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HCSP . VERSION 3.0 . February 2009
a series of fact sheets written by experts in the field of liver disease
An Overview of Extrahepatic Manifestations of Hepatitis C

The hepatitis C virus mainly affects the liver,
but there are many other conditions that are associated
with hepatitis C. Extrahepatic manifestation means diseases
or conditions that affect organs other than the liver.
Extrahepatic manifestations of hepatitis C can be found
in the skin, eyes, joints, immune system, nervous system
and kidneys. Some of these conditions - cryoglobulinemia,
for example - are somewhat more common and
well-documented, while others are infrequent or their
association with hepatitis C has not yet been proven.
Several studies have found that between 70-74% of HCV
patients experience extrahepatic manifestions. Some of
the most common symptoms and conditions reported
include fatigue, arthralgias (joint pain), paresthesias
(feeling of numbness and tingling), myalgias (muscle
pain), pruritus (severe itching), sicca syndrome (dryness
of the mouth and eyes), insulin resistance, type II diabetes,
kidney disease, thyroid disease and many other
conditions. Many of the conditions have in some way
been related to cryoglobulin (an abnormal blood protein)
production.
It is important to remember that the vast majority of
people with hepatitis C may never experience the more
severe types of these extrahepatic manifestations. However,
if you believe that you may have any of these conditions
talk to your medical provider for more informationand diagnosis.
If possible have your regular provider refer you
to a provider who specializes in these types of conditions.
Arthralgia is a common symptom of hepatitis C that is characterized
as joint pain, but without inflammation of the joints
that is associated with arthritis.
Arthritis is a condition characterized as inflammation of
the joints. Hepatitis C-related arthritis (HCVrA) is estimated
to affect about 4% of the HCV population, but since most
patients will not see an arthritis specialist the true number is
likely higher. Hepatitis C-related arthritis is classified into two
groups - polyarthritis and mono-oligoarthritis. Polyarthritis
is similar to rheumatoid arthritis but is less serious. Monooligorthritis
affects the medium and large-sized joints - typically
the ankles.
Behcet's Disease is a disease that presents as ulcerations
in the eyes, mouth and genitals but can also affect any organ
of the body and is caused by coagulation and destruction of
arteries and veins.
Canities is a condition believed to be associated with hepatitis
C that causes premature graying of the hair, but is uncommon
in people with hepatitis C.
Cerebral Vasculitis is a disorder that is characterized by
inflammation and cell death of arteries in the brain. The cause
of cerebral vasculitis is unknown, but it is thought to be caused
by immune dysfunction.
Cryoglobulinemia is one of the most common disorders associated
with hepatitis C. Cryoglobulinemia is a blood disorder
caused by abnormal proteins in the blood called cryoglobulins
that precipitate or clump together when blood is chilled and
dissolve when warmed. These proteins can be deposited in
the small and medium sized blood vessels, which restricts
blood flow and can lead to further problems. There is a blood
test used to detect cryoglobulinemia, but it is important that
the blood sample is kept at room temperature and handled
carefully. Even though the markers for cryoglobulinemia are
common in people infected with hepatitis C, most people with
hepatitis C are not symptomatic, but those who are symptomatic
can have mild, moderate or severe illness. Symptoms
of cryoglobulinemia include red or purple blotching skin, and
joint and generalized pain. Cryoglobulinemia can affect the
skin, kidneys, nerves and joints. Conditions associated
with cryoglobulinemia include vasculitis (inflammation
of the blood vessels), peripheral neuropathy, Reynaud's
Phenomenon (hands that are sensitive to cold temperature
and turn white, red, blue), and Non-Hodgkin's lymphoma (a
collection of diseases). Treating cryoglobulinemia consists
of treatment of the underlying disease (hepatitis C) as well
as the administration of medications to suppress the immune
system, and plasmapheresis (blood is taken from the
body, filtered and returned to the body).
Diabetes is a disorder caused when the body is unable
to process sugars. Diabetes that is seen in people with
hepatitis C is type 2 diabetes which is a slowly progressive
disease. A direct link between type 2 diabetes and hepatitis
C has not been clearly established; but it is found more
commonly in people with hepatitis C than in the general
population.
Fatigue is one of the most common symptoms of hepatitis
C and can range from mild to moderate to severe. It is
thought that the fatigue is caused by the body's immune
response to hepatitis C and as well as by direct affect of
the virus on the body.
Fibromyalgia is a disorder characterized by aches, pain,
stiffness, soft tissue tenderness, general fatigue and
sleep disturbances. Pain is the most common symptom
of fibromyalgia and it is usually confined to muscles and
ligaments. Although fibromyalgia has not been linked to
hepatitis C, it is a condition that is more commonly found
in people with hepatitis C than in the general population.
