Consensus statements on endoscopic ultrasound-guided tissue acquisition. Guidelines from the Asian Endoscopic Ultrasound Group.

Objectives: This consensus was developed by the Asian EUS Group (AEG), who aimed to formulate a set of practice guidelines addressing various aspects of endoscopic ultrasound-guided tissue acquisition (EUS-TA).

Methods: The AEG initiated the development of consensus statements and formed an expert panel comprising surgeons, gastroenterologists, and pathologists. Three online consensus meetings were conducted to consolidate the statements and votes.

Isoformic PD-1-mediated immunosuppression underlies resistance to PD-1 blockade in hepatocellular carcinoma patients.

Objective: Immune checkpoint blockade (ICB) has improved cancer treatment, yet why most hepatocellular carcinoma (HCC) patients are resistant to PD-1 ICB remains elusive. Here, we elucidated the role of a programmed cell death protein 1 (PD-1) isoform, Δ42PD-1, in HCC progression and resistance to nivolumab ICB.

Design: We investigated 74 HCC patients in three cohorts, including 41 untreated, 28 treated with nivolumab and 5 treated with pembrolizumab.

Non-alcoholic fatty liver disease: the pathologist's perspective.

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of diseases characterized by fatty accumulation in hepatocytes, ranging from steatosis, non-alcoholic steatohepatitis, to cirrhosis. While histopathological evaluation of liver biopsies plays a central role in the diagnosis of NAFLD, limitations such as the problem of interobserver variability still exist and active research is underway to improve the diagnostic utility of liver biopsies. In this article, we provide a comprehensive overview of the histopathological features of NAFLD, the current grading and staging systems, and discuss the present and future roles of liver biopsies in the diagnosis and prognostication of NAFLD.

Nestin as a diagnostic and prognostic marker for combined hepatocellular-cholangiocarcinoma.

Background & Aims: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer (PLC) associated with a poor prognosis. Given the challenges in its identification and its clinical implications, biomarkers are critically needed. We aimed to investigate the diagnostic and prognostic value of the immunohistochemical expression of Nestin, a progenitor cell marker, in a large multicentric series of PLCs.

Reliability of the nonalcoholic steatohepatitis clinical research network and steatosis activity fibrosis histological scoring systems.

Background And Aim: We aimed to determine whether lobular inflammation and ballooning grades in the Non-alcoholic Steatohepatitis Clinical Research Network (NASH CRN) scoring system can be directly translated into the same for the Steatosis Activity Fibrosis scoring system (SAF) and to look at intra-observer and inter-observer agreement for each individual histological component and for diagnosis of non-alcoholic steatohepatitis (NASH) using the two scoring systems.

Methods: Four pathologists from two Asian centers scored 20 digitalized slides, twice using the NASH CRN, twice using the SAF. Intra-observer and inter-observer agreement was analyzed using Fleiss' kappa, weighted kappa, or Cohen kappa, where appropriate.

Unique molecular characteristics of NAFLD-associated liver cancer accentuate β-catenin/TNFRSF19-mediated immune evasion.

Background & Aims: The hepatic manifestation of the metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), can lead to the development of hepatocellular carcinoma (HCC). Despite a strong causative link, NAFLD-HCC is often underrepresented in systematic genome explorations.

Methods: Herein, tumor-normal pairs from 100 patients diagnosed with NAFLD-HCC were subject to next-generation sequencing.

A selective HDAC8 inhibitor potentiates antitumor immunity and efficacy of immune checkpoint blockade in hepatocellular carcinoma.

Insufficient T cell infiltration into noninflamed tumors, such as hepatocellular carcinoma (HCC), restricts the effectiveness of immune-checkpoint blockade (ICB) for a subset of patients. Epigenetic therapy provides further opportunities to rewire cancer-associated transcriptional programs, but whether and how selective epigenetic inhibition counteracts the immune-excluded phenotype remain incompletely defined. Here, we showed that pharmacological inhibition of histone deacetylase 8 (HDAC8), a histone H3 lysine 27 (H3K27)-specific isozyme overexpressed in a variety of human cancers, thwarts HCC tumorigenicity in a T cell-dependent manner.

