-based environments. What’s more, alpha lipoic acid recycles other antioxidants, Vitamin C for example, thus helping to preserve the body’s antioxidant reserves. Like NAC, it is a chelator, or binder, of heavy metals.

Alpha-lipoic acid has a number of beneficial properties observed in studies. It prevents artificially cultured HIV viruses from replicating, prevents cataracts, protects the kidneys from being damaged by excess sugar in the urine, protects islet cells in the pancreas against inflammation, preserves thymus gland tissue, and increases helper T-cells in the blood. In Europe, alpha-lipoic acid has been used as a treatment for a variety of different liver diseases. (21)

One drawback to taking alpha lipoic acid as a supplement is its rapid elimination from the body. (22) Time-release lipoic acid products are now available which allow for less frequent doses.

Herbal Suplementation


Milk Thistle

Historically, milk thistle was used as a digestive tonic; a general tonic for the spleen, stomach, liver, and gallbladder. The herb promotes bile flow and stimulates milk flow in nursing mothers. (23) Milk thistle has been clinically tested as a liver protecting herb in the treatment of various liver disorders. (24) , (25) The active constituents of milk thistle are a combination of three flavonoid-like substances that neutralize free radicals in the liver: silybin, silydianin, and silychristin. (26)

Silymarin reportedly acts by blocking the passage of toxins into liver cells, making liver cells less permeable to toxins, and by stimulating regeneration of new liver cells through increased protein synthesis. (27) Silymarin also strengthens the liver’s antioxidant defenses by increasing its glutathione supply. (28)


Picrorhiza

Picrorhiza is a perennial herb that grows at high altitude in the Himalaya mountains. The underground parts of this plant have been used in the traditional Ayurvedic healing system of India since ancient times to treat liver and lung troubles. Picrorhiza is also used to treat infectious disease, reduce fevers, and alleviate indigestion. Recently, researchers and clinicians have reported the value of picrorhiza, both root and leaf, as an immune-supporting herb.

Like milk thistle, picrorhiza may promote liver regeneration. A 1992 study found that picrorhiza stimulated protein synthesis in rat livers. The authors stated the results were comparable to milk thistle. (29)

There have been over 15 studies conducted in laboratory animals regarding the effectiveness of standardized picrorhiza as a supplement in liver health. Studies report picrorhiza benefits the liver in viral hepatitis and exposure to toxins, such as alcohol and acetaminophen, that injure the liver. (30) , (31) , (32) , (33)

Bile production often suffers when the liver is overburdened with toxins, and this is another area where picrorhiza can help. The herb restores both the volume and flow of bile. Picrorhiza has been found to be a more effective herb at normalizing bile than milk thistle hepatotoxins, including paracetamol and ethynylestradiol, which tend to have a cholestatic effect. (34)

Picrorhiza has been tested in humans with acute viral hepatitis. A recent double-blind study, picrorhiza root powder improved liver function in patients with the disease after two weeks of use at a dose of 375 mg taken three times daily. (35)

As an antioxidant for the liver, picrorhiza is reported to help maintain liver stores of glutathione and its enzyme cousin, glutathione peroxidase. (36) As glutathione return to normal, the amount of an especially potent group of free radicals lipid peroxides in damaged liver tissues goes down. Picrorhiza seems to work in concert with the body’s own free radical-fighting enzymes. (37) One note of caution: Picrorhiza may enhance the metabolism of drugs in the liver, perhaps making them less effective. (38)


Schisandra

Schisandra has been used in Chinese medicine for centuries as a kidney tonifying and relaxing herb. It has historically been used to treat cough and wheezing, spontaneous sweating, chronic diarrhea, insomnia, and forgetfulness. (39) Recent research has focused on schisandra’s ability to protect the liver from damaging toxins. (40) , (41) Liver regeneration was reported in laboratory animals following partial liver removal. (42) Other uses included are as an expectorant and cough suppressant. The herb also has antioxidant properties. (43)

Schisandra has been reported to prevent liver damage, stimulate liver repair, and support normal liver function. (44) , (45) The herb contains active ingredients called "schisandrins" that improve liver health in a number of ways. Schisandrins protect liver cell membranes, help the liver metabolize drugs, and increase the liver’s ability to store glucose as glycogen. (46) , (47)


