Monday, August 11, 2014

Prescription for Ursodiol

So my return to the liver specialist reconfirmed my diagnosis and reveals for certain I am in the early stage of PBC. My doctor prescribed me Ursodiol 300 MG two times a day for the rest of my life. I will have to return to the office every three months for a review of blood work. Every two years I will require a liver biopsy to re-stage the disease and to look for signs of disease progression. Ursodiol is not a cure, but the medication should work in helping slow down the disease's progression. My doctor gave me some comfort by reiterating that PBC progresses slowly, and that I could go 20 or more years before I might require a transplant – While admittedly feeling some relief, I also found this unsettling and wondered if 20 years from now I would be physically strong enough to handle transplantation if necessary. For now, I'm diligent about taking the medication and continuing my research.  I've been taking the ursodiol for about four days now and I haven't noted too many side effects. I have noticed some shakiness in my hands on occasion, but I cannot yet attribute it to the use of this particular medication. 

Drug Efficacy 

According to the article appearing in “Gastroenterology (2002),” entitled “Primary biliary cirrhosis: Incidence and predictive factors of cirrhosis development in ursodiol-treated patients,” Christophe Corphechot, Fabrice Carrat, Raoul Poupon, and Renee-Eugenie Poupon, report some sufferers of PBC “escape and progress toward cirrhosis and end-stage disease,” despite receiving Ursodeoxycholic acid (UDCA) therapy. The group's study examined 183 PBC patients in various stages of the disease and the efficacy of UDCA. The findings revealed the following: 

Incidence of Cirrhosis in 5 years of UDCA Treatment 

Stage I = 4%
Stage II = 12%
Stage III = 59% 

Incidence of Cirrhosis in 10 years of UDCA Treatment 

Stage 1 = 17%
Stage II = 27%
Stage III = 76% 

Median Time for Cirrhosis Development 

Stage I = 25 years
Stage II = 20 years
Stage III = 4 years

Cirrhosis Predictive Factors 

Serum Bilirubin higher than 7 μmol/L
Serum Albumin less than 38 g/L
Moderate/severe piecemeal necrosis 

About Ursodiol 

Ursodiol (pronounced ur-so-DYE-all) is a generic name for my prescribed medication. This medication was approved by the FDA in 1987. It is also known by a variety of brand names including Urso DS, Urso Forte, Urso, and Actigall. The European identification of the drug is Ursofalk and the acid is marketed as Durlusan in France.

According to MedlinePlus, Ursodiol is naturally produced in the body. It's a bile acid called ursodeoxycholic acid and it's stored in a person's gallbladder. The medication helps to reduce the amount of cholesterol in the body and it dissolves the cholesterol in bile. According to, how Ursodiol works in slowing PBC progression is unclear.

Potential drug interactions include colestipol (Colstid), cholestyramine (Questran Light, Questran), and antacids can reduce the absorption and effectiveness of ursodiol. Oral contraceptives, estrogens, clofibrate (one of several cholesterol controlling medications) might minimize the effectiveness of ursodiol being used by patients with gallstones by increasing the liver's secretion of cholesterol and thereby increasing the chances of gallstone development. 

Active ingredients in ursodiol 


Inactive ingredients

Colloidal silicon dioxide
Ferric oxide
Magnesium Stearate
Corn Starch
Ferrosoferric oxide

Drug Interaction Summary

antacids/aluminum hydroxide
calcium carbonate
colestipol (Colstid)
cholestyramine (Questran Light, Questran)
oral contraceptives
sodium bicarbonate
sodium citrate/citric acid

Potential Side Effects

Note: Sources like the American Liver Foundation suggest that patients rarely experience side effects from the use of ursodiol.

