• biomarkers
• decision trees
• liver fat
• liver transplantation
• machine learning
• magnetic resonance spectroscopy
• metabolic dysfunction‐associated steatohepatitis
• metabolic syndrome

• Humans
• Machine Learning
• Liver Transplantation
• Liver/pathology
• Liver/diagnostic imaging
• Male
• Middle Aged
• Female
• Fatty Liver/diagnosis
• Fatty Liver/diagnostic imaging
• Elasticity Imaging Techniques
• Adult

• 00023001 Ministry of Health, Czech Republic
• LX22NPO5104 Ministry of Education, Youth and Sports, Czech Republic, Next Generation EU, programme EXCELES

• Additive fabrication
• automated processes
• computational drug design
• fused deposition modeling
• tailored medications

• Colorectal liver metastases
• Hepatocellular carcinoma
• Liver
• Reimbursement
• Resin microspheres
• Transarterial radioembolisation
• Yttrium-90

• Humans
• Liver Neoplasms/radiotherapy
• Liver Neoplasms/secondary
• Liver Neoplasms/therapy
• Liver Neoplasms/mortality
• Prospective Studies
• France
• Male
• Female
• Yttrium Radioisotopes/therapeutic use
• Yttrium Radioisotopes/administration & dosage
• Carcinoma, Hepatocellular/radiotherapy
• Carcinoma, Hepatocellular/therapy
• Carcinoma, Hepatocellular/mortality
• Carcinoma, Hepatocellular/pathology
• Microspheres
• Embolization, Therapeutic/methods
• Embolization, Therapeutic/economics
• Aged
• Middle Aged
• Quality of Life
• Registries
• Colorectal Neoplasms/pathology
• Treatment Outcome

• Sirtex Medical

• Autoimmune hepatitis
• IRG1/itaconate
• JAK3/STAT3/P53
• Tissue-resident memory T cells

• Animals
• Mice
• Antigens, CD/genetics
• Antigens, CD/metabolism
• Antigens, Differentiation, T-Lymphocyte/genetics
• Antigens, Differentiation, T-Lymphocyte/metabolism
• Apoptosis/drug effects
• CD8-Positive T-Lymphocytes/immunology
• CD8-Positive T-Lymphocytes/drug effects
• Cell Proliferation/drug effects
• Disease Models, Animal
• Hepatitis, Autoimmune/immunology
• Hepatitis, Autoimmune/pathology
• Hepatitis, Autoimmune/genetics
• Hepatitis, Autoimmune/drug therapy
• Integrin alpha Chains/genetics
• Integrin alpha Chains/metabolism
• Janus Kinase 3/genetics
• Janus Kinase 3/metabolism
• Janus Kinase 3/antagonists & inhibitors
• Lectins, C-Type/genetics
• Lectins, C-Type/metabolism
• Liver/pathology
• Liver/drug effects
• Liver/metabolism
• Liver/immunology
• Memory T Cells/immunology
• Memory T Cells/metabolism
• Memory T Cells/drug effects
• Mice, Inbred C57BL
• Mice, Knockout
• Signal Transduction/drug effects
• STAT3 Transcription Factor/metabolism
• STAT3 Transcription Factor/genetics
• Tumor Suppressor Protein p53/metabolism
• Tumor Suppressor Protein p53/genetics

• 81874184 Kaixiong Tao
• 82102299 Peng Zhang

• diffuse liver disease
• liver biopsies
• liver cirrhosis
• liver fibrosis
• liver inflammation
• liver steatosis

• Humans
• Liver/pathology
• Liver Diseases/pathology
• Liver Diseases/diagnosis
• Liver Diseases/epidemiology
• Biopsy
• Prognosis
• Metabolic Syndrome/pathology
• Metabolic Syndrome/epidemiology
• Metabolic Syndrome/diagnosis
• Liver Cirrhosis/pathology
• Liver Cirrhosis/diagnosis
• Liver Cirrhosis/epidemiology
• Animals

• cancer
• drug repositioning
• drug repurposing
• in silico methods
• scoping review

• Fundação Oswaldo Cruz

• embryonic development
• extramedullary hematopoiesis
• hematopoiesis
• hematopoietic progenitor cells
• stem cell

• R01 AI168322 NIAID NIH HHS

• CRISPR/Cas system
• Viral hepatitis
• Virus diagnosis tools

• Humans
• Hepatitis A
• CRISPR-Cas Systems
• Virus Diseases
• Hepatitis A virus
• Feces
• Persistent Infection

• drug development
• endpoints
• master protocols
• non-alcoholic steatohepatitis
• platform trials
• study designs

• Humans
• Non-alcoholic Fatty Liver Disease/drug therapy
• Bayes Theorem
• Drug Development
• Adaptive Clinical Trials as Topic

