Live Chat Transcript: Depression and HCV

Hepatitis C is the most common liver disease currently seen in clinical practice. The incubation period, from the time of exposure to the virus until the onset of the disease, is one to six months. Early symptoms include poor appetite, lack of interest in food, nausea, aching muscles and joints, and light fever. Some people experience only mild symptoms such as tiredness, periodical pressure below the right ribs caused by the enlarging liver, and aching muscles and joints. Only 1 in 10 patients with acute Hepatitis has symptoms. The remaining nine have no symptoms whatsoever. In 8 out of 10 patients, the infection becomes chronic. 

 Many patients remain asymptomatic until decompensation occurs. Lack of symptoms and minor liver enzyme elevations are typical of HCV infection and cannot be taken as evidence of lack of progression. HCV RNA testing confirms the diagnosis. Liver biopsy helps assess disease activity and stage the severity of fibrosis and is recommended for most patients with hepatitis C. Once this information is obtained, a rational program for treatment and monitoring can be planned. Patients with newly discovered hepatitis C infection require thorough education about the disease's natural history, transmission, interaction with alcohol, and treatment. In many cases, referral to a gastroenterologist or hepatologist may be the appropriate way to ensure necessary instruction and availability of the latest treatment options.

Symptoms commonly reported by persons with hepatitis C include:

 

	Flu-like illness
	Indigestion - gastrointestinal reflux disorder
	Irritable Bowel syndrome
	Muscle and joint pain    Myalgia is muscle pain or aching
	Night sweats
	Depression, mood swings
	Fatigue - mild to severe
	Abdominal bloating
	Diarrhea
	Headaches
	Numbness in extremities
	Mental confusion / 'brain fog
	Itchy skin
	Dizziness & peripheral vision problems
	Liver pain
	Cognitive dysfunction
	Shortness of Breath
	Loss of appetite
	Visual Changes
	Chest Pains
	Chills Fever
	Facial Puffiness
	Female Problems (irregular menses, severe PMS)
	Palpitations
	Yellowing of the Skin Jaundice
	Loss of Libido
	Spider Nevi
	Swelling of the lymph nodes

Other less common symptoms include pain or discomfort in the abdomen on the right side, itching, nausea, appetite/weight loss, mental fuzziness. Hepatitis C virus is one of many causes of swelling of the liver (hepatitis).  The liver plays a crucial role in cleaning the blood and metabolizing different substances we ingest.  When the liver isn't working correctly, "poisons" build up in the blood.  In addition, the liver makes bile, and if it isn't released correctly, it builds up in the body causing a yellowing of the skin and eyes (called jaundice and icterus, respectively).  People first infected with HCV commonly get mild flu-like symptoms with aches, fever, and chills.

Symptoms are most common in patients who have developed cirrhosis.

As the liver disease progresses, complications of cirrhosis and liver failure may occur, including jaundice, ascites (accumulation of fluid in the abdomen), variceal bleeding (bleeding from collateral vessels in the the esophagus, stomach or intestines secondary to impedence of blood flow through the liver), leg edema and encephalopathy (mental confusion due to the accumulation of toxic metabolic products that cannot be cleared by the liver).

Please see our section on Cirrhosis for photos of complications and symptoms.

 Joint pain can also be caused by a condition known as cryoglobulinemia. About 1/3 of people with hepatitis C have this problem, which is caused by antibodies attaching themselves to the hepatitis C virus. If you are having joint and muscle pain, let your doctor know. He or she may want to test you for cryoglobulinemia because it can also cause problems with blood vessels.

Frequently Asked Questions about Hepatitis C and Fatigue

Most people infected with chronic hepatitis C virus (HCV) have few symptoms or physical signs of the virus in the first two decades after infection. However, about 20 percent of those with HCV develop vague symptoms, including mild intermittent fatigue and malaise. Fatigue, which may lead to a significant decrease in quality of life, may be the first and only sign that the liver is being affected by the virus. Following are answers to some frequently asked questions about hepatitis C and fatigue.

Q. Why is fatigue associated with hepatitis C?

A. Much of the fatigue a person with HCV experiences is due to an activated immune system attempting to eliminate the virus. Despite the effective creation of antibodies against it, the hepatitis C virus can undergo frequent mutation, allowing it to avoid being eliminated from the body in 85 percent of those who contract it. In an ongoing effort to rid the body of the virus, the immune system continues to create weapons against the virus including antibodies, interleukins, and white blood cells. At times, the immune response leads to the production of immune complexes, collections of antibodies that course through the body. Immune complexes may deposit in the joints, the blood vessels in the skin, or in the kidney, leading to arthritis, rashes or glomerulonephritis (a form of kidney disease). These conditions are referred to as "extra-hepatic manifestations" of hepatitis. An immune system activated to fight a virus like HCV might also begin developing antibodies against other tissues in the body, including the thyroid. The resulting autoimmune illness, such as autoimmune thyroiditis, can result in still more symptoms of fatigue.