Back pain
Biliary pain
Cholecystitis/gallbladder inflammation
Cold symptoms – cough, sore throat, sneezing, and stuffy nose
Hair loss/Alopecia
Leukopenia/Reduced white blood cell concentration
Mild abdominal pain
Mild itching/Pruritus
Peptic ulcer
Peripheral edema
Thrombocytopenia/reduced amount of platelets.
Upper respiratory tract infection
Urinary tract infection
Weight gain

This medication needs to remain at room temperature or between 59 and 86 F.

My Initial Diagnosis with PBC

Primary biliary cirrhosis - I had never even heard of such a thing before, but there the words were in plain site when I accessed my blood tests online through an Internet patient portal. I hadn't even had a chance to discuss my initial blood tests with my rheumatologist before I saw the results.

Originally I was referred to a rheumatologist to explore the possibility of whether I have lupus or not. I had a blood test in 2002 indicating a high antinuclear antibody count of 1:1280 with a positive speckled pattern that hinted that I might have lupus. After seeing a bone and joint specialist shortly thereafter and being told I did not have the disease, I remained suspicious over the years that followed, and with good reason. I had chronic pain since 2000, and a string of illnesses since 2008. In fact, since 2008, I had cellulitis 8 times, four incidents of which landed me in the hospital, two incidents resulting in surgery, and one incident resulting in sepsis and nearly taking my life.

In April 2013, I was diagnosed with Type 2 Diabetes following an eye exam indicating that my vision had declined dramatically. Following the diagnosis, I made significant changes in my diet and lifestyle. I've lost 66 pounds to date and my AC1 went from 6.6 to 6.0 so I presently have my diabetes under control. Still, the chronic pain was ongoing, and I got cellulitis for the eighth time despite the management of my diabetes. The potential diagnosis of lupus remained in the back of my mind. Hence the referral to a rheumatologist, who sent me to a lab for blood tests.

Admittedly, I was nervous about the outcome of the tests. Then I find out that the labs somehow lost the tests and I would have to repeat them! Following the second blood tests, I checked the online patient portal for any results that might have been posted. The tests indicated that the normal range for antimitochondrial antibodies (M2 AMAs) is between 0.0 and 20.0. Mine blood test came back indicating 113.2 units. A note referred to the bottom of the page indicating that anything over 24.9 was positive and is indicative of the presence of antibodies that are found in 90 to 96% of patients with primary biliary cirrhosis. Of course, when I saw the note the first thing I thought was, what the heck is that?

Google can help you find out so much information, but sometimes the search engine can prove a monster. I searched the term primary biliary cirrhosis and was horrified at the information I found. I thought to myself, “this can't be true, it has to be a mistake.” I was emotionally numb. Immediately I called my husband and told him that I hope the blood tests are wrong because it suggests there is something wrong with my liver. My husband Mark did his best to keep me calm and told me not to rush to judgment until I could talk to my doctor. That's when I became upset with the fact that I wasn't called or asked to come into the office before the findings of the blood test were posted.

A follow up visit with the rheumatologist ensued. He wanted to run more tests to rule out any potential false positives. The second blood tests also indicated a high antimitochondrial antibody count: this time it was 121.8 units – five times higher than it should be. The second test resulted in a referral to a gastroenterologist. It took nearly two months to get in to see the specialist and it felt like the longest two months of my life. After discussing my symptoms with my doctor and his review of my blood work, the doctor said that there is only a 2% false positive with AMA tests which we have already ruled out by repeating the tests. He also said that despite my high AMA levels, at this time my liver functions were normal, and he recommended a biopsy to stage the disease and to confirm its presence. The doctor than informed me that the biopsy may not indicate anything initially and even if the results were normal, following the biopsy he would begin a course of treatment to slow the progression of the disease – he rather be safe than sorry.

I had the liver biopsy on Tuesday of last week and received the results yesterday. The biopsy confirms that I am in the early stages of primary biliary cirrhosis and I also have fatty liver disease. Next Tuesday I return to the doctor to begin my course of treatment. It was yesterday that I decided to write this blog – I was inspired by another author, editor, and friend of mine, Dinah Roseberry, who faces issues with breast cancer and shares her experiences online. I am also a firm believer in the fact that through research I can become empowered, and that writing is healing. The blog will also ultimately allow me to keep everyone current on my health condition, and I hope that my writings can prove helpful to others as well.

