John M. Vierling M.D. is Professor of Medicine and Surgery at the Baylor College of Medicine in Houston, Texas, where he also serves as Director of Baylor Liver Health and Chief of Hepatology. In addition, he is the Director of Advanced Liver Therapies, a center devoted to clinical research in hepatobiliary diseases at St. Luke's Episcopal Hospital. Dr. Vierling is board certified in internal medicine and gastroenterology and a Fellow of the American College of Physicians.
Dr. Schoenfield served as associate professor of medicine and consultant in gastroenterology on the faculty of the Mayo Clinic for seven years. He became a professor of medicine in residence at UCLA from 1972 to 1999 (now emeritus). He was the director of gastroenterology at Cedars-Sinai Medical Center in Los Angeles for 25 years, where he received the chief resident's teaching award, the president's award, and the pioneer of medicine award.
Between 95 and 98% of patients with PBC have autoantibodies in their blood
that react with the inner lining of mitochondria. These autoantibodies are
called antimitochondrial antibodies (AMA). Mitochondria are the energy factories
present inside all of our cells, not just the cells of the liver or bile ducts.
The mitochondria use the oxygen carried in the blood from the lungs as a fuel to
generate energy. AMA bind to protein antigens that are contained in multienzyme
complexes (packages of enzymes) within the inner lining of the mitochondria. The
multienzyme complexes produce key chemical reactions necessary for life. These
complexes are referred to as multienzyme because they are made up of multiple
enzyme units.
AMA specifically react against a component of this multienzyme complex called
E2. In PBC, AMA preferentially react with the E2 component of one of the
multienzymes that is called the pyruvate dehydrogenase complex (PDC).
Accordingly, the antigen is designated as PDC-E2. The practical importance of
all of this is that the PDC-E2 antigen is now used, as will be discussed below,
in a diagnostic test for detection of AMA. The PDC-E2 antigen is also referred
to as M2, a term introduced to designate it as the second mitochondrial antigen
discovered by researchers interested in PBC.
In as much as the bile ducts are the main targets of destruction in PBC, the question
was asked whether the AMA reacts with the epithelial cell lining of the bile
ducts. So, investigators prepared antibodies to PDC-E2. As expected, they found
that these antibodies bound to the mitochondria within cells. But, sure enough,
recent information suggests that these AMA autoantibodies also bind to PDC-E2
that lies outside the mitochondria yet within the epithelial cells lining the bile ducts.
Indeed, these cells are the main targets of destruction in PBC.
This accumulation of PDC-E2 within the biliary epithelial cells is observed
exclusively in the livers of patients with PBC, and not in normal livers or in
livers from patients with any other types of liver disease. Interestingly, it
was also observed in the livers of those two to five percent of PBC patients who
do not have AMA in their blood (AMA-negative PBC). Furthermore, intense binding
of these antibodies to biliary epithelial cells was also found to be the
earliest indication of recurrence of PBC in a transplanted liver. (PBC is
sometimes treated by liver transplantation, which will be discussed later.)
These observations led to a speculation that the antibodies were actually
reacting with an antigen from an infectious agent. The idea was that the
infectious agent was present in the biliary epithelial cells of patients with
PBC and that the agent could also infect the biliary cells of a transplanted
liver. (See the section below on the role of infection).
Gallstones are stones that form when substances in the bile harden. Gallstones (formed in the gallbladder) can be as small as a grain of sand or as large as a golf ball. There can be just one large stone, hundreds of tiny stones, or any combination. The majority of gallstones do not cause symptoms.
Hypothyroidism is any state in which thyroid hormone production is below normal. Normally, the
rate of thyroid hormone production is controlled by the brain at the pituitary.
Hypothyroidism is a very common condition and the symptoms of hypothyroidism are
often subtle.
Liver cancer is the fifth most common cancer in the world and the majority of patients with liver cancer will die within one year as a result. Patients with associated cirrhosis caused by chronic hepatitis B or C infections, alcohol, and hemochromatosis are at the greatest risk of developing liver cancer. Many patients with liver cancer do not develop symptoms until the advanced stages of the tumor which usually makes prognosis poor. The combination of an imaging study (ultrasound, CT, or MRI scans) and an elevated blood level of alpha-fetoprotein will most effectively diagnose liver cancer, while a liver biopsy can make a definitive diagnosis. Medical treatments, including chemotherapy, chemoembolization, ablation, and proton beam therapy, are not very effective. Surgical removal of the tumor or a liver transplant may be most effective in certain cases.
