Primary Sclerosing Cholangitis 

What Is Primary Sclerosing Cholangitis?

[dropcap]P[/dropcap]rimary sclerosing cholangitis (PSC) is an uncommon, slowly progressive bile duct disease that results in stagnation or build-up of bile in the liver, called cholestasis.

Primary sclerosing cholangitis is characterized by sclerosis, or scarring inflammation in bile ducts both within the liver (intra-hepatic ducts), and outside the liver (extra-hepatic ducts), causing progressive narrowing and, eventually, obliteration of the bile ducts.

Primary sclerosing cholangitis 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 happens when scarred bile ducts can no longer transport bile out of the liver?

A: Bile that cannot be removed from the liver by the biliary duct system backs up and damages the liver, causing cirrhosis.

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

Bile is a greenish brown liquid made by the liver. Bile ducts carry it out of the liver to the gall bladder for storage until needed to aid in the digestion and absorption of fat 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.

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. 

Build-up of bile in the liver is the end result of the inflammatory process in primary sclerosing cholangitis, that by swelling and scarring of bile ducts impedes and eventually prevents bile flow out of the liver, leading to liver failure. There is no curative treatment available for primary sclerosing cholangitis, besides liver transplantation.²

The appearance of the intrahepatic and extrahepatic biliary ducts can be assessed by use of cholangiography, and magnetic resonance (MR) imaging is the best way to identify patients.  See image above.³

MR cholangiography offers a noninvasive method of obtaining images of the biliary system without the use of a contrast agent. There is no radiation exposure. Pulse sequences can be chosen to obtain bright bile or black bile cholangiograms. Image processing algorithms can be selected to obtain a three-dimensional representation of biliary anatomy and pathology, and those images can be rotated in any plane so that ductal anatomy and pathology can be seen to best advantage.⁴

There is no cure for primary sclerosing cholangitis but there are symptom treatments one of which is supplementation for low levels of vitamins A,D,E, and K. Liver transplant is the only effective option.

What Is Primary Sclerosing Cholangitis In Celiac Disease and/or Gluten Sensitivity?

• Primary sclerosing cholangitis is an associated disorder in celiac disease. It was first found to be associated with celiac disease in 1988 in 3 patients with diarrhea and steatorrhea.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
• Since the association of celiac disease with liver autoimmunity has been largely validated, the first step is a serology test for celiac disease in all cases of primary sclerosing cholangitis, and at the time of celiac disease diagnosis, liver dysfunction should be concurrently evaluated. The endomysial antibody test (EMA) is more specific but slightly less sensitive than anti-tTG ,and as is well known, false-positive results for anti-tTG are found in patients with liver and autoimmune disorders. Therefore, determination of the levels of EMA is preferred to that of anti-tTG in patients with autoimmune liver disease. An exception is in children with inflammatory liver disease of unknown cause, where investigation for celiac disease should be started by determining the anti-tTG levels.⁷
• Importance must be placed on strict adherence to a gluten-free diet, as it can decrease the risk of possibly developing associated autoimmune diseases.⁸

How Prevalent Is Primary Sclerosing Cholangitis In Celiac Disease and/or Gluten Sensitivity?

• Liver abnormalities are often seen in bowel diseases.
• Primary sclerosing cholangitis and primary biliary cirrhosis are the most frequent hepatic disorders in celiac disease.²
• In a study of 13,818 patients with celiac disease and 66,584 age- and sex-matched individuals from the general Swedish population, the prevalence of primary sclerosing cholangitis in patients with celiac disease was 4.46%, a rate 4-8 times higher than that of the general population.
• In a survey by Zali et al. celiac disease was found in 3% patients with primary sclerosing cholangitis.⁹

What Are The Symptoms Of Primary Sclerosing Cholangitis?

The onset of primary sclerosing cholangitis is usually insidious and many patients are asymptomatic at diagnosis.

In early stages, patients have mild symptoms only such as:

• Gradual, progressive fatigue.
• Abdominal discomfort.
• Generalized itching that can become severe.
• Weight loss.

In later stages, these symptoms present:

• Spleen enlargement and jaundice (yellowing of skin and eyes) may be a feature.
• In most patients, the disease progresses to cirrhosis and liver failure.
• Cholangiocarcinoma (cancer of  bile ducts) develops in 8–30% of patients.¹⁰

How Does Primary Sclerosing Cholangitis In Celiac Disease and/or Gluten Sensitivity Develop?

• The pathogenesis of primary sclerosing cholangitis is not well understood but results most likely from altered immune mechanisms.
• Several important observations, coupled with the strong genetic association between certain human leukocyte antigen (HLA) haplotypes and frequency of concurrent extrahepatic autoimmune disorders, support the concept that it is an immune-mediated phenomenon.¹¹

Does Primary Sclerosing Cholangitis Respond To Gluten-Free Diet?

