Viral Hepatitis

Hepatitis is a serious disorder in which liver cells become inflamed. The inflammation is most occurs because of a virus. It can also be caused by an overactive immune system, and from drugs, alcoholism, chemicals, and environmental toxins. Viral hepatitis usually appears as type A, B, or C.

Type A, the most common form of viral hepatitis, often affects school-aged children. The disease is transmitted by contaminated food or water, or contact with a person ill with hepatitis A. The hepatitis A virus is shed in the stools of an infected person during the incubation period of 15 to 45 days before symptoms occur and during the first week that the person feels sick. Blood and other body fluids may also carry the infection. The virus does not stay in the body after the infection has resolved, and, unlike hepatitis types B and C, there is no "carrier" state (a person who spreads the disease to others but does not become ill).

Hepatitis types B and C affect people of all ages. Most people who become infected with hepatitis B get rid of the virus within 6 months. This type of short infection is known as an "acute" case of hepatits B. Approximately 10% of people infected with the hepatitis B virus develop a chronic, life-long infection. People with chronic infection may or may not have symptoms. Those who do not develop symptoms are referred to as carriers. Having chronic hepatitis B increases your chance of permanent liver damage, including cirrhosis (scarring of the liver) and liver cancer.

Signs and Symptoms

Acute Hepatitis

• Flu-like symptoms including fever, as well as aching or painful muscles and joints.
• Jaundice (yellow discoloration of both your skin and the whites of your eyes)
• Abdominal discomfort
• Fatigue
• Loss of weight
• Loss of appetite
• Nausea, vomiting
• Dark urine, colorless stool
• Diarrhea
• Whole body itching (called pruritus)
• Mild anemia
• Enlarged, tender liver

Chronic hepatitis may not be preceded by an acute phase or the acute symptoms may be quite subtle and go unnoticed. In fact, some people with hepatitis C only feel mild ongoing fatigue and, perhaps, whole body itching. The virus is then found by a blood test.

Causes

Hepatitis A is usually transmitted from feces on unwashed hands (putting dirty hands into the mouth) and by ingesting contaminated food and water (for example, seafood from sewage contaminated water). It can also be transmitted through close contact with someone who has the virus.

Hepatitis B and C are transmitted via blood; therefore, blood transfusion, intravenous (IV) drug use with contaminated needles, and sexual activity are all ways that people have contracted either of these viruses. In as many as 40% of the cases of hepatitis C, the specific cause of transmission is unknown. Blood and blood products that are used for transmission can now be tested for both hepatitis B and C. The latter test has been available since 1992.

Risk Factors

Hepatitis A

• Chronic institutionalization (nursing home or rehabilitation center)
• Day care employees or children
• Recent hepatitis A infection in a family member
• Recent travel or immigration from Asia, South or Central America
• Food industry workers
• Sewage workers

Hepatitis B

• Contact with blood in work setting: this puts physicians, nurses, dentists, and other healthcare personnel at particular risk
• Sex with multiple partners without the use of a barrier such as a condom
• History of blood transfusion prior to the early 1990's
• Receiving a tattoo with contaminated instruments
• IV drug use with sharing of contaminated needles
• Birth to a hepatitis B infected mother
• Travel to underdeveloped nations and immigrants from areas where disease rates are high (namely, the Asia Pacific and Mediterranean regions and southern Africa)
• Having the human immunodeficiency virus (HIV) puts you at greater risk for chronic hepatitis and its potential complications

Hepatitis C

• Blood transfusion prior to July 1992
• Solid organ transplantation from a donor who has hepatitis C
• IV drug use and sharing of contaminated needles
• Long-term kidney dialysis
• Contact with blood in work setting: this puts physicians, nurses, dentists, and other healthcare personnel at particular risk
• Sex with a person who has hepatitis C
• Birth to a hepatitis C infected mother, particularly if she has HIV
• Having HIV or hepatitis B puts you at greater risk for chronic hepatitis C and its potential complications

Diagnosis

First, your doctor will ask you a host of questions to assess your risk for the different types of viral hepatitis. Questions will inlude whether you:

