It has been suggested that oxidative stress (OxSt) accompanies the development of secondary biliary cirrhosis. If OxSt contributes to the pathogenesis of biliary cirrhosis, then antioxidants would be expected to attenuate the bile duct ligation (BDL)-induced fibrosis in rat liver caused by OxSt.

BDL, 50 female Wistar rats were grouped as following; vit E (n=10), vit C (n=10), and combination of vit E+C (n=10) and BDL only (placebo) (n=10), Sham-operated (n=10).

Rats in groups of E, C and EC were treated by vit E 15 mg/kg or vit C 10 mg/kg sc or both, respectively for 4 weeks. All the rats were sacrificed at the end. Liver collagen content was determined biochemically by the dye elution method described by Lopez de Leon.

Morphometric-densitometric measurements of hepatic fibrosis were quantified by computerized image analysis. Hyaluronate levels were determined by ELISA method. Histopathology was evaluated according to Scheuer system.

Results

The mean liver and spleen sizes, serum transaminases, cholestatic enzymes, bilirubins and histopathologicaly inflammation scores were not statistically different among the treatment groups.

However, fibrosis scores were better in Vit EC groups compared to placebo (p<0.05). The median fibrosis percentage on computerized image analysis, biochemically quantitative collagen content and mean serum hyaluronate value of all antioxidant groups were significantly better than placebo group (p<0.05, p<0.001, p<0.001; respectively).

The authors conclude, “Antioxidants vitamins E and C or combination of both improve hepatic fibrosis in the bile duct ligated rats.”

These findings may have implications for the use of these same antioxidants in persons with HCV-related fibrosis. Human studies are warranted in this population.

04/28/04

Reference
A R Soylu and others. ANTIOXIDANTS VITAMIN E AND C ATTENUATE HEPATIC FIBROSIS IN SECONDARY BILIARY CIRRHOSIS; AN EXPERIMENTAL ANIMAL STUDY. Abstract 331. 39^th EASL. April 14-18, 2004. Berlin, Germany.

www.hivandhepatitis.com

HealthWise: Herbs and Hepatitis C—Part 1 Through 3
Lucinda K. Porter, RN, CCRC

Over 5 years ago I wrote an information pamphlet called Herbs and Hepatitis C. Interest in herbs continues to be on the rise and since more information is available, it became clear it was time to update Herbs and Hepatitis C. The revised edition can be read in its entirety at www.hcvadvocate.org.

I have reformatted Herbs and Hepatitis C into a 3-part series for this newsletter. This article is not meant to be the final word on the issue of herbs. I hope the reader will use this as a tool towards gaining more insight and knowledge about the world of herbs. Of course, this information is not meant to be used for medical care. Always talk to your primary health provider before using herbs.

The use of herbs for medicinal purposes has a long and interesting history. The origins of some modern medications are actually plants, such as aspirin from white willow bark, digitalis from foxglove, morphine from poppies and warfarin (Coumadin) from sweet clover. Many cultures use indigenous plants for healing purposes. The use of herbs, however, is controversial in contemporary western medicine due to the lack of evidence-based research to support safety and efficacy. Couple this with the potential harm these substances can inflict and it is easy to see why physicians are reluctant to endorse herb use. Some patients are interested in alternative methods to use with or instead of the treatment their physicians have prescribed. This is particularly true for patients living with chronic hepatitis C virus (HCV). Although huge progress has been made in the HCV treatment arena, current antiviral therapy has many side effects and is not always effective. Add these elements to the symptoms some people experience from HCV and it is no wonder that herbs seem attractive.

Although herbs and other supplements may seem appealing, a number of herbs can cause harm. Some herbs are known to have potentially carcinogenic properties and to cause neurological damage. There are herbs that can be particularly harmful to the liver and can cause damage and death. It is because of the potential for hepatotoxicity (poisoning of the liver) that HCV patients are advised to avoid herbs or to use them cautiously.

The Food and Drug Administration (FDA) is the federal agency responsible for drug and food safety. Drugs undergo years of rigorous testing on animals and humans before the FDA allows them to be marketed. Herbs and supplements, on the other hand, are considered to be dietary supplements. This means that they are regulated by a different set of standards, as set out in the Dietary Supplement Health and Education Act of 1994 (DSHEA). Under this act, it is the manufacturer that ensures the safety of the dietary supplement. In general, the supplement manufacturers do not need FDA approval and do not need to register their product. They are required, however, to label the supplement in a truthful manner.

The point at which the FDA may become involved with herbs is after marketing. The FDA may monitor product labeling, information, and safety. Adverse event reporting is voluntary. Whether the FDA should regulate supplements is a hotly debated issue. The FDA has been criticized both for regulating and under-regulating dietary supplements. For a variety of reasons, the FDA's involvement with herb use has been minimal. To date, the notable excep-tion to this is the sale of dietary supplements containing ephedrine alkaloids. Ephedra, also called Ma Huang, is one of the plants that are a source of ephedrine alkaloids. Its use has been associated with an increase in blood pressure, a condition which will increase the risk of heart attack, stroke, and death.

There is very little independent research involving the use of herbs. The gold standard randomized, double blind placebo controlled studies are few in the area of botanical remedies, let alone the use of herbs and HCV. In 1991, the U.S. Congress established the Office of Alternative Medicine (OAM) within the National Institutes of Health (NIH). In 1998 The National Center for Complementary and Alternative Medicine (NCCAM) became a new center of the NIH. Responding to the need for more research concerning the safety and efficacy of herbs and supplements, NCCAM and the NIH Office of Dietary Supplements established the first Dietary Supplements Research Centers with an emphasis on botanicals. The specific subject of herbs and viral hepatitis was included in the Complementary and Alternative Medicine in Chronic Liver Disease conference in 1999 and a few clinical trials are being conducted in this area. Unfortunately funding is limited and evidence-based data about herbs and HCV is largely unavailable.

The insufficiency of independent research does not mean that there is no value in herbs.

Herbs have made a significant contribution to medicine. Herbal practice has been around for centuries and has produced some sound observations. Indigenous practitioners relied on botanicals for medicine. In these modern times it is common for people to self-treat a mild sunburn with aloe vera, a mild stomach ache with ginger, or a mild cold with peppermint or chamomile tea. Generally these are assumed to be safe alternatives. However, the use of herbs for treatment of more serious conditions such as HCV is more complicated and raises a number of questions. For example, when choosing an herb, which part of the plant is used, when is it harvested, and how is it processed? Botanicals are not made in a lab setting. This means that the consistency of the product is at risk. Is the herbal product safe, which brands are the best, and what is the recommended dose? Next month's column will attempt to answer some of these questions and will provide some tools that can be used towards making informed choices.

