Primary Biliary Cirrhosis, Basics 3

I’m pausing today before getting into how I was diagnosed with PBC, aka my year of living dreadfully. If you saw the kind comment for my next-to-last post, you probably want to know more about, and I’m happy to oblige.


The first stop site for those who have been diagnosed with PBC, suspect such a diagnosis is coming their way, or have a loved one with PBC is the Primary Biliary Cirrhosis Organization: This is their statement of purpose:

The Primary Biliary Cirrhosis Organization aka PBCers is a wonderful source of support and education for PBC patients, family members, friends and other autoimmune liver disease patients. Formed in 1996, the PBCers is the largest online PBC support group with almost 3,000 members worldwide.

As a group, we discuss medical information, pain management, medications, research, ask questions, transplantation, vent our anger & fears, speak freely on the ups and downs of daily living, share our personal experiences and build lasting friendships.

On its website, you will find  a chat room, doctors panel Q & A, contact info for local support groups, conference announcements, and other services. Educational materials are also there to download; one of the organization’s aims is to increase awareness of what PBC is.

To learn more about other people’s experiences with  PBC, I’d start with these two services at pbcers. org:

  • Yahoo Group Daily Digest: Because this is a daily digest of that day’s forum postings, you get a single email a day instead of an email each time someone posts a comment. There is also an archive of the past nine years’ messages on the sign-up page.
  • PBCers Organization on Facebook.

A clarification:

Yesterday when I wrote about factors associated with increased risk for PBC, I don’t think I was very clear. These are not causes of the disease. If they have any relevance at all, it is that they may be triggers for whatever mechanism sets the autoimmune process in motion. My understanding is that you can  have a set of people all of whom have a genetic predisposition for an autoimmune condition, but just a few ever actually develop one. So the mystery is what triggered the conditions in those who got sick — how do they differ from those who didn’t? Something — or more likely some combination of things — must have happened to light their fuses.

Another source of information:

There’s a good resource, copyright free, on  at the National Digestive Diseases Information Clearinghouse, part of the National Institutes of Health of the U.S. Department of Health and Human Services.

Here’s their summary statement, and a diagram showing those bile ducts you’re hearing so much about in these posts:

Primary biliary cirrhosis is a chronic disease that causes the bile ducts in the liver to become inflamed and damaged and, ultimately, disappear. Bile is a liquid produced in the liver that travels through

the bile ducts to the gallbladder and then the small intestine, where it helps digest fats and fat-soluble vitamins A, D, E, and K. When the bile ducts become damaged from chronic inflammation, bile builds up in the liver, injuring liver tissue. . . .

Primary biliary cirrhosis develops over time and may ultimately cause the liver to stop working completely. Most people are diagnosed early, before the disease progresses. Early treatment delays—but does not stop—the eventual onset of cirrhosis and liver failure. When a person has end-stage liver disease, a liver transplant is necessary for survival.

And these are their “Points to Remember”:

  • Primary biliary cirrhosis is a chronic disease that causes the bile ducts in the liver to become inflamed and damaged and, ultimately, disappear.
  • Injured liver tissue from chronic inflammation and the buildup of bile leads to cirrhosis, a condition in which the liver slowly deteriorates and malfunctions.
  • The cause of primary biliary cirrhosis is unknown. Most research suggests the disease is an autoimmune condition.
  • Primary biliary cirrhosis is more common in people who have a parent or sibling—articularly an identical twin—with the disease.
  • Most people are diagnosed early, before the disease progresses. The disease is often discovered when routine blood tests to check liver function are abnormal.
  • Many people with primary biliary cirrhosis do not have symptoms until after the disease is diagnosed.
  • The first and most common symptoms of the disease are itching, called pruritus, and fatigue. Other symptoms include dry eyes and mouth and jaundice.
  • The anti-mitochondrial antibody (AMA) blood test, the alkaline phosphatase blood test, and a liver biopsy may be necessary to confirm a diagnosis of primary biliary cirrhosis.
  • Some of the complications of primary biliary cirrhosis are osteoporosis and maldigestion.
  • Early treatment delays—but does not stop—the eventual onset of cirrhosis and liver failure.
  • Ursodiol (Actigall) is the only drug approved by the U.S. Food and Drug Administration for the treatment of primary biliary cirrhosis.
  • Liver transplantation is the only treatment that will cure primary biliary cirrhosis. A liver transplant is considered when complications cannot be controlled by treatment.



