Autoimmune hepatitis (ORPHA:2137)
A rare liver disease characterized by immune-mediated, acute or chronic liver inflammation, clinically presenting as cryptogenic hepatitis, with interface hepatitis on histological examination, elevated serum aminotransferase levels, and hypergammaglobulinemia / elevated immunoglobulin G, in the presence or absence of specific circulating autoantibodies. Patients may be asymptomatic, chronically ill, or present with acute liver failure. Concurrent autoimmune diseases are frequently observed.
Epidemiology
The incidence and prevalence of autoimmune hepatitis (AIH) varies across different age groups, ethnicities and geographical region. In Caucasian Europeans and North Americans, the prevalence is approximately 1/6,000. Although possibly under recognized, a lower occurrence is reported in Asian countries. All ages and both genders may be affected, although there is a clear female preponderance.
Clinical description
The disease occurs in both pediatric and adult patients. Presentation is highly variable; approximately 25% of patients present with an acute onset or an acute- on-chronic disease process. A subset has severe disease at presentation and may rapidly progress to liver failure. The most common clinical phenotype (two-thirds of patients) is characterized by an insidious onset either without any apparent symptom or with non-specific symptoms (including fatigue, general ill health, right upper quadrant pain, lethargy, malaise, anorexia, weight loss, nausea, pruritus, fluctuating jaundice and polyarthralgia of the small joints without arthritis). Half of patients have liver fibrosis at diagnosis, and one third have cirrhosis irrespective of the presence of symptoms. AIH subtypes are classed based on presence of auto-antibodies. AIH type 1 accounts for 90% of cases, occurs at any age and is defined by detection of either antinuclear antibodies (ANA), anti-smooth muscle antibodies (anti-SMA), or anti-soluble liver antigen/liver pancreas antigen antibodies (anti-SLA/LP). AIH type 2 is defined by the presence of anti-liver kidney microsome type 1 (anti-LKM1), anti-liver cytosol (anti-LC1) and, rarely, anti-liver-kidney microsomal antibody type 3 (anti-LKM3), onset is in childhood or young adulthood, and is typically of severe acute disease with frequent failure of treatment and frequent relapses after steroid withdrawal. Antibodies may be absent in up to one third of patients, particularly in severe, acute AIH, and is defined as seronegative AIH. Concurrent autoimmune or immune-mediated diseases in the patient are common.
Etiology
Environmental factors, genetic susceptibility, and impaired immunoregulatory networks are thought to play a role.
Diagnostic methods
AIH should be considered in any patient with acute or chronic liver disease. Diagnosis is very challenging, and is based in diagnostic scores comprised of typical, but mostly non-specific, findings of autoantibodies (for which testing is not currently standardized), hypergammaglobulinemia/elevated IgG, histological pattern of interface hepatitis, exclusion of other liver diseases and, eventually, the treatment response to steroids.
Differential diagnosis
The differential diagnosis is of other causes of acute or chronic liver failure such as the rare disorder Wilson disease as well as viral hepatitis, hepatotoxic drugs, and excessive alcohol consumption.
Management and treatment
The standard treatment is with a steroid-based induction and followed by thiopurine-based maintenance regime (typically prednisolone and azathioprine). Immunosuppressive treatment tends to be life-long. The aim of treatment is complete biochemical remission defined as normalized liver enzymes and gammaglobulins / IgG. Some patients require second- or third-line treatment due to intolerance or insufficient response to standard treatment. Repeated liver histology can be used to guide therapy. Therapy withdrawal can be considered where patients have stable biochemical remission for at least 24-36 months; however, relapses are common. Untreated autoimmune hepatitis can lead to cirrhosis, complications of cirrhosis, and eventually to liver failure.
Prognosis
Morbidity largely relates to treatment side effects. The risk of mortality is determined by disease progression to liver cirrhosis under insufficient treatment response and by acute severe presentation. Patients with AIH-onset under the age of 18 seem to be more prone to recurrent flares.

                            Last update: 
                            April 2021


                            - Expert reviewer(s): 
                            Dr Marcial SEBODE | RARE-LIVER*


                                * European Reference Network