Autoimmune hepatitis in Italy: The Bologna experience☆
Introduction
Autoimmune hepatitis (AIH) is a chronic disorder of the immune system targeting the liver characterized by loss of immunological tolerance against hepatocytes and inducing chronic inflammatory destruction of liver parenchyma, cirrhosis and eventually liver failure [1], [2]. In keeping with other autoimmune disorders, AIH predominantly affects female patients at any age and its onset may range from asymptomatic to hyper-acute with liver failure. Associated autoimmune extra-hepatic manifestations are often present. Immunosuppressive treatment is usually effective in controlling liver inflammation and inducing clinical and biochemical amelioration in most patients [3].
AIH is conventionally subdivided into type 1 and type 2 according to the autoantibody profile: antinuclear (ANA), anti-smooth muscle (SMA), perinuclear anti-neutrophil cytoplasmic antibody (pANCA), anti-double stranded DNA (anti-dsDNA) and anti-soluble liver antigen (anti-SLA) are deemed as markers of type 1 AIH [4], [5], [6], [7], [8], liver/kidney microsomal antibody type 1 (anti-LKM1) and liver cytosol antibody type 1 (anti-LC1) of type 2 AIH [9], [10], [11].
More than forty years after its original report, [12] the causes of AIH are mostly hypothetical, and the diagnosis is still based on descriptive criteria assembled in a scoring system first issued in 1993 [13], revised in 1999 [14] and recently proposed in a simplified form [15].
In recent years, several open issues have been raised on AIH concerning: (a) the clinical utility of the subclassification of AIH into type 1 and type 2 according to the autoantibody profile [14], [16], [17]; (b) the impact of sex on disease expression and prognosis [18], [19], [20]; (c) the significance of the age at onset (pediatric, adult, elderly) [21], [22], [23], [24], [25]; (d) the ultimate goal of the immunosuppressive treatment [26], [27], [28], [29].
In our Unit, a tertiary referral centre for AIH in Italy, we had the opportunity to diagnose and follow up a significant number of Italian AIH patients. This study aims to assess the clinical, biochemical, serological and genetic features and outcome of AIH in Italian patients. In addition, we also evaluate factors predictive of treatment response and long-term prognosis.
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Patients
Between 1992 and 2007, 163 patients with unexplained liver disease were referred to our Unit. All patients had seronegative viral markers (HbsAg negative, anti-HCV negative and HCV RNA negative by PCR assays), and the other known causes of chronic liver disease (genetic, toxic, metabolic) were ruled out using appropriate tests. Hepatotoxic drug usage and significant alcohol intake were carefully excluded. All patients fulfilled the AIH diagnosis according to the International Autoimmune
Clinical, immunological and genetic features at presentation
Over a period of 15 years, we identified 163 consecutive patients with “definite” (145 patients, 89%) or “probable” (18 patients, 11%) AIH, diagnosed according to the criteria issued in 1999 by the International Autoimmune Hepatitis Group [14]. The main clinical, biochemical, immunological and histological features at presentation are reported in Table 1.
Female sex was prevalent (82%), mean age at onset was 36 years (SD 21) with two peaks in the second and in the fifth decade. The most frequent
Discussion
We report the clinical, biochemical and immunological features of 163 consecutive Italian patients with AIH homogeneously diagnosed according to internationally recognized criteria [14], referred to our Unit in the last 15 years from all over Italy. In nearly 60% patients the presentation of the disease was devoid of relevant clinical features, being insidious or even asymptomatic and occasionally recognized, whereas in the remaining 40% the clinical onset was marked by signs and symptoms of
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The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.