• Work in health care setting, including either a medical laboratory or a dialysis unit
• Have a parent, sibling, or child infected with hepatitis
• Engage in unprotected sex or have a sexual partner with either hepatitis B or C
• Use drugs by injection
• Live in or are exposed to unsanitary conditions
• Consume possibly contaminated food or water
• Eat or handle raw shellfish

Next, your doctor will examine your abomen carefully including palpating your liver and spleen to see if either is enlarged or tender. Then, a blood test will be performed to assess your liver function and test for antibodies against the specific hepatitis viruses. Your doctor will likely request a urine test as well. For chronic hepatitis, a liver biopsy may be required, which must be done under general anesthesia. A liver biopsy is particularly important if you have chronic hepatitis C because this test assesses the degree of liver damage, which can occur even if you have no symptoms.

Preventive Care

Hepatitis A
Transmission of the virus can be reduced by faithfully following these practices, particularly in child daycare facilities and other institutions involving close contact with people:

• Avoid unclean food and water
• Wash hands thoroughly after using the toilet or changing a diaper, as well as before serving food
• Clean yourself thoroughly if you come into contact with any type of body fluid from an infected person (such as blood and feces)
• Those with the virus should not prepare food for others

Hepatitis B and C
Preventive measures are the same for both hepatitis B and C.

• Avoid contact with blood or blood products whenever possible
• Do not inject drugs of abuse, and especially do not share needles with anyone
• Avoid having multiple sexual partners
• Practice safer sex behaviors, including use of appropriate barrier methods such as condoms
• Go to a reputable shop for tattoos and body piercing
• Healthcare workers should practice universal precautions when handling blood and bodily fluids; this includes wearing gloves when performing any procedure with blood exposure, disposing of needles properly, and many other precautions, depending on your specific role.

Immunization

Hepatitis A
Candidates for the hepatitis A vaccine include:

• Anyone who lives or works in a community where outbreaks occur (such as a daycare center)
• Those who travel frequently or have long overseas stays in high-risk areas
• Sexually active homosexual men
• People who already have a chronic form of hepatitis; should be vaccinated against hepatitis A before the chronic form reaches late stages of liver disease
• Healthcare workers
• Those living in high-risk U.S. states, which include Alaska, Arizona, Arkansas, California, Colorado, Idaho, Missouri, Montana, Nevada, New Mexico, Oklahoma, Oregon, South Dakota, Utah, Washington, and Wyoming
• Those with intimate exposure to someone with hepatitis A; in this case, your doctor will decide if the vaccine or immunoglobulin (an immunizing agent) is most appropriate. This depends, in part, on the timing of the exposure.

Hepatitis B
There are several inactivated vaccines available for hepatitis B. Immunization provides the only definitive protection against hepatitis B. The hepatitis B vaccine is one of the recommended childhood immunizations, and is now part of routine pediatric care in the United States. Adults who are at higher risk, should also be vaccinated:

• Those who live with someone with hepatitis B
• Healthcare workers
• Travellers to high-risk areas
• Sexually active people who have multiple partners
• People on hemodialysis
• People who have suppressed immune systems (such as HIV)
• High-risk pregnant women

Hepatitis C
There is no vaccine for hepatitis C, but immunoglobulin helps protect against it after blood transfusions. Periodic doses in sexual partners of an infected person may also help to give protection.

Treatment Approach

Acute Hepatitis
The goals for treating acute viral hepatitis include:

• Assuring adequate nutrition and hydration
• Preventing further damage to the liver
• Avoiding transmission of the virus to others.

There are no medications to treat acute hepatitis, although your doctor may recommend drugs that alleviate some of the symptoms. Most cases of acute hepatitis are mild and do not even require hospitalization. Only people who are at high risk for complications, such as pregnant women, the elderly, people with serious underlying medical conditions, or those who become significantly dehydrated from excessive nausea and vomiting need to be hospitalized. The very rare cases of acute hepatitis that lead to liver failure (called fluminant acute hepatitis) not only require hospitalization, but also need liver transplantation. Chronic Hepatitis
The goals for treatment of chronic viral hepatitis include:

• Preserving liver function and preventing liver damage
• Boosting the immune system to help fend off damage from the virus

There are several medications from which your doctor will choose to help achieve these goals.

