• Hepatiis C
• hepatocellular carcinoma
• racial/ethnic disparity

• Humans
• United States/epidemiology
• Carcinoma, Hepatocellular
• Antiviral Agents/therapeutic use
• Liver Neoplasms
• Hepacivirus
• Sustained Virologic Response
• Retrospective Studies
• Hepatitis C, Chronic/drug therapy
• Early Detection of Cancer
• Hepatitis C/drug therapy

• Adjuvant therapies
• Amniotic membrane
• Hepatocellular carcinoma

• Humans
• Amnion/transplantation
• Carcinoma, Hepatocellular/therapy
• Carcinoma, Hepatocellular/pathology
• Carcinoma, Hepatocellular/drug therapy
• Liver Neoplasms/pathology
• Liver Neoplasms/therapy
• Liver Neoplasms/drug therapy
• Animals
• Signal Transduction/drug effects
• Chemotherapy, Adjuvant/methods

• Hepatocellular-carcinoma
• Mutations
• PIK3CA
• Schistosomiasis
• TP53

• Asian
• cirrhosis
• ethnicity
• hepatitis C virus
• hepatocellular carcinoma
• metabolic syndrome
• non-Asian
• predictive model
• risk score
• treatment-naïve

• cause of death
• hepatitis B virus
• hepatitis C virus
• liver cancer
• surveillance

Transporter associated with antigen processing 1 (TAP1) is a transporter protein that represent tumor antigen in the MHC I or HLA complex. Any defect in the TAP1 gene resulting in inadequate tumor tracking. TAP1 influences multidrug resistance (MDR) in human cancer cell lines and hinders the treatment during chemotherapeutic. The association of TAP1 in cancer progression remains mostly unknown and further study of the gene in relation with cancer need to conduct. Thus, the study has designed to analyze the association between the TAP1 with cancer by computationally. The expression pattern of the gene has determined by using ONCOMINE, GENT2, and GEPIA2 online platforms. The protein level of TAP1 was examined by the help of Human Protein Atlas. Samples with different clinical outcomes were investigated to evaluate the expression and promoter methylation in cancer vs. normal tissues by using UALCAN server. The copy number alteration, mutation frequency, and expression level of the gene in different cancer were analyzed by using cBioPortal server. The PrognoScan and KM plotter platforms were used to perform the survival analysis and represented graphically. Additionally, pathway and gene ontology (GO) features correlated to the TAP1 gene were analyzed and presented by bar charts. After arranging the data in a single panel like correlating expression to prognosis, mutational and alterations characteristic, and pathways analysis, we observed some interesting insights that emphasized the importance of the gene in cancer progression. The study found the relationship between the TAP1 expression pattern and prognosis in different cancer tissues and shows how TAP1 affects the clinical characteristics. The analytical data presented in the study is vital to learn about the effect of TAP1 in tumor tissue, where previously studies showing contradicting expression of TAP1 in cancer tissue. The analyzed data can also be utilized further to evade the threats against chemotherapy. Overall, the study provided a new aspect to consider the role of TAP1 gene in cancer progression and survival status.

• This study demonstrated, for the first time, a correlation between the TAP1 gene and tumor progression.

• An upregulation of TAP1 mRNA was demonstrated in various cancer types.

• This study reported a significant negative correlation for TAP1 gene expression and the survival rate in different cancer types.

The online version contains supplementary material available at 10.1007/s00109-021-02088-w.

• Co-expression
• Health informatics
• Methylation analysis
• Pathway analysis
• Survival analysis
• TAP1
• Transcriptional expression

• Animals
• Carotenoids/pharmacology
• Chlorophyceae/chemistry
• Liver/drug effects
• Liver/metabolism
• Liver/pathology
• Liver Cirrhosis/chemically induced
• Liver Cirrhosis/metabolism
• Liver Cirrhosis/pathology
• Male
• Metalloproteases/metabolism
• Oxidative Stress/drug effects
• Plant Extracts/chemistry
• Rats
• Thioacetamide/adverse effects

Direct acting antivirals (DAAs) have revolutionized the treatment of hepatitis C virus (HCV) infection, achieving high rates (≥ 95%) of sustained virological response, with a good safety profile and high compliance rates. Consequently, it had been expected that viral clearance will reduce morbidity and mortality rates, as well as the risk of hepatocellular carcinoma (HCC). However, since 2016, concerns have been raised over an unexpected high rate of HCC occurrence and recurrence after DAA therapy, which led to an avalanche of studies with contradictory results. We aimed to review the most recent and relevant articles regarding the risk of HCC after DAA treatment and identify the associated risk factors.

