Primary biliary cirrhosis (PBC) is a chronic cholestatic
liver disease
characterized by a striking predominance in female patients (with most
cases diagnosed between ages 40 and 60 yr) as well as serum
auto-antibodies to mitochondrial antigens, elevated serum immunoglobulin
M, progressive destruction of intrahepatic bile ducts, and, ultimately,
liver cirrhosis and failure.
There have been reports that environmental
chemicals, such as 2-octynoic acid, found in
perfumes, lipstick, or other
sources may contribute to the onset or aggravation of primary biliary cirrhosis.
Natural therapy or supplements for Primary Biliary Cirrhosis
Little research has been done in this area, and one study using the
antioxidants Vitamin A, C, E and selenium did not show benefits, although other
antioxidants, such as Lipoic
acid, flavonoids or carotenoids have not been tested to any extent. Silymarin from milk thistle was
tested once in a human trial but no major response was seen. The use of dietary
fiber, such as Psyllium,
has also been evaluated.
Sometimes the dose of a nutrient, herb or drug makes a
difference in the results of a study. Too little may not work, too high a dose
may be counterproductive, and there may be cases where a few people are helped
by a supplement, but when a study is done, and the results pooled, the benefits
in those few people may not be picked up when the overall statistics are
completed.
Environmental concerns
Minimizing exposure to environmental chemicals,
including perfume, lipstick, makeup, etc, is advised.
Primary Biliary Cirrhosis - Genetics or Environment? What are the causes?
Primary biliary cirrhosis is an
autoimmune disease caused by a
combination of inherited and environmental reasons. It is exceptional among
autoimmune diseases in showing strong heritability according to familial
occurrence and monozygotic twins concordance, yet with weak associations with
the usual genetic risk elements for autoimmunity, such as the HLA alleles. Some
studies implicate polymorphisms of genes for cytotoxic T-lymphocyte antigen-4,
interleukin-2, or interleukin-10; polymorphisms of the
vitamin D receptor could
synergize with low sunlight exposure to create deficiency of the immunoregulatory factor, activated vitamin D. African-American women have a low
rate of Primary biliary cirrhosis. Several factors point toward an auto-immune
pathogenesis for primary biliary cirrhosis (PBC), mostly based on the presence
of serum auto-antibodies to mitochondrial antigens (AMAs) and autoreactive T
cells (both helper and cytotoxic). Recent evidence points to a role for either
foreign substances or chemicals or novel infectious agents in the induction of
the disease.
Symptoms and signs of Primary Biliary Cirrhosis
Fatigue, which may
have a significant impact on quality of life, is the most common reported
symptom. Others
include pruritus, arthralgia, jaundice, and splenomegaly. Chronic cholestasis is the main feature of primary biliary
cirrhosis.
Medical and Surgical Treatment of Primary Biliary
Cirrhosis
Clin Liver Disease. 2016. Novel Therapies on Primary Biliary Cirrhosis. All
patients with primary biliary cirrhosis (PBC) and abnormal liver biochemistry
should be considered for specific therapy. Ursodeoxycholic acid is the only
FDA-approved drug for treating PBC. Approximately 40% of patients with PBC
respond incompletely to treatment with Ursodeoxycholic acid, thus having
increased risk of death or need for liver transplantation. No second-line
therapies for patients with inadequate response to Ursodeoxycholic acid therapy
have been approved.
PBC usually slowly progresses to cirrhosis, liver failure, and death, unless liver transplantation is performed. Ursodeoxycholic acid (UDCA), a hydrophilic dihydroxy bile acid, is the only drug currently approved for the treatment of patients with PBC. In addition to UDCA, patients with PSC should be referred to endoscopic dilatation of major bile duct stenoses. Several potential mechanisms of action of UDCA have been proposed, including intracellular modulationof signaling events and secretion. Various immunosuppressive drugs have been evaluated alone or in combination with UDCA. Of these drugs, the topical corticosteroid budesonide, together with UDCA.
Gastroenterol Res Pract. 2013. Combination Therapy of Ursodeoxycholic Acid and Corticosteroids for Primary Biliary Cirrhosis with Features of Autoimmune Hepatitis: A Meta-Analysis. A meta-analysis was performed of RCTs comparing therapies that combine UDCA and corticosteroids with UDCA monotherapy. In this paper, we found that the combination therapy of UDCA and corticosteroids was more effective for PBC-AIH.
Racial differences
African Americans and Hispanics with primary biliary cirrhosis often present
with more severe disease than their Caucasian counterparts
Cirrhosis of the Liver in England
The number of Britons dying from cirrhosis of the liver linked to heavy drinking
is increasing at a much faster rate than in any other European country .
An analysis of European cirrhosis mortality rates from 1950 to 2002 published in
The Lancet medical journal showed the number of deaths increased in Britain
while it fell in other European countries.
