Cirrhosis, Primary Biliary

What Is Primary Biliary Cirrhosis?

[dropcap]P[/dropcap]rimary biliary cirrhosis (PBC) is a biliary tract disease characterized by chronic cholestasis (build-up of bile) and gradual destruction of bile ducts within the liver, called intrahepatic bile ducts, caused by chronic inflammation.

Primary biliary cirrhosis comes under the umbrella term autoimune liver disease in which the end result is immune-mediated hepatocellular (liver cell) or hepatobiliary (bile duct) injury.¹

Q: What is the end result of destruction of bile ducts?

A: The end result of destruction of bile ducts is liver damage.

Injured liver tissue from chronic inflammation and the buildup of bile leads to cirrhosis, a condition in which the liver slowly deteriorates and malfunctions.

Scar tissue replaces healthy liver tissue, partially blocking the flow of blood through the liver. Scarring also impairs the liver’s normal ability to control infections, remove bacteria and toxins from the blood, process nutrients, hormones, and drugs, make proteins that regulate blood clotting, produce bile, and effectively replace its own cells when they become damaged.²

The liver is the largest organ within the body. It lies mostly in the upper part of the abdomen on the right side just under the diaphragm. About 70% of liver tissue is made up of cube shaped cells called hepatocytes that do the main work of the liver. Other cells (epithelial) form structure and are arranged in single layers around blood vessels, sinusoids, and bile ducts.

Bile ducts carry bile, a greenish brown liquid made by the liver to the gall bladder for storage until needed to aid in the digestion and absorption of fat and fat-soluble vitamins A, D, E, and K from the small intestine. Bile emulsifies fat eaten in the diet so that the pancreatic enzyme called lypase can break it down into its fatty acid and glycerol components which can then be absorbed into the body.

Bile also carries away waste products produced by normal metabolism and toxic substances that are removed by the liver for eventual elimination in stool. Bile is continually made by the liver from phospholipids, bile acids, cholesterol, and aging blood cells it removes from circulation. As such, bile must continually flow out of the liver to prevent build-up in the liver.

There is no cure for primary biliary cirrhosis.

What Is Primary Biliary Cirrhosis In Celiac Disease and/or Gluten Sensitivity?

• Primary biliary cirrhosis is an associated disorder in celiac disease and one of the most frequent hepatic disorder in celiac disease (the other is primary sclerosing cholangitis).³
• In a study that tested stored blood from 378 patients with primary biliary cirrhosis, Gillett et al. demonstrated patients with primary biliary cirrhosis should be considered at high risk for celiac disease.⁴
• In 1978, Logan et al. described the first cases of primary biliary cirrhosis with celiac disease. Later, numerous additional cases have been reported. In both disorders, other conditions having an immunological basis have been described, including diabetes and thyroiditis. In addition, co-existence of primary biliary cirrhosis and celiac disease has not only been reported in Europe and the Americas, but also in migrants from South Asia and the Coast Salish, an aboriginal population inhabiting the west coast of Canada thought to be of Asian descent.⁵
• The association between celiac disease and other immune disorders may be due to the sharing of a common genetic background, such as HLA antigens. However, in a very large study, involving 909 patients with celiac disease, Ventura and his associates found that the development of immune disorders in celiac disease was clearly related to the duration of exposure to gluten.⁶
• Celiac disease associated with primary biliary cirrhosis does not reduce patient survival.⁷

How Prevalent Is Primary Biliary Cirrhosis In Celiac Disease and/or Gluten Sensitivity?