Artichoke

The flower head of the globe artichoke has been used as a food and medicinal agent for centuries. In medicine, the globe artichoke has historically been used for poor digestion, along with "sluggish" liver, atherosclerosis, elevated cholesterol levels, and as a mild diuretic. It has reportedly been used in Europe since Roman times as a bile-stimulator and diuretic. Artichoke leaf is claimed to be a potent antioxidant. (48)

Artichoke has been reported to have significant liver protecting and regenerating effects. (49) In one study, the authors concluded that artichoke protected laboratory animals exposed to the liver toxic substance tert-butylhydroperoxide. (50) Some of the liver-protecting qualities of artichoke seem to be linked to its antioxidant capacity, due mainly to chlorogenic acid content in the leaves. Cyarin demonstrates an ability to restore healthy growth and reproduction of liver cells. (51)

Artichoke is also reported to promote bile production in the liver. (52) Bile emulsifies fats, breaking them down into small particles that can be digested. Stimulating bile flow promotes healthy digestion and absorption of nutrients. Studies have reported people with poor digestion taking artichoke, symptoms such as pain, nausea, retching, and the sensation of fullness quickly disappear. (53) Cynarin seems to be the active ingredient responsible for these results.

Diet & Lifestyle

Limiting animal protein, avoiding refined sugars and carbohydrates, and increased intake of fresh vegetables, fruits, and whole grains. Limit soda intake as well.

