History and exam

Key diagnostic factors

common

presence of risk factors

Key risk factors include female sex, genetic pre-disposition, and immune dysregulation.

fatigue/malaise

Common, but non-specific symptom.[1]

anorexia

Common, but non-specific symptom.[14]

abdominal discomfort

Common, but non-specific symptom.[14]

hepatomegaly

May be present.

jaundice

Up to 50% of patients, even with an insidious onset of disease, may be clinically jaundiced or report previous episodes of icterus.[36]

uncommon

encephalopathy

Associated with portal hypertension.[14]

Other diagnostic factors

common

pruritus

Severe pruritus is not typical; pruritus, if present, is usually mild.[35]

arthralgia

Arthralgia involving small joints is common; joint pains, sometimes flitting, are reported in 30% to 60% of patients, although joint swelling is uncommon.[1][36]​​

nausea

Common, but non-specific symptom.[36]

amenorrhoea

Common, but non-specific symptom.[26][36]

spider angiomata

A sign of advanced chronic liver disease.[26]

uncommon

fever

Unexplained low-grade fever is a rare feature; temperature is usually 40°C (104°F) or less.[26]​

maculopapular skin rash

An uncommon and non-specific symptom.[26][36]

gastrointestinal bleeding

Associated with portal hypertension.[1]

splenomegaly

A sign of advanced chronic liver disease.[26]

ascites

A sign of advanced chronic liver disease.[26]

Risk factors

strong

female sex

Female adults and children are more frequently affected than males.[5]​[6]​​[7][8][9][10]

AIH type 1 is the most common form of AIH; 78% of patients are women (female:male ratio is 4:1).[12] In type 2 AIH, approximately 95% of patients are female.[3][13]

genetic pre-disposition

For type 1 AIH, association has been established with human leukocyte antigen (HLA)-DR3 (found in linkage disequilibrium with HLA-B8 and HLA-A1) and HLA-DR4 (among patients who are HLA-DR3-negative). Type 2 AIH has been associated with the HLA-DQB1 and HLA-DRB1 alleles.[3]

immune dysregulation

Other autoimmune diseases, including thyroiditis, type 1 diabetes, ulcerative colitis, coeliac disease, and rheumatoid arthritis, are often found in patients with AIH (38% of patients with type 1 and 34% with type 2).[13]

AIH may develop as a component of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome in 10% to 20% of patients.[2][18]

weak

measles virus

There has been evidence implicating measles virus as a trigger of AIH.[3] This is difficult to prove, since viruses may be part of a hit-and-run phenomenon, in which induction of the autoimmune process occurs many years before overt disease, making it impossible to identify the trigger.

cytomegalovirus

There has been evidence implicating cytomegalovirus as a trigger of AIH.[3] This is difficult to prove, since viruses may be part of a hit-and-run phenomenon, in which induction of the autoimmune process occurs many years before overt disease, making it impossible to identify the trigger.

Epstein-Barr virus

There has been evidence implicating Epstein-Barr virus as a trigger of AIH.[3] This is difficult to prove, since viruses may be part of a hit-and-run phenomenon, in which induction of the autoimmune process occurs many years before overt disease, making it impossible to identify the trigger.

hepatitis viruses A, C, and D

There has been evidence implicating hepatitis viruses as triggers of AIH.[3] This is difficult to prove, since viruses may be part of a hit-and-run phenomenon, in which induction of the autoimmune process occurs many years before overt disease, making it impossible to identify the trigger.

certain drugs

Certain drugs (including oxyphenisatin, minocycline, ticrynafen, dihydralazine, methyldopa, nitrofurantoin, diclofenac, atorvastatin, interferon, pemoline, infliximab, and ezetimibe) and some herbal agents (such as black cohosh and dai-saiko-to) can induce hepatocellular injury that resembles AIH.[3][15][16][17] It is not clear whether they induce or unmask AIH, or cause a drug-induced hepatitis with accompanying autoimmune features.

Use of this content is subject to our disclaimer