• A study by Floriani et al. found  the rate of celiac disease that occurs in patients with primary biliary cirrhosis is 3.4%  and 3.7% rate of primary biliary cirrhosis occurs in celiac disease patients.⁸
• Kingham and Parker used a patient registry in the United Kingdom and defined the prevalence of primary biliary cirrhosis in 143 celiac patients as 3%, while the prevalence of celiac disease in 67 primary biliary cirrhosis patients was 6%. As a result, in primary biliary cirrhosis, serological screening with gliadin antibodies or small intestinal biopsy was suggested.
• Dickey et al. found similar findings of 7% primary biliary cirrhosis patients had celiac disease based on initial evaluation using endomysial antibodies (EMA), followed by later duodenal biopsy confirmation.⁹
• A prospective study found a prevalence of celiac disease in 2.5% of cirrhotic patients who were scheduled for an upper endoscopy to assess and treat gastro-esophageal varices.¹⁰
• Casella et al. found at diagnosis 43 out of 245 (17.5%) patients had elevated values of one or both aminotransferases (liver enzymes); the elevation was mild (less than 5 times the upper reference limit) in 41 (95%) and marked (more than 10 times the upper reference limit) in the remaining 2 (5%) patients. After 1 year of gluten-free diet, aminotransferase levels normalized in all but four patients with hepatitis C infection or primary biliary cirrhosis.¹¹

What Are The Symptoms Of Primary Biliary Cirrhosis?

The first and most common symptoms of primary biliary cirrhosis include these:¹²

• Fatigue, or feeling tired.
• Itching skin, and darkened skin in itching areas due to scratching.
• Dry eyes and mouth.
• Jaundice may develop later.

How Does Primary Biliary Cirrhosis In Celiac Disease and/or Gluten Sensitivity Develop?

• Primary biliary cirrhosis results from a common immune mechanism. To date, however, a definitive genetic predisposition or specific immunological alteration has not been clearly identified.¹³
• The increased prevalence of celiac-related antibodies in patients with primary biliary cirrhosis suggests that the two conditions are associated, although the reason for the association remains unclear.¹⁴
• A public health study of patients admitted to a hospital (13, 260 patients with vitamin D deficiency, 5,191 with osteomalacia, 1,228 with rickets) investigating a possible association between vitamin D deficiency and the risk of developing immune-mediated diseases found that patients with vitamin D deficiency may have an increased risk of developing primary biliary cirrhosis and celiac disease.¹⁵

Does Primary Biliary Cirrhosis Respond To Gluten-Free Diet?

Yes. Case reports show that patients diagnosed with celiac disease and primary biliary cirrhosis at the same time responded to gluten free diet. ((Logan RF, Ferguson A, Finlayson ND, Weir DG. Primary biliary cirrhosis and coeliac disease: an association? Lancet. 1978 Feb 4;1(8058):230-3.))

Casella et al. found at diagnosis 43 out of 245 (17.5%) patients had elevated values of one or both aminotransferases (liver enzymes). After 1 year of gluten-free diet, aminotransferase levels normalized in all but four patients with HCV infection or primary biliary cirrhosis.¹¹

A prospective prevalence study found that after a gluten free diet, cirrhosis patients with celiac disease showed a return to normal levels of their celiac serology, small bowel biopsy and liver enzyme abnormalities.¹⁰

6 Steps To Improve Primary Bilary Cirrhosis In Celiac Disease and/or Gluten Sensitivity:

• [dropcap]1[/dropcap]Remove the Trigger. Maintain a Strict, Nutritious Gluten Free Diet:

[box type=”shadow” ]Treatment. This condition responds to the complete elimination of gluten, which is the required treatment that improves both primary biliary cirrhosis and gut health.

• Gut health is the foundation to restore ALL health. Restored health will enable you to maintain a strict gluten free diet, just as other life tasks will be easier.
• A strict gluten free diet means removing 100% of wheat, barley, rye and oats from the diet.
• Cutting out bread and other obvious sources of gluten is not good enough for recovery. Even 1/8th teaspoon of flour or bread crumb is enough to sustain the inflammation that is damaging your small intestine, causing increased permeability (leaky gut) and allowing undigested gluten to enter your body where it can damage structures and function, and instigate immune inflammatory responses.

Correct Your Individual Nutritional Needs.

• Eat foods that can replenish missing nutrients. Find them under NUTRIENT DEFICIENCIES.
• Take nutritional supplements as needed. Find them under NUTRIENT DEFICIENCIES.

Recovery. You should begin to feel better within a week and notice more energy as inflammation subsides and the  absorbing cells that make up the surface lining of your small intestine are better able to function.

