A literature review recently published in Hepatology highlights the leading and expanding role of genomic medicine in the diagnosis of alpha-1 antitrypsin deficiency (AATD) and other liver diseases, which, in turn, allows for individualized treatment. 

“Advances in next generation sequencing technologies, human genome variation analysis, and interpretation is moving genomic medicine from niche to widespread, paving the way for expansion of genomics-informed hepatology practice and marking a new era in molecular hepatology,” the authors wrote.

Because of a recently published strategic vision for genomics in human health issued by the National Human Genome Research Institute (NHGRI), the authors made 5 predictions regarding these statements in the context of hepatology.

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First, genomic analysis in patients with unexplained liver disease will reveal a genetic cause in at least 20% of cases. A previous study performed whole-exome sequencing in 19 adults with unexplained liver disease, leading to a genetic diagnosis in 25% of them. This finding showcases the importance of encouraging physicians to consider such diseases and test accordingly. 

The second prediction mentions the inclusion of genomic analysis in clinical care and either training practitioners on the subject or incorporating qualified personnel into multidisciplinary discussions.

Third, a centralized liver disease gene database will constantly be updated and reviewed will aid in exposing novel genes that are causative of currently unexplained liver disease.

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The fourth prediction is about identifying rare pathogenic genetic variants that may expose therapeutic targets and promote the development of noninvasive treatments.

Finally, the fifth prediction announces therapeutic strategies using messenger RNA (mRNA) and other mechanisms to deliver DNA or mRNA molecules to emend defective physiological pathways.

In the case of AATD, understanding the genetic defect that causes the disease is possible thanks to individualized phenotypic characterization and the analysis of family pedigree. Currently, in patients with suspected AATD, single-gene sequencing for the SERPINA1 gene is routinely performed.

Genomic medicine emerged in 2003 from the Human Genome Project and has already innovated diagnostic and treatment approaches in most subspecialties. It currently plays a key role in oncology and pediatrics, and its scope is consistently growing.

In the span of just 2 decades, genetic tests previously allocated only to research due to their high cost are now much more affordable; however, physician expertise and clinical correlation of the results remain as limitations. “Training of adult and pediatric hepatologists in genomic medicine will be vital for excellent patient care in the coming years,” the authors concluded.


Zheng M, Allington G, Vilarinho S. Genomic medicine for liver disease. Hepatology. Published online January 25, 2022. doi:10.1002/hep.32364