Autoimmune Hepatitis and Liver Transplant

What is Autoimmune Hepatitis?

Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease where the body’s immune system mistakenly attacks its liver cells. This leads to ongoing liver inflammation, which, if left untreated, can result in cirrhosis, liver failure, or even the need for a liver transplant.

Autoimmune Hepatitis can occur de novo in a transplanted liver.

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Symptoms of Autoimmune Hepatitis

Symptoms of autoimmune hepatitis can vary widely. Some individuals may be asymptomatic, with elevated liver enzymes noted only during routine lab tests. Others may experience a range of symptoms, including:

• Fatigue
• Malaise (general feeling of discomfort)
• Jaundice (yellowing of the skin and eyes)
• Abdominal pain or discomfort
• Enlarged liver (hepatomegaly)
• Joint pain (arthralgias)
• Skin rash
• Irregular blood vessels on the skin (spider angiomas)
• Loss of menstrual periods

It can also present as cirrhosis or acute liver failure in some cases.

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Risk Factors for Autoimmune Hepatitis

Multifactorial = Genetics+ Immunologic+Environment

This condition can affect both children and adults, and although it’s more common in women, it can occur in any gender or age group.

• Genetic predisposition (family history of autoimmune diseases)
• Viral infections (like hepatitis A, B, or C)
• Environmental triggers (certain medications or toxins)
• Hormonal factors (women are more commonly affected)
• Coexisting autoimmune conditions (thyroid disorders, type 1 diabetes, celiac disease)

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Types of Autoimmune Hepatitis

Autoimmune Hepatitis should be considered in all patients.

Most adult females (71-95%) have a bimodal peak in the 2nd and 5th decades of life.

Type 1 Autoimmune Hepatitis

• Most common form
• 4 times more common in females
• Seen in any age
• Associated with antinuclear antibodies (ANA) or anti-smooth muscle antibodies (ASMA)
• Half of the population has other autoimmune diseases like Coeliac disease, Rheumatoid arthritis, and Ulcerative colitis.

Type 2 Autoimmune Hepatitis

• Rare and typically seen in children and teenagers
• Associated with liver kidney microsomal antibody (anti-LKM1) and anti-LC antibodies (liver cytosol )

Type 3 Autoimmune Hepatitis

• Proposed based on the presence of: Anti-SLA/LP (Soluble Liver Antigen / Liver Pancreas Antibody)
  Sometimes overlaps with AIH-1 and may indicate a more severe or atypical form.

⚠️ Note on Type 3 AIH:
The designation of Type 3 AIH has been largely abandoned. This is because anti-SLA/LP antibodies are often found in Type 1 AIH patients as well. Therefore, patients with anti-SLA positivity are now generally classified under Type 1 AIH.

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Overlap Syndrome

Features of both autoimmune hepatitis and other liver diseases, like primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC)

🔍 When to Suspect an Overlap Syndrome

• If a patient with AIH has cholestatic liver enzyme elevation (ALP/GGT), think of AIH-PBC or AIH-PSC overlap.
• In children, always consider underlying sclerosing cholangitis (PSC), even if enzymes are not very high.
• In adults, if ALP/GGT are high, PBC-specific autoantibodies (like AMA) should be tested first.

🧪 Must-Do Investigations

1. Magnetic Resonance Cholangiography (MRC):
   • Recommended in all childhood AIH cases at diagnosis, even without elevated cholestatic enzymes.
   • Also advised in young adults with cholestasis, incomplete treatment response, or recurring activity.
   • In adults, MRC should be done if:
     • There’s persistent cholestasis
     • And AMA or other PBC antibodies are negative
2. Autoantibody Testing:
   • Look for AMA (anti-mitochondrial antibody) and other PBC-specific antibodies first in any adult AIH patient showing cholestasis.

🧠 Why This Matters: Overlap syndromes may need different treatment strategies, and delayed diagnosis can lead to rapid progression to cirrhosis or bile duct complications.

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Autoimmune Hepatitis in Adults vs Paediatrics

• Adults: Often present with fatigue, joint pain, or incidental abnormal liver tests. Cirrhosis at diagnosis is common.
• Paediatrics: Symptoms may be more acute and progress rapidly.
• Treatment goals are similar, but children may respond differently and require ongoing growth and developmental monitoring.

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How Is Autoimmune Hepatitis Diagnosed?

1. Clinical History & Physical Exam
   • Fatigue, jaundice, abdominal discomfort, joint pain
2. Liver Function Tests (LFTs)
   • Elevated ALT, AST, and sometimes bilirubin
3. Autoantibody Tests
   • ANA, ASMA, anti-LKM1, anti-SLA
4. Immunoglobulin G (IgG) Levels
   • Often elevated in AIH
5. Viral Hepatitis Exclusion
   • Rule out hepatitis A, B, C, and other viral causes
6. Liver Biopsy
   • Confirms diagnosis; shows interface hepatitis, plasma cell infiltration
7. Scoring Systems
   • International AIH Group scoring to support diagnosis

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🔬 Autoantibodies and Significance

• Serum IgG: Elevated levels above the upper limit of normal (ULN) are considered significant.
• ANA (Antinuclear Antibody) and ASMA (Anti-Smooth Muscle Antibody): Titers ≥1:40 are significant.
• LKM (Liver Kidney Microsomal Antibody): A titer ≥1:40 is considered significant.
• SLA (Soluble Liver Antigen): If positive, it strongly supports autoimmune hepatitis, especially in seronegative cases.
• Other Autoimmune Screening:
  • P-ANCA (Perinuclear Anti-Neutrophil Cytoplasmic Antibody)
  • TTG (Tissue Transglutaminase Antibody)
  • AMA (Anti-Mitochondrial Antibody)
  • These are useful in differentiating or detecting overlapping autoimmune disorders such as celiac disease, primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC), or autoimmune overlap syndromes.