HealthWise: Herbs and Hepatitis C—Part 2
Lucinda K. Porter, RN, CCRC

Last month's column provided an overview on the subject of herbs and hepatitis C virus (HCV) infection. This month I suggest some guidelines and tools that can be used for making informed choices about the use of herbs.

When choosing an herb, start with the label. Herbs can vary in strength and purity, so it may be wise to take a standardized and certified form. Certification and standardization is voluntary. The goal of the United States Pharmacopeia (USP) is to set industry standards for drugs and dietary supplements in the U.S. The label of a supplement that displays the USP seal is worth considering. A product that is certified by NSF International (formerly the National Sanitation Foundation) is another indicator that the manufacturer complies with particular standards. A seal of approval from ConsumerLab.com (CL) also carries some distinction. Another standard is that of the world's leading authority on herbs, the German Commission E. This agency is the German equivalent of the Food and Drug Administration (FDA). The American Herbal Pharmacopoeia is also developing standardization guidelines for the American marketplace. ConsumerLab.com has provided a much-needed service by testing popular supplements. This company has discovered that many products do not contain the levels of key ingredients that are on the products' labels. A product that passes their inspection may carry the triangular label with the ConsumerLab.com quality of approval. The use of this service does have a fee associated with it. Companies that belong to the American Herbal Products Association and submit to this organization's code of ethics are another good choice.

Suggested Guidelines for Herbal Use
• Assess your overall health. If you smoke, drink alcohol, and have other unhealthy habits, do not expect herbs to offset the potential damage these habits can cause. Adopting healthy habits will provide far more benefit than any herb can possibly give.
• Discuss herb and supplement use with your healthcare provider. Identify all the herbs and supplements you take, even if you think your doctor might disapprove. Drugs and supplements can interact with each other as well as with other health conditions.
• Apply the same commonsense approach and standards to herbs as you would to any drug. If you are reluctant to take any prescription or over-the-counter drug, be equally as reluctant to take an herb.
• Be informed and be sure your information is current.
• Before you take an herb or supplement, find out if it is compatible with other drugs or supplements you are taking. Verify that the supplement is not contraindicated for any other condition you may have (see A Warning about Milk Thistle and Drug Interactions in Part 3).
• Take extra precautions if you have a history of allergies. Botanical products can cause allergic reactions.
• Follow the label's dosage recommendations. More is not better.
• Know your source. Herbs may be contaminated. Before ingesting anything, ask yourself what you know about what you are about to take.
• Choose herbs and supplements that are standardized.
• Buy products that submit to voluntary self-regulation.
• Natural does not equal healthy or safe. Snake venom is natural but not healthy.
• Do not be swayed by bargain prices. Herbs are not all equal.
• Check the expiration date on the container.
• Do not rely on the health food store staff for health care information. Although they may be helpful, remember that salespeople are usually not licensed to practice medicine. Do not treat your condition on the advice of a salesperson.
• Be skeptical. Claims made by the product manufacturer or seller may vastly differ from independent evidence-based research.
• Do not be swayed by personal testimonies. Although individuals may benefit from botanical use, the notion that "one size fits all" does not apply in medicine.
• Do not be influenced by the latest supplement to make headlines. Dietary supplements can be compared to cars. When new models are introduced, sometimes it takes time before problems develop. A product that really has value will be around for awhile.
• Herbs and supplements should not be given to children or taken by pregnant or nursing women without a physician's approval. Older adults and those with various health conditions should also exercise extra caution before taking non-prescribed supplements. Herbs should never be used with decompensated cirrhosis.
• Some herbs prolong bleeding times or interfere with anesthetics. Stop all herb use at least a week prior to any surgery or procedure that uses anesthesia. Tell your attending physician and anesthesiologist about any herbs you are using, particularly if the procedure occurs before you have sufficient time to observe this "wash-out" period.
• Report any suspected adverse reactions to an herb or supplement to the FDA's monitoring program, Medwatch. Call 800-322-1088 or www.fda.gov/medwatch.

HealthWise: Herbs and Hepatitis C—Part 3
Lucinda K. Porter, RN, CCRC

The first installment of this three-part series presented an overview on the subject of herbs and hepatitis C virus (HCV) infection. Last month's column suggested guidelines and tools that can be used for making informed choices about the use of herbs. This month's column focuses on a few herbs that may be helpful or problematic for those with liver disease. A list of resources has been provided at the end of this article for those who want more information about herbs.

HCV Treatment and Herbs
There is virtually no research on the safety of herbs and supplements co-administered with pegylated interferon/ribavirin therapy. Because of this, it is common for patients to abstain from milk thistle and herb use while undergoing antiviral therapy. Even commonly used botanicals need to be used with caution. Quite a few herbs can alter laboratory results. Some herbs and supplements can hinder the ability of the blood to clot. For instance, ginger is widely used to relieve nausea. However, patients with gallstones should talk to their healthcare provider prior to using ginger. Additionally, ginger has an anticlotting action and should not be taken if you have reduced blood clotting ability. Interferon therapy and/or cirrhosis can also interfere with blood clotting, so there may be an increased risk if some herbs are used simultaneously under these conditions. Other commonly used herbs, such as chamomile and St. John's Wort carry a warning of potential drug interactions. The rule of thumb is to be informed and talk to your healthcare provider prior to using any botanical product.

Milk Thistle
Milk thistle, (Silybum marianum), is the most commonly used herb for liver problems. A frequently asked question regarding chronic HCV infection concerns the use of this herb. If you are considering taking a milk thistle product, talk to your doctor and find out if it is compatible with other drugs or supplements you are taking. Verify that the supplement is not contraindicated for any other condition you may have (see “A Warning about Milk Thistle and Drug Interactions” below). Do not use milk thistle if you have decompensated cirrhosis.

Medical consultants for the Consumers Union recommended the following in the April 2001 issue of Consumer Reports On Health:

• Patients should not use milk thistle to replace a conventional treatment for viral hepatitis;
• Patients should not take milk thistle while on a conventional treatment for viral hepatitis;
• Milk thistle is probably safe and no one should be discouraged from taking it if there are no other options;
• Choose a brand that contains silibin and phosphotidyl choline, which may be better absorbed.

There is insufficient research to establish a suggested daily dose of milk thistle. Typical dosages are in the range of 140-420 mg in divided doses, 2-3 times a day, of 70-80% silymarin. See the section "Suggested Guidelines for Herbal Use" in part 2 of this series for more information on choosing milk thistle and other herbal products.

A Warning About Milk Thistle and Drug Interactions
Raman Venkataramanan and colleagues¹ at the University of Pittsburg reported observations about silymarin, a compound found in milk thistle. In short, this report raised concerns that silymarin may impair the metabolism of certain drugs when taken together. Further, the potential exists for increased toxicity of co-administered drugs in the presence of silymarin.

