HEPV-L's HEPATITIS C FAQ v3.0
December 7, 1998

This FAQ is dedicated to the memory of David H. Kehrer, LTC John Heintz (Peters) and his wife Patricia Heintz (Peters), Dr. Horst Irmler, Daniel Bodiford, Cliff Reno and John Savala.

PART 0: ADMINISTRIVIA

0.01 Introduction
0.02 Disclaimer

PART I: THE BASICS

I.0.1 What is Hepatitis?
I.0.2 What Happens in the Body?
I.0.3 What is the Incubation Period?
I.0.4 How Does Hepatitis C Usually Begin?
I.0.5 What Are the Different Types of Hepatitis?
I.0.6 What is the Function of the Liver?
I.0.7 Hepatitis C (HCV)
I.0.7a When was Hepatitis C Discovered?
I.0.8 Who Gets Hepatitis?
I.1.0 How is it Transmitted?
I.1.0a How is it NOT Transmitted?
I.1.1 HCV and Blood Transfusion
I.1.2 HCV and Intravenous Drug Use
I.1.3 HCV and IV Immunoglobulin
I.1.4 Neonatal Transfer of HCV
I.1.5 Other Means of HCV Transmission
I.1.5a Sexual Transmission
I.1.5b Occupational Exposure (Health Care Workers)
I.1.5c Toothbrushes/Razors/Nail Clippers
I.1.5d Hemodialysis
I.1.6 Highly Speculative Modes of Transmission
I.1.6a Tears, Saliva, Urine, Other Body Fluids
I.1.6b Cat Scratches
I.1.6c Mosquitoes
I.1.6d Alternative Medical Procedures
I.1.6.e Household Transmission
I.1.6f Other
I.1.6g Is HCV Anything Like HIV?
I.1.7 Prevention
I.1.7a When and How Long Can it be Spread?
I.1.7b How Can the Spread of HCV be Prevented?
I.1.7c Cleaning Up Blood Spills
I.1.7d What to do in Case of an Accidental Needlestick
I.1.8 Who Should I Tell?
I.1.9 Can You Get Hepatitis More Than Once?
I.1.10 Vaccines

PART II: MEDICAL ISSUES

II.0.1 How Do I Find Good Medical Care for Hepatitis
II.0.2 Hepatologists and Gastroenterologists
II.1.0 How is it Diagnosed?
II.1.1 Antibody Tests
II.1.2 What is a PCR?
II.1.2a What is a Genotype?
II.1.3 Is it Possible the Test Could be Wrong?
II.2.0 Biopsy
II.2.0a What is a Liver Biopsy
II.2.0b What Are the Dangers of Liver Biopsy?
II.2.0c Will it Hurt?
II.2.1 Chronic Active and Chronic Persistent
II.2.2 What Are the Main Symptoms of HCV?
II.2.2a Fatigue
II.2.2b Right-Side Pain
II.2.2c Loss of Libido
II.2.2d Red Palms
II.2.2e Nausea
II.2.2f Brain Fog (Confusion/Forgetfulness)
II.2.2g Itching
II.2.2h Vision Problems
II.2.2i Dizziness
II.3.0 It's Not All In Your Head!
II.3.1 What is the Evolution of the Disease?
II.4.0 What Other Medical Problems Are Related to HCV?
II.4.0a Cryoglobulinemia
II.4.0b Thyroid and Autoimmune Problems
II.4.0c Rheumatoid Arthritis-Like Symptoms
II.4.0d Fibromyalgia
II.4.0e Dermatological Manifestations
II.4.0f Porphyrins
II.4.0g Lichen Planus
II.5.0 Cycles and Flareups
II.6.0 Should I be Vaccinated Against Other Types?
II.7.0 HCV and Women's Concerns
II.7.1 How Does HCV Relate to Pregnancy?
II.8.0 How Does HCV Affect Children?
II.9.0 What Are the Different Clinical Indications?
II.9.1 Elevated Liver Enzymes
II.9.2 Jaundice
II.9.3 Hepatomegaly/Splenomegaly
II.9.4 Spider Nevi
II.9.5 Ascites
II.9.6 Portal Hypertension/Varices
II.9.7 Hepatic Encephalopathy
II.9.8 Cirrhosis
II.9.9 Fulminant Hepatitis
II.9.10 Does HCV Increase the Likelihood of Cancer?
II.10.0 How Many of Us Are There?

PART III: TREATMENT (Conventional Medicine)

III.1.0 Interferon
III.1.0a When is Interferon Treatment Not Indicated?
III.1.0b Interferon "Breakthrough" and "Non-Response"
III.2.0 Iron Reduction Therapy
III.3.0 Ribavirin
III.3.1 Rebetron (Interferon and Ribavirin Combined)
III.3.2 Consensus Interferon
III.3.3 Alferon
III.3.4 Lymphoblastoid Interferon
III.3.5 Protease Inhibitors
III.3.5 Interferon and GM-CSF - Combined
III.4.0 Amantadine
III.4.1 Rybozyme Gene Therapy
III.4.2 Antisense Based Therapies
III.5.0 Ofloxacin
III.6.0 Thymosin
III.7.0 Cyclosporine Therapy
III.8.0 Reticulose
III.9.0 Transplant
III.10.0 Others

PART IV: TREATMENT (Alternative Medicine)

IV.0.1 Acupuncture
IV.0.2 Chiropractic
IV.0.3 Energy Healing
IV.0.4 Reflexology
IV.0.5 Homeopathy
IV.1.0 Herbal Treatments and Vitamins
IV.1.1 Kombucha Tea
IV.1.2 Reishi/Shitake Mushrooms
IV.1.3 Dandelion
IV.1.4 Milk Thistle
IV.1.5 Artichoke
IV.1.6 Licorice Root
IV.1.7 Spirulina
IV.1.8 Garlic
IV.1.9 Thymic Factors
IV.1.10 Vitamin C
IV.1.11 Vitamin B12
IV.1.12 Vitamin E
IV.1.13 Natural Interferon Boosters
IV.1.14 Other Herbs or Vitamins
IV.2.0 Exercise
IV.3.0 Stress Management
IV.4.0 Positive Attitude
IV.5.0 Tai Chi/Chi Kung/Yoga/Meditation
IV.6.0 Other Ways to Keep Yourself Healthy

PART V: NUTRITION

V.1.0 What Should I Do About Nutrition?
V.1.1 Foods to Avoid
V.2.0 Nutrition and Cirrhosis
V.3.0 Coffee, Tea, Caffeine and Other Stimulants
V.4.0 Salt

PART VI: DRUGS AND ALCOHOL

VI.1.0 Alcohol
VI.2.0 Tobacco
VI.3.0 Marijuana
VI.4.0 What are the Effects of Recreational Drugs?
VI.4.1 Intravenous Drug Use Precautions
VI.4.2 Cleaning Fits
VI.4.3 Methadone

PART VII: HOW CAN HCV AFFECT MY EMOTIONAL LIFE?

VII.1.0 How is Depression Related to Hepatitis?
VII.1.1 Mood Changes
VII.1.2 Dealing with a Chronic Disease
VII.1.3 Dealing with a Lower Level of Energy
VII.1.4 Irritability
VII.1.5 How Can HCV Affect My Sex Life?
VII.1.6 Helping a Friend with Hepatitis C
VII.1.6a What Can I Say?
VII.1.6b What *Shouldn't* I Say?

