It is very important to find a health practitioner who is familiar with this illness. The symptoms of hepatitis can be mimicked by other illnesses (autoimmune illnesses, cancer, chronic fatigue syndrome, lupus, arthritis, etc.), and if you in fact have another illness that is not properly diagnosed, you may be losing out on getting treatments that might be effective for you.

It is still an uphill struggle to find a doctor who is experienced in diagnosing and treating hepatitis C. Hepatologists specialize in diseases of the liver, and would be your best choice in physicians, followed by a gastroenterologist (a digestive disease specialist) or an infectious disease specialist. If there is a hepatitis support group nearby, they would be an excellent source of advice in identifying local doctors who may be familiar with hepatitis, or you can contact the American Liver Foundation (ALF), The HEP project in Seattle, the Hepatitis C Support Project in San Francisco, HepCBC in Victoria, British Columbia, or a host of other hepatitis C organizations for a list of doctors near you. If there are no hepatitis knowledgeable doctors in your area and you wish to find an out-of-town specialist contact the organization nearest you for help. For a list of hepatitis C organizations in your area see Part XII of the FAQ.

If your own doctor is sympathetic but not knowledgeable, you might gather together some medical articles on hepatitis and hepatitis treatments and encourage your doctor to study them. Or you can just give him or her a copy of the FAQ.

See Appendix D for a list of Hepatologists and Gastroenterologists in Canada.

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II.0.2 WHAT IS THE DIFFERENCE BETWEEN A GASTROENTEROLOGIST AND A HEPATOLOGIST?

A hepatologist specializes in treating liver disease. A gastroenterologist does guts, essentially. I recommend finding a hepatologist, as they are more likely to be on top of the latest information concerning treatment of hepatitis C. Unfortunately hepatologists, especially in Canada, are few and far between.

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II.1.0 HOW IS IT DIAGNOSED?

There are 3 major tests for HCV.

1) The ELISA test detects antibody to the virus.

2) The RIBA test is the confirmatory test for HCV.

3) The Quantitative HCV PCR test, which measures the amount of virus circulating in a person’s blood stream.

While the newer HCV antibody tests are better; false positive results still occur, and further testing should be used to confirm the antibody test. Abnormal liver function tests (LFTs) suggest chronic disease, but there is no correlation between the level of the liver function tests and how severe the disease is. Many physicians still assume there is (especially primary care physicians), and this has led to complications and even death because of misdiagnosis. Recent studies show that testing for enzyme level elevation is not an accurate diagnostic for the presence of hepatitis C (Digestive Disease Week 2000).

Before 1990 doctors could diagnose HCV only by ruling out other possibilities (thus the old name for HCV “non-A, non-B hepatitis).

Hepatitis C antibodies may not develop for two to six months after infection, so only two-thirds of patients who go to the doctor with possible hepatitis C infection can be diagnosed with blood tests. Diagnosis may have to exclude other possible causes such as HAV, HBV, cytomegalovirus, Epstein-Barre virus infection, as well as non-viral liver problems such as fatty liver, or alcohol or drug-related diseases.

Follow-up blood tests are very important in order to determine if the disease has become chronic. The blood tests for antibodies are usually repeated three and six months after the original illness.

Diagnosis is most commonly made after detecting an antibody to a portion of HCV in the blood. This indicates that the person was exposed to the virus and that their immune system made an antibody. The test can show false positive reactions and therefore confirmation is necessary by finding evidence that the Hepatitis C virus is actually in the blood using the polymerase chain reaction (PCR), an extremely sensitive test for viral RNA.

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II.1.1 ANTIBODY TESTS

Antibody tests indicate whether the body has been exposed to the virus and has produced antibodies to fight it. They do not determine whether or not someone still has the virus, or how long they’ve been infected.

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II.1.2 WHAT IS A PCR?

