Autoimmune hepatitis

Overview

Autoimmune hepatitis is a liver condition characterized by persistent inflammation. Autoimmune disease occurs when the body's immune system attacks another component of the body. Hepatitis is a liver inflammation that can range from moderate to severe. Autoimmune hepatitis is characterized by varying degrees of severity, with relapses and remissions in the great majority of patients.

 

What is Autoimmune hepatitis?

Autoimmune hepatitis is a condition in which the body's own immune system destroys and inflames the liver. The sickness is chronic, which means it lasts for a long time. It can progress to cirrhosis and liver failure if left untreated.

This illness comes in two varieties. The most prevalent kind is type 1, or classic, autoimmune hepatitis. This is the most common kind that affects young women and is frequently accompanied with other autoimmune diseases. Type 2 autoimmune hepatitis is less prevalent and mostly affects girls aged 2 to 14.

Autoimmune Hepatitis is rare. It is believed that between 10 and 17 persons per 100,000 are affected throughout Europe. This suggests that roughly 10,000 persons in the UK are likely to have AIH.

Autoimmune Hepatitis can affect both men and women, however it is three to four times more frequent in women. It can occur at any age, however it is most typically diagnosed in women over the age of 45. It can affect people of various ethnicities. Thirty to fifty percent of persons with Autoimmune Hepatitis also have thyroid disease, rheumatoid arthritis, ulcerative colitis, or Type 1 diabetes.

 

What are Autoimmune Diseases?

Autoimmune illnesses are conditions in which the body's immune system assaults its own cells and organs with proteins known as autoantibodies; this is known as autoimmunity.

To help the body fight infections, the immune system generally produces a huge number of proteins known as antibodies. However, in rare circumstances, the body produces autoantibodies. Certain environmental factors can cause autoimmunity. Environmental triggers include germs, viruses, poisons, and drugs that originate outside the body.

 

What causes autoimmune hepatitis?

The etiology of autoimmune hepatitis is unknown. It is associated with a condition known as hypergammaglobulinemia. This condition develops when your blood has an abnormally high level of protein antibodies. A long-term (chronic) infection or certain blood illnesses can cause it. Type 1 autoimmune hepatitis has been connected to other conditions in which the body fights itself (autoimmune disorders). These might include:

• Thyroiditis
• Grave's disease
• Type 1 diabetes
• Rheumatoid arthritis
• Hemolytic anemia
• Immune thrombocytopenia
• Celiac disease
• Ulcerative colitis

 

What are the symptoms of autoimmune hepatitis?

A variety of clinical symptoms of autoimmune hepatitis exist. A third of the patients present to the clinic with acute icteric hepatitis, and in rare cases, fulminant hepatic failure. The majority of individuals have lesser illness, with some perhaps having subclinical disease. They may seek medical help due to nonspecific symptoms such as widespread weariness.

Furthermore, many people have arthralgias without arthritis, which may necessitate a thorough examination. AIH is increasingly being recognized in people who have increased liver function tests as part of standard medical testing. At least one-third of patients had cirrhosis at the time of presentation, indicating that the illness has been undiagnosed for some time. Even in individuals with acute illness, a liver biopsy frequently reveals extensive fibrosis or cirrhosis.

Acute icteric hepatitis is more prevalent in children and young adults, and fulminant hepatic failure can develop in this age range. Even persons in their eighties can develop fulminant hepatitis and subacute liver failure, thus prompt diagnosis and treatment are crucial. A significant level of suspicion is required.

An acute relapsing course is a distinguishing trait in certain people. Untreated acute autoimmune hepatitis may not always result in rapid liver failure; nonetheless, the majority of patients who are not recognized or are not treated for other reasons will see a spontaneous partial recovery, and in some cases, complete normalization of liver function tests. Histological disease activity, on the other hand, frequently remains, and another acute exacerbation occurs within a few months.

Others develop chronic hepatitis, usually with a variable course. Patients with acute autoimmune hepatitis or an acute flare are nearly always icteric and have significant jaundice. The majority of these patients also report general symptoms such malaise, weariness, lack of appetite, and, as previously noted, arthralgias. This latter symptom represents a marker of disease activity for many individuals, which might be useful in therapeutic therapy. Persistence of arthralgia in individuals with biochemical remission typically indicates persistence of inflammatory activity in the liver, as proven by liver biopsy.