References

  1. Porth CM. Pathophysiology, 3rd ed. Philadelphia: JB Lippincott; 1990.
  2. View Abstract: Centers for Disease Control and Prevention. Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease. Morbidity and Mortality Weekly Report. Oct1998;47(RR-19):1-33.
  3. View Abstract: Centers for Disease Control and Prevention. Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease. Morbidity and Mortality Weekly Report. Oct1998;47(RR-19):1-33.
  4. View Abstract: Polish LB, Gallagher M, Fields HA, et al. Delta hepatitis: molecular biology and clinical and epidemiological features. Clin Microbiol Rev. Jul1993;6(3):211-29.
  5. View Abstract: Jenkins DJ, Kendall CW, Vuksan V. Inulin, oligofructose and intestinal function. J Nutr. Jul1999;129(7 Suppl):1431S-3S.
  6. View Abstract: Ben-Chetrit E, Levy M. Colchicine: 1998 update.Semin Arthritis Rheum. Aug1998;28(1):48-59.
  7. View Abstract: Torresi J, Locarnini S. Antiviral chemotherapy for the treatment of hepatitis B viral infections. Gastroenterology. Feb2000;118(2 suppl 1):S83-103.
  8. View Abstract: Rodriguez-Moreno F, et al. Zinc, Copper, Manganese, and Iron in Chronic Alcoholic Liver Disease. Alcohol. 1997;14(1):39-44.
  9. View Abstract: Kelly GS. Clinical applications of N-acetylcysteine. Altern Med Rev. Apr1998;3(2):114-27.
  10. View Abstract: Montanini S, et al. Use of acetylcysteine as the life-saving antidote in Amanita phalloides (death cap) poisoning. Case report on 11 patients. Arzneimittelforschung. Dec1999;49(12):1044-7.
  11. View Abstract: Buckley NA, et al. Oral or intravenous N-acetylcysteine: which is the treatment of choice for acetaminophen (paracetamol) poisoning? J Toxicol Clin Toxicol. 1999;37(6):759-67.
  12. View Abstract: Girardi G, Elias MM. Effectiveness of N-acetylcysteine in protecting against mercuric chloride-induced nephrotoxicity. Toxicology. Apr1991;67(2):155-64.
  13. View Abstract: Osman E, et al. Review article: S-adenosyl-L-methionine--a new therapeutic agent in liver disease? Aliment Pharmacol Ther. Feb1993;7(1):21-8.
  14. View Abstract: Van Gossum A, Neve J. Low Selenium Status in Alcoholic Cirrhosis is Correlated with Aminopyrine Breath Test. Biological Trace Element Research. 1995;47:201-207.
  15. View Abstract: Ademuyiwa O, et al. Vitamin C in CC14 hepatotoxicity--a preliminary report. Hum Exp Toxicol. Feb1994;13(2):107-9.
  16. View Abstract: Yao T, et al. Inhibition of carbon tetrachloride-induced liver injury by liposomes containing vitamin E. Am J Physiol. Sep1994;267(3 Pt 1):G476-84.
  17. View Abstract: Bode JC, et al. Hepatic zinc content in patients with various stages of alcoholic liver disease and in patients with chronic active and chronic persistent hepatitis. Hepatology. Nov1988;8(6):1605-9.
  18. View Abstract: Marchetti P, et al. Zinc deficiency in liver cirrhosis: a curiosity or a problem? Ann Ital Med Int. Jul1998;13(3):157-62.
  19. View Abstract: Hong RW, et al. Glutamine Preserves Liver Glutathione After Lethal Hepatic Injury. Annals of Surgery. Feb1992;215(2):114-119.
  20. View Abstract: Ito A, Higashiguchi T. Effects of glutamine administration on liver regeneration following hepatectomy. Nutrition. Jan1999;15(1):23-8.
  21. Berkson MB. Alpha-Lipoic Acid (Thioctic Acid): My Experience With This Outstanding Therapeutic Agent. Journal of Orthomolecular Medicine. 1998;13(1):44-48.
  22. View Abstract: Breithaupt-Grogler K, et al. Dose-proportionality of oral thioctic acid--coincidence of assessments via pooled plasma and individual data. Eur J Pharm Sci. Apr1999;8(1):57-65.
  23. Cardui mariae fructus (Milk Thistle fruit). Commission E Monograph. Mar1986;Bundesanzeiger:50.
  24. View Abstract: Flora K, et al. Milk Thistle (Silybum marianum) for the Therapy of Liver Disease. Am J Gastroenterol. 1998;93(2): 139-43.
  25. View Abstract: Salmi H, et al. Effect of Silymarin on Chemical, Functional, and Morphological Alterations of the Liver. A Double-blind Controlled Study. Scand J Gastroent. 1982;17: 517-21.
  26. Wichtl M in Bissett NA, ed. Herbal Drugs and Phytopharmaceuticals. Stuttgart: Scientific Press; 1994:121-23.
  27. View Abstract: Campos R, et al. Silybin Dihemisuccinate Protects Against Glutathione Depletion and Lipid Peroxidation Induced by Acetaminophen on Rat Liver. Planta Medica. 1989;55:417-19.
  28. View Abstract: Valenzuela A, et al. Selectivity of Silymarin on the Increase of the Glutathione Content in Different Tissues of the Rat. Planta Medica. 1989;55:1550-52.
