Clinical manifestations and diagnosis of autoimmune hepatitis

Type 1 autoimmune hepatitis – ANA and/or smooth muscle (ASMA);
ASMA with titers of 1:320 or greater generally reflect the presence of AAA.
 ELISA for antiactin antibodies (IgG anti F-actin)

 Type 2 autoimmune hepatitis –
 antibodies to liver/kidney microsomes (ALKM-1) and/or to a liver cytosol antigen (ALC-1)



 EPIDEMIOLOGY — all ethnic groups and can occur at any age, often in 40s or 50s
female to male ratio of 3.6 to 1

 CLINICAL MANIFESTATIONS —  variability in its clinical manifestations, asymptomatic patients, acute liver failure or subclinical disease

 mild or severe nonspecific symptoms, such as fatigue, lethargy, malaise, anorexia, nausea, abdominal pain, and itching, arthralgia small joints

 Diseases commonly seen with autoimmune hepatitis include hemolytic anemia, immune thrombocytopenia (ITP), type 1 diabetes mellitus, thyroiditis, celiac sprue, and ulcerative colitis (which is more often associated with primary sclerosing cholangitis).  polyglandular autoimmune syndrome can occur in children with type 2 autoimmune hepatitis.

 Complications —  progression to carcinoma is less frequent than in chronic viral hepatitis. One report found an increased risk of nonmelanoma skin cancer in patients with autoimmune hepatitis treated with long-term immunosuppression

 AASLD 2010:

• The diagnosis should be made in patients with compatible clinical signs, symptoms, and laboratory abnormalities. Compatible laboratory and histological abnormalities include abnormal liver biochemical tests, an increased total IgG or gamma-globulin levels, serologic markers (ANA, SMA, anti-LKM-1, or anti-LC1), and interface hepatitis. Other conditions that can cause chronic hepatitis should be excluded.
• In unclear cases (such as those who have few or atypical findings), a standardized scoring system should be used in the assessment. 
• In those who are negative for conventional autoantibodies, additional autoantibodies should be sought. At minimum, this should include anti-SLA and atypical pANCA.
• Cholangiographic studies should be considered to exclude primary sclerosing cholangitis in adults who do not respond to corticosteroid therapy after three months.
• In children, cholangiographic studies should be considered to exclude autoimmune sclerosing cholangitis.
• All patients with autoimmune hepatitis and inflammatory bowel disease should undergo cholangiographic studies to exclude primary sclerosing cholangitis.

Laboratory features — aminotransferase elevations

In some cases, however,  cholestatic picture (high levels of conjugated bilirubin and ALP. Extrahepatic obstruction (diagnosed by imaging studies), and cholestatic forms of viral hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, and the variant syndromes must be considered.

- elevation in serum globulins, particularly gamma globulins and, generally, IgG. Hyperglobulinemia is generally associated with circulating autoantibodies,
- partial IgA deficiency is seen particularly in children with both type 1 and, more frequently, type 2 disease

Histology — Anonspecific findings:

• A portal mononuclear cell infiltrate, 
• The periportal lesion, sometimes referred to as piecemeal necrosis or interface hepatitis, There may also be centrizonal necrosis.
• Bile duct changes (destructive and nondestructive cholangitis and ductopenia)25%. Granulomas are uncommonly seen.
• An exuberant plasma cell infiltrate, and multinucleated giant cells, may be seen 
• Fibrosis is present in all but the mildest forms of autoimmune hepatitis. Advanced fibrosis connects portal and central areas (bridging), resembles regenerating nodules, results in cirrhosis.

 There are some patients who present with all the features of autoimmune hepatitis but lack circulating ANA, ASMA, anti SLA/LP, ANCA, or ALKM-1 antibodies. -cryptogenic chronic hepatitis or cryptogenic cirrhosis. A therapeutic response to anti-inflammatory therapy may be the only indication that autoimmune hepatitis is the underlying disease in these patients.

 simplified criteria :.

• Autoantibodies:  one point if the ANA or SMA are 1:40 OR two points if the ANA or SMA are ≥1:80 (OR if the LKM ≥1:40 OR if the SLA is positive).
• IgG:  one point if the IgG is > the upper limit of normal OR  two points if the IgG is >1.10 times the upper limit of normal.
• Liver histology (evidence of hepatitis is a mandatory condition): assign one point if the histological features are compatible with autoimmune hepatitis OR two points if the histological features are typical of autoimmune hepatitis. Typical histologic features were defined as the presence of interface hepatitis, lymphocytic/lymphoplasmacytic infiltrates in the portal tracts and extending into the lobule, emperipolesis (active penetration of one cell into and through a large cell), and hepatic rosette formation. Compatible features were defined as a picture of chronic hepatitis with lymphocytic infiltration without all the features considered typical.
• Absence of viral hepatitis: assign two points ,mainly for hepatitis B and C. However, other forms of hepatitis should be considered depending upon the clinical setting.

probable autoimmune hepatitis - six, while a definite diagnosis, points are ≥seven.
study involving 11 international centers, the simplified scoring system had 88 % sensitivity and 97 % specificity

 limitation of scoring system is  lack of standardization of some of the autoantibody tests across testing facilities.

 -difficult to distinguish autoimmune hepatitis from overlap syndromes
 -identify patients with overlap who have a treatable autoimmune component.
 -The validation study did not include patients with differential diagnosis
- The prevalence of ANAs or ASMAs did not correlate with the clinical or histologic severity of autoimmune hepatitis or the response to immunosuppressive therapy














Acute hepatitis —  to distinguish autoimmune  from acute viral hepatitis,  hepatitis C virus RNA (PCR) is required to rule out hepatitis C (Ab up to 6 months)

Chronic hepatitis C — The nonspecific antibody response  in  autoimmune hepatitis may make it difficult to distinguish between autoimmune diseases and chronic hepatitis C- to measure circulating hepatitis C RNA; as a result, patients with autoimmune hepatitis who have false positive hepatitis C antibodies can be identified. chronic hepatitis C may make a variety of autoantibodies including rheumatoid factor and cryoglobulins;



 In addition to clinical features, the magnitude of fatty infiltration, and the presence of polymorphonuclear leukocytes and central fibrosis in the biopsy may point to steatohepatitis.


Although ANA can be seen in both conditions, ASMA and AMA are rare in lupus; thus, their presence suggests that the patient has autoimmune hepatitis. Systemic lupus erythematosus is differentiated from autoimmune hepatitis,by presence of antiribosomal P protein antibodies


It is probable that autoimmune hepatitis also accounts for some cases of cryptogenic chronic hepatitis or cirrhosis in which autoantibodies are absent or will eventually become detectable

certain histologic features (eg, portal neutrophils, which are more common in DILI) can help distinguish between drug induces hepatitis and autoimmune

 Iron overload — On occasion, a raised serum ferritin, sometimes accompanied by elevated transferrin saturation, occurs in autoimmune hepatitis or chronic viral hepatitis. Differentiated from genetic hemochromatosis can be excluded by the measurement of hepatic iron concentration and subsequent calculation of the hepatic iron index and HFE mutations

Wilson disease — Almost exclusively a disease of children, Wilson disease can present as a chronic hepatitis or as fatty liver disease