Because the conventional medications used to treat chronic hepatitis have a lot of unpleasant side effects, many people with this condition turn to alternative medical therapies instead. Despite the popularity of herbs, particularly milk thistle (Silybum marianum), to treat this liver condition, none are proven absolutely effective and safe. Other practices that may help boost your immune function and help make you feel stronger and less tired while taking conventional medications include homeopathy, acupuncture, and massage therapy. Make sure that the therapist knows that you have hepatitis so that the necessary precautions can be taken to avoid spread of the virus.

Lifestyle
Your doctor will talk with you about measures you can take to keep from spreading the virus. For hepatitis A, these measures include:

• Washing clothes thoroughly with hot water
• Washing your hands after using the toilet
• Heating contaminated articles for one minute, which should kill the virus
• Using household bleach for disinfecting hard surfaces
• Separating the eating and cooking utensils used by the household member with the virus from those used by other people living there
• Abstaining from sexual activity while acutely infected

For hepatitis B and C, these measures include:

• Avoiding sharing personal items such as toothbrushes and razors (microscopic blood particles may be on these items)
• Abstaining from sexual activity, or taking strict precautions such as always using a condom. Women should abstain during menstruation in particular.
• Handling objects contaminated with blood with special care, like wearing gloves when drawing blood if you work in a hospital
• Not sharing drug needles if you use street drugs intravenously and making sure that tatoo artists, body piercers, and acupuncturists use sterile needles. (Note: due to the standard use of sterile, disposable needles by licensed acupuncturists, there have been no reports of hepatitis infection from acupuncture therapy in the United States.)

If you are traveling to a high-risk country, take the following precautions:

• Get vaccinated against hepatitis A and possibly hepatitis B
• Use bottled water for drinking and brushing teeth
• Eat heated food promptly. Heated food should be hot to the touch.
• Avoid buying food from street vendors
• Avoid sliced fruit. It may have been washed in contaminated water.
• Avoid raw or undercooked fish and shellfish

Other general lifestyle measures to take include:

• Don't drink alcohol during the acute phase of hepatitis or if you become a carrier of types B or C.
• Quit smoking because new evidence suggests that cigarette smoking is associated with more severe infection.

Medications

Interferons – this group of medications are natural proteins that activate immune functions in the body and have anti-viral properties. These drugs do not work for everyone who takes them, but for those who do respond, the possible benefits include:

• Diminished viral levels of hepatitis B and C
• Reduced symptoms
• Improved survival rates

Drawbacks for this class of drugs include:

• Need to administer via injection
• Hepatitis B and C can become resistant to the medication; in other words, the drugs become ineffective over time
• Side effects from the interferons are often very unpleasant, even intolerable to some people as they may be worse than the symptoms from chronic hepatitis itself (particularly since some people with hepatitis C have no symptoms). Common side effects are flu-like symptoms including fever, chills, and muscle aches. Additional side effects include depression, hair loss, weight loss, and drop in white blood cells (the cells in the body that help fight infection).

Corticosteroids – may be used in the early stages of chronic hepatitis to enhance the effects of interferon.

Nucleoside Analogues – this class of drugs, including lamivudine and ribavirin, are used to stop replication of the virus. Advantages of lamivudine, often used to treat chronic hepatitis B, over interferon include:

• Can be taken orally
• Fewer side effects
• Less expensive

Like interferon, nucleoside analogues can lose their effectiveness over time.

Ribavarin is often used in combination with interferon for chronic hepatitis C. Although ribavarin improves the response rate for those with hepatitis C, side effects from the interferon become more likely when this second drug is added. Potential side effects from the ribavarin itself include:

• Anemia
• skin disorders
• coughing and shortness of breath
• sleep disturbance
• depression or anxiety
• heartburn
• weight loss

Surgery and Other Procedures

People with the following conditions may qualify for a liver transplant:

• Life-threatening cirrhosis and life expectancy is, otherwise, more than 12 years
• Liver cancer that remains confined to the liver
• Fulminant acute hepatitis

Five-year survival rate after liver tranplantation is between 60% and 80%. Unfortunately, in about 50% of those with chronic hepatitis who receive a liver transplant, the infection recurs.

