Autoimmune liver disease in Asian children.

Abstract

Juvenile (i.e. affecting children and adolescents) autoimmune liver diseases are progressive inflammatory liver disorders that include autoimmune hepatitis and autoimmune sclerosing cholangitis. Autoimmune hepatitis (AIH) is characterized serologically by high levels of transaminases and immunoglobulin G (IgG), as well as presence of autoantibodies, and histologically by interface hepatitis, in the absence of a known etiology [1]. Three fourths of patients are girls, some 20 % have associated autoimmune disorders—including thyroiditis, vitiligo, type 1 diabetes, inflammatory bowel disease, IgA nephropathy—and about 40 % have a family history of autoimmune disease [2]. In children and adolescents, AIH has a more aggressive course than in middleage and elderly patients and often presents acutely, though its mode of presentation is very variable, and the disease should be suspected and excluded in all children with symptoms and signs of liver disease not ascribable to more common pathologies. If diagnosed early, AIH responds satisfactorily to immunosuppressive treatment, which should be started as soon as possible, as if left untreated, AIH progresses rapidly to cirrhosis and liver failure. The disease course is often fluctuating, with flares and spontaneous remissions, a pattern that may unfortunately result in delayed referral and diagnosis. The majority of children, however, on physical examination have clinical signs of an underlying chronic liver disease (e.g. spider nevi, palmar erythema, leukonychia, striae), firm liver and splenomegaly. Moreover, at ultrasound imaging, the liver parenchyma is often nodular and heterogeneous. The epidemiology of childhood AIH is unknown, but AIH type 1 (AIH-1) [anti-nuclear antibody (ANA) and/or anti-smooth muscle antibody (SMA) positive] accounts for 2/3 of the cases and presents often around puberty [2], whereas AIH-2 [positive for anti-liver kidney microsomal antibody type 1 (anti-LKM1) and/or anti liver cytosol type 1 antibody (anti-LC1)] tends to present at a younger age and also during infancy. IgG is usually raised at presentation in both types, though 15 % of children with AIH-1 and 25 % of those with AIH-2 have normal levels. IgA deficiency is common in AIH-2 [2]. Severity of disease is similar in the two types, but anti-LKM1-positive children usually have higher levels of bilirubin and transaminases at presentation than those who are ANA/SMA-positive and present significantly more frequently with fulminant hepatic failure [2]. Excluding children with the fulminant presentation, a severely impaired hepatic synthetic function (prolonged prothrombin time and hypoalbuminaemia) is usually more common in AIH-1 than in AIH-2. The severity of interface hepatitis at diagnosis is similar in both types, but cirrhosis on initial biopsy is more frequent in AIH-1 than in AIH-2, suggesting a more chronic course of disease in the former. Progression to cirrhosis during treatment is more frequent in AIH-1. In pediatrics, sclerosing cholangitis is often associated with florid autoimmune features, including elevated titres of autoantibodies, in particular ANA and SMA, elevated IgG, and interface hepatitis [3]. This AIH/sclerosing cholangitis overlap syndrome, called autoimmune sclerosing cholangitis (ASC) has been reported in between 15 and 21 % [4, 5] of patients in retrospective pediatric autoimmune liver disease series, where bile duct imaging was G. Mieli-Vergani (&) Paediatric Liver, GI and Nutrition Centre, King’s College Hospital, Denmark Hill, London SE5 9RS, UK e-mail: giorgina.vergani@kcl.ac.uk