PART VIII: LIVING WITH HCV

VIII.1.0 Life Problems Created by HCV

PART IX: DEALING WITH INTERFERON THERAPY

IX.1.1 Hair Loss
IX.1.2 Nausea
IX.1.3 Fatigue
IX.1.4 Importance of Water
IX.1.5 Timing of Injections
IX.1.6 Injection Hints
IX.1.7 Needle Size
IX.1.8 Help! I Think I Hit a Vein!
IX.1.9 What to do When You Can't Afford the Interferon

PART X: WHERE DO WE GO FROM HERE?

X.1.0 Long-Term Prognosis (Am I Going to Die?)
X.2.0 Current Research, Testing, New Drugs

PART XI: EMPLOYMENT AND DISABILITY

XI.1.0 Income Security: Job and/or Disability Benefits
XI.1.1 How Do I Handle Problems About My Job?
XI.1.2 Problems in Seeking Disability Benefits
XI.1.3 Applying for SSI/SSDI

PART XII: IMPORTANT INFORMATION

XII.1.0 What Else is Important to Know About HCV?
XII.1.1 HCV Information Resources
XII.1.2 National (USA)
XII.1.3 Canada
XII.1.4 Australia/New Zealand
XII.1.5 Great Britain
XII.1.6 Germany
XII.1.7 Local (USA) Associations and Support Groups
XII.1.8 HCV Resources on the Internet and Usenet
XII.1.9 Bibliography: Suggested Reading
XII.1.10 Newsletters, Magazines and Videos

APPENDIX A: Where to Get the Current Version of the FAQ
APPENDIX B: Common Abbreviations and Medical Terms
APPENDIX C: Some Recommended World Wide Web Sites

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Subject: Part 0: Administrivia

Subject: 0.00 Copyright

The HEPV-L FAQ is copyright © 1996-99 by Patricia Johnson on behalf of the HEPV-L Internet Mailing List. Permission is granted to redistribute or quote this document for non-commercial purposes provided that you include an attribution to HEPV-L, the contact address of CLOTHO@BELLATLANTIC.NET or HEPVL-REQUEST@MAELSTROM.STJOHNS.EDU, the FAQ’s version number and date, and at least two locations from which a current version of this FAQ may be retrieved (see Appendix 1). For any other use, permission must be obtained in writing from Patricia Johnson (clotho@bellatlantic.net).

This is a document whose development is in progress. Please make comments to help improve it. Please send suggestions for additions, corrections, or changes privately to the author (Patricia Johnson) at address: clotho@bellatlantic.net

If you want your contribution to be anonymous, please state so.

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HEPV-L is a list devoted to people with chronic hepatitis, and related liver diseases. Its address is HEPV-L@MAELSTROM.STJOHNS.EDU.

Subscribe by addressing a message to:

LISTSERV@MAELSTROM.STJOHNS.EDU

and in the body of the message, on the first line, type:

SUB HEPV-L FIRSTNAME LASTNAME (substituting your name for the first and last name)

Any questions, or problems signing on—or off—the list, please contact one of the listowners at HEPVL-REQUEST@MAELSTROM.STJOHNS.EDU -------------

This document answers frequently asked questions (FAQ) about the hepatitis C virus (HCV), its treatment, and related complications.

This FAQ is not comprehensive, and there will be further FAQs describing other types of hepatitis (viral - A,B,D,E,G, Autoimmune, toxic) and related liver disorders and complications, as well as treatments, electronic resources and other specialized topics sometime in the near future. These related FAQs will likely be found near where you have found this one.

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The information presented in this document was written and developed by patients and members of the HEPV-L mailing list.

It represents an informal catalog of accumulated knowledge by people who for the most part are not medical professionals. As this file is developed further, we hope to include references and citations which will document more of the statements that are made here. Much of the information contained in this FAQ was compiled from the varied and personal experiences and opinions on the HEPV-L mailing list. As useful as this information may be, it must not be considered medical advice, and must not be used as a substitute for medical advice. And as always, don’t forget to use your common sense. It is important that anyone who has, or thinks they may have, hepatitis should consult with a licensed health care practitioner who is familiar with liver disease.

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Hepatitis is an inflammation of the liver. "Hepato" is Greek for "liver," and "itis" means "inflammation." The different types of hepatitis are caused by different things, but they all produce inflammation of the liver. Viral hepatitis refers to several common contagious diseases caused by viruses that attack the liver.

The most important types of viral hepatitis are hepatitis A, hepatitis B, and hepatitis C. Newly discovered forms of viral hepatitis also include hepatitis D, E, and G. Non-viral forms of hepatitis can be caused by toxic agents (drugs or chemicals), alcohol, or autoimmune processes. Another form of hepatitis is toxic hepatitis.

Toxic hepatitis can be caused by viruses or by liver damage due to toxic substances. Toxic hepatitis is a deterioration of the liver cells caused by chemicals, alcohol, drugs, and industrial compounds.

Alcohol abuse is a common cause of toxic liver damage.

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The hepatitis A and E viruses first enter the gut and begin reproducing.

They spread to the liver and multiply in liver cells. Hepatitis B, C, D, and G enter the bloodstream; when they pass through the liver, they enter liver cells and begin to reproduce. The body attacks the infected cells, which causes the liver to become inflamed. In hepatitis B infection, the liver usually repairs itself, leaving antibodies to the surface antigen, which shows that the infection occurred, but that the body defeated it.

When someone catches the hepatitis C virus, their body produces antibodies to try to destroy it. More often than not, the antibodies fail to identify the hepatitis C virus properly. The infection then remains long-term. Most infected people don’t know they have the virus. This is because for some people there will be no symptoms and for others, symptoms may take an average 13 years to develop. Some people may have hepatitis C for 20 years or more before finding out.

The way that hepatitis affects people is different for different people. Some are not affected by the condition, but others are affected very badly.

It currently seems that if 100 people catch hepatitis C:

	Stores iron reserves, as well as vitamins and minerals
	Makes bile to help digest food
	Detoxifies poisonous chemicals, including alcohol, beer, wine, and drugs - prescribed and over-the-counter as well as illegal substances. Acts as a filter to convert them to substances that can be used or excreted from the body
	Converts food we eat into stored energy, and chemicals necessary for life and growth
	Makes your blood
	Manufactures new proteins
	Makes clotting factors to help blood clot
	Removes poisons from the air, exhaust, smoke and chemicals we breathe.
	Manufactures and exports important body chemicals used by the body. One of these is bile, a greenish-yellow substance essential for the digestion of fats in the small intestine.

"Relax...you have cooties...but they aren’t as bad as you are imagining." - Cindy Torchin: swarren@idir.net polled 50 people on the HEPV-L list and compiled the following results:

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The main symptom of most people with hepatitis C is chronic fatigue, ranging from simply getting tired easily to extreme, debilitating fatigue.

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Even though the liver itself contains no nerve endings, and does not feel pain, many people with HCV experience a pain on the upper right side of their body, just beneath the ribs.

This is thought by some to be "referred pain" from the swelling of the liver capsule due to the disease process. This pain may also be referred to the right shoulder or to the back between the shoulder blades.

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Many hepatitis C patients find that they are no longer interested in sex. This tends to be especially true for those undergoing interferon treatment. This is not necessarily directly related to the hepatitis, but is most likely due to the stress, discomfort and exhaustion caused by the struggle with a chronic illness.

