Autoimmune hepatitis (AIH) in the elderly: A systematic retrospective analysis of a large group of consecutive patients with definite AIH followed at a tertiary referral centre

Background/Aims

A few reports have suggested that AIH may be less severe in the elderly and may be underdiagnosed, but there is a paucity of data.

Methods

We have undertaken a systematic analysis of 164 consecutive patients (36 males, 128 females) with definite AIH (median score 23, range 18–28) attending our clinics, comparing those presenting at age >60 years (Group 1, n = 43) with those presenting at <60 years (Group 2, n = 121).

Results

Median (range) duration of follow-up was 9 years (1–28) in Group 1 and 14 years (1–33) in Group 2. Median ages (ranges) at presentation were: Group 1 = 65 (60–79) and Group 2 = 41 (6–59). Group 1 patients had a significantly increased incidence of ascites at presentation (p < 0.001) and a lower incidence of relapse (42% vs. 70%, p = 0.002), but there were no significant differences between the groups with respect to mode of onset (acute, insidious, asymptomatic), other clinical signs at presentation, biochemical parameters, types or titres of autoantibodies, incidence of histological cirrhosis, response to therapy or related side effects. There were also no significant differences in liver-related deaths or transplantation, or the frequencies of HLA DR3 or DR4 – although there was an increased frequency of the A1-B8-DR3/4 haplotype in Group 2 (40% vs. 22%, p = 0.138).

Conclusions

These findings suggest that AIH often presents in older patients, who frequently have severe disease. Active management in these patients can lead to a normal life expectancy.

Introduction

Autoimmune hepatitis (AIH) is an uncommon chronic disease of the hepatic parenchyma which is characterised by hypergammaglobulinaemia, circulating autoantibodies and the morphological changes of interface hepatitis, which is responsive to immunosuppressive therapy in the majority of cases [1], [2], [3]. The pathogenesis of AIH is still unclear but the condition appears to have an immunogenetic basis, as evidenced by its well-recognised association in northern European caucasoids with inheritance of the extended HLA haplotype A1-B8-DR3 and particularly with the DR3 and DR4 allotypes – which are also associated with other autoimmune diseases [4], [5]. The DR3 and DR4 allotypes are independent risk factors for, and are associated with different clinical expressions of, the disease [6]. DR3 is more frequently associated with a younger age at presentation and greater severity of disease while DR4 is more prevalent among older patients with generally milder AIH [4]. The latter is especially the case in Japan, where DR3 is rare in the normal population and the primary association is with DR4 [7].

AIH was originally described in peripubertal females [8], and for many years it was considered to be a condition that mainly affected young women and that it was uncommon in older patients [9]. It is now known that the disease also affects males, although females predominate (4:1 to 6:1 in most series), and that it can present at any age [2]. Indeed, recent studies indicate that it is predominantly a disease of the elderly, with a peak of presentation at between 50 and 70 years of age [7], [10], [11].

Studies of AIH in elderly patients have, however, been fairly limited and (perhaps in part because of the above-mentioned tendency for them to have milder disease) there has been controversy over whether or not they benefit from treatment [12]. One early study concluded that elderly patients received less benefit from treatment and suffered more adverse side effects [9], while another showed good responses to treatment and few adverse side effects [13]. Two more recent studies noted that elderly patients can present with severe disease and suggested that this may have been due partly to delays in diagnosis and institution of therapy [11], [14]. All of these studies have been of relatively small numbers and heterogeneous populations of patients, including patients with both probable and definite AIH as well as some with features of primary sclerosing cholangitis or primary biliary cirrhosis (so-called overlap syndromes). Additionally, it is possible that the earlier reports [prior to the discovery of the hepatitis C virus (HCV)] may have included patients with chronic HCV infection.

The present study was therefore undertaken in an attempt to resolve some of these issues. It has involved a systematic review of a large, and as homogeneous as possible, group of consecutive patients with definite AIH which has provided the basis for an analysis of the influence of age on presenting features, severity of disease, response to treatment and outcome by comparing patients presenting above and below the age of 60 years.