Polymerase Chain Reaction (PCR) . HCV PCR tests are a newly developed test that came onto the market in late 1994. HCV PCR tests look for the presence of the virus. Information gained from the HCV PCR can be useful in interpreting unclear antibody test results.

The HCV PCR cannot tell how long someone has been infected.

Basically, your blood sample is broken up and certain parts are “fed” to E.coli bacteria, which grow real fast. When there are enough of them, they are put into the “bacteria-matic.”

Then that stuff is separated, and the remains are x-rayed, producing that pretty sheet of stripes that you see in cops and robbers shows and the OJ trial.

There are two sets, one side is the control, which is a known HCV, the other side is you. If they match you have the virus.

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II.1.2a WHAT IS A GENOTYPE?

A genotype is the “family” to which our specific virus belongs. Our genotype does not change, but we can be re-infected with a different genotype. The most common genotypes are as follows: 1a, 1b, 1c, 2a, 2b, 2c, 3a, 3b, 4, 5 and 3a has the highest response rate to interferon, and people with this genotype are generally younger in age and usually IV drug users.

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II.1.3 IS IT POSSIBLE THE TEST COULD BE WRONG?

Antibody tests are usually positive or negative, but sometimes they come back unclear. Tests that come back positive are redone to confirm they are right. Unclear results are repeated and if still unclear, different types of blood tests are done. If you get a positive test result and have no risk background (for example, blood transfusions or injecting drug use) it’s a good idea to check with your doctor to make sure that the blood laboratory double checked the result by using confirmatory tests.

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II.2.0 BIOPSY

If viral hepatitis infection occurs, it may resolve on its own or become chronic. However, patients with chronic hepatitis often do not experience symptoms. On the other hand, others complain of excessive fatigue, weakness, and a reduced capacity for exercise.

Since liver damage may occur even in asymptomatic cases (no patient complaints), it is important to perform a biopsy and determine whether there is ongoing liver damage. As chronic hepatitis progresses, damage to liver cells may impair liver function. The biopsy of the damaged liver indicates the degree of cellular necrosis (death of liver cells), inflammation (cellular infiltration and swelling), and scarring (scar tissue beginning to replace functioning liver cells). - “Understanding Chronic Hepatitis” - Schering - 10/92 INH-001/17098403

II.2.0a WHAT IS A LIVER BIOPSY?

Liver biopsy is a diagnostic procedure used to obtain a small amount of liver tissue, which can be examined under a microscope to help identify the cause or stage of liver disease.

The most common way a liver sample is obtained is by inserting a needle into the liver for a fraction of a second. This can be done in the hospital with a local anesthetic, and the patient may be sent home within 3-6 hours if there are no complications.

The physician determines the best site, depth, and angle of the needle puncture by physical examination or ultrasound. The skin and area under the skin is anaesthetized, and a needle is passed quickly into and out of the liver. Approximately half of individuals have no pain afterwards, while another half will experience brief localized pain that may spread to the right shoulder.

Some persons, however, have had to be hospitalized afterwards due to extreme pain, shock or puncture of another organ. Many patients have commented that taking an atavan before the procedure helped reduce the pain since this drug will relax the internal muscles and prevent spasms.

Patients are monitored for several hours after a biopsy to make sure serious bleeding has not occurred. Some patients occasionally have a sudden drop in blood pressure after a biopsy that is caused by a “vagal” reflex and not by blood loss; this is caused by sudden irritation of the peritoneal membrane. The characteristics that distinguish this from a bleeding event are: 1) slow pulse rather than rapid, 2) sweating, and 3) nausea.

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II.2.0b WHAT ARE THE DANGERS OF LIVER BIOPSY ?

The risk of a liver biopsy is minimal. The primary risk is bleeding from the site of needle entry into the liver, although this occurs in less than 1% of patients. Other possible complications include the puncture of other organs, such as the kidney, lung or colon.

Biopsy, by mistake, of the gallbladder rather than the liver may be associated with leakage of bile into the abdominal cavity, causing peritonitis. Fortunately, the risk of death from liver biopsy is extremely low, ranging from 0.1% to 0.01%.

