Autoimmune Hepatitis (AIH): Overview, Types and Biomarker Tests 

What Is Autoimmune Hepatitis?

Autoimmune hepatitis is a chronic inflammatory liver disease in which resulting in ongoing inflammation and tissue damage. Unlike viral or toxin-related hepatitis, this condition arises from an overactive immune response that treats healthy liver tissue as a threat, resulting in ongoing inflammation and tissue damage.

It can occur at any age but is most commonly seen in women between 15 and 40 years old. Over time, persistent inflammation can cause scarring (fibrosis) and, if left untreated, may progress to cirrhosis or even liver failure.

According to the National Institutes of Health (2023), autoimmune hepatitis is believed to result from a combination of genetic susceptibility, environmental triggers, such as infections or certain medications, and failure of immune regulation, together causing chronic inflammation of liver cells and eventual fibrosis.

Types of Autoimmune Hepatitis

Understanding the different types of autoimmune hepatitis helps doctors determine the most appropriate treatment approach for each patient.

Type 1 Autoimmune Hepatitis

Type 1 autoimmune hepatitis is the most common form, accounting for about 80% of cases and usually affecting adults. It is marked by antibodies such as ANA and ASMA in the blood and often occurs alongside other autoimmune diseases such as thyroid disorders, rheumatoid arthritis, or inflammatory bowel disease. Most people with Type 1 disease respond well to standard immunosuppressive treatment.

Type 2 Autoimmune Hepatitis

Type 2 autoimmune hepatitis mainly affects children and young adults, accounting for about 20% of cases and is identified by anti-LKM1 antibodies in blood tests. It is usually more aggressive than Type 1, often presenting with severe symptoms and requiring prompt treatment to prevent rapid liver damage.

What Causes Autoimmune Hepatitis?

Autoimmune hepatitis causes likely develop from a combination of genetic susceptibility and environmental triggers. In genetically predisposed individuals, viral infections such as hepatitis A, B, C, Epstein–Barr virus, or measles, as well as certain medications and toxins, may trigger an abnormal immune response directed against the liver.

Hormonal factors also influence disease risk, which may explain why women are affected more frequently than men. The condition may become more noticeable during periods of hormonal change, such as pregnancy or menopause.

Risk Factors for Autoimmune Hepatitis

Several factors may increase your likelihood of developing autoimmune hepatitis:

• Gender: Women are four times more likely to develop this condition than men
• Age: Most commonly diagnosed between ages 15-40, though it can occur at any age
• Family history: Having relatives with autoimmune diseases increases your risk
• Existing autoimmune conditions: Having conditions like type 1 diabetes, thyroid disease, or rheumatoid arthritis
• Genetic factors: Certain genetic markers, particularly HLA-DR3 and HLA-DR4, are associated with increased risk
• Ethnicity: Some populations show higher prevalence rates

Autoimmune Hepatitis Symptoms

Recognizing autoimmune hepatitis symptoms early can lead to prompt treatment and better outcomes. However, symptoms often develop gradually and may be subtle initially.

Common symptoms include:

• Persistent fatigue and weakness
• Abdominal pain, particularly in the upper right area
• Joint pain and muscle aches
• Nausea and loss of appetite
• Unintentional weight loss
• Jaundice (yellowing of the skin and eyes)
• Dark-coloured urine
• Pale or clay-coloured stools
• Skin rashes or itching
• Easy bruising or bleeding

Early vs Advanced Symptoms

Complications of Untreated Autoimmune Hepatitis

Without proper treatment, autoimmune hepatitis can lead to serious complications:

• Liver fibrosis: Progressive scarring that replaces healthy liver tissue
• Cirrhosis: Advanced scarring that severely impairs liver function
• Portal hypertension: Increased pressure in the liver blood vessels
• Liver failure: Complete loss of liver function that may require liver transplantation
• Hepatic encephalopathy: Brain dysfunction due to toxin buildup
• Increased cancer risk: Higher likelihood of developing liver cancer

When to See a Doctor

You should seek medical attention if you experience:

• Persistent fatigue lasting several weeks
• Unexplained abdominal pain or swelling
• Yellowing of your skin or eyes
• Dark urine combined with pale stools
• Unusual bruising or bleeding
• Significant loss of appetite or weight loss

How Autoimmune Hepatitis Is Diagnosed

Diagnosing autoimmune hepatitis involves several steps:

1. Medical history and physical examination: Your doctor will assess symptoms and look for signs of liver disease
2. Blood tests: Including liver function tests to check for elevated liver enzymes
3. Autoantibody testing: Identifying specific antibodies that indicate autoimmune hepatitis
4. Liver biopsy: Obtaining a small tissue sample to confirm inflammation patterns
5. Imaging studies: Ultrasound or CT scans to assess liver structure

Key Autoantibodies in Autoimmune Hepatitis

Different antibodies help identify specific types:

• Type 1: ANA (antinuclear antibodies) and ASMA (anti-smooth muscle antibodies)
• Type 2: Anti-LKM1 (anti-liver/kidney microsomal) and anti-LC1 (anti-liver cytosol)
• Additional markers: Anti-SLA/LP (soluble liver antigen/liver pancreas) antibodies

Liver Function Test Indicators

Blood tests revealing elevated liver enzymes often provide the first clue to autoimmune hepatitis:

• Autoimmune antibody panels (Autoimmune Liver Disease Profiles, LKM1, SLA, LC-1) to detect specific autoantibodies linked to Type 1 and Type 2 autoimmune hepatitis.
• Liver function tests (LFTs), AST (SGOT) and ALT (SGPT) to assess liver inflammation and overall liver health.
• Fibrosis assessment (ActiTest, FibroTest, FibroMax) and liver biopsy to grade inflammation, stage fibrosis, and guide long-term management.