It more than doubled in men in Scotland between the periods of 1987-1991 and
1997-2001 while it rose by over two-thirds in England and Wales.
Symptom of Cirrhosis of the Liver
Cirrhosis symptoms vary, depending on severity. Mild cirrhosis may not
show any symptoms at all. The following are the most common symptoms of
cirrhosis: ascites (build-up of fluid in the abdominal cavity), breast
enlargement in men, coughing up or vomiting blood, gallstones, itching,
and jaundice.
Alcoholic cirrhosis - Cirrosis hepatica
Continued alcohol abuse in many people will result in the development of
alcoholic cirrhosis, leading to permanent scarring of the liver.
Cirrhosis treatment
If you have cirrhosis, you must stop drinking alcohol. Also, do not take
medicines that can cause damage to the liver, including nonsteroidal
anti-inflammatory drugs, such as ibuprofen (Advil or Motrin) and naproxen
(Aleve), acetaminophen, and other liver damaging drugs. Start a low-sodium diet
if fluid retention is occurring. Reducing your sodium intake can help prevent
fluid buildup in your abdomen (ascites) and chest. Get immunized (if you have
not already) against
hepatitis A and hepatitis B, influenza, and pneumococcus.
Primary Biliary Cirrhosis Research
Chemical xenobiotics and mitochondrial autoantigens in primary biliary
cirrhosis: identification of antibodies against a common environmental,
cosmetic, and food additive, 2-octynoic acid.
J Immunol. 2005.
Amano K, Leung PS, Rieger R, Quan C, Wang X, Marik J, Suen YF, Kurth MJ, Nantz
MH, Ansari AA, Zeniya M, Matsuura E, Coppel RL, Gershwin ME.
Division of Rheumatology, Allergy and Clinical Immunology, Genomic and
Biomedical Sciences Facility, University of California, Davis, CA
Emerging evidence has suggested environmental factors as causative agents in
the pathogenesis of primary biliary cirrhosis (PBC). We have hypothesized that
in PBC the lipoyl domain of the immunodominant E2 component of pyruvate
dehydrogenase (PDC-E2) is replaced by a chemical xenobiotic mimic, which is
sufficient to break self-tolerance. To address this hypothesis, based upon our
quantitative structure-activity relationship data, a total of 107 potential
xenobiotic mimics were coupled to the lysine residue of the immunodominant 15
amino acid peptide of the PDC-E2 inner lipoyl domain and spotted on microarray
slides. Sera from patients with PBC, primary sclerosing cholangitis, and healthy volunteers were assayed for Ig reactivity. PBC sera
were subsequently absorbed with native lipoylated PDC-E2 peptide or a
xenobiotically modified PDC-E2 peptide, and the remaining reactivity analyzed.
Of the 107 xenobiotics, 33 had a significantly higher IgG reactivity against PBC
sera compared with control sera. In addition, 9 of those 33 compounds were more
reactive than the native lipoylated peptide. Following absorption, 8 of the 9
compounds demonstrated cross-reactivity with lipoic acid. One compound,
2-octynoic acid, was unique in both its quantitative structure-activity
relationship analysis and reactivity. PBC patient sera demonstrated high Ig
reactivity against 2-octynoic acid-PDC-E2 peptide. Not only does 2-octynoic acid
have the potential to modify PDC-E2 in vivo but importantly it was/is widely
used in the environment including perfumes, lipstick, and many common food
flavorings.
Study of antioxidant enzymes level and phagocytic activity in chronic
liver disease patients.
Egypt J Immunology. 2003.
Patients with chronic cholestasis, particularly those with associated
cirrhosis, are susceptible to infectious complications. A predictable
consequence of cholestasis is malabsorption of fat-soluble vitamins and free
radical scavengers. On the other hand, it has been postulated that cholestasis
affects polymorphonuclear leukocytes function by impeding chemotaxis,
phagocytosis and superoxide anion release in experimental animals. This work is
aimed to evaluate the antioxidant status and phagocytic activity of neutrophils
in chronic liver disease patients. 15 primary biliary cirrhosis (PBC) patients,
15 primary sclerosing cholangitis (PSC) patients, 15 chronic viral hepatitis C (HCV)
patients, and 15 healthy individuals (control group) were included in this
study. Levels of catalase (Cat), superoxide dismutase (SOD), reduced glutathione
(GSH), glutathione peroxidase (GPx) and malondialdehyde (MDA) were assessed in
both serum and neutrophils homogenates. Neutrophils function was estimated by
nitroblue tetrazolium (NBT) reduction assay. A marked decrease in the
antioxidant status was observed in serum and neutrophils' homogenate of patients
with chronic liver diseases compared to healthy subjects. Significant elevation
of lipid peroxides was found in all groups of liver disease patients. The
majority of patients had reduced value in NBT reduction assay, which suggested a
lack of response to infection by neutrophils. In conclusion, deficient
antioxidant defense mechanisms may lead to excess oxygen free radicals formation
that promote the pathological process in the liver. The use of free radicals
scavengers by chronic liver patients may potentiate the antioxidant defense
system against oxidative stress.
