Autoimmune Hepatitis

 Definition

Autoimmune hepatitis (AIH) is a chronic, progressive, immune-mediated inflammatory liver disease characterized by:

  • Interface hepatitis on histology,
  • Presence of autoantibodies,
  • Elevated serum IgG, and
  • Exclusion of other causes of hepatitis (viral, drug-induced, metabolic).

It results from loss of tolerance to hepatic autoantigens, leading to T-cell–mediated hepatocyte injury.


 Pathophysiology

1. Immunogenetic Susceptibility

  • HLA associations:
    • AIH type 1: HLA-DR3, DR4
    • AIH type 2: HLA-DR7, DQ2
    • AIH type 3: Similar to type 1
  • Trigger: Environmental factors (viral infections, drugs like minocycline or nitrofurantoin) in genetically predisposed individuals.

2. Immune Mechanism

  • CD4+ T-helper cells activate cytotoxic CD8+ T cells and B cells.
  • Autoantibodies form against hepatocellular antigens (e.g., ANA, SMA, LKM1).
  • Cytokine-mediated inflammation → interface hepatitis → bridging necrosis → fibrosis → cirrhosis.


 Classification (Types of AIH)

Type

Autoantibodies

Typical Age / Sex

Associated Conditions

Type 1

ANA, SMA

Adolescents / Adults (♀)

Thyroiditis, RA, UC, DM1

Type 2

Anti-LKM1, anti-LC1

Children / Young adults

Celiac disease, other AI disorders

Type 3

Anti-SLA/LP

Adults

Often overlaps with Type 1


 Clinical Features

1. Presentation

  • Variable onset: Acute, chronic, or asymptomatic.
  • Symptoms:
    • Fatigue, malaise, anorexia, arthralgia
    • Jaundice, right upper quadrant pain
    • Amenorrhea (women)
  • Acute severe hepatitis (may mimic viral hepatitis)
  • Chronic liver disease / cirrhosis features in late stages: ascites, spider nevi, splenomegaly, hepatic encephalopathy.

2. Physical Findings

  • Hepatomegaly, splenomegaly
  • Stigmata of chronic liver disease
  • Extrahepatic autoimmune features:
    • Arthritis, thyroiditis, vitiligo, hemolytic anemia, glomerulonephritis


 Diagnostic Criteria (Simplified IAIHG Scoring System, 2008)

Parameter

Score

ANA or SMA ≥1:40 or LKM1 ≥1:40

1

ANA or SMA ≥1:80 or LKM1 ≥1:80 or SLA positive

2

IgG > ULN

1

IgG > 1.1 × ULN

2

Liver histology compatible

1

Liver histology typical

2

Absence of viral hepatitis

2
  • Probable AIH: ≥6 points
  • Definite AIH: ≥7 points


🧬 Laboratory Findings

Parameter

Typical Findings

Transaminases (AST, ALT)

Markedly elevated (up to >1000 IU/L)

Bilirubin

Elevated in acute phase

Serum IgG

Elevated (>1.1× upper limit of normal)

Autoantibodies

ANA, SMA, anti-LKM1, anti-SLA

Other tests

Negative viral serology (HBsAg, anti-HCV)


 Histopathology

Liver biopsy is essential for diagnosis and prognosis.

Typical features:

  • Interface hepatitis (piecemeal necrosis): Lymphoplasmacytic infiltrate at portal–parenchymal junction
  • Plasma cell infiltration
  • Rosetting of hepatocytes
  • Bridging necrosis (severe disease)
  • Fibrosis / cirrhosis (chronic)


 Differential Diagnosis

Condition

Distinguishing Features

Viral hepatitis

Positive viral serology

Drug-induced hepatitis (DILI)

Temporal drug relation; RUCAM score

Wilson’s disease

↓ Ceruloplasmin, KF rings, high urinary copper

NAFLD/NASH

Metabolic syndrome, obesity

Primary biliary cholangitis (PBC)

AMA positive, cholestatic ALP rise

Primary sclerosing cholangitis (PSC)

MRCP: beading; often overlap with IBD


 Overlap Syndromes

  1. AIH–PBC overlap:
    • Features of both diseases
    • AMA positive, raised ALP
    • Histology: bile duct injury + interface hepatitis
  1. AIH–PSC overlap:
    • Seen in young males
    • MRCP: beaded ducts + elevated IgG and autoantibodies


 Management (AASLD / EASL Guidelines)

1. Indications for Treatment

Treat all with:

  • AST/ALT >10× ULN, or
  • AST/ALT >5× ULN + IgG >2× ULN, or
  • Bridging necrosis / interface hepatitis on biopsy.