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Red palms can occur in any chronic liver disease and are not specifically caused by the virus. The cause for the redness is unknown, but it’s speculated that it may involve upset hormone metabolism or microcirculatory changes.

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A few of the more popular nausea aids are chewing candied ginger, putting a (small) drop of peppermint oil on the end of your tongue, eating small frequent meals, dry crackers and weak tea, and popsicles.

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This is the mental fuzziness and forgetfulness that some people experience. It’s not the same as encephalopathy, and seems to occur in all stages of the illness. Some people have found taking CoEnzyme Q10, also known as CoQ10, to be helpful (2 30mg capsules per day). Another listmember recommends taking Gingko Biloba.

The build-up of bilirubin in the skin may cause itching.

Itching can be treated with antihistamines, or cholestyramine (which binds bile in the intestines). Actigall and Questran are two drugs reported to help with this problem.

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Some hepatitis patients complain of blurring vision, and dry eyes. This can be especially true while undergoing interferon treatment.

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Some people have found that wearing "Sea Bands" helps with their dizziness. Sea Bands are elastic bands that can be bought, usually in sporting goods stores, which press against pressure points in the wrist. They were designed for use in seasickness.

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There are two products (mouthwash and toothpaste) by the name of Biotene, which are designed to help with the problem of a dry mouth and gum problems as a result of medication use.

Several listmembers have reported great relief by using these products.

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Some doctors (but thankfully fewer than there used to be) insist on believing that HCV usually has no symptoms, and dismiss the patient’s complaints as being "all in their head".

Some HCV+ patients have been treated for depression for many years before their actual diagnosis of HCV was uncovered. Much is still unknown about the hepatitis C virus, and many physicians have not had much experience treating it. Many doctors are not yet familiar with the research which legitimizes the various symptoms which go along with this virus.

Emerging illnesses such as HCV typically go through a period of many years before they are accepted by the medical community, and during that interim time patients who have these new, unproven symptoms are all too often dismissed as being "psychiatric cases". This has been the experience with HCV as well.

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Three out of four people infected with hepatitis C - not 50%, as once thought - will remain infected for life. Up to half of those people will develop cirrhosis, scarring of the liver, and up to 10,000 will die this year, say doctors and disease trackers meeting in San Diego. The latest findings are sobering because about 1.4% of the U.S. population is infected with the virus - "Hepatitis C Chronic 75% of the Time", USA Today, 05-15-1995

At least 50-80% of people infected with HCV will develop chronic hepatitis; ultimately, 20-30% of those will progress to cirrhosis.

Another 20-30% may develop chronic HCV infection without abnormal elevations of liver enzymes in the blood. - "Prevention, Diagnosis, and Management of Viral Hepatitis", AMA

Chronic hepatitis C infection occasionally causes problems for parts of the body beyond the liver. The organs most often affected include the blood vessels, skin, joints, kidneys, and thyroid gland. If chronic hepatitis C infection causes liver cirrhosis (severe scarring of the liver rarely caused by hepatitis C), many problems may arise from the cirrhosis, per se. Potential problems from cirrhosis include fluid accumulation in the abdomen, bleeding into the stomach, jaundice, confusion, poor blood clotting, and susceptibility to infection.

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Hepatitis has so many symptoms that it’s easy to ascribe all new anomalies to this disease. But HCV patients are not exempt from getting other illnesses also, therefore it is important to regularly monitor your health and to consult with your doctor about the changes as they progress.

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One-third to one-half of people with chronic hepatitis C infection have cryoglobulinemia (antibodies in the bloodstream attached to the hepatitis C RNA that happen to solidify when cold).

Hepatitis C is recognized as the most common cause of mixed cryoglobulinemia.

Most of the people with cryoglobulinemia from hepatitis C have had their hepatitis for a long time or have cirrhosis. People with higher concentrations of hepatitis C RNA in their blood do not seem to have a higher risk of having cryoglobulinemia. Usually the cryoglobulins are in low concentration and cause no symptoms.

About twenty-percent of people with hepatitis C and cryoglobulinemia have symptoms. Symptoms most often associated with cryoglobulinemia include mild fatigue, joint pains, or itching.

Occasionally, people with cryoglobulinemia develop vasculitis (inflammation of the blood vessels) which can cause purpura (purple skin lesions), Raynaud’s phenomenon (the hands turn white, then blue, and then red from constriction and subsequent dilation of the blood vessels), or numbness in the hands and feet. The presence of cryoglobulinemia does not effect people’s response to interferon.

In fact, some people with vasculitis have improvement in the vasculitis as their liver tests improve on interferon.

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Chronic hepatitis C infection is also associated with many autoimmune diseases (where the body develops antibodies which attack parts of itself). For example, about one-tenth of people with chronic hepatitis C infection (more often in women and older people) have antibodies to the thyroid gland, one-half of whom may develop hypothyroidism (an underactive thyroid gland).

Additionally, interferon therapy causes hypothyroidism or hyperthyroidism (an overactive thyroid gland) in about one-tenth of those treated.

People with hypothyroidism may suffer from fatigue poor memory, weakness, constipation, weight gain, muscle cramps, intolerance to cold, hoarse voice, coarse skin, and brittle hair. People with hyperthyroidism may suffer from anxiety, insomnia, weakness, diarrhea, weight loss, intolerance to heat, velvet-like skin, and brittle nails. Hypothyroidism can be treated with thyroid hormone pills.

Hyperthyroidism can be treated with pills that block thyroid hormone synthesis. If the thyroid gland dysfunction is from interferon treatment and is caught early, the thyroid gland will return to normal once interferon is stopped.

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Hepatitis C infection can present with rheumatic manifestations indistinguishable from rheumatoid arthritis. The predominant clinical findings include palmar tenosynovitis: small joint synovitis, and carpal tunnel syndrome. Risk factors such as transfusions and IV drug abuse or a history of hepatitis or jaundice should be included in the history of present illness of any patient with acute or chronic polyarthritis or unexplained positive RF. In such patients, gammaglutamyl aminotransferase, serologic studies for hepatitis C, and other tests appropriate for chronic liver disease should be performed. - " Journal of Rheumatology, June 1996;23(6):979-983.

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Fibromyalgia is the name for a condition that typically includes widespread muscle pain, fatigue and abnormal sleep patterns.

Until a few years ago, doctors called the condition fibrositis or muscular rheumatism and believed that for the most part, the condition was "all in the patient’s head". Today, fibromyalgia is recognized by medical organizations as a genuine and serious problem.

The symptoms of fibromyalgia typically include pain in many muscles, and around ligaments and tendons, persistent fatigue, waking up feeling tired even after a full night’s sleep, headaches, bouts of constipation and diarrhea, abdominal pain, painful menstrual periods, sensitivity to cold, numbness or tingling, and difficulty exercising.

Symptoms vary widely among patients and tend to wax and wane over time. An illness, injury, cold weather or emotional stress may trigger a fibromyalgia episode or make ongoing symptoms worse.

A study at the Oregon Health Sciences University and Portland Adventist Hospital suggests hepatitis C may trigger fibromyalgia ( "Fibromyalgia: A prominent feature in patients with musculoskeletal problems in chronic hepatitis C, A report of 12 patients," by A. Barkhuizen, G.S. Schoepflin, and R.M. Bennett, Journal of Clinical Rheumatology, Vol. 2, No. 4, August 1996 ) . This study is the first to show a link between the two illnesses.