A biopsy should not be done if: 1) you have taken aspirin in the last 5-7 days, 2) the hemoglobin is below 9-10 grams/dl, 3) the platelets are below 50,000-60,000, or 4) the prothrombin time INR is above 1.4. Those with bleeding disorders such as hemophilia which can be temporarily corrected with transfused clotting factors can be biopsied safely.

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II.2.0c WILL IT HURT?

Most doctors will not do percutaneous needle liver biopsies under anesthesia. This is because the liver is directly under the diaphragm and moves as you breathe. When the needle is inserted through the skin and body wall, the liver must not be moving or else there is danger of a laceration. To keep the liver from moving, the patient has to stop breathing momentarily. Doctors prefer to have you alert and following directions, but if you are very anxious you may want to ask for a sedative to help you relax.

The injections of the local anesthetic and the actual puncture of the liver capsule itself can be a little painful for some people, but it only takes a second and is over very quickly. Other people feel no pain at all, and don’t even realize it’s over with until the doctor tells them they’re finished.

Occasionally there will be a small to moderate amount of pain afterwards. If you find that you are uncomfortable, your doctor will generally prescribe a light painkiller immediately after the biopsy. The pain may be well away from the biopsy site, possibly in the pit of your stomach or typically in the right shoulder. Some doctors are really hesitant to give pain killers to those with hepatitis C. Please make sure you have some just in case, by clearing up this matter before hand. After my second biopsy, I was in so much pain I was crying for hours, and I had to argue with the nurse to get some medication. The pain subsided after 24 hours, but both Joan and I were very worried (squeeky).

The liver itself has no pain-sensing nerve fibers, but a small amount of blood in the abdominal cavity or up under the diaphragm can be irritating and painful. Very occasionally, small adhesions (scar tissue) may form at or near the biopsy site, and can cause a chronic pain that persists near the liver area after the biopsy.

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II.2.1 CHRONIC PERSISTENT OR CHRONIC ACTIVE - WHAT’S THE DIFFERENCE?

Hepatitis C is considered to be “chronic” if it has persisted for longer than 6 months. The term “Chronic Persistent” used to be used to define hepatitis which persisted for longer than 6 months, but which was not currently causing active damage to the liver. The term “Chronic Active” was used to define hepatitis which persisted for longer than 6 months, and which was actively destroying the liver. The differentiation between “persistent” and “active” is not commonly used any more, with the assumption being that if the virus exists, it is causing damage whether it is moving quickly or not.

About 85 percent of HCV-infected individuals fail to clear the virus by 6 months and develop chronic hepatitis with persistent, although sometimes intermittent viremia. This capacity to produce chronic hepatitis is one of the most striking features of HCV infection. The majority of patients with chronic infection have abnormalities in ALT levels that can fluctuate widely. About one-third of HCV patients with chronic infection have persistently normal serum ALT levels. Antibodies to HCV or circulating viral RNA can be demonstrated in virtually all patients with chronic HCV hepatitis.

Chronic HCV is typically an insidious process, progressing, if at all, at a slow rate without symptoms or physical signs in the majority of patients during the first two decades after infection.

A small proportion of patients with chronic HCV hepatitis - perhaps less than 20 percent - develop non-specific symptoms, including mild intermittent fatigue and malaise. Symptoms first appear in many patients with chronic HCV hepatitis at the time of development of advanced liver disease. If by advanced we mean cirrhosis, then this is most definitely not the case. Symptoms can occur well before cirrhosis occurs.

Although patients with HCV infection and normal ALT levels have been referred to as “healthy” HCV carriers, liver biopsies can show histological evidence of chronic hepatitis in many of these patients. - National Institutes of Health Consensus Statement on Hepatitis C 1997

It is thus possible to have low enzyme levels and few if any symptoms and yet have dangerously advanced liver disease. The problem with this scenario is that the carrier does not know he or she is ill, and does not make modifications to his or her behavior—alcohol consumption, sexual protection, fatty foods, and so forth.