 Q. What underlying conditions might an HCV-infected patient have that could contribute to his or her fatigue?

A. Fatigue in HCV-infected individuals is most likely due to the virus' presence. However, a number of conditions that are readily diagnosed and treated may add to the level of fatigue. Iron deficiency anemia and hypothyroidism are both common among women and can certainly contribute to loss of energy. Depression is also common and often manifests itself as excessive sleepiness and fatigue. In fact, being diagnosed with a chronic condition can actually worsen an individual's depression.

Q. How should conditions associated with HCV be treated?

 A. In general, these conditions may be treated independently of the hepatitis. Those that are clearly related to HCV may respond to treatment with approved therapy for HCV. All medications ingested by a patient with HCV should be reviewed by his or her physician because many drugs are metabolized by the liver, which may already be compromised by the virus. Some medications, particularly some antidepressants, can lead to fatigue if serum levels are too high. Therefore, in some cases, drug dosages may need to be reduced.

Q. What changes can a person make to ease the impact of the fatigue on his or her life?

A. Most doctors recommend HCV patients eat a well-balanced diet, drink alcohol only in moderation and stop smoking. With these changes, energy levels may improve. In addition, coping with fatigue means balancing activity and rest. Some suggestions include taking short naps between activities and crafting a schedule that balances strenuous activities with ones that are less strenuous. For those with exhausting jobs, devising a flexible work schedule or telecommuting from home may be good options.

Some people with hepatitis also complain about headaches. These headaches may go away completely after a while, but then come back. Sometimes they are mild, but at other times they are severe. They are not like migraine headaches. You can treat the headaches with over-the-counter medication. (Again, check with your doctor about what to use.) Also, take time to relax and drink plenty of fluids. Staying rested and drinking lots of fluids may prevent headaches.

Sometimes people with hepatitis have nausea and loss of appetite. You should try to eat, even if you don't feel like it. It may help to eat many small meals rather than 3 large ones. But some patients find it is easier to eat a larger meal in the morning. Dry crackers, weak tea, ginger ale, and ice pops may be easier for you to eat than other foods. If the nausea lasts, or if you are vomiting, let your doctor know. He or she may be able to prescribe a medication to relieve the problem.

Having an illness can be very stressful and sometimes downright depressing. Some of your coworkers and friends may believe false information, particularly about how the disease is spread, and this may change their attitudes toward you. You may also feel somewhat isolated because your friends and family don't understand how you feel. You might feel tired all the time, or that you don't have enough energy, or that no matter how much you sleep, you just don't feel like getting out of bed. By 9 AM, you feel as if you've put in an entire workday. But you can get help to cope with these feelings.

Hepatitis and Depression

A diminished interest in recreational or pleasure activities or other activities that used to be enjoyable; a diminished ability to think or concentrate—indecisiveness; trouble sleeping or, alternatively, sleeping all the time; a significant weight loss or weight gain when not when not trying to lose or gain weight; fatigue or loss of energy; feelings of worthlessness or excessive or inappropriate guilt; recurrent thoughts of death or thinking about suicide; and taken together, these characteristic may cause significant distress or impairment in social, occupational, or other important areas of functioning. *These are all symptoms reported by people who suffer from hepatitis.* *They are also the clinical diagnostic criteria for Major Depression.* Many with hepatitis have said they were mistakenly diagnosed with depression when they were trying to find out what was wrong with their bodies (the “it’s all in your mind” diagnosis). There have also been those who thought they were depressed and in the process of being evaluated for medication for depression were diagnosed with hepatitis. It is however possible, and even probable, to have both: a diagnosis of Viral Hepatitis *and* a diagnosis of Clinical Depression. It can become sort of a self perpetuating downward spiral. That is, low energy, chronic fatigue, consistently not feeling well, along with the decrease in functioning that comes with these symptoms, all from hepatitis; combined with the impact of having a potentially fatal disease, are all very depressing things. An increase in depression leads to even lower energy, more decrease in functioning and even the possibility of making physical symptoms worse. Depression alone can be a serious debilitating disease. Combined with hepatitis it can be devastating. So how can you tell and what can you do? First, if you experience five or more of the symptoms above, talk to your doctor about depression. You might also want to consider seeing a therapist. Depressed or not, someone to talk to about the feelings that you experience around having hepatitis can really be a help in sorting things out sometimes. Your medical doctor or your therapist may refer you to a psychiatrist to prescribe one of the anti-depressant medications. Many of these have been shown to be very effective in treating depression. As with all medications, it is always good to be an informed consumer.

