Autoimmune hepatitis: when the immune system attacks the liver

Autoimmune Hepatitis: When the Immune System Attacks the Liver

Autoimmune hepatitis is a chronic inflammation of the liver where, for unexplained reasons, the immune system targets the liver's own cells. Left untreated, it often leads to cirrhosis and liver failure over several years. Treatment can dampen the inflammation, but the course is individual, and treatment is planned and monitored by a specialist. The disease is seen most often in women and can begin at any age.

Autoimmune hepatitis is rare. Symptoms can be non-specific and resemble other liver diseases such as viral hepatitis, fatty liver, or drug-induced liver injury.

What are the symptoms?

Autoimmune hepatitis can manifest in many different ways. Typical symptoms include:

• Fatigue disproportionate to sleep and work
• Abdominal pain or discomfort under the right rib cage
• Loss of appetite, nausea, and weight loss
• Joint pain, often in fingers and knees, that migrates
• Itching and jaundice (yellow eyes and skin) when liver enzyme levels are highly elevated
• Dark urine and pale stools
• Minor bleeding and bruising if the liver is severely affected

Up to a third of patients have no symptoms at diagnosis and are discovered incidentally through a blood test showing elevated liver enzymes. Another group presents acutely with severe jaundice and may clinically resemble an acute viral infection.

Why does it happen?

The exact cause is unknown, but three interacting factors are involved:

• Genetic predisposition with certain HLA types (HLA-DR3, DR4)
• Triggering factor such as a viral infection, a drug reaction, or a hormonal change
• Loss of tolerance leading the immune system to produce antibodies against liver cells

Up to a quarter of patients also have another autoimmune disease: thyroid disease (Hashimoto's), coeliac disease, type 1 diabetes, vitiligo, or rheumatoid arthritis.

The disease is divided into two main types:

• Type 1: the most common, affecting all age groups, predominantly women, positive for antinuclear antibodies (ANA) and smooth muscle antibodies (SMA)
• Type 2: rare, most often seen in children and young women, more aggressive, positive for anti-LKM1

How is the diagnosis made?

Diagnosis relies on a comprehensive assessment, as no single test is definitive.

Blood tests:

• Elevated liver enzymes (ALT, AST) often 5-20 times normal
• Elevated IgG (gamma globulin)
• Autoantibodies: ANA, SMA, anti-LKM1, anti-LC1, anti-SLA/LP
• Bilirubin, INR, and albumin to assess liver function

Exclusion of other conditions:

• Viral hepatitis A, B, C, E
• Drug-induced liver injury (statins, nitrofurantoin, minocycline, supplements)
• Alcohol-related and fatty liver disease
• Wilson's disease and haemochromatosis

Liver biopsy is crucial for initial diagnosis. It typically shows so-called interface hepatitis with lymphocyte infiltration and rosette formation, and also provides information on the extent of fibrosis development.

The international IAIHG criteria are used to score the likelihood. Many cases are not textbook-classic, and an experienced hepatologist often needs to evaluate the overall picture.

Treatment

The aim of treatment is to settle the inflammation in the liver. How well and how quickly that works varies from person to person.

Induction therapy (to bring the disease under control):

• Prednisolone in moderate doses, often daily, tapered down over weeks to months
• Azathioprine is often added early to allow for reduction of the prednisolone dose
• Budesonide can, according to the Danish DSGH guideline (2024), be offered to patients without cirrhosis who do not tolerate prednisolone; it causes fewer steroid side effects, but evidence for histological remission is lacking [6]. The European EASL guideline from 2025 likewise does not recommend budesonide as first-line treatment and advises against it in cirrhosis [2]

The goal is normalisation of liver enzymes and IgG, as well as histological remission.

Maintenance:

• Azathioprine in low doses, often, for many years
• Low-dose steroids for some patients
• Mycophenolate in case of azathioprine intolerance or insufficient effect; the 2025 EASL guideline also lists mycophenolate as a possible first-line option alongside azathioprine [2]
• Calcineurin inhibitors (tacrolimus, ciclosporin) if standard treatment fails

Treatment is usually long-term. DSGH recommends that maintenance treatment continues for at least two years with normal liver tests, and that a liver biopsy is offered before any attempt to stop medication is considered [6]. Relapse is common. Whether and when it can be attempted is assessed by the treating department, and medication must never be stopped on your own.

