2.4.0 What Other Medical Problems Are 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 also immune to other diseases; 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).
- Diabetes melitis
- Lichen planus
- Non-Hodgkin's lymphoma
- Peripheral neuropathy
- Porphyria cutanea tarda
- Sicca syndrome
- Sjogren's syndrome
- Thyroid disorders
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, i.e., 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
One-third to one-half of people with chronic hepatitis C infection has cryoglobulinemia. Cryoglobulinemia is a condition where antibodies which are attached to the hepatitis C virus 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 20% 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 affect people’s response to interferon.
In fact, some people with vasculitis have improvement in the vasculitis as their liver tests improve on
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 the creation of the thyroid hormones. If the thyroid gland dysfunction is from interferon treatment and is caught early, the thyroid gland will return to normal once interferon is stopped.
Hepatitis C infection can mirror rheumatoid arthritis symptoms. 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.
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 mostly that 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.
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.)
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.
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.
Often people with HCV suffer from peripheral neuropathy. Peripheral neuropathy refers to an inflammatory disease (-pathy) of the nerves (neuro-) and “peripheral” refers to the extremities: hands and feet. The problem may be related to many illnesses or disorders, such as diabetes, Sjogren’s syndrome, vasculitis, rheumatoid arthritis, and especially to cryoglobulinemia in hepatitis C patients. It can be hereditary, or can be an autoimmune problem. It can be caused by compression (carpal tunnel), or can be caused by some drugs, but the inflammatory kind is the kind usually related to hepatitis C. The symptoms are numbness, pain and/or tingling in the feet or hands. It is the most common symptom in HCV patients who have mixed cryoglobulinemia. The cryo often responds to IFN treatment, but it doesn’t always help the neuropathy.
Peripheral neuropathy may have the same cause as encephalopathy, which is also caused by inflammation of the small blood vessels, but in the brain. Some doctors believe that HCV causes our immune system to produce rheumatoid factors, which are deposited in the capillaries, causing inflammation called vasculitis and may lead to a kidney disease called glomerulonephritis, or to arthralgias or skin lesions, and of course, neuropathy. Peripheral neuropathy can cause weakness and loss of productivity, even if the liver is not seriously damaged.
Diagnosis can be as simple as a doctor testing the patient’s reflexes, or testing the feet for sensibility. Other tests can be done to confirm the diagnosis, such as blood tests, a nerve biopsy, urinalysis for glomerular injury, and a nerve conduction test.
What can be done? Try to get rid of the cause, rather than just treat symptoms. Standard Hep C treatment helps some patients, so it may be worth a try. Others, however, develop the problem while on treatment, in which case, treatment may have to be stopped. Steroids may help some people, but may increase HCV viral load. Plasma exchange was used successfully in one patient with a serious case.
If you have pain because of neuropathy, remember that most pain remedies can damage the liver, and eventually make the situation worse. Having said that, sometimes you just have to deal with the pain. Start out by talking to your doctor. He may recommend vitamin B. You may, with your doctor’s approval, wish to start with alternative therapies, such as magnets, acupuncture, massage, visualization or biofeedback. A healthy diet and exercise may delay symptoms and prevent progression. TENS (transcutaneous electrical nerve stimulation) won’t hurt your liver. A simple remedy for pain is Tylenol or aspirin (not too much). You can try Capsaicin, from chili peppers, in a cream form. Neurontin has been used for the pain, with good results, but it has quite a list of side-effects, and is not good for people with kidney problems. Antidepressants such as Elavil, and anti-seizure medications, such as Tegretol may help the pain. If necessary, a nerve block may be considered.
Here are some things you can do:
- Check your feet every day for blisters, calluses or cuts.
- Throw away those tight shoes and socks.
- Use a hoop from the medical supply store to keep sheets and covers off your sensitive feet.
- Don’t smoke
- Massage your hands and feet
- Don’t cross your knees or lean on your elbows
Remember, if you go to a podiatrist for the care of your feet, take your own pedicure tools to avoid getting other people’s infections, or spreading your own.
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