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II.2.2 WHAT ARE THE MAIN SYMPTOMS OF HEPATITIS C?

Acute hepatitis C is almost indistinguishable from acute hepatitis B infection. Patients with acute hepatitis C are frequently asymptomatic (meaning that they have no symptoms), even when liver tests are abnormal. - “Hepatitis C & E: how much of a threat?” Special Issue: Emerging Infectious Diseases, Brown, Edwin A., May 15 1994, v28, n9, p105(8).

Soon after contracting the infection many people have a flu-like illness with fatigue, fever, muscular aches and pain, nausea and vomiting. About 10% of patients become jaundiced (their skin turns yellow). Generally these symptoms resolve and the patient has no symptoms of liver disease for many years. Symptoms may occur from two weeks to six months after exposure but usually within two months.

What are the symptoms of chronic infection and cirrhosis? The symptoms of chronic infection range from no symptoms at all, to gradually progressive fatigue and lack of energy, to complete debility. The effects of the virus vary widely between individuals.

The symptoms of cirrhosis include progressive fatigue, jaundice (yellow skin), icterus (yellow eyes), dark urine (the color of cola), abdominal swelling, muscle wasting, itching, disorientation and confusion, loss of appetite, and easy bruisability.

In an informal survey of hepatitis C symptoms, Scott Warren swarren@idir.net polled 50 people on the HEPV-L list and compiled the following results:

FATIGUE, WEAKNESS, TIREDNESS - 72%

JOINT, MUSCLE PAINS - 52%

MEMORY LOSS, MENTAL CONFUSION - 50%

SKIN PROBLEMS-DRY\ITCHY\RASHES\SPOTS - 44%

DEPRESSION, ANXIETY, IRRITABILITY, ETC - 44%

INDIGESTION, NAUSEA, VOMITING, GAS - 34%

SLEEP DISTURBANCES - 32%

PAIN OR DISCOMFORT IN ABDOMEN - 32%

CHILLS, SWEATING, HOT \ COLD FLASHES - 26%

EYE OR EYESIGHT PROBLEMS - 24%

SENSITIVITY TO HEAT OR COLD - 22%

NO SYMPTOMS - 20%

VERTIGO, DIZZINESS, COORDINATION - 18%

FLU LIKE SYMPTOMS - 18%

HEADACHES - 18%

URINARY PROBLEMS, ODOR, COLORATION - 16%

FEVER - 16%

SLOW HEALING AND RECOVERY - 14%

SUCCEPTIBILITY TO ILLNESS \ FLU - 14%

WEIGHT GAIN, WATER RETENTION - 10%

MENSTRUAL PROBLEMS - 10%

APPETITE \ WEIGHT LOSS - 8%

SWELLING OF STOMACH, LEGS OR FEET - 8%

ORAL, OR MOUTH SORES \ PROBLEMS - 8%

EXCESSIVE BLEEDING - 4%

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II.2.2a FATIGUE

The main symptom of most people with hepatitis C is chronic fatigue, ranging from simply getting tired easily to extreme, debilitating fatigue. The fatigue is often not recognized as such. Many people suffering from this “fatigue” do not have a desire to sleep because they are tired. Rather, they are suffering a very low level muscle pain (which often they do not recognize) that just wears them down. Taking a nap really helps. “It took me years to figure out that it was pain. When nurses would say to me, you look tired, I wouldn’t know what they meant. I did not always want to go to sleep. Now much of that has changed. I do get sleepy-tired and must nap often” (squeeky).

