What Are The Types Of Autoimmune Hepatitis
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. About 70 percent of people with type 1 autoimmune hepatitis are female.1
People with type 1 autoimmune hepatitis commonly have other autoimmune disorders, such as
Type 2 autoimmune hepatitis is less common and occurs more often in children than adults.1 People with type 2 can also have any of the above autoimmune disorders.
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Glutathione plays a very important role in establishing immune tolerance . Studies have demonstrated that glutathione enhances the function of T cells and modulates immune activity . In this way, optimizing glutathione levels are extremely important for reducing collateral damage associated with inflammation and autoimmune reactions .
This article goes into more detail on glutathione and its role in reducing inflammation. Hopefully, this article has given you hope and several major action steps to reduce inflammation and heal autoimmune disease.
Treatments For Autoimmune Hepatitis
Treatment works best when AIH is diagnosed early. The goal in treating AIH is to slow or stop the bodys immune system from attacking the liver. The medications used are immunosuppressants, such as prednisone and Imuran® . Physicians usually prescribe a high initial dose of prednisone, and then taper it down progressively as symptoms and liver enzymes improve. Most people will need to take medication for the rest of their lives. Since prednisone can cause a wide range of side effects, Imuran® is often used in conjunction to allow for a lower dose of the prednisone.
Some people may go into remission, during which physicians can effectively discontinue treatment others will relapse after stopping treatment, and will then need to restart the medication and continue on long-term maintenance therapy. A few patients may eventually be tapered off the prednisone completely and stay solely on Imuran®. For those who do not respond to, or relapse from, the combination regimen, then stronger immunosuppressive agents such as mycophenolate mofetil, cyclosporine, or tacrolimus may be considered. When medications do not halt the progress of the disease, or complications from cirrhosis have developed, the remaining option is a liver transplant. Fortunately, the success rate of transplantation in people with AIH is excellent.
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How To Diagnose Autoimmune Hepatitis
It is difficult to suspect autoimmune hepatitis only based on the symptoms since several liver diseases cause similar symptoms. It is therefore important to rule out other causes of liver disease like viral hepatitis, alcoholic hepatitis and drug-induced hepatitis while making the diagnosis of autoimmune hepatitis. Diagnosis of autoimmune hepatitis is based on the following:
- Medical history of the patient where the patient will complain of the symptoms mentioned above. The patient may also give a history of suffering from another autoimmune disease
- Physical examination may reveal the presence of jaundice, pain over the liver, an enlarged liver, and other signs of liver disease as mentioned above.
- Blood tests: Blood tests done for autoimmune hepatitis include liver function tests and tests for autoantibodies
- Liver function tests will indicate high bilirubin levels, increase in liver enzymes, and prolonged bleeding and clotting times
Genetics And Predisposing Factors
Autoimmune hepatitis is thought to result from an environmental trigger in a genetically predisposed individual, leading to loss of tolerance of T lymphocytes with subsequent hepatocyte attack.
It is a polygenic disease and does not follow a Mendelian distribution. Therefore there is no need to screen family members of patients with AIH. There is a strong genetic association with the alleles of the major histocompatibility complex class II. The presence of human leukocyte antigen genes HLA DRB1*03 and HLA DRB1*04 predisposes to AIH type 1 and affect the disease course and response to treatment. Individuals who are positive for HLA DRB1*03 are younger, respond less favorably to corticosteroid therapy, and progress more often to liver failure. On the other hand, the presence of HLA DRB1*04 is associated with higher rates of concomitant autoimmune disorders.
Autoimmune hepatitis can also be associated with autoimmune polyendocrinopathy candidiasis ectodermal dystrophy syndrome, an autosomal recessive disease characterized by hypoparathyroidism, adrenal insufficiency, and chronic mucocutaneous candidiasis. Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy is the only AIH-associated disease that follows a Mendelian pattern of inheritance and genetic counseling should be offered for patients and family members.
Table 1: Drugs Associated With Drug-Induced Autoimmune-Like Hepatitis
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Screening For Viral Hepatitis
The purpose of screening for viral hepatitis is to identify people infected with the disease as early as possible, even before symptoms and transaminase elevations may be present. This allows for early treatment, which can both prevent disease progression and decrease the likelihood of transmission to others.
Hepatitis A causes an acute illness that does not progress to chronic liver disease. Therefore, the role of screening is to assess immune status in people who are at high risk of contracting the virus, as well as in people with known liver disease for whom hepatitis A infection could lead to liver failure. People in these groups who are not already immune can receive the hepatitis A vaccine.
Those at high risk and in need of screening include:
- People with poor sanitary habits such as not washing hands after using the restroom or changing diapers
- People who do not have access to clean water
- People in close contact with someone who has hepatitis A
- People who use illicit drugs
- People with liver disease
- People traveling to an area with endemic hepatitis A
The presence of anti-hepatitis A IgG in the blood indicates past infection with the virus or prior vaccination.
