Liver biochemical tests show a hepatitic profile with moderately elevated serum aminotransferase levels and bilirubin concentrations, but normal or only mildly elevated serum alkaline phosphatase. Gammaglutamyl transferase activities may be raised but are of uncertain significance. Hyperglobulinemia is marked and is due mainly to elevation of serum immunoglobulin G. These abnormalities tend to fluctuate and may even spontaneously normalize despite ongoing liver damage. Thus, they do not reliably reflect the histological severity of the disease. Serum concentrations of alpha-1-antitrypsin, ceruloplasmin and copper are normal. Patients are seropositive for ANA and/or SMA or occasionally anti-LKM1 at titres of 1:40 or more (lower titres may be significant in children), and are seronegative for antimitochondrial antibodies and for markers of current infection with hepatotropic viruses. Liver biopsy shows features of interface hepatitis (formerly ‘CAH’), including a dense, predominantly lymphoplasmacytic portal and periportal inflammatory infiltrate and piecemeal necrosis of periportal hepatocytes, without evidence of bile duct damage or other changes suggestive of other causes. In severe cases, there may be a lobular hepatitis, rosetting of liver cells, and portal-portal or porto-septal bridging necrosis. Find very low prices on non-prescription drugs – cialis professional online for smart customers.
‘Atypical’ presentations: The Brighton report acknowledged that recognition of atypical presentations of AIH and prompt institution of therapy are crucial to avoid potentially life-threatening sequelae. Up to 30% of patients, particularly in the younger age groups, present with an acute hepatitis that mimics acute viral hepatitis. Serum aminotransferase activities are often more than 20 times the upper normal limits, and patients may be deeply jaundiced, with serum bilirubin concentrations higher than 100 pmol/L. At the other end of the spectrum, 10% to 20% of patients are either apparently healthy, or have signs or symptoms that do not immediately suggest liver disease. Such ‘asymptomatic’ cases usually come to light through the incidental finding of mild to moderate elevations of serum aminotransferases on routine health screening or during investigation of some other condition (most commonly an endocrinological, rheumatological or dermatological disorder). Cirrhosis is as common in these ‘atypical’ cases as in those who present as typical chronic hepatitis, and up to one-third of ‘asymptomatic’ patients with cirrhosis may present with hematemesis and/or melena as the first evidence of their liver disease. Precisely why there is such variability in the clinical presentation of AIH is unclear, but it reinforces the impression that the disease has a protracted subclinical prodrome that may go undetected for long periods in many cases or flare up acutely in others.
Additionally, the report noted that many of the 10% to 20% of cases who present without ANA, SMA or anti-LKM1 may become seropositive for these autoantibodies later in the course of the disease, especially during relapses. It was also noted that most such patients have other autoantibodies against various liver-derived antigens, although tests for these were not widely available. Nonetheless, the diagnosis could still be made on the basis of the other suggestive features of AIH (Table 1). Otherwise, with respect to demographics, liver histology and response to treatment, ‘atypical’ cases were indistinguishable from those with a more typical presentation.
Typical features of autoimmune hepatitis
|• Elevated serum aminotransferase levels and bilirubin concentrations with normal or only mildly elevated serum alkaline phosphatase activities|
|• Hyperglobulinemia with selective elevation of serum immunoglobulin G|
|• Seropositivity for antinuclear and/or smooth muscle antibodies or type 1 liver-kidney microsomal antibodies at titres of 1:40 or more (lower titres may be significant in children)|
|• Seronegativity for antimitochondrial antibodies and for markers of current infection with hepatotropic viruses|
|• No recent history of hepatotoxic drug use or excessive alcohol consumption|
|• Normal serum copper, ceruloplasmin and alpharantitrypsin concentrations|
|• History of other autoimmune diseases in the patient or the patient’s family|
|• Liver histology showing interface hepatitis with predominantly lymphoplasmacytic portal and periportal inflammatory infiltrate, and piecemeal necrosis of periportal hepatocytes, without bile duct damage or other prominent features that usually are more suggestive of other liver disorders|