Seminars in liver disease最新文献

The association between liver and brain health has gained attention as biomarkers of liver function have been revealed to predict neurodegeneration. The liver is a central regulator in metabolic homeostasis. However, in nonalcoholic fatty liver disease (NAFLD), homeostasis is disrupted which can result in extrahepatic organ pathologies. Emerging literature provides insight into the mechanisms behind the liver-brain health axis. These include the increased production of liver-derived factors that promote insulin resistance and loss of neuroprotective factors under conditions of NAFLD that increase insulin resistance in the central nervous system. In addition, elevated proinflammatory cytokines linked to NAFLD negatively impact the blood-brain barrier and increase neuroinflammation. Furthermore, exacerbated dyslipidemia associated with NAFLD and hepatic dysfunction can promote altered brain bioenergetics and oxidative stress. In this review, we summarize the current knowledge of the crosstalk between liver and brain as it relates to the pathophysiology between NAFLD and neurodegeneration, with an emphasis on Alzheimer's disease. We also highlight knowledge gaps and future areas for investigation to strengthen the potential link between NAFLD and neurodegeneration.

Obesity is strongly associated with nonalcoholic fatty liver disease as well as advanced forms of the disease such as nonalcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma. While lifestyle and diet modifications have been the cornerstone of treatment for NASH thus far, they are only effective for less than half of the patients. New endoscopic bariatric therapies (EBTs) have already proved to be safe and effective for the treatment of obesity and type 2 diabetes mellitus, and may provide an intermediate, less invasive, cost-effective option for patients with NASH. In this review, we aim to describe the data and evidence as well as outline future areas of development for endobariatric therapies for the treatment of NASH. In conclusion, EBTs present an effective and safe therapeutic modality for use in the growing pandemic of obesity-related liver disease and should be investigated further with large-scale trials in this patient population.

The excessive accumulation of extracellular matrix proteins results in fibrosis-a condition implicated in several diseased conditions, such as nonalcoholic steatohepatitis, viral hepatitis, and autoimmune hepatitis. Despite its prevalence, direct and effective treatments for fibrosis are lacking, warranting the development of better therapeutic strategies. Accumulating evidence has shown that liver fibrosis-a condition previously considered irreversible-is reversible in specific conditions. Immune cells residing in or infiltrating the liver (e.g., macrophages) are crucial in the pathogenesis of fibrosis. Given this background, the roles and action mechanisms of various immune cells and their subsets in the progression and recovery of liver fibrosis, particularly concerning nonalcoholic steatohepatitis, are discussed in this review. Furthermore, the development of better therapeutic strategies based on stage-specific properties and using advanced techniques as well as the mechanisms underlying recovery are elaborated. In conclusion, we consider the review comprehensively provides the present achievements and future possibilities revolving around fibrosis treatment.

Diet could be both culprit and solution of NAFLD. Dietary modifications have been associated with histological features improvement in NAFLD. The Western diet was related to a greater risk of disease progression while the Mediterranean diet (MD) could promote regression of histological lesions. Modifications in the nutrient composition seems to have lesser impact on NAFLD than dietary modifications. An intrinsic interaction between nutrients in the diet support a specific effect not seen when added separately. Dietary modifications should focus on promoting weight loss but also look for patterns that are able to promote histological improvement. Although several micronutrients' deficit has been related to NAFLD progression, prescribing these micronutrients' supplementation did not reach a positive impact. However, an enriching diet with specific nutrients could be useful, like olive oil supplemented in MD. Geometry of nutrition defines a framework to better understand the interaction between nutrients, foods, and dietetic pattern in the model of diseases and how we could approach taking into consideration the interaction between meals and disease features. After analyzing baseline diet and histological lesions, we could calculate the distance to optimal diet and to promote changes in lifestyle to reach all these goals. A standard MD menu would be recommended.

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.