The natural course of chronic hepatitis B virus (HBV) infection is widely studied; however, follow-up studies of the same patients are scanty. Here, we studied the dynamic changes of serum HBV RNA and cytokines in hepatitis B virus e antigen (HBeAg)-positive patients treated with entecavir (ETV) to explore the relationship between the HBV serum viral nucleic acids and host immunity.

Thirty-three chronic hepatitis B patients who are HBeAg-positive, with high virus load (HBV DNA >20,000 IU/mL), and received standard nucleos(t)ide analogue (NA) antiviral therapy (ETV) for more than 48 weeks were included. The serum levels of HBV nucleic acids and selected cytokines were measured at 0, 12, 24, and 48 weeks respectively.

Serum HBV RNA could still be detected while serum HBV DNA had fallen below the detection limit in patients treated with ETV. There was a strong positive correlation between HBV RNA and HBeAg, with a concomitant decrease in the secretion of cytokines from type 1 helper T (Th1)/type 2 helper T (Th2)/interleukin (IL)-17 producing T (Th17) cells. IL-4 and IL-10 were the main cytokines negatively associated with serum HBV RNA.

HBeAg can be used to reflect the load of HBV RNA indirectly, because serum HBV RNA has not been widely used in clinical practice. Meanwhile, serum IL-4 and IL-10 might be explored in combination with HBV RNA in guiding future clinical antiviral therapy.

Primary synovial osteochondromatosis, also known as synovial chondromatosis, is a rare benign arthropathy caused by synovial cartilage metaplasia. The tumor is rarely seen outside the knee joint cavity, especially in the infrapatellar fat pad (IFP). This case presents an older woman who complained of left knee joint pain with a growing isolated mass for 2 years. Physical examination showed that a hard mass was palpable below the patella. X-ray and computed tomography examination of the knee joint revealed cluster calcification foci under the patella. Under arthroscopy, the mass was found in the IFP and removed, with pathological examination indicating synovial osteochondromatosis. The patient recovered well after the operation, and no sign of recurrence was observed at the 4-year follow-up. This case report proposes that synovial osteochondromatosis in atypical sites, such as IFP, should heighten our attention and could be treated by arthroscopy.

LPAR6 is the most recently determined G protein-coupled receptor of lysophosphatidic acid, and hardly any study has demonstrated the performance of LPAR6 in cancers. We sought to clarify the relationship of LPAR6 to prognosis potential and tumor infiltration immune cells in different cancers.

The expression of LPAR6 and its clinical characteristics were evaluated on various databases. The association between LPAR6 and immune infiltrates of various types of cancer were investigated via TIMER.

We determined that higher LPAR6 expression level was associated with a better overall survival. Additionally, high LPAR6 expression level was significantly associated with better disease-specific survival (DSS) in bladder cancer, and better overall survival (OS)/ progression-free survival (PFS)/ distant metastasis-free survival (DMFS)/ relapse-free survival (RFS) in breast cancer and some other types of cancers. Moreover, LPAR6 significantly affects the prognosis of various cancers via The Cancer Genome Atlas (TCGA). Further research exposed that the mRNA level of LPAR6 was positively coordinated with infiltrating levels of devious immune cells in hepatocellular carcinoma.

Our results imply that LPAR6 is associated with prognosis potential and immune infiltration levels in liver cancer. Moreover, LPAR6 expression possibly contributes to the activation of CD8+ T, naive T, effector T cells and natural killer cells and inactivates T regulatory cells, decreases T cell exhaustion and regulate T helper cells in liver cancer. These discoveries imply that LPAR6 could be a novel biomarker of prognosis for indicating prognosis potential and immune-infiltrating level in hepatocellular carcinoma.

Metabolic dysfunction-associated fatty liver disease (commonly known as MAFLD) impacts global health in epidemic proportions, and the resulting morbidity, mortality and economic burden is enormous. While much attention has been given to metabolic syndrome and obesity as offending factors, a growing incidence of polypharmacy, especially in the elderly, has greatly increased the risk of drug-induced liver injury (DILI) in general, and drug-induced fatty liver disease (DIFLD) in particular. This review focuses on the contribution of DIFLD to DILI in terms of epidemiology, pathophysiology, the most common drugs associated with DIFLD, and treatment strategies.

