Immune-Mediated Liver Injury From Checkpoint Inhibitor: An Evolving Frontier With Emerging Challenges.

Over the past decade, immune checkpoint inhibitors (ICIs) have transformed the treatment of cancer, though they come with the risk of immune-related adverse (irAEs) events such as hepatotoxicity or Immune-mediated Liver Injury from Checkpoint Inhibitors (ILICI). ILICI is a serious irAE that, when severe, requires cessation of ICI and initiation of immunosuppression. Cytotoxic T Lymphocytes (CTLs) play a central role in ILICI; however, they are just part of the picture as immunotherapy broadly impacts all aspects of the immune microenvironment and can directly and indirectly activate innate and adaptive immune cells.

Zinc finger protein 169 promotes tumor progress of hepatocellular cancer via up-regulating cyclin-dependent kinase 19.

Hepatocellular carcinoma (HCC) ranks among the most prevalent types of cancer globally. Zinc finger protein 169 (ZNF169) holds significant importance as a transcription factor, yet its precise function in HCC remains to be elucidated. This study aims to examine the clinical importance, biological functions, and molecular pathways associated with ZNF169 in the development of HCC.

Opportunistic assessment of steatotic liver disease in lung cancer screening eligible individuals.

Background: Steatotic liver disease (SLD) is a potentially reversible condition but often goes unnoticed with the risk for end-stage liver disease.

Purpose: To opportunistically estimate SLD on lung screening chest computed tomography (CT) and investigate its prognostic value in heavy smokers participating in the National Lung Screening Trial (NLST).

Material And Methods: We used a deep learning model to segment the liver on non-contrast-enhanced chest CT scans of 19,774 NLST participants (age 61.

Associations between circulating amino acids and metabolic dysfunction-associated steatotic liver disease in individuals living with severe obesity.

Metabolic dysfunction-associated steatotic liver disease (MASLD) describes liver diseases caused by the accumulation of triglycerides in hepatocytes (steatosis) as well as the resulting inflammation and fibrosis. Previous studies have demonstrated that accumulation of fat in visceral adipose tissue compartments and the liver is associated with alterations in the circulating levels of some amino acids, notably glutamate. This study aimed to investigate the associations between circulating amino acids, particularly glutamate, and MASLD.

Metabolic Dysfunction-Associated Steatotic Liver Disease and Pancreatic Disease-A Population-Based Nationwide Cohort and Sibling-Controlled Study.

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) has been linked to pancreatic diseases, but evidence from population-based studies with liver histology is lacking.

Aims And Methods: In this population-based cohort including all Swedish adults (n = 8563) with biopsy-proven MASLD, we aimed to investigate incidences of pancreatic diseases compared with matched reference individuals from the general population (n = 38,858) and full siblings (n = 6696). Using Cox proportional hazard models, we calculated multivariable adjusted hazard ratios (aHRs) and confidence intervals (CIs).

Genetic Variants of GBP4: Reduced Risks for Drug-Induced Acute Liver Failure in Non-Finnish European Population.

Background And Aims: Acute liver failure (ALF) is a serious condition, typically in individuals without prior liver disease. Drug-induced ALF (DIALF) constitutes a major portion of ALF cases. Our research aimed to identify potential genetic predispositions to DIALF.

Continuous Blood Gas Control Based on Active Disturbance Rejection Control During Ex Vivo Porcine Liver Perfusion.

Background: Membrane oxygenators facilitate extracorporeal gas exchange, necessitating the monitoring of blood gas. Recent advances in normothermic machine perfusion (NMP) for ex vivo liver offer solutions to the shortage of donor liver. However, maintaining physiological blood gas levels during prolonged NMP is complex and costly.

Long-Term Effects of Direct-Acting Antivirals on Hepatitis C: Trends in Liver Disease-Related Hospitalisations in Italy.