• Intestinal lining cells are replaced every 5 days. The healing process is like sunburn where the damaged surface layer of skin sloughs off and is replaced with new normal cells.
• Leaky gut normally resolves in two month after starting a gluten free diet and brings about a big improvement in health. Improvement in intestinal permeability precedes morphometric recovery (cell appearance and structure) of the small intestine in celiac disease.¹⁶
• The intestinal lining may take up to a year to heal.[/box]

• [dropcap]2[/dropcap] Reduce Inflammation. Foods to Eat and Foods Not to Eat:

Because gluten is inflammatory, eliminate OTHER inflammatory foods from your diet to reduce an additive effect to gluten. At the same time, try to eat foods that reduce inflammation (anti-inflammatory).

[box type=”shadow” ]Here Are Major Inflammatory Food Types That Reduce Healing:

• Damaging Foods. In susceptible persons, includes corn, dairy (cow), and soy. Lactose, the sugar in any animal milk disrupts intestinal permeability causing leaky gut.¹⁷
• Allergenic Foods. Includes foods that trigger the immune sytem to produce IgE antibodies. Allergy testing is the usual way to discover these offending foods.
• Shelf Stable Processed Foods. Includes any that contain additives and preservatives. Look for them on the nutrition label of the box or package. Additives and preservatives also disrupt intestinal permeability causing leaky gut.¹⁷
• Fats. Limit deep fried foods, trans-fats, saturated fats (animal fat/butter), and EXCESSIVE omega-6 fatty acid oils like corn oil. Rancid fats, sodium caprate (a medium chain fat), and sucrose monester fatty acid (a food grade surfactant) induce significant disruption of the intestinal barrier that causes leaky gut.¹⁷.
• Excessive Refined White Flours (bran layer removed). Includes products made from them such as cookies, bread, cakes, pies. Bran contains the vitamins and minerals that metabolize grains and slows the otherwise rapid entry of sugar from their digestion into the bloodstream. Also disrupt intestinal permeability causing leaky gut.¹⁷
• Refined Sugars.  Includes white sugar, corn fructose and high fructose corn syrup.
• Certain Spices. Includes paprika and cayenne pepper which disrupt intestinal permeability causing leaky gut.¹⁷
• Alcohol and Caffeine. Disrupt intestinal permeability causing leaky gut.¹⁷
• Cocoa and Black Tea increase blood sugar.
• Rosemary. Increases blood sugar levels and should not be used by persons with insulin resistance or diabetes. [/box]

[box type=”shadow” ]Here Are Important Anti-Inflammatory Food Types to Promote Health:

• Fruits. Contain ample amounts of vitamins, minerals and phytochemicals which are naturally occuring components in plants that detoxify toxins, carcinogens (reducing the risk by 50%) and mutagens.
• Non-Starchy Vegetables. Support intestinal integrity and provide ample amounts of vitamins, minerals and phytochemicals. Includes green leafy vegetables such as lettuce and kale, also onion, broccoli, garlic, and others.
• High Quality Complex Carbohydrates. Provide vitamins, minerals, and fiber while boosting serotonin levels to help you relax and feel calm. Includes whole grains, legumes, and root vegetables such as carrots, parsnips, sweet potatoes, turnips, red beets, and others.
• Antioxidants. Protect the body from inflammatory oxidant molecules that continually occur and help us handle stress and reduce irritability. Includes vitamin C-containing foods such as lemon, grapefruit, apricot, Brussels sprouts and strawberries, and others. Also, includes vitamin E-containing foods such as nuts, seeds, avocado, olive oil, and others. Cocoa is good, too.
• Omega-3 Fatty Acids. Balance opposing omega-6 fatty acids and bad fats. Fish sources includes tuna, salmon, cod, and others. Plants sources include flax, chia seeds, canola oil, and others.
• Probiotics. Supply normal microbes needed for colon health and health of the body such as these fermented foods: yogurt, kefir, and unpasteurized apple cider vinegar.
• Prebiotics/ High Fiber Foods.  Food with fiber keeps our population of colonic microbes healthy.
• Protective Herbs and Spices.  See below #6 below for examples.[/box]

• [dropcap]3[/dropcap] Information Sheet You Can Take to Your Doctor or Other Health Professional:

Click here.