Nutrition and Dietary Supplements

Although no special diets have been shown to help treat acute hepatitis, eating small snacks during the day, with larger ones in the morning, may be recommended. Eating this way helps optimize digestion, prevent weight loss, and reduce nausea. Avoid drinking alcohol as this may further damage the liver.

Alpha-lipoic acid combination
There have been several case reports of use of alpha-lipoic acid in combination with silymarin (milk thistle) and selenium (a substance with liver-protecting and antioxidant properties) to help treat hepatitis C. Alpha-lipoic acid is an antioxidant that your body makes and is also available as a supplement. Experts suggest that additional alpha-lipoic acid may prove useful in the treatment of chronic hepatitis because it relieves stress on the liver and helps rid the body of toxins.

Cysteine (N-acetyl-L-cysteine [NAC])
Cysteine is an amino acid that can be found in many proteins throughout the body. This supplement is thought to help detoxify harmful substances in the body. Preliminary evidence suggests that NAC supplements may help treat hepatitis C when combined with standard medical therapy.

S-Adenosylmethionine (SAMe)
S-Adenosylmethionine or SAMe is a naturally occurring compound that is involved in many biochemical processes in the body. This chemical has been under investigation for many years in Europe for the treatment of liver disease. Preliminary research suggests that it may provide protection against liver damage and scarring and may improve survival rates in people with cirrhosis due to alcohol abuse. Animal studies also suggest that SAMe may protect the liver from damage after acetaminophen overdose (a pain-relieving medication purchased without a prescription). While the results for treating liver damage from either alcohol or acetaminophen over dose are encouraging, more research is needed to understand whether taking supplemental SAMe will impact viral hepatitis.

Selenium
Selenium (found, for example, in fish, Brewer's yeast, wheat germ, garlic, whole grain,) is an essential mineral found in trace amounts in the body. Lower than normal selenium levels may be associated with an increased risk for liver cancer in people with hepatitis B and/or C. Low selenium levels may also worsen the toxic effects of alcohol on the liver. It is not clear, however, whether taking selenium supplements can help prevent or treat liver damage. There have been a few case reports of the use of selenium in combination with alpha-lipoic acid and silymarin (milk thistle) to help treat hepatitis C.

Spirulina
Spirulina is a type of blue-green algae found in most lakes and ponds. This supplement, which is thought to stimulate the immune system and have anti-viral effects, is considered a complete protein because well over half of it consists of amino acids -- the building blocks of protein. It is also a rich source of other nutrients including B complex vitamins, beta-carotene, vitamin E, carotenoids, manganese, zinc, copper, iron, selenium, and gamma linolenic acid (an essential fatty acid). There is some preliminary evidence suggesting that spirulina may help protect against liver damage and cirrhosis (liver scarring and failure) in those with chronic hepatitis. More research is needed in this area.

Zinc
One small study suggests that zinc supplements may improve the response to interferon therapy in people with chronic hepatitis C. More research would be helpful.

Herbs

Herbs, like medications, have potential side effects and may interact with prescription or over the counter drugs. They should, therefore, be used with caution and only under the guidance of a professionally trained and qualified herbalist. Milk thistle (Silybum marianum)
Milk thistle has been used since Greco-Roman times as an herbal remedy for a variety of ailments, particularly liver problems. Today, many professional herbalists recommend milk thistle extract for the prevention and/or treatment of various liver disorders including viral hepatitis. Several scientific studies lend support to this traditional use because they suggest that active substances in milk thistle (particularly silymarin) protect the liver from damage caused by viruses and a variety of toxins.

This early evidence is encouraging. However, despite the fact that milk thistle is widely used in the treatment of hepatitis (particularly hepatitis C), results from studies testing this use have been contradictory. Some researchers have found improvements in liver function in those with viral hepatitis taking milk thistle, while others have failed to detect these benefits. None of the studies have compared milk thistle with interferon or other conventional medications for this condition.

The bottom line is that more research is needed. In the interim, talk to your doctor about whether it is safe and worthwhile to try milk thistle for chronic hepatitis, particularly if medications did not work well for you or you could not tolerate the drugs due to side effects.

