Researchers reported advancements made in terms of our understanding of the genetic, epigenetic, and environmental aspects of rare liver diseases, such as Alagille syndrome, as published in the European Journal of Medical Genetics.

“The human liver is a remarkable organ with hundreds of life-sustaining functions, from food and drug metabolism to production of bile to aid digestion and eliminate bilirubin and excess copper,” the authors said in an editorial.

“Liver pathology or dysfunction therefore impacts essential homeostatic functions and can result in life-threatening liver failure or liver cancer.”

Continue Reading

They provided a summary of the various insights we have gained into liver pathology, with one being the mapping of mutations or putative modifiers in patients with rare liver diseases. For example, a study mapped the spectrum of ATP7B mutations in patients with Wilson disease, and another provided a comprehensive overview of mutations in progressive familial intrahepatic cholestasis (PFIC) disease.

Read more about Alagille syndrome etiology

Although some liver diseases are monogenic in nature and can be described in fairly straightforward genetic terms, others involve the complex interaction between genetic and environmental factors. Medical researchers have described these interactions in diseases such as primary biliary cholangitis, primary sclerosing cholangitis, and autoimmune hepatitis.

In addition, advancements have been made in our understanding of the impact of environmental insults, such as in the case of viral infection, on liver disease. Studies have reported the impact of cytomegalovirus infection on PFIC type 4, alpha-1 antitrypsin deficiency, and Alagille syndrome. 

“In conclusion, both monogenic and complex rare liver diseases require earlier and more widely available reliable diagnostic testing, allowing better definitions of disease and informed patient care. Expert care in expert centers is needed to provide essential clinical knowledge for rare diseases,” the authors wrote.


Andersson ER, Lohse AW. Advances in genetic, epigenetic and environmental aspects of rare liver diseasesEur J Med Genet. Published online December 20, 2021. doi:10.1016/j.ejmg.2021.104411