Artificial intelligence in prediction of non-alcoholic fatty liver disease and fibrosis.

Artificial intelligence (AI) has become increasingly widespread in our daily lives, including healthcare applications. AI has brought many new insights into better ways we care for our patients with chronic liver disease, including non-alcoholic fatty liver disease and liver fibrosis. There are multiple ways to apply the AI technology on top of the conventional invasive (liver biopsy) and noninvasive (transient elastography, serum biomarkers, or clinical prediction models) approaches.

Chemotherapy-induced recruitment of myeloid-derived suppressor cells abrogates efficacy of immune checkpoint blockade.

Background & Aims: Immune checkpoint blockade (ICB) has been approved for treatment of hepatocellular carcinoma (HCC). However, many patients with advanced HCC are non-responders to ICB monotherapy. Cytotoxic chemotherapy has been proposed to modulate the tumor microenvironment (TME) and sensitize tumors to ICB.

A Sequential Algorithm Combining ADAPT and Liver Stiffness Can Stage Metabolic-Associated Fatty Liver Disease in Hospital-Based and Primary Care Patients.

Introduction: Metabolic-associated fatty liver disease is common, with fibrosis the major determinant of adverse outcomes. Population-based screening tools with high diagnostic accuracy for the staging of fibrosis are lacking.

Methods: Three independent cohorts, 2 with both liver biopsy and liver stiffness measurements (LSMs, n = 254 and 65) and a population sample (n = 713), were studied.

EBV-encoded miRNAs can sensitize nasopharyngeal carcinoma to chemotherapeutic drugs by targeting BRCA1.

Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated epithelial malignancy. The high expression of BART-miRNAs (miR-BARTs) during latent EBV infection in NPC strongly supports their pathological importance in cancer progression. Recently, we found that several BART-miRNAs work co-operatively to modulate the DNA damage response (DDR) by reducing Ataxia-telangiectasia-mutated (ATM) activity.

Cell cycle-related kinase reprograms the liver immune microenvironment to promote cancer metastasis.

The liver is an immunologically tolerant organ and a common metastatic site of multiple cancer types. Although a role for cancer cell invasion programs has been well characterized, whether and how liver-intrinsic factors drive metastatic spread is incompletely understood. Here, we show that aberrantly activated hepatocyte-intrinsic cell cycle-related kinase (CCRK) signaling in chronic liver diseases is critical for cancer metastasis by reprogramming an immunosuppressive microenvironment.

NADPH oxidase 5α promotes the formation of CD271 tumor-initiating cells in oral cancer.

Oral tongue squamous cell carcinoma (OTSCC) has a distinctive cell sub-population known as tumor-initiating cells (TICs). CD271 is a functional TIC receptor in head and neck cancers. The molecular mechanisms governing CD271 up-regulation remains unclear.

Macromolecular proton fraction mapping based on spin-lock magnetic resonance imaging.

Purpose: In MRI, the macromolecular proton fraction (MPF) is a key parameter of magnetization transfer (MT). It represents the relative amount of immobile protons associated with semi-solid macromolecules involved in MT with free water protons. We aim to quantify MPF based on spin-lock MRI and explore its advantages over the existing MPF-mapping methods.

Development of a Novel Inflammation-Based Index for Hepatocellular Carcinoma.

Background: The aim of current study was to (1) construct and validate a novel hepatocellular carcinoma (HCC)-specific inflammatory index; (2) compare the performances of the Integrated Liver Inflammatory Score (ILIS) to existing 4 inflammatory indices in HCC; (3) explore the association between the inflammatory indices and systemic/intratumoral inflammatory markers.

Methods: Two cohorts from Hong Kong (HK; = 1,315) and Newcastle ( = 574) were studied. A novel index was constructed from the HK training set ( = 627).

Positive Hepatitis B Core Antibody Is Associated With Cirrhosis and Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease.