This study aimed to evaluate the effectiveness of direct-acting antivirals (DAAs) on hepatitis C virus (HCV) hospitalisation trends in Italy, the country with not only the highest burden of HCV-related disease but also the highest number of patients treated for chronic HCV infection in Europe. Incident hospital discharge records in Italy from 2012 to 2019 that included a liver cirrhosis diagnosis without mention of alcohol, hepatocellular carcinoma (HCC), HCV and liver cirrhosis without mention of alcohol and/or HCC, cirrhosis with mention of alcohol, as defined by the International Classification of Diseases (ICD-9-CM) were reviewed. An interrupted time series analysis compared the incidence of cirrhosis and HCC before and after the introduction of DAAs (Year 2015).

Association of MASLD Phenotypes With Liver Fibrosis in Hepatitis C: The Role of Cardiometabolic Risk Factors.

Steatotic liver disease is prevalent among people with hepatitis C virus (HCV). The new definition of metabolic dysfunction-associated steatotic liver disease (MASLD) emphasises the metabolic drivers of steatosis and recognises its frequent coexistence with other chronic liver diseases, including HCV. We aimed to evaluate the association of coexisting MASLD and HCV with liver fibrosis.

Impact of Hepatoblastoma on Infectious Complications Following Pediatric Liver Transplantation.

Background: Liver transplantation is the standard therapy for end-stage liver disease in pediatric patients with biliary atresia (BA), congenital and metabolic conditions, and for an unresectable malignant tumor like hepatoblastoma (HB). BA is the leading indication for pediatric liver transplantation, while HB is the most common childhood liver cancer. Despite improved outcomes through advanced surgical techniques and novel immunosuppression, pediatric liver transplantation (pLT) is complicated by post-transplant infections.

[Metastatic pheochromocytoma in multiple endocrine neoplasia type 2A].

Pheochromocytoma (PHEO) currently is considered to be malignant due to metastatic potential. One of the most common familial forms of PHEO is multiple endocrine neoplasia syndrome (MEN) type 2. The penetrance of PHEO in MEN2 syndrome is up to 50% of cases.

Efficacy and safety of the combination of anlotinib and envafolimab in the treatment of unresectable or metastatic liposarcoma: findings from a single-center retrospective study.

Objective: To evaluate the efficacy and safety of anlotinib combined with envafolimab in the treatment of unresectable or metastatic liposarcoma.

Methods: This single-center, retrospective study enrolled 15 patients with unresectable or metastatic liposarcoma, who were treated at the Retroperitoneal Tumor Surgery Research Center of Qingdao University Affiliated Hospital between April 2022 and November 2023. The treatment regimen consisted of anlotinib combined with envafolimab.

Mechanistic insights on lycopene usage against diabetes and associated complications.

Lycopene is a tetraterpene compound belonging to carotenoids that are widely present in tomatoes and similar products. It is known as a powerful anti-oxidant and a non-provitamin A carotenoid. Lycopene has been found to effectively improve diabetes mellitus and its complications, such as cardiac complications, disorders caused by oxidative stress, and liver and neurological disorders.

Role of Locoregional Therapy on Survival After Living Donor Liver Transplantation for Hepatocellular Carcinoma--Experience from a High-volume Center.

Background: Locoregional therapy (LRT) in patients with hepatocellular carcinoma (HCC) before liver transplantation (LT) has a role in improving the tumor biology and post-LT survival outcome apart from downstaging and bridging. We retrospectively analyzed our database of adult living donor liver transplants (LDLT) for HCC, to compare the survival outcomes in Group-1 (upfront-LT, HCC within Milan/UCSF/AFP<1000 ng/ml) and Group-2 (LT post-LRT, HCC beyond UCSF/irrespective of tumor burden with AFP>1000 ng/ml). We also explored the risk factors for recurrence on follow-up.

Community characteristics and relationship between gut microbiota and intratumoral microbiota in hepatocellular carcinoma.

Background: The combination of local therapy with lenvatinib and programmed cell death protein-1 (PD-1) inhibitors represents an emerging treatment paradigm for unresectable hepatocellular carcinoma (uHCC). Our study sought to investigate the interrelationship between gut microbiota and intratumoral microbiota in the context of triple therapy, with a view to identifying potential biological markers.