Clinical examination may reveal symptoms of chronic liver disease. Palmar erythema is not solely associated with cirrhosis. It may vanish in some cases after effective immunosuppressive medication. The liver may be visible as enlarged, swelling, and painful. Nodularity may be apparent in advanced illness.

Because autoimmune hepatitis has a hereditary propensity and is connected with a number of autoimmune illnesses, both family and personal history should be carefully considered. Different autoimmune illnesses in the same patient generally appear sequentially and very rarely simultaneously, as with most autoimmune disorders.

 

How is autoimmune hepatitis diagnosed?

A doctor will diagnose autoimmune hepatitis based on symptoms, a physical exam, blood tests, and a liver biopsy. A health care professional does a physical exam and evaluates the patient's medical history, including alcohol and drug usage that can affect the liver. A person with autoimmune hepatitis may exhibit symptoms similar to those of other liver illnesses or metabolic disorders, necessitating blood testing for an accurate diagnosis.

• Blood tests 

A blood test entails extracting blood at a doctor's office or a commercial facility and sending it to a lab for analysis. Blood testing for autoantibodies will be required to differentiate autoimmune hepatitis from other liver illnesses with comparable symptoms, such as viral hepatitis, primary biliary cirrhosis, steatohepatitis, or Wilson disease.

• Liver biopsy 

A liver biopsy is a process in which a portion of liver tissue is removed and examined under a microscope for evidence of injury or illness. Before the liver biopsy, the doctor may urge the patient to temporarily cease using certain drugs. He or she may also request that the patient fast for 8 hours before to the surgery.

During the process, the patient rests on a table with his or her right hand above the head. A local anesthetic will be applied to the location where the biopsy needle will be inserted by a health care practitioner. He or she will administer sedatives and pain medicines as needed. The needle will then be used to extract a tiny bit of liver tissue, and the needle may be guided by ultrasound, computed tomography scans, or other imaging modalities. Following the biopsy, the patient must rest on his or her right side for up to 2 hours and is observed for another 2 to 4 hours before being discharged.

A liver biopsy is performed by a health care practitioner at a hospital or an outpatient clinic. The liver sample is sent to a pathology lab, where a pathologist (a specialist who specializes in disease diagnosis) examines the tissue under a microscope and reports to the patient's health care practitioner.

A liver biopsy can be used to detect autoimmune hepatitis and assess the presence of cirrhosis. Cirrhosis is frequently seen when people are diagnosed with autoimmune hepatitis. A liver biopsy can also be used by a doctor to check for changes in the degree of liver damage before discontinuing therapy for autoimmune hepatitis.

 

How is Autoimmune Hepatitis Treated?

Medication to reduce or slow down an overactive immune system is used to treat autoimmune hepatitis. A liver transplant may potentially be considered as part of the treatment. Treatment is most effective when autoimmune hepatitis is detected early. In most situations, people with autoimmune hepatitis respond to normal therapy and the condition may be managed. Long-term treatment response can prevent the condition from worsening and may even repair some liver damage.

• Medications

Individuals with autoimmune hepatitis who have no symptoms or a moderate form of the illness may or may not require treatment. A health care practitioner will determine whether or not a person need treatment. Some persons with moderate autoimmune hepatitis may experience remission. Remission is a time in which a person is symptom-free and blood tests and a liver biopsy reveal that his or her liver function has improved.

• Corticosteroids

Corticosteroids are drugs that suppress inflammation and immune system activity. Both kinds of autoimmune hepatitis are treated with a daily dosage of prednisone, a corticosteroid. Treatment may begin with a high dosage, which is gradually reduced as the disease progresses. The objective of treatment is to discover the lowest feasible dose that will help manage the condition.

Side effects of prednisone may include:

• Weight gain
• Weakness of the bones, called osteoporosis or osteomalacia
• Thinning of the hair and skin
• Acne
• Diabetes
• High blood pressure
• Cataracts, a clouding in the lens of the eyes
• Glaucoma, elevated pressure in the eyes
• Anxiety and confusion

As large dosages of prednisone are frequently recommended to treat autoimmune hepatitis, a health care professional will actively monitor and manage any adverse effects that may arise.