2. First-Line Therapy

Drug

Dose

Comments

Prednisone (or prednisolone)

30–60 mg/day

Taper to maintenance (5–10 mg/day)

+ Azathioprine

50 mg/day (1–2 mg/kg/day)

Steroid-sparing, maintenance drug
  • Combination preferred (better remission, fewer steroid side effects).
  • Response: Normalization of ALT, IgG, and histology.

3. Second-Line / Refractory

  • Mycophenolate mofetil (MMF)
  • Cyclosporine / Tacrolimus
  • 6-Mercaptopurine
  • Budesonide (non-cirrhotic AIH; less systemic effect)

4. Liver Transplantation

  • For fulminant hepatic failure, decompensated cirrhosis, or treatment failure.
  • Recurrence in graft in 20–30%.


⏱️ Monitoring and Follow-up

Parameter

Frequency

AST, ALT, IgG

Every 1–3 months during induction

CBC, bilirubin, INR

Regularly during therapy

Azathioprine toxicity

CBC, LFTs, TPMT levels

Biopsy (optional)

To confirm histological remission

Relapse: common (50%) after withdrawal → may require lifelong maintenance.


 Prognosis

Untreated

5-year survival ≈ 50%

With treatment

10-year survival > 90%

Predictors of poor outcome: Cirrhosis at diagnosis, treatment delay, nonresponse, overlap syndromes



 Key Points 

  • Female predominance (70–80%)
  • Interface hepatitis + plasma cells = hallmark
  • Type 1 = ANA/SMA positive; Type 2 = anti-LKM1 positive
  • Elevated IgG (not IgM as in PBC)
  • Responds dramatically to corticosteroids
  • Overlap with PBC and PSC possible
  • Azathioprine maintenance prevents relapse
  • Transplant indicated for fulminant hepatic failure


🧾 References

  1. Harrison’s Principles of Internal Medicine, 21st Edition.
  2. AASLD Practice Guidance: Diagnosis and Management of Autoimmune Hepatitis (2020).
  3. EASL Clinical Practice Guidelines: Autoimmune Hepatitis (2015).
  4. UpToDate: Clinical manifestations and diagnosis of autoimmune hepatitis.
  5. Journal of Hepatology, 2021; 75: 1423–1449.


 When to Suspect Autoimmune Hepatitis (AIH)

AIH should be suspected in any patient—especially a young or middle-aged woman—with unexplained elevation of aminotransferases or features of hepatitis after excluding viral, alcoholic, and drug causes.


 1️⃣ Clinical Situations That Should Raise Suspicion

Scenario

Why AIH Should Be Considered

Young or middle-aged woman with acute or chronic hepatitis

AIH has strong female predominance (≈ 80%)

Acute hepatitis with negative viral serology

AIH can mimic acute viral hepatitis (ALT/AST > 1000 IU/L)

Fluctuating transaminases without clear etiology

Characteristic waxing–waning pattern

Chronic hepatitis or cirrhosis in non-drinker, non-obese patient

AIH may present first as cirrhosis

Postpartum hepatitis

AIH often triggered after pregnancy due to immune rebound

History of other autoimmune diseases (thyroiditis, RA, type 1 DM, vitiligo, celiac, UC)

Autoimmune clustering common

Unexplained liver dysfunction after viral/drug trigger

Viral infections and drugs can unmask latent AIH

Hypergammaglobulinemia or isolated IgG elevation

Key biochemical clue

Unexplained hepatic failure (acute severe or subacute)

AIH can cause fulminant hepatic failure, especially in young females



 When to Proceed With Diagnostic Work-up

Once suspicion is raised:

Step 1 — Exclude other causes

  • Viral hepatitis panel (A, B, C, E)
  • Alcohol history, drug history
  • Metabolic tests (ceruloplasmin, ferritin, α1-antitrypsin)

Step 2 — Check Autoimmune Markers

  • ANA, SMA, anti-LKM1, anti-SLA/LP, pANCA
  • Quantitative IgG

Step 3 — Imaging

  • Ultrasound or transient elastography to assess fibrosis, exclude obstruction

Step 4 — Confirm with Liver Biopsy

  • Interface hepatitis with plasma cells → diagnostic hallmark


 Clinical Pearl (for Exams & ICU Rounds)

“Think AIH when a young woman presents with hepatocellular enzyme elevation, negative viral serology, high IgG, and ANA/SMA positivity.”
Even if the patient looks like viral hepatitis, repeat testing and consider biopsy if enzymes persist >6–8 weeks.