CLASSIFICATION:

AIH can be of three types [148, 158]:
1. Type I
• In classic (type I) autoimmune hepatitis, ANA or smooth muscle antibody (either or both) is detected in serum.
• Serum gamma globulin levels are typically elevated (up to 5-6 g/dL).
• In patients with the latter, the EIA for antibody to HCV may be falsely positive.
• Other antibodies, including atypical perinuclear antineutrophil cytoplasmic antibodies (ANCA) and antibodies to histones, may be found
• Present worldwide
• Age at presentation may be 10 years older than other types.
• 78% effected are women and 43% have associated autoimmune disease
• Associated with B8, DR3, DR4 and 45 % progress to cirrhosis
2. Type II
A second type, seen more often in Europe, is characterized by circulating antibody to liver-kidney microsomes (anti-LKM1) directed against cytochrome P450 2D6 without anti-smooth muscle antibody or ANA.
In some cases, anti-liver cytosol type 1, directed against formiminotransferase cyclodeaminase, is detected.
This type of autoimmune hepatitis can be seen in patients with autoimmune polyglandular syndrome type 1.
Present worldwide but rare in north America
Age at presentation is usually 2 – 14 years and rare in adults
89% effected are women and 34% have associated autoimmune disease
Associated with B14, Dr3, C4AQO and 82 % progress to cirrhosis
They may occasionally have low IgA
Requires life long maintenance therapy

3. Type III
A third variant is characterized by antibodies to soluble liver antigen-liver pancreas (anti-SLA/LP) and may represent a variant of type I autoimmune hepatitis characterized by severe disease, a high relapse rate after treatment, and absence of the usual antibodies (ANA and smooth muscle antibody).
Anti-SLA/LP appears to be directed against a transfer RNA complex responsible for incorporating selenocysteine into peptide chains.