Methods: The gut microbial community profiles of patients with primary untreated hepatocellular carcinoma (HCC) and those treated with local therapy combined with lenvatinib and PD-1 inhibitors were analyzed by 16S rRNA gene amplicon sequencing.

Prognosis prediction of α-FAtE score for locoregional immunotherapy in hepatocellular carcinoma.

Purpose: The α-FAtE score, composed of alpha-fetoprotein, alkaline phosphatase, and eosinophil levels, has been reported as a predictor of prognosis in hepatocellular carcinoma (HCC) patients treated with atezolizumab plus bevacizumab. This study aimed to investigate the predictive ability of α-FAtE score for the efficacy and safety of locoregional immunotherapy as the treatment of HCC patients.

Methods And Patients: We conducted a retrospective study of 446 HCC patients at Sun Yat-sen University Cancer Center from January 1 2019 to January 1 2023.

Hepatic arterial infusion chemotherapy combined with immune checkpoint inhibitors and molecular targeted therapies for advanced infiltrative hepatocellular carcinoma: a single-center experience.

Background: Infiltrative hepatocellular carcinoma (HCC) remains a therapeutic challenge due to its aggressive course and poor prognosis. Hepatic arterial infusion chemotherapy (HAIC) plus immune checkpoint inhibitors (ICIs) and molecular targeted therapies (MTTs) has shown early promise for advanced HCC, but its role in advanced infiltrative HCC is unclear. This study aims to investigate the efficacy and safety of HAIC combined with ICIs and MTTs in the treatment of advanced infiltrative HCC.

Desensitization With Imlifidase for HLA-Incompatible Deceased Donor Kidney Transplantation: A Delphi International Expert Consensus.

Highly sensitized (HS) patients in need of kidney transplantation (KTx) typically spend a longer time waiting for compatible kidneys, are unlikely to receive an organ offer, and are at increased risk of antibody-mediated rejection (AMR). Desensitization using imlifidase, which is more rapid and removes total body immunoglobulin G (IgG) to a greater extent than other methods, enables transplantation to occur between HLA-incompatible (HLAi) donor-recipient pairs and allows patients to have greater access to KTx. However, when the project was launched there was limited data and clinical experience with desensitization in general and with imlifidase specifically.

Sudden cardiac death associated with fatty liver disease.

Background: Fatty liver disease or steatotic liver disease (SLD) affects 25% of the global population and has been associated with heart disease. However, there is a lack of postmortem studies in the context of sudden cardiac death (SCD).

Objectives: To investigate the relationship between SLD and SCD.

Overweight and glucose/lipid metabolism abnormality associated with SSRIs: a pharmacovigilance study based on the FDA adverse event reporting system.

Background: In the past few decades, selective serotonin reuptake inhibitors (SSRIs) became widely used antidepressants worldwide. Therefore, the adverse reactions of patients after SSRI administration became a public and clinical concern. In this study, we conducted a pharmacovigilance study using the Adverse Event Reporting System (FAERS) database of the US Food and Drug Administration.

Mechanisms of Cancer-Induced Bone Pain.

Bone is a common site of advanced cancer metastasis, second only to the lungs and liver. Cancer-induced bone pain (CIBP) is a persistent and intense pain that is caused by a combination of inflammatory and neuropathic factors. As CIBP progresses, the degree of pain intensifies.

Liver fibrosis classification on trichrome histology slides using weakly supervised learning in children and young adults.

Background: Traditional liver fibrosis staging via percutaneous biopsy suffers from sampling bias and variable inter-pathologist agreement, highlighting the need for more objective techniques. Deep learning models for disease staging from medical images have shown potential to decrease diagnostic variability, with recent weakly supervised learning strategies showing promising results even with limited manual annotation.

Purpose: To study the clustering-constrained attention multiple instance learning (CLAM) approach for staging liver fibrosis on trichrome whole slide images (WSIs) of children and young adults.