Autoimmune Hepatitis

 

What Is Autoimmune Hepatitis?

[dropcap]A[/dropcap]utoimmune hepatitis is an autoimmune attack against liver cells that is characterized by inflammation and results in chronic liver disease which includes low blood albumin and cirrhosis.

Autoimmune hepatitis is diagnosed by detection of autoantibodies in blood and liver biopsy.

Q: What is cirrhosis?

A: Cirrhosis is a degenerative process of the liver that can be fatal. Normal lobular liver structure is distorted and replaced with nodules of regenerating liver cells separated by bands of fibrous tissue that cannot properly carry out liver function and block the necessary flow of blood through the liver, ending in liver failure.

The liver is the largest organ within the body and 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 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 from the small intestine. Bile emulsifies fat eaten in the diet so that the pancreatic enzyme called lipase can break it down into its fatty acid and glycerol components.

The liver is a very busy organ, carrying out over 500 metabolic processes! Nutritionally, it is the first to receive all the blood carrying nutrients freshly absorbed from the digestive tract. Hepatocytes then convert the nutrients to provide the body with energy, a host of amino acids as building blocks for numerous cell activities, and proteins such as albumin and fibrinogen. In fact, hepatocytes build the structural proteins for the liver itself. Imagine the array of nutrients the liver uses and keeps at its disposal for its metabolic functions. Included in liver storage are vital vitamins and minerals such as vitamin A and vitamin B12.

As a detoxifier, Kupffer cells located in the sinusoids act like amoebas to engulf and digest unwanted matter. As a blood cleanser, the liver removes waste products produced by normal metabolism and toxic substances and rids it by preparing these substances for elimination in urine, such as ammonia converted to urea, and/or excreting them in bile for eventual elimination in stool. Bile is continually made by the liver from phospholipids salt, cholesterol, aging blood cells it removes from circulation.

Autoimmune hepatitis is classified into several types. Type 1 autoimmune hepatitis is the most common form in North America. Type 1 can occur at any age; however, it most often starts in adolescence or young adulthood. People with type 1 autoimmune hepatitis commonly have other autoimmune disorders (see listed below).

Type 2 autoimmune hepatitis is less common and occurs more often in children than adults. People with type 2 can also have any of the autoimmune disorders (see listed below).

Both types of autoimmune hepatitis are treated with prednisone, a corticosteroid hormone to control inflammation and reduce the body’s immune activity against the liver.¹

What Is Autoimmune Hepatitis In Celiac Disease and/or Gluten Sensitivity?

• Autoimmune hepatitis is a severe associated immune disorder in celiac disease.
• 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, it was found that the development of immune disorders in Celiac Disease was clearly related to the duration of exposure to gluten.²
• Persons with type 1 autoimmune hepatitis commonly have other autoimmune disorders that are also associated with celiac disease. They include the following:

• Crohn’s disease, which causes inflammation and irritation of any part of the digestive tract.
• Graves’ disease, the most common cause of hyperthyroidism in the United States.
• Hashimoto’s disease, also called chronic lymphocytic thyroiditis or autoimmune thyroiditis, a form of chronic inflammation of the thyroid gland.
• Proliferative glomerulonephritis, or inflammation of the glomeruli, which are tiny clusters of looping blood vessels in the kidneys.
• Primary sclerosing cholangitis, which causes irritation, scarring, and narrowing of the bile ducts inside and outside the liver.
• Rheumatoid arthritis, which causes pain, swelling, stiffness, and loss of function in the joints.
• Sjögren’s syndrome, which causes dryness in the mouth and eyes.
• Systemic lupus erythematosus, which causes kidney inflammation called lupus nephritis.
• Type 1 diabetes, a condition characterized by high blood glucose, also called blood sugar, levels caused by a total lack of insulin.
• Ulcerative colitis, a chronic disease that causes inflammation and sores, called ulcers, in the inner lining of the large intestine.

• Type 2 autoimmune hepatitis is less common and occurs more often in children than adults. Persons with type 2 can also have any of the above autoimmune disorders.¹
• Because celiac disease may be a cause of unexplained elevated liver enzymes levels, a high index of suspicion is required.³

How Prevalent Is Autoimmune Hepatitis In Celiac Disease and/or Gluten Sensitivity?