CLINICAL FEATURES [147,148,158]
• Clinical features of autoimmune hepatitis can be
Autoimmune hepatitis may present as acute hepatitis, chronic hepatitis, or well-established cirrhosis.
o Approximately one third of patients present with symptoms of acute hepatitis marked by fever, hepatic tenderness, and jaundice. In some patients, the acute illness may appear to resolve spontaneously;
o Patients invariably develop signs and symptoms of chronic liver disease. Other patients experience rapid progression of the disease to acute liver failure, as marked by coagulopathy and jaundice.
o Ascites and hepatic encephalopathy can occur.
o Clinicians must consider the diagnosis of autoimmune hepatitis when confronted with a patient who has acute hepatitis or acute liver failure (defined by the new onset of coagulopathy).
o The chronic hepatitis associated with autoimmune hepatitis may range in severity from a subclinical illness without symptoms and with abnormal results on liver chemistries to a disabling chronic liver disease. Symptoms and physical examination findings may stem from the various extrahepatic diseases associated with autoimmune hepatitis. Common symptoms include the following:
 Fatigue
 Upper abdominal discomfort
 Mild pruritus
 Anorexia
 Myalgia
 Diarrhea
 Cushingoid features
 Arthralgias
 Skin rashes (including acne)
 Edema
 Hirsutism
 Amenorrhea
 Chest pain from pleuritis
 Weight loss and intense pruritus (unusual)
o As many as 20% of patients present initially with signs of decompensated cirrhosis. In other patients, chronic hepatitis progresses to cirrhosis after years of unsuccessful immunosuppressant therapy marked by multiple disease relapses. This is said to occur in 20-40% of patients.
o Patients with cirrhosis may experience classic symptoms of portal hypertension like variceal bleeding, ascites, and hepatic encephalopathy.
• Disease associations: Autoimmune hepatitis, especially type 2, is associated with a wide variety of other disorders. Involvement of other systems may present at disease onset or may develop during the course of active liver disease. These conditions, most of which are immunologic in origin, include the following:
o Hematologic complications
 Hematologic manifestations of hypersplenism
 Autoimmune hemolytic anemia
 Coombs-positive hemolytic anemia
 Pernicious anemia
 Idiopathic thrombocytopenic purpura
 Eosinophilia
o Gastrointestinal complications
 Inflammatory bowel disease (6%): The presence of ulcerative colitis in patients with autoimmune hepatitis should prompt performance of cholangiography to exclude PSC.
 Celiac disease
o Proliferative glomerulonephritis
o Fibrosing alveolitis
o Pericarditis and myocarditis
o Endocrinologic complications
 Graves disease (6%) and autoimmune thyroiditis (12%)
 Juvenile diabetes mellitus
Rheumatologic complications
Rheumatoid arthritis and Felty syndrome
Sjögren syndrome
Systemic sclerosis
Mixed connective-tissue disease
Erythema nodosum
Leukocytoclastic vasculitis: Patients may present with symptoms of leg ulcers.
Febrile panniculitis
Lichen planus
Uveitis
• Association with hepatitis C
o The hepatitis C virus (HCV) has several important associations with autoimmune hepatitis. The prevalence rate of HCV infection in patients with autoimmune hepatitis is similar to that in the general population.
o This implies that HCV is not an important factor in the etiology of autoimmune hepatitis; however, patients who are seropositive for anti–LKM-1 frequently are infected with HCV.
o These patients have predominant features of chronic viral hepatitis and frequently lack antibodies to P-450 IID6.
o Such patients respond to treatment with interferon. They should be distinguished from anti–LKM-1-positive patients who have a positive anti–P-450 IID6, are seronegative for anti-HCV, and are responsive to steroid therapy.
o False-positive results on anti-HCV enzyme-linked immunoassay (ELISA) tests are described in the setting of hypergammaglobulinemia, including that observed in patients with autoimmune hepatitis.
o In patients with ANA and/or ASMA seropositivity and a positive anti-HCV, a false-positive reaction to HCV should be excluded by performing a test for HCV RNA using the polymerase chain reaction (PCR).
o In general, patients with definite autoimmune hepatitis have median serum titers of ASMA and ANA of 1:160 and 1:320, respectively. In contrast, these titers may be in the range of 1:80 or less in patients with true chronic viral hepatitis.
o Although autoimmune hepatitis and chronic HCV have similar histologic features, moderate-to-severe plasma cell infiltration of the portal tracts is more common in patients with autoimmune hepatitis. Portal lymphoid aggregates, steatosis, and bile duct damage are more common in patients with chronic HCV.
• Overlap syndromes: Patients with autoimmune hepatitis may present with features that overlap those classically associated with patients with PBC and PSC.
o About 7% of patients with autoimmune hepatitis have a disease that overlaps with PBC. They may have a detectable AMA (usually in low titer), histologic findings of bile duct injury and/or destruction, and the presence of hepatic copper. The natural history of the disease tends to echo type 1 autoimmune hepatitis.
 About 6% of patients with autoimmune hepatitis have a disease that overlaps with PSC. Patients with the autoimmune hepatitis-PSC overlap syndrome frequently have concurrent inflammatory bowel disease. The liver biopsy findings reveal bile duct injury. Findings from cholangiograms are abnormal.
• Autoimmune cholangitis is characterized by mixed hepatic and cholestatic liver chemistries, positive ANA and/or ASMA, negative AMA, antibodies to carbonic anhydrase, and histology that resembles PBC. Some authors contend that this condition is AMA-negative PBC. Patients may have an unpredictable response to therapy with steroids or ursodiol.
• Cryptogenic autoimmune hepatitis is characterized by a clinical picture that is indistinguishable from autoimmune hepatitis. Here, the diagnosis is made by liver biopsy. ANA, ASMA, and anti–LKM-1 are negative at disease onset and may appear late in the disease course, as might anti-SLA. The disease usually is responsive to steroid therapy.
SIGNS:
• Common findings on physical examination are as follows:
o Hepatomegaly (83%)
o Jaundice (69%)
o Splenomegaly (32%)
o Spider angiomata (58%)
o Ascites (20%)
o Encephalopathy (14%)
• All of these findings may be observed in patients with disease that has progressed to the point of cirrhosis with ensuing portal hypertension; however, hepatomegaly, jaundice, splenomegaly, and spider angiomata also may be observed in patients who do not have cirrhosis
DIFFRENTIAL DIAGNOSIS
Other autoimmune liver diseases
• Primary biliary cirrhosis
• Primary sclerosing cholangitis
• Autoimmune hepatitis/primary biliary cirrhosis overlap syndrome
• Autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome
• Autoimmune cholangiopathy
Chronic viral hepatitis
• Chronic hepatitis B
• Chronic hepatitis C
• Chronic hepatitis delta
• Chronic hepatitis due to other viruses
Other
• Chronic drug-induced hepatitis
• Alpha-1-antitrypsin deficiency
• Wilson's disease
• Cholangiopathy related to AIDS
• Steatohepatitis
• Nonalcoholic
• Alcoholic
• Granulomatous hepatitis
• Systemic lupus erythematosus
• Graft-versus-host disease
• Cryptogenic chronic hepatitis or cirrhosis
Acute hepatitis
• Acute viral hepatitis secondary to hepatitis A to E
• In some parts of the world, cytomegalovirus, Epstein-Barr virus, and herpes viruses
• Acute drug induced hepatitis