• Akt
• Nrf2
• O-GlcNAcylation
• cell proliferation
• hypopharyngeal squamous cell carcinoma
• tumor progression

• ACTL6A
• TAZ
• YAP
• non-small cell lung cancer

The Adenosine diphosphate-Ribosylation Factor (ARF) family belongs to the RAS superfamily of small GTPases and is involved in a wide variety of physiological processes, such as cell proliferation, motility and differentiation by regulating membrane traffic and associating with the cytoskeleton. Like other members of the RAS superfamily, ARF family proteins are activated by Guanine nucleotide Exchange Factors (GEFs) and inactivated by GTPase-Activating Proteins (GAPs). When active, they bind effectors, which mediate downstream functions. Several studies have reported that cancer cells are able to subvert membrane traffic regulators to enhance migration and invasion. Indeed, members of the ARF family, including ARF-Like (ARL) proteins have been implicated in tumorigenesis and progression of several types of cancer. Here, we review the role of ARF family members, their GEFs/GAPs and effectors in tumorigenesis and cancer progression, highlighting the ones that can have a pro-oncogenic behavior or function as tumor suppressors. Moreover, we propose possible mechanisms and approaches to target these proteins, toward the development of novel therapeutic strategies to impair tumor progression.

• ARL
• GTPase-activating protein
• guanine nucleotide exchange factor
• invasion
• membrane traffic
• migration
• tumorigenesis

• diseases
• acute inflammation

• Animals
• Hepatocytes/metabolism
• Humans
• Immunity, Innate/genetics
• Intracellular Signaling Peptides and Proteins/antagonists & inhibitors
• Liver
• Mice
• Mice, Knockout
• Phosphate-Binding Proteins/antagonists & inhibitors
• Pyroptosis/drug effects
• Reperfusion Injury/genetics
• Reperfusion Injury/prevention & control

• LSEC
• LSEC targeting
• endothelial dysfunction
• hepatic stellate cells
• inflammation
• liver
• liver fibrosis resolution
• liver regeneration
• liver sinusoidal endothelial cells
• oxidative stress

• Endothelium/metabolism
• Humans
• Liver Cirrhosis/physiopathology
• Liver Regeneration/physiology
• Signal Transduction

• Bioinformatics
• Hepatitis
• Hepatology

• Adipose Tissue, Brown
• Adipose Tissue, White
• Animals
• Fatty Liver
• Mice
• Thermogenesis

• Carcinoma, Hepatocellular
• Hepatic Stellate Cells
• Humans
• Liver Cirrhosis
• Liver Neoplasms
• Myosins
• Receptors, Retinoic Acid
• Retinoids

• R01 DK068437 NIDDK NIH HHS
• R01 DK101251 NIDDK NIH HHS

• Expression profiling
• Gastroenterology
• Hepatology
• Molecular genetics
• Mouse models

Over the last years it has started a real revolution in the treatment of chronic hepatitis C. This occurred for the availability of direct-acting antiviral agents that allow to reach sustained virologic response in approximately 90% of cases. In the near future further progress will be achieved with the use of pan-genotypic drugs with high efficacy but without side effects.

• Direct-acting antiviral agents
• Nucleoside inhibitors
• Boceprevir
• Sofosbuvir
• Telaprevir
• Hepatitis C
• Simeprevir
• Daclatasvir
• Ledipasvir
• Faldaprevir
• Ritonavir
• Ombitasvir
• Dasabuvir

Hepatic encephalopathy (HE) is a severe neuropsychiatric syndrome that most commonly occurs in decompensated liver cirrhosis and incorporates a spectrum of manifestations that ranges from mild cognitive impairment to coma. Although the etiology of HE is not completely understood, it is believed that multiple underlying mechanisms are involved in the pathogenesis of HE, and one of the main factors is thought to be ammonia; however, the ammonia hypothesis in the pathogenesis of HE is incomplete. Recently, it has been increasingly demonstrated that inflammation, including systemic inflammation, neuroinflammation and endotoxemia, acts in concert with ammonia in the pathogenesis of HE in cirrhotic patients. Meanwhile, a good number of studies have found that current therapies for HE, such as lactulose, rifaximin, probiotics and the molecular adsorbent recirculating system, could inhibit different types of inflammation, thereby improving the neuropsychiatric manifestations and preventing the progression of HE in cirrhotic patients. The anti-inflammatory effects of these current therapies provide a novel therapeutic approach for cirrhotic patients with HE. The purpose of this review is to describe the inflammatory mechanisms behind the etiology of HE in cirrhosis and discuss the current therapies that target the inflammatory pathogenesis of HE.