• The presence of celiac disease in autoimmune hepatitis is high (at least one in 36 patients or 4%) and celiac disease is predominantly asymptomatic.⁴
• Villalta et al. found 3 of the 47 patients with autoimmune hepatitis (6.4%) in their study were positive for IgA anti-tTG and EMA celiac antibodies, and were subsequently confirmed to be affected with celiac disease by small-bowel biopsy findings. The crude prevalence rate of celiac disease in autoimmune hepatitis was 63.8 per 1,000, and it was significantly higher than that found in the general population in Italy was 4.9 per 1,008. The results of this study showed a high prevalence of celiac disease in patients with autoimmune hepatitis. For this reason, early serological screening testing for celiac disease is strongly recommended for all autoimmune hepatitis patients.⁵

What Are The Symptoms Of Autoimmune Hepatitis?

Autoimmune hepatitis is marked by elevated liver enzymes detected by blood analysis and signs of liver disease that may be chronic including these symptoms:

• Low albumin.
• Amenorrhea in younger women.
• Possibly fever.
• Liver tenderness.
• Fatigue.
• Joint Pain.
• Nausea.
• Loss of appetite.
• Pale stool.
• Jaundice (yellowing) of skin, eyes and urine (dark yellow).

How Does Autoimmune Hepatitis Develop In Celiac Disease and/or Gluten Sensitivity?

• Autoimmune hepatitis results from an autoimmune mechanism.⁶
• High blood levels of immunoglobulin G (IgG) antibodies are characteristic of autoimmune hepatitis, which is also associated with the generation of autoantibodies, some of which are implicated directly in disease pathogenesis. Thus, the levels of antibodies against the hepatocyte liver-specific protein correlate with disease severity and liver injury.
• Type 1 autoimmune hepatitis is characterized by the presence of anti-SMA, and type 2 autoimmune hepatitis is defined by the presence of LKM-1 antibodies that recognize a hepatic cytochrome P450, CYP2D6, expressed on the hepatocyte membrane.⁷
• The rate of hepatitis is significantly elevated in patients with vitamin D deficiency.⁸

Does Autoimmune Hepatitis Respond To Gluten-Free Diet?

Yes. In the majority of patients, celiac disease-related elevated liver enzyme levels will normalize on gluten free diet.³

6 Steps To Improve Autoimmune Hepatitis 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 autoimmune hepatitis 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.⁹
• 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.¹⁰
• 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.¹⁰
• 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.¹⁰.
• 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.¹⁰
• 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.¹⁰
• Alcohol and Caffeine. Disrupt intestinal permeability causing leaky gut.¹⁰[/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 used to treat autoimmune hepatitis cause nutritional deficiencies that complicate celiac disease.  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.

ANTI-INFLAMMATORIES disrupt intestinal permeability which complicates celiac disease.

• Corticosteroids (Prednisone, Medrol®, Aristocort®, Decadron) deplete Calcium, Vitamin D, Magnesium, Zinc, Vitamin C, Vitamin B6, Vitamin B12, Folic Acid, Selenium, Chromium, Phosphorus.
• NSAIDS (Motrin®, Aleve®, Advil®, Anaprox®, Dolobid®, Feldene®, Naprosyn® and others) deplete Folic acid.

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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.
• Calcium citrate is the best absorbed of calcium supplements. Calcium carbonate is a poor choice.
• Vitamin D3 as prescribed following blood test for status.
• Chelated magnesium  as prescribed but do not take at same time as calcium because they compete for absorption.
• Others as prescribed.

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.
• 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 Autoimmune Hepatitis In Celiac Disease and/or Gluten Sensitivity?

RESEARCH STUDY SUMMARIES

“Hospital admissions for vitamin D related conditions and subsequent immune-mediated disease: record-linkage studies.” This study investigating the reported association between vitamin D deficiency and the risk of developing immune-mediated diseases showed that  patients with vitamin D deficiency may have an increased risk of developing some immune-mediated diseases including hepatitis, although  reverse causality or confounding cannot  be ruled out.

