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previous knowledge of the causal pathogenesis of pancreatitis in common pancreatic diseases and thus are better able to apply knowledge of AIH-associated CP to clinical practice. A pancreatitis-associated CP score was recently validated and used by Grigalet *et al.* in validation studies.[[@ref60][@ref61]] Pancreatic CDI is less common in AIH (1%) compared to Biliary CDI (20-40%). As previously described, Biliary CDI is often more severe than pancreatic CDI. In AIH, pancreatic CDI is more common in patients with other features of severe disease, such as portal hypertension and a high serum IgG level. Performing a pancreatic biopsy is still associated with obscure clinical scenarios as there are no predictive factors for development of pancreatic CDI in AIH. It is widely accepted that although most cases of AIH are caused by the presence of an environmental trigger, the nature of this trigger is unknown. Since environmental exposure is usually considered a common cause in the pathogenesis of most forms of GS, one might speculate that rather than a role of characteristic environmental triggers, the chronic, persistent, immune-mediated inflammatory process initiated by the environmental trigger (e.g., hepatitis virus infections) leads to autoimmune disease. A genetic predisposition to persistent inflammation with the development of autoimmunity in response to a common environmental trigger is considered an essential genetic polymorphism in AIH. It is more likely that the multifactorial pathogenesis of AIH is intrinsically linked to HLA polymorphisms. Gene therapy using gene transfer strategies has recently been suggested as a novel strategy for future therapies. Recent data from two separate clinical trials using gene transfer strategies have provided evidence for long-term persistence of antibody expression in patients. Furthermore, data suggesting effective autologous tolerance induction are promising. CONCLUSIONS {#sec1-11} =========== Biliary CDI, PSC, PSC-AIH overlap and CDI-PSC overlap are now established as unique entities, though are often difficult to distinguish due to overlapping clinical, biochemical, radiological, pathological, and histological features. The evolving technologies are changing the diagnosis and prognostic significant of these entities. The new classification will help in identifying a uniform treatment for these diseases. d2c66b5586
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