Licorice root (Glycyrrhiza glabra)
Licorice root has been used in both Eastern and Western medicine to treat a variety of illnesses, including liver disease. In one study of Japanese patients with hepatitis C, those who received intravenous treatment with glycyrrhizin (an active compound in licorice), cysteine, and glycine for an average of 10 years were significantly less likely to develop liver cancer and cirrhosis (scarring of the liver) than those who received placebo. In a second study of 57 patients with hepatitis C, glycyrrhizin significantly improved liver function after only one month. These effects diminished after glycyrrhizin treatment was discontinued.

Green tea (Camellia sinensis)
Results from several studies of animals and people suggest that one of the active ingredients in green tea, known as catechin, may help treat viral hepatitis. In these studies, catechin was isolated from green tea and used in very high concentrations. It is not clear at this time whether drinking green tea (which contains a lower concentration of catechins than the isolated forms used in these studies) confers these same benefits.

Others Other herbs that may be considered include:

• Turmeric (Curcuma longa) -- in animal studies, turmeric has been shown to have a protective effect on the liver. This may be related to turmeric's ability to help clear toxins. It is not known whether or not such liver protection applies to people.
• Astragalus (Astragalus membranaceus) -- has been used in traditional Chinese medicine for thousands of years. This herb is also used for its immune enhancing properties, especially for the prevention and treatment of the common cold and chronic hepatitis.

Homeopathy

There have been few studies examining the effectiveness of specific homeopathic remedies. A professional homeopath, however, may recommend one or more of the following treatments for viral hepatitis based on his or her knowledge and clinical experience. Before prescribing a remedy, homeopaths take into account a person's constitutional type. In homeopathic terms, a person's constitution is his or her physical, emotional, and intellectual makeup. An experienced homeopath assesses all of these factors when determining the most appropriate remedy for a particular individual.

• Aconitum — used during initial phases of hepatitis when the individual has a fever, jaundice, and sharp pains in the liver; can be used in newborns
• Belladonna— used in early stages of hepatitis when the individual has occasional liver pains that are worsened by inhalation and movement
• Chelidonium— for individuals with pain that originates in the liver and extends to the back and right shoulder; this remedy is most appropriate for individuals who have gray or yellow loose stools, fever, and jaundice; a craving for milk may be present; lying on the left side and ingesting hot food or drink may bring some relief
• China— for individuals with a tender liver and a sensation of fullness in the stomach; the individual may burp frequently although it provides no relief; he or she may also have cravings for sweets, cold drinks, or coffee
• Lycopodium— one of the primary remedies for hepatitis in children and adults; this remedy is most appropriate for individuals who feel tension in the liver area, have difficulty standing up, and feel full after eating only small amounts of food
• Mercurius— for individuals with a swollen, tender liver and jaundice; the tongue may also be yellow and swollen; this remedy is most appropriate for individuals with clammy perspiration, excessive salivation, a sensitivity to temperature variations, and bleeding gums; lying on the right side is painful and stools may be light gray or green
• Phosphorus— for individuals with burning pains under the right rib cage and in the back between the shoulder blades that are relieved by cold drinks; this remedy may be used in newborns with jaundice

Traditional Chinese Medicine (TCM)

When assessing a person with hepatitis, a TCM practitioner might make one of the following diagnoses:

• Hepatic qi stasis
• Hepatic yang excess with yin deficiency
• Hepatic yin insufficiency

Once the diagnosis is established, the practitioner is likely to use acupuncture, moxibustion (a burning of an herb called mugwort over acupuncture sites), and herbal drugs to address the imbalances of hepatic qi and yin-yang.

A few scientific reviews of the use of Traditional Chinese herbal combination remedies have suggested that this is a valuable treatment approach for hepatitis B in particular. Further research is needed. One popular TCM herb, Phyllanthus amarus, was not supported in these reviews, however, as an effective therapy for viral hepatitis, despite popularity of its use for this purpose. Glycyrrhizin (an active compound in the herb licorice) is frequently used in TCM; see the earlier section entitled Herbs for more details about the use of this substance for viral hepatitis.