• Immune system suppressors

Immunosuppressive medications prevent the body from producing autoantibodies and inhibit the immunological response that contributes to inflammation. In most situations, azathioprine (Azasan, Imuran) is used in combination with prednisone to treat autoimmune hepatitis. When azathioprine is used, a health care practitioner can use a lower dose of prednisone, which may lessen the negative effects of prednisone.

Side effects of azathioprine include:

• Low white blood cell count
• Nausea
• Vomiting
• Skin rash
• Liver damage
• Pancreatitis, or inflammation of the pancreas

Because azathioprine suppresses the immune system, patients who take it should have regular blood tests to evaluate their white blood cell levels. Bone marrow failure can result from a low white blood cell count. The tissue located inside bones that creates new blood cells, including platelets, is known as bone marrow. When blood tests are performed, a health care professional will also assess the platelet count. Prednisone or azathioprine may need to be stopped if they induce significant adverse effects. Side effects are more likely in persons who already have cirrhosis.

In persons who demonstrate recovery, a health care professional may gradually lower the amount of medicine, albeit symptoms may recur. When a person stops taking medication, a health care practitioner will take routine blood tests and closely monitor the person's condition for the recurrence of symptoms. Low dosages of prednisone or azathioprine may be required on and off for several years.

Other immunosuppressive medicines, such as mycophenolate mofetil, cyclosporine, or tacrolimus, may aid those who do not react to traditional immune treatment or have significant adverse effects from the medications.

Medications that inhibit the immune system have been linked to a variety of cancers. People who take modest dosages of azathioprine for an extended length of time are at a low risk of acquiring cancer.

• Liver Transplant

In certain cases, autoimmune hepatitis leads to cirrhosis and end-stage liver failure, necessitating a liver transplant. Cirrhosis and liver failure symptoms include autoimmune hepatitis and liver failure.

• Generalized itching
• A longer-than-usual amount of time for bleeding to stop
• Easy bruising
• A swollen stomach or swollen ankles
• Spiderlike blood vessels, called spider angiomas, that develop on the skin
• Abdominal bloating due to an enlarged liver
• Fluid in the abdomen—also called ascites
• Forgetfulness or confusion

A liver transplant involves surgery to replace a damaged or injured liver with a healthy one from another person, known as a donor. In a hospital, a team of surgeons conducts a liver transplant. Fasting for 8 hours before surgery is recommended whenever feasible. The patient is admitted to the hospital for one to two weeks to ensure that the transplanted liver is working appropriately. The patient will be monitored for bleeding, infections, and symptoms of liver rejection. To prevent infections and rejection, the patient will be on long-term prescription drugs. In most situations, liver transplant surgery for autoimmune hepatitis is successful.

 

Autoimmune hepatitis and Pregnancy

Autoimmune hepatitis primarily affects young girls, emphasizing the issue of pregnancy with this condition. Several centers have gathered their data and attempted to provide suggestions based on their findings. Despite the fact that these studies necessarily leave a significant level of ambiguity due to the small number of patients studied and their observational nature, the message is encouragingly consistent: pregnancy with AIH is typically safe for both mother and child.

There appears to be a slightly greater risk of (mainly early) miscarriage, although this appears to be unrelated to the therapy. Despite being a class D medicine with unknown safety in pregnancy, azathioprine was not linked to miscarriage or other pregnancy problems. AIH activity is generally reported to be milder during pregnancy, as has been recorded for other autoimmune disorders, and this may allow immunosuppression to be tapered, particularly in the early stages.

Due to the possibility of occasional flare-ups to fulminant liver failure during pregnancy, immunosuppression should be maintained at a suitable level that has been carefully determined for each patient. Furthermore, post-partum flares of the condition are common, therefore we recommend increasing the steroid dose just before the predicted date of delivery and regularly monitoring liver enzymes and IgG levels in the weeks after birth.

 

Prognosis

Individuals with symptomatic autoimmune hepatitis have a 50% ten-year survival rate without therapy. With therapy, however, the ten-year survival rate exceeds 90%. Despite therapeutic advantages, persons with autoimmune hepatitis have a poorer transplant-free survival rate than the general population. The outcomes of liver transplantation are typically excellent, with a five-year survival rate of more than 80%.

