What is Hepatology looking for version 2.0?

The inaugural issue of Hepatology was published in 1981, more than 41 years ago. The founding editor Irwin Arias envisioned a major journal in which important clinical, pathologic, and basic liver related research would be published in one journal. He hoped the journal would bridge the gap between the amazing advances in biology and their application to liver physiology and disease. He sought to create a home for the continuum of advances along the discovery‐translation‐application paradigm as related to liver pathobiology and clinical hepatology. This vision and its execution carried out by Dr. Irwin Arias and a series of subsequent, highly talented editors has been and is remarkably successful.

The success of the journal ultimately resulted in more submissions than could possibly be published. This imbalance resulted in increasing rejection rates for manuscripts submitted to Hepatology. To address this issue and provide transparency to the process, Dr. Michael Nathanson, then Editor‐in‐Chief of Hepatology, published a commentary in 2015 entitled, “What is Hepatology looking for?” Within this commentary, he clearly outlined the continued mission of Hepatology and highlighted the necessity of publishing only the minority of submitted manuscripts. With impressive lucidity and precision, he outlined the tenets of an accepted manuscript including novelty, focus on mechanistic insights, the robustness and rigor of the experimental design, impact of the study, relevance to the readership at Hepatology, and appropriate discussion of the findings in the context of this field. These qualities of an acceptable manuscript remain true today and are critical for acceptance by the current editorial team of Hepatology.

The content characteristics of what Hepatology wants, however, continues to evolve, and in this commentary, we discuss version 2.0 of what Hepatology prioritizes for publication. As Dr. Michael Nathanson stipulated in 2015, “articles that might have been acceptable for publication just a few years ago, no longer may be.” This statement remains true. There have been transformational changes in science and clinical care over the last 7 years. For example, note the current focus on studies regarding cell heterogeneity due to advances in single cell technology and spatial transcriptomics; also, the continued development of human‐based model systems such as organoids. There is an increasing emphasis on human disease pathogenesis as opposed to discovery science per se. In vivo confirmation and implications need to be fully explored and defined experimentally in studies focusing on cell biology and biochemistry. Where once exploration of “target genes and proteins” in disease processes was sufficient to warrant publication if well done, current science demands unbiased approaches to define the spectrum of alterations occurring in pathways and cellular networks. Clinical trial design continues to evolve, and what constitutes adequate definitions of the disease, appropriate stratification of patients, and validation of endpoints is ever changing. Data science and computational biology have now emerged as a major‐forces guiding scientific inquiry as noted by the pervasive application of machine learning and artificial intelligence. These are a few examples of the changing landscape of science.

Medicine in general is undergoing a transformation, and Hepatology must be proactive in promoting and defining the transformation within our discipline. We will do this, in part, by prioritizing the articles we review and accept for publication. Priority will be provided to those articles that are helping to lead the transformation of our discipline broadly including a balance between experimental and clinical hepatology. Herein, we describe the types of articles that will facilitate this transformation.

Regarding disease pathogenesis, there remain many black boxes in hepatology, including cholestatic liver diseases, steatohepatitis syndromes, hepatobiliary malignancies, and immune‐mediated diseases including allograft rejection. Unraveling these processes will require a deeper understanding of liver pathobiology. With the advent of deep immunophenotyping, spatial transcriptomics, single cell analysis, and loss of function paradigms, we anticipate quantum leaps in our understanding of liver pathobiology and immunology and its application to human liver diseases and liver transplantation. We encourage multiomics articles on immune mediated processes in the liver and big data articles that advance structure–function relationships in liver diseases.

Not only will fundamental science expedite and illuminate the pathways to achieve our goal of eliminating suffering and mortality from liver diseases, but the mechanisms of dissemination and delivery of these advances to patients must also rapidly evolve. Without doing do, already prevalent healthcare disparities will widen. As a discipline, we must guide policy makers, instruct health care systems, and provide the tools and knowledge to resolve the disparities. Hepatology, as a journal, must become a forum for describing the disparities and providing unique insights into their resolution. Health care delivery models and systems will need to be developed to reach patients regardless of socioeconomic status and geography. Such articles have not been previously prominent in the journal. However, Hepatology will need to become the home for well‐done articles addressing these national concerns.

Clinical trials are undergoing rapid change, providing the field an opportunity to reimagine the future state of clinical trials including remote consenting and monitoring, well‐designed health care platforms to reach to and recruit more participants, smart wearables, at‐home testing, and synthetic controls. Pragmatic clinical trials testing different approaches for rational healthcare options need to be conducted to identify cost‐effective care strategies. We look forward to these new types of clinical trials describing their implementation and results. A quiet revolution is ongoing on gene and viral therapy, regenerative medicine, and tissue and cellular engineering. Although nascent in its application to human disease, early‐stage studies will provide the foundation for future success and are to be encouraged. In this regard, we encourage submission of early phase trials that provide insight into these future therapies. In summary, we look forward to receiving manuscripts that will illuminate and define the pathways leading this transformation in Hepatology.