A recent study by Goh J, Coughlan B, Quinn J, O'Keane JC, Crowe J Department of Hepatology, Mater Misericordiae Hospital and University College Dublin, Ireland found that fatigue does not correlate with the degree of hepatitis or the presence of autoimmune disorders in chronic hepatitis C infection. The doctors concluded that the perceived functional impact of fatigue on quality of life is significantly higher in patients with chronic HCV genotype 1b infection compared to healthy controls. However, it is unrelated to the degree of hepatitis and cannot be accounted for by the co-existence of autoimmune disorders alone. Eur J Gastroenterol Hepatol 1999 Aug;11(8):833-8

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II.2.2b UPPER RIGHT QUADRANT (URQ) PAIN (SIDE PAIN)

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. It varies from a dull ache and bruised feeling, to sharp stabbing pain which is quite different from “gas pains.”

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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II.2.2c LOSS OF LIBIDO

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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II.2.2d RED PALMS

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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II.2.2e NAUSEA

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. Sometimes the nausea is caused by disturbances to the inner ear, in which case your doctor might be able to prescribe treatment. Many persons on the list have developed autoimmune inner ear disease as a complication of hepatitis C.

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II.2.2f BRAIN FOG

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.

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II.2.2g ITCHING

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.

Recently many of our members have taken to using “bag balm,” an ointment used on horses. It is apparently effective and harmless. It can be obtained from any equestrian or farm supply store

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II.2.2h VISION PROBLEMS

Some hepatitis patients complain of blurring vision, and dry eyes. This can be especially true while undergoing interferon treatment. Interferon treatment can and does trigger retinal complications, such as hemorrhages, as well as vitreous detachments, cotton wool spots, cataracts and even strokes (infarcts). Be sure to get your eyes tested before beginning treatment. There are products to counteract dry eyes. If you are on treatment, use sunglasses outdoors.

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II.2.2i DIZZINESS

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.

Hepatitis C is becoming increasingly associated with a host of autoimmune disorders. Some of these disorders affect the inner ear. The inner ear regulates balance. Symptoms of autoimmune inner ear disease are dizziness, ringing in the ears (tinitus) and hearing loss.

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II.2.2j DRY MOUTH

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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II.3.0 IT’S NOT ALL IN YOUR HEAD!

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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II.3.1 WHAT IS THE EVOLUTION OF THE DISEASE?

Over fifty-nine percent of people infected with hepatitis C will remain infected for life, but among those with genotype 1b, that figure zooms up to 92%. 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

Approximately 85% of people infected with HCV will develop chronic hepatitis; ultimately, 20-30% of those will progress to cirrhosis. (JAMA Vol. 284 No. 4, July 26, 2000). 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

Progression of the disease depends on several factors: mode of transmission (transfused victims usually progress faster), age at transmission (people infected older progress faster), gender (men usually progress faster than women) and alcohol use.

II.4.0 WHAT OTHER MEDICAL PROBLEMS CAN BE RELATED TO HCV?

Chronic hepatitis C infection causes problems for parts of the body beyond the liver. The organs most often affected include the blood vessels, skin, joints, kidneys, thyroid gland, heart and brain. The virus itself has been found in the heart, muscles, nerves and lymphatic system. 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, coma, and susceptibility to infection.

During the last years many autoimmune manifestations have been correlated with HCV infection; namely, sicca syndrome, chronic polyarthritis, polydermatomyositis, fibromyalgia, autoimmune thyroiditis, lung fibrosis, and diabetes mellitus. (Curr Opin Rheumatol 2000 Jan;12(1):53-60)

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.

Hep C Illness - Outside the Liver

By Paul Harvey

In considering the possible impact of hepatitis C on our health, we should first question our definition of good health. Some clinicians suggest that good health is not so much a specific state such as "absence of disease or illness". They believe that good health is an overall approach: one that accommodates a certain level of illness as normal and has people working positively towards overcoming the physical and emotional problems caused by disease (Lorig et al.). This is quite a useful approach when considering that most people will develop some type of chronic illness in their life.