The medication levels of the following may increase if taken by people who are also using milk thistle. The source for this list is the Community AIDS Treatment Information Exchange (CATIE). It is not meant to be complete.

• protease inhibitors
• non-nucleoside analogues
• methadone
• heart drugs - Tambocor (flecainide), Rythmol (propafenone)
• antibiotics - erythromycin, rifampin
• anti-seizure drugs - carbamazepine (Tegretol)
• antidepressants - St. John's wort, Zyban/Wellbutrin (bupropion), Paxil (paroxetine), Prozac (fluoxetine), Luvox (fluvoxetine), Serzone (nefazodone), Zoloft (sertraline), Effexor (venlafaxine)
• antifungals - itraconazole (Sporanox), ketoconazole (Nizoral)
• gastrointestinal motility agents - Prepulsid (Cisapride)
• ergot drugs - Ergonovine, Ergomar (ergotamine)
• anti-psychotics - Clozaril (clozapine), Orap (pimozide)
• sedatives/sleeping pills - Ambien (zolpidem), Halcion (triazolam), Versed (midazolam)
• lipid-lowering drugs (statins) - Lescol (fluvastatin), Mevacor (lovastatin), Pravachol (pravastatin) and Zocor (simvastatin), Baycol (ceriva-statin)
• transplant drugs - cyclosporine (Neoral, Sandimmune), ProGraf (tacrolimus)
Milk thistle also has the potential to lower levels of the following drugs:
• anti-parasite drugs - Mepron (atovaquone)
• sedatives/sleeping pills - Ativan (lorazepam)
• hormones - estrogen

Some Herbs Associated with Liver Toxicity
This list is primarily liver specific and by no means exhaustive. The substances on this list are referred to in their oral form only.

• Blue-green Algae
• Borage (Borago officianalis)
• Bupleurum
• Chaparral (Larrea tridentata)
• Comfrey (Symphytum officinale and S. uplandicum)
• Dong Quai (Angelica polymorpha)
• Germander (Teucrium chamaedrys)
• Jin Bu Huan (Lycopodium serratum)
• Kava
• Mistletoe (Phoradendron leucarpum and Viscum album)
• Pennyroyal (Mentha pulegium)
• Sassafras (Sassafras albidum)
• Shark Cartilage
• Skullcap (Scutellaria lateriflora)
• Valerian

Warning: Bupleurum is a popular herb used in a variety of traditional Chinese and Japanese medicine mixtures for liver conditions. At least 16 deaths have been reported in Japan in HCV patients being treated simultaneously with alpha interferon and Xiao Chai Hu Tang (Minor Bupleurum).

Ephedra
Although not specifically associated with liver toxicity, products containing ephedrine alkaloids (ephedra) should be avoided. Reports of heart attacks, strokes, seizures, psychosis, and death have been linked to the use of ephedrine alkaloids. The FDA has banned the sale of dietary supplements containing ephedrine alkaloids, including ephedra and Ma Huang.

Final Words
Herbs have been part of the healing arts for centuries. Clearly more research needs to be conducted in this area in order to better understand and incorporate the use of botanical products into current health practices. In the meantime, make informed decisions regarding your health. Your future depends on it.

References

¹Venkataramanan R, Ramachandran V, Komoroski BJ, et al. Milk thistle, a herbal supplement, decreases the activity of CYP3A4 and uridine diphosphoglucuronosyl transferase in human hepatocyte cultures. Drug Metabolism and Disposition 2000;28(11):1270-1273.

Resources:

Books

•The American Pharmaceutical Association Practical Guide to Natural Medicines, by Andrea Peirce
•The ABC Clinical Guide to Herbs, edited by Mark Blumenthal, et al at the American Botanical Council
•ConsumerLab.com's Guide to Buying Vitamins & Supplements: What's Really in the Bottle, by Tod Cooperman, M.D., William Obermeyer, Ph.D., Denise Webb, R.D., Ph.D.
•The Green Pharmacy, by James A. Duke
•Herbs of Choice, by James E. Robbers and Varro E. Tyler
•PDR for Herbal Medicines, published by the Medical Economics Company
•Tyler's Honest Herbal: A Sensible Guide to the Use of Herbs and Related Remedies, by Stephen Foster and Varro E. Tyler, Ph.D.

Organisations

•American Botanical Council - 512-926-4900, www.herbalgram.org
•American Herbal Products Association www.ahpa.org
•ConsumerLab.com www.consumerlab.com
•FDA Dietary Supplement website - http://vm.cfsan.fda.gov/~dms/supplmnt.html
•HerbMed - www.herbmed.org
•Memorial Sloan-Kettering Cancer Center www.mskcc.org/aboutherbs
•National Center for Complementary and Alternative Medicine - 888-644-6226, http://nccam.nih.gov
•National Institutes of Health Clincal Trial Information www.clinicaltrials.gov
•National Sanitation Foundation (NSF International) www.nsf.org
•The United States Pharmacopeia - 800-822-8772, www.usp.org
•UC Berkeley Wellness Letter www.wellnessletter.com

©July 2004 Lucinda Porter, RN and the Hepatitis C Support Project / HCV Advocate www.hcvadvocate.org - All Rights Reserved.

Reprint is granted and encouraged with credit to the author and to the Hepatitis C Support Project

Copyright, June 2004 Lucinda Porter, RN and the Hepatitis C Support Project / HCV Advocate www.hcvadvocate.org - All Rights Reserved.

Reprint is granted and encouraged with credit to the author and to the Hepatitis C Support Project

Docs Evaluate Alternative Therapies for Hepatitis C
by John C. Martin	Article Date: 04-28-04

A new study evaluating the effectiveness of complementary and alternative therapies for hepatitis C has concluded that they may be "promising" treatments.¹

No Definite Conclusions
Complementary therapies have been widely promoted as treatments for hepatitis C. But their efficacy is controversial, and are not regulated by the Food and Drug Administration.

A 2002 survey found that, among nearly 1000 patients being treated for various liver diseases at six U.S. clinics, as many as 39 percent had used some form of alternative therapy, mostly herbals and botanicals.²

Consequently, doctors at Peninsula Medical School at the Universities of Exeter and Plymouth in Exeter, England wanted to find out which complementary therapies, if any, might have potential against hepatitis C.

Confirming Study Findings
Joanna Thompson-Coon, Ph.D., and Edzard Ernst, M.D., Ph.D., both of the School of Complementary Medicine at Peninsula, researched the medical literature for previous studies testing the efficacy of a range of alternative therapies for HCV.

"Systematic searches were conducted in six databases, reference lists of all papers were checked for further relevant publications, and information was requested from experts," the two researchers reported.

Coon and Ernst found 27 previously published clinical trials that were relevant, all involving herbal products and supplements. In about half of the trials, patients had received interferon-alfa treatment along with a complementary therapy. But only 11 of these trials were of sufficient quality, making their results plausible. The other trials, Coon and Ernst determined, had questionable outcomes because their designs were also questionable.