Studies are inadequate to determine response of primary sclerosing cholangitis to gluten free diet.⁹

People with advanced primary sclerosing cholangitis are often deficient in the fat-soluble vitamins A, D, E, K and replacement therapy can be given. In osteoporosis, physical exercise and maintenance of adequate calcium and vitamin D may be sufficient in the early stages.¹²

6 Steps To Improve Primary Sclerosing Cholangitis 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 sclerosing cholangitis 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.¹³
• 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.¹⁴
• 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.¹⁴
• 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.¹⁴.
• 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.¹⁴
• 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.¹⁴
• Alcohol and Caffeine. Disrupt intestinal permeability causing leaky gut.¹⁴
• 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:

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Certain medications further deplete the fat soluble vitamins A, D, E, and K which result from fat malabsorption due to 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, Vitamin A.
• Magnesium and Aluminum Antacid preparations (Gaviscon®, Maalox®, Mylanta®) deplete Vitamin D, Vitamin A.

ANTIBIOTICS disrupt intestinal permeability which complicates celiac disease.

• Gentomycin, Neomycin, Streptomycin, Cephalosporins, Penicillins deplete Vitamin K.
• Dapsone depletes vitamin K.
• Penicillins deplete Vitamin K.¹⁵
• Erythromycin depletes Vitamin K.¹⁶

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, Vitamin A.

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, Vitamin A, Vitamin E, Vitamin K.

LAXATIVES

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

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

• Zenicol (Orlistat®) depletes Vitamin D, Vitamin A, Vitamin E, Vitamin K.

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

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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.
• B-complex vitamins improve health in patients with celiac disease living on a gluten-free diet.¹⁷
• Vitamin A as prescribed following blood test for status.
• Vitamin D3 as prescribed following blood test for status.
• Vitamin E as prescribed following blood test for status.
• Vitamin K 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 Sclerosing Cholangitis In Celiac Disease and/or Gluten Sensitivity?

“Ulcerative colitis, primary sclerosing cholangitis and coeliac disease: two cases and review of the literature.” This case report of two patients with primary sclerosing cholangitis and ulcerative colitis describes investigation and diagnosis with celiac disease when patients failed to respond to treatment. Review of the literature suggests an increased malignancy potential in these patients. Annual colonoscopic surveillance with early liver and bowel imaging is recommended in patients with combination of primary sclerosing cholangitis, ulcerative colitis and celiac disease having clinical deterioration and weight loss.¹⁸

“Celiac disease in autoimmune cholestatic liver disorders.”  In this study, serological screening for celiac disease was performed in patients with autoimmune cholestasis (stagnation of bile) to define the prevalence of such an association and to evaluate the impact of gluten withdrawal on liver disease associated with gluten sensitive enteropathy. Results showed a prevalence of 3.5% for celiac disease and that cholestasis did not improve on a gluten-free diet.

Immunoglobulin A endomysial, human and guinea pig tissue transglutaminase antibodies, and immunoglobulin A and G gliadin antibodies were sought in 255 patients with primary biliary cirrhosis, autoimmune cholangitis, and primary sclerosing cholangitis. Imunoglobulin A endomysial and human tissue transglutaminase antibodies were positive in nine patients (seven primary biliary cirrhosis, one autoimmune cholangitis, and one primary sclerosing cholangitis), whose duodenal biopsy results showed villous atrophy consistent with celiac disease. Two of these patients had a malabsorption syndrome, and one had iron-deficiency anemia. Clinical and biochemical signs of cholestasis did not improve after gluten withdrawal in the three patients with severe liver disease. A longer follow-up of the six celiac patients with mild liver damage is needed to clarify whether gluten restriction can contribute to slow down the progression of liver disease.¹⁹

“Celiac disease, enteropathy-associated T-cell lymphoma, and primary sclerosing cholangitis in one patient: a very rare association and review of the literature.” This case report discusses the first case of a 54-year-old male who presented simultaneously with two rare diseases: enteropathy-associated T-cell lymphoma (EATL), which is mostly associated with celiac disease, and primary sclerosing cholangitis. This patient stopped a gluten-free diet for more than 8 years after a 15 years history of celiac disease.

The patient was admitted to the hospital for evaluation of vomiting and weight loss; the history was negative for fever or night sweats. Clinical examination revealed pallor of the skin, splenomegaly +1 cm without ascites or lymphadenopathy. The diagnosis was based on the histological examination of duodenal biopsy and the diagnosis of primary sclerosing cholangitis was made on liver biopsy, as well as the magnetic resonance cholangiogram that shows moderate stricturing of intrahepatic bile ducts alternating with areas of dilatation.

The treatment of EATL is mainly based on chemotherapy in addition to the optimal management of complications and adverse events that impact on the response to treatment and clinical outcomes, although the prognosis remains remarkably very poor.

The aim of this paper is to emphasize the importance of strict adherence to a gluten-free diet, as it can decrease the risk of developing enteropathy-associated T-cell lymphoma and possibly associated autoimmune diseases. Additionally, patients who are unresponsive to a gluten-free diet or with deteriorating clinical condition should be investigated for the development of lymphoma.²⁰

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