Our complex biological system

An additional issue before examining the possible impact of hepatitis C on health is consideration of the incredibly complex biological nature of our bodies. Modern technologies are forever changing our world but they remain crude in comparison to the fantastic interaction of electrical, chemical and biological processes that exist within us. Given this level of complex interactions, it is not unusual that a disease most noticeably causing illness in one major organ or body system will have some level of impact on other parts of the body.

Non-liver HCV illness

Studies suggest that hepatitis C related fatigue is not primarily related to actual liver disease but is linked either to disorders of the immune system (Eur J Gastro Hept 1999 Aug;11(8):833-8) and (Am J Gastro 1999 May;94(5):1355-60), or to altered neurotransmission (brain tissue) function (Lancet 1999 Jul 31;354(9176:397).

The most commonly reported symptom of hepatitis C is fatigue. Clinicians are yet to confirm if this is an extrahepatic condition (an illness affecting parts of the body other than in the liver), or if it is related to actual liver damage (see p16). Aside from fatigue and possible complications of actual liver damage, hepatitis C infection has comparatively little impact on the rest of our body - although several conditions have been observed. Of the range of other health conditions linked to hepatitis C, some have been observed and well documented by clinicians (see below), while the occurrence of many others have been noted in only a small number of cases and may yet be explained as simple coincidence.

The publication Hepatitis C: a management guide for general practitioners (Aust Family Physician 1999;28 SI:27-31) recently listed a range of HCV extrahepatic conditions (below). Many of these are reported in The Hep C Review, ED30, September 2000, by Dr Bryan Speed (page 12), Dr Tony Jones (page 16), Doug Mellors (page 29), Dr Ed Gane (page 30) and Tina Pirola (page 34).

Arthralgia

Cyroglobulinaemia

Diabetes melitis

Glomerulonephritis

Lichen planus

Non-Hodgkin's lymphoma

Peripheral neuropathy

Porphyria cutanea tarda

Sicca syndrome

Sjogren's syndrome

Thrombocytopaenia

Thyroid disorders

Vasculitis

Summary

The majority of all people in our culture experience chronic illness at some point in their life. So although it's great to have good health, it's probably unreasonable to expect to have perfect health. In a small number of cases, hepatitis C can cause imbalance and illness in various parts of the body - other than the liver. Given the complexity of our bodies, the fact that such extra hepatic HCV conditions can occur should not be seen as abnormal. These "extra hepatic conditions" are not necessarily serious and properly diagnosed and treated, they should not cause alarm if they occur. Certainly, they do not warrant unnecessary anxiety.

If anyone suspects they may be experiencing extra hepatic conditions, they should consult their GP and if necessary, ask for referral to a hepatologist or other hepatitis specialist. Prior to such consultation, people should do a "work up" with their doctor; ie. noting the frequency of possible symptoms and having any relevant blood tests done.

* Paul Harvey is Special Projects Officer with the Hepatitis C Council of NSW, Australia.

Source: The Hep C Review, Ed30, September 2000

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II.4.0a CRYOGLOBULINEMIA

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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II.4.0b THYROID AND AUTOIMMUNE PROBLEMS

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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II.4.0c RHEUMATOID ARTHRITIS-LIKE SYMPTOMS

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; Rev Med Chil 1998 Jun;126(6):725-6.

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II.4.0d FIBROMYALGIA

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. A more recent study (Curr Opin Rheumatol 2000 Jan;12(1):53-60) suggests that a causative role of HCV seems to be likely in the development of fibromyalgia.

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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II.4.0e DERMATOLOGICAL MANIFESTATIONS

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 Sjogren’s syndrome.

