Autoimmune Hepatitis (AIH) ~ CME presentation (By Dr. Usman Javed)

An inflammatory liver disease of unknown cause characterized by suppressor T-cell defects with autoantibodies directed against hepatocyte surface antigens. AIH predominantly affects young or middle-aged women (bimodal, i.e 10–30yrs or >40yrs old).

Presentation:

​Up to 40% present with acute hepatitis and signs of autoimmune disease such as fever, malaise, urticarial rash, polyarthritis. The remainder present with gradual jaundice or are asymptomatic and diagnosed incidentally with signs of chronic liver disease.

Pathogenesis:

Involves the combination of genetic predisposition and environmental triggers. 

Genetic predisposition

• Genetic susceptibility to developing autoimmune hepatitis has been associated with the HLA haplotypes B8, B14, DR3, DR4, and Dw3
• C4A gene deletions are associated with the development of autoimmune hepatitis

Environmental triggers include 

• Viruses:

eg Rubella, Epstein-Barr, and hepatitis A, B, and C.

• Drugs

eg Aspartame

​Investigations:

• CBC (pancytopenia secondary to hyperspleenism)
• Bilirubin, ALT, AST, ALP (usually all raised)
• Autoantibodies
  • ANA
  • ASMA
  • Anti-LKM
  • Anti – SLA
• Serum IGg Levels
• Liver Biopsy
• Investigations to rule out other causes of CLD
  • AntiHCV, HBsAg

​Liver Biopsy

“Piecemeal necrosis” or interface hepatitis with lobular or panacinar inflammation (lymphocytic and plasmacytic infiltration) are the histologic hallmarks of the disease.
It refers specifically to a loss and degeneration of (limiting plate) hepatocytes at the lobular-portal-interface, producing a moth-eaten irregular appearance.

• In Autoimmune Hepatitis Bridging  or interface hepatitis occurs

How to Diagnose:

​Differential Diagnosis

AIH is a diagnosis of exclusion; Viral and drug-induced causes must be ruled out.

• Primary Biliary Cirhosis
• Primary Sclerosing Cholangitis
• Chronic Viral Hepatitis
• Overlap Syndrome
  • AIH plus PBC, AIH plus PSC

​Overlap Syndromes:

​Associated Conditions

• Type I diabetes mellitus
• Thyroiditis
• Idiopathic thrombocytopenic purpura
• Ulcerative colitis
• Rheumatoid arthritis
• Primary biliary cirrhosis and primary sclerosing cholangitis occasionally overlap with AIH

​Indications for treatment

Treatment

Immunosuppressant therapy
First Line Drugs:

• Prednisolone
• Azathioprine

Second Line Drugs:

• Cyclosporine
• Tacrolimus
• Mycophenolate Mofetil

Liver transplantation

Prednisolone monotherapy and prednisolone in combination with Azathioprine are equally effective in induction and maintenance of remission

Combination therapy is preferred in:

• Osteoporosis, Diabetes, HTN, Obesity, Acne, Depression

Prednisone alone preferred in

• Cytopenias
• Pregnancy

Second Line drugs are considered if there is no improvement in clinical, lab and histological features after 6 weeks of therapy

​Endpoints of treatment

Primary End Point

• Normalization of ALT

Secondary End Point

• Normalization of  Histologic activity

Final Goal

• To achieve sustained remission without need of drug therapy or at lowest dose possible, and maintaining the hepatic reserve

Follow Up:

ALT and IgG level may be followed two weekly on a regular basis as a marker of disease responsiveness to therapy.

Reference:

​AASLD Guidelines