• Hepatocellular carcinoma
• Direct acting antivirals therapy
• Hepatitis C virus infection
• Sustained virological response
• Risk factors of hepatocellular carcinoma
• Review

• Antiviral Agents/adverse effects
• Carcinoma, Hepatocellular/drug therapy
• Carcinoma, Hepatocellular/epidemiology
• Hepacivirus/genetics
• Hepatitis C/complications
• Hepatitis C/drug therapy
• Hepatitis C/epidemiology
• Hepatitis C, Chronic/complications
• Hepatitis C, Chronic/drug therapy
• Hepatitis C, Chronic/epidemiology
• Humans
• Liver Neoplasms/drug therapy
• Liver Neoplasms/epidemiology
• Neoplasm Recurrence, Local/drug therapy

• Aggressiveness index
• HCV related HCC
• Hepatocellular carcinoma
• Tumor pattern

• direct-acting antivirals
• hepatitis C
• hepatocellular carcinoma
• recurrence
• time interval

• Aged
• Aged, 80 and over
• Antiviral Agents/therapeutic use
• Carcinoma, Hepatocellular/etiology
• Carcinoma, Hepatocellular/prevention & control
• Female
• Hepatitis C, Chronic/complications
• Hepatitis C, Chronic/drug therapy
• Humans
• Immunotherapy
• Interferons/therapeutic use
• Liver Neoplasms/etiology
• Liver Neoplasms/prevention & control
• Male
• Middle Aged
• Neoplasm Recurrence, Local/epidemiology
• Neoplasm Recurrence, Local/prevention & control
• Proportional Hazards Models
• Retrospective Studies
• Secondary Prevention/methods

Due to the recent alarming increase in the incidence of hepatocellular carcinoma (HCC) in thalassemias, the present report reviews briefly the frequency, the major risk factors, and the surveillance of HCC in β-thalassemias. Over the past 33 years, 153 cases of HCC were reported in patients with thalassemia, mainly in Italy and Greece. Among HCV-infected patients, additional factors promoting the development of HCC included: advanced age, male sex, chronic hepatitis B (CHB) co-infection, and iron overload. For early diagnosis of HCC, sequential ultrasound screening is recommended especially for thalassemia patients with chronic hepatitis C (CHC), which coincides with (one or more) additional risk factors for HCC. Here we report also the preliminary data from thalassemic patients, above the age of 30 years, followed in 13 ICET-A centers. The total number of enrolled patients was 1,327 (males: 624 and 703 females). The prevalence of HCC in thalassemia major patients [characterized by transfusion-dependency (TDT)] and thalassemia intermedia [characterized by nontransfusion dependency (NTDT)] was 1.66 % and 1.96 %, respectively. The lowest age at diagnosis of HCC was 36 years for TDT and 47 years for NTDT patients. We hope that this review can be used to develop more refined and prospective analyses of HCC magnitude and risk in patients with thalassemia and to define specific international guidelines to support clinicians for early diagnosis and treatment of HCC in thalassemic patients.

• Hepatocellular carcinoma
• Risk factors
• Surveillance
• Thalassemias

• Carcinoma, hepatocellular
• Chemoembolization, therapeutic
• Survival

• Aged
• Carcinoma, Hepatocellular/drug therapy
• Carcinoma, Hepatocellular/mortality
• Carcinoma, Hepatocellular/pathology
• Chemoembolization, Therapeutic/adverse effects
• Chemoembolization, Therapeutic/mortality
• Disease Progression
• Female
• Humans
• Liver Neoplasms/drug therapy
• Liver Neoplasms/mortality
• Liver Neoplasms/pathology
• Male
• Middle Aged
• Neoplasm Recurrence, Local
• Retrospective Studies
• Risk Assessment
• Risk Factors
• Seoul
• Time Factors
• Treatment Outcome
• Tumor Burden