Primary Biliary Cirrhosis, Basics 2: Triggered Self-Destruction & the Loss of Self-Tolerance

At the end of this post you’ll find lengthy quotations, exiled there because I found myself not writing a blog but a review paper. I want to resist that habit.

You are your own worst enemy

I’ve heard that before, lots of times. And now it appears to be true.

In primary biliary cirrhosis (PBC), the cells lining the bile ducts that allow bile to leave the liver are destroyed, so the bile backs up and this accumulation damages liver cells and cirrhosis occurs. And what is attacking these bile ducts? My own immune system: hence, auto-immune.

What’s an autoimmune disease? has a succinct definition:

They are caused by the body’s own immune system getting confused and wrongly attacking the body’s good cells. . . .the immune system itself gets tricked into killing good normal cells. The immune system wrongly makes antibodies to normal cells, which cause these cells to be attacked and killed, just as if they were recognized as unhealthy virus-infected cells.

As if this weren’t bad enough, there is a second theory, that of the

Apoptosis error: cells commit suicide for some aberrant reason, and the immune system is only there to clean up afterward.

In spite of my desire to disassociate PBC from the stigma attached to the word cirrhosis, in an odd way primary biliary and alcoholic cirrhosis have something in common. Both are illnesses of self-destruction. But the difference is that the self-destruction of the alcoholic is one that the self can summon the will to inhibit. Not so with an auto-immune illness.

Some time I need to look for studies of the psychological reaction to auto-immune illness (I’m sure someone somewhere is working on this).

Putting it medically, my immune system is attacking my bile ducts. Putting it metaphorically, I am attacking myself.

OK, I know,  it is my cells attacking my body. You can call my metaphor anthropomorphism on the cellular level, but you can’t deny that I am my cells, I am my body.

I may be more than this, but if my self has no body to inhabit, although my soul or spirit may survive,  this self  — my self –won’t.

And that is hard to get my head around.  Am I so incompetent that my immune system can’t tell what’s normal and what isn’t?

Slow Suicide?

I found the second theory, the apoptosis error, a lot more disturbing until I saw the more common phrase for apoptosis: programmed cell death and learned that “between 50 and 70 billion cells die each day due to apoptosis in the average human adult.” But from what I can figure, it is one of those to everything there is a season/ A time to be born and a time to die problems. I have cells that aren’t observing this maxim. Moreover, it is altogether possible if not likely that a “vicious cycle” is set up involving the attacking and self-annihillating cells.

It’s like there’s this troop of cells and one company is relentlessly determined to destroy one of its own platoons, and that platoon is so traumatized that it turns its weapons on itself.

How dysfunctional is that?

The Loss of Self-Tolerance

Doesn’t this sound like a favorite topic of psychoanalysts, as in  “When did you lose tolerance for yourself?”

Sorry, it’s not. It’s a term from immunology. When your immune system is working right, you have self-tolerance. When it goes to hell in a hand basket, it’s a loss of self-tolerance.

Who Gets PBC?

Remember that this is an uncommon disease: PBC has a worldwide prevalence of approximately 5/100,000 ( 5 out of a 100,000 people have it), and an annual incidence of approximately 6 out of  a 1,000,000 (6 out of a million people will be newly diagnosed in a year).

