Hepatology Communications最新文献

Background: Acute liver failure (ALF) is a rare condition leading to morbidity and mortality. Liver transplantation (LT) is often required, but patients are not always listed for LT. There is a lack of data regarding outcomes in these patients. Our aim is to describe outcomes of patients with ALF not listed for LT and to compare this with those listed for LT.

Methods: Retrospective analysis of all nonlisted patients with ALF enrolled in the Acute Liver Failure Study Group (ALFSG) registry between 1998 and 2018. The primary outcome was 21-day mortality. Multivariable logistic regression was done to identify factors associated with 21-day mortality. The comparison was then made with patients with ALF listed for LT.

Results: A total of 1672 patients with ALF were not listed for LT. The median age was 41 (IQR: 30-54). Three hundred seventy-one (28.9%) patients were too sick to list. The most common etiology was acetaminophen toxicity (54.8%). Five hundred fifty-eight (35.7%) patients died at 21 days. After adjusting for relevant covariates, King's College Criteria (adjusted odds ratio: 3.17, CI 2.23-4.51), mechanical ventilation (adjusted odds ratio: 1.53, CI: 1.01-2.33), and vasopressors (adjusted odds ratio: 2.10, CI: 1.43-3.08) (p < 0.05 for all) were independently associated with 21-day mortality. Compared to listed patients, nonlisted patients had higher mortality (35.7% vs. 24.3%). Patients deemed not sick enough had greater than 95% survival, while those deemed too sick still had >30% survival.

Conclusions: Despite no LT, the majority of patients were alive at 21 days. Survival was lower in nonlisted patients. Clinicians are more accurate in deeming patients not sick enough to require LT as opposed to deeming patients too sick to survive.

HCC, the most common type of primary liver cancer, is a leading cause of cancer-related mortality worldwide. Although the advancement of immunotherapies by immune checkpoint inhibitors (ICIs) that target programmed cell death 1 or programmed cell death 1-ligand 1 has revolutionized the treatment for HCC, the majority is still not beneficial. Accumulating evidence has pointed out that the potent immunosuppressive tumor microenvironment in HCC poses a great challenge to ICI therapeutic efficacy. As a key component in tumor microenvironment, tumor-associated macrophages (TAMs) play vital roles in HCC development, progression, and ICI low responsiveness. Mechanistically, TAM can promote cancer invasion and metastasis, angiogenesis, epithelial-mesenchymal transition, maintenance of stemness, and most importantly, immunosuppression. Targeting TAMs, therefore, represents an opportunity to enhance the ICI therapeutic efficacy in patients with HCC. While previous research has primarily focused on biochemical cues influencing macrophages, emerging evidence highlights the critical role of biophysical signals, such as substrate stiffness, topography, and external forces. In this review, we summarize the influence of biophysical characteristics within the tumor microenvironment that regulate the phenotype and function of TAMs in HCC pathogenesis and progression. We also explore the possible mechanisms and discuss the potential of manipulating biophysical cues in regulating TAM for HCC therapy. By gaining a deeper understanding of how macrophages sense and respond to mechanical forces, we may potentially usher in a path toward a curative approach for combinatory cancer immunotherapies.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide, affecting >30% of the global population. Metabolic dysregulation, particularly insulin resistance and its subsequent manifestation as type 2 diabetes mellitus, serves as the fundamental pathogenesis of metabolic liver disease. Clinical evidence of the recent nomenclature evolution is accumulating. The interaction and impacts are bidirectional between MASLD and diabetes in terms of disease course, risk, and prognosis. Therefore, there is an urgent need to highlight the multifaceted links between MASLD and diabetes for both hepatologists and diabetologists. The surveillance strategy, risk stratification of management, and current therapeutic achievements of metabolic liver disease remain the major pillars in a clinical care setting. Therefore, the Taiwan Association for the Study of the Liver (TASL), Taiwanese Association of Diabetes Educators, and Diabetes Association of the Republic of China (Taiwan) collaboratively completed the first guidance in patients with diabetes and MASLD, which provides practical recommendations for patient care.