• DNA methylation
• Gene expression
• Hepatitis B virus
• Hepatitis C virus
• Hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the top causes of cancer mortality worldwide. Although HCC has been researched extensively, there is still a need for novel and effective therapeutic interventions. There is substantial evidence that initiation of carcinogenesis in liver cirrhosis, a leading cause of HCC, is mediated by cancer stem cells (CSCs). CSCs were also shown to be responsible for relapse and chemoresistance in several cancers, including HCC. MicroRNAs (miRNAs) constitute important epigenetic markers that regulate carcinogenesis by acting post-transcriptionally on mRNAs, contributing to the progression of HCC. We have previously shown that co-culture of cancer cells with mesenchymal stem cells (MSCs) could induce the reprogramming of MSCs into CSC-like cells. In this review, we evaluate the available data concerning the epigenetic regulation of miRNAs through methylation and the possible role of this regulation in stem cell and somatic reprogramming in HCC.

• cancer stem cell
• hepatocellular carcinoma
• mesencymal stem cells
• methylation
• miRNA

Hepatocellular carcinoma (HCC) is sexually disparate in humans, with a significantly increased prevalence in males. The molecular mechanisms by which the inhibition or development of liver cancer are facilitated require further investigation with regard to sex factors affecting disease progression. In the present study, functional signatures of differentially expressed genes (DEGs) were screened in female and male tumors via bioinformatics analysis. The following gene chip expression profiles were downloaded from the Gene Expression Omnibus: GSE19665, GSE23342 and GSE9843. They comprised cancerous and non-cancerous tissue from patients with HCC and included critical sex features. Further evaluation of selected DEGs in the two sexual groups was performed via hierarchical clustering analysis. Venn diagram and functional protein-protein interaction (PPI) network analyses were performed. Survival analysis of patients with differences in gene expression levels was subsequently performed using the Kaplan-Meier Plotter database. Certain identified DEGs were common in female and male tumor samples, whereas others exhibited a sexually-biased expression profile. Gene Ontology revealed that the cell cycle module ‘biological process’ was enriched in tumors derived from both sexes, whereas the metabolic pathways and drug metabolism modules were only significantly enriched in cancer tissues from male subjects. A number of hub DEGs in the cell cycle and p53 signaling pathways were involved in significant protein-protein interaction (PPI) modules, including CDK1 and CCNB1. These DEGs were upregulated in tumors derived from female subjects compared with those derived from male subjects, and could be used as markers of poor prognosis in male patients. Other genes, such as CYP3A4 and SERPINA4, were identified in metabolic pathways, and were downregulated in male compared with female subjects. These genes were associated with a decreased survival rate. The data demonstrated that sex differences in physiology may regulate the levels of gene expression and/or activity, including gene function associated with oncogenesis and the outcomes of liver cancer. Additional surveys are required to explore in detail the molecular mechanisms underlying the differences in gene expression between the two sexes during the development of liver cancer.

• AFP
• Hepatocellular carcinoma
• Liver cirrhosis

• Cancer therapy
• Hepatoma
• LHRH-MPG△NLS
• siRNA delivery

Cytokines play an important role in the pathogenesis of cirrhosis and hepatocellular carcinoma (HCC), most cases of which are related to either hepatitis B virus (HBV) or hepatitis C virus (HCV). Prior studies have examined differences in individual cytokine levels in patients with chronic liver disease, but comprehensive cytokine profiling data across different clinical characteristics are lacking. We examined serum cytokine profiles of 411 patients with HCC (n = 102: 32% HBV, 54% HCV, 14% non-viral) and without HCC (n = 309: 39% HBV, 39% HCV, 22% non-viral). Multiplex analysis (Luminex 200 IS) was used to measure serum levels of 51 common cytokines. Random forest machine learning was used to obtain receiver operator characteristic curves and to determine individual cytokine importance using Z scores of mean fluorescence intensity for individual cytokines. Among HCC and non-HCC patients, cytokine profiles differed between HBV and HCV patients (area under curve (AUC) 0.82 for HCC, 0.90 for non-HCC). Cytokine profiles did not distinguish cirrhotic HBV patients with and without HCC (AUC 0.503) or HCV patients with and without HCC (AUC 0.63). In conclusion, patients with HBV or HCV infection, with or without HCC, have distinctly different cytokine profiles, suggesting potential differences in disease pathogenesis and/or disease characteristics.