Effective CAM
In each of the previous trials, patients had been divided into two groups; one, taking the active therapy, and the second group (control group) taking a non-active treatment as a comparison. "Compared with the control group, significant improvements in virological and/or biochemical response were seen in trials of vitamin E, thymic extract, zinc, traditional Chinese medicine, Glycyrrhiza glabra, and oxymatrine," the researchers concluded.

Vitamin E
Vitamin E has been shown to reduce the ill-effects of oxidative stress in the livers of people with hepatitis C.³ In fact, this vitamin is known as an antioxidant, nutrients that act to protect your cells against the effects of free radicals, molecules that are damaging by-products of the body's metabolism. Free radicals can cause cell damage that can contribute to disease.⁴

Thymic Extract
Thymic extract is made from the thymus of cows. The thymus has an important role in immune function by enticing white blood cells to become T cells that recognize particular foreign invaders in the body, and become part of the body's defenses against infection.⁵

While one study at the University of Alabama found thymic extract monotherapy was not effective against hepatitis C,⁶ other studies using thymosin (a hormone of the thymus) combined with interferon-alfa as combination treatment for HCV was effective at reducing viral load.⁷ And one pilot study showed this combination treatment was more effective than interferon-alfa monotherapy.⁸

Zinc
Zinc, an antioxidant like vitamin E, has been shown to enhance patients' responses to interferon therapy.^9,10

Chinese Medicine
Traditional Chinese medicine has involved the use of schisandra, a plant whose effects have been studied mostly in animals. The studies have suggested that fruit from the plant can protect the liver, benefits liver enzymes, and provides an antioxidant effect.^11,12 But other herbs used in this category have also been implicated as a possible treatment.

Glycyrrhiza glabra is also known as a licorice plant. Its dried root contains a potentially therapeutic substance known as glycyrrhizin, and has been used for centuries as part of traditional Chinese medicine.¹³

While some previous research has only involved lab studies, it has suggested that glycyrrhizin may have antiviral properties.¹⁴ But a review of previous clinical trials found glycyrrhizin has the potential to reduce long-term complications in chronic hepatitis C in patients who have not responded previously to interferon.¹⁵

And a study in 1997 suggested glycyrrhizin may help prevent liver cancer in chronic HCV patients.¹⁶

Oxymatrine
Oxymatrine is a substance found in sophora roots. In a comparison of oxymatrine versus vitamins in one study, nearly half of 43 patients had reduced their viral load to non-detectable levels, compared to only one patient taking vitamins, researchers at the University of Shanghai in China reported.¹⁷

However, while liver enzyme levels were higher in the treatment group after two months of treatment, they were generally the same between both groups after 3 months, the researchers reported.

In the end, Coon and Frist "identified several promising complementary therapies", but definitive conclusions couldn't be drawn because of questionable designs of the studies they had researched.

"More research is warranted to establish the role of these and other therapies in the treatment of hepatitis C," they wrote.

1. Coon JT, Frist E. Complementary and alternative therapies in the treatment of chronic hepatitis C: A systematic review. J Hepatol 2004 Mar;40(3):491-500.
2. Strader DB, Bacon BR, Lindsay KL et al. Use of complementary and alternative medicine in patients with liver disease. Am J Gastroenterol 2002;97(9):2391-7.
3. Mahmood S, Yamada G, Niiyama G, Kawanaka M et al. Effect of vitamin E on serum aminotransferase and thioredoxin levels in patients with viral hepatitis C. Free Radic Res 2003 Jul37(7):781-5.
4. NIH Clinical Center. National Institutes of Health.
5. Dr. Andrew Weil. Ask Dr. Weil.
6. Raymond RS, Fallon MB, Abrams GA. Oral thymic extract for chronic hepatitis C in patients previously treated with interferon. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 1998 Nov 15;129(10):797-800.
7. Andreone P, Gramenzi A, Cursaro C et al. Thymosin-alpha 1 plus interferon-alpha for naïve patients with chronic hepatitis C: Results of a randomized controlled pilot trial. J Viral Hepat 2004 Jan;11(1):69-73.
8. Moscarella S, Buzzelli G, Romanelli RG et al. Interferon and thymosin combination therapy in naïve patients with chronic hepatitis C: Preliminary results. Liver 1998 Oct;18(5):366-9.
9. Takagi H, Nagamine T, Abe T et al. Zinc supplementation enhances the response to interferon therapy in patients with chronic hepatitis C. J Viral Hepat 2001 Sep;8(5):367-71.
10. Nagamine T, Takagi H, Takayama H et al. Preliminary study of combination therapy with interferon-alpha and zinc in chronic hepatitis C patients with genotype 1b. Biol Trace Elem Res 2000 Summer;75(1-3):53-63.
11. Sinclair S. Chinese herbs: A clinical review of Astragalus, Ligusticum and Schizandrae. Altern Med Rev 1998;3(5):338-44.
12. Liu GT. Pharmacological actions and clinical use of fructus schizandrae. Chinese Medical Journal 1989;102(10):740-9.
13. National Center for Complementary and Alternative Medicine. (NCCAM).
14. Shibata S. A drug over the millennia: Pharmacognosy, chemistry and pharmacology of licorice. Yakugaku Zasshi 2000;120(10):849-62.
15. van Rossum TG, Vulto AG, de Man RA et al. Review article: Glycyrrhizin as a potential treatment for chronic hepatitis C. Alimentary pharmacology & Therapeutics 1998;12(3):199-205.
16. Arase Y, Ikeda K, Murashima N et al. The long term efficacy of glycyrrhizin in chronic hepatitis C patients. Cancer 1997;79(8):1494-1500.
17. Li J, Li C, Zeng M. Preliminary study on therapeutic effect of oxymatrine in treating patients with chronic hepatitis C. Zhongguo Zhong Xi Yi Jie He Za Zhi 1998 Apr;18

John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include coverage of health news for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.

www.hepatitisneighborhood.com

http://nccam.nih.gov/health/hepatitisc/

Hepatitis C and Complementary and Alternative Medicine: 2003 Update

On this page

Introduction

Hepatitis C is a disease of the liver that is caused by the hepatitis C virus. The disease occurs in acute and chronic forms; symptoms can range from mild (or even no symptoms) to severe. There are conventional medical treatments available for hepatitis C, but some patients also try complementary and alternative medicine (CAM).^a This Research Report answers some frequently asked questions on hepatitis C and CAM, reviews findings from scientific research on some dietary supplements that have been used as CAM treatments for hepatitis C (milk thistle, licorice root, ginseng, thymus extract, schisandra, and colloidal silver), and suggests sources for further information.