It was determined that the relationship between the hepatitis C virus and fibromyalgia followed three distinct patterns:

In nine patients, fibromyalgia developed as a long-term complication of the hepatitis, arising on average 13.4 years after the virus was acquired.

In two patients, fibromyalgia arose simultaneously with the hepatitis C infection.

In one patient, pre-existing fibromyalgia was significantly worsened by the hepatitis C.

It is unknown why the hepatitis C virus and fibromyalgia may be linked, but the authors suggest that hepatitis C causes chronic activation of the immune system that leads to muscle aching, fatigue, mental changes, sleep abnormalities, and alterations of the neuroendocrine system.

The patients with both hepatitis C and fibromyalgia could be distinguished from most other patients with fibromyalgia alone because they had symptoms unusual to fibromyalgia. These symptoms included synovitis (inflammation of the membrane around a joint, bursa, or tendon) and vasculitis (inflammation of a blood or lymph vessel).

In addition, laboratory findings pointed to a disease process other than fibromyalgia.

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The main dermatological disorders in HCV infection include (1) vasculitis (mainly cryoglobulin-associated vasculitis, the cause of which is HCV in most cases, and, possibly, some cases of polyarteritis nodosa); (2) sporadic porphyria cutanea tarda; (3) cutaneous and/or mucosal lichen planus; and (4) salivary gland lesions, characterized by lymphocytic capillaritis, sometimes associated with lymphocytic sialadenitis resembling that of Sjoegren’s syndrome.

Hepatitis C virus is the cause of, or is associated with, various dermatological disorders. In patients with such disorders, HCV infection must be sought routinely because antiviral therapy may be beneficial in some of them. - Arch Dermatol. 1995; 131:1185-1193

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Porphyrins are a group of compounds that are mainly synthesized in the bone marrow. They play an important role in many chemical reactions in the body, e.g. with proteins to build hemoglobin. They are later converted to bile pigments mainly in the liver. Porphyrinuria increase of porphyrins in the urine) may be caused by chronic liver diseases. Hepatitis C is a major cause of porphyria throughout the world and may cause many symptoms, including excess blood iron - important in conjunction with an interferon therapy (since elevated blood iron seems to reduce the effect of interferon).

Porphyria cutanea tarda is a rare deficiency of a liver enzyme essential for cellular metabolism. The enzyme deficiency may cause sun exposed skin to blister, ulcerate, turn dark, or bruise. Hair may increase on the forehead, cheeks, or forearms, and the urine may turn pink or brown. It now appears that hepatitis C is the most common trigger of porphyria in people who are predisposed.

Topical sunscreens do not prevent the skin lesions. Avoidance of alcohol and removal of iron by repeated phlebotomy (blood removal) or taking medication that binds to iron sometimes helps. Chloroquine (an anti-malaria drug), which removes a toxic by-product of the enzyme deficiency, may help, as well.

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Occasionally, people with chronic hepatitis C develop a skin condition called lichen planus. It is a grouping of small, itchy, irregular, flat-topped reddened bumps. The bumps often have a network of very fine gray lines on their tops. The bumps show up most often on the wrists, shins, lower back, or genitals.

Lichen planus also frequently occurs in the mouth, where it looks like a white, net-like plaque. It sometimes shows up as mouth ulcers and can be treated with a steroid mouth rinse called Dexamethasone Elixir or Nystatin tablets.

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Hepatitis flare-ups tend to occur in cycles, where for a while you may feel pretty good, then bad (maybe days to weeks for each period), then good again. It can be frustrating to obtain some relief, but then not know whether you have recovered or if you are merely between cycles.

Some people claim that they begin to feel better in the Spring, then start to feel worse again in August/September, with a low point usually around November/December.

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Patients with chronic hepatitis C who are at risk for hepatitis B should be offered vaccination during their first contact with healthcare professionals, according to a report from Great Britain’s University of Cambridge. ( "Prospective Study of Hepatitis B Vaccination in Patients with Chronic Hepatitis C," British Medical Journal, May 25, 1996;312:1336-1337 ).

Chronic hepatitis C (HCV) infection is estimated to occur in between 70- and 92 percent of intravenous drug users. These IV drug users are also at risk for parenterally or sexually transmitted hepatitis B. Coinfection with hepatitis B virus (HBV) may accelerate underlying liver damage due to hepatitis C.

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Women can be affected by hepatitis C in a different way from men. This is possibly due to hormonal effects and liver damage.

MENSTRUATION : The hormonal effects of HCV can involve menstrual irregularities, particularly if you are experiencing significant hepatitis C symptoms. It is important that your general health is checked as well as your hepatitis C monitored. Tampons and sanitary napkins should be secured in plastic bags before going into the trash.

BIRTH CONTROL : If you are experiencing significant hepatitis symptoms, using the estrogen-based contraceptive pill may be inadvisable.

In these cases, the progesterone-only pill or Depo-Provera may be preferable.

HORMONE REPLACEMENT THERAPY : If you have severe hepatitis symptoms you may need to discuss with your doctor whether hormones should be used for menopausal symptoms. If this is the case, external vaginal creams and skin patches are probably better than pills.

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Dysfunctional uterine bleeding and premature menopause, and most any other sort of hormonal aberration is pretty common with chronic liver disease. The liver processes these hormones, and they tend to not get processed properly when the liver is damaged.

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While on interferon therapy, many woman find that they come down with one yeast infection after another, due to the immunosuppression.

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Waste paper products (napkins and tampons) which have been exposed to blood should be securely wrapped and disposed of in a safe manner. A 10% bleach (soak for 30 minutes) should be used on all contaminated surfaces, and in the laundry for clothing and linens which have been exposed to blood.

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Sexual intercourse during your period is not safe.

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A substantial proportion of pregnant women with hepatitis C virus infection have circulating HCV RNA, even when they are asymptomatic, according to a report from Italy. Researcher A.

Floreani and colleagues noted, however, that these women do not have an increased risk of obstetric complications and that pregnancy does not appear to induce symptomatic liver disease. - "Obstetrics (HCV); Circulating HCV RNA Does Not Increase Pregnancy Complications", Hepatitis Weekly, June 24, 1996

If a baby is born to an HCV+ mother and its blood was tested at birth for hepatitis C antibodies, the test would come back positive.

This is because the baby has some of its mother’s antibodies.

These antibodies clear naturally over time. A test at 12 months usually confirms a toddler has the virus.

BREASTFEEDING : The hepatitis C virus has not been found in samples of breastmilk taken from HCV+ women. Transmission risk via breastmilk is therefore very unlikely. There are many advantages to breastfeeding. Breastfeeding mothers should check their nipples before each feed and avoid breastfeeding if they are cracked or bleeding.

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Circulating HCV RNA does not increase pregnancy complications.

A substantial proportion of pregnant women with hepatitis C virus infection have circulating HCV RNA, even when they are asymptomatic, however, these women do not have an increased risk of obstetric complications and that pregnancy does not appear to induce symptomatic liver disease. "There is no risk to the outcome of pregnancy in an anti-HCV positive pregnant mother. The majority of pregnant women have normal transaminase levels during the course of pregnancy, although a substantial proportion have circulating HCV RNA. Pregnancy does not induce a deterioration of liver disease, and HCV infection does not increase the risk of obstetric complications." - - "HCV Infection in Pregnancy," British Journal of Obstetrics and Gynecology, 1996;103:325- 329

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Children with chronic hepatitis cannot be treated simply like miniature adults. Specific issues and questions need to be addressed when dealing with the pediatric age group.