Hepatitis B and C
What Is Autoimmune Disease
One job of the immune system is to protect the body from viruses, bacteria, and other living organisms. The immune system usually does not react against the bodys own cells. However, sometimes it attacks the cells it is supposed to protect this response is called autoimmunity. Researchers think certain bacteria, viruses, toxins, and drugs trigger an autoimmune response in people who are genetically susceptible to developing an autoimmune disorder.
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How Is Autoimmune Hepatitis In Children Diagnosed
Your childs health care provider will do several tests to look for autoimmune hepatitis and other related diseases. These tests may include:
- Blood tests
- Liver biopsy
- Special scans of the liver, such as ultrasound and magnetic resonance cholangiopancreatography
- Exam of the inside of the intestines , under anesthesia
What Is The Outlook For Someone With Autoimmune Hepatitis
Autoimmune hepatitis is a chronic disease, meaning you will have it for the rest of your life. With proper treatment, its possible to enjoy years of remission without symptoms and healthy liver function.
The Canadian Society of Intestinal Research suggests that people who respond well to treatment can expect to have a normal life expectancy.
Also, a 2020 study found that with proper immunosuppressant therapy, about 90 percent of the 86 people with autoimmune hepatitis in this study achieved complete remission.
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Chronic Inflammation Vs Autoimmunity
Chronic inflammatory processes and autoimmunity have a lot of similarity but also some differences. Autoimmunity is usually associated with an overall chronic inflammatory process. However, one could have a chronic inflammatory condition without having autoimmunity.
A chronic inflammatory process is when some sort of trigger initiates a strong inflammatory process that causes collateral damage to other tissues of the body such as the gut lining, blood vessels, the sinuses, the lungs, the joints, etc. This would create conditions such as inflammatory bowel disease, heart disease, allergies, asthma, osteoarthritis, etc.
An autoimmune condition is when the bodies white blood cells produce a specific antibody to target a particular tissue or enzyme within a tissue of the body. For example, in Hashimotos thyroiditis, the body will produce an anti-body to attach certain enzymes such as thyroid peroxidase or thyroglobulin that work to produce thyroid hormone.
So the big difference between chronic inflammatory conditions and autoimmunity is that in CICs we have tissue damage resulting as an indirect effect of the inflammatory process. While in autoimmunity we see tissue damage as a direct effect of the inflammatory process.
How Is Autoimmune Hepatitis Diagnosed
Your healthcare provider will look at your health history and give you a physical exam.
Some lab blood tests used to diagnose autoimmune hepatitis include:
- Liver function tests. These check for inflammation or damage to your liver.
- Complete blood count or CBC. Looks at the number and types of cells in your blood.
- Coagulation panel. This test looks at how well the clotting proteins are working.
- Electrolyte panel. Checks to see if you have an electrolyte imbalance.
- Autoimmune antibodies. These are used to see if you have autoimmune hepatitis or another liver disease with similar symptoms.
- Other liver tests. These are done to check for other possible types of liver disease.
You may also have imaging tests such as:
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What Are The Side Effects Of Prednisone And Azathioprine
Both prednisone and azathioprine have side effects. Because high doses of prednisone are often needed to control autoimmune hepatitis, managing side effects is very important. However, most side effects appear only after a long period of time.
Some possible side effects of prednisone are
- weight gain
- thinning of the bones, a condition called osteoporosis
- thinning of the hair and skin
Azathioprine can lower white blood cell counts and sometimes causes nausea and poor appetite. Rare side effects are allergic reaction, liver damage, and pancreatitis, which is an inflammation of the pancreas gland with severe stomach pain.
What Causes Autoimmune Hepatitis In Children
It is not known exactly why the immune system begins attacking liver cells in children with autoimmune hepatitis.
Experts are looking at a number of possible causes, including:
- Genetics. Physical traits passed down from parents
- Environment. Causes of disease from outside the body, such as toxic substances, certain medicines, or germs
- Problems with the immune system. For example, in patients with autoimmune hepatitis, it seems that some cells that regulate the immune system are fewer or weaker, while other cells that make the immune system attack are more frequent or more active.
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Initial Therapy For Adults And Children
The American Association for the Study of Liver Diseases published detailed guidelines regarding the management of autoimmune hepatitis in 2010 and 2019.
The 2010 AASLD guideline delineated absolute and relative indications for immunosuppressive treatment. See Table 2, below.
Table 2. Indications for Treatment of Autoimmune Hepatitis in Adults
Serum aspartate transaminase 10-fold the upper limit of
Serum AST 5-fold the ULN and gamma-globulin level 2-fold the ULN
Serum AST and/or gamma-globulin less than absolute criteria
Bridging necrosis or multiacinar necrosis on
Note that many patients with cirrhosis and active autoimmune hepatitis respond well to immunosuppression.
The 2010 AASLD guideline also described the following contraindications to treatment :
Asymptomatic patients with normal or near normal aspartate aminotransferase and gamma globulin levels
Severe osteoporosis, psychosis, brittle diabetes, or uncontrolled hypertension
Severe cytopenias or patients with complete deficiency of thiopurine methyltransferase
In addition, treatment might not be appropriate in patients with decompensated liver disease . Such individuals might be better served by liver transplantation.