Other Considerations

Food handlers should be extremely careful in the case of hepatitis A and healthcare workers should always exercise universal precautions, as described earlier in the section entitled Prevention, to avoid contraction or transmission of hepatitis B or C.

Support groups are available for those with chronic hepatitis B or C. It is often difficult to cope with having this particular disease. Talking with people who also have this condition in a formal setting is often very helpful. Check with your doctor or area hospital to locate a support group near you.

Pregnancy

Hepatistis B and hepatitis C can be transmitted during pregnancy or childbirth. Women who are pregnant or planning to become pregnant soon cannot take interferon or nucleoside analogues.

Warnings and Precautions

Because the liver processes many types of medications, you will most likely be advised to stop taking all drugs other than those recommended for treatment.

Similarly, certain herbs and supplements are known to cause harm to the liver:

• Kava kava (an herb used for anxiety and tension) can be toxic to the liver and cause severe hepatitis and even liver failure if taken excessively. Liver-related risks have prompted regulatory agencies in other countries, including Germany, Switzerland, France, Canada, and the United Kingdom, to warn consumers about the potential risks associated with kava use and to remove kava-containing products from the marketplace. Similarly, the United States FDA issued an advisory in March of 2002 regarding the potential risk of liver failure associated with kava-containing products, but this herb has not been taken off the market in this country.
• Vitamin A in large quantities can be toxic to the liver.

Prognosis and Complications

In terms of the acute phase of hepatitis, jaundice generally disappears in two to eight weeks. Occasionally, hospitalization is necessary during the acute phase (for example, if you become significantly dehydrated), but most people completely recover. Full recovery of normal liver function tests, however, may take up to several months.

Rare yet serious complications of acute hepatitis include aplastic anemia (when the bone marrow makes no new cells) which can be fatal, pancreatitis, very low blood sugar, and polyarteritis (inflammation of blood vessels). Also quite rare is the acute phase of hepatitis leading to liver failure (called fulminant hepatitis) with bleeding from the gastrointestinal tract and brain damage, known as hepatic encephalopathy. Occasionally, the acute phase of hepatitis B or C is more mild yet prolonged, with recovery taking up to one year; 5% to 10% of people with this prolonged acute phase go on to develop chronic hepatitis.

After the acute phase, long term prognosis depends on many factors, including the cause of the hepatitis, whether you go on to become a carrier of type B or develop a chronic form of the disease, and whether you have any other underlying medical problems. Approximately 5% to 10% of people with hepatitis B become carriers and about 25% of carriers progress to chronic hepatitis. The vast majority of people infected with hepatitis C go on to become life-long carriers and anywhere from 50% to 90% of these carriers go on to develop chronic hepatitis.

The chronic form of hepatitis can ultimate lead to scarring of the liver (known as cirrhosis) and liver failure. There are two types of chronic hepatitis – chronic active and chronic persistent. The latter is mild and either doesn't get worse or only does so very slowly. Chronic active hepatitis, on the other hand, is much more likely to lead to cirrhosis, permanent damage to the liver. Cirrhosis occurs in 5% to 10% of those with chronic hepatitis from hepatitis B and as many as 20% to 30% of those with chronic hepatitis from hepatitis C. Approximately 14% of people with cirrhosis develop liver cancer.

References

Agency for Healthcare Research and Quality. Milk thistle: effects on liver disease and cirrhosis and clinical adverse effects. Summary, evidence report/technology assessment: number 21, September 2000. Accessed at: http://www.ahrq.gov/clinic/milktsum.htm on November 15, 2002.

Alter MJ. Hepatitis C virus infection in the United States. J Hepatol. 1999;31(suppl 1):88-91.

Anonymous. Immunization of health-care workers: recommendations of the Advisory Committee on Immunizationn Practices (ACIP) and the Hospital Infection Control Practices Advisory Committee (HCIPAC). MMWR Morb Mortal Wkly Rep. 1997;46(RR-18):1-42.

Arase Y, et al. The long term efficacy of glycyrrhizin in chronic hepatitis C. Cancer. 1997;79:1494–1500.

Beloqui O, Prieto J, Suarez M, et al. N-acetyl cysteine enhances the response to interferon-alpha in chronic hepatitis C: a pilot study. J Interferon Res. 1993;13:279-282.