^aConventional medicine is medicine as practiced by holders of M.D. (medical doctor) or D.O. (doctor of osteopathy) degrees and their allied health professionals, such as physical therapists, psychologists, and registered nurses. Other terms for conventional medicine include allopathy; Western, mainstream, orthodox, and regular medicine; and biomedicine. Some conventional medical practitioners are also practitioners of CAM. CAM, as defined by NCCAM, is a group of diverse medical and health care systems, practices, and products that are not presently considered to be part of conventional medicine.

Top

Key Points

Conventional medical treatment (consisting of a combination drug regimen) for hepatitis C has shown sustained benefit in approximately 55 percent of patients.
Some of the reasons hepatitis C patients try CAM are that they find conventional drug treatment difficult to tolerate or they do not experience a sustained response to treatment.
No CAM treatment has yet been proven safe and effective for treating hepatitis C.
There are many CAM treatments for which benefits for health are claimed. However, it is important to find out what scientific studies have been done on the safety and effectiveness of the CAM treatment in which you are interested. Clinical trials^b are needed of CAM therapies that may show some potential for benefit for hepatitis C, such as milk thistle. The National Center for Complementary and Alternative Medicine (NCCAM) is sponsoring a clinical trial of milk thistle.
It is important to inform all of your health care providers about any therapy that you are currently using or considering, including any dietary supplements. This is to help ensure a safe and coordinated course of care.

^bClinical trials are research studies in people. To find out more, see "About Clinical Trials and Complementary and Alternative Medicine."

Quick Facts About Hepatitis C

Hepatitis C is the most common bloodborne infection in the United States. About 35,000 new cases are diagnosed in the United States each year.
Hepatitis C is transmitted primarily when an infected person's blood comes into contact with the blood of a noninfected person.
- People who are at the highest risk for HCV infection are those who have used or experimented with injection drugs; received a blood transfusion, blood product, or organ transplant before July 1992; worked in health care and had a needlestick accident involving HCV-infected blood; or had multiple sex partners.
- A risk exists but is low (1 to 5 percent) for babies born to a mother with hepatitis C and for people who are in a monogamous sexual relationship with someone with hepatitis C; who have had other sexually transmitted diseases; who have had tattooing or body piercing done with unsterilized tools; or who have used cocaine intranasally (i.e., "snorted" it).
- Hepatitis C is not spread through sneezing, coughing, kissing, hugging, food or water, or casual contact.
People who are newly infected have what is called acute hepatitis C. For about 15 to 40 percent of this group, the infection is short-term, goes away, and does not return. Others develop chronic (or long-lasting) hepatitis C, in which the virus stays in the liver, replicates itself, and injures the liver over time.
Among people with chronic hepatitis C, most show no symptoms for up to 20 to 30 years; some have mild symptoms; and some have more serious symptoms.
Chronic hepatitis C can cause liver disease, cirrhosis (scarring of the liver), liver cancer, and liver failure. However, persons who have been diagnosed with hepatitis C need to know that serious illness or death from the disease is by no means inevitable--especially if they take proper care of themselves and get the health care they need.

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What is hepatitis C?

Hepatitis C is a communicable (contagious) disease of the liver caused by the hepatitis C virus (HCV).^c The liver, the largest organ in the body, is found behind the ribs on the right side of the abdomen. It has many important functions, including removing harmful material from the blood and converting food into substances needed for life and growth. The term "hepatitis" means inflammation of the liver. There are other viruses in the hepatitis family (such as hepatitis A and hepatitis B), but HCV is not related to them.

^cTo find out more about hepatitis C and conventional treatment for it, consult the Federal agencies listed under "For More Information."

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What does conventional treatment for chronic hepatitis C consist of?

People who have a mild case of hepatitis C may only need to manage it by visiting their doctor regularly and following their doctor's recommendations--such as eating a nutritious diet, avoiding alcohol (because of its impact on the liver), and getting regular exercise.

For people with more severe hepatitis C, however, drug therapy may be needed. A drug called interferon is the mainstay of conventional treatment. Interferon is often combined with an antiviral (virus-fighting) drug called ribavirin. Such combination therapies are usually taken for 6 months to 1 year. Approximately 55 percent of patients treated with the combination of interferon and ribavirin for 1 year will achieve a sustained response (that is, a sustained benefit from treatment).¹ If a patient does not achieve a sustained response, his doctor may decide whether another course of treatment (re-treatment) is appropriate.

Combination regimens benefit many patients. However, their side effects can be difficult for some patients to tolerate. These side effects can include flu-like symptoms (such as body aches, fever, chills, and fatigue); nausea and other gastrointestinal problems; hair loss; emotional changes; skin reactions; and, in more severe cases, depression, organ damage, blood conditions, and other problems.

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Why do people use CAM for hepatitis C?

There are various reasons why people use CAM for hepatitis C, including:

They have not had a response to initial treatment or to re-treatment with drugs.
They are not willing to have drug treatment or continue it--for example, because of the side effects or length of treatment.
They would like to support their body's fight against damage by hepatitis C, and they hear of benefits claimed for some CAM treatments--such as "strengthens the immune system" or "cleanses or rejuvenates the liver" (or other organs).
They are experiencing problems from other diseases and conditions that can be caused by or worsened by hepatitis C.
They are not satisfied with their conventional medical treatment.

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How commonly do people with hepatitis C use CAM therapies, and what do they use?

While there have been no surveys yet on the use of CAM by persons with hepatitis C specifically, there is some data from a survey published in 2002 on the use of CAM by persons who have chronic liver diseases (such as hepatitis, liver cancer, alcoholic liver disease, or cirrhosis).² This survey of 989 patients being treated for various liver diseases at six clinics in the United States found that 39 percent used some form of "alternative therapy." The therapy they used the most was herbals or botanicals^d (21 percent). However, the herbals and botanicals were used for reasons besides liver disease, such as depression. Thirteen percent of all survey participants used herbals or botanicals specifically for their liver disease, and they used only milk thistle (12 percent) or licorice root (1 percent). The other most commonly used CAM therapies were self-prayer^e (18 percent), and (from 6 to 9 percent each) relaxation, megavitamins, massage, chiropractic, and spiritual healing.²

^dHerbs are plants or plant parts valued for their flavor, scent, and/or therapeutic properties. "Herbals" and "botanicals" are synonyms and mean herbal and botanical products.

^eSelf-prayer is when an individual prays for himself. It can be contrasted with intercessory prayer, in which an individual prays for others.

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What CAM therapies are discussed in this Research Report?

There is a range of medical concerns associated with hepatitis C, and the number of CAM therapies that are tried is large.^f Therefore, it is beyond the scope of this Research Report to discuss all possible CAM therapies used for hepatitis C. The report focuses on a number of dietary supplements that are used: milk thistle, licorice root, ginseng, thymus extract, schisandra, and colloidal silver (See Scientific Research Findings: Selected CAM Treatments for Hepatitis C).