Objectives: Previous exposure to hepatitis B virus (HBV) may increase the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C. We aim to study the impact of previous HBV infection on the severity and outcomes of patients with nonalcoholic fatty liver disease (NAFLD).

Methods: This was a multicenter study of 489 patients with biopsy-proven NAFLD and 69 patients with NAFLD-related or cryptogenic HCC.

Targeting the Oncogenic p53 Mutants in Colorectal Cancer and Other Solid Tumors.

Colorectal cancer (CRC) is a kind of solid tumor and the third most common cancer type in the world. It is a heterogeneous disease characterized by genetic and epigenetic aberrations. The mutation is the key step driving the transition from adenoma to adenocarcinoma.

Performance of Simple Fibrosis Scores in Nonobese Patients With Nonalcoholic Fatty Liver Disease.

Because only a minority of patients with nonalcoholic fatty liver disease (NAFLD) have advanced fibrosis and would eventually develop liver-related complications, current guidelines recommend initial assessment with noninvasive tests of fibrosis. Most previous studies focused on overweight and obese patients. Despite a strong association between obesity and NAFLD, 3%-30% of people with relatively normal body mass index (BMI) may still have NAFLD.

Quantifying and monitoring fibrosis in non-alcoholic fatty liver disease using dual-photon microscopy.

Objective: Fibrosis stage is strongly associated with liver-related outcomes and is a key surrogate endpoint in drug trials for non-alcoholic steatohepatitis. Dual-photon microscopy allows automated quantification of fibrosis-related parameters (q-FPs) and may facilitate large-scale histological studies. We aim to validate the performance of q-FPs in a large histological cohort.

A comparability study of immunohistochemical assays for PD-L1 expression in hepatocellular carcinoma.

Programmed death ligand 1 (PD-L1) protein expression by immunohistochemistry is a promising biomarker for PD-1/PD-L1 blockade in hepatocellular carcinoma. There are a number of commercially available PD-L1 assays. Our study aimed to compare the analytical performance of different PD-L1 assays and evaluate the reliability of pathologists in PD-L1 scoring.

Impact of Obesity and Alanine Aminotransferase Levels on the Diagnostic Accuracy for Advanced Liver Fibrosis of Noninvasive Tools in Patients With Nonalcoholic Fatty Liver Disease.

Introduction: Some evidence suggests an interference of obesity and alanine aminotransferase (ALT) levels on the diagnostic accuracy for advanced fibrosis of noninvasive tools such as liver stiffness measurement (LSM) by FibroScan, Fibrosis-4 (FIB-4), and nonalcoholic fatty liver disease fibrosis score (NFS). We assessed whether the diagnostic accuracy of LSM, Fibrosis-4 (FIB-4), and NFS and strategies based on the combination of these tools is affected by obesity and/or ALT levels.

Methods: We analyzed data from 968 patients with a histological diagnosis of nonalcoholic fatty liver disease.

The ATP-binding cassette transporter ABCF1 is a hepatic oncofetal protein that promotes chemoresistance, EMT and cancer stemness in hepatocellular carcinoma.

ATP-binding cassette (ABC) transporters mediate multidrug resistance and cancer stem cell properties in various model systems. Yet, their biological significance in cancers, especially in hepatocellular carcinoma (HCC), remains unclear. In this study, we investigated the function of ABCF1 in HCC and explored its potential as a therapeutic target.

Laparoscopic Hepatectomy (with or without Robotic Assistance) versus Radiofrequency Ablation as a Minimally Invasive Treatment for Very Early-Stage or Early-Stage Hepatocellular Carcinoma.

Background: The advantages of radiofrequency ablation (RFA) over hepatectomy as a treatment for early-stage hepatocellular carcinoma (HCC) include reduced morbidity and more rapid recovery. Although minimally invasive surgery provides similar benefits, few studies have compared the long-term oncological outcomes of these techniques. This study aimed to compare the outcomes of minimally invasive hepatectomy (MIH) and RFA.