Presents with anything from subtle anorexia, fatigue, rashes, abdo/joint pain to acute liver failure. Jaundice does not relate to degree of histological fibrosis.
Check Prothrombin time, glucose, ammonia, lactate to monitor liver disease. Response to Vitamin K at 8 hours is prognostic, so refer to specialist centre if poor.
Type 1 (60%) is ANA/SMA (=small muscle) positive, usually presents as a viral hepatitis ie jaundice, raised transaminases, but can present insidiously, even with established portal hypertension, or as acute on chronic. Type 2 is LKM1 (liver/kidney/microsomal) positive, similar clinical presentation but probably more jaundice and cirrhosis, less impairment in synthesis. Seronegative hepatitis has been described in up to 20%. Antibodies to soluble liver antigen described. Quite common to see pANCA, too (not sensitive or specific). The role of these autoantibodies in disease is unclear!
As with other autoimmune diseases, strong association with HLA types. DR4 associated with less severe disease, lower rate of relapse (but older presentation). Has been reported in association with immune disorders eg autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED).
Alkaline phosphatase rarely exceeds 4x normal and generally remains less than 2x normal. Raised immunoglobulins are a clue, with a selective increase in IgG (up to 3x higher than the upper level of normal) seen in 75-85% (kids and acute less likely). But not specific – also seen in Wilson’s disease; other causes should be excluded too. Interface hepatitis on biopsy, with sharp differentiation between inflammatory zone and normal liver tissue. Findings don’t always match biochemistry. Nonetheless, diagnosis is ultimately clinical! Diagnostic scoring system available. Differential also includes chronic hepatitis C and drug induced liver injury.
Treat with steroids, azathioprine (remember TPMT polymorphisms) when improving, else mycophenylate. 85% achieve remission, biochemically within 6-12 weeks, histologically 6-12 months. More than double normal enzymes is an indication for treatment, else bridging or multilobular necrosis. Progressive fibrosis is associated with liver inflammation, and poor response to treatment (inability to suppress inflammation within 12 months) is associated with progression to cirrhosis (54%) and transplantation (15%). But fibrosis can be stopped or slowed in the majority, and even cirrhosis can regress with treatment. Aim is normal transaminases, immunoglobulins, histology – biopsy is still gold standard for assessing fibrosis.
Unlikely to outgrow. Some trials of withdrawing treatment after remission, only a minority manage more than a year without relapse. Azathioprine 2mg/kg daily effective. Ciclosporin and MMF are second line agents. Hepatobiliary cancers and lymphoma risk is increased and should be screened for.
Transplant may be necessary eg severe acute presentation with poor response to treatment. Results are good, recurrence is rare but well described.
Variants
Can be features of other disorders eg primary biliary cirrhosis, primary sclerosing cholangitis. Biliary changes are commonly seen in autoimmune hepatitis in any case.
Can be part of polyendocrine syndrome type 1.
[Heneghan, Lancet 2013; 382: 1433–44 http://dx.doi.org/10.1016/S0140-6736(12)62163-1]
See also PMID 22495399