Autoimmune hepatitis (AIH) does not have a single presentation, and the way it comes to medical attention shapes both its prognosis and its management.
The spectrum of presentation
Asymptomatic disease is common. About a third of cases are picked up without specific symptoms, often through abnormal liver tests, or with only chronic non-specific complaints such as fatigue, malaise, arthralgia or amenorrhoea. The frequency of moderate-to-severe interface hepatitis and of fibrosis at diagnosis is similar to that in symptomatic patients, and progression and treatment response are also similar. The frequency of concurrent skin and autoimmune disorders is higher in asymptomatic patients than in symptomatic ones. Untreated asymptomatic disease still progresses to cirrhosis — more slowly than untreated severe symptomatic disease — so it should not be left untreated; compared with severe symptomatic patients who are receiving treatment, untreated asymptomatic patients do poorly.
Symptomatic disease with acute onset can arise in two ways. It may be true acute AIH, the first acute attack of hepatitis, or it may be an acute exacerbation of previously undiagnosed subclinical chronic AIH, in which laboratory or histological evidence of long-standing chronic hepatitis is already present.
Acute severe or fulminant hepatitis is the most dangerous end of the spectrum. Acute severe AIH is an acute icteric presentation with impaired clotting (INR ≥ 1.5) but without encephalopathy; when hepatic encephalopathy develops within 26 weeks of the onset of symptoms, the presentation is fulminant. Acute severe or fulminant hepatitis accounts for 3-6% of AIH patients in the US and Britain.
The picture is characterised by a marked increase in AST and ALT, centrilobular necrosis with haemorrhage, plasma cell infiltration, and lymphoid follicles on biopsy. Clues that would normally support AIH may be missing: serum IgG is in the normal range in about 40% of cases, and ANA is absent or only weakly positive. A MELD score above 12 is associated with a failure rate of treatment of more than 97%, and patients who have not improved after 2 weeks of treatment have a very high mortality rate.
Autoantibody-negative disease accounts for about 13% of cases. These patients have the full clinical and histological picture and respond to treatment and progress in the same way as serologically positive patients, but the conventional antibodies are negative. In about 15-20% of them, atypical pANCA and anti-SLA are positive. Follow-up serology is suggested, because some patients become positive for the conventional antibodies over time.
Overlap syndromes
Patients with AIH who have cholestatic laboratory findings and histological evidence of bile duct injury or loss are considered to have an overlap syndrome. No treatment strategy is established; treatment is chosen according to whichever component — cholestatic or AIH — dominates.
Two cholestatic diseases are the usual partners. Primary biliary cholangitis (PBC) is marked by AMA, the anti-mitochondrial antibody, and primary sclerosing cholangitis (PSC) shows focal stricture of the bile duct with dilatation on cholangiography. About 8% of patients with AIH have cholestatic changes without the AMA of PBC and without the cholangiographic changes of PSC.
A further variant is IgG4-associated AIH, in which plasma cells infiltrating the liver are positive for IgG4 in 3-35% of cases. It sits within the spectrum of IgG4-related disease, which also includes IgG4-associated cholangitis and autoimmune pancreatitis — the latter accompanied by liver injury in 60-70% of cases. The diagnostic criteria are more than 10 IgG4-positive plasma cells per high-power field (HPF) together with a serum IgG4 above 135 mg/dl, and they are met in only 3.5% of AIH patients.