• [dropcap]4[/dropcap] Manage Your Medications Safely:

[box type=”shadow” ]

Certain medications deplete vitamin D which is associated with primary biliary cirrhosis. Ask your doctor or pharmacist about this possible adverse effect if you are taking any of the drugs listed below. Do not stop prescribed medications without supervision.

This is not a complete listing.

ANTACIDS / ULCER MEDICATIONS

• Pepcid®, Tagamet®, Zantac® deplete Vitamin D.
• Magnesium and Aluminum Antacid preparations (Gaviscon®, Maalox®, Mylanta®) deplete Vitamin D.

ANTI-INFLAMMATORIES disrupt intestinal permeability which complicates celiac disease.

• Corticosteroids (Prednisone, Medrol®, Aristocort®, Decadron) Vitamin D.

ANTICONVULSANTS

• Phenobarbital and Barbituates; and Dilantin®, Tegretol®, Mysoline®, Depakane/Depacon® Vitamin D.

BRONCHODILATORS

• Inhaled corticosteroid inhalers (Flovent, Pulmicort and others) that are breathed in on a daily basis as a long term therapy to reduce inflammation in airways deplete Vitamin D.

CHOLESTEROL DRUGS

• Colestid® and Questran® deplete Vitamin D.

LAXATIVES

• Metamucil, FiberCon, Citrucel, Colace, Glycolax, Milk of magnesia, Dulcolax deplete: Vitamin D.

WEIGHT LOSS DRUGS THAT BIND FAT also interfere with absorption of some nutrients.

• Zenicol (Orlistat®) depletes Vitamin D.

[/box]

• [dropcap]5[/dropcap]Nutritional Supplements To Help Correct Deficiencies:

[box type=”shadow” ]

The type and quantity of nutritional supplements that may be needed depend on which nutrients are deficient.

• Multivitamin/mineral combination that provides 100% once a day is useful to improve overall nutrient levels. This is a safe dose, but always check with your doctor to avoid interactions with medications.
• Vitamin D3 as prescribed following blood test for status.

Storage Note: Store container tightly sealed, away from heat, moisture and direct light to avoid loss of potency. That is, in a safe kitchen cabinet – not in the bathroom or on the kitchen table.[/box]

• [dropcap]6[/dropcap]Manage Natural Remedies: 

[box type=”shadow” ]Hydration:

• Eight glasses of water are recommended per day unless there is a contraindication such as kidney or heart disease. The Institute of Medicine recommends approximately 2.7 liters (91 ounces) of total water, from all beverages and foods, each day for women and 3.7 liters (125 ounces) daily of total water for men.
• If you are thirsty, drink water. Add fresh, squeezed lemon to water. Lemon is anti-inflammatory, alkalizing and provides vitamin C.
• Hydration Test: Urine should be pale yellow. Fingertips should be plump, without pruning but this may not be reliable when fingers are swollen with edema. Lips should be plump, without puckering. The feeling of thirst can be unreliable.
• What is wrong with soda, coffee, tea, and alcohol? These drinks are dehydrating, increase acid, and deplete nutrients.[/box]

[box type=”shadow” ]Carminatives. The following  anti-inflammatory plant sources called carminitives help heal the digestive tract. They also tone the digestive muscles which improves peristalsis, thus aiding in the expulsion of gas from the stomach and intestine to relieve digestive colic and gastric discomfort.

Carminative Food Remedies:

• Raspberry.
• Carrot is also a cleansing digestive tonic.
• Grape is also bile stimulating and a cleansing remedy for sluggish digestion and laxative.
• Redbeets also stimulate and improve digestion and are easily digested.
• Cabbage also stimulates and improves digestion and is also a liver decongestant.
• Lettuce also stimulates and improves digestion and is also an alterative, meaning it improves the function of organs involved with the digestion and excretion of waste products to bring about a gradual change.
• Potatoes are antispasmodic (due to atropine like properties) and a liver remedy.