Berkson BM. A conservative triple antioxidant approach to the treatment of hepatitis C. Combination of alpha lipoic acid (thioctic acid), silymarin, and selenium: three case histories. Med Klin. 1999;94 Suppl 3:84-89.

Chen J, Chen M, Zhao B, Wang Y. Effects of acupuncture on the immunological functions in hepatitis B virus carriers. J Tradit Chin Med. 1999;19(4):268-272.

Chen TS and Chen PS. The liver in traditional Chinese medicine. J Gastroenterol Hepatol. 1998;13:437-442.

Cohen MR. Herbal and complementary and alternative medicine therapies for liver disease. A focus on Chinese traditional medicine in hepatitis C virus. Clin Liver Dis. 2001;5(2):461-478, vii.

Cummings S, Ullman D. Everybody's Guide to Homeopathic Medicines. 3rd ed. New York, NY: Penguin Putnam; 1997: 170-171.

Ferenci P, Dragosics B, Dittrich H, Frank H., Benda L, Lochs H, et al. Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. J Hepatol. 1989;9:105-113.

Flora K, Hahn M, Rosen H, Benner K. Milk thistle (Silybum marianum) for the therapy of liver disease. Am J Gastroenterol. 1998;93:139–43.

Gorban EM, Orynchak MA, Virstiuk NG, Kuprash LP, Panteleimonov TM, Sharabura LB. [Clinical and experimental study of spirulina efficacy in chronic diffuse liver diseases.] Lik Sprava. 2000(6):89-93.

Haley RW, Fischer RP. Commercial tattooing as a potentially important source of hepatitis C infection. Clinical epidemiology of 626 consecutive patients unaware of their hepatitis C serologic status. Medicine (Baltimore). 2001;80(2):134-151.

HEPATITIS, VIRAL. NMIHI. Accessed at http://www.nmihi.com/h/viral-hepatitis.htm on December 2, 2018.

Viral Hepatitis. The Johns Hopkins University. Accessed at hopkinsmedicine.org on October 29, 2018.

Imai K, Nakachi K. Cross sectional study of effects of drinking green tea on cardiovascular and liver diseases. BMJ. 1995;310(6981):693-695.

Koshy A, Marcellin P, Martinot M, Madda JP. Improved response to ribavirin interferon combination compared with interferon alone in patients with type 4 chronic hepatitis C without cirrhosis. Liver. 2000;20(4):335-339.

Lai MY. Firstline treatment for hepatitis C: combination interferon/ribavirin versus interferon monotherapy. J Gastroenterol Hepatol. 2000;15 Suppl:E130-133.

Langmead L, Rampton DS. Review article: herbal treatment in gastrointestinal and liver disease--benefits and dangers. [Review]. Aliment Pharmacol Ther. 2001;15(9):1239-1252.

Leung NW. Management of viral hepatitis C. J Gastroenterol Hepatol. 2002;17 Suppl: S146-S154.

Liaw YF, Leung NW, Chang TT, et al. Effects of extended lamivudine therapy in Asian patients with chronic hepatitis B. Asia Hepatitis Lamivudine Study Group. Gastroenterology. 2000;119(1):172-180.

Lieber CS. Liver disease by alcohol and hepatitis C: early detection and new insights in pathogenesis lead to improved treatment. Am J Addict. 2001;10 Suppl:29-50.

Lindsay KL. Treatment of chronic hepatitis C: comparative virologic response rates among the different interferons. J Hepatol. 1999;31 Suppl 1:232-236.

Liu JP, Manheimer E, Tsutani K, Gluud C. Medicinal herbs for hepatitis C virus infection. Cochrane Database Syst Rev. 2001;(4):CD003183.

Liu JP, McIntosh H, Lin H. Chinese medicinal herbs for asymptomatic carriers of hepatitis B. Cochrane Database Syst Rev. 2001;(2):CD002231.

Liu JP, McIntosh H, Lin H. Chinese medicinal herbs for chronic hepatitis B. Cochrane Database Syst Rev. 2001;(1):CD001940.

Luper S. A review of plants used in the treatment of liver disease: part two. Alt Med Rev. 1999;4(3):178-188.