• hepatocellular carcinoma
• hepatoma
• liver cirrhosis
• liver transplantation
• orthotopic liver transplantation

• Fibrosis
• Hepatitis C virus
• Hepatocellular carcinoma
• Il-17F

Chronic hepatitis C virus (HCV) infection and its progression are major health problems that many countries including Saudi Arabia are facing. Determination of HCV genotypes and subgenotypes is critical for epidemiological and clinical analysis and aids in the determination of the ideal treatment strategy that needs to be followed and the expected therapy response. Although HCV infection has been identified as the second most predominant type of hepatitis in Saudi Arabia, little is known about the molecular epidemiology and genetic variability of HCV circulating in the Jeddah province of Saudi Arabia. The aim of this study was to determine the dominance of various HCV genotypes and subgenotypes circulating in Jeddah using partial sequencing of the NS5B region. To the best of our knowledge, this is the first study of its kind in Saudi Arabia. To characterize HCV genotypes and subgenotypes, serum samples from 56 patients with chronic HCV infection were collected and subjected to partial NS5B gene amplification and sequence analysis. Phylogenetic analysis of the NS5B partial sequences revealed that HCV/1 was the predominant genotype (73%), followed by HCV/4 (24.49%) and HCV/3 (2.04%). Moreover, pairwise analysis also confirmed these results based on the average specific nucleotide distance identity: ±0.112, ±0.112, and ±0.179 for HCV/1, HCV/4, and HCV/3, respectively, without any interference between genotypes. Notably, the phylogenetic tree of the HCV/1 subgenotypes revealed that all the isolates (100%) from the present study belonged to the HCV/1a subgenotype. Our findings also revealed similarities in the nucleotide sequences between HCV circulating in Saudi Arabia and those circulating in countries such as Morocco, Egypt, Canada, India, Pakistan, and France. These results indicated that determination of HCV genotypes and subgenotypes based on partial sequence analysis of the NS5B region is accurate and reliable for HCV subtype determination.

• Genotype
• Hepacivirus/classification
• Hepacivirus/genetics
• Humans
• Phylogeny
• Polymerase Chain Reaction
• RNA, Viral/genetics
• Saudi Arabia
• Viral Nonstructural Proteins/genetics

• King Abdulaziz City for Science and Technology

• Liver
• alcoholic liver disease
• c-Myc Avian Myelocytomatosis Viral Oncogene Homolog
• hepatitis B virus
• hepatitis C virus
• hepatoblastoma
• hepatocellular carcinoma

• Chronic HCV infection
• Clearance of HCV infection
• HIV/HCV coinfection
• Plasma RNA sequencing
• Sequence analysis

• background liver factors
• hepatocellular carcinoma
• intrahepatic metastases
• molecular alterations
• multicentric occurrence

• Hepatitis C virus
• Rapid virological response
• Toll-like receptor

• Aged
• Antiviral Agents/therapeutic use
• Female
• Gene Expression
• Genotype
• Hepatitis C, Chronic/drug therapy
• Hepatitis C, Chronic/genetics
• Hepatitis C, Chronic/immunology
• Humans
• Interferon alpha-2
• Interferon-alpha/therapeutic use
• Male
• Middle Aged
• Monocytes/metabolism
• Polyethylene Glycols/therapeutic use
• RNA, Messenger/genetics
• Recombinant Proteins/therapeutic use
• Ribavirin/therapeutic use
• Toll-Like Receptor 4/blood
• Toll-Like Receptor 4/genetics
• Viral Load

• Chang Gung Memorial Hospital-Kaohsiung Medical Center, Taiwan

• HCV
• HCV antiviral therapy
• HIV
• Insulin resistance
• Insulin sensitizer
• Liver fibrosis
• Metformin

Approximately 180 million people worldwide, (3 % of the world’s population) are infected with hepatitis C (HCV). Insulin resistance (IR) and type 2 diabetes (T2DM) are common extrahepatic manifestations of chronic HCV infection and associated with poor treatment and liver-related outcomes. The presence of these metabolic complications have been associated with poor response to interferon-based HCV antiviral therapy and increased risk of liver-related outcomes. Metformin, an insulin sensitizer is known to improve HCV treatment response and has been associated with a reduced risk of developing hepatocellular carcinoma (HCC). This study will evaluate the effect of metformin on preventing progression or promoting regression of liver fibrosis, rate of virologic cure (SVR) and other metabolic measures in HCV-HIV co-infected and HCV mono-infected study participants who have IR and are planning on initiating HCV treatment.