Oral antioxidant supplementation for fatigue associated
with primary biliary cirrhosis: results of a multicentre, randomized,
placebo-controlled, cross-over trial.
Aliment Pharmacol Ther. 2003. Centre for Liver Research, Newcastle
University Medical School, Framlington Place, Newcastle, Tyne & Wear, NE2 4LL,
UK
We have previously reported, in an uncontrolled trial, an improvement in
fatigue scores in patients with primary biliary cirrhosis given oral antioxidant
supplementation. We now present data from a controlled trial. Sixty-one patients
with primary biliary cirrhosis-associated fatigue were randomized into a
double-blind, placebo-controlled, cross-over trial. Participants received 12
weeks each of placebo and antioxidant supplementation (vitamins A, C and E,
selenium, methionine and ubiquinone) in random order, separated by a 4-week
washout period. The primary trial outcome (fatigue) was assessed using the Fisk
scale. Other symptoms of primary biliary cirrhosis were measured using Likert
and visual analogue scales. Forty-four patients completed both arms of the
trial. No significant changes in fatigue were recorded in the active phase of
treatment. Small improvements in Fisk scores were recorded during placebo
therapy. Neither medication was associated with improvement in any other
symptoms related to primary biliary cirrhosis. Adverse effects were more common
during active therapy and were mild and self-limiting. One patient died from
unrelated causes during active treatment. Although oral antioxidant
supplementation appears to be safe, we could not find any evidence for a
beneficial effect on fatigue or other liver-related symptoms.
Antifibrotic effect of silymarin in rat secondary biliary fibrosis is
mediated by downregulation of procollagen alpha1(I) and TIMP-1.
J Hepatol. 2001.
Silymarin reduces hepatic collagen accumulation by 35% in rats with secondary
biliary cirrhosis. The aim of the present study was to explore its antifibrotic
mechanism. Thirty female adult Wistar rats were allocated to (1) bile
duct occlusion, (2) bile duct occlusion and oral silymarin at 50 mg/kg per day,
and (3) sham operation and oral silymarin at 50 mg/kg per day. Steady-state mRNA
levels for procollagen alpha1(I), tissue inhibitor of metalloproteinases-1
(TIMP-1), and transforming growth factor (TGF) beta1 were determined by
multi-probe ribonuclease protection assay. After 6 weeks of bile duct
occlusion, liver collagen content was increased 12-fold, when compared with the
sham-operated controls. These animals displayed 17-, 6.5- and 16-fold higher
transcript levels for procollagen alpha1(I), TIMP-1 and TGFbeta1). Silymarin downregulated elevated procollagen alpha1(I), TIMP-1 and TGFbeta1 mRNA
levels by 40-60%. These lowered hepatic profibrogenic transcript
levels correlated with decreased serum levels of the aminoterminal propeptide of
procollagen type III. Silymarin suppresses expression of
profibrogenic procollagen alpha1(I) and TIMP-1 most likely via downregulation of
TGFbeta1 mRNA in rats with biliary fibrosis. The serum procollagen type III
propeptide level mirrors profibrogenic mRNA expression in the liver.
Silymarin in the treatment of patients with primary biliary cirrhosis with
a suboptimal response to ursodeoxycholic acid.
Hepatology. 2000.
Angulo P, Patel T, Jorgensen RA, Therneau TM, Lindor KD.
Division of Gastroenterology and Hepatology, Mayo Clinic and Foundation,
Rochester, MN
Ursodeoxycholic acid (UDCA) is a safe and effective medical therapy for most
patients with primary biliary cirrhosis (PBC), but some patients show an
incomplete response. Silymarin is a potent antioxidant with immunomodulatory and
antifibrotic properties. The aim of this study was to evaluate the safety and
assess the efficacy of silymarin in patients with PBC who had shown a suboptimal
response to UDCA. Twenty-seven patients with PBC who had been on UDCA (13-15
mg/kg/day) therapy for 7 to 221 months and had shown a persistent elevation of
alkaline phosphatase activity at least 2 times the upper limit of normal for
more than 6 months were enrolled. Oral silymarin, 140 mg 3 times daily was given
for 1 year, and patients continued on the same dosage of UDCA. No significant
changes in serum alkaline phosphatase activity, total bilirubin, aspartate
transaminase (AST), albumin, or Mayo risk score were
noted after 1 year of treatment with combination therapy. Transitory
gastrointestinal adverse events occurred in 2 patients. In conclusion, although silymarin was well tolerated, this medication did not provide benefit to
patients with PBC responding suboptimally to UDCA. The results of this pilot
study would seem to discourage further controlled trials of silymarin in
patients with PBC.
