Autoimmune Hepatitis isn't just a liver issue-it's your immune system attacking your own liver. Over 100,000 people in the U.S. alone have it, but most don't know it exists until symptoms hit hard. This rare condition affects 10-25 people per 100,000 globally, with women four times more likely to develop it than men. Without treatment, it can lead to cirrhosis or liver failure. Here's what you need to know about diagnosis, why steroids and azathioprine are the standard treatment, and what to expect long-term.
What is Autoimmune Hepatitis?
Autoimmune Hepatitis (AIH) is a chronic disease where your immune system mistakenly targets liver cells. First described as 'lupoid hepatitis' in the 1950s, it was recognized as a distinct condition in the 1960s when researchers found autoantibodies and saw patients respond to immunosuppressants. Today, the 2025 European Association for the Study of the Liver (EASL) guidelines confirm it affects 2-18 people per 100,000 annually, with rising cases worldwide.
How is Autoimmune Hepatitis Diagnosed?
Diagnosis isn't simple. Doctors use blood tests, biopsies, and exclusion of other liver diseases. Here's how it works:
- Blood tests check for elevated immunoglobulin G (IgG) levels (over 1.5x normal) and autoantibodies like Antinuclear antibodies (ANA) or Smooth muscle antibodies (SMA) at titers ≥1:40. For type 2 AIH, Liver-kidney microsomal antibodies (LKM1) are key.
- Liver biopsy is mandatory. It must show interface hepatitis (inflammation at the portal-parenchymal boundary) in at least 20 portal tracts. Biopsies use ultrasound guidance with a 16-18 gauge needle, carrying a 0.1-0.3% risk of major complications like bleeding.
- Diagnostic scoring uses the Revised IAIHG system. Scores over 15 mean probable AIH; over 20 confirm definite AIH. ALT and AST levels typically show 5-10x the upper limit of normal in active disease.
The 2025 EASL guidelines no longer subclassify AIH based on autoantibody profiles. Experts agree these distinctions don't change treatment decisions-only the overall clinical picture matters.
Steroids and Azathioprine: The Standard Treatment
Since the 1970s, the go-to treatment has been prednisone and azathioprine. Here's why:
- Prednisone starts at 0.5-1 mg per kg of body weight daily (max 60 mg/day), tapered down to 10-15 mg/day by week 8. It quickly reduces liver inflammation.
- Azathioprine begins at 50 mg/day, increasing to 1-2 mg/kg (max 150 mg/day). This drug helps maintain remission while allowing lower prednisone doses.
Combination therapy cuts steroid side effects by half compared to prednisone alone. Studies show 70-80% reduction in prednisone dose by six months, with 60-80% of patients achieving full biochemical remission within 18-24 months.
Managing Treatment Side Effects
While effective, these drugs come with challenges. Prednisone side effects include:
- Moon face and rapid weight gain (52% of patients)
- Mood swings and insomnia (47%)
- Increased diabetes risk (15%) and osteoporosis (20%)
Azathioprine can cause:
- Severe nausea or pancreatitis (35% of cases)
- Bone marrow suppression (12%)
- Fatigue (28%)
Thiopurine S-methyltransferase (TPMT) testing before starting azathioprine is critical. This prevents severe blood issues in the rare 0.3% with complete enzyme deficiency. The 2025 EASL guidelines require this test, though only 45% of U.S. centers currently follow it. Real-world data from the 2024 Global Autoimmune Institute Patient Registry shows 68% of patients experience at least one treatment-related side effect. One Reddit user described steroid effects as 'moon face that made me unrecognizable, 30 pounds of fluid weight in 3 weeks, and insomnia that felt like permanent jet lag.' Another reported azathioprine caused pancreatitis at 100mg, forcing a switch to mycophenolate.
Long-Term Monitoring and Care
Regular check-ups are critical. During initial treatment, blood tests for Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) happen every 2-4 weeks. After stabilization, they drop to every 3 months. IgG levels are checked quarterly. A repeat liver biopsy after 18-24 months confirms histological remission in 50-70% of cases. Before starting treatment, hepatitis B testing is mandatory due to 15-20% risk of reactivation. Vaccinations for hepatitis A and B should be done before immunosuppression, as vaccine efficacy drops to 40-60% in treated patients versus 90% in healthy people.
What's New in AIH Treatment?
The 2025 EASL guidelines introduced major changes, like removing autoantibody-based subclassification. Second-line options include Mycophenolate mofetil (CellCept) for patients who don't respond to first-line therapy. Ongoing trials for JAK inhibitors like tofacitinib show 55% response rates in refractory cases. The FDA recently designated obeticholic acid as a breakthrough therapy for AIH, with phase 3 trials showing 42% complete response compared to 28% with standard treatment.
Frequently Asked Questions
How is autoimmune hepatitis diagnosed?
Diagnosis involves blood tests for autoantibodies (ANA, SMA, LKM1), IgG levels, and a liver biopsy. The biopsy must show interface hepatitis in at least 20 portal tracts. The Revised IAIHG scoring system confirms diagnosis-scores over 20 indicate definite AIH. Doctors also rule out viral hepatitis and other liver conditions before confirming AIH.
Why are steroids and azathioprine used together?
Steroids like prednisone reduce inflammation quickly, but long-term use causes severe side effects. Azathioprine acts as a steroid-sparing agent, allowing doctors to lower the prednisone dose. This combo cuts steroid-related side effects by half while maintaining effectiveness. Studies show 70-80% reduction in prednisone dose by six months with this approach.
What are common side effects of prednisone?
Prednisone side effects include weight gain, moon face, mood swings, insomnia, and increased risk of diabetes or osteoporosis. About 70% of patients on steroid-only treatment experience side effects, but combining it with azathioprine reduces this to 30%. Regular bone density scans and blood sugar monitoring help manage these risks.
Can autoimmune hepatitis be cured?
There's no cure, but treatment can achieve remission. About 60-80% of patients reach biochemical remission within 18-24 months. However, 50-90% relapse if treatment stops, so most need lifelong maintenance therapy. Some patients may eventually stop treatment after years of remission, but this requires careful monitoring under a specialist's guidance.
What happens if treatment doesn't work?
If no improvement after 12-18 months, doctors switch to second-line therapies like mycophenolate mofetil or calcineurin inhibitors. About 10-15% of patients require these alternatives. New treatments like JAK inhibitors and monoclonal antibodies targeting interleukin-6 are showing promise in clinical trials, offering hope for refractory cases.
Why is TPMT testing important before azathioprine?
TPMT testing checks for enzyme activity that breaks down azathioprine. The rare 0.3% with complete deficiency face a 30-fold higher risk of severe bone marrow suppression. The 2025 EASL guidelines require this test before starting azathioprine, though only 45% of U.S. centers currently follow this protocol. Skipping this test can lead to life-threatening complications.