Global Disparities and Their Implications in the Occurrence and Outcome of Autoimmune Hepatitis

Abstract

Autoimmune hepatitis has a variable occurrence, clinical phenotype, and outcome, and the factors contributing to this variability are uncertain. The goals of this review are to examine the global disparities in the occurrence and outcome of autoimmune hepatitis, suggest bases for these disparities, and encourage investigations that extend beyond single-center experiences. Disparities in the incidence and prevalence of autoimmune hepatitis in different age groups, genders, ethnicities, and geographical regions suggest that factors other than genetic predisposition are involved. Age- and gender-related antigen exposures from the external (infections, toxins, and medications) and internal (intestinal microbiome) environment may affect the incidence of the disease, and the timeliness and nature of treatment may influence its prevalence. The increasing incidence of autoimmune hepatitis in Spain, Denmark, and the Netherlands suggests that a new etiological trigger has been introduced or that the susceptible population has changed. Variations in mortality between Western and Asian-Pacific countries may result from differences in disease detection or management, and variations in gender predilection, peak age of onset, frequency of concurrent immune diseases, and serological profile may reflect gender-biased and age-related antigen exposures and genetic predispositions. Global collaborations, population-based epidemiological studies that identify case clustering, and controlled interview-based surveys are mechanisms by which to understand these disparities and improve management. In conclusion, autoimmune hepatitis has a rising incidence in some countries and variable occurrence, phenotype, and outcome between countries and subgroups within countries. These disparities suggest that unrecognized population-based environmental, infectious, or socioeconomic factors are affecting its character.

Systematic review and meta‐analysis on the incidence and prevalence of autoimmune hepatitis in Asian, European, and American population

“…38 The role of estrogen, X-chromosomal, and fetal microchimerism has been cited to explain the propensity of women to develop AIH and other autoimmune diseases. 35 This is well fit with the previous report that gender has an impact on the incidence and prevalence of AIH. 39 Furthermore, our study also suggests that elderly people are more inclined to be affected by AIH, with a peak rate at patients aged ≥ 60 years.…”

“…that 75% of affected AIH people are female . The role of estrogen, X‐chromosomal, and fetal microchimerism has been cited to explain the propensity of women to develop AIH and other autoimmune diseases . This is well fit with the previous report that gender has an impact on the incidence and prevalence of AIH …”

“…They might also have other comorbidities carrying a higher risk of death from other disease such as cardiovascular diseases or cancers. 35 The patients in Asian often experience an increased risk of early death (5-year survival rate: 71% in Singapore and 78.6% in Brunei), 3,36 in line with a perspective by Wong that Asian patients have a poorer survival outcome than both Hispanics and White patients. 37 Therefore, late onset and shorter survival may result in a lower prevalence rate of AIH.…”

Epigenetic changes and their implications in autoimmune hepatitis

“…Numbers in brackets are references. 21 have been differentially elevated in Japanese patients with autoimmune hepatitis, and serum levels of miR-21 and miR-122 have reflected serum alanine aminotransferase levels [44] (Table 3). Furthermore, the miR-21 level has correlated directly with the histological grade of inflammation and inversely with the histological stage of fibrosis [44].…”

Autoimmune Hepatitis: Surviving Crises of Doubt and Elimination

“…[88][89][90] The shortfall of risk based on associations with human leukocyte antigens and genetic polymorphisms has stimulated interest in environmental factors, the intestinal microbiome, and epigenetic changes as pathogenic elements. 91,92 AIH has now established itself as an immune-mediated disease that must be recognized in all age groups, 93,94 genders, 95 and ethnicities, 96,97 and in all forms of hepatitis before and after liver transplantation (LT) [98][99][100][101] (Fig. 1).…”