Autoimmune hepatitis, one disease with many faces: Etiopathogenetic, clinico-laboratory and histological characteristics

Table 2 Clinical features of autoimmune hepatitis

Characteristic
Age at presentation	Any age of both sexes and all ethnic groups; bimodal distribution usually with peaks around puberty and between 4th and 6th decades although a considerable number of patients are even older (above 65 years of age)
Types of disease onset	Broad range from asymptomatic (‘‘en passant’’ diagnosis) to acute/severe or even fulminant hepatitis
	Most common clinical phenotype of the disease (two thirds of patients) is characterized by an insidious onset with unspecific symptoms, such as fatigue, right upper quadrant pain, lethargy, malaise, anorexia, nausea, pruritus, fluctuating jaundice and polyarthralgia without arthritis, sometimes dating back years
	Acute onset of AIH does exist and contains two different clinical entities (the acute exacerbation of chronic AIH and the true acute AIH without histological findings of chronic liver disease)
	One third of patients at diagnosis have already developed cirrhosis irrespective of the presence of symptoms or not, suggesting a delay in diagnosis due to unfamiliar clinicians, histopathologists and/or laboratories
Physical findings	Depends on the clinical status of the disease, ranging from completely normal to signs and symptoms of chronic liver disease and/or portal hypertension
Clinical features in special conditions	Presentation of AIH during pregnancy or more frequently after delivery
	Development of AIH after liver transplantation for other liver diseases (de novo AIH or post-transplant plasma cell hepatitis)
	Development of AIH after drugs, supplements or herbals (drug-induced AIH, nitrofurantoin and minocycline implicated in 90% of cases)
Specific characteristics	Frequent presence in the patient or first-degree relatives of other autoimmune or immune-mediated diseases like Hashimoto thyroiditis, Grave’s disease, vitiligo, alopecia, rheumatoid arthritis, diabetes mellitus type-1, inflammatory bowel disease, psoriasis, systemic lupus erythematosus, Sjögren’s syndrome and celiac disease
	An unusual form of AIH has been reported in 10%-18% of patients with APECED, also known as APS-1
Complications	HCC development in AIH is less common than other liver diseases but it does exist and is associated with cirrhosis, suggesting surveillance in all cirrhotic patients with AIH
	Drug-related complications are also significant in 10%-25% of patients; these complications are most commonly related to long-term corticosteroid use or azathioprine toxicity and/or intolerance

AIH: Autoimmune hepatitis; HCC: Hepatocellular carcinoma; APECED: Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy; APS-1: Autoimmune polyglandular syndrome type 1.