About Dietary Supplements

Dietary supplements were defined in a law passed by Congress in 1994. A dietary supplement must meet all of the following conditions:

It is a product (other than tobacco) intended to supplement the diet, which contains one or more of the following: vitamins; minerals; herbs or other botanicals; amino acids; or any combination of the above ingredients.
It is intended to be taken in tablet, capsule, powder, softgel, gelcap, or liquid form.
It is not represented for use as a conventional food or as a sole item of a meal or the diet.
It is labeled as being a dietary supplement.

Sources for this 2003 update consist of the peer-reviewed medical and scientific journals indexed in the National Library of Medicine's MEDLINE/PubMed database, in English, from January 1999 through May 2003.^g Sources that you can use to research additional science-based information are in the "Sources" sections.

^fTo read about the major of areas of CAM, see the NCCAM fact sheet "What Is Complementary and Alternative Medicine?"

^gThis report also incorporates information from the NCCAM fact sheet "Hepatitis C: Treatment Alternatives," published in 2000.

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What is known from the scientific evidence about CAM modalities for hepatitis C?

No CAM treatment has been scientifically proven to successfully treat hepatitis C.
Authors who have done recent analyses of the scientific work have found some results that are intriguing and even promising, but they have noted that more research--especially in the form of controlled clinical trials--is needed before firm conclusions can be drawn.
- The authors of a 2003 systematic review of medicinal herbs for hepatitis C concluded that there is not enough evidence to support using herbs to treat the disease. This team identified 13 clinical trials that were of sufficient quality for them to analyze. Compared to placebo,^h they found that none of the herbs tested showed effects on liver enzymes or reduced the amount of HCV in the bloodstream, except for milk thistle, which did show a significant reduction of liver enzymes in one trial.³
- Two general reviews from 2000 that covered a variety of CAM modalities for hepatitis C concluded that conventional therapies are the only scientifically proven treatments for the disease.^4,5
- NIH released a Consensus Statement in 2002 on the management of hepatitis C.ⁱ This assessment by a panel of medical and scientific experts found that "alternative and nontraditional medicines" should be studied.

^hA placebo is designed to resemble as much as possible the treatment being studied in a clinical trial, except that the placebo is inactive. An example of a placebo is a pill containing sugar instead of the drug or other substance being studied. By giving one group of participants a placebo and the other group the active treatment, the researchers can compare how the two groups respond and get a truer picture of the active treatment's effects. In recent years, the definition of placebo has been expanded to include other things that could have an effect on the results of health care, such as how a patient and a health care provider interact, how a patient feels about receiving the care, and what he or she expects to happen from the care.

ⁱSee "Sources: General," item A.

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What should I do to take care of myself if I have hepatitis C?

Make sure you have received an accurate diagnosis. Hepatitis C can be diagnosed reliably only through sophisticated blood tests used in conventional medicine.
See your health care provider regularly.
Discuss treatment options with your provider. Ask any questions you have to make sure you understand any treatment and possible side effects. Follow her recommendations for any changes to your diet and/or lifestyle.
Tell your provider about any herbal supplements, other dietary supplements, or medications (whether prescription or over-the-counter) that you are using or considering. This is important for your safety. Even if your provider does not know about the actions or interactions of an herbal supplement or other CAM treatment, he can access the most current medical guidance.
Get vaccinated against hepatitis A and B. Infection with hepatitis C does not prevent a person from becoming infected with other types of hepatitis; if this happens, it can be serious, even life-threatening.
Be an informed consumer. Seek high-quality, science-based information on any CAM modality that you are using or considering. There is free information from NCCAM, the National Library of Medicine, and other Federal sources to help you distinguish science-based information from other types, including word-of-mouth and manufacturers' claims.
If you decide to try herbal supplements, do so with care. (See the NCCAM fact sheet "Herbal Supplements: Consider Safety, Too.")
If you would like to find out about clinical trials of treatments for hepatitis C, go to www.clinicaltrials.gov or contact the NCCAM Clearinghouse.

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Scientific Research Findings: Selected CAM Treatments for Hepatitis C

This section describes six CAM therapies that people have used to treat hepatitis C. More-detailed discussions of individual studies are available in the Appendix. Reviews are discussed where available.^j

^jThere are different types of review articles: In a general review, a broad picture of the scientific studies and evidence available on a particular topic is presented. In a systematic review, data from a set of studies on a particular question or topic are collected, analyzed, and critically reviewed. A meta-analysis uses statistical techniques to analyze results from a collection of individual studies.

Milk Thistle
Milk thistle (scientific name Silybum marianum) is a plant from the aster family. The active extract of milk thistle believed to be responsible for the herb's medicinal qualities is silymarin, found in the fruit.⁶ Milk thistle has been used in Europe as a treatment for liver disease and jaundice since the 16th century.⁷

Summary of the research findings

The results of scientific studies to date do not definitively find that milk thistle is beneficial in treating hepatitis C in humans.
Studies in laboratory animals suggest that silymarin may have various benefits to the liver, such as promoting the growth of certain types of liver cells, having a protective effect upon liver cells, fighting a chemical process called oxidation that can damage cells, and inhibiting inflammation.^7-14 However, in some cases, a consistent pattern of benefit was not seen, and these studies did not specifically examine the effects of silymarin on
hepatitis C.
There have been some studies on silymarin or milk thistle in humans. These studies have generally been small and on liver diseases rather than on hepatitis C infection specifically, and the results have been contradictory (with some positive and some negative).^15-17 A review and a meta-analysis published in 2001 on silymarin in the treatment of liver diseases found it to be generally safe, but contained no firm conclusions with regard to its use to treat viral hepatitis.^18,19 A 2002 systematic review on milk thistle for liver disease found "no reduction in mortality (frequency of death as an outcome), in improvements in histology (tissue studies) observed through liver biopsy, or in biochemical markers of liver function" and that the data was too limited to support recommending milk thistle for treatment of liver disease.²⁰

To obtain more extensive and reliable data, NCCAM is sponsoring a clinical trial on the use of milk thistle for hepatitis C.

Side effects and other risks
Milk thistle is generally well-tolerated and has shown few side effects in clinical trials. It can cause a laxative effect; less common effects include nausea, diarrhea, abdominal bloating, fullness, and pain. Milk thistle can produce allergic reactions, which tend to be more common among people who are allergic to plants in the same family (e.g., ragweed, chrysanthemum, marigold, and daisy).