Treatment Options for Autoimmune Hepatitis

Effective autoimmune hepatitis treatment focuses on suppressing the immune system to reduce liver inflammation and prevent further damage. Treatment success depends on early diagnosis and consistent medication adherence.

The primary goal is achieving remission, where liver inflammation subsides, and liver function tests normalise. Most patients require long-term treatment to maintain remission and prevent disease flares.

First-Line Medications

Standard treatment typically begins with:

• Prednisolone: A corticosteroid that rapidly reduces liver inflammation
• Azathioprine: An immunosuppressant often combined with steroids
• Combination therapy: Using both medications together often provides optimal results
• Budesonide: An alternative steroid with fewer side effects for some patients

Second-Line or Alternative Medications

When first-line treatments aren't effective or cause intolerable side effects:

• Mycophenolate mofetil: Alternative immunosuppressant
• Tacrolimus: Calcineurin inhibitor for resistant cases
• Cyclosporine: Another calcineurin inhibitor option
• Rituximab: Biological therapy for severe cases
• 6-mercaptopurine: Metabolite of azathioprine

Long-Term Medication Management

Managing autoimmune hepatitis requires careful monitoring and gradual dose adjustments. Your doctor will regularly assess your response to treatment through blood tests and adjust medications accordingly.

Most patients need to continue treatment for several years, with some requiring lifelong therapy. The goal is to find the lowest effective dose that maintains remission while minimizing side effects.

Lifestyle Changes for Autoimmune Hepatitis

Supporting your treatment with healthy lifestyle choices can improve outcomes:

• Avoid alcohol completely: Alcohol can worsen liver inflammation and interfere with medications
• Maintain a balanced diet: Focus on nutrient-rich foods to support liver health
• Exercise regularly: Engage in light to moderate exercise to maintain overall health and reduce fatigue
• Get adequate rest: Proper sleep supports immune system function
• Manage stress: Chronic stress may worsen autoimmune conditions
• Stay up-to-date with vaccinations: Immunosuppressive medications increase infection risk

When a Liver Transplant Is Needed

Liver transplantation becomes necessary when autoimmune hepatitis progresses to end-stage liver disease despite treatment. This typically occurs in patients diagnosed late or those who don't respond adequately to immunosuppressive therapy.

Transplant candidates undergo extensive evaluation to ensure they're suitable for surgery. The five-year survival rate after liver transplantation for autoimmune hepatitis is approximately 85–90%, making it an effective treatment for advanced cases.

Autoimmune Hepatitis After Liver Transplant

Interestingly, autoimmune hepatitis can recur in the transplanted liver in approximately 20–30% of patients. This recurrence typically develops several years after transplantation and requires resumed immunosuppressive treatment.

Regular monitoring after transplantation includes blood tests and periodic liver biopsies to detect early signs of recurrence or rejection.

Prognosis & Long-Term Outlook

With proper treatment, the prognosis for autoimmune hepatitis is generally good. About 80% of patients achieve remission within two years of initiating treatment. Many people with well-controlled autoimmune hepatitis can expect a normal lifespan.

However, long-term success depends on early diagnosis, appropriate treatment, and consistent medication adherence. Regular monitoring helps detect any changes in disease activity and adjust treatment accordingly.

Biomarkers in Autoimmune Hepatitis

A series of specialized blood tests can be used to determine the proper functioning of the liver. These include:

1. Antinuclear Antibody (ANA) Test

This blood test looks for the presence of antinuclear antibodies in the blood. Proteins made by your immune system to fight foreign substances are known as antibodies, but antinuclear antibodies attack healthy cells. ANA is positive in about 50-75% of patients who have autoimmune hepatitis. Antinuclear Antibody Test serves as a key diagnostic finding in autoimmune hepatitis (AIH) type 1.

2. Smooth Muscle Antibody (SMA) Test

This test looks for the presence of smooth muscle antibodies — a type of autoantibody — in the blood. Smooth muscle tissues in the liver and other parts of the body are attacked by SMAs. In addition to diagnosing the presence of AIH, this test is also used to determine if the disorder is type 1 or type 2.

3. Liver Kidney Microsome Type 1 (anti-LKM-1) Test

Liver kidney microsome type 1 is a type of autoantibody that recognises and targets its own enzyme called cytochrome P450 2D6 (CYP2D6), which is a protein found primarily in the liver cells. Liver kidney microsome type 1 (anti-LKM-1) test detects and measures the amount of anti-LKM-1 in the blood. The presence of this indicates autoimmune hepatitis type 2.