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Pre-Treatment Workup Before Starting Autoimmune Hepatitis Therapy

Before starting immunosuppressive therapy, these pre-treatment assessments are recommended:

• Complete blood count (CBC) and differential
• Liver and renal function tests
• Blood glucose and HbA1c
• Viral markers: Hepatitis A, B, C; HIV; CMV; EBV
• Chest X-ray (to rule out latent TB)
• Quantiferon TB Gold or Mantoux test (for latent tuberculosis)
• Immunoglobulin levels (especially IgG)
• Baseline bone mineral density (DEXA scan), especially if steroids are planned
• Abdominal ultrasound or elastography (to assess liver fibrosis)
• Pregnancy test for women of reproductive age

These tests ensure safe initiation of corticosteroids or other immunosuppressive agents and help monitor for potential complications.

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Treatment Options Before Liver Transplant

• First-line:
  • Corticosteroids (e.g., prednisone or budesonide)
  • Azathioprine (as a steroid-sparing agent)
• Second-line (if poor response):
  • Mycophenolate mofetil, cyclosporine, or tacrolimus
• Lifestyle measures:
  • Avoid alcohol, maintain a healthy weight, and manage comorbidities
• Monitoring:
  • LFTs, IgG levels, and side effects of long-term immunosuppression

Most patients go into remission with medication. With improved or normal AST/ALT and TgG levels.

Some may relapse if drugs are stopped too early.

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🔍 Monitoring for Long-Term Complications in AIH

Once autoimmune hepatitis (AIH) has progressed to cirrhosis, the journey doesn’t stop; it simply shifts focus from treatment to careful monitoring. This helps catch serious complications early and improve long-term outcomes.

🧭 What Should Be Monitored?

1. Portal Hypertension
   A common complication of cirrhosis, where increased pressure in the liver’s blood vessels can lead to:
   • Variceal bleeding (internal bleeding from swollen veins)
   • Fluid accumulation in the abdomen (ascites)
   • Confusion due to toxins in the brain (hepatic encephalopathy)
2. Liver Cancer (Hepatocellular Carcinoma – HCC)
   Even when AIH is under control, cirrhosis increases the risk of liver cancer over time.
   Regular screening helps detect HCC at an early, treatable stage.

📅 Surveillance Guidelines

• Every AIH patient with cirrhosis should undergo:
  • Ultrasound of the liver
  • AFP blood test (tumour marker for HCC)
• If portal hypertension is suspected:
  • Endoscopy may be recommended to look for varices
  • Non-invasive tools like FibroScan or liver stiffness monitoring may guide follow-up

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When Is a Liver Transplant Needed?

Liver Transplant is an option for end-stage liver disease.

• Failure to respond to treatment
• Fulminant liver failure at first presentation
• Cirrhosis with complications (ascites, variceal bleed, encephalopathy)
• Hepatocellular carcinoma

A transplant is often life-saving and allows patients to return to a relatively normal life.

Liver Transplant Success Rate in Autoimmune Hepatitis

Liver transplant outcomes in autoimmune hepatitis are excellent:

• 1-year survival: Over 90%
• 5-year survival: 80–85%
• 10-year survival: Still above 70% in many centres

75% graft survival at 5 years.

Patients with AIH do as well, provided there is good compliance with medications and follow-up.

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Can Autoimmune Hepatitis Recur After Liver Transplant?

Yes, recurrence is possible. Studies suggest:

• Recurrence rate: 36- 68%
• Timing: Often within 2–5 years post-transplant
• Risk factors for recurrence:
  • Younger age at transplant
  • Inadequate immunosuppression
  • High IgG or autoantibodies pre-transplant

Despite recurrence, most patients can be managed successfully with reintroduction or adjustment of immunosuppressive therapy (treat like AIH).

Monitoring Guidelines After Liver Transplant in Autoimmune Hepatitis

Note: for interpretation and to know more about the FIB-4 index, check this link>>https://livertransplanthelp.com/fib-4-index-calculator/

• Routine follow-ups with LFTs and autoantibody levels
• FIB-4 Index score trend, especially useful at the community level or primary health care centres
• Liver biopsy if LFTs are persistently abnormal
• Drug level monitoring (tacrolimus, cyclosporine)
• Bone health surveillance (DEXA every 1–2 years)
• Regular screening for infections and malignancies due to long-term immunosuppression

Latest Advances in Autoimmune Hepatitis and Transplant

• Budesonide is a steroid with fewer systemic side effects
• Biologics like rituximab for refractory cases
• Improved HLA typing to assess transplant rejection risk
• Non-invasive fibrosis monitoring with FibroScan and elastography
• Personalised immunosuppression protocols to reduce side effects and recurrence

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Autoimmune Hepatitis and Pregnancy

Preconception and pregnancy counselling are important.

• AIH flare risk, especially postpartum, up to 6 months postpartum.
• Advised remission 1 year before conception.
• Mycophenolate Mofetil is contraindicated during pregnancy

• AIH can be managed during pregnancy with careful monitoring.
• Prednisone is generally safe in pregnancy.
• Close collaboration between a hepatologist, an obstetrician, and a paediatrician is essential.
• Risks include:
  • Preterm birth
  • Flare-ups during pregnancy or postpartum
• Liver transplant recipients can conceive successfully, but timing and medications must be carefully planned.

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Frequently asked questions

Stay informed, stay strong. Autoimmune hepatitis may sound daunting, but with timely diagnosis and expert care, including liver transplant when needed, you or your loved one can live a full, vibrant life.

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