AASLD 2020 | Prof.Scott L. Friedman: Ten years of progress in hepatology, precision medicine brings great opportunities

 Editor's note: in 2020, in the field of liver disease study, three scientists found that hepatitis c virus (HCV) won the Nobel Prize in physiology or medicine, this will be our line of sight to the progress in viral hepatitis, and even can lead to chronic liver disease, also let us to further understand "from discovery to cure" by relying on the liver disease learning new technology and new ideas.

Hepatology Digest specially planned and invited professor Scott L. Friedman, head of the Department of Therapeutic discovery at Mount Sinai, to introduce the important progress and changes in the field of hepatology in recent years, and to forecast the new technologies and new ideas in the exploration.

Hepatology Digest:  The practice of hepatology has undergone profound shifts driven by new pathophysiologic insights which, in many cases, force us to rethink traditional medical dogma. Clinicians and researchers should embrace new goals and objectives for treating many liver diseases. Could you review the important progress of hepatology in the past few decades, introduce the conceptual changes, and give the young people some advice in the new era? 

Prof. Scott L. Friedman： There are many advances in the past decade. The most obvious and important was the development of curative therapies for hepatitis C using oral medications. This has been the most transformative development in the treatment of liver disease in many years and is slowly but surely curing most patients with hepatitis C both in the United States and throughout the world. This discovery of new treatments really was a direct consequence of the work recognized by this year's Nobel Prize for the discovery of the hepatitis C agent, recognizing Michael Houghton, Charles Rice and Harvey Alter. Now that we have curative therapies for hepatitis C the major responsibility for health care providers is to screen for hepatitis C to identify the disease so that we may cure all patients around the globe. The consequence is that already, and even more in the next few years, we will see a diminishing number of patients with advanced hepatitis C cirrhosis or hepatocellular carcinoma. This is an extraordinary success story for basic research, but also for drug development and for public health. That's the most dramatic improvement. 

In addition, we are harnessing the power of newer molecular techniques to both discover new diseases and to classify those diseases that we are already familiar with. For example, genetic studies are now uncovering the basis for a large and growing number of disorders of a biliary development and bile duct development that are leading to greater understanding of classifications for congenital liver disease. At the same time, there are dramatic efforts or improvements in our understanding of non-alcoholic fatty liver disease, in particular the discovery of many key pathways that are driving the disease that represent potential therapeutic targets. There has also been a huge investment in developing new technologies to diagnose liver disease, both in patients with suspected non-alcoholic fatty liver disease, but also for other disorders. This is a critically important need for because currently clinical trials rely on liver biopsy. However, this limits our ability to conduct clinical trials. Therefore, progressive developments in non-invasive methods of liver disease diagnosis will steadily replace the need for biopsy in the next few years. No therapies for NAFLD have been approved yet by the FDA but we are very confident that new agents will become progressively established. Both basic, translational and clinical efforts in research are steadily advancing the prospects for good health in patients with liver disease.

Hepatology Digest:   In order to maximize the benefit of patients, the concept of “Personalized Medicine” were proposed, considering the complexity of liver disease mechanisms. Could you introduce the current situation of personalized medicine in hepatology practice and your thoughts on the future development of personalized medicine?

Prof. Scott L. Friedman： Personalized medicine is slowly advancing for many kinds of liver disease. The most important application is the discovery of causes for unknown liver disease. There have been a few publications that identify novel causes of liver disease in patients who lack a diagnosis. More broadly, genetic technologies like whole exome sequencing and whole genome sequencing are discovering previously unknown causes and defects underlying liver disease. In addition, these techniques are being used increasingly to subdivide or subclassify forms of liver disease, both diseases in children that are congenital, but also NAFLD and NASH. We are discovering a growing list of genetic variants that increase or decrease the risk of fatty liver disease. These variants are not yet being used clinically for managing patients, but I believe that over time they will emerge into a clinical risk score that will both define the underlying drivers of liver disease and perhaps refine the choice of therapies.  We should also remember that the concept of personalized medicine extends not just to the genome but also to the epigenome, as well as to the microbiome, or metagenome. There are very exciting studies indicating that the composition of the microbiome maybe an important determinant of both the onset and severity of liver disease. We are at very early stages in understanding the microbiome, but I believe that over time understanding the genetic and secretory phenotypes of gut bacteria will lead us to uncover novel pathways of disease, causality, and potentially novel therapeutic targets. So, as we advance the technologies underpinning personalized medicine, we will steadily refine our ability to both diagnose, classify, as well as treat different forms of liver disease.

Hepatology Digest:   The bespoke therapies proposed in recent years are considered to have opened a new era of highly individualized therapies. What do you think of bespoke therapies, the opportunities, challenges and hopes?

Prof. Scott L. Friedman：There are still many challenges. One is that the technologies underlying personalized medicine are not equally available throughout the world. There are major centers that have the capacity to do genetic analysis, but it's not available widely in clinical practice. So, the first challenge will be to broaden the availability of the infrastructure necessary to use personalized medicine, in order to refine patient management and treatment. The second obstacle or challenge is education. Very few clinicians understand the genetic basis for many of these diseases. So, as we begin to integrate genetic information into patient profiles, we need to educate providers so they understand what the information means and how to act upon it. Related to that, we need improved software and computer-based solutions that can not only seamlessly integrate genetic information into the patient record, but can also provide treatment advice, because busy clinicians will not have the time to interpret genetic analyses. Genetic information will also influence screening, management, and genetic counseling for family members of those with heritable liver disease. We have many challenges ahead but the technologies are there. As we learn more and reduce the cost of these technologies, we will be able to integrate them into clinical management.