Autoimmune hepatitis

Ascites

Diagnosis

Spider Angiomas

• Liver biopsy
• Show severity of disease
• Ex. Mild chronic active hepatitis, advanced chronic active hepatitis with scarring (fibrosis), fully developed cirrhosis
• Distinguish between autoimmune hepatitis from other diseases that resemble it

What is autoimmune hepatitis?

• Liver disease
• Immune system attacks liver cells - hepatocytes
• Progressive Inflammation-> fibrosis-> cirrhosis
• Acute/chronic
• Environment & genetic predisposition
• Infants to elderly
• 70% women
• Incidence rate: 1.9 per 100,000
• Prevalence rate: 16.9 per 100,000
• Affects 100,000 to 200,000 each yr. in the U.S.
• Frequencies of concurrent immune diseases (34% women vs. 17% men)

Jaundice

Diagnosis

Symptoms

• Rule out:
• Drug-induced liver disease
• Hereditary conditions: Wilson's disease
• Chronic viral infections: hepatitis B or C viruses
• Chronic cholestatic disorder of primary biliary cirrhosis & primary sclerosing cholangitis

Autoimmune Hepatitis

• Fatigue – most common
• Abdominal discomfort
• Joint pain
• Itching
• Skin rashes
• Nausea
• Vomiting

• Enlarged liver
• Spider angiomas
• Ascites
• Jaundice
• Dark urine
• Pale/gray colored stool

**34% asymptomatic**

Keith Starwalt

Type I or II

Diagnosis

References

• Type I: most common in U.S.
• ~50% have other autoimmune disorders
• Targets smooth muscle & nucleus of liver cells
• Anti-smooth muscle Ab’s directed against actin – found in the cytoskeleton of the hepatocytes

• Type 2: predominantly girls and young women(2-14 yr. old)
• Europe
• Anti-liver/kidney microsomal Ab’s directed against apoprotein of cytochrome P450 & anti-liver cytosol Ab’s
• Cytochrome P450 enzymes metabolize toxins (drugs) & endogenous metabolism products (bilirubin)

• Physical exam
• Blood tests:
• Specific autoantibodies
• Antinuclear antibodies (ANA)
• Smooth muscle antibodies (SMA)
• Liver/kidney microsomal antibody (LKM-1,-2,-3 Ab)
• Anti-soluble liver antigen (anti-SLA/LP)
• Anti-mitochondrial antibody (AMA)
• Anti-liver cytosol antibody (ALC1)
• Increased levels of IgG and aminotransferase

• Czaja, Albert J. "Autoimmune Hepatitis – Approach to Diagnosis." Medscape General Medicine 55th ser. 8.2 (2006): US National Library of Medicine National Institutes of Health. NCBI. Web
• Czaja, Albert J., and Deborah K. Freeze. "Diagnosis and Treatment of Autoimmune Hepatitis." AASLD PRACTICE GUIDELINES. 2002. Web.
• Granito, Alessandro, Paolo Muratori, Silvia Ferri, Georgios Pappas, Chiara Quarneti, Marco Lenzi, Francesco Bianchi, and Luigi Muratori. "Diagnosis and Therapy of Autoimmune Hepatitis." Mini-Reviews in Medicinal Chemistry 9.7 (2009): 847-60. EBSCOhost. Web.
• Jothimani, Dinesh, Matthew Cramp, Jonathon Mitchell, and Tim Cross. "Treatment of Autoimmune Hepatitis: A Review of Current and Evolving Therapies." Journal of Gastroenterology and Hepatology 26 (2011): 619-27. EBSCOhost. Web.
• Malik, Talha, and Shehzad Saeed. "Autoimmune Hepatitis: A Review." Autoimmune Hepatitis: A Review. Journal of Pakistan Medical Association, May 2010. Web.
• Van Den Berg, A. P. "Autoimmune Hepatitis: Pathogenesis, Diagnosis and Treatment." Autoimmune Hepatitis 33.225 (1998): 66-69. EBSCOhost. Web.
• Vergani, D., and G. Mieli-Vergani. "Mechanisms of Autoimmune Hepatitis." Pediatr Transplantation 8 (2004): 589-93. EBSCOhost. Web.
• Vergani, Diego, Maria Longhi, Dimitrios Bogdanos, Yum Ma, and Giorgina Mieli-Vergani. "Autoimmune Hepatitis." Semin Immunopathol 31 (2009): 421-35. EBSCOhost. Web.

Genetic Factors

Future Studies

• Research on:
• different steroids
• alternatives to steroids
• other immunosuppressants will lead to more effective treatments
• Research to find out who gets AIH and why

• Associated with HLA alleles
• influence occurrence, expression, and treatment outcome
• Type 1: HLA DR3 & HLA DR4 alleles
• 85% of Caucasians
• Type 2: HLA DR7 and HLA-DQB alleles
• HLA-DR3 serotype – early-age onset, girls & young women, diminished response to corticosteroids
• HLA-DRB1*0404 and HLA-DRB1*0405 are susceptibility alleles in Mexican, Japanese, Argentine, and Chinese
• HLA-DRB1*1301 allele predisposition for South America patients

Treatment

Pathogenesis

• Main goal is to suppress the body’s overactive immune system
• Immunosuppressive drugs:
• Corticosteroids – Prednisone
• Azathioprine
• 70-80% response
• Cyclosporin A and tacrolimus – inhibit calcineurin (activation of T lymphocytes)
• Mycophenolate mofetil (MMF) – reduces lymphocyte proliferation
• Remission within 2 yrs
• Control rather than cure
• Relapse within 6 months after therapy is ended
• Liver transplant
• autoantibodies and hypergammaglobulinemia disappear w/in 1 yr
• 1 yr survival rate of 90%
• 10 yr survival rate of 75%

• Unknown mechanism
• “Molecular Mimicry” hypothesis
• Immune response to certain pathogens directed at self for susceptible individuals
• Share structurally similar epitopes that resemble self-antigens
• Ex. Viruses (Hepatitis A &C, Epstein-Barr, Herpes virus type 6, etc.) and drugs (minocycline, propylthiouracil, nitrofurantoin, etc.)
• Defect in CD4+CD25+ regulatory Tcells
• Controls response to self antigens & prevent autoreactive Tcells