Carminative Herb Remedies:

• Sage is also a digestive, astringent, bile stimulant and energy tonic that heals the mucosa.  Drink as tea or use in cooking.
• Chamomile, lemon balm, and fennel, (as a tea) also help relieve nervous tension.
• Parsley also relieves indigestion.
• Rosemary as a tea and in cooking also is a nervous system tonic for stress and fatigue, bile stimulant, and can relieve headaches and indigestion. However, because it increases blood sugar levels, it should not be used by persons with insulin resistance or diabete.
• Thyme is also soothing remedy useful for stimulating digestion of rich, fatty foods.

Carminative Spice Remedies:

• Cloves are also antispasmodic.
• Nutmeg is also useful for indigestion.
• Ginger.[/box]

[box type=”shadow” ]Exercise Helps:

Exercise improves circulation and rids the body of toxins.

• Walking is aerobic exercise that reconditions the whole body to improve stamina. Read more about Exercise and Fitness.
• Weight training builds muscle. Read more about Exercise and Fitness.
• Stretching improves flexibilty. Read more about Exercise and Fitness.

Note: Exercise is important, but the amount and type of exercise undertaken depends on your health. Your first priority is to heal. [/box]

What Do Medical Research Studies Tell About Primary Biliary Cirrhosis In Celiac Disease and/or Gluten Sensitivity?

RESEARCH STUDY SUMMARIES

“Prevalence of celiac disease in cirrhosis and outcome of cirrhosis on a gluten free diet: a prospective study.” This study investigated the prevalence of celiac disease in cirrhosis, to characterize cirrhotic patients with abnormal celiac serology and normal small bowel biopsy, and to evaluate the effect of a gluten free diet on the liver. It was found that celiac disease is at least twice more common in cirrhotic patients than in the general population and gluten free diet improves liver tests; celiac disease can occur coincidentally with other liver disorders and screening may be warranted during the evaluation of patients with cirrhosis; and abnormal EMA and high hTTG antibody levels can be used to diagnose celiac disease in cirrhosis.

A total of 204 consecutive patients with biopsy proven cirrhosis scheduled for an upper endoscopy (EGD) to assess and treat gastro-esophageal varices (GEV) at the Cleveland Clinic between 5/1/2008 and 5/30/2010 were enrolled in the study and followed for 2 years.

RESULTS: Celiac disease affects 2.5% of cirrhotic patients and more than twice the prevalence in the general population. Abnormal EMA >1/10 and high hTTG levels >20 IU can be used to diagnose celiac disease in cirrhosis. Sensitivities and specificities are 100% for EMA and 80% and 94% for hTTG, respectively. After a gluten free diet, patients with celiac disease showed a return to normal levels of their celiac serology, small bowel biopsy and liver enzyme abnormalities.¹⁰

“Prevalence and causes of abnormal liver function in patients with coeliac disease.” This study investigating the cause and prevalence of altered liver function tests in celiac patients, at diagnosis and after 1 year of gluten-free diet found that hypertransaminaseaemia (elevated liver enzymes) at diagnosis and the lack of normalization of liver enzymes after 12 months of diet suggest coexisting liver disease. In such instance, further evaluation is recommended to exclude the liver disease. Early recognition and treatment of celiac disease in patients affected by liver disease are important to improve the liver function and prevent complications.

Data from 245 untreated celiac disease patients (196 women and 49 men, age range 15-80 years) were retrospectively analysed and the liver function tests before and after diet, as well as associated liver pathologies, were assessed.

RESULTS: Overall, 43 out of 245 (17.5%) patients had elevated values of one or both aminotransferases; the elevation was mild (<5 times the upper reference limit) in 41 (95%) and marked (>10 times the upper reference limit) in the remaining 2 (5%) patients. After 1 year of gluten-free diet, aminotransferase levels normalized in all but four patients with HCV infection or primary biliary cirrhosis.¹¹

“Hospital admissions for vitamin D related conditions and subsequent immune-mediated disease: record-linkage studies.” This public health study investigating a possible association between vitamin D deficiency and the risk of developing immune-mediated diseases found that patients with vitamin D deficiency found significantly elevated rates of primary biliary cirrhosis among others.

