Seminars in liver disease最新文献

Nonalcoholic fatty liver disease (NAFLD) and cardiovascular diseases are both highly prevalent conditions around the world, and emerging data have shown an association between them. This review found several longitudinal and cross-sectional studies showing that NAFLD was associated with coronary artery disease, cardiac remodeling, aortic valve remodeling, mitral annulus valve calcifications, diabetic cardiomyopathy, diastolic cardiac dysfunction, arrhythmias, and stroke. Although the specific underlying mechanisms are not clear, many hypotheses have been suggested, including that metabolic syndrome might act as an upstream metabolic defect, leading to end-organ manifestations in both the heart and liver. Management of NAFLD includes weight loss through lifestyle interventions or bariatric surgery, and pharmacological interventions, often targeting comorbidities. Although there are no Food and Drug Administration-approved nonalcoholic steatohepatitis-specific therapies, several drug candidates have demonstrated effect in the improvement in fibrosis or nonalcoholic steatohepatitis resolution. Further studies are needed to assess the effect of those interventions on cardiovascular outcomes, the major cause of mortality in patients with NAFLD. In conclusion, a more comprehensive, multidisciplinary approach to diagnosis and management of patients with NAFLD and cardiovascular diseases is needed to optimize clinical outcomes.

Liver cancer, mainly hepatocellular carcinoma (HCC), remains a major cause of cancer-related death worldwide. With the global epidemic of obesity, the major HCC etiologies have been dynamically shifting from viral to metabolic liver diseases. This change has made HCC prevention difficult with increasingly elusive at-risk populations as rational target for preventive interventions. Besides ongoing efforts to reduce obesity and metabolic disorders, chemoprevention in patients who already have metabolic liver diseases may have a significant impact on the poor HCC prognosis. Hepatitis B- and hepatitis C-related HCC incidences have been substantially reduced by the new antivirals, but HCC risk can persist over a decade even after successful viral treatment, highlighting the need for HCC-preventive measures also in these patients. Experimental and retrospective studies have suggested potential utility of generic agents such as lipophilic statins and aspirin for HCC chemoprevention given their well-characterized safety profile, although anticipated efficacy may be modest. In this review, we overview recent clinical and translational studies of generic agents in the context of HCC chemoprevention under the contemporary HCC etiologies. We also discuss newly emerging approaches to overcome the challenges in clinical testing of the agents to facilitate their clinical translation.

Acute kidney injury (AKI) is a frequent complication in patients with cirrhosis that is associated with poor outcomes and decreased survival. The definition of AKI in cirrhosis is currently based on changes of serum creatinine levels with respect to baseline values. Differential diagnosis of the causes of AKI is of major relevance, considering that some causes of AKI, such as hepatorenal syndrome, have specific treatment options and different prognosis. Prediction of kidney function recovery and patients' survival is also crucial in this patient population to guide clinical decisions. AKI biomarkers in cirrhosis have emerged as a promising tool for differential diagnosis and prognosis in this situation. There are consistent data showing that some urine biomarkers, particularly neutrophil gelatinase-associated lipocalin, may be useful in daily clinical practice for the differential diagnosis of the cause of AKI in cirrhosis. AKI biomarkers may constitute a useful tool for use in differential diagnosis, prognosis of renal function, and survival in patients with cirrhosis. This review focuses on the current state of knowledge and future perspective of novel biomarkers of AKI in cirrhosis.

Despite the rising prevalence of nonalcoholic fatty liver disease (NAFLD), the underlying disease pathophysiology remains unclear. There is a great need for an efficient and reliable "human" in vitro model to study NAFLD and the progression to nonalcoholic steatohepatitis (NASH), which will soon become the leading indication for liver transplantation. Here, we review the recent developments in the use of three-dimensional (3D) liver organoids as a model to study NAFLD and NASH pathophysiology and possible treatments. Various techniques that are currently used to make liver organoids are discussed, such as the use of induced pluripotent stem cells versus primary cell lines and human versus murine cells. Moreover, methods for inducing lipid droplet accumulation and fibrosis to model NAFLD are explored. Finally, the limitations specific to the 3D organoid model for NAFLD/NASH are reviewed, highlighting the need for further development of multilineage models to include hepatic nonparenchymal cells and immune cells. The ultimate goal is to be able to accurately recapitulate the complex liver microenvironment in which NAFLD develops and progresses to NASH.