  • Children don’t get it. In fact, it is unusual in teens and young adults up to about age 25.
  • About 90% of those who have it are women.
  • The highest number of cases have been found in the UK, Scandinavia, Canada, and the US. The lowest is in Australia. This may have more to do with health care procedures than with the illness.
  • Some of the hypotheses about factors associated with increased risk include:
  • living near contaminated land
  • hormone replacement therapy
  • frequent use of nail polish
  • smoking
  • appendectomy or other abdominal surgeries
  • tonsillectomy
  • More on these topics:

    More from

    Autoimmunity is a large disease category that contains almost 100 diseases. They are called “autoimmune diseases“. They are caused by the body’s own immune system getting confused and wrongly attacking the body’s good cells. Which autoimmune diseases occur from the immune confusion depends on which body cells are mistakenly attacked. Some of the best known diseases that are believed to be autoimmune include juvenile diabetes, lupus, celiac disease, multiple sclerosis, and many less common ones.

    Autoimmunity as a theory states that the immune system itself gets tricked into killing good normal cells. The immune system wrongly makes antibodies to normal cells, which cause these cells to be attacked and killed, just as if they were recognized as unhealthy virus-infected cells. The key questions about the cause of autoimmune diseases are:

    • Triggers: what starts the immune system on the wrong path?
    • Conversion: what causes the immune system to respond to the trigger?
    • Progression: what makes the immune system keep on with the autoimmune response?

    The article concludes that:

    . . autoimmunity itself is only a theory, and in fact a relatively recent theory from the last few decades.  . . . There could be other possible theories of autoimmune diseases. If we assume that the disease involves cell death (another assumption), then a list might look something like:

    • Theory 1: Autoimmunity: immune system kills the cells
    • Theory 2: Apoptosis error: cells commit suicide for some aberrant reason, and the immune system is only there to clean up afterwards
    • Theory 3: External cell damage: some virus, bacteria, toxin, or event kills the cells, and the immune system cleans up

    The following is from a sort of state-of-the-art review article (it refers to 332 articles) on PBC available on PubMed [ID#: PMC2758170] and originally published in Seminars in Immunopathology, Issue Volume 31, Number 3 / September, 2009. Authors are Simon Hohenester, Ronald P. J. Oude-Elferink and Ulrich Beuers. It is not written for the layman.

    PBC occurs in individuals of all ethnic origins and accounts for up to 2.0% of deaths from cirrhosis [15]. It primarily affects women with a peak incidence in the fifth decade of life, and it is uncommon in persons under 25 years of age. Incidence and prevalence vary strikingly in different geographic regions (as does the quality of epidemiological studies related to PBC), ranging from 0.7 to 49 and 6.7 to402 per million, respectively [16–23]. The highest incidence and prevalence rates are reported from the UK [16,21], Scandinavia [17], Canada [18], and the USA [19, 22], all in the northern hemisphere, whereas the lowest was found in Australia [20]. There is no clear evidence to support or exclude the concept of “a polar–equatorialgradient,” as it has been reported for other autoimmune conditions [24].

    A significant role for environmental factors was supported by the identification of geographic disease “hot spots,” as first reported in the northeast of England, using formal cluster analysis. The original UK analysis reported an increased frequency of PBC in former industrial and/or coal mining areas [127]. Another recent study from New York examined the prevalence of PBC and PSC near superfund areas and reported significant clusters of PBC surrounding toxic sites [128]. In synopsis, these observations gave rise to the hypothesis of a chemical environmental factor, potentially associated with contaminated land, which could either trigger disease or cause disease through a direct toxic effect [84]. This hypothesis would also provide one possible explanation for the tissue tropism of PBC if the toxin or toxins are excreted into bile (and thereby concentrated in the biliary tree) [84]. The observation that hormone replacement therapy and frequent use of nail polish are linked to the risk of developing PBC further supports the potential impact of environmental factors in the pathogenesis of PBC [117]. Smoking also seems to be a risk factor for PBC and has been demonstrated to accelerate progression [117, 129]. Associations of exposure to chemical environmental compounds and xenobiotics (including drugs, pesticides, or other organic molecules) with various human autoimmune diseases have been described as summarized in [86].