A comprehensive approach with many different healthcare
providers (including the person suffering from Fibro) is the
best strategy.
Hypertrophic Cardiomyopathy (HCM) is a form of a
disease of the heart where enlargement and thickening
develops in one part of the heart. Very rarely has it been
associated with hepatitis C.
Insulin Resistance (IR) is a condition caused by the inability
of cells to absorb glucose. This leads to the pancreas
releasing more insulin so there is an excess amount of both
glucose and insulin in the bloodstream. HCV can induce
IR. IR lowers treatment response and can speed up HCV
disease progression.
Lichen myxoedematosus (LM) is also known as papular
mucinosis. LM is a rare chronic condition that has been
linked to HIV infection, hepatitis C infection, and exposure to
toxic oil and contaminated L-tryptophan. LM is characterized
by small papules (bumps) that affect the face, trunk
and extremities that can progress on to skin tightening and
hardening.
Lichen Planus is a skin disorder that is characterized by
small elevated bumps or pimples and usually appears on
flexor surfaces (the muscle that brings two bones together,
causing flexion of the part) - arms, trunk, genitals, nails and
scalp. Symptoms can include scaling, itching, hair loss, skin
lesions, plaque, and pain. Hepatitis C-related lichen planus
is caused by HCV replication in epithelial (skin) cells. Treatment
consists of treating the underlying cause (hepatitis
C), but treatment with HCV medications in managing or
relieving symptoms of lichen planus has been inconsistent.
Cortisone creams/ointments and cortisone injections are
also used for managing the symptoms. Avoid substances
that can trigger a flare-up of symptoms including alcohol,
tobacco, spicy foods, peppermint, cinnamon, citrus type
foods and stressful situations.
Lung Abnormalities and diseases can be triggered by
hepatitis C. Idiopathic pulmonary fibrosis is defined as
scarring of the lungs. Chronic Obstructive Pulmonary
Disease (COPD) involves two diseases - chronic bronchitis
and emphysema. Asthma is a chronic disease that inflames
and narrows the airways. Hypoxemia is a condition
in which there is an abnormally low amount of oxygen in
the blood due to the inability of the lungs to perform their
chief function of gas exchange. Interferon can also cause
various lung abnormalities.
Membranoproliferative Glomerulonephritis (MPGN)
is a condition affecting the kidneys that is usually (but
not always) associated with cryoglobulinemia. Symptoms
include weakness, edema and arterial hypertension. Treatment
consists of treating the underlying disease (hepatitis
C). However, if there is severe kidney impairment, ribavirin
should be avoided.
Membranous Nephropathy is a disease of the kidneys
that is associated with hepatitis C but not with cryoglobulinemia.
It is believed that circulating HCV antibodies andviral particles are
deposited in the kidneys causing damage.
Treatment consists of interferon plus ribavirin. If there is
severe kidney damage then the use of ribavirin should be
avoided.
Mooren Corneal Ulceration is associated with hepatitis
C and can cause pain, inflammation, tearing and loss of
sight.
Multiple Myeloma is a form of cancer of the plasma
cells in the bone marrow that causes excessive growth of
the plasma cells. This interferes with the production of red
and white blood cells and platelets, and can cause anemia,
infections, and bleeding.
Neutropenia is defined as an abnormally low white blood
cell (netrophils, lymphocytes, monocytes, eosinophils, and
basophils) count. Decreased production of white blood
cells can lead to increased risk for infections. Interferon
can also cause neutropenia.
Non-Hodgkin's Lymphomas (NHL) are cancers of lymphoid
tissues. NHL can be low-grade (slow growing) or
high-grade (rapidly growing) cancer. NHL is uncommon,
but the incidence of NHL is higher in people with hepatitis
C than in the general population. Studies have found that
successful treatment with interferon and ribavirin can lead
to remission of NHL.
Paresthesia is a sensation of tingling, pricking, or numbness
of skin. The exact cause of HCV-related paresthesia
is unknown but it has been linked to other conditions found
in people with hepatitis C such as fibromyalgia, peripheral
neuropathy and hypothyroidism.
Peripheral Neuropathy (PN) is characterized by numbness,
burning, pins and needles sensations, crawling skin,
and itching that occurs most often in the hands and feet,
but can appear in other areas of the body. People with
HCV-related PN should be tested for Cryoglobulinemia.
In one study, it was found that 15.3% of people with HCV
were diagnosed with PN. Treatment consists of treating
the underlying disease (HCV) and avoiding any medications
that cause or that can make neuropathy worse. It is
also advised that patients should avoid or reduce alcohol
consumption.
Porphyria Cutanea Tarda (PCT) is a skin disorder caused
by the reduced activity of an enzyme resulting in an overproduction
of and build up of the protein uroporphyrinogen
in the blood and urine of patients, and hepatitis C has been
suggested as a cause. Other causes include hereditary
hemochromatosis (accumulation of iron in the liver), heavy
alcohol use and estrogens. Characteristics of PCT develop
in areas that are exposed to the sun with resulting skin
