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.