 Fog (HCV Affects Cerebral Function) ______________________________________

Evidence for a cerebral affect of the hepatitis C virus Choline/creatine ratios are elevated in regions of the brain of patients with hepatitis C, according to research published in the latest issue of the Lancet. A team from London, England, investigated whether hepatitis C virus (HCV) affects cerebral function. Patients with HCV infection frequently complain of symptoms akin to the chronic fatigue syndrome. They also score worse on health-related quality of life indices than matched controls. The researchers used proton magnetic-resonance spectroscopy (1H MRS) to measure cerebral choline/creatine ratios in subjects. "This suggests that a biological process underlies the extrahepatic symptoms in chronic HCV infection. " Daniel Forton. This was performed in 30 patients with histologically-defined mild chronic HCV infection, 29 age-matched and sex-matched healthy controls, and in 12 patients with chronic hepatitis B. They found that the choline/creatine ratios were significantly higher in the white matter and basal ganglia of the HCV group, compared with both the hepatitis B group and healthy volunteers. This elevation was found to be unrelated to hepatic encephalopathy or a history of intravenous drug abuse. Daniel M Forton, of Imperial College School of Medicine, St Mary's Hospital, London, concluded on behalf of the group, "The elevation in choline/creatine ratios suggests that a biological process underlies the extrahepatic symptoms in chronic HCV infection. "These findings have implications for the direction of future research and ultimately for patient treatment." Lancet 2001; 358: 38-9 10 July 2001

HEPATITIS/LIVER PAIN?

The liver has no nerves, but the liver is surrounded by a capsule (a bit like a sausage skin). The capsule has nerves in it which are sensitive to stretching and to inflammation and thus some people can occasionally experience pain if the liver becomes enlarged or inflamed. However, there are other causes for pain in that area. The brain is not very good at distinguishing pain from different organs. Liver pain is comparatively rare and usually the pain is actually from the large bowel (colon) as it squeezes bowel contents around (it acts like a wriggling worm and is always active) - thus most of the activity that the brain receives is from the colon which can "tie itself in figurative knots" sometimes with trapped wind and increased contractions. There are other organs that also lie in close proximity to the liver and could be responsible for discomfort including the gall bladder and the pancreas and the bile ducts. However for the most part the issues are often with the colon, but the liver, even in people without liver disease, can be uncomfortable if the colon is hyperactive.

Many Hepatitis C patients feel a variety of abdominal pains and discomfort, but unfortunately too often these pains are dismissed as having nothing to do with chronic liver disease. This is because abdominal organs are not responsive to many things what would normally elicit severe pain.  The pain fibers in the large interior organs, such as the liver , are usually sensitive only to stretching or increased wall tensions, which is what happens as the liver becomes inflamed. About 20 percent of patients complain of pain over the liver area, in the right upper side of the abdomen just beneath the ribs. Some experts suspects this could be Referred pain caused by inflammation and swelling of the covering of the liver. This pain also may occur in the right shoulder or to the back between the shoulder blades.

Pain that is caused by sensory nerves in the liver may cause a pain that is hard to describe- Dull cramping or aching, appearing anywhere from the midline to the lover abdominal area. It may be accompanied by nausea and vomiting , swearing , pale skin and restlessness during sleep. Patients often move about in bed, occasionally finding relief with a change in position.

Moreover, bacterial or viral infection of any organ in the abdominal are including the liver may cause abdominal pain.

VISCERAL PAIN

Visceral pain may be referred to a remote area of the body, where it is perceived as cutaneous pain (sensation of pain in the skin) in an area supplied by the same spinal cord level as the affected abdominal organ. Referred pain is usually well localized and appears when noxious visceral stimuli become more intense. Thus, swelling of the liver capsule by a hematoma (swollen blood vessels) after liver biopsy is first perceived in the abdomen but may be referred to the right shoulder.

Sensory Pain

Pain resulting from stimulation of sensory afferent nerves innervating abdominal organs. The pain is often difficult to describe (usually as cramping or aching), dull in nature, and poorly localized to the midline from the upper (epigastrium) to the lower abdominal area. The pain may be accompanied by nausea, vomiting, sweating, pallor, and restlessness. 

