Autoimmune hepatitis (AIH) is diagnosed by combining serology, immunoglobulins and biopsy, and by excluding the chronic liver diseases that can look the same. No single test confirms it.
A definitive diagnosis
A definitive diagnosis of AIH requires all four of the following:
- positivity for one or several combinations of ANA, SMA and anti-LKM1
- hypergammaglobulinaemia with an elevated IgG — in up to one-third of patients with acute-onset AIH this can be in the normal range
- histological evidence of interface hepatitis — the biopsy should be taken before treatment starts, because treatment changes the morphology
- exclusion of the other chronic disorders that resemble AIH
Excluding the mimics
The diseases to exclude are Wilson’s disease, chronic viral hepatitis, drug-induced liver disease, non-alcoholic fatty liver disease (NAFLD) and the immune cholangiopathies.
Drug-induced liver disease is a recognised mimic: 9% of patients who satisfy the presentation of AIH are instead suffering from a drug-induced liver injury that mimics it. Two drugs account for about 90% of cases: nitrofurantoin and minocycline. The typical patient is a woman (80-90%) who develops jaundice (70%) with an acute onset after drug exposure, at a median of 40 days, and features of hypersensitivity such as fever, rash and eosinophilia in about 20%. Biopsy findings that favour a drug cause are portal neutrophils and intercellular cholestasis. The key to the diagnosis is the interval between drug exposure and the onset of disease, together with how the condition behaves after the drug is withdrawn.
A probable diagnosis
A probable diagnosis is justified when the clues point to AIH but are not sufficient for a definitive one. This is the situation in patients who are negative for the conventional antibodies but positive for atypical p-ANCA, anti-SLA, anti-LC1 or anti-actin.
When a patient strongly suspected of AIH has negative antibody results, two possibilities should be considered: incompetent laboratory performance, in which case a second laboratory should be used, or a genuinely antibody-negative case of AIH.
Laboratory testing
Antibody testing follows two lines. The first line is screening by immunofluorescence (IFL). The threshold for positivity differs by age — 1:40 in adults and 1:20 in children — so results should be reported with the level of dilution and the cellular pattern, which can be speckled or diffuse. The second line is ELISA, which is more specific.
Scoring systems
Because AIH is so heterogeneous, scoring systems are used to guide diagnosis. There are two: the comprehensive (revised original) system and the simplified system. The comprehensive system is more sensitive (100% versus 95%), while the simplified system is more specific (90% versus 73%).
Treatment
The mainstay of treatment for both types is high-dose corticosteroids. In practice, first-line treatment combines a corticosteroid with azathioprine, which allows a lower steroid dose and reduces the side effects of steroids. Budesonide, a steroid that is mostly cleared on its first pass through the liver, is an alternative for patients without cirrhosis and without an acute severe presentation; it is not used in either of those groups.
With high-dose prednisolone alone, the remission rate is 65% at 18 months and 80% at 3 years. Remission is defined as complete resolution of the laboratory abnormalities — AST, ALT and the immunoglobulin level — together with resolution of interface hepatitis on biopsy. In acute severe AIH, treatment is started urgently and liver transplantation is considered early if there is no improvement.