ESSENTIALS OF DIAGNOSIS
Usually young to middle-aged women.
Chronic hepatitis with high serum globulins and characteristic liver histology.
Positive antinuclear antibody (ANA) and/or smooth muscle antibody in most cases in the United States.
Responds to corticosteroids.
Although autoimmune hepatitis is usually seen in young women, it can occur in either sex at any age. The incidence, which has been rising, and prevalence are estimated to be 8.5 and 107 per million population, respectively. Affected younger persons are often positive for HLA-B8 and HLA-DR3; older patients are often positive for HLA-DR4. The principal susceptibility allele among white Americans and northern Europeans is HLA DRB1*0301; HLA DRB1*0401 is a secondary but independent risk factor. Variants of the SH2B3 and CARD10 genes have also been identified. The risk of autoimmune hepatitis is increased in first-degree relatives of affected patients.
The onset is usually insidious. About 20% of cases present with acute hepatitis (and occasionally acute liver failure), and some cases follow a viral illness (such as hepatitis A, Epstein-Barr infection, or measles) or exposure to a drug or toxin (such as nitrofurantoin, minocycline, hydralazine, methyldopa, or infliximab). Exacerbations may occur postpartum. Amenorrhea may be a presenting feature, and the frequency of depression appears to be increased. Thirty-four percent of patients, and particularly elderly patients, are asymptomatic. Examination may reveal a healthy-appearing young woman with multiple spider telangiectasias (see eFigure 16–3), cutaneous striae, acne, hirsutism, and hepatomegaly. Extrahepatic features include arthritis, Sjögren syndrome, thyroiditis, nephritis, ulcerative colitis, and Coombs-positive hemolytic anemia. Patients, especially elderly patients, with autoimmune hepatitis are at increased risk for cirrhosis, which, in turn, increases the risk of hepatocellular carcinoma (at a rate of about 1% per year).
Serum aminotransferase levels may be greater than 1000 units/L, and the total bilirubin is usually increased. Autoimmune hepatitis has been classified as type I or type II, although the clinical features and response to treatment are similar between the two types. In type I (classic) autoimmune hepatitis, ANA or smooth muscle antibodies (either or both) are usually detected in serum. Serum gamma-globulin levels are typically elevated (up to 5–6 g/dL [0.05–0.06 g/L]); in such patients, the EIA for antibody to HCV may be falsely positive. Other antibodies, including atypical perinuclear antineutrophil cytoplasmic antibodies (pANCA) and antibodies to histones, F-actin, and alpha-actinin may be found. Antibodies to soluble liver antigen (anti-SLA) characterize a variant of type I that is marked by severe disease, a high relapse rate after treatment, and absence of the usual antibodies (ANA and smooth muscle antibodies). Anti-SLA is directed against a transfer RNA complex responsible for incorporating selenocysteine into peptide chains—Sep (O-phosphoserine) tRNA: Sec (selenocysteine) tRNA synthase, or SEPSECS. Type II, seen more often in girls under age 14 in Europe, ...