Autoimmune Hepatitis: Symptoms, Diagnostics, and Modern Treatment Approaches

What is autoimmune hepatitis?

Autoimmune hepatitis (AIH) is a rare, complex, and chronic immune-mediated disease in which the body's immune system mistakenly attacks its own liver cells (hepatocytes). This leads to T-cell-mediated inflammation and is usually accompanied by the presence of autoantibodies and elevated levels of immunoglobulin G (IgG) in the blood [3]. The mechanisms of AIH development are not fully understood [1].

Although the cause of AIH often remains unknown, there are factors that can trigger its development. These include:

• Viral infections: Certain viral hepatitides, such as hepatitis A, can act as a trigger for the development of AIH [1].
• Medications: Immune checkpoint inhibitors used in oncology to treat metastatic melanoma and other cancers can cause immune-mediated hepatitis, which may be fatal [8].
• Other autoimmune diseases: AIH is frequently associated with inflammatory bowel disease (IBD), such as ulcerative colitis, and may manifest as part of an overlap syndrome or be triggered by drugs used to treat IBD (e.g., tumor necrosis factor-alpha inhibitors) [7].
• Latent infections: Latent hepatitis B virus (HBV) infection can worsen the response to AIH treatment [5].

Symptoms and clinical manifestations

The clinical picture of autoimmune hepatitis is extremely diverse, which complicates its diagnosis [3]. Symptoms can be nonspecific and resemble other liver diseases or even malignancies. Among the most common manifestations of AIH are:

• General weakness and fatigue [1].
• Jaundice (yellowing of the skin and sclera) [1, 2].
• Abdominal pain [2].
• Low-grade fever [2].
• Skin itching (pruritus) [2].
• Loss of appetite (anorexia) [2].

In some cases, AIH can mimic other serious conditions, such as malignancies of the pancreas or biliary tract. For example, one patient with AIH presented with jaundice, abdominal pain, low-grade fever, pruritus, and anorexia, and a computed tomography scan revealed enlargement of the pancreatic head and dilation of the common bile duct, which initially raised suspicion of cancer [2].

How is autoimmune hepatitis diagnosed?

Diagnosing AIH requires a comprehensive approach and the exclusion of other causes of liver damage. The main stages include:

1. Blood tests:

   • Elevated levels of liver enzymes (aspartate aminotransferase (AST) and alanine aminotransferase (ALT)), indicating hepatocyte damage [1, 2].
   • Elevated total bilirubin, especially conjugated, in the presence of jaundice [2].
   • High titers of antinuclear antibodies (ANA) and elevated total immunoglobulin G (IgG) levels are characteristic markers of AIH [1, 2, 3].
   • Exclusion of viral hepatitis (A, B, C, E) using a corresponding viral panel [2].
   • Sometimes the tumor marker CA 19-9 may be elevated, further complicating differential diagnosis with malignant tumors [2].

2. Liver biopsy: This is a key method for definitive confirmation of the diagnosis. Histological examination of a liver sample allows for the identification of characteristic features of AIH, as well as the exclusion of other diseases [1, 2].

3. Scoring systems: International scoring systems, such as the revised scoring system of the International Autoimmune Hepatitis Group or simplified international diagnostic criteria, are used to establish the diagnosis [1, 2].

4. Instrumental studies: Computed tomography (CT) or ¹⁸F-FDG PET/CT can be used to rule out other pathologies and assess liver condition. In cases of immune-mediated hepatitis, PET/CT may show increased FDG uptake in the liver [8].

Modern treatment methods

The treatment of autoimmune hepatitis aims to suppress the immune response and reduce inflammation in the liver. The main first-line medications are corticosteroids (prednisolone) combined with immunosuppressants, such as azathioprine or mycophenolate mofetil [3]. These drugs are vital and allow the disease to be controlled.

However, despite their effectiveness, there are significant challenges:

• Nonspecificity: These drugs do not possess high specificity, leading to a wide range of side effects [3].
• Side effects: The side-effect profile (e.g., weight gain, osteoporosis, increased risk of infections) negatively impacts patient adherence to treatment and quality of life [3]. More than 20% of patients are forced to discontinue medications due to adverse reactions [3].
• Incomplete response: Less than 70% of patients achieve a complete biochemical response (normalization of aminotransferase and IgG levels) within 6 months of therapy [3].
• High relapse rate: A high rate of disease relapse is observed after drug withdrawal [3].

In some cases, especially with an acute onset, conservative supportive methods such as intravenous crystalloid solutions (e.g., lactated Ringer's solution), ursodeoxycholic acid, and silymarin may be used [1].

Features and complexities of therapy

Understanding the mechanisms of AIH remains limited, and clinical manifestations are heterogeneous, leading to variability in clinical practice [3]. There are certain patient groups for whom AIH treatment has specific features and complexities:

• Patients with latent HBV infection: Studies show that AIH patients with latent hepatitis B virus infection (even with negative HBsAg but positive anti-HBc IgG) demonstrate a poorer biochemical response to standard immunosuppressive therapy. They maintain elevated liver enzyme levels and impaired liver function parameters compared to patients without latent infection [5]. This underscores the need to screen for latent HBV in all AIH patients.
• Patients with inflammatory bowel disease (IBD): In IBD patients suffering from AIH, treatment may be less effective than in patients without IBD [7]. This may be due to a more complex immune response or interactions with drugs used to treat IBD.
• Immune-mediated hepatitis after cancer immunotherapy: Patients receiving immune checkpoint inhibitors (e.g., ipilimumab and nivolumab) for oncological diseases may develop immune-mediated hepatitis. This is a serious adverse event that can be fatal and requires immediate attention and therapy adjustment [8].

The evidence base for second- and third-line AIH treatments is primarily based on real-world clinical practice studies without control groups [3]. There is an urgent need to develop more specific and safer treatments that could improve patients' quality of life and reduce the frequency of side effects and relapses [3].

Sources

1. Acute Hepatitis A-Induced Autoimmune Hepatitis: A Case Report and Literature Review. (Medicina (Kaunas, Lithuania), 2022) https://pubmed.ncbi.nlm.nih.gov/35888564/
2. Autoimmune Hepatitis Mimicking Pancreatico-Biliary Malignancy. (Cureus, 2026) https://pubmed.ncbi.nlm.nih.gov/42756834/
3. Autoimmune hepatitis: special groups and treatment gaps. (JHEP reports : innovation in hepatology, 2026) https://pubmed.ncbi.nlm.nih.gov/42697485/
4. The Effect of Latent Hepatitis B Infection on Autoimmune Hepatitis Treatment Outcomes. (Cureus, 2025) https://pubmed.ncbi.nlm.nih.gov/40896063/
5. Clinical Presentation and Outcomes of Autoimmune Hepatitis in Inflammatory Bowel Disease. (Digestive diseases and sciences, 2015) https://pubmed.ncbi.nlm.nih.gov/25999245/
6. ¹⁸F-FDG PET/CT-visualised immune-related hepatitis after immune checkpoint inhibitor combination treatment in a patient with metastatic melanoma. (BMJ case reports, 2026) https://pubmed.ncbi.nlm.nih.gov/42716692/

The information presented in this article is for informational purposes only and should not be used for self-diagnosis or self-treatment. Always consult a qualified physician for a diagnosis and the prescription of adequate therapy.