Liver fibrosis is a life-threatening disease, with challenging morbidity and mortality for healthcare systems worldwide. It imparts an enormous economic burden to societies, making continuous research and informational updates about its pathogenesis and treatment crucial. This review′s focus is on the current knowledge about the Wnt signaling pathway, serving as an important pathway in liver fibrosis development and activation of hepatic stellate cells (HSCs). Two types of Wnt pathways are distinguished, namely the ß-catenin-dependent canonical and non-canonical Ca2+ or planar cell polarity (PCP)-dependent pathway. The dynamic balance of physiologically healthy liver and hepatocytes is disturbed by repeated liver injuries. Activation of the ß-catenin Wnt pathway prevents the regeneration of hepatocytes by the replacement of extracellular matrix (ECM), leading to the appearance of scar tissue and the formation of regenerated nodular hepatocytes, lacking the original function of healthy hepatocytes. Therefore, liver function is reduced due to the severely advanced disease. Selective inhibition of ß-catenin inhibits inflammatory processes (since chemokines and pro-inflammatory cytokines are produced during Wnt activation), reduces growth of activated HSCs and reduces collagen synthesis and angiogenesis, thereby reducing the progression of liver fibrosis in vivo. While the canonical Wnt pathway is usually inactive in a physiologically healthy liver, it shows activity during cell regeneration or renewal and in certain pathophysiological conditions, such as liver diseases and cancer. Targeted blocking of some of the basic components of the Wnt pathway is a therapeutic approach. These include the frizzled transmembrane receptor (Fz) receptors using the secreted frizzled-related protein family (sFRP), Fz-coreceptors low-density LRP 5/6 through dickkopf-related protein 1 (DKK1) or niclosamide, glycogen kinase-3 beta (GSK-3β) using SB-216763, cyclic-AMP response element-binding protein (CBP) using PRI-724 and ICG-001, the lymphoid enhancer binding factor (LEF)/T cell-specific transcription factor (TCF) system as well as Wnt inhibitory factor 1 (WIF1) and miR-17-5p using pinostilbene hydrate (PSH). Significant progress has been made in inhibiting Wnt and thus stopping the progression of liver fibrosis by diminishing key components for its action. Comprehending the role of the Wnt signaling pathway in liver fibrosis may lead to discovery of novel targets in liver fibrosis therapeutic strategies’ development.

Depression is a severe and recurrent mental disease and contributes to the global disease burden. However, there are limited effective treatments for depression. This study evaluated the effect of a compound Gaoziban tablet (CGZBT) on depression and explored its potential mechanisms that underlie its action in rats.

CGZBT was analyzed by high-performance liquid chromatography. Sprague-Dawley rats were randomized into the control, chronic unpredictable mild stress (CUMS), CUMS + 0.4 g/kg CGZBT, CUMS + 0.8 g/kg CGZBT, CUMS + 1.6 g/kg CGZBT, and CUMS + 10 mg/kg fluoxetine (Flu) groups. CGZBT was administered once a day for 14 days, which started on day 28 after the induction of CUMS. Animal behaviors were assessed using the sucrose preference test, forced swimming test, and open field test weekly. The levels of neurotransmitters were identified by liquid chromatography-mass spectrometry, cytokines were quantified by enzyme-linked immunosorbent assay, and CA1 cells were counted after hematoxylin-eosin staining. The expression levels of the proteins of interest were assessed using immunohistochemistry and western blotting.

Compared with the controls, the administration of CGZBT significantly increased the levels of norepinephrine, 5-hydroxytryptamine, and 5-hydroxyindoleacetic acid and serum interleukin (IL) 4 and IL10, but decreased tumor necrosis factor-alpha (TNF-α), IL1β, and IL6 in rats. The number of cells in the hippocampal CA1 area increased. In addition, CGZBT reduced the levels of Axin and adenomatous polyposis coli expression in the hippocampus and significantly upregulated the levels of Wnt1, β-catenin expression, and glycogen synthase kinase-3β (GSK-3β) phosphorylation in the brains of rats.

Our results demonstrated that CGZBT significantly ameliorated depression by promoting GSK-3β phosphorylation to enhance Wnt/β-catenin activation. Our findings might provide a basis for the clinical application of CGZBT.