Early palliative and supportive care referral is the standard of care for many malignancies. This paradigm results in improvements in patients' symptoms and quality of life and decreases the costs of medical care and unnecessary procedures. Leading oncology guidelines have recommended the integration of early referral to palliative and supportive services to care pathways for advanced malignancies. Currently, early referral to palliative care within the hepatocellular carcinoma (HCC) population is not utilized, with gastroenterology guidelines recommending referral of patients with Barcelona Clinic Liver Cancer stage D to these services. This review addresses this topic through analysis of the existing data within the oncology field as well as literature surrounding palliative care intervention in HCC. Early palliative and supportive care in HCC and its impact on patients, caregivers, and health services allow clinicians and researchers to identify management options that improve outcomes within existing service provisions.

Although the underlying cause may vary across countries and demographic groups, liver disease is a major cause of morbidity and mortality globally. Orthotopic liver transplantation is the only definitive treatment for liver failure but is limited by the lack of donor livers. The development of drugs that prevent the progression of liver disease and the generation of alternative liver constructs for transplantation could help alleviate the burden of liver disease. Bioengineered livers containing human induced pluripotent stem cell (iPSC)-derived liver cells are being utilized to study liver disease and to identify and test potential therapeutics. Moreover, bioengineered livers containing pig hepatocytes and endothelial cells have been shown to function and survive after transplantation into pig models of liver failure, providing preclinical evidence toward future clinical applications. Finally, bioengineered livers containing human iPSC-derived liver cells have been shown to function and survive after transplantation in rodents but require considerable optimization and testing prior to clinical use. In conclusion, bioengineered livers have emerged as a suitable tool for modeling liver diseases and as a promising alternative graft for clinical transplantation. The integration of novel technologies and techniques for the assembly and analysis of bioengineered livers will undoubtedly expand future applications in basic research and clinical transplantation.

The burden of nonalcoholic fatty liver disease (NAFLD) is rising globally. Cardiovascular disease is the leading cause of death in patients with NAFLD. Nearly half of individuals with NAFLD have coronary heart disease, and more than a third have carotid artery atherosclerosis. Individuals with NAFLD are at a substantially higher risk of fatal and nonfatal cardiovascular events. NAFLD and cardiovascular disease share multiple common disease mechanisms, such as systemic inflammation, insulin resistance, genetic risk variants, and gut microbial dysbiosis. In this review, we discuss the epidemiology of cardiovascular disease in NAFLD, and highlight common risk factors. In addition, we examine recent advances evaluating the shared disease mechanisms between NAFLD and cardiovascular disease. In conclusion, multidisciplinary collaborations are required to further our understanding of the complex relationship between NAFLD and cardiovascular disease and potentially identify therapeutic targets.

The human liver is a complex organ made up of multiple specialized cell types that carry out key physiological functions. An incomplete understanding of liver biology limits our ability to develop therapeutics to prevent chronic liver diseases, liver cancers, and death as a result of organ failure. Recently, single-cell modalities have expanded our understanding of the cellular phenotypic heterogeneity and intercellular cross-talk in liver health and disease. This review summarizes these findings and looks forward to highlighting new avenues for the application of single-cell genomics to unravel unknown pathogenic pathways and disease mechanisms for the development of new therapeutics targeting liver pathology. As these technologies mature, their integration into clinical data analysis will aid in patient stratification and in developing treatment plans for patients suffering from liver disease.

Nonalcoholic liver disease is a component of metabolic syndrome associated with obesity, insulin resistance, and hyperlipidemia. Excessive alcohol consumption may accelerate the progression of steatosis, steatohepatitis, and fibrosis. While simple steatosis is considered a benign condition, nonalcoholic steatohepatitis with inflammation and fibrosis may progress to cirrhosis, liver failure, and hepatocellular cancer. Studies in rodent experimental models and primary cell cultures have demonstrated several common cellular and molecular mechanisms in the pathogenesis and regression of liver fibrosis. Chronic injury and death of hepatocytes cause the recruitment of myeloid cells, secretion of inflammatory and fibrogenic cytokines, and activation of myofibroblasts, resulting in liver fibrosis. In this review, we discuss the role of metabolically injured hepatocytes in the pathogenesis of nonalcoholic steatohepatitis and alcohol-associated liver disease. Specifically, the role of chemokine production and de novo lipogenesis in the development of steatotic hepatocytes and the pathways of steatosis regulation are discussed.