What is PBC

Primary biliary cirrhosis (PBC) is a chronic autoimmune disease where the body's immune system begins creating antibodies that attack, damage, and eventually destroy the liver. The immune system's job is to protect the body, but with PBC, antimitochondrial antibodies (AMAs) are produced and, in turn, the antibodies attack the mitochondria in liver cells. In the medical field, the disease is sometimes called “a loss of self tolerance.”

According to the Mayo Clinic Online, the liver produces bile: a fluid that has a significant role in ridding the body of toxins, red blood cells, and cholesterol. In people suffering from PBC, the bile ducts are destroyed over the course of time. Bile is a necessary part of the digestive process; the fluid travels from the liver into bile ducts, the gallbladder, and small intestines where it aids in the digestion of fats and several fat-soluble vitamins (A, D, E, and K).

The destruction of bile ducts starts with the accumulation of T lymphocytes in the liver. T lymphocytes (pronounced: lim-fuh-sytes), are sometimes called T cells. The T cells are one of two kinds of lymphocytes that are supposed to protect the body from germs and invasions. Lymphocytes are what help the body to recognize and remember invaders and destroy them. In those that have PBC, the T cells start to attack and destroy the lining of cells belonging to the small bile ducts in the liver. The small bile ducts become inflamed and nearby liver cells are destroyed over the course of time. When the liver cells are destroyed it results in scarring (fibrosis). The fibrosis eventually leads to cirrhosis of the liver.

Primary biliary cirrhosis is often diagnosed in middle aged women between the ages of 40 and 60, but there have been cases diagnosed in people as young as 20 and as old as 90 years of age. This disease is most prominent in women, with about 90 percent of sufferers being female and 10 percent being male: this results in a ratio of women to men who get PBC of 10:1.  The number of people affected by PBC every year varies, depending on the part of the world.  There is a higher rate of disease occurrence in Wales and England, although a reason for this is unknown - one in every 3,000 individuals is afflicted by primary biliary cirrhosis.  According to a review appearing in the Journal of Hepatology (2010, vol 52, pages 754-758), the highest incidents of the disease are not only in England, but in Scotland, the Northern United States, and Minnesota.  According to the Cleveland Clinic in Ohio, the incidence of PBC in Japan is lower than in other areas of the world; the same site shares estimates on PBC prevelance ranging between 40 to 400 cases per 1,ooo,ooo people, with about 4 to 30 new cases per 1,000,000 occurring each year.

The causes of primary biliary cirrhosis are unknown, but there are a number of theories pertaining to the origin of the disease. This disease has nothing to do with the excessive consumption of alcohol. The word “primary” suggests “spontaneous” since a specific cause for the disease is unknown. The word “biliary” indicates that the bile ducts are affected. The word “cirrhosis” indicates the eventual outcome of the disease. The inclusion of the word “cirrhosis” in the name of the disease is somewhat misleading; cirrhosis is not immediately present during the early stages of the disease and only appears in the end stages of PBC. Primary biliary cirrhosis is also less commonly called “Primary Autoimmune Cholangitis” and “Chronic Nonsuppurative Destructive Cholangitis.” It is surmised that the disease originates from genetic factors, environmental factors, or a combination of the two.

To date, there is still no cure for PBC. The disease progresses slowly, and the use of medications can slow the course of the disease. At the end stages of the disease however, due to the extensive damage of the liver, a transplant is required for survival. Not all individuals with PBC will reach the end stage of the disease as medications can slow the progression down. The effectiveness of medications varies from one individual to the next, but the earlier a person is diagnosed, the better.