Finasteride. NMIHI. Accessed at http://www.nmihi.com/f/finasteride.html

Mato JM, Camara J, Fernandez de Paz J. S-adenosylmethionine in alcoholic liver cirrhosis: a randomized, placebo-controlled, double-blind, multicenter clinical trial. J Hepatol. 1999;30:1081-1089.

McCulloch M, Broffman M, Gao J, Colford JM Jr. Chinese herbal medicine and interferon in the treatment of chronic hepatitis B: a meta-analysis of randomized, controlled trials. Am J Public Health. 2002;92(10):1619-1628.

Milliman WB, Lamson DW, Brignall MS. Hepatitis C; a retrospective study, literature review, and naturopathic protocol. Altern Med Rev. 2000;5(4):355-371.

Misoprostol. NMIHI. Accessed at http://www.nmihi.com/m/misoprostol.html

Patrick L. Hepatitis C: Epidemiology and review of complementary/alternative medicine treatments. Alt Med Rev. 1999;4(4):220-238.

Pessione F, Ramond MJ, Njapoum C, et al. Cigarette smoking and hepatic lesions in patients with chronic hepatitis C. Hepatology. 2001;34(1):121-125.

Pianko S, McHutchison JG. Treatment of hepatitis C with interferon and ribaviron. J Gastroenterol Hepatol. 2000;15(6)581-586.

Rizzetto M. Therapy of chronic viral hepatitis: a critical view. Ital J Gastroenterol Hepatol. 1999;31(8):781-793.

Saller R, Meier R, Brignoli R. The use of silymarin in the treatment of liver diseases. Drugs. 2001;61(14):2035-2063.

Scalzo R. Therapeutic botanical protocol for viral hepatitis. Protocol J Botan Med. 1995;1(2):159-160.

Schalm SW, Brouwer JT, Bekkering FC, van Rossum TG. New treatment strategies in non-responder patients with chronic hepatitis C. [Review]. J Hepatol. 1999;31 Suppl 1:184-188.

Seeff LB, Lindsay KL, Bacon BR, Kresina TF, Hoofnagle JH. Complementary and alternative medicine in chronic liver disease. Hepatology. 2001 Sep;34(3):595-603.

Stern E. Two cases of hepatitis C treated with herbs and supplements. J Altern Complement Med. 1997;3(1):77-82.

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;8(5):367-371.

Ullman D. Homeopathic Medicine for Children and Infants. New York, NY: Penguin Putnam; 1992: 96-97.

van Rossum TG, Vulto AG, Hop WC, Brouwer JT, Niesters HG, Schalm SW. Intravenous glycyrrhizin for the treatment of chronic hepatitis C: a double-blind, randomized, placebo-controlled phase I/II trial. J Gastroenterol Hepatol. 1999;14(11):1093-1099.

van Rossum TG, Vulto AG, Hop WC, Schalm SW. Glycyrrhizin-induced reduction of ALT in European patients with chronic hepatitis C. Am J Gastroenterol. 2001;96(8):2432-2437.

Viral Hepatitis. Physicians' Desk Reference for Consumers. Accessed at www.pdr.net on October 29, 2019.

Viral Hepatitis. Centers for Disease Control and Prevention. Accessed at https://www.cdc.gov/hepatitis/index.htm on October 29, 2018.

Walsh B, Maguire H, Carrington D. Outbreak of hepatitis B in an acupuncture clinic. Commun Dis Public Health. 1999;2(2):79-81.

Wang BE. Treatment of chronic liver diseases with traditional Chinese medicine. J Gastroenterol Hepatol. 2000;15 Suppl:E67-E70.

Yang H, Chen Y, Xu R, Shen W, Chen G. Clinical observation on the long-term therapeutic effects of traditional Chinese medicine for treatment of liver fibrosis. J Tradit Chin Med. 2000;20(4):247-250.

Yu MW, Horng IS, Hsu KH, Chiang YC, Liaw YF, Chen CJ. Plasma selenium levels and risk of hepatocellular carcinoma among men with chronic hepatitis viral infection. Am J Epidemiol. 1999;150(4):367-374.