Cirrhosis of the liver refers to a disease in which normal liver cells are replaced by scar tissue caused by alcohol and viral hepatitis B and C. This disease leads to abnormalities in the liver's ability to handle toxins and blood flow, causing internal bleeding, kidney failure, mental confusion, coma, body fluid accumulation, and frequent infections. Symptoms include yellowing of the skin, itching, and fatigue.
Sjögren's syndrome is an autoimmune disease involving the abnormal production of extra antibodies that attack the glands and connective tissue. Sjögren's syndrome with gland inflammation (resulting dry eyes and mouth, etc.) that is not associated with another connective tissue disease is referred to as primary Sjögren's syndrome. Sjögren's syndrome that is also associated with a connective tissue disease, such as rheumatoid arthritis, systemic lupus erythematosus, or scleroderma, is referred to as secondary Sjögren's syndrome. Though there is no cure for Sjögren's syndrome, the symptoms may be treated by using lubricating eye ointments, drinking plenty of water, humidifying the air, and using glycerin swabs. Medications are also available to treat dry eye and dry mouth.
Edema is the swelling of tissues as a result of excess water accumulations. Peripheral edema occurs in the feet and legs. There are two types of edema, non-pitting edema and pitting edema. Causes of pitting edema is caused by systemic diseases, most commonly involving the heart, liver, and kidneys. Local conditions that cause edema are thrombophlebitis and varicose veins. Edema is generally treated with medication.
Itching can be a common problem. Itches can be localized or generalized. There are many causes of itching to include: infection (jock itch, vaginal itch), disease (hyperthyroidism, liver or kidney), reactions to drugs, and skin infestations (pubic or body lice). Treatment for itching varies depending on the cause of the itch.
Jaundice is a yellowish staining of the skin and whites of the eyes (sclerae) with bilirubin, the pigment found in bile. Jaundice can be an indicator of liver or gallbladder disease, or it may result from the rupture of red blood cells (hemolysis).
Ulcerative colitis is a chronic inflammation of the colon. Symptoms include abdominal pain, diarrhea, and rectal bleeding. Ulcerative colitis is closely related to Crohn's disease, and together they are referred to as inflammatory bowel disease. Treatment depends upon the type of ulcerative colitis diagnosed.
Learn about osteoporosis, a condition characterized by the loss of bone density, which leads to an increased risk of bone fracture. Unless one experiences a fracture, a person may have osteoporosis for decades without knowing it. Treatment for osteoporosis may involve medications that stop bone loss and increase bone strength and bone formation, as well as quitting smoking, regular exercise, cutting back on alcohol intake, and eating a calcium- and vitamin D-rich balanced diet.
Scleroderma is an autoimmune disease of the connective tissue. It is characterized by the formation of scar tissue (fibrosis) in the skin and organs of the body, leading to thickness and firmness of involved areas. Scleroderma is also referred to as systemic sclerosis, and the cause is unknown. Treatment of scleroderma is directed toward the individual features that are most troubling to the patient.
The liver is the largest solid organ in the body, and is actually an gland. The liver has a wide variety of critical functions such as manufacturing proteins and metabolizing fats and carbohydrates. The liver also eliminates harmful biochemical waste products from the body (alcohol, drugs, toxins). The liver secretes bile that aids in digestion. Examples of diseases of the liver include cirrhosis, hepatitis, cancer, and fatty liver. Symptoms of liver disease include bleeding, easy bruising, edema, fatigue, and jaundice.
Digestion is the complex process of turning food you eat into the energy you need to survive. The digestive process also involves creating waste to be eliminated, and is made of a series of muscles that coordinate the movement of food.
Thyroiditis is the inflammation of the thyroid gland. The inflamed thyroid gland can release an excess of thyroid hormones into the blood stream, resulting in a temporary hyperthyroid state. Some forms of thyroiditis can be diagnosed based on tenderness and enlargement of the thyroid gland. A thyroid scan sometimes is used in making the diagnosis. Thyroiditis can also be diagnosed with a biopsy of the thyroid gland.
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