Pediatric patients are less likely than adults to have symptoms of infection with hepatitis C, leaving the viruses undetected and possibly unknowingly spread. According to information available on the natural history of HCV, the percentage of children who become chronic and the long-term outcomes are similar to the percentage of adults. Children who are chronic carriers of HCV have normal growth patterns.

Liver biopsy appears to be less valuable in children than adults.

Chronic hepatitis rarely progresses to cirrhosis in children.

In 16 HCV children followed for up to 14 years, encephalopathy (mental confusion), ascites (swollen stomach), or bleeding did not develop. The lack of cirrhosis in children with HCV is consistent that a time period of 10 to 20 years or more is required for cirrhosis to occur. Hepatocellular carcinoma occurs very rarely in the pediatric group.

Few studies exist examining interferon use in children with chronic HCV, however a recent study in Hepatology suggests that interferon therapy may be beneficial The rates of initial and long-lasting response were higher in the study than those observed in adults treated with standard schedules. Possible explanations include the shorter time of infection in children, and that most have a mild form of liver disease. The results of this study are encouraging, according to the researchers, but more investigation needs to be conducted.

Many questions still remain about chronic hepatitis C in children.

Further studies need to be done to determine the disease’s course and progress as well as the role of interferon treatment.

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There are two general categories of "liver enzymes." The first group includes the alanine aminotransferase (ALT) and the aspartate aminotransferase (AST), sometimes referred to as the SGPT and SGOT. These are enzymes that are indicators of liver cell damage. The other frequently used liver enzymes are the alkaline phosphatase and gamma-glutamyltranspeptidase (GGT and GGTP) that indicate obstruction to the biliary system, either within the liver or in the larger bile channels outside the liver.

The ALT and AST are enzymes that are located in liver cells and leak out and make their way into the general circulation when liver cells are injured. The ALT is thought to be a more specific indicator of liver inflammation, since the AST may be elevated in diseases of other organs such as heart disease or muscle disease.

ALT and AST are often used to monitor the course of chronic hepatitis and the response to treatments, such as prednisone and interferon.

The alkaline phosphatase and the GGT are elevated in a large number of disorders that affect the drainage of bile, such as a gallstone or tumor blocking the common bile duct, or alcoholic liver disease or drug-induced hepatitis, blocking the flow of bile in smaller bile channels within the liver. The alkaline phosphatase is also found in other organs, such as bone, placenta, and intestine.

For this reason, the GGT is utilized as a supplementary test to be sure that the elevation of alkaline phosphatase is indeed coming from the liver or the biliary tract. In contrast to the alkaline phosphatase, the GGT tends not to be elevated in diseases of bone, placenta, or intestine. Mild or moderate elevation of GGT in the presence of a normal alkaline phosphatase

is difficult to interpret and often caused by changes in the liver cell enzymes induced by alcohol or medications, but without causing injury to the liver.

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It is fairly common for alfa-phetoprotein markers to be elevated in patients with hepatitis C. Alfaphetoprotein is a marker for tumors, but unless your numbers are extremely high (for example, in the hundreds), there is no need for alarm. Your doctor will probably want to perform further studies, such as an ultrasound or CT scan, just to be on the safe side

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Jaundice (yellow skin) may appear as a symptom occasionally, but is most common during an acute attack. Jaundice is caused by the buildup of bile pigment that is passed by the liver into the intestines. This same bile buildup can also cause intense itching.

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Some people experience a swelling of the liver (hepatomegaly) or the spleen (splenomegaly) as a result of hepatitis.

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Spider nevi are small capillaries that are seen on the surface of your skin. Branches form (grow) from the one capillary and it can either look like a small red spider or a splat (kind of like a squashed spider). They are also referred to as spider angiomas. If you have less than 10 that can be considered normal, more than that and it’s an indication of chronic liver disease.

They can be found only above the waist, usually on the chest, upper arms, shoulders, face, neck and upper back.

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Occurring in cirrhosis, the accumulation of fluid in the abdominal cavity, or ascites, is related to portal hypertension, significant reduction in serum albumin, and renal retention of sodium. The volume of abdominal ascites in adults with cirrhosis may reach levels as great as 10 to 12 litres (10.6 to 12.7 quarts).

Ascitic fluid may accumulate in the scrotum and in the chest cavity, where its presence, combined with the upward pressure on the diaphragm from the abdominal fluid, may severely affect breathing. Appetite also is often reduced by the abdominal distension.

Ascites are treated by the removal of enough fluid directly from the abdomen by needle puncture to ease discomfort and breathing.

Patients are placed on diets low in salt, and they are given diuretic drugs to increase the output of water by the kidneys. If these measures do not control massive ascites, ascites can be drained internally into the general venous blood system by running a plastic tube from the abdominal cavity, under the skin of the chest, into the right internal jugular vein of the neck (peritoneovenous shunt of LeVeen).

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Sometimes occurring in cirrhosis, portal hypertension is the increased pressure in the portal vein and its tributaries resulting from blockages to the blood flow into the liver. It is usually caused by the scarring processes of cirrhosis. The increased pressure causes varices, or dilations of the veins leading into the portal vein. When varices are located in superficial tissues, they may rupture and bleed profusely. Two such locations are the lower esophagus and the perianal region.

Esophageal varices are likely to bleed most heavily, and this bleeding is frequently associated with the onset of hepatic encephalopathy or coma. Because of their location at the lower end of the esophagus or the upper portion of the stomach, bleeding from varices is often difficult to control. If variceal bleeding persists, surgical formation of a shunt, or artificial passageway, from the portal vein to an abdominal vein may be done.

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Hepatic encephalopathy refers to the changes in the brain that occur in patients with advanced acute or chronic liver disease. If liver cells are damaged, certain substances that are normally cleansed from the blood by the healthy liver are not removed (mainly ammonia, or possibly certain fatty acids). A patient with chronic hepatic encephalopathy may develop progressive loss of memory, disorientation, untidiness, and muscular tremors, leading to a form of chronic dementia. The ingestion of protein invariably aggravates these symptoms.

The treatment of hepatic encephalopathy involves, first, the removal of all drugs that require detoxification in the liver and, second, the reduction of the intake of protein. Restricting the amount of protein in the diet will generally lower the levels of amino acids and ammonia in the bloodstream and brain. Most physicians advise their patients with this condition to eat only about 40 grams of protein a day, and will prescribe lactulose or neomycin to lower amino acid production. Non-meat proteins, such as those found in vegetables and milk, are also recommended. Certainamino acids are used in treatment, since they are considered less likely to cause mental impairment. A dietary supplement rich in these amino acids is used at many liver treatment centers.

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When chronic diseases cause the liver to become permanently injured and scarred, the condition is called cirrhosis. The scar tissue that forms in cirrhosis harms the structure of the liver, blocking the flow of blood through the organ. The loss of normal liver tissue slows the processing of nutrients, hormones, drugs, and toxins by the liver. Also slowed is production of proteins and other substances made by the liver.