Licorice Root
Licorice root is the peeled or unpeeled dried root of the licorice plant (Glycyrrhiza glabra). The primary active component of licorice root is a substance called glycyrrhizin. Licorice root has been in use in China since the second and third century B.C. and in the West since Egyptian, Greek, and Roman times.²¹

Summary of the research findings

Laboratory studies of glycyrrhizin in cell cultures suggest that it may have antiviral properties.²¹
In a review of several randomized controlled trials, researchers reported that glycyrrhizin has potential for reducing long-term complications in chronic hepatitis C in those patients who may not respond to interferon.²² Several of the trials reviewed indicated improvements in liver tissue damaged by hepatitis. Some also showed improvements in how well the liver did its job after treatment.
A 1997 study and a 2002 review suggest that long-term administration of glycyrrhizin might prevent liver cancer in patients with chronic hepatitis C.^23,24
The use of glycyrrhizin as a complementary therapy (i.e., used in addition to conventional interferon therapy) has been studied, but no significant benefit has been found.^25,26
Recent clinical trials have shown that taking glycyrrhizin lowers the levels of liver enzymes (increased levels of certain liver enzymes indicate liver damage or inflammation). However, taking the herb did not reduce the amount of HCV in patients' blood, a critical indicator of the long-term progress of the infection.^27-29

Side effects and possible risks
Taking licorice over a prolonged period of time can lead to potentially serious side effects, including high blood pressure, salt and water retention, swelling, depletion of potassium, headache, and/or sluggishness.³⁰ Glycyrrhizin can worsen ascites, the accumulation of fluid in the abdominal cavity, a condition that can be caused by cirrhosis.³¹ The herb also can interact with certain drugs, such as diuretics, digitalis, antiarrhythmic agents, and corticosteroids.

Ginseng
The herb ginseng comes in two types: American ginseng (Panax quinquefolius) and Asian ginseng (Panax ginseng). Among the Asian forms of ginseng are Chinese, Japanese, and Korean ginseng. (So-called "Siberian ginseng" is not a true ginseng.) Ginseng has been used for thousands of years in Asia. It is usually used with the belief that it will boost the immune system and increase stamina; such properties are thought to be more useful for the elderly and those recovering from illness.³²

Summary of the research findings

The research on ginseng that has been done to date has been primarily in animal models and human tissue in the laboratory. Some beneficial effects of ginseng on the liver were seen in these studies. Researchers concluded that ginseng may also help strengthen glandular systems and the ability to resist disease.^33-36
One study found that ginseng may be helpful for elderly people with liver conditions similar to hepatitis.³⁷
No conclusions can be drawn about the possible usefulness and safety of ginseng as a treatment in people who have hepatitis C, because it has not been studied formally yet in people.

Side effects and possible risks
General adverse (negative) effects of ginseng can include insomnia, headache, nosebleed, nervousness, and vomiting. Prolonged use of caffeine and a high dose of ginseng may be associated with hypertension, which is of particular concern for people with cardiovascular disease or diabetes. In addition, people with diabetes who use insulin should be aware that ginseng has demonstrated hypoglycemic effects (lowering of the blood sugar). Ginseng has been shown in laboratory studies to inhibit grouping of platelets in the blood, increasing bleeding risk. Because of this, using ginseng along with NSAIDs (non-steroidal anti-inflammatory drugs), such as aspirin or ibuprofen, should be discussed with your health care provider.³²

Thymus Extract
The thymus is a gland that is involved in the regulation of the body's immune response. Thymus extract products consist of peptides taken from the thymus glands of cows or calves and are sold as dietary supplements. Often, these products carry claims of boosting immune system functioning to combat diseases, such as hepatitis C. These over-the-counter supplements should not be confused with the prescription drug thymosin alpha-1.

Summary of the research findings
There has been little testing of bovine thymus extract for treatment of hepatitis C. A small clinical trial of a product called Complete Thymic Formula, which contains bovine thymus extracts along with vitamins, herbs, minerals, and enzymes, did not find the product beneficial for hepatitis C patients who had not responded previously to interferon therapy.³⁸ However, this small study does not provide sufficient evidence to draw firm conclusions about either Complete Thymic Formula or thymus extracts in general.

Side effects and possible risks
In the study of Complete Thymic Formula, one adverse event was reported: a patient developed thrombocytopenia, a drop in the number of platelet cells in the blood; the patient recovered after treatment was stopped.³⁸ In general, no adverse effects from thymus extracts have been reported. However, since thymus extracts are derived from animals, there can be concern related to possible contamination from diseased animal parts.^k Accordingly, people on immunosuppressive drugs or who have suppressed immune systems, such as transplant recipients or persons with HIV/AIDS, should use caution about thymus extracts and consult with their health care provider.

^kWith regard to side effects, see "Sources: General," item F, entry on thymus extract.

Schisandra
Schisandra is a plant that has been used (through extracts from its fruit) in traditional Chinese medicine and in Kampo, traditional Japanese medicine. There are several species, including Schisandra chinensis, native to northeastern China and Korea, and Schisandra sphenanthera, native to China.

Summary of the research findings

Research has primarily focused on the various lignans (a class of plant nutrients) and essential oils in the dried fruit of schisandra.³⁹ Major constituents include the lignans gomisin A, schizandrins and schizandrol, vitamins C and E, and others.
Studies of the effects of schisandra in the liver have mostly been in animal models. These studies have suggested that extracts of the fruit have a liver-protective effect, a helpful effect on some liver enzymes, and an antioxidant effect.^l^,39,40
Schisandra is also used in herbal formulas. For example, an herbal medicine called TJ-108 (Ninjin-yomei-to is one of its Japanese names) used in Kampo has schisandra fruit among its herbal components. In one very small study, TJ-108 was compared with two other Kampo herbal formulas for effects in 37 patients who had chronic hepatitis C and had been treated before with interferon.⁴¹ The findings were that TJ-108 may have antiviral properties, which the authors attributed to schisandra fruit and its lignan gomisin A.^7,41 These findings need to be interpreted with caution because of the study's small size and because use of an herbal formula, not schisandra alone, was evaluated; herbal formulas contain many ingredients that could cause a variety of effects.
There are no reports on the safety and effectiveness of using schisandra alone for treatment of hepatitis C in humans in the sources reviewed for this report.

Side effects and other risks
Schisandra is considered generally safe. In some people, however, it may cause heartburn, acid indigestion, decreased appetite, stomach pain, or allergic skin rashes.

^lAntioxidants are substances (such as vitamin E) that help prevent oxygen from reacting with other chemicals in cells (oxidation), a process that can have negative effects.

Colloidal Silver
Silver is a metallic element that is found both in nature and in living organisms. Colloidal silver consists of tiny silver particles suspended in a solution. As a dietary supplement, colloidal silver is marketed with a variety of health claims, including for immunity, diabetes, cancer, and AIDS.