Researchers analyzed a database of linked statistical records of hospital admissions and death registrations for the whole of England (from 1999 to 2011). 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, and significantly reduced risks for asthma and myxoedema.⁸

“High prevalence of celiac disease in autoimmune hepatitis detected by anti-tissue tranglutaminase autoantibodies.” This study investigated the relation between autoimmune hepatitis (AIH) and celiac disease by assessing the prevalence of IgA and IgG anti-tissue transglutaminase (tTG) antibodies in AIH, and by verifying whether the findings were associated with clinical and histological features of celiac disease. Forty-seven consecutive patients with AIH (type I: n = 39; type II: n = 8) were studied. One hundred patients with chronic hepatitis C, and 120 healthy blood donors were also studied as controls. Sera was analyzed for the presence of IgA and IgG anti-tTG antibodies using a specific human recombinant tTG immunoenzymatic assay. Anti-tTG positive patients and controls were further tested for anti-endomysium antibodies (EMA) and HLA typing, and those found positive by either of these tests underwent duodenal biopsy to confirm a possible diagnosis of celiac disease.

Three of the 47 AIH patients (6.4%) were positive for IgA anti-tTG and EMA antibodies, and were subsequently confirmed to be affected with celiac disease by small-bowel biopsy findings. No IgG anti-tTG positivity was found in the AIH patients. None of the controls were positive for IgA anti-tTG, and only one with chronic hepatitis C had a low positive reaction for IgG anti-tTG, which resulted as a false positive. The crude prevalence rate of celiac disease in AIH was 63.8 per 1,000 (95% CI, 13.2-186.1), and it was significantly higher than that found in the general population in Italy (4.9 per 1,000; 95% CI, 2.8-7.8). The results of this study showed a high prevalence of celiac disease in patients with AIH. For this reason, early serological screening testing for celiac disease is strongly recommended for all AIH patients.¹¹

“Frequency and significance of anti-gliadin and anti-endomysial antibodies in autoimmune hepatitis.” This study investigating the frequency of Celiac Disease in 157 patients with autoimmune hepatitis, demonstrated that the presence of celiac disease is high (4% or one in 36 patient) and that it is predominantly asymptomatic. Subtotal villous atrophy was present in all patients undergoing duodenal biopsy. Screening with anti-endomysial and anti-gliadin antibodies should be performed and results confirmed with intestinal biopsy.⁶

Sources:

1. National Digestive Diseases Information Clearinghouse [↩] [↩]
2. 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. [↩]
3. Abdo A, Meddings J, Swain M. Liver abnormalities in celiac disease. Clinical Gastroenterology and Hepatology. Feb 2004;2(2):107-12. [↩] [↩]
4. Volta U, De Franceschi L, Molinaro N, et al. Frequency and significance of anti-gliadin and anti-endomysial antibodies in autoimmune hepatitis. Digestive Diseases and Sciences. Oct 1998;43(10):2190-5. [↩]
5. Villalta D, Girolami D, Bidoli E, Bizzaro N, Tampoia M, Liguori M, Pradella M, Tonutti E, Tozzoli R. High prevalence of celiac disease in autoimmune hepatitis detected by anti-tissue tranglutaminase autoantibodies. J Clin Lab Anal. 2005;19(1):6-10. [↩]
6. Volta U, De Franceschi L, Molinaro N, et al. Frequency and significance of anti-gliadin and anti-endomysial antibodies in autoimmune hepatitis. Digestive Diseases and Sciences. Oct 1998;43(10):2190-5. [↩] [↩]
7. Oo  Y, Hubscher S, Adam D. Autoimmune hepatitis: new paradigms in the pathogenesis, diagnosis, and management. Hepatol Int. June 2010;4(2):475-493. [↩]
8. Ramagopalan SV, 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. [↩] [↩]
9. 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. [↩]
10. 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. [↩] [↩] [↩] [↩] [↩] [↩]
11. Villalta D, Girolami D, Bidoli E, Bizzaro N, Tampoia M, Liguori M, Pradella M, Tonutti E, Tozzoli R. High prevalence of celiac disease in autoimmune hepatitis detected by anti-tissue tranglutaminase autoantibodies. J Clin Lab Anal. 2005;19(1):6-10. [↩]