People with liver cirrhosis may develop many problems beyond the liver. When the liver is scarred, the blood cannot easily get through the liver, and backs up under higher than normal pressure (portal hypertension). This often causes ascites, which is yellow fluid that leaks out of the bloodstream into the abdominal cavity.

If the ascites becomes tense, it can cause an umbilical hernia (a protruding belly button). The backed-up blood also often creates varices, in which the pressure causes the blood vessels around the esophagus to burst causing significant blood loss. Varices can be treated with beta blockers, or can be obliterated using endoscopically-placed rubber bands or injections of liquid that cause the varices to scar. If endoscopy fails to stop bleeding, a TIPS (transjugular intrahepatic portosystemic shunt) can be created by inserting a short metal mesh tube through a neck vein into the liver and connecting the portal vein in the liver to a regular vein in the liver. Another alternative is to surgically redirect some of the blood flow around the liver.

People with cirrhosis sometimes may develop jaundice (a yellowing of the whites of the eyes or the skin) due to an accumulation of bilirubin in the blood. If the bilirubin is excreted in the urine, the urine may turn dark.

People with cirrhosis are also at risk for hepatic encephalopathy, which is fatigue or confusion caused by ammonia and other products of protein digestion which are inadequately cleared from the bloodstream by the liver.

People with cirrhosis often bruise easily because the liver manufactures reduced amounts of clotting factors. Additionally, platelets may be lower than normal in the circulation if the spleen is enlarged.

A spleen enlarged from portal hypertension may hold onto too many platelets.

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Chronic HCV infection leads to cirrhosis in at least 20 percent of patients within 2 decades of the onset of infection. Cirrhosis and end-stage liver disease may occasionally develop rapidly, especially among patients with concomittant alcohol use. - National Institutes of Health Consensus Statement on Hepatitis C 1997

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In very rare cases hepatitis symptoms develop quickly and become very severe. This less common form of hepatitis is called fulminant hepatitis or fast-progressing hepatitis, and it requires prompt medical attention. It can be fatal in up to 70 to 80 percent of cases. The kidneys may fail, and the liver shrinks as cells are killed. The person may fall into a coma and die. Fulminant liver failure following HCV infection has been reported but is a rare occurrence.

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Chronic infection by HCV is associated with an increased risk of liver cancer. The prevailing concept is that hepatocellular carcinoma (HCC) occurs against a background of inflammation and regeneration associated with chronic hepatitis over the course of approximately 3 or more decades. Most cases of HCV-related HCC occur in the presence of cirrhosis. The risk for a person with chronic HCV hepatitis developing HCC appears to be 1-5 percent after 20 years, with striking variations in rates in different geographic areas of the world. Once cirrhosis is established, the rate of development of HCC is 1-4 percent per year. - National Institutes of Health Consensus Statement on Hepatitis C 1997

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Chronic infection with hepatitis C virus (HCV) is regarded as a risk factor for hepatocellular cancer, mostly in patients with liver cirrhosis. We looked for HCV genomes in the livers of patients with hepatocellular cancer who did not have cirrhosis to see whether HCV was directly oncogenic. Cancerous and non-cancerous liver tissue, and serum samples from 19 patients negative for hepatitis B surface antigen were analysed by polymerase chain reaction for the presence of HCV genome, HCV replication, HCV genotyping, and HBV genome. 13 of 19 patients were HCV RNA-positive in cancerous and non-cancerous liver tissue; 8 of 17 tested were anti-HCV positive.

Among the 13 HCV RNA-positive patients, 11 had genotype 1b and 2 had genotype 2a. 7 of 13 serum samples were HCV RNA positive.

7 of 19 patients were HBV DNA positive in cancerous and non-cancerous liver tissue, 5 of them anti-HBc positive. 4 patients were both HCV RNA and HBV DNA positive and 3 were both HCV RNA and HBV DNA negative. The results provide evidence for the association of HCV, mostly genotype 1b, with hepatocellular cancer without the intermediate step of cirrhosis. - "HCV-associated liver cancer without cirrhosis", De Mitri MS; Poussin K; Baccarini P; Pontisso P; D’Errico A; Simon N; Grigioni W; Alberti A; Beaugrand M; Pisi E; et al, Department of Internal Medicine, University of Bologna, Italy, Lancet 345: 413-5 (1995 )

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Previously, we reported the high prevalence of hepatitis C virus (HCV) infection in patients with oral cancer or oral lichen planus in Kyushu, Japan. We now report a 61-year-old man with chronic hepatitis C and no oral lesions who developed oral cancer 6 months after interferon therapy (interferon alpha, 6 million units (MU) daily for 2 weeks and then 3 times a week for 14 weeks). This case emphasizes the need for periodic oral cavity examinations of hepatitis C patients and contributed to the investigation of oral cancer and HCV. - "Oral cancer and hepatitis C virus (HCV): can HCV alone cause oral cancer?--a case report." Kurume Medical Journal, 1996 Vol 1, Issue 43, pp 97-100

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It is thought that treatment with interferon reduces the risk of later developing liver cancer. "The low incidence of hepatocellular carcinoma in patients treated with interferon suggests that interferon may prevent the development of hepatocellular carcinoma." - "Risk Factors and the Effect of Interferon Therapy in the Development of Hepatocellular Carcinoma," Journal of Gastroenterology and Hepatology 1997 Feb;12(2):149-155

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An association between chronic hepatitis C infection and non-Hodgkin’s lymphoma has been reported. " HCV Infection and Extrahepatic Malignancies," Journal of Clinical Gastroenterology 1997 Mar;24(2):87-89

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Hepatitis C accounts for 20% of community-acquired hepatitis in the US. Approximately 200 case of hepatitis C are reported in New York State each year. -- "Prevention, Diagnosis, and Management of Viral Hepatitis", AMA

Each year, 150,000 new cases of hepatitis C infection occur in the United States.—" Hepatitis C & E: how much of a threat?" Special Issue: Emerging Infectious Diseases, Brown, Edwin A., May 15 1994, v28, n9, p105(8)

The (US) Center for Disease Control and Prevention, estimates that at least 17 ½ million people (in the US) are living with chronic hepatitis C infections and as many as 150,000 Americans are newly infected with hepatitis C each year.

A number of new therapies for hepatitis C are emerging in clinical practice. Combination approaches of Interferon and Ribavirin are currently being tested and will likely prove to be beneficial. Within two to three years we expect to see a whole new class of drugs which will be oral, have low toxicities, and improved efficacy. These drugs will likely need to be taken lifelong and may need to be taken in combination with each other as is currently the case in HIV disease. - "Emerging Therapies for HCV," - Scripps Clinic and Research Foundation, Liver Disease Study Group

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Interferon is a genetically engineered product originally licensed in 1986 to treat hairy cell leukemia. It is a copy of a protein found naturally in low levels in the human body. It was OK’d by (US) FDA Feb. 25, 1991, to treat hepatitis C. The product, alpha interferon, is the first effective treatment against this form of hepatitis, which affects an estimated 150,000 Americans each year.

According to the manufacturer’s (Schering-Plough) literature for using Interferon in the treatment of Hepatitis C: 3 million units per dose 3 times a week Interferon has an effective cure rate of about 25% .

