Autoimmune HepatitisErmias Kacha(MD)

Autoimmune Hepatitis

Chronic hepatitis of unknown etiology

Can progress to cirrhosis Characteristics include:

presence of autoimmune antibody evidence of hepatitis elevation of serum globulins

Other names

Active chronic hepatitis or chronic active hepatitis

Chronic aggressive hepatitis Lupoid hepatitis Plasma cell hepatitis Autoimmune chronic active hepatitis

Epidemiology

First described in 1950’s Accounts for 5.6% of liver

transplants in the US Affects women more than men

(3.6:1) If untreated approximately 40% die

within 6 months 40% develop cirrhosis

Pathogenesis Unknown mechanism Triggers : presumed to be certain viruses, toxins,

drugs Oxyphenisatin,Methyldopa,Nitrofurantoin,Dicl

ofenac,Minocycline,statins Genetic predisposing factors:

HLA-DR3: early onset, severe form HLA-DR4: caucasian, late onset, better

response to steroids, higher incidence of extrahepatic manifestations

Antigenic mimicry Autoantigen - the cytochrome mono-oxygenase,

CYP2D6

Classification Type 1 Type 2 Overlap Syndromes(18%)

96%4%

80%

Classification

15%-34%

Classification

Autoimmune Extra hepatic Diseases

Type 1 AIH Thyroiditis (12%) Graves (6%) UC

16% of AIH have UC

5% of AIH have UC and PSC and PSC

Less commonly with RA, pernicious anemia, systemic sclerosis, ITP, SLE

Type 2 AIH DM1 Thyroiditis Vitiligo Autoimmune

Polyglandular disease10% have AIH

Overlap Syndromes Overlap with PBC

“Overlap” (“ AMA+ AIH”) Histologic AIH, Serologic PBC

Behaves like AIH type 1 “Autoimmune Cholangiopathy” (“AMA negative PBC )

Serologic AIH, Histologic PBC� Overlap with PSC ( “true AIH/PSC

overlap” ) Serologic AIH, Histologic AIH and PSC,

Cholangiographic PSC Suspect in IBD patients with AIH

Overlap Syndromes

Overlap with Viral Hepatitis Principle: Treat the predominant

diseases Review of AIH patients: 4% hep C + Review of Hep C patients: 28% ANA +,

11% SMA+ 10% of these are > 1:160, and rarely ANA+

and SMA+ AIH

Median ANA 1:320, SMA 1:160 60% + for both

Clinical Manifestations

Heterogeneous and fluctuating disease Asymptomatic (34%-45%)

Identified at routine testing, surgery, etc. Chronic symptoms

Fatigue, jaundice, anorexia, amenorrhea Fulminant hepatic failure

Acute, severe hepatitis

Clinical Manifestations

Diagnosis

Diagnostic Criteria for Autoimmune Hepatitis

Diagnostic Criteria for Autoimmune Hepatitis

Simplified Diagnostic Criteria for Autoimmune

Hepatitis

Histology

Plasma cell and Lymphocyte infiltration of Portal Field

Periportal Piecemeal Necrosis (aka Interface hepatitis) Sparing of Bile Ducts

Lobular Inflammation Bridging Necrosis and Cirrhosis

Histology

Interface Hepatitis

Treatment

Should be based on: Severity of symptoms Degree of elevation in transaminases

and IgG Histologic findings Potential side effects of treatment

AASLD Recommendations

Standard and Novel Therapies for

Autoimmune Hepatitis

Treatment Regimens for Adults

10% versus 44%

End Points of Treatment70% to 80%; 20 % sustained response

9%

End Points of Treatment13%

13%

Prednisone-Related Side Effects

Azathioprine-Related Side Effects

Special Populations at Risk for Drug Toxicity

Patients with Cirrhosis. Pregnant Patients Patients with Low Thiopurine

Methyltransferase Activity

Relapse After Drug Withdrawal

Recrudescence of disease activity after induction of remission and termination of therapy

Characterized by an increase in the serum AST level to more than three-fold the ULN and/or increase in the serum c-globulin level to more than 2 g/dL.

Liver Transplantation

Acute liver failure, decompensated cirrhosis with a MELD score >15, or hepatocellular carcinoma meeting criteria for transplantation

Recurrence of disease after transplant is common (30%).

Recurrent AIH should be treated with prednisone and azathioprine

Inability to normalize LFT justifies the addition of mycophenolate (2 g daily) to the regimen of corticosteroids and calcineurin inhibitor.

Liver Transplantation If inadequate in recurrent disease,

tacrolimus should be replaced with cyclosporine or the calcineurin inhibitors replaced with sirolimus

Retransplantation must be considered for patients with refractory recurrent AIH that is progressing to allograft loss.

5-year and 10-year patient survivals of approximately 75%

The prognosis of patients treated for recurrent AIH is comparable to patients transplanted for AIH who do not experience recurrence

Prognosis

Prognosis 40% of all pts with AIH develop cirrhosis 54% develop esophageal varices within 2 years Hepatocellular carcinoma occurs in 4% of

patients with type 1 AIH, and the 10-year probability of developing this neoplasm is 2.9%(ultrasonography at 6 months)

Poor prognosis if has presence of ascites or hepatic encephalopathy

13-20% of patients can have spontaneous resolution

Of patients who survive the most early and active stage of disease, approximately 41% of them develop inactive cirrhosis.

Of patients who have severe initial disease and survive the first 2 years, typically survive long term.

References Update on autoimmune hepatitis,

World J Gastroenterol March 7, 2009

Diagnosis and Treatment of Autoimmune Hepatitis ,HEPATOLOGY, August 2002

AASLD PRACTICE GUIDELINES,Diagnosis and Management of Autoimmune Hepatitis 2010

HEPATOLOGY, January 2005, Treatment Challenges and Investigational Opportunities in Autoimmune Hepatitis

References

Autoimmune Hepatitis, From Mechanisms to Therapy, HEPATOLOGY, Vol. 43, No. 2, Suppl. 1, 2006

Current concepts in autoimmune hepatitis, Annals of Hepatology 4(1) 2005: 6-24

Clinical features and management of autoimmune hepatitis, World J Gastroenterol June 7, 2008

Autoimmune Hepatitis, n engl j med 354;1 www.nejm.org january 5, 2006

References

Autoimmune Hepatitis: A Review, J Pak Med Assoc

Uptodate 17.3 Harrison, 17 th edition