Autoimmune Hepatitis Research Paper

Autoimmune hepatitis is a chronic inflammatory disorder characterized by periportal inflammation, elevated immunoglobulins, autoantibodies, and a dramatic response to immunosuppression. Autoimmune hepatitis occurs when the body's immune system, which ordinarily attacks viruses, bacteria and other pathogens, instead targets the liver. This attack on your liver can lead to chronic inflammation and serious damage to liver cells. Just why the body turns against itself is unclear, but researchers think autoimmune hepatitis could be caused by the interaction of genes controlling immune-system function and exposure to particular viruses or drugs. Autoimmune hepatitis can lead to cirrhosis and liver failure. Cirrhosis occurs when scar tissue replaces

healthy liver tissue and blocks the normal flow of blood through the liver. Autoimmune hepatitis is classified into several types.

Type 1 autoimmune hepatitis is the most common form in North America. About 70 percent of people with type 1 autoimmune hepatitis are female. Type 2 autoimmune hepatitis is less common and occurs more often in children than adults. Signs and symptoms of autoimmune hepatitis can range from minor to severe and they include, fatigue, abdominal discomfort, an enlarged liver and in women, loss of menstruation. Tests and procedures used to diagnose autoimmune hepatitis include, blood tests which is used for autoantibodies to help distinguish autoimmune hepatitis from other liver diseases that have similar symptoms, such as viral hepatitis, primary biliary cirrhosis, steatohepatitis, or Wilson disease. Liver biopsy is when Doctors perform a liver biopsy to confirm the diagnosis and to determine the degree and type of liver damage. Possible Complication of autoimmune hepatitis and cirrhosis is that people are at risk of developing liver cancer. Treatment for autoimmune hepatitis includes medication to suppress, or slow down, an overactive immune system. Treatment may also include a liver

transplant.
Autoimmune hepatitis (AIH) is a chronic inflammatory disease of unknown etiology characterized by the presence of circulating autoantibodies, hypergammaglobulinemia, necroinflammatory changes on hepatic histology, and a dramatic response to immunosuppressive therapy. Earliest descriptions include those by Amberg in 1942 [1] and Leber in 1950 describing a form of chronic liver disease prevalent among young women and characterized by an excessive increase in serum protein and gamma-globulins. In 1951, Kunkel et al. termed the condition “hypergammaglobulinemic chronic hepatitis” (2). Since then, it has been known by various names including chronic active hepatitis, chronic aggressive hepatitis, plasma cell hepatitis, and autoimmune chronic active hepatitis. Cowling and Mackay coined the term “lupoid hepatitis” after they noted the association of this entity with autoimmune syndromes and the LE cell phenomenon.
The disease is rare with a mean incidence of 1-2 per 100,000 and a point prevalence of 11–17 per 100,000. Although more frequently seen in young women (sex ratio 3:6: 1), it can affect children and adults of all ages and ethnicities. A minority of patients may present with acute liver failure and need liver transplantation, but for the majority, the prognosis of AIH is good and mostly determined by response to corticosteroid therapy. In general, long-term survival and average life expectancy are excellent and estimated to be comparable to the normal population.
The classification of AIH into different types is based on serum autoantibody profiles. Type I AIH is characterized by the presence of antinuclear antibody (ANA), anti-smooth muscle antibody (SMA), or both and constitutes 80% of AIH cases. About 25% have cirrhosis at presentation, and association with other autoimmune diseases is common (celiac disease, ulcerative colitis, autoimmune thyroid disease). Type 2 AIH is characterized by the presence of anti-liver kidney microsomal (LKM) 1 and/or anti-LKM3 and/or anti-liver cytosol 1 (LC1) antibodies. Most patients are children, acute severe presentation can occur, and progression to cirrhosis commonly ensues.
AIH is associated with chronic inflammation that may proceed to cirrhosis and end-stage liver disease which also puts AIH patients at risk of developing HCC. However, unlike other cohorts of cirrhotic patients, the majority of patients with AIH respond well to immunosuppression and in those whom enter a sustained remission, the potential exists to retain a near normal life expectancy. However, the interactions of disease activity, response to treatment, and other factors in relation to the risk of HCC development in AIH are unknown. Although the development of HCC in patients with AIH and cirrhosis is considered a rare occurrence, the true incidence remains unknown due to the paucity of published data addressing this issue (3).
Autoimmune disease is caused when the body's immune system, which ordinarily attacks viruses, bacteria and other pathogens, instead targets the liver. There are many symptoms of Autoimmune hepatitis. Signs and symptoms of autoimmune hepatitis can range from minor to severe and may come on suddenly. Some people have few, if any, recognized problems in the early stages of the disease, whereas others experience signs and symptoms that may include:
Fatigue, abdominal discomfort, yellowing of the skin and whites of the eyes (jaundice), an enlarged liver, Abnormal blood vessels on the skin (spider angiomas), skin rashes, joint pains in women, loss of menstruation (4).
Factors that may increase your risk of autoimmune hepatitis include, beigna a female: Although both men and women can develop autoimmune hepatitis, the disease is more common in women.