Besides hairy cell leukemia and hepatitis C, alpha interferon is licensed for treatment of AIDS-related Kaposi’s sarcoma and genital warts. Schering-Plough Corporation of Kenilworth, N.J., which markets a version of the product under the trade name Intron-A, received approval for the product’s use for hepatitis.

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Treatment: Interferon has been approved for chronic HCV. Patients are selected for therapy on the basis of persistently abnormal liver function (blood) tests, rather than on the presence or absence of symptoms. It’s not known what should be done for patients with mild chronic HCV infection; since some patients with mild disease can go on to develop cirrhosis, a trial of therapy with interferon is usually recommended. It’s recommended that such patients be referred to specialists with knowledge in liver disease (gastroenterologist/hepatologists). -- "Prevention, Diagnosis, and Management of Viral Hepatitis", AMA

About half of patients treated with interferon respond, with better blood tests and better liver biopsies. Half the patients who respond relapse once the interferon is stopped. -- "Prevention, Diagnosis, and Management of Viral Hepatitis", AMA

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Alpha interferon seems to work better the sooner it is used after infection. However, in many cases of hepatitis C the symptoms get worse again when the treatment is stopped. In one study, half of the chronic hepatitis C sufferers who had responded to alpha interferon had a relapse within six months after treatment stopped.

Thus only 25 percent of HCV patients respond favorably without relapsing.

The average six months of injections three times a week are expensive ($75 a week). Many patients also suffer side effects, such as flulike symptoms, a reduction in the number of disease fighting white blood cells, and a decreased number of platelets in the blood. (Platelets are needed for blood clotting.)

Factors most closely associated with response to interferon are: 1) absence of fibrosis or cirrhosis in the pretreatment liver biopsy; 2) HCV genotype other than 1; 3) lower RNA levels in the blood (e.g., less than 2 million/ml); and 4) shorter duration of infection (which often isn’t known).

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Patients with chronic hepatitis B or C, with fluid in the abdomen ascites), bleeding from dilated veins in the esophagus (variceal bleeding), or mental confusion (encephalopathy) should be treated only in a clinical trial. Others not suitable for treatment are those with symptomatic heart, lung or kidney disease, with human immunodeficiency virus (HIV) infection or organ transplant recipients on prednisone, cyclosporine and FK-506 and patients on antidepressants or with a history of suicide attempts. Interferon should not be given to women considering pregnancy, nor to the intended father. Patients with active substance abuse (alcohol or illegal drugs) should not be offered this therapy. - "Interferon Treatment for Hepatitis B and C Fact Sheet", American Liver Foundation

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Recombinant interferon alfa (r-IFN alpha 2) has been shown to normalize the aminotransferase levels in approximately 50% of patients with chronic hepatitis C virus (HCV). Few patients experience a relapse during the eatment, in spite of a complete initial response (breakthrough). Continued treatment with r-IFN alpha 2, even at higher doses, did not restore the previous response in any patient. All of them were then switched to natural lymphoblastoid IFN, and this rapidly restored a complete response in all of the patients. - "Breakthrough during recombinant interferon alfa therapy in patients with chronic hepatitis C virus infection: prevalence, etiology, and management." - Hepatology Vol. 21 no. 3 pp. 645-9 1995 Mar

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A report in the Archive of Virology 1997 ;142(3):535-544 suggests that an inapparent coinfection of the hepatitis B virus (HBV) along with the hepatitis C virus may be implicated in cases of resistance to interferon treatment. In addition, HBV replication may persist in patients in whom HCV replication was inhibited by interferon treatment.

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A new study published in the fall issue of American Journal of Gastroenterology, Vol 89, No. 7, suggests that using "Iron Reduction Therapy" along with interferon can result in an effective cure rate in the area of 75-80% and that adding cytokines and antivirals such as ribavirin can improve effectiveness even further. The theory behind this is that viruses need iron to replicate, and by reducing the hepatic iron in the liver you prevent them from replicating. It should be noted that this new procedure is not yet FDA approved and is still in the early trial stages.

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Iron is an element required for replication of virtually all virulent microorganisms. Reducing the amount of iron helps to limit the replication of the hepatitis C virus. The role of iron influencing the natural history of viral hepatitis was reported in a study more than 15 years ago ( Blumberg BS, Lustbader ED, Whitford PL. "Changes in serum iron levels due to infection with hepatitis B virus." Proc Natl Acad Sci USA 1981;78:3222-4 ). In this study it was observed that patients with hepatitis B viral infection with higher serum iron or ferritin levels had greater likelihood of development of chronic infections than those with lower levels, who more often resolved their infections spontaneously.

Increases in levels of serum ferritin, iron, and transferrin saturation also have been noted with high frequencies in patients with chronic hepatitis C,2 and the higher levels have, in general, been associated with lesser likelihood of response to interferon therapy.

Complete responders to interferon have, on average, lower hepatic iron concentrations than do noncomplete responders.

In a report by Hayashi and colleagues ("Improvement of serum aminotransferase levels after phlebotomy in patients with chronic active hepatitis C and excess hepatic iron." Am J Gastroenterol 1994;89:986-8 ) it was reported that iron reduction alone, by repeated venesection (bloodletting), led to significant improvement in serum alanine aminotransferase (ALT) levels in chronic hepatitis C.

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Many hepatitis C patients show a clear-cut biochemical response to ribavirin, with a lowering of liver enzyme levels.

However, the ribavirin does not clear circulating hepatitis C virus RNA and relapses occur after they discontinue taking the drug.

Recently the U.S. Food and Drug Administration approved the Rebetron combination therapy (interferon-alpha2b plus ribavirin) for the treatment of chronic hepatitis C patients who have relapsed following alpha interferon therapy. At six months post treatment, 45.7% who received the combination therapy had undetectable virus levels, compared to the 25% response rate to interferon alone.

The recommended dosage for this combination therapy is 3MIU of interferon-alpha2b (Schering-Plough brand name Intron A) injected subcutaneously three times per week and 1000 - 1200mg of ribarivin (Schering-Plough brand name Rebetol) capsules administered orally in a divided daily dose for a duration of 24 weeks. This combination therapy is packaged as Rebetron by the drug company Schering-Plough, with the interferon and ribavirin bundled together in one package.

A six-month treatment with Rebetron is estimated to cost between $6,400 and $8,600 depending upon dosage.

The most common side effects associated with the combination therapy are: Flu-like symptoms, such as headache, fatigue, muscle pain, fever, and the destruction of red blood cells which may be severe enough to result in anemia.

Psychiatric disorders have also been reported. Depression is a fairly common side effect, and in some cases it may become severe. Rare cases of suicidal thoughts and suicidal attempts have been reported.

The combination therapy is associated with a significant risk of abnormal fetal development, and women of childbearing potential should not begin combination therapy until a report of a negative pregnancy test has been obtained.

At the present time, the FDA has approved Rebetron combination therapy only for HCV patients who have previously undergone alpha interferon therapy and who have relapsed. It has not yet been approved for "naive" patients (meaning those who have not yet taken interferon alone), but FDA approval for this use is expected shortly. However, physicians can prescribe drugs for individuals for whom they think it will be helpful.

Therefore, physicians can prescribe combination therapy for naive patients prior to FDA approval for that specific use.