This study is a prospective 48-week single-centre, randomized, open-label, controlled trial of HIV-HCV co-infected and HCV mono-infected patients with IR (HOMA-IR ≥ 2.0) who are planning to initiate HCV antiviral therapy. Sixty participants will be recruited from The Ottawa Hospital Viral Hepatitis Clinic. Participants will be randomized in a 1:1 ratio to either arm 1, metformin 2 g (1 g twice daily) plus lifestyle, or to arm 2, lifestyle alone. The primary outcome will be the change in FibroScan® score (kPa) from baseline to week 12 (start of HCV treatment), the end of HCV treatment (week 24) and 24 weeks post HCV treatment (week 48). Secondary outcomes include changes in liver fibrosis using AST to platelet ratio index, changes in glucose and lipid levels, anthropometric measures, changes in alpha-fetoprotein levels, patient acceptability, and changes in dietary and physical activity parameters.

This pilot study will be the first to evaluate the role of metformin on liver fibrosis in HCV-HIV co-infected and HCV mono-infected patients with IR receiving DAA HCV treatment. If metformin is effective in reducing liver fibrosis in this patient population, this will represent a well-tolerated, easy-to-administer, inexpensive therapy that will protect against negative HCV outcomes. This study will also be an opportunity to evaluate the impact of insulin resistance and hyperglycemia on viral clearance in HCV-infected patients treated with interferon-free regimens.

ClinicalTrials.gov NCT02306070 version 4.0 (June 29, 2015)

The online version of this article (doi:10.1186/s13063-016-1454-6) contains supplementary material, which is available to authorized users.

• HCV
• HCV antiviral therapy
• HIV
• Insulin resistance
• Insulin sensitizer
• Liver fibrosis
• Metformin

To evaluate the accuracy of shear wave elastography (SWE) in the quantitative diagnosis of liver fibrosis severity.

The published literatures were systematically retrieved from PubMed, Embase, Web of science and Scopus up to May 13^th, 2016. Included studies reported the pooled sensitivity, specificity, positive and negative predictive values, as well as the diagnostic odds ratio of SWE in populations with liver fibrosis. A bivariate mixed-effects regression model was used, which was estimated by the I² statistics. The quality of articles was evaluated by quality assessment of diagnostic accuracy studies (QUADAS).

Thirteen articles including 2303 patients were qualified for the study. The pooled sensitivity and specificity of SWE for the diagnosis of liver fibrosis are as follows: ≥F1 0.76 (p<0.001, 95% CI, 0.71–0.81, I² = 75.33%), 0.92 (p<0.001, 95% CI, 0.80–0.97, I² = 79.36%); ≥F2 0.84 (p = 0.35, 95% CI, 0.81–0.86, I² = 9.55%), 0.83 (p<0.001, 95% CI, 0.77–0.88, I² = 86.56%); ≥F3 0.89 (p = 0.56, 95% CI, 0.86–0.92, I² = 0%), 0.86 (p<0.001, 95% CI, 0.82–0.90, I² = 75.73%); F4 0.89 (p = 0.24, 95% CI, 0.84–0.92, I² = 20.56%), 0.88 (p<0.001, 95% CI, 0.84–0.92, I² = 82.75%), respectively. Sensitivity analysis showed no significant changes if any one of the studies was excluded. Publication bias was not detected in this meta-analysis.

Our study suggests that SWE is a helpful method to appraise liver fibrosis severity. Future studies that validate these findings would be appropriate.

• Area Under Curve
• Elasticity Imaging Techniques/methods
• Humans
• Liver/diagnostic imaging
• Liver Cirrhosis/diagnostic imaging
• ROC Curve
• Sensitivity and Specificity

• This study was supported by the opening foundation of the State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital of Medical College, Zhejiang University, grant NO. 2015KF06.

• Agent Orange
• Hepatocellular cancer (HCC)
• hepatitis C virus (HCV)

• 90Y radioembolization
• Hepatic metastases
• Unresectable hepatocellular carcinoma

• Catheter Ablation
• Chemoembolization, Therapeutic
• Cryosurgery
• Humans
• Liver Neoplasms/secondary
• Liver Neoplasms/therapy

• Chronic hepatitis C
• Cirrhosis
• Decompensated liver disease
• Fibrosis
• Hepatitis C virus
• Natural history

• hepatocellular carcinoma
• interventional radiology
• liver cancer
• radioembolization
• therapy

AIM: To investigate the efficacy (survival) and safety of treatments for recurrent hepatocellular carcinoma (HCC) in liver transplantation (LT) patients.