4. Antimitochondrial Antibody (AMA) M2 Test

Antimitochondrial antibodies (AMA) are formed against mitochondria — the energy source of your cells. The presence of the M2 antigens of AMA indicates AIH.

5. M2 3E Test

M2 3E is a fusion protein that consists of different subunits of the M2 enzyme complex of mitochondria. Its presence is used to aid in the diagnosis of primary biliary cirrhosis and AIH.

6. Sp100 Test

Sp100 antibodies are typically detected in patients with liver ailments such as primary biliary cholangitis and AIH. The test is recommended when patients test negative for AMA.

7. PML Test

Promyelocytic leukaemia (PML) protein is a type of antinuclear antibody (ANA) that is associated with the presence of autoimmune hepatitis.

8. GP-210 Test

Gp210 is an integral glycoprotein of the nuclear pores. Patients suffering from AIH frequently produce autoantibodies against gp-210. Thus, this test is used in conjunction with others to determine the presence of liver ailments such as AIH and even primary biliary cirrhosis (PBC). Research suggests that the presence of antibodies is a strong marker for the disease and is also associated with an aggressive disease course.

9. LC-1 Antibody Test

The Liver Cytosolic Antigen Type 1 (LC-1) Antibody test is used to evaluate for autoimmune hepatitis of unknown aetiology in combination with Liver-Kidney Microsome - 1. More than 50% of cases with type 2 AIH show the presence of antibodies against LC-1.  Although it is most commonly seen with LKM-1 antibodies, there have been instances of its presence as isolated occurrences in about 10% of cases. A high level of anti-LC-1 is associated with a more serious disease course.

10. Anti SLA/LP Test

Antibodies against soluble liver antigen/liver pancreas (anti-SLA/LP) are highly specific for autoimmune hepatitis (AIH) type 1. It is a strong marker for the disease and has been linked with a more aggressive strain of the disease, frequent relapses after treatment withdrawal and challenging clinical outcomes. Anti-SLA may occur without the presence of ANA and or SMA.

11. Anti Ro-52 Test

The Ro-52 antigen is a complex ribonucleoprotein, and antibodies against Ro-52 are associated with several different autoimmune conditions, including autoimmune hepatitis.

The Bottom Line

Autoimmune Hepatitis is a challenging disease, but one which can be controlled and managed if diagnosed early and you undergo treatment for the same. The above-mentioned biomarkers are indicators of the disease and serve as determinants of the disease’s presence as well as sub-type. Metropolis conducts a complete spectrum of liver profile tests to diagnose autoimmune hepatitis and provide definitive results which can help your healthcare provider determine your future course of treatment. Do understand that a further series of tests along with a liver biopsy may be required for confirmation of the disease as well as its progressive stage.

Please do not hesitate to connect with us or with your healthcare provider for a greater understanding of the above-mentioned biomarkers.

Conclusion

Autoimmune hepatitis is a long-term condition, but with early diagnosis, proper treatment, and regular monitoring, many people can prevent serious complications like liver fibrosis and cirrhosis. Recognizing symptoms early, getting the right tests, and maintaining consistent follow-up care are key to protecting your liver health.

For this, you need reliable diagnostics. Metropolis Healthcare offers 4000+ tests, including specialised liver and autoimmune panels, as well as comprehensive health checkups with quick turnaround and accurate results. With 10,000+ home collection touchpoints and easy booking via website, app, call, or WhatsApp, you can get speciality testing done from the comfort of your home—so you can focus on treatment while Metropolis takes care of your diagnostic needs.

FAQs

What triggers autoimmune hepatitis?

• Genetic predisposition
• Viral infections
• Certain medications
• Environmental toxins
• Immune system imbalance

What are the early symptoms of autoimmune hepatitis?

• Mild fatigue
• Joint pain
• Elevated liver enzymes
• Loss of appetite

Is autoimmune hepatitis curable?

Autoimmune hepatitis is not fully curable, but it is highly manageable. With lifelong monitoring and medication, most people achieve remission and prevent liver damage.

How serious is autoimmune hepatitis?

If not treated promptly, it can lead to cirrhosis, liver failure, or the need for a transplant. With proper treatment, the prognosis is significantly improved.

What foods should be avoided in autoimmune hepatitis?

• Alcohol
• Fried foods
• High-sodium packaged foods
• Sugary beverages
• Excessive red meat

How is autoimmune hepatitis diagnosed?

Diagnosis is made through blood tests, autoantibody panels, imaging studies, and liver biopsy to confirm inflammation and fibrosis.

Can autoimmune hepatitis lead to cirrhosis?

Yes. Chronic inflammation can cause scarring (liver fibrosis), which may progress to cirrhosis if untreated.

Can autoimmune hepatitis come back after treatment?

Relapses are common if medications are stopped abruptly. Lifelong monitoring is necessary to maintain remission.

Does stress worsen autoimmune hepatitis?

Stress does not directly cause autoimmune hepatitis but may worsen symptoms or trigger flare-ups in some individuals.