Autoimmune hepatitis (AIH)

Autoimmune hepatitis is a liver disease resulting from the immune system’s attack on liver cells (hepatocytes). This process leads to progressive organ damage, causing inflammation and fibrotic replacement of the liver tissue.

The cause of autoimmune hepatitis is an error in recognizing hepatocytes as foreign to the body; however, why this occurs is not yet fully understood. The immune system’s primary role is to defend the body against pathogens, such as bacteria and viruses. In certain conditions, not well elucidated, it may mistakenly target certain organs, including the liver. Recent research indicates that, in genetically predisposed individuals, specific drugs or certain infections may contribute to triggering the disease.

It’s important not to confuse autoimmune hepatitis with other forms of hepatitis, such as viral hepatitis (A, B, C, or E), where a recognized virus causes damage to liver cells. Unlike viral hepatitis, autoimmune hepatitis is not transmissible from person to person.

Left untreated, liver damage can progress, and inflammation can lead to the destruction of liver tissue, replaced by scar tissue (fibrosis). In advanced stages, this can result in cirrhosis, accompanied by various complications.

As is common in most autoimmune diseases, autoimmune hepatitis predominantly affects women and can develop at any age, with a peak frequency between 40 and 70 years. The estimated prevalence is approximately 15 individuals per 100,000. However, the disease can also manifest at a young age, with more aggressive symptoms and a faster progression. There are three forms of the disease:

• Type 1: The most common form, occurring at any age, is characterized by positivity to antinuclear antibodies (ANA) or anti-smooth muscle antibodies (ASMA). In approximately half of the patients, it is associated with other autoimmune diseases (ulcerative colitis, thyroiditis, rheumatoid arthritis, etc.).
• Type 2: More frequent in young women with other autoimmune-based pathologies, distinguished by positivity to liver-kidney microsomal antibodies (LKM1).
• Type 3: Characterized by positivity to other types of autoantibodies (anti ALS/LP).

The clinical manifestations of autoimmune hepatitis can vary widely. Initial acute symptoms can be severe and evident, presenting with fever and scleral and skin jaundice (yellowing of the skin and eyes). Symptoms may manifest more subtly with abdominal pain or heaviness in the upper right part of the abdomen, along with nausea and vomiting. Other, more nonspecific manifestations may include widespread joint pain, itching, fatigue, and loss of the menstrual cycle in women.

As fibrosis advances and the disease progresses to cirrhosis, typical symptoms of advanced liver disease become apparent, common to all forms of chronic damage:

• Abnormalities of the small capillaries of the skin (cutaneous angiomas)
• Yellow discoloration of the skin and eyes (jaundice)
• Swelling of the ankles and feet (edema)
• Accumulation of fluid in the abdomen (ascites)
• Gastrointestinal bleeding caused by the rupture of esophageal veins, secondary to increased pressure in the venous system upstream of the liver.
• Mental confusion and motor slowing (porto-systemic encephalopathy), resulting from the accumulation of waste circulating in the blood and secondary to liver malfunction.

The association with other autoimmune diseases, such as celiac disease, autoimmune thyroid disorders, rheumatoid arthritis, scleroderma, etc., is well-known.

Autoimmune hepatitis can also be linked to other autoimmune liver diseases within the framework defined as an “overlap“ syndrome. This may involve an association between autoimmune hepatitis and primary biliary cholangitis, where the characteristics and diagnostic criteria for both diseases are present in the same individual. Alternatively, there may be an association between autoimmune hepatitis and primary sclerosing cholangitis, wherein a coexistence of characteristics from these two pathological processes is observed.

The clinical suspicion of autoimmune hepatitis is based on clinical manifestations, the patient’s medical history, and tests, including laboratory and radiological examinations, as well as histological data obtained through a liver biopsy.

Specific checks include:

• Laboratory tests: liver function tests (transaminase, gammaGT, alkaline phosphatase, bilirubin), measurement of specific immunoglobulins (IgG, IgA, and IgM).
• Measurement of autoantibodies in the blood, particularly ANA (anti-nucleus antibodies), ASMA (anti-smooth muscle antibodies), and LKM (anti-liver-kidney microsomal antibodies).
• Abdominal ultrasound.
• Liver biopsy, necessary to identify histological findings typical of autoimmune hepatitis, determining the degree of fibrosis and inflammation, and the stage of liver fibrosis at diagnosis.

Second-level radiological tests may be required, such as abdominal CT with contrast, magnetic resonance imaging with and without contrast, especially with a cholangiographic study of the biliary ducts. Once the diagnosis is confirmed, the specialist can request specific exemptions for pathology (code 016.571.4), providing patients with free access to certain diagnostic tests like blood tests and abdominal ultrasound for monitoring and treating the disease.

The therapeutic goal for autoimmune hepatitis is to reduce or, if possible, eliminate inflammation in the liver, preventing or limiting the formation of fibrosis.

The drugs used act on the immune system, reducing its activity. The most commonly used medications are corticosteroids such as prednisone, taken orally every day at progressively reduced doses. After an initial period, another immunosuppressant, azathioprine, is often added, also in tablet form for daily intake. This treatment typically requires long-term use, often for years, and, in many cases, becomes a lifelong regimen for the patient.

The response to this treatment regimen is usually favorable. For patients who do not respond, alternative immunosuppressant treatments are considered, depending on the experience of the medical center.

In cases where the disease progresses, is diagnosed at advanced stages, or has an acute onset, the patient may be considered a candidate for a liver transplant.