METHODS: Literature search was performed on available online databases without a time limit until January 2015. Clinical studies describing survival after HCC recurrence in LT patients were retrieved for a full-text evaluation. A total of 61 studies were selected: 13 case reports, 41 retrospective case series, and 7 retrospective comparative studies.

RESULTS: Based on all included studies, the mean HCC recurrence rate was 16% of all LTs for HCC. A total of 1021 LT patients experienced HCC recurrence. The median time from LT to HCC recurrence was 13 mo (range 2-132 mo). The majority of patients (67%) presented with HCC extra-hepatic recurrences, involving lung, bone, adrenal gland, peritoneal lymph nodes, and rarely the brain. Overall survival after HCC recurrence was 12.97 mo. Surgical resection of localized HCC recurrence and Sorafenib for controlling systemic spread of HCC recurrence were associated with the higher survival rates (42 and 18 mo, respectively). However, Sorafenib, especially when combined with mTOR, was frequently associated with severe side effects that required dose reduction or discontinuation

CONCLUSION: Management of recurrent HCC in LT patients is challenging and associated with poor prognosis independently of the type of treatment.

• Recurrent hepatocellular carcinoma
• Liver transplantation
• Tumor recurrence
• Surgical resection
• Trans-arterial chemoembolization
• Sorafenib
• Systematic review

• Antineoplastic Agents/adverse effects
• Antineoplastic Agents/therapeutic use
• Carcinoma, Hepatocellular/mortality
• Carcinoma, Hepatocellular/secondary
• Carcinoma, Hepatocellular/surgery
• Humans
• Liver Neoplasms/mortality
• Liver Neoplasms/pathology
• Liver Neoplasms/surgery
• Liver Transplantation/adverse effects
• Liver Transplantation/mortality
• Neoplasm Recurrence, Local/mortality
• Neoplasm Recurrence, Local/pathology
• Neoplasm Recurrence, Local/therapy
• Niacinamide/adverse effects
• Niacinamide/analogs & derivatives
• Niacinamide/therapeutic use
• Phenylurea Compounds/adverse effects
• Phenylurea Compounds/therapeutic use
• Protein Kinase Inhibitors/adverse effects
• Protein Kinase Inhibitors/therapeutic use
• Reoperation
• Risk Factors
• Sorafenib
• Survival Analysis
• Time Factors
• Treatment Outcome

Patient: Male, 49

Final Diagnosis: Type 2 diabetes

Symptoms: —

Medication: —

Clinical Procedure: —

Specialty: Endocrinology and Metabolic

To compare the diagnostic values of magnetic resonance elastography (MRE) and diffusion-weighted imaging (DWI) in staging hepatic fibrosis (HF) in an animal model.

This study consisted of 44 rabbits served as HF group and 9 normal rabbits. HF group was divided into two subgroups: Group A (n = 32) and Group B (n = 12). Rabbits in Group B were served as a complementary group when rabbits in Group A suddenly died during the study. Rabbits from control and Group A underwent abdominal MR imaging (MRI), MRE, and DWI. In Group A, random eight rabbits underwent MRI examinations at 4, 5, 6, 10 weeks after carbon tetrachloride oil subcutaneous injection. Liver stiffness (LS) and apparent diffusion coefficient (ADC) values of liver parenchyma were measured. The diagnostic performance of MRE and DWI for staging HF was compared using the receiver operating characteristic curve analysis on the basis of the histopathological analysis of HF.

Significant differences of LS and DWI values were present among HF stages (P < 0.005). The LS values measured on MRE (r = 0.838, P < 0.001) were more strongly correlated with the HF stages than with ADC values (r = −0.527, P < 0.001). The area under the receiver operating characteristic curve values of LS were significantly larger than those of DWI were for discriminating two stages of HF (0.979 vs. 0.712 for ≥ S1, 0.922 vs. 0.699 for ≥ S2). MRE showed higher specificity for predicting all stages of HF compared to DWI.

MRE more strongly correlated with the HF stages than DWI and is more specific in predicting all HF stages.