Numerous extrahepatic disorders have been recognised in association with HCV infection among which dermatological diseases occupy a central part. Cutaneous necrotising vasculitis, mixed cryoglobulinemia, porphyria cutanea tarda and lichen planus are the major skin diseases frequently associated with HCV infection, but other skin disorders, such as Adamantiadis-Behcet syndrome, erythema multiforme and nodosum, malacoplakia, urticaria and pruritus, may also be linked to hepatitis C. Further studies are necessary to establish or refute an aetiopathogenetic role of HCV in these conditions. Skin manifestations are also part of the clinical picture of other extrahepatic disorders associated with HCV infection, such as thyroid dysfunction and HCV-related thrombocytopenia. The response to interferon alpha (alpha-IFN) therapy in skin diseases is unpredictable with some patients ameliorating, others remaining stationary and others deteriorating. J Eur Acad Dermatol Venereol 1998 Jan;10(1):12-21.

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.

II.4.0f PORPHYRIA CUTANEA TARDA (PCT)

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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II.4.0g LICHEN PLANUS

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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II.5.0 CYCLES AND FLARE-UPS

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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II.6.0 SHOULD I BE VACCINATED AGAINST OTHER TYPES OF HEPATITIS?

All persons with hepatitis C should be vaccinated against hepatitis A and B. An editorial in the New England Journal of Medicine warned that fulminant hepatitis is associated with hepatitis A virus superinfection in Patients With Chronic Hepatitis C. What this means is that persons with hepatitis C who get hepatitis A are at significant risk for fulminant hepatitis and death. From June 1990 to July 1997, the scientists examined 163 adults with chronic hepatitis B and 432 patients with chronic hepatitis C who were seronegative for HAV antibodies; tests were conducted every four months for serum IgM and IgG antibodies to HAV. Over the course of the study, 10 patients with HBV infections and 17 with HCV infections acquired HAV superinfection. Of these patients, fulminant hepatic failure developed in seven of the HCV-infected individuals, six of whom died. All but one of the HBV patients who developed HAV had uncomplicated courses. Since HAV infection rarely has a fulminant course and is usually non-fatal, the scientists note that "the high mortality rate among our patients with chronic hepatitis C and HAV superinfection (35 percent) is thus surprising, as is the even higher percentage of such patients with fulminant hepatitis (41 percent)." The authors suggest, therefore, that individuals with chronic HCV infection be vaccinated against the hepatitis A virus. AUTHOR: Vento, Sandro; Garofano, Tiziana; Renzini, Carlo; et al. SOURCE: New England Journal of Medicine (01/29/98) Vol. 338, No. 5, P. 286

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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II.7.0 HCV AND WOMEN’S CONCERNS

Women can be affected by hepatitis C in a different way from men. This is possibly due to hormonal effects and liver damage. A study presented at the 3rd International Conference on Therapies for Viral Hepatitis. December 12-16, 1999; Maui, USA and Antiviral Therapy 1999; 4 (Supplement 4), 38. suggested that pre-menopausal women have better response rates to alfa interferon for chronic hepatitis C. Interestingly, menstruation protects women from organ damage until after menopause. This is thought to be caused by the protective effects of estrogen and the lower amounts of iron in the blood in pre-menopausal women.

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.

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.

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

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.

Sexual intercourse during your period is not safe.

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II.7.1 PREGNANCY AND BREASTFEEDING

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 whether or not a toddler has the virus. The rate of fetal infections in HCV+ mothers is about 6%. The rate goes up if the mother is co-infected with HIV.

Any woman, or partner of a man, who has taken Ribavirin must wait 6 months after the end treatment before becoming pregnant to avoid birth defects.

BREASTFEEDING : There has been no documented case of HCV being transmitted by breastfeeding, and the rates of infant infection are identical in both breast- and bottle-fed infants. There are many advantages to breastfeeding. Breastfeeding mothers should check their nipples before each feed and avoid breastfeeding if they are cracked or bleeding. They may want to consider using breast shields.

It is not known if interferon or Ribavirin are passes on to the baby through breast milk.

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

There is a high mortality rate among pregnant patients infected with hepatitis E, which sometimes accompanies hepatitis C. There have been no studies on pregnant women taking interferon.

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II.8.0 HOW DOES HCV AFFECT CHILDREN?

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 nor