Symptoms of PBC

According to the American Liver Foundation, individuals with primary biliary cirrhosis (PBC) may not have any symptoms in the earliest stages of the disease. The most common symptoms include pruritus and fatigue. Pruritus is extreme itchiness occurring in various parts of the body, including the back and upper and lower limbs. The degree of fatigue a person with PBC experiences varies, from day to day and from one individual to the next, with some sufferers experiencing extreme, chronic fatigue.

As the disease progresses, a person with primary biliary cirrhosis might experience edema (fluid retention) in the abdomen and ankles, skin darkening, and fatty deposits on the skin near and around the eyes. When the disease enters into the later stages, an individual can develop jaundice. Symptoms also include diarrhea and weight loss. Some symptoms occurring in the end stages of the disease include ascites, encephalopathy, and varices bleeding.

Ascites is a word used to describe the fluid build up that occurs within the peritoneal cavity. The peritoneal cavity is a space located between to membranes in the abdomen (the parietal peritoneum and visceral peritoneum) that separate the abdominal wall from the abdominal cavity. Hepatic encephalopathy is a result of liver failure and its occurrence includes a changed level of consciousness, confusion, and coma. Xanthelasma, the appearance of fatty deposits under the skin in and around the eyes, is another symptom of the disease.

Primary biliary cirrhosis often runs hand in hand with other diseases, especially those that are autoimmune in origin. The occurrence of other diseases along with PBC is called comorbidity. People with PBC might develop gallstones, renal stones, Osteoporosis, and malabsorption, as well as other digestive issues. Additional complications that can result from PBC include anemia (low iron levels in the blood), splenomegaly (spleen enlargement), cholesterol elevation, and vitamin deficiencies. This disease sometimes appears with Sjögren's syndrome, another autoimmune disease, that causes a person's white blood cells to attack and destroy two different exocrine glands: the lacrimal glands that produce tears and salivary glands that produce saliva. Thus, the primary symptoms of Sjögren's syndrome include xerostomia (dry mouth), and keratoconjuctivitis sicca (dry eyes). PBC sufferers can also develop rheumatoid arthritis.  A person with PBC might also develop portal hypertension in the portal vein system, including the vein and its tributaries and branches. The portal vein (sometimes called the hepatic portal vein), is a blood vessel that carries blood from the spleen and gastrointestinal tract to a person's liver. Cirrhosis, the end product of primary biliary cirrhosis, can cause portal hypertension and the latter can lead to esophageal varices (sometimes called oesophageal varices). Esophageal varices appear in the lower portion of the esophagus and can result in bleeding caused by the dilation of submucosal veins.

Symptoms Recap 

  • Edema (Fluid Retention)
  • Fatigue (Potentially Chronic)
  • Jaundice
  • Pruritus (itchiness)
  • Skin darkening

 Comorbidity and Complications

  • Anemia
  • Ascites
  • Arthritis
  • Cholesterol elevation
  • Digestive issues
  • Esophageal varices bleeding
  • Gallstones
  • Hepatic encephalopathy
  • Keratoconjuctivitis sicca (dry eyes)
  • Malabsorption
  • Osteoporosis
  • Portal hypertension
  • Renal stones
  • Rhuematoid arthritis
  • Sjögren's syndrome or sicce syndrome (dry eyes and mouth)
  • Splenomegaly (Spleen enlargement)
  • Thyroid issues (Hypothyroidism)
  • Vitamin deficiencies (particularly A, D, E, and K).
  • Xanthelasma (Fatty deposits on the skin around the eyes)
  • Xerostomia (dry mouth)

Causes of PBC

The cause(s) of primary biliary cirrhosis are unknown. The word “primary” suggests the disease has a spontaneous onset. The term “biliary” indicates the intrahepatic bile ducts are affected. Cirrhosis is the end result of the disease once a person enters into the final stages. A liver transplant is the only known cure for the disease at this time. However, medication is offered to slow the progress of PBC.