PARIETAL PERITONEAL PAIN

When the parietal peritoneum (abdominal membrane that encloses that body cavity) becomes involved as a result of abdominal pathology (disease process), nerves supplying the area are stimulated and generally produce pain that is more intense and more precisely localized than is visceral pain. The classic example is the localized pain of acute appendicitis. Parietal pain is often aggravated by movement; hence the patient's desire to lie completely still.

PSYCHOGENIC PAIN

This is obviously abdominal pain that is perceived but without any local cause. Unfortunately, this may be a pain mechanism that some physicians choose to attribute to some chronic hepatitis patients' episodes of pain. However, as cited above, physicians should take the time to explain and concede that there are valid causes for different types and intensities of abdominal pain that arise from our internal organs due to inflammation and toxic conditions.

FURTHERMORE.....

When the hollow structures of the gallbladder and biliary tract dilate due to the disease process, pain is experienced in the upper abdomen or right upper abdomen. Pain may also be referred to the back between the shoulder blades. Pain from the pancreas is also felt in the upper abdomen and is often referred to the middle of the back. In a manner analagous to the liver, gallbladder, and biliary tract on the right, lesions in the tail of the pancreas that involve the diaphragm, may result in referred pain to the left shoulder. Bacterial or viral infection of any intraabdominal organ may cause abdominal pain. Interference with venous or arterial blood flow can affect the abdominal organs. Clinically this may present as severe abdominal pain and shock.

Pain and Liver Disease

In many patients that have been diagnosed with hepatitis and/or
liver disease, many complain of abdominal pain, located mostly in
the right upper quadrant, right flank or epigastric area. Although
less frequent, left upper quadrant and lower abdominal pain has
also been reported.

Abdominal pain:

The nervous system pathways that convey abdominal pain messages are
known as the visceral and somatic pathways. Both of these pathways
are part of the sympathetic nervous system. The visceral fibers are
sensitive to stretch and spasm but are not affected by temperature
or sectioning of the nerve. The somatic pathways innervate the
abdominal cavity wall, parietal peritoneum, and parts of the
diaphragm. These fibers are sensitive to pressure, tension,
traction, chemical and bacterial toxins, enzymes, infiltrative
processes and edema. The central parts of the diaphragm and biliary
tract have axon fibers that carry messages in conjunction with the
phrenic nerve and are responsible for complaints of referred pain
to the shoulder area.

Biliary system pain:

Gallbladder and biliary tract spasms can cause pain that radiates
to the right shoulder and subscapular area. Inflammation of the
gallbladder wall can cause localized subcostal pain and rebound
tenderness.

Intestinal pain:

Most acute or chronic abdominal pain is bowel related. Right upper
quadrant pain is frequently due to large bowel distention (hepatic
flexure area) and small bowel ileus producing spasms and/or cramps.
Pain in the left upper quadrant can also be caused by distention of
the colon in the splenic flexure area. Lower abdominal pain would
be more likely caused by bladder or rectal problems.

Liver pain:

Liver pain (right upper quadrant) is due to the distention of the
liver capsule which has pain receptors. Rapid increases in liver
size from inflammation (viral hepatitis or alcohol induced) or a
tumor are the most common causes of liver pain. When the liver
becomes cirrhotic, specific liver pain is rarely the cause of right
upper quadrant complaints.

Pancreatic pain:

In viral or alcohol induced liver disease, the pancreas may become
inflamed, stimulating somatic nerve endings, causing severe pain
that radiates to lateral quadrants, back and left shoulder, going
through the back. It is made worse by lying down and improved when
in the knee chest position or bending forward.

Splenic pain:

Splenomegaly or infarction of the spleen may be present with liver
disease. Pain complaints will be most likely right upper quadrant.

Pain in acute or chronic liver disease may be difficult to manage
due to the excretion of many analgesics by the liver and/or
kidneys. Reduced dosages, and careful monitoring of hematological
and neurological function is critical to prevent accumulation and
toxicity. Acute or chronic hepatic failure may lower plasma
clearance of opiates such as Morphine, prolong the terminal
elimination half-life, and increase oral bioavailability
(Hasselstrom, Eriksson, Persson, Rane, Svensson, and Sawa, 1990).
Non- opiate analgesics are often contraindicated in patients with
hepatic or renal dysfunction. Acute pain in the face of chronic
disease needs prompt investigation, to rule out ulcer,
gastrointestinal bleeding, thrombosis of the portal system or
spleen, presence of tumor or development of inflammation or
infection.

Hepatitis Patients at Risk for Accidental Acetaminophen Toxicity

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.

WHAT IS THE EVOLUTION OF THE DISEASE?