• Inflammation
• Hepatic encephalopathy
• Pathogenesis
• Treatment

• Animals
• Anti-Inflammatory Agents/therapeutic use
• Hepatic Encephalopathy/diagnosis
• Hepatic Encephalopathy/drug therapy
• Hepatic Encephalopathy/etiology
• Hepatic Encephalopathy/metabolism
• Humans
• Inflammation Mediators/antagonists & inhibitors
• Inflammation Mediators/metabolism
• Liver Cirrhosis/complications
• Liver Cirrhosis/diagnosis
• Signal Transduction/drug effects
• Treatment Outcome

Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of autosomal recessive genetic diseases with a major clinical manifestation of severe intrahepatic cholestasis and an incidence rate of 1/10000 to 1/5000. PFIC is usually first diagnosed in infancy or childhood and eventually develops into liver failure and death. Based on clinical manifestations, laboratory tests, and genetic defects in liver tissue, PFIC is roughly divided into three types: PFIC-1, PFIC-2 and PFIC-3. Studies have demonstrated that all three types of PFIC are associated with the mutations of bile transport system genes in the liver. Promoting transporter expression has important clinical significance for the treatment of PFIC. In this paper, we summarize the etiology and treatment status of PFIC and discuss the treatment of PFIC by promoting the expression of transporters.

• Transporter
• Expression
• Progressive familial intrahepatic cholestasis

Liver biopsy is still the golden standard in the diagnosis of chronic liver diseases, but it is invasive, which limits its application. Therefore, the search for a reliable noninvasive diagnostic method has attracted more and more attention. Since Fibroscan (FS) was launched in 2003, scholars have paid more attention to this modality, because it is non-invasive, painless, rapid and objective. In this paper, we will review the value of FS in the diagnosis and treatment of chronic liver disease.

• Fibroscan
• Transient elastography
• Chronic liver disease
• Noninvasive diagnosis

AIM: To improve an asialoglycoprotein receptor (ASGPR)-based enrichment method for detection of circulating tumor cells (CTCs) of hepatocellular carcinoma (HCC).

METHODS: Peripheral blood samples were collected from healthy subjects, patients with HCC or various other cancers, and patients with hepatic lesions or hepatitis. CTCs were enriched from whole blood by extracting CD45-expressing leukocytes with monoclonal antibody coated-beads following density gradient centrifugation. The remaining cells were cytocentrifuged on polylysine-coated slides. Isolated cells were treated by triple immunofluorescence staining with CD45 antibody and a combination of antibodies against ASGPR and carbamoyl phosphate synthetase 1 (CPS1), used as liver-specific markers, and costained with DAPI. The cell slide was imaged and stained tumor cells that met preset criteria were counted. Recovery, sensitivity and specificity of the detection methods were determined and compared by spiking experiments with various types of cultured human tumor cell lines. Expression of ASGPR and CPS1 in cultured tumor cells and tumor tissue specimens was analyzed by flow cytometry and triple immunofluorescence staining, respectively.

RESULTS: CD45 depletion of leukocytes resulted in a significantly greater recovery of multiple amounts of spiked HCC cells than the ASGPR⁺ selection (Ps < 0.05). The expression rates of either ASGPR or CPS1 were different in various liver cancer cell lines, ranging between 18% and 99% for ASGPR and between 9% and 98% for CPS1. In both human HCC tissues and liver cancer cell lines, there were a few HCC cells that did not stain positive for ASGPR or CPS1. The mixture of monoclonal antibodies against ASGPR and CPS1 identified more HCC cells than either antibody alone. However, these antibodies did not detect any tumor cells in blood samples spiked with the human breast cancer cell line MCF-7 and the human renal cancer cell line A498. ASGPR⁺ or/and CPS1⁺ CTCs were detected in 29/32 (91%) patients with HCC, but not in patients with any other kind of cancer or any of the other test subjects. Furthermore, the improved method detected a higher CTC count in all patients examined than did the previous method (P = 0.001), and consistently achieved 12%-21% higher sensitivity of CTC detection in all seven HCC patients with more than 40 CTCs.

CONCLUSION: Negative depletion enrichment combined with identification using a mixture of antibodies against ASGPR and CPS1 improves sensitivity and specificity for detecting circulating HCC cells.

• Asialoglycoprotein receptor
• Carbamoyl phosphate synthetase 1
• Circulating tumor cells
• Hepatocellular carcinoma
• Negative depletion

• Asialoglycoprotein Receptor/blood
• Biomarkers, Tumor/blood
• Carbamoyl-Phosphate Synthase (Ammonia)/blood
• Carcinoma, Hepatocellular/blood
• Carcinoma, Hepatocellular/pathology
• Case-Control Studies
• Cell Separation/methods
• Female
• Flow Cytometry
• Fluorescent Antibody Technique
• Hep G2 Cells
• Humans
• Leukocyte Common Antigens/blood
• Liver Neoplasms/blood
• Liver Neoplasms/pathology
• MCF-7 Cells
• Male
• Neoplastic Cells, Circulating/metabolism
• Neoplastic Cells, Circulating/pathology
• Reproducibility of Results