Metabolic (dysfunction)-associated fatty liver disease (MAFLD) is currently the most common chronic liver disease and affects at least a quarter of the global adult population. It has rapidly become one of the leading causes of hepatocellular carcinoma and cirrhosis in Western countries. In this review, we discuss the nomenclature and definition of MAFLD as well as its prevalence and incidence in different geographical regions. Although cardiovascular disease remains the leading cause of death in MAFLD patients, the proportion of patients dying from hepatic complications increases sharply as the disease progresses to advanced liver fibrosis and cirrhosis. In addition, patients with MAFLD are at increased risk of various extrahepatic cancers. Although a causal relationship between MAFLD and extrahepatic cancers has not been established, clinicians should recognize the association and consider cancer screening (e.g., for colorectal cancer) as appropriate.

With the global popularization of vaccination against coronavirus disease 2019 (COVID-19), the reports of cases of vaccine-related adverse events are gradually increasing. The most common events are local pain at the injection site and atypical symptoms, such as fever, headache, myalgia, and general discomfort. However, a few people might develop serious cardiovascular complications, such as myocarditis, coronary spasm, and thrombosis. Elderly people and adolescents should be more alert to vaccine-related cardiovascular adverse events due to their underlying chronic comorbidities or compromised immune systems.

CorMatrix acts as a tissue scaffold and is intended to promote the proliferation of small vessels and tissue remodeling to replicate normal tissue function.

At Temple University Hospital, Philadelphia, PA, USA from 2013 to 2016, CorMatrix material was utilized during mitral valve anterior leaflet augmentation repair in 25 adult patients, and four patients required repeat interventions at 4–12 months (8.25 ± 4.35 months) after the initial repair. This study evaluated the pathological changes in four patients.

Histological examination of the CorMatrix showed matrix degradation in all cases. At 4 months after repair, mixed acute and chronic inflammatory cells that included eosinophils were visible within the matrix, which was more severe around the suture material. Later, the extent of inflammation abated and became more chronic with macrophage dominance. Some macrophages and multinucleated cells were visible deep in the matrix. The neovascularization was limited to the tissue–matrix boundary at early time points; the more mature vessels with dilated lumens extended deeper into the matrix as time increased, combined with some elongated fibroblast-like cells. In addition, marked acute and chronic inflammation with neutrophil and eosinophil infiltrate was identified in the surrounding native tissue at 4 months, especially around the suture material. Marked granulomatous inflammation was identified in all cases, with prominent multinucleated giant cells present at later time points (50%). Immunohistochemical staining for CD68 and CD163 showed prominent M2 macrophages in the CorMatrix and surrounding tissue.

Our results demonstrated time-dependent changes in failed CorMatrix repaired valves after mitral valve repair, with macrophages and neovascularization in the matrix 12 months after the initial repair.

Nonalcoholic fatty liver disease (NAFLD) affects about a quarter of the world’s population and poses a major health and economic burden globally. Recently, there have been hasty attempts to rename NAFLD to metabolic-associated fatty liver disease (MAFLD) despite the fact that there is no scientific rationale for this. Quest for a “positive criterion” to diagnose the disease and destigmatizing the disease have been the main reasons put forth for the name change. A close scrutiny of the pathogenesis of NAFLD would make it clear that NAFLD is a heterogeneous disorder, involving different pathogenic mechanisms of which metabolic dysfunction-driven hepatic steatosis is only one. Replacing NAFLD with MAFLD would neither enhance the legitimacy of clinical practice and clinical trials, nor improve clinical care or move NAFLD research forward. Rather than changing the nomenclature without a strong scientific backing to support such a change, efforts should be directed at understanding NAFLD pathogenesis across diverse populations and ethnicities which could potentially help develop newer therapeutic options.

With high rates of recurrence post-treatment, hepatocellular carcinoma (HCC) is one of the most common types of cancer worldwide and the major cause of cancer death. To improve the overall survival of HCC patients, identification of a reliable biomarker and precise early diagnosis of HCC remain major unsolved problems.

We initially screened data from the Cancer Genome Atlas liver cancer cohort to identify potential prognosis-related genes. Then, a meta-analysis of five international HCC cohorts was implemented to validate such genes. Subsequently, artificial intelligence models (random forest and neural network) were trained to predict prognosis accurately, and a log-rank test was performed for validation. Finally, the correlation between the molecular hepatocellular carcinoma prognostic score (mHPS) and the stromal and immune scoring in HCC were explored.