A database of linked statistical records of hospital admissions and death registrations for the whole of England (from 1999 to 2011) were analyzed. Rate ratios for immune-mediated disease were determined, comparing vitamin D deficient cohorts (individuals admitted for vitamin D deficiency or markers of vitamin D deficiency) with comparison cohorts. After hospital admission for either vitamin D deficiency, osteomalacia or rickets, there were significantly elevated rates of Addison’s disease, ankylosing spondylitis, autoimmune hemolytic anemia, chronic active hepatitis, celiac disease, Crohn’s disease, diabetes mellitus, pemphigoid, pernicious anemia, primary biliary cirrhosis, rheumatoid arthritis, Sjogren’s syndrome, systemic lupus erythematosus, thyrotoxicosis.¹⁸

“Prevalence of celiac disease in primary biliary cirrhosis and of antimitochondrial antibodies in adult coeliac disease patients in Italy.” This study investigating both the prevalence of celiac disease in a series of primary biliary cirrhosis patients and that of antimitochondrial antibodies in a series of adult biopsy proven celiac disease patients demonstrated significant association between primary biliary cirrhosis and celiac disease. Screening with anti-endomysium antibodies in primary biliary cirrhosis is justified and screening for antimitochondrial antibodies is advisable in adult celiac disease patients.¹⁹

“Prevalence of IgA antibodies to endomysium and tissue transglutaminase in primary biliary cirrhosis.” This study investigating the association between primary biliary cirrhosis and celiac disease by testing stored sera from 378 patients with primary biliary cirrhosis demonstrated patients with primary biliary cirrhosis should be considered at high risk for celiac disease.²⁰

CASE REPORT SUMMARIES

“Primary biliary cirrhosis and coeliac disease: an association?” This early case report describes an association of primary biliary cirrhosis and celiac disease, not previously reported, observed in 4 patients. In each case, the two conditions were diagnosed simultaneously, and although symptoms were due to celiac disease, initial investigation drew attention to the liver condition. All the patients responded to a gluten-free diet and remain well 2 years later. Primary biliary cirrhosis remains asymptomatic in 3 patients, but pruritus (itching) has developed in the 4th. The significance of this association is unclear and may merit formal study. Celiac disease should be considered as a possible cause of unexplained weight loss in primary biliary cirrhosis.²¹

 

Sources:

1. Trivedi PJ, Adams DH. Mucosal immunity in liver autoimmunity: a comprehensive review. J Autoimmun. 2013 Oct;46:97-111. doi: 10.1016/j.jaut.2013.06.013. [↩]
2. http://digestive.niddk.nih.gov/ddiseases/pubs/primarybiliarycirrhosis/ [↩]
3. Kummen M, Schrumpf E, Boberg KM. Liver abnormalities in bowel diseases. Best Pract Res Clin Gastroenterol. 2013 Aug;27(4):531-42. doi: 10.1016/j.bpg.2013.06.013. [↩]
4. Gillett HR, Cauch-Dudek K, Jenny E, Heathcote EJ, Freeman HJ. Prevalence of IgA antibodies to endomysium and tissue transglutaminase in primary biliary cirrhosis. Canadian Journal of Gastroenterology. Sep 2000;14(8):672-5. [↩]
5. Hugh James Freeman. Hepatobiliary and pancreatic disorders in celiac disease. ISSN 1007-9327 CN 14-1219/R World J Gastroenterol. 2006 March 14;12(10):1503-1508 [↩]
6. La Villa G, Pantaleo P, Tarquini R, Cirami L, Perfetto F, Mancuso F, Laffi G. Multiple immune disorders in unrecognized celiac disease: a case report. World J Gastroenterol. 2003;9(6):1377-1380, Available at: http://www.wjgnet.com/1007-9327/9/1377.asp. Accessed Jan 3, 2005. [↩]
7. Floreani A, Franceschet I, Cazzagon N, Spinazzè A, Buja A, Furlan P, Baldo V, Gershwin ME. Extrahepatic Autoimmune Conditions Associated with Primary Biliary Cirrhosis. Clin Rev Allergy Immunol. 2014 May 9. [↩]
8. Floreani A, Betterle C, Baragiotta A, et al. Prevalence of celiac disease in primary biliary cirrhosis and of antimitochondrial antibodies in adult coeliac disease patients in Italy. Digestive and Liver Disease. Apr 2002;34(4):258-61. [↩]
9. Hugh James Freeman. Hepatobiliary and pancreatic disorders in celiac disease. ISSN 1007-9327 CN 14-1219/R World J Gastroenterol 2006 March 14;12(10):1503-1508. [↩]
10. Wakim-Fleming J, Pagadala MR, McCullough AJ, Lopez R, Bennett AE, Barnes DS, Carey WD. Prevalence of celiac disease in cirrhosis and outcome of cirrhosis on a gluten free diet: a prospective study. J Hepatol. 2014 Sep;61(3):558-63. doi: 10.1016/j.jhep.2014.05.020. [↩] [↩] [↩]
11. Casella G, Antonelli E, Di Bella C, Villanacci V, Fanini L, Baldini V, Bassotti G. Prevalence and causes of abnormal liver function in patients with coeliac disease. Liver Int. 2013 Aug;33(7):1128-31. doi: 10.1111/liv.12178. [↩] [↩] [↩]
12. http://digestive.niddk.nih.gov/ddISeases/pubs/primarybiliarycirrhosis/#symptoms [↩]
13. Freeman HJ. Hepatobiliary and pancreatic disorders in celiac disease. ISSN 1007-9327 CN 14-1219/R World J Gastroenterol. 2006 March 14;12(10):1503-1508 [↩]
14. Gillett HR, Cauch-Dudek K, Jenny E, Heathcote EJ, Freeman HJ. Prevalence of IgA antibodies to endomysium and tissue transglutaminase in primary biliary cirrhosis. Canadian Journal of Gastroenterology. Sep 2000;14(8);672-5. [↩]
15. Ramagopalan SV1, Goldacre R, Disanto G, Giovannoni G, Goldacre MJ. Hospital admissions for vitamin D related conditions and subsequent immune-mediated disease: record-linkage studies. BMC Med. 2013 Jul 25;11:171. doi: 10.1186/1741-7015-11-171. [↩]
16. Cummins AG, Thompson FM, Butler RN, et al. Improvement in intestinal permeability precedes morphometric recovery of the small intestine in coeliac disease. Clinical Science. Apr 2001;100(4):379-86. [↩]
17. Farhadi A, Banan A, Fields J, Keshavarzian A. Intestinal barrier: an interface between health and disease. Journal of Gastroenterology and Hepatology. 2003;18:479-91. [↩] [↩] [↩] [↩] [↩] [↩]
18. Ramagopalan SV1, Goldacre R, Disanto G, Giovannoni G, Goldacre MJ. Hospital admissions for vitamin D related conditions and subsequent immune-mediated disease: record-linkage studies. BMC Med. 2013 Jul 25;11:171. doi: 10.1186/1741-7015-11-171. [↩]
19. Floreani A, Betterle C, Baragiotta A, et al. Prevalence of coeliac disease in primary biliary cirrhosis and of antimitochondrial antibodies in adult coeliac disease patients in Italy. Digestive and Liver Disease. Apr 2002;34(4):258-61. [↩]
20. Gillett HR, Cauch-Dudek K, Jenny E, Heathcote EJ, Freeman HJ. Prevalence of IgA antibodies to endomysium and tissue transglutaminase in primary biliary cirrhosis. Canadian Journal of Gastroenterology. Sep 2000;14(8);672-5. [↩]
21. Logan RF, Ferguson A, Finlayson ND, Weir DG. Primary biliary cirrhosis and coeliac disease: an association? Lancet. 1978 Feb 4;1(8058):230-3. [↩]