Background: Autoimmune liver disease (AILD) encompasses 3 main distinct clinical diseases: autoimmune hepatitis, primary biliary cholangitis (formally known as cirrhosis, PBC) and primary sclerosing cholangitis (PSC). These conditions are an important, yet under-appreciated cause of patient morbidity and mortality with ongoing unmet needs for further research and clinical advances. Key Messages: There is observational evidence for genetic predisposition, with all 3 conditions being more common in first degree relatives. AILD is associated with the presence of auto-antibodies and higher risks of other non-hepatic auto-immune conditions. Genetic risk association studies have identified HLA and non-HLA risk loci for the development of disease, with some HLA loci providing prognostic information. This re-enforces the concept that genetic predisposition to autoimmunity is important, likely in the context of environmental exposures. Such environmental triggers are unclear but relevant risks include smoking, drug and xenobiotic exposure as well as the complexities of the microbiome. There is evidence for a loss of immune tolerance to self-antigens playing a part in the development of these conditions. In particular the IL-2 and IL-12 regulatory pathways have been implicated in pre-disposing to an unopposed inflammatory response within the liver. Main immunological themes revolve around loss of immune tolerance leading to T-cell mediated injury, imbalance in the regulation of immune cells and defective immune response to foreign antigens. For PBC and PSC, there is then the added complexity of the consequences of cholestasis on hepato-biliary injury, immune regulation and liver fibrosis. Conclusions: Whilst specific disease causes and triggers are still lacking, AILD arises on the background of collective genetic and environmental risk, leading to chronic and abnormal hepato-biliary immune responses. Effective and more rational therapy will ultimately be developed when the multiple pathways to liver injury are better understood.
Noninvasive monitoring of disease activity in autoimmune hepatitis (AIH) has potential advantages for patients for whom liver biopsy is invasive and with risk. We sought to understand the association of multiparametric magnetic resonance imaging (mpMRI) with clinical course of patients with AIH. We prospectively recruited 62 patients (median age, 55 years; 82% women) with clinically confirmed AIH. At recruitment, patients underwent mpMRI with LiverMultiScan alongside clinical investigations, which were repeated after 12‐18 months. Associations between iron‐corrected T1 (cT1) and other markers of disease were investigated at baseline and at follow‐up. Discriminative performance of cT1, liver stiffness, and enhanced liver fibrosis (ELF) to identify those who failed to maintain remission over follow‐up was investigated using the areas under the receiver operating characteristic curves (AUCs). Baseline cT1 correlated with alanine aminotransferase (Spearman’s correlation coefficient [rS] = 0.28, P = 0.028), aspartate aminotransferase (rS = 0.26, P = 0.038), international normalized ratio (rS = 0.35 P = 0.005), Model for End‐Stage Liver Disease (rS = 0.32, P = 0.020), ELF (rS = 0.29, P = 0.022), and liver stiffness rS = 0.51, P < 0.001). After excluding those not in remission at baseline (n = 12), 32% of the remainder failed to maintain remission during follow‐up. Failure to maintain remission was associated with significant increases in cT1 over follow‐up (AUC, 0.71; 95% confidence interval [CI], 0.52‐0.90; P = 0.035) but not with changes in liver stiffness (AUC, 0.68; 95% CI, 0.49‐0.87; P = 0.067) or ELF (AUC, 0.57; 95% CI, 0.37‐0.78; P = 0.502). cT1 measured at baseline was a significant predictor of future loss of biochemical remission (AUC, 0.68; 95% CI, 0.53‐0.83; P = 0.042); neither liver stiffness (AUC, 0.53; 95% CI, 0.34‐0.71; P = 0.749) nor ELF (AUC, 0.52; 95% CI, 0.33‐0.70; P = 0.843) were significant predictors of loss of biochemical remission. Conclusion: Noninvasive mpMRI has potential to contribute to risk stratification in patients with AIH.
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