The use of dietary supplements by patients with chronic liver disease is prevalent and rising. Despite the known risks of dietary supplements, including hepatotoxicity, adulteration, and contamination, patients with chronic liver disease often turn to dietary supplements to support their liver and/or overall health but are not necessarily empowered with the information or guidance from their liver practitioner to do so. This article provides practitioners with a framework for balancing the risks and benefits of dietary supplements in patients with chronic liver disease, offering examples of independent resources and certifications to use this framework in clinical practice. We offer 3 common clinical scenarios to highlight how the use of this framework can improve communication and decision-making in clinical practice. By adapting principles from Integrative Medicine, this article advocates for a patient-centered approach to dietary supplements in patients with chronic liver disease, encouraging open dialogue between clinicians and their patients to facilitate informed decision-making and personalized care.

Zinc homeostasis could play a role in compensated advanced chronic liver disease, and its supplementation has been linked to improvement in liver function, a decrease of hepatic complications, and reduction in HCC incidence. Compensated advanced chronic liver disease encompasses a heterogeneous group of patients with variable risks of clinically significant portal hypertension and clinical events. The ANTICIPATE model is a validated model for stratifying these risks. Our aim is to demonstrate that zinc administration can reduce the rate and risk of presenting clinical events (first decompensation, HCC, death, and liver transplantation). This study protocol describes an ongoing phase III, national, multicenter, randomized, double-blind clinical trial that will enroll 300 patients to receive either the trial treatment (zinc acexamate) or placebo. An inclusion period of 42 months is planned, with a minimum follow-up of 2 years. Our principal hypothesis is that zinc could modify the natural history of patients with compensated advanced chronic liver disease, with an overall improvement in prognosis.

Bacterial infections in patients with cirrhosis lead to a 4-fold increase in mortality. Immune dysfunction in cirrhosis further increases the risk of bacterial infections, in addition to alterations in the gut microbiome, which increase the risk of pathogenic bacteria. High rates of empiric antibiotic use contribute to increased incidence of multidrug-resistant organisms and further increases in mortality. Despite continous advances in the field, major unknowns regarding interactions between the immune system and the gut microbiome and strategies to reduce infection risk and improve mortality deserve further investigation. Here, we highlight the unknowns in these major research areas and make a proposal for a research agenda to move toward improving disease progression and outcomes in patients with cirrhosis and infections.

Background: Transarterial chemoembolization (TACE) is the first-line treatment for patients with advanced HCC, but there are limited studies on the microenvironment alterations caused by TACE.

Methods: Six fresh HBV-related HCC specimens with or without TACE intervention were used to perform single-cell RNA sequencing. The 757 bulk samples from 3 large-scale multicenter cohorts were applied for comprehensive analysis. The biological functions of the biomarkers were further validated by phenotypic experiments.

Results: Using single-cell RNA sequencing analysis, we delineated the global cell atlas of post-TACE and demonstrated elevated tumor heterogeneity and an enhanced proinflammatory microenvironment induced by TACE. Cell-cell communication analysis revealed that markedly elevated interactions between NABP1+ malignant hepatocytes, neutrophils, and CD8+ T cells after TACE might accelerate the shift from CD8+ effector memory T cells to CD8+ effector T cells. This result was substantiated by the developmental trajectory between the 2 and dramatically decreased resident scores along the pseudotemporal trajectory. Integrating bulk data, we further found that the increased estimated proportion of NABP1+ malignant hepatocytes was related to poor TACE response and dismal prognosis, and its biomarker role could be replaced by NABP1. In vitro, multiple biological experiments consistently verified that NABP1 knockdown significantly inhibited the proliferation and migration of HCC cells.

Conclusions: Based on our depicted global map of post-TACE, we confirmed that the enhanced interactions within the microenvironment after TACE may be the culprits for postoperative progression. NABP1 may become an attractive tool for the early identification of patients sensitive to first-line TACE in clinical practice.