Liver transplantation is rare but an effective option for medical treatment failure or advanced cirrhosis. Outcomes are good.

General advice:

• Alcohol should be completely avoided
• Hepatitis A and B vaccination is recommended
• Caution with supplements and herbal medicines that can strain the liver
• Bone density measurement and vitamin D/calcium supplementation during steroid treatment

When should you see a doctor?

Contact your GP if you experience:

• Persistent fatigue with newly developed itching or jaundice
• Dark urine and pale stools
• Incidental finding of elevated liver enzymes that cannot be explained by alcohol or medication
• Pain under the right rib cage combined with joint pain and exhaustion

Call 112 for reduced consciousness, collapse or heavy bleeding. Contact the acute medical helpline (1813 in the Capital Region of Denmark, otherwise your local out-of-hours doctor) straight away and ask for urgent hospital assessment for increasing jaundice, new confusion or a bleeding tendency, as these can be signs of acute liver failure.

Frequently Asked Questions

Is autoimmune hepatitis contagious? No. It is an immune disease, not an infection.

Can I live a normal life with the diagnosis? The course is individual. On maintenance treatment, everyday life can continue with few limitations for some, while others need closer adjustment. The follow-up interval is agreed with the treating department.

Can I get pregnant? Yes, but plan it carefully. According to DSGH, both prednisolone and azathioprine can be used during pregnancy and breastfeeding [6]. Mycophenolate is teratogenic and must not be used during pregnancy in autoimmune hepatitis; the European product information states that use during pregnancy can cause miscarriage and serious harm to a developing baby [5]. EASL recommends stopping mycophenolate at least three months before a planned pregnancy [2]. Treatment must therefore be planned with a hepatologist before you become pregnant, and the pregnancy must be closely managed by the liver clinic. Never stop or switch the medicine on your own, not even if you find out you are pregnant; contact your hepatologist immediately instead.

What about painkillers? Paracetamol may in some situations be considered as an alternative to NSAIDs after medical assessment. In liver disease both the dose and the daily maximum must be agreed with your doctor. NSAIDs are generally discouraged in cirrhosis. All new medicines, including over-the-counter products and supplements, should be discussed with a hepatologist. Never start, stop or change prescribed medicine without agreeing it with your treating doctor.

Does it lead to liver cancer? The risk is minimal without cirrhosis. For established cirrhosis, semi-annual screening with liver ultrasound is performed.

References

1. Mack CL, Adams D, Assis DN, et al. Diagnosis and management of autoimmune hepatitis in adults and children: 2019 practice guidance and guidelines from the AASLD. Hepatology. 2020;72(2):671-722. PubMed
2. European Association for the Study of the Liver. EASL Clinical Practice Guidelines on the management of autoimmune hepatitis. J Hepatol. 2025;83(2):453-501. DOI 10.1016/j.jhep.2025.03.017. PubMed. Replaces the 2015 EASL guideline. The full text was reviewed for the statements marked [2] (budesonide, mycophenolate as a first-line option, stopping mycophenolate before pregnancy). The remaining treatment statements are based on DSGH 2024 [6].
3. Sundhed.dk. Autoimmun hepatitis (lægehåndbogen).
4. Lohse AW, Sebode M, Bhathal PS, et al. Consensus recommendations for histological criteria of autoimmune hepatitis from the International AIH Pathology Group. Liver Int. 2022;42(5):1058-1069. PubMed
5. European Medicines Agency. Product information for CellCept (mycophenolate mofetil), EPAR: "Using CellCept during pregnancy can cause miscarriage and serious harm to a developing baby." (retrieved 14 August 2026). EMA
6. Danish Society for Gastroenterology and Hepatology (DSGH). Autoimmune hepatitis, national treatment guideline, final revision 23 October 2024 with addendum 11 November 2024 (revision date on front page 1 October 2024). PDF

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This article provides general information and does not replace a medical consultation. Contact your GP if you experience symptoms.