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

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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

WHAT OTHER MEDICAL PROBLEMS CAN BE RELATED TO HCV?

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.

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.

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.

From NATAP http://www.natap.org/

Thyroid disease - Thyroid disorders are common in patients with chronic HCV, particularly women [57,58]. One of the largest studies included 630 consecutive patients with HCV (without cirrhosis) who were compared with 389 subjects from an iodine-deficient area, another control group of 268 persons from an area of iodine sufficiency, and 86 patients with chronic hepatitis B [58]. Mean TSH levels were significantly higher and free T3 and T4 levels significantly lower in patients with HCV than in all other groups. Patients with HCV were more likely than controls to have hypothyroidism (13 versus 3 to 5 percent ), anti-thyroglobulin antibodies (17 versus 9 to 10 percent), and anti-thyroidperoxidase antibodies (21 versus 10 to 13 percent). Another report suggested that thyroid abnormalities were seen predominantly in women [57]. (See "Pathogenesis of Hashimoto's thyroiditis (chronic autoimmune thyroiditis)").
 
Overall, antithyroid antibodies are present in 5 to 17 percent of patients with HCV infection, and thyroid disease, primarily hypothyroidism, occurs in 2 to 13 percent of patients [57,58]. The highest prevalence of both thyroid antibodies and thyroid disease is found in older women. However, whether or not the prevalence is higher than in age- and sex-matched controls is controversial [59,60].
 
A separate issue is the development of thyroid disease in patients with HCV infection who are treated with interferon alfa. Approximately 1 to 5 percent of such patients develop painless thyroiditis. Other thyroid abnormalities can also occur, including Graves' disease and permanent hypothyroidism, or increased serum antithyroid antibody concentrations without thyroid dysfunction [59-62]. The changes in thyroid function usually appear after three months of therapy, but can occur as long as interferon alfa is given.
 
The risk of any form of thyroid disease is greater in those patients who have increased serum antithyroid antibody concentrations before the initiation of therapy, a finding which suggests that interferon alfa in some way exacerbates underlying thyroid autoimmune disease. (See "Principles of interferon therapy in liver disease and the induction of autoimmunity", section on Thyroid disease). The presence of antithyroid peroxidase antibodies appears to be the most significant risk factor for the development of thyroid dysfunction during interferon therapy [62]. Other risk factors may include female gender, older age, and the presence of other autoantibodies [60]. Women with chronic hepatitis C and high antithyroid peroxidase antibody titers are at particular risk.
 
Thyroid dysfunction may resolve following the discontinuation of interferon treatment.
 
In summary, all patients receiving interferon alfa should be monitored for thyroid disease, particularly women and patients with preexisting antithyroid antibodies. Interferon therapy usually can be continued while hypothyroidism is being treated. On the other hand, we have usually stopped interferon in patients who develop clinically apparent hyperthyroidism.

MUSCULOSKELETAL

- Hepatitis C-associated osteosclerosis is a rare disorder characterized by a marked increase in bone mass during adult life. While most cases have been reported in patients with a history of intravenous drug abuse, it has also been seen with hepatitis C after blood transfusion [85]. Periosteal, endosteal and trabecular bone thickening occurs throughout the skeleton with the exception of the cranium. During active disease, forearm and leg pain are common, bone remodeling (turnover) is high, and bone mineral density is two- to three-fold higher than age-matched norms. The increased remodeling may respond to bisphosphonates or calcitonin, but spontaneous remission has also been described. Abnormalities in insulin-like growth factors (IGF-1 and IGF-II) or their binding proteins may contribute to the increase in bone formation in this disorder [86].
 
Arthritis is noted in 2 to 20 percent of HCV patients. The arthritis is an evanescent rheumatoid-like picture in two-thirds of the cases and an oligoarthritis in the rest. (See "Specific viruses that cause arthritis").
 

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.

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.It was determined that the 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.

DERMATOLOGICAL MANIFESTATIONS

The main dermatologic 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 dermatologic 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

Necrolytic acral erythema -

Necrolytic acral erythema is a pruritic, psoriasis-like skin disease characterized by a sharply marginated, erythematous to hyperpigmented plaques with variable scale and erosion on the lower extremities. In a series of 30 patients who presented with the disorder, all were found to have antibodies to HCV [81]. Biopsy specimens showed psoriaform changes, keratinocyte necrosis and papillomatosis. Improvement was observed in a patient who had been treated for HCV with interferon alfa (and subsequent relapse nine months after discontinuation). Topical and systemic corticosteroids had a variable benefit. Other reports have confirmed improvement

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 theurine) 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