    Appendectomy, other abdominal surgeries, and tonsillectomy were significantly more frequently reported in patients with PBC in an epidemiological study in North America [155]. However, an earlier population-based case control study conducted in England did not show such associations [156]. More recently, another case–control study provided evidence that there was at least no association between PBC and the occurrence of appendectomy and pointed out the selection bias present in the previous study done in North America [157].

    It is worth mentioning that autoimmunity, defined by the presence of autoantibodies and autoreactive lymphocytes, does occur naturally. It appears that such naturally occurring autoantibodies and autoreactive lymphocytes are modulators for the suppression of early infections, clearance of apoptotic bodies, immune surveillance against cancer cells, among others, as reviewed in [160]. In this not yet completely unraveled system regulating immune response, the mechanisms responsible for the development of autoimmunity and autoimmune diseases remain enigmatic.

    However, a common causative pathway to PBC, if it exists, could not yet be identified, and it is still controversial which of the outlined factors predispose most to PBC. It may well be speculated that the search for “the cause” of PBC might lead into the dark, and the identified pathogenetic factors may contribute to a different extent in each patient. Why should the cause of PBC not be variable as is the clinical picture? The latter is highly variable: We define PBC today as the presence of cholestasis and AMAs, but only 90–95% of patients are AMA-positive and some AMA-positives hardly develop PBC. Most patients respond to UDCA treatment, but one third does not and disease progression is highly variable, to mention only the most obvious variabilities. The clinical picture that, by convention, we call PBC may well emerge from an individual composition of the described and other pathological factors.

    Once an autoimmune reaction is initiated, various vicious cycles are conceivable. Inflammatory reaction secondary to loss of tolerance will lead to further cholangiocellular damage and apoptosis, increasing presentation of (altered) self-PDC and increase autoreactivity. Once bile duct loss and cholestasis are established, retention of bile salts and other toxic compounds perpetuates damage to BECs and subsequently to the entire liver. Maintenance of these vicious cycles may be supported by an immune system that is genetically dysregulated and insufficiently capable of suppressing autoimmune reactions.

    Primary Biliary Cirrhosis: Basics, 1

    My last post was a personal account of my ongoing experience with primary biliary cirrhosis (PBC), and I’ll be offering more of that, but first I need to explain a bit about this condition. I have yet to encounter someone outside the medical world who knows about it, although “PBC is considered to be an uncommon disease, but not rare,”  according to MedicineNet, the source I will most rely on here.

    Of course there are a number of sites like MedicineNet which have been written and reviewed by the medical profession. This is no substitute for those by any means. But I’ve had some experience with the kinds of questions that people who are not worried about personally being affected ask first, while the health sites I think are usually written for people who have been diagnosed and need more systematically organized info.

    First, the name. The unfortunate name.

    The primary is OK — it is primary because not secondary or tertiary. It isn’t a result of another condition.

    Same goes for biliary: it involves the bile ducts.

    As for cirrhosis, it’s unfortunate on two counts.

    To begin with, it isn’t entirely accurate. The condition eventually leads to cirrhosis; it isn’t a special variety of cirrhosis.

    Secondly, cirrhosis is a loaded word. I bet most people think they know what causes cirrhosis of the liver: chronic alcohol abuse. Some might come up with another cause: hepatitis C (and what causes that? Dirty needles?). And, yes, these are the two most common causes of cirrhosis, and both are, to a greater (chronic alcohol abuse) or lesser (hepatitis C) extent  related to choices people make. And we all know that there are those who lack sympathy for alcoholics’ or IV drug users’ health problems.

    There are, by the way, a number of other causes of cirrhosis of the liver besides those two, including, in addition to PBC, others that have nothing to do with substance abuse, like haemochromatosis (too much iron in the blood) and Wilson’s Disease (too much copper).

    The problem is that

    … the name primary biliary cirrhosis is actually a misnomer for patients in the earlier stages of the illness. The more technically correct and ponderous term for PBC, chronic non-suppurative destructive cholangitis. . . has never been widely used and is unlikely to replace PBC.

    Chronic non-suppurative destructive cholangitis: I’ve got to agree, that’s not likely to catch on, is it?

