Introduction
Autoimmune hepatitis (AIH) is an autoinflammatory disease (when the immunity works against liver cells). It is a chronic disease that usually affects women but can occur at all ages. The exact cause is unclear, but a loss of immune tolerance (unresponsiveness of the immune system) due to genetic and environmental factors is the potential disease trigger).
Untreated AIH can lead to cirrhosis (liver damage due to scarring) and end-stage liver disease. AIH can be controlled with drugs that suppress the immune system when diagnosed and treated early. However, a liver transplant is done in end-stage liver disease or when AIH does not respond to drug treatments.
The characteristics of AIH are hypergammaglobulinemia (a condition in which the white blood cells make excess antibodies), circulating auto-antibodies (antibodies against self), and distinctive microscopic patterns. Based on these, the International Autoimmune Hepatitis Group (IAIHG) has established diagnostic criteria for a correct diagnosis. However, AIH diagnosis is clinical, as there are no exact guidelines.
How is Autoimmune Hepatitis Diagnosed?
Doctors diagnose AIH based on medical history, physical examination, and investigations.
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Medical History- The doctor enquires about the symptoms and other factors for liver damage. Symptoms include abdominal pain, fatigue, weight loss, nausea, confusion, and itchy skin. Other autoimmune diseases associated with AIH are inflammatory bowel disease (IBD) and thyroid conditions.
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Physical Examination- Physical examination checks for liver damage signs, such as jaundice (yellowish discoloration of the whites of the eyes), skin changes, liver or spleen enlargement, abdominal swelling or tenderness, and edema (swelling).
What Are the Various Investigations for Autoimmune Hepatitis?
The diagnosis of acute AIH is challenging. AIH typically exhibits as a chronic disease with a subtle onset. Hence, patients may get diagnosed after the incidental discovery of abnormal liver function tests (LFTs). Up to 20 percent of patients may develop acute liver failure (ALF). The acute presentation of the disease is more common in children. On the other hand, the subtle onset is more frequently observed in adults. There is no single diagnostic test for AIH. The diagnosis is primarily based on clinical, serological, biochemical, and histological findings.
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Blood Panel- A complete blood count (CBC) checks the red and white blood cells and platelet counts. Further, testing the blood sample for antibodies can distinguish AIH from viral hepatitis and other liver conditions. Antibody tests also can pinpoint the type of AIH.
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Liver Tests- Liver tests check alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels (liver enzymes). ALT and AST are raised significantly in AIH patients. ALT and AST levels are assessed to follow the disease progress and treatment response.
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Antibody Tests- The autoantibodies raised in AIH are antinuclear antibodies (ANA) and anti-smooth muscle antibodies (SMA). Type 1 AIH (AIH-1; the predominant type of AIH in adults and children) shows positivity for antinuclear antibodies (ANA) and anti-SMA, which can be detected in many patients. ANAs are variable markers during AIH. On the contrary, higher SMA concentration positively correlates with histologic and biochemical disease activity.
Type 2 AIH (AIH-2; accounts only for about five to ten percent of cases in children) has predominant levels of anti-liver/kidney microsomal type 1 (anti-LKM-1) or anti-liver cytosol type 1 (anti-LC-1) antibody. Antibody tests warrant repeated examination in children as liver-related antibody concentrations correlate with disease activity and age. Further, the treatment response corresponds to the reduction or disappearance of serum antibodies. Regular autoantibody testing in adults is currently not done due to insufficient data for antibodies as inflammatory disease activity markers. Furthermore, hypergammaglobulinemia is assessed by blood tests to check levels of immunoglobulin G (IgG).
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Liver Histology- Liver histology involves a liver biopsy. It comprises removing a piece of tissue from the liver. Further, a pathologist assesses liver damage and features of specific liver diseases. It is also helpful for AIH features and to check scarring if a patient has cirrhosis. Liver biopsy is a critical element in the differential diagnosis of liver disease and an independent factor to distinguish AIH from other liver illnesses. Liver histology is paramount in the initial diagnosis and long-term follow-up as it allows for disease staging, treatment monitoring, and assessment for inflammation and fibrosis.
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Imaging-
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Ultrasound- Ultrasound uses a transducer (a hand-held device) that reflects safe and painless sound waves from organs to create images on a screen. An ultrasound can show liver enlargement, abnormal shape, texture, and blocked bile ducts.
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Computed Tomography (CT)- CT uses X-rays and computer technology to create images. A CT scan can show the liver's size and shape. Furthermore, it is helpful to check the signs of cirrhosis.
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Magnetic Resonance Imaging (MRI)- MRI produces detailed images of organs and soft tissues (X-rays are not used) with radio waves. Similarly to CT, an MRI scan can reveal cirrhosis. Advanced MRI scans can also estimate the fat amount in the liver.
What Are the Diagnostic Criteria for Autoimmune Hepatitis?
The first diagnostic criteria were established in 1992 by the IAIHG, and revised in 1999. However, the revised criteria included complex and questionable parameters. The revised criteria were proposed to compare studies from different centers.
Consequently, scientists suggested simplified criteria to facilitate applicability in routine clinical practice. These criteria include the measurement of autoantibodies (ANA, SMA, anti-LKM-1), immunoglobulin G levels (serum concentrations of globulins or IgG above a normal range), liver histology evaluation, and viral hepatitis exclusion (exclusion of viral markers for HAV, HBV, and HCV). A score of 6 is considered a probable AIH, and a score of ≥7 is a definite AIH. Data show that the simplified criteria have a sensitivity (positive disease result) of more than 80 percent and a specificity (negative disease result) of more than 95 percent for AIH diagnosis.
The final diagnosis of AIH is clinical despite the availability of diagnostic criteria. However, a physical examination does not add substantial value to a solid diagnosis. It is because symptoms such as fatigue, abdominal pain, jaundice, and itching are nonspecific and only indicate liver failure. However, AIH should be considered in any acute or chronic liver disease patient. Also, it should be speculated if there are increased serum aminotransferases, high immunoglobulins, high concentrations of circulating antibodies, and other autoimmune diseases.
Conclusion
The AIH scoring systems display acceptable sensitivity and specificity for clinical practice. However, exact diagnostic tools are still in demand. Establishing a correct diagnosis of AIH takes time and effort. Further, the clinical management of AIH is also a challenging journey. Although AIH diagnosis is made clinically by applying diagnostic scores, the varied disease presentation makes the rapid determination of the disease difficult.