Effect of dietary fiber on serum bile acids in patients with chronic
cholestatic liver disease under ursodeoxycholic acid therapy.
Digestion. 1995.
During ursodeoxycholic acid therapy for chronic cholestatic liver disease,
the serum levels of lithocholic acid increase about twofold. Lithocholic acid
has been shown to be hepatotoxic in some animal species. Administration of
psyllium hydrophilic mucilloid (PHM), a dietary fiber, has been reported to
increase the bile acid mass excreted by the feces. We, therefore, studied the
effect of PHM (3 x 3.25 g/day) on serum bile acids including lithocholic acid in
12 patients with primary sclerosing cholangitis (n = 7) and primary biliary
cirrhosis receiving ursodeoxycholic acid therapy. After 2 and 6 weeks of
treatment with PHM, the serum levels of ursodeoxycholic acid increased by 52.4
+/- 72.8% and 40.5 +/- 69.6% (NS), respectively. The absolute serum
levels of lithocholic acid were not significantly changed. This led to a
decrease of the relative amount of lithocholic acid as referred to total bile
acids and to ursodeoxycholic acid in serum after 6 weeks of psyllium hydrophilic
mucilloid treatment.
Effects of selenium supplementation on blood and urine selenium levels and
liver function in patients with primary biliary cirrhosis.
Clin Chim Acta. 1991.
To study the mechanism of the reduced serum selenium concentration in
patients with liver damage we administered 200 micrograms (2.53 mumol) selenium
daily as selenium-rich yeast to 8 patients with primary biliary cirrhosis and 8
healthy controls over 16 weeks. Initially selenium concentrations in serum were
24% lower (P less than 0.001) in patients than controls. During supplementation
serum selenium levels increased in both groups but the difference between them
persisted. Throughout the study whole blood selenium levels and glutathione
peroxidase activities were also somewhat lower (P = NS) in patients than
controls. Selenium supplementation had no effect on whole blood glutathione
peroxidase activities in either group. The basal 24 h urinary excretion of
selenium was similar in both groups but was increased more by supplementation in
patients than controls. Selenium administration did not influence the liver
function of the patients. We conclude that impaired hepatic production of
selenium-containing serum compounds is the most likely explanation for the
reduced serum selenium concentration in patients with primary biliary cirrhosis.
Questions
Q. What is an average amount of psyllium for primary biliary cirrhosis, how much
is an appropriate dosage.
A. It's difficult to say, but it would safe for most people to take
half or one teaspoon of psyllium in a glass of water twice a day with meals.
Q. I'm very pleased to see that you have so much
information on primary biliary cirrhosis on your website. You mentioned alpha
lipoic acid and said that it's unknown whether it is of value in this disease. I
can tell you that
Dr. Eric Gershwin, one of the prime researchers on the disease, has cautioned us
who have it not to take that supplement. I'm not clear on the reasons but he
just said, "don't take it." Actually, he's very leery of us taking any
supplements at all but he's especially strong on that one.
A. Perhaps Dr. Eric Gershwin is aware of some research or has
experience with alpha lipoic acid and primary biliary cirrhosis that has made
him come to that conclusion. Or, perhaps he has a negative viewpoint of
supplements in general that has clouded his viewpoint. I look forward to
research in this area to determine what role, if any, alpha lipoic acid has in
this medical condition.
Testimonial received in 2016
Just wanted to let you know I am still in remission from my primary biliary
cirrhosis, hashimotos hypothyroid and sjogrens due to alpha lipoic acid and
ursodiol. I also take plaquenil, not sure if that helps much though. I went into
remission within a month of starting ala and urso. That's too soon for the urso
to work. I do believe the urso helps some. My TPOs are normal still and I'm off
synthroid. I have vitiligo and have repigmented some, though patchy. My liver
enzymes are normal. My arthritis is better off pain meds. I also have pulmonary
fibrosis that appears to not be progressing. It may be scarring at this point. I
have developed miners and ocular myasthenia during this time, perhaps I had them
before but they are worse now. I have lost forty pounds which significantly
improved my heart and lung health, at least part of that was fluid up around my
lungs. I have improved stamina and am more active. I lost weight on a bypass
diet called five bite diet and have maintained my weight loss. We have two
hundred friends and family on ala now and many of them have been able to go off
their blood pressure medicine and are solely controlling it with the ala. Not
sure why that is. One woman was on three meds after triple bypass and now on
nothing but ala. It also put lupus into remission in one person who got it from
implants. I have never been as healthy as I am now on ala. I think it plays a
critical role in treating pbc and all liver diseases. Thanks for your info. Oh
and first clean scope from colon cancer. My GI attributes this to the
antioxidants I take.