Contemporary epidemiology of autoimmune liver disease and clinical outcomes in seronegative autoimmune hepatitis

Abstract

Autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are immune-mediated chronic progressive inflammatory liver diseases. Precise aetiology of these autoimmune liver diseases continues to remain elusive. Epidemiological research remains important, not only to understand the current burden of disease, but relevant trends or changes in disease occurrence can help identify potential aetiopathogenic factors. There is significant paucity of population-based epidemiological data, especially from Southern hemisphere relating to AIH, PBC and PSC.

In this thesis, we describe historical perspective as well as provide a review of current understanding of aetiopathogenesis of AIH, PBC and PSC in chapter 1. We further undertake a detailed systematic literature review and qualitatively synthesise epidemiological data on incidence, prevalence, and trends of autoimmune liver diseases. These findings are discussed in detail in chapter 2. In chapter 3, we discuss results of our prospective population-based epidemiological study from Canterbury, New Zealand concerning AIH, PBC and PSC. In chapter 4, using the prospective Canterbury cohort, we describe clinical and serological characteristics as well as long-term outcomes in patients with seronegative AIH, compared to classical AIH.

The main findings of our study are:

1. The incidence of AIH in Canterbury increased significantly during the study period. The mean annualised incidence rate of AIH per 100,000 was 2.93 (95%CI 1.72-3.23) for year 2014-2016, compared to 1.37 (95%CI 0.85-2.05) for year 2008-2010

2. The prevalence of AIH in Canterbury on 31/12/2016 was 27.5 per 100,000. This is one of the highest reported prevalence rates for AIH.

3. The incidence rate for PBC in Canterbury remains low. The mean annualised incidence rate for PBC per 100,000 was 0.51 (95%CI 0.33-1.17), which is 2-9 times lower than compared to the European data.

4. Patients with seronegative AIH presented more commonly with advanced fibrosis or cirrhosis, when compared to patients with classical AIH (75% and 49.4% respectively, p<0.05) at diagnosis. Patients with seronegative AIH had significantly higher rates of decompensation within 90 days of diagnosis compared to classical AIH (18.2% and 0.5% respectively, p<0.05).

5. Patients with seronegative AIH responded well to conventional immunosuppressive therapy. Rates of alanine transaminase (ALT) normalisation at 6 months in seronegative and classical AIH patients were 69.2% and 71.1% respectively (p=0.89).

6. There was no significant difference in 5-year transplant free survival in patients with seronegative AIH and classical AIH.