The Role of the Immune System

While the causes for PBC remain unidentified, there are a number of theories pertaining to disease origin. Primary biliary cirrhosis is thought to be a disease that affects immune system functioning. Thus, PBC is considered an autoimmune disease. It is sometimes called “a loss of self tolerance.” The immune system's primary job is to protect the body and organs from germs, viruses, bacteria, and other foreign invaders. Instead, in the case where an autoimmune disease is present, the immune system begins attacking the body, organs, and healthy tissue.
While the causes for PBC remain unidentified, there are a number of theories pertaining to disease origin. Primary biliary cirrhosis is thought to be a disease that affects immune system functioning. Thus, PBC is considered an autoimmune disease. It is sometimes called “a loss of self tolerance.” The immune system's primary job is to protect the body and organs from germs, viruses, bacteria, and other foreign invaders. Instead, in the case where an autoimmune disease is present, the immune system begins attacking the body, organs, and healthy tissue.

According to the Cleveland Clinic in Ohio, it is believed the immune system causes destruction to biliary epithelial cells via “direct cytoxicity” (cellular toxification) and through “lymphokine-mediated cell damage,” all of which leads to the progression of PBC. Lymphokines call immune system responses into action, promote the activation and control the movement of cells, destroy targeted cells for destruction, and play a role in the immune system's inflammatory response. In people who have PBC, for reasons unknown, the immune system begins attacking the small bile ducts in the liver.

The immune system sends T-cells (cells that destroy bacteria and viruses) to the bile ducts. The T-cells are responsible for the slow destruction of the surface of the small bile ducts in the liver. The bile ducts are slowly scarred and the scar tissue disrupts the natural movement of bile. The bile begins to build up in the liver, and this, in turn, causes additional inflammation and scarring. The scarring process leads to fibrosis and eventual cirrhosis. 

The Role of Genetics & Environmental Factors 

It is believed genetics and environmental factors both play a role in the disease's onset. According to the National Digestive Diseases Information Clearinghouse (NDDIC), genetics play in PBC onset by making a person more likely to develop the autoimmune disease. People who have a sibling or parent with the condition are more likely to develop PBC, and this is particularly true in the case of identical twins. It is surmised in people who are genetically predisposed to developing primary biliary cirrhosis, certain environmental factors might trigger the disease or worsen the condition.

Some of the environmental factors suspected to have a role in triggering the onset of primary biliary cirrhosis include infections, exposure to toxins and chemicals, and smoking. According to NHS Choices, additional environmental factors are thought to have some connection with the onset of PBC, including urinary tract infections, hormone replacement therapy, cosmetics, nail varnish, and living near a location where toxic waste is dumped. The NHS cautions however, there are no proven triggers of primary biliary cirrhosis, and all of the latter mentioned triggers are causes in theory only.

An article entitled Common Bacteria Activating Natural Killer T Cells May Cause Autoimmune Liver Disease, on ScienceDaily online reveals a potential cause of primary biliary cirrhosis is a ubiquitous bacterium. Researchers from the Cincinnati Children's Hospital Medical Center injected mice with Novosphingobium aromaticivorans (N. aromaticivorans), which in turn, activated the killer T-cells triggering autoimmune reactions that induce liver disease (May, 2008). N. aromaticivorans, a pervasive bacterium responsible for activating environmental estrogens and metabolizing xenobiotics, plays a role in PBC development. Xenobiotics is a term derived from the Greek work xenos meaning “foreign” and bios meaning “life” – thus, xenobiotics are foreign substances in the body, whether the substances are organic compounds, medications, or pollutants. N. aromaticivorans is found in water and soil.

Dr Jochen Mattner, a researcher and physician from the Children's Hospital Medical Center's Division of Immunobiology at Cincinnati, also stresses that the findings in no way implicate N. aromaticivorans as a single cause for the disease, and there may be additional causes of primary biliary cirrhosis that remain unknown. However, the findings now provide researchers with a model that can help in further understanding autoimmunity and immunologic tolerance.