Autoimmune hepatitis may develop after you’re infected with the measles, herpes simplex or Epstein-Barr virus. The disease is also linked to hepatitis A, B or C infection. Evidence suggests that a predisposition to autoimmune hepatitis may run in families. People who already have an autoimmune disease, such as celiac disease, rheumatoid arthritis or hyperthyroidism (Graves’ disease or Hashimoto’s thyroiditis), may be more likely to develop autoimmune

hepatitis.
The diagnosis of AIH requires the presence of characteristic clinical features and exclusion of other chronic liver conditions, such as viral hepatitis, drug-induced hepatitis, fatty liver disease, alcohol related liver disease, Wilson’s disease, alpha 1 antitrypsin deficiency, or hemochromatosis. The characteristic circulating autoantibodies seen in AIH include ANA, SMA, and (LKM-1) autoantibodies. They are helpful in diagnosis as well as for classification of AIH into type 1 and type 2 diseases. The reader is referred to excellent reviews for description of methodology, sensitivity, and assay performance. Except for pANCA, which is readily available and can be positive in 50–90% of type I AIH, only antiactin can be easily in measured in some laboratories. Recently, antibodies to cyclic citrullinated peptides (CCP) have been described in 9–11% of patients with AIH in absence of rheumatoid arthritis. These patients have a propensity to develop cirrhosis and liver failure. Antimitochondrial antibodies are sometimes present in patients with AIH and an overlap syndrome of AIH and PBC should be considered in these patients.
The histologic hallmark of AIH is a lymphoplasmacytic periportal infiltrate invading the limiting plate, also called piecemeal necrosis or “interface hepatitis” (that eventually progresses to lobular hepatitis. There is often an abundance of plasma cells and eosinophils are frequently present. The portal lesion typically spares the biliary tree. A lobular, or panacinar hepatitis is also frequently observed. Fibrosis is present in all but the mildest forms of AIH. It causes distortion of the hepatic lobule and the appearance of regenerative nodules, resulting in cirrhosis. Many patients with acute presentation may have chronic features on liver biopsy indicating a subclinical phase of disease and several patients with mild clinical disease may have advanced fibrosis on biopsy. Of important note is the fact that the fibrosis and even cirrhosis in AIH is reversible to a significant degree with immunosuppressive therapy unlike in other chronic liver diseases (5)
Tests and procedures used to diagnose autoimmune hepatitis include, Blood tests. Testing a sample of your blood for antibodies can distinguish autoimmune hepatitis from viral hepatitis and other disorders with similar symptoms. Antibody tests also help pinpoint the type of autoimmune hepatitis you have. Liver biopsy. Doctors perform a liver biopsy to confirm the diagnosis and to determine the degree and type of liver damage. During the procedure, a small amount of liver tissue is removed, using a thin needle that's passed into your liver through your skin. The sample is then sent to a laboratory for analysis. Your doctor may use ultrasound to guide the biopsy (3).
Autoimmune hepatitis that goes untreated can cause permanent scarring of the liver tissue (cirrhosis). Complications of cirrhosis include: Fluid in your abdomen (ascites) which is when liver disease can cause large amounts of fluid to accumulate in your abdomen. Ascites can be uncomfortable and may interfere with breathing and is usually a sign of advanced cirrhosis. It can also cause liver failure. This occurs when extensive damage to liver cells makes it impossible for your liver to function adequately. At this point, a liver transplant is needed. Lastly it causes liver cancer. People with cirrhosis have an increased risk of liver cancer (6).