    So what does cause PBC?

    Most of the introductions I’ve read say it is an autoimmune condition, but MedicineNet is a little more cautious in answering the question:

    The cause of PBC remains unclear. Current information suggests the cause may involve autoimmunity, infection, or genetic (hereditary) predisposition, acting either alone or in some combination.

    . . . PBC is presumed by most experts to be an autoimmune disease, which is an illness that occurs when the body’s tissues are attacked by its own immune (defense) system. (Auto means self.)

    . . . Despite strong evidence to support the concept that PBC likewise is an autoimmune disease, some features of PBC are uncharacteristic of autoimmunity. For example, all other autoimmune diseases occur in both children and adults, while, as already mentioned, PBC has never been diagnosed in childhood.


    Next time: Who gets it

    Varicose Veins in my Esophagus?

    “And if the dam breaks open many years too soon…”

    I was doing a pretty good job of cultivating indifference toward my bad luck at having somehow acquired primary biliary cirrhosis [PBC], taking my 1000 mg of  Ursodiol most days (sometimes I forget), and not scouring the internet hourly looking for the article that would tell me my future, confining that process to just the week before what had become an annual appointment at the University of Alabama at Birmingham liver clinic.

    After all, my alkaline phosphatase levels had dropped from the high 400s to the upper limit of normal, 117,  indicating the Ursodiol is doing its job, increasing bile flow from the damaged bile ducts, thereby theoretically slowing the progression of liver damage caused by backed-up toxic bile.

    Typically it would make sense to judge a treatment’s effectiveness  not quite so objectively, but in this situation, I’ve only the numbers to rely on.

    Do I feel better than I did in December 2006 when I started on the Urso Forte (my favorite brand name for a drug, roughly translatable, or so I claim, as Strength of the Bears)?

    Not dramatically. The only symptoms of PBC before the liver is damaged significantly are fatigue and itching, and I never experienced the itching and who among us doesn’t complain of fatigue?

    This week the only bad marks on my blood tests were for ones I’ve scored poorly on for at least four years: low white blood cell count and low platelet counts. In the past, these scores were considered not bad enough for alarm, just an anomaly, perhaps.

    So I was surprised to be told I should have an upper GI endoscopy to detect whether large varices, or swollen veins (like varicose veins), caused by portal hypertension (itself caused by cirrhosis) are in my esophagus. Left untreated these could “burst and bleed into the gut.

    But I gather that an association has recently been made, or at least suggested, between portal hypertension and low white blood cell count (leucopenia), and/or low platelet count (thrombocytopenia). Moreover, in 2006, on the long and wearying road to the PBC diagnosis, an ultrasound showed a very much enlarged spleen, and hypersplenism is another red flag.

    My first impulse was to say no to this test based on a strong and irrational desire not to submit to another test, a resistance that I couldn’t explain and thus ignored.

    Afterwards, after I started processing this new information, that impulse seemed less irrational: if I do have varicose veins in my esophagus, it probably means that I can no longer tell myself that my mostly normal blood test numbers  mean the PBC was diagnosed  and treatment begun in time to escape cirrhosis, at least for a while. It will mean that  my liver is already dying.

    Or so it seems to me. Surprises during doctor appointments frustrate me: I need time to think to know what questions to ask.


    Resources for the curious or those in a similar fix:

    A simple intro to PBC is at PBC Foundation

    A much more thorough one is at

    The “bad luck” link in the first sentence of this post refers to the rarity of the disease. In “Food for Thought about Primary Biliary Cirrhosis in 2006,” an essay on the website of the UC-Davis Immunology Lab, there’s this statement:

    PBC is thought to be more commonly found in specific areas of the world. In particular, disease frequency varies between 10 and 400 cases per million population. It has been suggested that PBC is more common in northern countries, including England, Sweden, and Northern American states.

    MedicineNet says:

    Studies indicate that the number of people with PBC at a given time (referred to as the prevalence of disease) ranges from 19 to 251 per million population in various countries.