lesions (blisters) on the hands, forearms, back of the neck
and face. PCT can also cause skin discoloration, either
darkening or lightening of the skin, increased facial hair,
thickening of the skin, and alopecia (hair loss). Treatment of
PCT can involve phlebotomy, dietary iron restriction, reducing
alcohol consumption, avoiding exposure to the sun or
the use of sunscreen, and avoiding or minimizing estrogen
exposure. (See Figure 1)
Pruritus is one of the most common symptoms reported
by people with hepatitis C (15%), but is more commonly
found in people with end stage liver disease. Pruritus is
itching that may be localized to a specific part of the body
such as hands and feet, but it can also be a generalized
itching all over the body. It can be related to high bilirubin
levels, autoimmune disease or dry skin, and can be a side
effect of treatment. Use of moisturizing lotions, oatmeal
baths or lotions, antihistamines, and cortisone creams and
opiate drugs can help.
Raynaud's Syndrome is a disorder that causes the blood
vessels in the fingers, toes, ears, and nose to constrict or
narrow. Treatment consists of managing the condition since
there is no cure for Raynaud's.
Sialadenitis is an inflammatory disease that causes dry
mouth and eyes and is associated with hepatitis C infection.
Sialadenitis destroys the salivary glands.
Sjogren's Syndrome (SS) is an autoimmune disease that
affects the eyes and mouth, making them dry. Although
hepatitis C has not been directly linked to SS, it is found
more often in people with hepatitis C than in the general
population. There is no cure for SS. Treatment consists of
managing or lessening the symptoms.
Spider Nevi is characterized by the appearance on the skin
of small red dots with radiating lines resembling a spider
web. Spider nevi can be found anywhere on the body but
usually affects the face and trunk.
Systemic Lupus Erythematosus (SLE) is an autoimmune
disease. The exact cause of SLE is unknown, but it
is thought that the immune system mistakenly recognizes
proteins in the blood as foreign invaders and destroys
normal proteins. Symptoms vary widely from patient to
patient as do episodic attacks or flare-ups. The disease
usually attacks one organ, but over time other organs can
be affected and after many years SLE can lead to death.
There are many strategies for managing SLE including the
use of NSAIDs, acetaminophen, corticosterioids, immunomodulating
drugs, and anticoagulants.
Thrombocytopenia is generally defined as a platelet
count below 100,000 to 150,000 cells per microliter of
blood. The normal range of platelets is between 150,000
and 450,000 cells per microliter of blood. Most studies
have found a correlation between the stage of fibrosis and
thrombocytopenia in HCV patients. Platelets are proteins
that help the blood clot. Treatment with interferon can also
cause thrombocytopenia.
Thyroid Disease can be caused by many factors including
hyperthyroidism (too much thyroid hormone) and hypothyroidism
(too little thyroid hormone) released by the thyroid
gland. The direct link between hepatitis C and thyroid disease
(usually hypothyroidism) is unclear, but thyroid disease
is more commonly seen in people with hepatitis C than in
the general population. HCV treatment can also induce
thyroid disease, but thyroid function will return to normal
for about 95% of people who develop treatment-related
hypothyroidism when treatment is stopped.
Vasculitis (essential cryoglobulinemic vasculitis) is the inflammation
of blood and lymphatic vessels and is caused by
cryoglobulins - antibodies that precipitate (clump together)
under cold conditions and dissolve on rewarming. Vasculitis
is associated with hepatitis C-related cryoglobulinemia
(see cryoglobulinemia above). Symptoms include purpura
(discoloration of the skin caused by bleeding vessels) petechiae,
(red pin point rash caused by minor hemorrhaging),
and usually affects the lower extremities of the body. Other
symptoms include fever, itching welts, muscle ache and pain
and enlarged lymph nodes as well as peripheral neuropathy
Treatment consists of treating the underlying cause (HCV)
with interferon plus ribavirin, but has shown mixed results.
Vasculitis can also affect other organs such as the kidneys,
liver, lungs, heart and central nervous system, but this is
uncommon. A skin biopsy will show inflammation of the
small blood vessels. (See Figure 2)
Vitiligo is a condition in which there is loss of pigmentation
- usually around the mouth, eyes, nose, elbows, knees
and wrists.
Waldenstrom Macroglobulinemia (WM) is a chronic
low-grade type of cancer of the lymph cells. Treatment of
WM depends on the degree of disease progression.

granted and encouraged with credit to
the Hepatitis C Support Project.
.hcspFACTsheet.

A publication of the Hepatitis C Support Project
For more information about hepatitis C, hepatitis B and
HCV coinfections, please visit www.hcvadvocate.org.

I'm impatient. I sure hope it doesn't take too long. I do want to share
that I feel my energy came from taking some herbals. I'm taking CoQ10,
selenium, milk thistle and lipoic acid. When I ran out I went back to
being a couch potato.

I have a small business hauling appliances around and I'm just a 5 ft 2
inch woman. Yeah, I'm tired at the end of the day but I'm able to do it.
I think the exercise has also helped my energy levels.