• Acute rejection
• Human leukocyte antigen
• Killer immunoglobulin-like receptor
• Liver transplantation
• Primary sclerosing cholangitis

• Adolescent
• Adult
• Aged
• Alleles
• Cholangitis, Sclerosing/genetics
• Cholangitis, Sclerosing/immunology
• End Stage Liver Disease/immunology
• End Stage Liver Disease/surgery
• Female
• Genotype
• Graft Rejection
• Graft Survival
• HLA Antigens/genetics
• HLA Antigens/immunology
• Humans
• Immunohistochemistry
• Liver Transplantation
• Male
• Middle Aged
• Receptors, KIR/genetics
• Retrospective Studies
• Risk Factors
• Treatment Outcome
• Young Adult

• 100140 Wellcome Trust
• G0901682 Medical Research Council

Fatty liver is a growing health problem worldwide. It might evolve to nonalcoholic steatohepatitis, cirrhosis and cause hepatocellular carcinoma. This disease, which has increased because of eating habits, changes in food content and lifestyle, affects people from childhood. The most important risk factors are obesity and insulin resistance. Besides these factors, gender, ethnicity, genetic predisposition and some medical problems are also important. Cirrhosis in children is rare but is reported. Nonalcoholic fatty liver disease (NAFLD) has no specific symptoms or signs but should be considered in obese children. NAFLD does not have a proven treatment. Weight loss with family based treatments is the most acceptable management. Exercise and an applicable diet with low glycemic index and appropriate calorie intake are preferred. Drugs are promising but not sufficient in children for today.

• Nonalcoholic fatty liver disease
• Nonalcoholic steatohepatitis
• Children
• Obesity
• Metabolic syndrome
• Insulin resistance
• Chronic liver disease

AIM: To investigate the hepatoprotective effect of baicalein against carbon tetrachloride (CCl₄)-induced liver damage in mice.

METHODS: Mice were orally administered with baicalein after CCl₄ injection, and therapeutic baicalein was given twice a day for 4 d. The anti-inflammation effects of baicalein were assessed directly by hepatic histology and serum alanine aminotranferease and aspartate aminotransferase measurement. Proliferating cell nuclear antigen was used to evaluate the effect of baicalein in promoting hepatocyte proliferation. Serum interleukin (IL)-6, IL-1β and tumor necrosis factor-α (TNF-α) levels were measured by enzyme-linked immunosorbent assay and liver IL-6, TNF-α, transforming growth factor-α (TGF-α), hepatocyte growth factor (HGF) and epidermal growth factor (EGF) genes expression were determined by quantitative real-time polymerase chain reaction.

RESULTS: CCl₄-induced acute liver failure model offers a survival benefit in baicalein-treated mice. The data indicated that the mRNA levels of IL-6 and TNF-α significantly increased within 12 h after CCl₄ treatment in baicalein administration groups, but at 24, 48 and 72 h, the expression of IL-6 and TNF-α was kept at lower levels compared with the control. The expression of TGF-α, HGF and EGF was enhanced dramatically in baicalein administration group at 12, 24, 48 and 72 h. Furthermore, we found that baicalein significantly elevated the serum level of TNF-α and IL-6 at the early phase, which indicated that baicalein could facilitate the initiating events in liver regeneration.

CONCLUSION: Baicalein may be a therapeutic candidate for acute liver injury. Baicalein accelerates liver regeneration by regulating TNF-α and IL-6 mediated pathways.

• Baicalein
• Carbon tetrachloride
• Liver injury
• Liver regeneration
• Hepatocyte proliferation

Liver transplantation is indicated in patients with acute liver failure, decompensated cirrhosis, hepatocellular carcinoma and rare liver-based genetic defects that trigger damage of other organs. Early referral to a transplant center is crucial in acute liver failure due to the high mortality with medical therapy and its unpredictable evolution. Referral to a transplant center should be considered when at least one complication of cirrhosis occurs during its natural history. However, because of the shortage of organ donors and the short-term mortality after liver transplantation on one hand and the possibility of managing the complications of cirrhosis with other treatments on the other, patients are carefully selected by the transplant center to ensure that transplantation is indicated and that there are no medical, surgical and psychological contraindications. Patients approved for transplantation are placed on the transplant waiting list and prioritized according to disease severity. Thus, the appropriate timing of transplantation depends on recipient disease severity and, although this is still a matter of debate, also on donor quality. These two variables are known to determine the “transplant benefit” (i.e., when the expected patient survival is better with, than without, transplantation) and should guide donor allocation.

• Liver transplantation
• Referral
• Waiting list
• Prioritization
• Allocation
• Timing
• Cirrhosis
• Hepatocellular carcinoma
• Indications
• Contraindications