Summary of the research findings
Silver has had past uses in medicine, dating back to the Middle Ages. However, the advent of drugs has eliminated the vast majority of these uses. Reviews in the scientific literature on colloidal silver, including by staff of the U.S. Food and Drug Administration (FDA), have concluded that^42,43:

The use of colloidal silver can cause serious side effects.
Silver has no known role in the body.
Silver is not an essential nutrient and should not be promoted as one.
It has not been proven that silver has any role in immunity or any effectiveness against any diseases.
The amounts of silver in silver supplements have been analyzed and found to vary greatly.

Side effects and other risks
Animal studies have shown that silver accumulates substantially in the body. In humans, this accumulation can have a serious side effect called argyria, a bluish-gray discoloration of the body, especially of the skin, nails, and gums. How this happens is not fully known, but silver-protein complexes are thought to deposit in the skin and then be catalyzed by sunlight, in a process similar to traditional photography.^44,45 Argyria is not treatable or reversible. Other possible problems include gastrointestinal distress, headaches, and seizures.

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For More Information

NCCAM Clearinghouse
Toll-free in the U.S.: 1-888-644-6226
International: 301-519-3153
TTY (for deaf and hard-of-hearing callers): 1-866-464-3615

E-mail: info@nccam.nih.gov
NCCAM Web site: nccam.nih.gov
Address: NCCAM Clearinghouse, P.O. Box 7923, Gaithersburg, MD 20898-7923

Fax: 1-866-464-3616
Fax-on-Demand service: 1-888-644-6226

NCCAM is a component of NIH. The NCCAM Clearinghouse provides information on CAM and on NCCAM. Services include fact sheets, other publications, and searches of Federal databases of scientific and medical literature. The Clearinghouse does not provide medical advice, treatment recommendations, or referrals to practitioners.
The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) is also a component of NIH. NIDDK's National Digestive Diseases Information Clearinghouse provides materials about hepatitis C and its conventional treatment. Go to digestive.niddk.nih.gov or call 1-800-891-5389 or 301-654-3810.
The National Institute of Allergy and Infectious Diseases, also a component of NIH, has hepatitis C information. Go to www.niaid.nih.gov/publications/hepatitis.htm or call 301-496-5717.
The Centers for Disease Control and Prevention provides information on hepatitis C. Go to www.cdc.gov/ncidod/diseases/hepatitis/index.htm or call 1-888-443-7232.
The National Library of Medicine's (NLM's) PubMed database contains citations from over 4,500 peer-reviewed scientific and medical journals. Most citations include an abstract, and a number link to the full text of the article. Go to www.ncbi.nlm.nih.gov/entrez/query.fcgi.
CAM on PubMed, a subset of PubMed (see above), contains citations to literature on CAM. It is sponsored by NCCAM and NLM. Go to www.nlm.nih.gov/nccam/camonpubmed.html.
The FDA provides information on dietary supplements at www.cfsan.fda.gov/~dms/supplmnt.html or via an information line at 1-888-723-3366.
The NIH Office of Dietary Supplements provides information on supplements at ods.od.nih.gov and through its International Bibliographic Information on Dietary Supplements (IBIDS) database (ods.od.nih.gov/health.aspx).
ClinicalTrials.gov is a database of information on clinical trials, primarily in the United States and Canada, for a wide range of diseases and conditions. It is sponsored by the NIH and the FDA. Go to www.clinicaltrials.gov.

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Sources

General

National Institutes of Health. National Institutes of Health Consensus Development Conference Statement. Management of Hepatitis C: 2002. National Institutes of Health Web site. Accessed at odp.od.nih.gov/consensus/cons/116/116cdc_intro.htm on July 15, 2003. Also available from the NIH Consensus Program Information Center; toll-free in the U.S.: 1-888-644-2667.
National Institute of Diabetes and Digestive and Kidney Diseases. Viral Hepatitis: A Through E and Beyond. National Digestive Diseases Information Clearinghouse Web site. Accessed at digestive.niddk.nih.gov/ddiseases/pubs/viralhepatitis/index.htm on July 15, 2003. Also available from the National Digestive Diseases Information Clearinghouse; toll-free in the U.S.: 1-800-891-5389 (NIH publication no. 03-4762, 2003).
National Institute of Diabetes and Digestive and Kidney Diseases. What I Need To Know About Hepatitis C. National Digestive Diseases Information Clearinghouse Web site. Accessed at digestive.niddk.nih.gov/ddiseases/pubs/hepc_ez/index.htm on July 15, 2003. Also available from the National Digestive Diseases Information Clearinghouse; toll-free in the U.S.: 1-800-891-5389 (NIH publication no. 02-4229, 2002).
National Institute of Allergy and Infectious Diseases. What You Should Know About Hepatitis C. National Institute of Allergy and Infectious Diseases Web site. Accessed at www.niaid.nih.gov/dmid/hepatitis/hepcfacts.htm on July 15, 2003.
Gruenwald J, Brendler T, Jaenicke C, eds. PDR for Herbal Medicines. 2nd ed. Montvale, NJ: Medical Economics Company, Inc.; 2000.
Natural Medicines Comprehensive Database. Accessed at www.naturaldatabase.com on May 15, 2003.
Herrine SK. Approach to the patient with chronic hepatitis C virus infection. Annals of Internal Medicine. 2002;136(10):747-757.
Bren L. Hepatitis C: an update. FDA Consumer. July-August 2001. Accessed at www.fda.gov/fdac/features/2001/401_hepc.html on July 15, 2003.

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Tsubota A, Kumada H, Arase Y, et al. Combined ursodeoxycholic acid and glycyrrhizin therapy for chronic hepatitis C virus infection: a randomized controlled trial in 170 patients. European Journal of Gastroenterology & Hepatology. 1999;11(10):1077-1083.
van Rossum TG, Vulto AG, Hop WC, et al. Glycyrrhizin-induced reduction of ALT in European patients with chronic hepatitis C. The American Journal of Gastroenterology. 2001;96(8):2432-2437.
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Abebe W. Herbal medication: potential for adverse interactions with analgesic drugs. Journal of Clinical Pharmacy and Therapeutics. 2002;27(6):391-401.
Jeong TC, Kim HJ, Park JI, et al. Protective effects of red ginseng saponins against carbon tetrachloride-induced hepatotoxicity in Sprague Dawley rats. Planta Medica. 1997;63(2):136-140.
Matsuda H, Samukawa K, Kubo M. Anti-hepatitic activity of ginsenoside Ro. Planta Medica. 1991;57(6):523-526.
Nguyen TD, Villard PH, Barlatier A, et al. Panax vietnamensis protects mice against carbon tetrachloride-induced hepatotoxicity without any modification of CYP2E1 gene expression. Planta Medica. 2000;66(8):714-719.
Tran QL, Adnyana IK, Tezuka Y, et al. Hepatoprotective effect of majonoside R2, the major saponin from Vietnamese ginseng (Panax vietnamensis). Planta Medica. 2002;68(5):