Clinical practice guidelines recommend hepatocellular cancer (HCC) surveillance in patients with cirrhosis from any etiology and those with chronic hepatitis B virus (HBV) infection and additional risk factors. However, HCC incidence varies across groups. Several risk stratification models using clinical factors and/or biomarkers have been derived to facilitate tailored HCC surveillance. Although risk stratification models are used for patients with hepatitis B, few have been sufficiently validated in patients with cirrhosis. Indeed, many unanswered questions related to the development, validation, and impact evaluation of risk stratification models must be addressed before widespread implementation can be recommended. The National Cancer Institute’s Translational Liver Cancer (TLC) Consortium was established to advance research focused on risk stratification and early detection of liver cancer. The TLC convened a multidisciplinary group, including clinicians, scientists, biostatisticians, and technology experts from the United States, Asia, and Europe, to provide a framework for the development, validation, and implementation of risk stratification models. The framework defines 4 phases of risk stratification model development and validation: phase 1—development and internal validation, phase 2—decision rule development, phase 3—external validation, and phase 4—impact evaluation. The group also defined a set of recommendations to improve the rigor of development and validation of HCC risk stratification strategies. This framework can inform best practices and highlight necessary steps for endorsement by practice guidelines and regulatory agencies, highlighting a path toward implementation in clinical practice.

End-stage liver disease represents a critical hepatic condition with high mortality, for which liver transplantation remains the only effective treatment. However, the scarcity of suitable donors results in numerous patients dying while awaiting transplantation. Novel strategies, including cell therapies and technologies mimicking liver organogenesis, offer promising alternatives for treating end-stage liver disease by potentially providing new sources of liver grafts. Recently, significant progress has been made in this field, including stem cell transplantation, hepatocyte transplantation, in vitro liver tissue generation, and liver replacement technologies. Several clinical studies have demonstrated that stem cell transplantation and hepatocyte transplantation can prolong patient survival and serve as a bridge to liver transplantation. Furthermore, in vitro liver tissue generation technologies, such as liver organoids and three-dimensional bioprinting, can generate hepatic tissues with sophisticated structures and functions, making them promising transplantation materials. Notably, liver replacement technologies hold considerable potential for producing biologically functional and transplantable liver grafts. In this review, we discuss the fundamental principles and recent advancements in cell therapies and liver organogenesis technologies while also addressing the challenges and future prospects in this rapidly evolving field.

Advanced liver fibrosis and “At-Risk” metabolic dysfunction-associated steatohepatitis (At-Risk MASH) are present in 5% and 10%, respectively, of community-based patients with steatotic liver disease and metabolic risk factors and/or excess alcohol consumption. Identification of these patients is critical to guide prognosis and management due to their increased risk of liver decompensation and HCC. In addition, identification of At-Risk MASH will assist in targeting those eligible for pharmacotherapy. Screening pathways for detecting advanced liver fibrosis, consisting of sequential Fibrosis-4 Index and elastography or direct liver fibrosis biomarkers in patients with clinical risk factors, are recommended; however have suboptimal sensitivity and specificity. Biomarkers based on serum and/or elastography for At-Risk MASH have been developed in specialist centres; however lack broad validation, particularly in the community. Currently a range of barriers have retarded adoption of liver fibrosis screening in primary care, including knowledge gaps regarding non-invasive testing, cost, and limited access of non-invasive tests, and lack of integrated ordering and reporting systems. Once target patients are identified, robust pathways for linkage to specialist care are needed. Despite these challenges, studies performed in primary care have confirmed that liver fibrosis screening programs increase the detection of unrecognized advanced liver disease and may reduce unnecessary specialist referrals. Furthermore, some data suggest that community-based screening of liver fibrosis in patients with metabolic dysfunction and alcohol-associated steatotic liver disease is cost-effective. Widespread implementation of systematic evidence-based diagnostic pathways in the community is needed to reduce liver-related morbidity related to steatotic liver disease.