Nonalcoholic fatty liver disease (NAFLD) is reported to affect 20-30% of adults and is accompanied by various metabolic comorbidities, where the economic and clinical burden of NAFLD is attributed to the progression of liver disease as well as the presence of extrahepatic diseases. Chronic kidney disease (CKD), which has a high incidence rate, high morbidity and mortality rates, and high medical costs, has been linked to NAFLD. CKD is associated with some metabolism-related risk factors that overlap with metabolic comorbidities of NAFLD. Therefore, to investigate the potential factors that influence CKD occurrence, the association between NAFLD and CKD should be clarified. Some studies have confirmed that NAFLD influences the occurrence and severity of CKD, whereas some studies have indicated that there is no correlation. In this review, the results of a few studies have been discussed, the potential risk factors for CKD in NAFLD are explored, and the respective biological mechanisms are elaborated to help clinicians identify CKD in patients much earlier than it is diagnosed now and thus help in reducing the incidence of liver and kidney transplants.

Histoplasma capsulatum is the most common cause of endemic mycosis in developing countries. It is a self-limited and asymptomatic disease in immunocompetent individuals but remains a frequent cause of opportunistic infection in patients with compromised immune status. Liver involvement as a part of disseminated histoplasmosis is well known. However, liver infection as a primary manifestation of histoplasmosis without evidence of primary lung involvement is rare. In conclusion, clinicians should be aware of isolated histoplasmosis affecting the hepatobiliary system, and careful evaluation is warranted to confirm the diagnosis. Given the appropriate clinical context, histoplasmosis should be considered in both immunocompetent and immunocompromised patients, regardless of pulmonary symptoms, in non endemic as well as endemic areas.

The novel coronavirus disease 2019 (COVID-19) pandemic has impacted health care worldwide, with specific patient populations, such as those with diabetes, cardiovascular disease, and chronic lung disease, at higher risk of infection and others at higher risk of disease progression. Patients with decompensated cirrhosis fall into the latter category and are a unique group that require specific treatment and management decisions because they can develop acute-on-chronic liver failure. In liver transplant recipients, the atypical immunity profile due to immunosuppression protects against downstream inflammatory responses triggered by COVID-19. This exhaustive review discusses the outcomes associated with COVID-19 in patients with advanced cirrhosis and in liver transplant recipients. We focus on the immunopathogenesis of COVID-19, its correlation with the pathogenesis of advanced liver disease, and the effect of immunosuppression in liver transplant recipients to provide insight into the outcomes of this unique patient population.

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.

Drugs are used to prevent, diagnose, and treat diseases, as well as improve physiological function and health level. With the increasing number of drug types and the lack of formal drug methods, the incidence of adverse reactions to drugs is also rising. Drug-induced liver disease is so common that in addition to poor drug quality, irrational drug use is the main reason, including drug abuse, misuse, low medical quality, and knowledge level of patients and their families; in addition, social problems such as lack of scientific management, medical ethics, and medical staff. Therefore, it is imperative to strengthen drug management, improve drug safety, and reduce the incidence of adverse reactions. Here we it is introduce and elaborate the current situation and progress in the diagnosis of drug-induced liver disease in recent years, so as to build a learning platform for the prevention and treatment of drug-induced liver disease in China.

A 75 year old male with no prior medical illness presented with upper gastrointestinal bleeding (UGIB) which was confirmed endoscopically and histologically to be a result of a periampullary adenocarcinoma. computed tomography (CT) abdomen revealed a periampullary mass. Staging laparoscopy revealed multiple bilobar liver lesions which excluded the option of curative surgery. Intraoperatively, the transverse colon was noted to be adhered to segment 4B of the liver and upon release of the adhered loop, bile leak was seen from the liver parenchyma. The affected segment was sutured which arrested further emanation of bile. Two days later patient underwent a laparoscopic washout for suspected bile peritonitis. An attempt of on table endoscopic retrograde cholangiopancreatography (ERCP) failed due to papilla inaccessibility. We proceeded with an endoscopic ultrasound-guided choledochoduodenostomy (EUS CDS). With the linear echoendoscope in long position, a 19G needle was punctured into the dilated proximal portion of the CBD. Bile was aspirated to confirm its position and a 0.025 visiglide wire was then advanced into the intrahepatic ducts. The tract was dilated with an 8F cystotome followed by deployment of a 10 x 60 mm self-expandable fully covered metal stent under fluoroscopic guidance. After four days the abdominal drain was removed and the patient was discharged. At the third month follow-up clinic review, patient was well with no evidence of stent migration. To the best of our knowledge this is the first reported case of an EUS CDS approach being utilized in a case of post-operative bile leak.

Since the end of year 2019, whole world is struggling with the epidemic of the century, the Corona Virus Disease 2019 (COVID-19). Millions of people around the globe have been affected by this contagious virus; many even lost their battle against it. This deadly virus majorly affects our pulmonary system followed by other organs like gastrointestinal tract (GIT), liver, heart, central nervous system (CNS) and other tissues; consequences of which in many cases is death. Our health experts worked day and night to find the weapon that could save human race from this deadly virus and they succeeded in no time by inventing lifesaving vaccines against COVID-19, some of which are now approved by various health authorities around the world. But, for the first time vaccines are made in such short period of time, whereas, in normal course it takes years to invent a vaccine against any virus. Now, this arose many questions on the efficacy and safety of these newly made vaccines; which are the only way, till date, to put a halt in the disastrous path of COVID-19. Thus, worldwide studies are been done to collect the data regarding its efficacy and safety to encourage common people to get vaccinated soon. This article would give the readers a little overview regarding the same.

Hepatoblastoma (HB) is the most common malignant liver tumor in children. Although surgery and chemotherapy have greatly improved the survival rate of children, the emergence of chemotherapy resistance still threatens the survival of most patients. Baicalin (Ba) is a kind of flavonoid bioactive substance with strong anti-tumor effect, but the effect of Ba on HB remains to be explored. Therefore, studying the effect and mechanism of Ba on HB may provide new opportunities for improving chemotherapy resistance.

To explore the effect and mechanism of Ba on the anti-tumor effect and cisplatin sensitivity of HB cell line Hep G2 and hepatocellular carcinoma cell line Hep 3B.

The anti-tumor effects of Ba on Hep G2 and Hep 3B cells and its influence on cisplatin sensitivity were evaluated by phenotypic experiments; Western blotting and colony formation assay are used to detect the influence of Ba on the stemness potential of two cell lines; Finally, the effect of Ba on the sensitivity of Hep G2 tumor-bearing mice to cisplatin was further verified in vivo.

Ba can significantly inhibit the malignant phenotype and stemness potential of Hep G2 in vitro, and increase its sensitivity to cisplatin, but it has no effect on Hep 3B. Further mechanism studies have shown that Ba can inhibit the clone ball formation of Hep G2 cells and down-regulate the expression of Oct4 and Sox2 proteins, but this effect has not been found in Hep 3B cell lines. Further in vivo verification showed that Ba increases the sensitivity of Hep G2 tumor-bearing mice to cisplatin.

Our study confirms the important role of Ba in HB chemotherapy resistance. Ba increases its chemotherapeutic sensitivity to cisplatin by reducing the stemness of HB cells, and this effect is selective for tumor types and has no effect on hepatocellular carcinoma.

We herein report an unusual case of rupture of hepatic cyst adenoma. Clinical and radiographic, histopathological features of this case are discussed below. Surgical management was undertaken due to the hemodynamic instability of this patient.

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.