A comprehensive list of 65 prognosis-related genes was obtained, most of which have been not extensively studied thus far. A universal HCC mHPS system depending on the expression pattern of only 23 genes was established. The mHPS system had general applicability to HCC patients (log-rank p<0.05) in a platform-independent manner (RNA sequencing or microarray). The mHPS was also correlated with the stromal and immune scoring in HCC, reflecting the status of the tumor immune microenvironment.

Overall, the mHPS is an easy and cost-effective prognosis predicting system, which can disclose previously uncovered heterogeneity among patient subpopulations. The mHPS system can further stratify patients who are at the same clinical stage and should be valuable for precise treatment. Moreover, the prognosis-related genes recognized in this study have potential in targeted and immune therapy.

The effect of ginsenoside Rb1 on D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced acute liver injury (ALI) is unknown. The aim of this study was to evaluate the effect of ginsenoside Rb1 on ALI and its underlying mechanisms.

Mice were pretreated with ginsenoside Rb1 by intraperitoneal injection for 3 days before D-GalN/LPS treatment, to induce ALI. The survival rate was monitored every hour for 24 h, and serum biochemical parameters, hepatic index and histopathological analysis were evaluated to measure the degree of liver injury. ELISA was used to detect oxidative stress and inflammatory cytokines in hepatic tissue and serum. Immunohistochemistry staining, RT-PCR and western blotting were performed to evaluate the expression of toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB), and NLR family, pyrin domain-containing 3 protein (NLRP3) in liver tissue and Kupffer cells (KCs).

Ginsenoside Rb1 improved survival with D-GalN/LPS-induced ALI by up to 80%, significantly ameliorated the increased alanine and aspartate transaminase, restored the hepatic pathological changes and reduced the levels of oxidative stress and inflammatory cytokines altered by D-GalN/LPS. Compared to the control group, the KCs were increased in the D-GalN/LPS groups but did not increase significantly with Rb1 pretreatment. D-GalN/LPS could upregulate while Rb1 pretreatment could downregulate the expression of interleukin (IL)-1β, IL-18, NLRP3, apoptosis associated speck-like protein containing CARD (ASC) and caspase-1 in isolated KCs. Furthermore, ginsenoside Rb1 inhibited activation of the TLR4/NF-κB signaling pathway and NLRP3 inflammasome induced by D-GalN/LPS administration.

Ginsenoside Rb1 protects mice against D-GalN/LPS-induced ALI by attenuating oxidative stress and the inflammatory response through the TLR4/NF-κB signaling pathway and NLRP3 inflammasome activation.

The immune system plays vital roles in hepatocellular carcinoma (HCC) initiation and progression. The present study aimed to construct an immune-gene related prognostic signature (IRPS) for predicting the prognosis of HCC patients.

Gene expression data were retrieved from The Cancer Genome Atlas database. The IRPS was established via least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis. The prognostic values of the IRPS were further validated using the International Cancer Genome Consortium (ICGC) dataset.

A total of 62 genes were identified as candidate immune-related prognostic genes. According to the results of Lasso and multivariate Cox regression analysis, we established an IRPS and confirmed its stability and reliability in the ICGC dataset. The IRPS was significantly associated with advanced clinicopathological characteristics. Both Cox regression analyses revealed that the IRPS could be independent risk factors influencing prognosis of HCC patients. The relationships between the IRPS and infiltration of immune cells demonstrated that the IRPS was associated with immune cell infiltration. Furthermore, a nomogram was constructed to estimate the survival probability of HCC patients.

The IRPS was effective for predicting prognosis of HCC patients, which might serve as novel prognostic and therapeutic biomarkers for HCC.

Ewing’s sarcoma (ES) is a tumor that often occurs in the long bones and rarely arises from visceral organs primarily. Here, we report a case of primary hepatic ES, discuss its computed tomography (CT) and gadobenate dimeglumine-enhanced magnetic resonance (MRI) features. This is the first Chinese and fifth primary hepatic ES case reported, based on a literature review. Imaging examinations showed that the tumor was solid, with necrosis and hemorrhage. Contrast-enhanced images showed that the tumor was hypervascular and especially had heterogeneous signal intensity on hepatobiliary phase MRI images. Intratumoral vessels and vascular invasion were also present.

