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Understanding Immune Globulin's Role in Hepatitis

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The Relationship Between Hepatitis C and Vascular Disease

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Mixed cryoglobulinemia is a common extrahepatic manifestation of Hepatitis C. Although not much is known about why this vascular disease frequently accompanies the Hepatitis C virus, researchers have uncovered some new information.

As one of the most infectious viruses to affect the liver, Hepatitis C has been associated with a wide range of systemic problems. Called extrahepatic manifestations, the immune system is typically involved when the Hepatitis C virus (HCV) reveals itself in organs other than the liver. A vascular autoimmune disease that can become problematic, mixed cryoglobulinemia is an extrahepatic manifestation that has developed a close relationship with HCV.

What Is Mixed Cryoglobulinemia?

Literally meaning “cold antibody in the blood,” cryoglobulinemia is defined by abnormal proteins in the blood that become thick or gel-like in cold temperatures. Scientists have yet to discover why the antibodies known as cryoglobulins solidify at low temperatures. When cryoglobulins congeal, they can block blood vessels throughout the body, a situation capable of causing many complications ranging from skin rashes to kidney failure.

One of the diseases causing vasculitis, cryoglobulinemia causes damage and inflammation to the blood vessels throughout the body. Depending on the type of antibody affected, cryoglobulinemia is categorized into Type I, II or III. While Type I cryoglobulinemia is most often related to cancer of the blood or immune systems, Types II and III are referred to as mixed cryoglobulinemia and are usually found in people who have chronic HCV.

Cryoglobulinemia can cause different problems depending on the antibody type and the organs affected. Potential symptoms include:

  • Difficulty breathing or fatigue
  • Enlargement of the liver and spleen
  • Glomerulonephritis – a type of kidney disease that reduces the kidneys’ ability to remove waste and excess fluids.
  • Joint or muscle pain
  • Purpura – the appearance of red or purple discolorations caused by bleeding underneath the skin.
  • Raynaud’s phenomenon – when the smallest arteries that bring blood to the fingers or toes constrict from cold temperatures or strong emotions.
  • Skin ulceration or death

The Immune System and Cryoglobulinemia

Normally increasing in quantity to fight an illness, the immune system’s B cells make antibodies to fight infection. As these B cells multiply, the antibodies they make are released into the blood where they latch onto the invading pathogens, marking them for destruction. In mixed cryoglobulinemia, the B cells continually multiply, sending the body into a spiral descent of pathological vascular conditions that increasingly cause damage.

Why HCV Is Connected to Cryoglobulinemia

As far back as 1990, researchers observed that most patients with Hepatitis C also developed mixed cryoglobulinemia. Worldwide, an estimated 100 to 170 million people have both HCV and mixed cryoglobulinemia. Ever since the association between these two conditions was realized, researchers have been perplexed about the origin of their relationship. Because HCV primarily infects the liver, scientists have been trying to understand why the B cells of someone with Hepatitis C replicate out of control to cause cryoglobulinemia.

A popular theory proposed that a protein scattered around the outer coat of the Hepatitis C virus binds to a certain receptor. Called CD81, this receptor is found on the surface of almost every cell in the body – including B cells. If the viral protein directly latches onto the surface of a B cell, it may elicit uncontrolled B cell proliferation resulting in cryoglobulinemia. Researchers from Rockefeller University say that this decade-old explanation of how one disease causes the other is likely wrong and instead offer a new theory: that the factor associated with HCV and cryoglobulinemia pursues a specific, as yet unidentified, cellular target.

In the immune system, billions of B cells are on guard. Each B cell can produce only one kind of antibody, which ordinarily can recognize and fight off only one specific pathogen. Rockefeller University clinicians isolated B cells from patients with both conditions and found they had remarkably similar antibodies. For those with Hepatitis C, their findings suggest that the CD81 receptor was not the vehicle for activating B cells. If this were the case, B cells with different antibody molecules and markers would have been activated.

Published in the February 2008 edition of the journal Blood, Rockefeller University researchers enrolled HCV-infected patients and looked at their antibody genes. They found the activated B cell genes to be identical in almost every mixed cryoglobulinemia participant. Although technical obstacles and the nature of the disease have prevented scientists from identifying the exact pathogen that triggers mixed cryoglobulinemia, they are hopeful that finding this elusive disease-causing factor will provide new insight into recovery, prevention and treatment of cryoglobulinemia.

Despite a clear understanding of why Hepatitis C often coexists with mixed cryoglobulinemia, there is an unmistakable association between these two diseases. Although the coexistence of these ailments is still poorly understood, the mechanism linking them together could end up providing us with a way to eliminate both diseases from future generations.

References:, Rituximab to Treat Hepatitis C-Associated Cryoglobulinemic Vasculitis, National Institutes of Health, 2008.

Kayali Z, Labrecque DR, Schmidt WN, Treatment of hepatitis C cryoglobulinemia: mission and challenges, Current Treatment Options in Gastroenterology, December, 2006., Extrahepatic Manifestations of Chronic Hepatitis C, Roderick Remoroza MD, Herbert Bonkovsky, MD, Hepatitis C Support Project, 2008., Essential Mixed Cryoglobulinemia, William C. Shiel Jr., MD, FACP, FACR, MedicineNet, Inc., 2007., The University of Chicago, 2007., Cryoglobulinemia, National Institutes of Health, 2008., New Theory Suggests How Hepatitis C May Cause Rare Immune Disease, ScienceDaily LLC, May 2008.

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Understanding Immune Globulin's Role in Hepatitis

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Medivir AB and Tibotec Partner Up To Develop Hepatitis C Polymerase Drug

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