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According to a news release from Amarillo Biosciences, Inc, dated May 12, 1997, a study is commencing to test low dose oral interferon alpha as a combination treatment with high dose injectable interferon alpha in hepatitis C patients in Canada and Mexico. The company has compiled preliminary data indicating that pretreatment with low dose oral interferon alpha preconditions patients to respond better to injectable interferon alpha. A clinical trial will be conducted with Dr. Elliott Alpert of Montreal as the principal investigator and another hepatitis expert located in Mexico as co-investigator. The study is expected to eventually enroll 180 patients and could take 2-3 years to complete.

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Consensus interferon, or CIFN, is a synthetic form of one type of interferon. Created by Amgen scientists, the drug has undergone extensive clinical testing for treating hepatitis C, cirrhosis and a form of cancer.

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According to the NIH Consensus Development Conference on Management of Hepatitis C 1997:

Consensus interferon at a dose of 9 ug administered tiw for 24 weeks is safe and effective for the treatment of chronic HCV infection in interferon-naive patients and results in a sustained HCV RNA response rate of 12 percent.

When compared with MU (15 ug) IFN alfa-2b, 9 ug CIFN may result in higher sustained HCV RNA response rates in patients with genotype 1 and in patients with high pretreatment viral loads.

In patients failing prior CIFN or IFN alfa-2b therapy, retreatment with a higher dose of CIFN (15 ug) for 24 weeks results in sustained HCV RNA response rates in 8 percent of nonresponders and 32 percent of relapsers and is well tolerated.

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Alferon, produced by Interferon Sciences Inc., is an injectable, natural-source, multispecies alpha interferon produced from human peripheral blood leukocytes which is currently in clinical trials for the treatment of hepatitis C. The preliminary results of the trials are encouraging and further studies are planned.

It is thought that the chance of "breakthrough" is less when using natural source interferon, than with the standard interferon alpha 2b preparation. If the results at the end of clinical trials are favorable, the company intends to seek FDA approval of Alferon N Injection for the treatment of hepatitis C by the end of the third quarter 1998.

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PEG-Intron A is a modified form of Schering-Plough’s Intron A (interferon alfa-2b, recombinant), developed by Enzon, Inc. to have longer-acting properties. Currently in Phase III clinical trials, PEG-Intron A is administered once a week, compared to the normal dosage of 3 times a week for Intron A.

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Effects of granulocyte/monocyte colony stimulating factor (GM-CSF) have generally been disappointing: it is expensive, poorly tolerated, and without beneficial effect except perhaps in a rare patient who develops severe neutropenia due to interferon, in whom GM-CSF may permit continuation of higher doses of interferon.

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An open label trial of GM-CSF plus high-dose interferon (IFN) alpha 2b was performed in 16 patients with chronic hepatitis C, who either failed to clear virus with 6 months of daily high-dose IFN (5 MU daily) therapy (n = 22) or were considered untreatable because of advanced disease and leukopenia (n = 2). The dose of GM-CSF used was 500 mu g subcutaneously twice weekly, The dose of IFN used was 5 MU daily, Both agents were administered for 4 months. Five of the 16 hepatitis C virus patients responded to combined therapy having previously failed IFN therapy alone.

No such differences for responders and non-responders were seen with the hepatitis C virus patients, These data suggest that the combination of GM-CSF and IFN may be more effective at achieving viral clearance than IFN alone. - "A Preliminary Experience with GM-CSF Plus Interferon in Patients with HBV and HCV Resistant to Interferon Therapy," Journal of Viral Hepatitis 1997 ;4:101-106

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According to a report in the Journal of Interferon and Cytokine Research 1997 Jan; 17(1):27-30, the intramuscular administration of interferon-beta (IFN-beta) at a dosage of 6 million units three times per week for 6 months was evaluated in 90 patients included in a multicenter, randomized, controlled trial for the treatment of chronic hepatitis C. At the end of the study, the researchers concluded that intramuscular IFN-beta at the dosage used has little efficacy in the treatment of chronic hepatitis C.

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While the efficacy of beta-interferon has been proven to be ineffective when administered intramuscularly, a study reported at the 1996 Annual AASLD conference (" Therapy of Chronic Hepatitis C Non-Responders to Alfa-Interferon: A Preliminary Report of Intravenous Natural Beta-Interferon" ) reports that beta-interferon has been proven to be efficacious when administered by intravenous infusion, and that intravenous beta-interferon can be a well tolerated effective treatment for patients with chronic hepatitis C non-responders to [alpha]-IFN.

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Another study reported at the 1996 Annual AASLD conference ("Analysis of Amino Acid Residues 2209 to 2248 of NS5A of HCV-1b in Relation to the Response to Interferon Beta Therapy"), suggests that some HCV patients with genotype 1b who have a mutant type of the NS5A2209-2248 gene are sensitive to interferon beta therapy regardless of lower doses and shorter treatment periods compared to interferon alpha. HCV-1b patients with the intermediate or the wild type of the NS5A2209-2248 gene are resistant to interferon beta therapy.

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Ursodeoxycholic acid (UDCA) has been used in chronic liver diseaes and can limit hepatocyte injury. The various mechanisms of action of this hydrophilic bile acid include direct cytoprotection, detergent action on dysfunctional microtubules, immunomodulation and induction of hypercholeresis. It has recently been used in the management of chronic hepatitis, cirrhosis, post liver transplant rejection, graft -versus-host disease and acute viral hepatitis, where it not only relieves symptoms of cholestasis but also arrests ongoing hepatocyte necrosis.

According to a study reported at the American Gastroenterology Association Digestive Disease Week meeting in Washington in May 1997 (Treatment of chronic hepatitis C with interferon with or without ursodeoxycholic acid: a randomized prospective trial), combination therapy with UDCA plus interferon was no more effective than interferon monotherapy in inducing a biochemical response in previously untreated patients with chronic hepatitis C. UDCA was, however, useful in prolonging the sustained biochemical response of IFN therapy in this small pilot study

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Ribozymes are enzymes which have the ability to cause a catalytic cleavage of a targeted RNA. Ribozymes directed against the hepatitis C virus RNA have been developed which have the ability to destroy the virus’ replicative material. Although these compounds have been produced using recombinant bench techniques they have not yet been proven safe or effective in vivo. It is anticipated that these compounds may have unpredictable and non-specific effects on other cells and therefore may be potentially toxic. More work is needed on these drugs before they will reach the clinic. - "EMERGING THERAPIES FOR HCV," From the Scripps Clinic and Research Foundation, Liver Disease Study Group

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Antisense drugs are large, highly charged molecules which form DNA-RNA or RNA -RNA hybrids with the target RNA receptor.

In the case of hepatitis C this hybrid would form with the hepatitis C RNA which is the viral replicative material. This occurs by simple Watson-Crick base pairing. Once an anti-sense DNA hybrid has been formed it inactivates the viral replication process.

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A new drug discovered by Israeli scientists Professor David Lavi, formerly the director of Organic Chemistry Department at the Weizmann Institute and his son, Dr. Gad Lavi, a senior lecturer at N.Y.U., is in the second stage of clinical testing in humans with AIDS and hepatitis and the reports are very promising.

The new drug neutralizes viruses like hepatitis C as if it were an antibiotic, according to Dr. Lavi. The drug is produced from a plant that grows primarily in Europe and North American and is called Hifritzin. It is claimed the active substances in the drug neutralizes the virus and causes it to lose its power to attack healthy cells in the body. - The Jewish Free Press, Friday March 7, 1997

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Thymosin alpha 1 is a protein produced by the human body