Depending on race, the presentation and response to therapy may differ. African Americans tend to have more aggressive illness, which is associated with poorer results. Patients with autoimmune hepatitis have a higher risk of developing mental health problems such as schizophrenia and bipolar disorder later in life.

 

Difficult to treat patients

Most patients, although not all, react well to therapy. Non-response, treatment intolerance, or pharmacological adverse effects can all contribute to management issues in AIH. Patients with AIH who also have sclerosing cholangitis or primary biliary cirrhosis (overlap syndromes) may provide a treatment challenge. Finally, co-morbidities may limit therapy options and consequently impact autoimmune hepatitis care.

• Non-response

Response to immunosuppression is so common in AIH that it is used as a diagnostic criteria. As a result, non-response should call the diagnosis into doubt, as should adherence to therapy. Nonetheless, a few individuals may not respond adequately to normal immunosuppression, and some reactivate when steroid dosages are reduced to levels higher than can be tolerated. The therapeutic care of these situations might be difficult.

Because of the rarity of this scenario, only a few case series that can guide therapy have been published. In the beginning, intravenous prednisolone at dosages of 100 mg daily or higher may be necessary in a few aggressive cases of acute jaundice, as these patients may also suffer from malabsorption. Mycophenolate mofetil appears to be a pretty excellent option in people intolerant to azathioprine. It appears to be of very limited efficacy in patients with an inadequate response to azathioprine, but data in children is more positive than in adults.

Stronger immunosuppressive medications appear to be necessary in these individuals, and favorable outcomes have been documented with cyclophosphamide, methotrexate, cyclosporine, tacrolimus, and infliximab. There are no comparable statistics available. As a result, the selection should be based on local and personal expertise.

Although the calcineurin inhibitors cyclosporine and tacrolimus appear to be effective, they are not immunomodulatory and hence require long-term therapy, whereas immunomodulatory drugs such as cyclophosphamide or infliximab may allow for gradual decrease of immunosuppression. Specific research on second-line therapy for difficult-to-treat patients is required.

• Non-compliance

Compliance is rarely an issue in acute illness, although it might be during follow-up. Pediatric children entering puberty are a particularly tough population to handle. Non-adherence to treatment is especially common in teenagers, who refuse to accept medication side effects and ignore their condition in an attempt to be "normal," resulting in a high recurrence rate, which can lead to liver failure.

During puberty management, like other chronic diseases, requires careful motivation of children and their parents, which is better done in specialized transition services with a multidisciplinary approach that includes pediatric and adult hepatologists, psychologists, and nurse experts.

• Drug intolerance

Azathioprine intolerance occurs in 3-5% of people and is idiosyncratic. Intolerance occurs within a few weeks, usually within the first few days of therapy. It is critical to discover intolerance and discontinue the treatment quickly, which typically leads in symptom relief within a few days. If in doubt, re-exposure with a low dose should be undertaken, since real intolerance will result in a quick reemergence of symptoms.

Mycophenolate mofetil looks to be a promising option in patients intolerant to azathioprine, with a long-term response rate of over 70%, and should be the first choice medicine in individuals resistant to azathioprine. Steroid monotherapy in patients with moderate illness and few steroid risk factors, or any of the immunosuppressives used in non-responders, such as methotrexate, cyclophosphamide, calcineurin inhibitors, or infliximab, are potential options.

 

Conclusion 

Autoimmune hepatitis (AIH) is an immune-mediated inflammatory liver disease with unknown origin that affects people of various ages, genders, and races. Patients may be asymptomatic, chronically unwell, or present with acute liver failure (ALF), and the diagnosis must be addressed in all patients with acute or chronic liver inflammation, including those who have graft malfunction following liver transplant.

AIH lacks a trademark diagnostic trait, and the presence of a constellation of typical signs, which might vary across patients with the same illness and can exist in other liver disorders, is required for a diagnosis. Possible consequences include extensive hepatic fibrosis, cirrhosis, death from liver failure, or liver transplant. Immunosuppressive therapy has saved lives, but treatment regimens can be lengthy, accompanied by substantial side effects, and vary in effectiveness.