  29. View Abstract: Singh V, et al. Effect of Picroliv on Protein and Nucleic Acid Synthesis. Indian J Exp Biol. Jan1992;30(1):68-9.
  30. View Abstract: Visen PK, et al. Curative Effect of Picroliv on Primary cultured Rat Hepatocytes Against Different Hepatotoxins: An In Vitro Study. J Pharmacol Toxicol Methods. Oct1998;40(3):173-9.
  31. View Abstract: Santra A, et al. Prevention of Carbon Tetrachloride-induced Hepatic Injury in Mice by Picrorhiza kurrooa. Indian J Gastroenterol. Jan1998;17(1):6-9.
  32. View Abstract: Vaidya AB, et al. Picrorhiza kurroa (Kutaki) Royle ex Benth As a Hepatoprotective Agent--Experimental & Clinical Studies. J Postgrad Med. Dec1996;42(4):105-8.
  33. View Abstract: Rastogi R, et al. Picroliv Protects Against Alcohol-induced Chronic Hepatotoxicity in Rats. Planta Med. Jun1996;62(3):283-5.
  34. View Abstract: Saraswat B, et al. Ex Vivo and In Vivo Investigations of Picroliv from Picrorhiza kurroa in An Alcohol Intoxication Model in Rats. J Ethnopharmacol. Sep1999;66(3):263-9.
  35. View Abstract: Vaidya AB, et al. Picrorhiza kurroa (Kutaki) Royle ex Benth As a Hepatoprotective Agent--Experimental & Clinical Studies. J Postgrad Med. Dec1996;42(4):105-8.
  36. View Abstract: Chander R, et al. Effect of Picroliv on Glutathione Metabolism in Liver and Brain of Mastomys natalensis Infected with Plasmodium berghei. Indian J Exp Biol. Aug1992;30(8):711-4.
  37. View Abstract: Chander R, et al. Picroliv, Picroside-I and Kutkoside from Picrorhiza kurrooa are Scavengers of Superoxide Anions. Biochem Pharmacol. Jul1992;44(1):180-3.
  38. View Abstract: Dwivedi Y, et al. Picroliv Protects Against Aflatoxin B1 Acute Hepatotoxicity in Rats. Pharmacol Res. Feb1993;27(2):189-99.
  39. View Abstract: Liu GT. Pharmacological Actions and Clinical Use of Fructus Schizandrae. Chin Med J (Engl). Oct1989;102(10):740-49.
  40. View Abstract: Liu KT, et al. Pharmacological Properties of Dibenzo[a,c]Cyclooctene Derivatives Isolated from Fructus Schizandrae Chinensis III. Inhibitory Effects on Carbon Tetrachloride-induced Lipid Peroxidation, Metabolism and Covalent Binding of Carbon Tetrachloride to Lipids. Chem Biol Interact. Jul1982;41(1):39-47.
  41. View Abstract: Maeda S, et al. Effects of Gomisin A on Liver Functions in Hepatotoxic Chemicals-treated Rats. Jpn J Pharmacol. Aug1985;38(4):347-53.
  42. View Abstract: Kubo S, et al. Effect of Gomisin A (TJN-101) on Liver Regeneration. Planta Med. Dec1992;58(6):489-92.
  43. Lin TJ, et al. Antioxidant Mechanism of Schisandrin and Tanshinonatic Acid A and Their Effects on the Protection of Cardiotoxic Action of Adriamycin. Shen Li Ko Hsueh Chin Chan. 1991;22(4):342-345.
  44. View Abstract: Shiota G, et al. Rapid Induction of Hepatocyte Growth Factor mRNA after Administration of Gomisin A, a Lignan Component of Shizandra Fruits. Res Commun Mol Pathol Pharmacol. Nov1996;94(2):141-46.
  45. View Abstract: Ohtaki Y, et al. Deoxycholic Acid as an Endogenous Risk Factor for Hepatocarcinogenesis and Effects of Gomisin A, a Lignan Component of Schizandra Fruits. Anticancer Res. Mar1996;16(2):751-55.
  46. View Abstract: Yamada S, et al. Preventive Effect of Gomisin A, a Lignan Component of Shizandra Fruits, on Acetaminophen-induced Hepatotoxicity in Rats. Biochem Pharmacol. Sep1993;46(6):1081-85.
  47. View Abstract: Nagai H, et al. The Effect of Gomisin A on Immunologic Liver Injury in Mice. Planta Med. Feb1989;55(1):13-17.
  48. View Abstract: Gebhardt R. Antioxidative and Protective Properties of Extracts from Leaves of the Artichoke (Cynara scolymus L.) Against Hydroperoxide-induced Oxidative Stress in Cultured Rat Hepatocytes. Toxicol Appl Pharmacol. Jun1997;144(2):279-86.
  49. View Abstract: Adzet T, et al. Hepatoprotective Activity of Polyphenolic Compounds From Cynara scolymus Against CCl4 Toxicity in Isolated Rat Hepatocytes. J Nat Prod. Jul1987;50(4):612-17.
  50. View Abstract: Gebhardt R. Antioxidative and protective properties of extracts from leaves of the artichoke (Cynara scolymus L.) against hydroperoxide-induced oxidative stress in cultured rat hepatocytes. Toxicol Appl Pharmacol. Jun1997;144(2):279-86.
  51. Khadzhai I, et al. Effect of Artichoke Extracts on the Liver. Farmakol Toksikol. Nov1971;34(6):685-87.
  52. Khadzhai I, et al. Effect of Artichoke Extracts on the Liver. Farmakol Toksikol. Nov1971;34(6):685-87.
  53. Newall CA, et al. Herbal Medicine: A Guide for Health-Care Professionals. Cambridge: Pharmaceutical Press; 1996:36-37.