Whatever type of autoimmune hepatitis you have, the goal of treatment is to slow or stop the immune system attack on your liver. This may help slow the progression of the disease. To meet this goal, you’ll need medications that lower immune-system activity. Treatment with prednisone is generally used initially. A second medication, azathioprine may be recommended in addition to prednisone. Prednisone, especially when taken long term, can cause a wide range of serious side effects, including diabetes, thinning bones (osteoporosis), broken bones (osteonecrosis), high blood pressure, cataracts, glaucoma and weight gain.
Doctors typically prescribe prednisone at a high dose for about the first month of treatment. Then, to reduce the risk of side effects, they gradually reduce the dose over the next several months until reaching the lowest possible dose that controls the disease. Adding azathioprine also helps you avoid prednisone side effects. Most people need to continue taking the prednisone for at least 18 to 24 months, and many remain on it for life. Although you may experience remission a few years after starting treatment, the disease often returns if the drug is discontinued.
When medications don't halt the progress of the disease, or you develop irreversible scarring (cirrhosis) or liver failure, the remaining option is a liver transplant. During a liver transplant, your diseased liver is removed and replaced by a healthy liver from a donor. Liver transplants most often use livers from deceased organ donors. In some cases, a living-donor liver transplant can be used. During a living-donor liver transplant, you receive only a portion of a healthy liver from a living donor. Both livers begin regenerating new cells almost immediately (7,8).
Autoimmune hepatitis is one of the few liver diseases with excellent response to therapy. On the other hand, it still remains a liver disease with many unanswered questions, particularly in respect to its etiology and pathogenesis. There is significant heterogeneity in its presentation that may mask its identity, affect its clinical behavior, and confound its management. It may start with a fulminant course, and the diagnosis should not be overlooked when dealing with patients with acute liver failure. Alternatively, it may behave as a slowly progressing disease, and it is still controversial whether those patients need immunosuppressive treatment at all. There is no prescribed minimum or maximum duration of treatment. Over the last decade, remarkable progress has been made in understanding and clarifying the areas of diagnosis with introduction of classification criteria, and broadening therapeutic options, with trial of several new medications like budesonide and mycophenolate mofetil, and more in the pipeline. Management, however, still faces several other important issues, such as in children, the elderly, in males, and during the preconception period, pregnancy, and lactation. A key to successful management is thinking of it, recognizing the nonclassical presentations, and individualizing therapy.

References
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2. H. G. Kunkel, A. E. Eisenmenger, A. M. Bougiovanni, and R. J. Slater, “Extreme hypergammaglulinemia in young women with liver disease of unknown etiology,” Journal of Clinical Investigation, vol. 30, pp. 654–659, 1951.
3. Makol, Ashima, Kymberly D. Watt, and Vaidehi R. Chowdhary. "Autoimmune hepatitis: a review of current diagnosis and treatment." Hepatitis research and treatment 2011 (2011).
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5. Manns, Michael P., et al. "Diagnosis and management of autoimmune hepatitis." Hepatology 51.6 (2010): 2193-2213.
6. Roberts, STUART K., Terry M. Therneau, and ALBERT J. Czaja. "Prognosis of histological cirrhosis in type 1 autoimmune hepatitis." Gastroenterology 110.3 (1996): 848-857.
7. Czaja, Albert J. "AUTOIMMUNE HEPATITIS: TREATMENT." GI/Liver Secrets Plus (2014): 133.
8. Chu, Z. Q., and L. Y. Sun. "Autoimmune hepatitis and liver transplantation." Zhonghua gan zang bing za zhi= Zhonghua ganzangbing zazhi= Chinese journal of hepatology 15.1 (2007): 74.