Vibration-controlled transient elastography (VCTE) is a noninvasive tool that uses liver stiffness measurement (LSM) to assess fibrosis. Since real-life data during everyday clinical practice in the USA are lacking, we describe the patterns of use and diagnostic performance of VCTE in patients at an academic medical center in New York City.

Patients who received VCTE scans were included if liver biopsy was performed within 1 year. Diagnostic performance of VCTE in differentiating dichotomized fibrosis stages was assessed via area under the receiver operating characteristics (AUROC). Fibrosis stage determined from VCTE LSM was compared to liver biopsy.

Of 109 patients, 49 had nonalcoholic fatty liver disease, 16 chronic hepatitis C, 15 congestive hepatopathy, and 22 at least two etiologies. AUROC was 0.90 for differentiating cirrhosis (stage 4) with a positive predictive value (PPV) range of 0.28 to 0.45 and negative predictive value range of 0.96 to 0.98. For 31 (32%) patients, VCTE fibrosis stage was at least two stages higher than liver biopsy fibrosis stage. Thirteen of thirty-five patients considered to have cirrhosis by VCTE had stage 0 to 2 and 12 stage 3 fibrosis on liver biopsy.

VCTE has reasonable diagnostic accuracy and is reliable at ruling out cirrhosis. However, because of its low PPV, caution must be exercised when used to diagnose cirrhosis, as misdiagnosis can lead to unnecessary health care interventions. In routine practice, VTCE is also sometimes performed for disease etiologies for which it has not been robustly validated.

The incidence of hepatocellular carcinoma (HCC) is significantly lower in women than men, implying that estrogen receptors (ERs) may play an important role in this sex dimorphism. Recently, considerable progress has been made in expanding our understanding of the mechanisms of ERs in HCC. As one of the most important ERs, ERα functions as a tumor suppressor in the progression of HCC through various pathways, such as STAT3 signaling pathways, lipid metabolism-related signaling pathways, and non-coding RNAs. However, the function of ERα was reduced with the changes of some molecules in the liver, which may develop further into HCC and make it difficult to achieve an effective hormone treatment effect. Intriguingly, there are signs that individualized hormone therapy according to the activity of ERα will overcome this challenge. Based on these observations, it is particularly imperative to reassess and extend the function of ERα. In this review, we mainly elucidated molecular mechanisms associated with ERα in HCC and investigated the individualized hormone therapy based on these mechanisms, with the aim of providing new insights for HCC treatment.

The proportions of patients with hepatocellular carcinoma (HCC) involving portal vein tumor thrombus (PVTT) varies greatly in different countries or regions, ranging from 13% to 45%. The treatment regimens for PVTT recommended by HCC guidelines in different countries or regions also vary greatly. In recent years, with the progress and development of surgical concepts, radiotherapy techniques, systematic therapies (for example, VEGF inhibitors, tyrosine kinase inhibitors and immune checkpoint inhibitors), patients with HCC involving PVTT have more treatment options and their prognoses have been significantly improved. To achieve the maximum benefit, both clinicians and patients need to think rationally about the indications of treatment modalities, the occurrence of severe adverse events, and the optimal fit for the population. In this review, we provide an update on the treatment modalities available for patients with HCC involving PVTT. Trials with large sample size for patients with advanced or unresectable HCC are also reviewed.

Irreversible electroporation (IRE) is an emerging local ablation therapy which may be effective for unresectable tumors. This study aimed to evaluate the safety and efficacy of percutaneous IRE in the treatment of hepatocellular carcinoma (HCC) abutting the diaphragm.

A total of 26 participants with 39 tumors abutting the diaphragm were prospectively evaluated between July 2015 and September 2018. Complications associated with IRE were recorded, and the survival benefit of IRE was analyzed. The factors associated with time to local tumor progression (LTP) were analyzed using univariate and multivariate Cox regression models.

No major complications or treatment-related deaths occurred. The technical success rate was 96.2% (25/26) and complete ablation rate was 92.3% (36/39). The median follow-up period was 16.7 months (range: 3.0–43.0 months), the LTP occurred in 15.2% of tumors and median time to LTP was 20.4 months. Overall, tumor size (hazard ratio: 1.24 [95% confidence interval: 0.38, 3.81], p=0.03) was the only factor associated with time to LTP.

This study shows for the first time that percutaneous IRE is a safe and effective ablation technology for HCC abutting the diaphragm.