The 2010 AASLD guideline also recommended initial treatment strategies for adults as shown in Table 3, below.
Table 3. Treatment Regimens for Adults
Table 4. Treatment Regimens for Children
Symptoms Of Autoimmune Hepatitis
Falk: Patients with autoimmune hepatitisyou describe them as asymptomatic, they dont know its happening, but something there are associated symptoms, right? Everyone with autoimmune disease is fatigued or tired. What else would a patient with autoimmune hepatitiswhat other kinds of symptoms might appear?
Darling: Theres a huge spectrum of presentation with autoimmune hepatitis, from asymptomatic with minor liver enzyme elevations to a much more dramatic presentation in which the persons liver is really not functioning well. These patients usually present with mild jaundice, meaning they have yellowing of the eyes and darkening of urine, they can present confusedthe liver processes a lot of toxins and the toxins build up if the livers not working. They can also present quite ill in full liver failure. So theres a huge spectrum.
Falk: Like many autoimmune diseases, there is a relapsing and remitting course, and a waxing and waning course. Since most autoimmune diseases come and go, and youve just described beautifully that patients can have mild disease almost on presentation have a very aggressive liver disease, arguing that prompt referral to somebody who treats liver disease its pretty important to find out where on that spectrum you are.
Falk: Or primary care provider.
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How Is Autoimmune Hepatitis Treated
Treatment works best when autoimmune hepatitis is found early. The goal of treatment is to control the disease and to reduce or get rid of any symptoms .
To do this, medicines are used to help slow down or suppress your overactive immune system. They also stop your body from attacking your liver.
Once you have started treatment, it can take 6 months to a few years for the disease to go into remission. Some people can stop taking medicine, but often the disease comes back. You may need treatment now and then for the rest of your life. Some people need to remain on treatment if they have relapsed many times or if their disease is severe.
In some cases autoimmune hepatitis may go away without taking any medicines. But for most people, autoimmune hepatitis is a chronic disease.
It can lead to scarring of the liver . The liver can become so badly damaged that it no longer works. This is called liver failure.
If you have liver failure, a liver transplant may be needed.
Be sure to ask your healthcare provider about recommended vaccines. These include vaccines for viruses that can cause liver disease.
What Are The Causes Of Autoimmune Hepatitis
Autoimmune hepatitis occurs when the white blood cells of the body produce an inappropriate immune response against the liver cells, thereby causing inflammation and damage. The exact cause of autoimmune hepatitis is not known. Affected people may have a genetic predisposition for the condition, which may be triggered by an environmental factor. Around 20% patients suffering from a genetic condition called autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome suffer from autoimmune hepatitis.
The environmental trigger could be:
- Drugs like infliximab, minocycline, atorvastatin, diclofenac, isoniazid, methyldopa, nitrofurantoin, and propylthiouracil, the hepatitis A vaccine, and herbal agents like black cohosh and dai-saiko-to. The autoimmune hepatitis may improve after stopping the medication
- Viruses such as hepatitis A, B, or C, or measles virus
Autoimmune hepatitis is of two main types, type 1 and type 2
- Type 1 autoimmune hepatitis usually first manifests in adolescence or young adults. Females are most commonly affected.
- Type 2 autoimmune hepatitis is less common than type 1 and usually first manifests in children. Its prognosis or outcome is often worse than type 1 disease.
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Types Of Autoimmune Hepatitis
Type 1 Autoimmune Hepatitis:
It is the most common disease. Around half of those with autoimmune hepatitis may have rheumatoid arthritis, celiac disease, or ulcerative colitis.
Type 2 Autoimmune Hepatitis:
Adults are more likely to contract this form of hepatitis. However, it is most prevalent among infants and teenagers. Other autoimmune disorders can also accompany this form of illness.
What Is Chronic Hepatitis
Hepatitis is an inflammation of the liver. In chronic hepatitis, liver inflammation continues for at least six months. This condition may be mild, causing relatively little damage, or more serious, causing many liver cells to be destroyed. Some cases lead to cirrhosis and liver failure.
Chronic hepatitis from infection is most often caused by these viruses:
- Hepatitis B and C. Often the person infected is unaware of any initial symptoms. Or the symptoms were so mild that the person did not seek medical attention. This is especially true for chronic hepatitis C. Over time, perhaps a decade or more, both types may lead to the serious complication of cirrhosis due to ongoing destruction of liver cells and resultant scarring. A minority of patients with cirrhosis develop liver cancer over time.
- Hepatitis D. Hepatitis D infects only patients already infected with hepatitis B, and it generally results in a flare of active hepatitis.
This information helps to determine the best treatment and to assess your risk of developing cirrhosis and liver failure. A liver biopsy also can help to check for other disorders, such as alcoholic liver injury or fatty liver.
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