Hepatocellular carcinoma (HCC)-related mortality is high because early detection modalities are hampered by inaccuracy, expense and inherent procedural risks. Thus there is an urgent need for minimally invasive, highly specific and sensitive biomarkers that enable early disease detection when therapeutic intervention remains practical. Successful therapeutic intervention is predicated on the ability to detect the cancer early. Similar unmet medical needs abound in most fields of medicine and require novel methodological approaches. Proteomic profiling of body fluids presents a sensitive diagnostic tool for early cancer detection. Here we describe such a strategy of comparative proteomics to identify potential serum-based biomarkers to distinguish high-risk chronic hepatitis C virus infected patients from HCC patients. In order to compensate for the extraordinary dynamic range in serum proteins, enrichment methods that compress the dynamic range without surrendering proteome complexity can help minimize the problems associated with many depletion methods. The enriched serum can be resolved using 2D-difference in-gel electrophoresis and the spots showing statistically significant changes selected for identification by liquid chromatography-tandem mass spectrometry. Subsequent quantitative verification and validation of these candidate biomarkers represent an obligatory and rate-limiting process that is greatly enabled by selected reaction monitoring (SRM). SRM is a tandem mass spectrometry method suitable for identification and quantitation of target peptides within complex mixtures independent on peptide-specific antibodies. Ultimately, multiplexed SRM and dynamic multiple reaction monitoring can be utilized for the simultaneous analysis of a biomarker panel derived from support vector machine learning approaches, which allows monitoring a specific disease state such as early HCC. Overall, this approach yields high probability biomarkers for clinical validation in large patient cohorts and represents a strategy extensible to many diseases.

• Hepatocellular carcinoma
• Biomarkers
• Early detection
• Selected reaction monitoring
• Targeted proteomics

• R01 ES026874 NIEHS NIH HHS

Indoleamine 2,3-dioxygenase (IDO) is an immunoregulatory enzyme. It plays a key role in various malignancies, infection and autoimmune diseases. IDO induces immunosuppression through the depletion of tryptophan and its downstream metabolites. Hepatitis C virus (HCV) has infected more than 12 million individuals in Pakistan. The aim of the present study was to assess the expression and activity of IDO in HCV-infected patients. The functional enzymatic activity of IDO was measured by colorimetric assay. Serum samples from 100 HCV-infected patients were taken to examine IDO activity and samples from 100 healthy volunteers were used as controls. Liver sections from patients with HCV (n=35) and healthy controls (n=5) were used for immunohistochemical studies. Immunohistochemical analysis revealed that IDO was overexpressed in 28 of 35 (80%) cirrhotic liver samples, whereas 5 of 35 (14.2%) cases presented moderate and 2 of 35 (5.7%) cases presented mild expression of IDO. The enzymatic activity of IDO was significantly higher in the serum samples of HCV-infected patients as compared with those in the control. These data indicate that the expression of IDO correlated with the pathogenesis of disease. In summary, it is suggested that the high expression of IDO in the progressively cirrhotic livers of HCV-infected patients might contribute to the development of hepatocellular carcinoma. IDO may characterize a novel therapeutic target against HCV.

• hepatitis C virus
• indoleamine 2,3-dioxygenase
• liver cirrhosis

• Animals
• CD11c Antigen/metabolism
• Dendritic Cells/immunology
• Dendritic Cells/metabolism
• Epitopes/immunology
• Female
• HLA-A2 Antigen/genetics
• HLA-DRB1 Chains/genetics
• Hepacivirus/immunology
• Hepatitis C/prevention & control
• Humans
• Interferon-gamma/biosynthesis
• Mice
• Mice, Transgenic
• Programmed Cell Death 1 Receptor/metabolism
• Spleen/immunology
• Tumor Necrosis Factor-alpha/biosynthesis
• Vaccination/methods
• Vaccines, DNA/genetics
• Vaccines, DNA/immunology
• Vaccines, Subunit/genetics
• Vaccines, Subunit/immunology

• U19 AI082642 NIAID NIH HHS

• Hepatocellular Carcinoma
• MicroRNAs
• Regulation
• Therapeutic Targets

• cancer treatment
• gene therapy
• hepatoma
• nanoparticles
• targeted gene delivery

Hepatocellular carcinoma (HCC) is a vicious and highly vascular cancer with a dismal prognosis. It is a life-threatening illness worldwide that ranks fifth in terms of cancer prevalence and third in cancer deaths. Most patients are diagnosed at an advanced stage by which time conventional therapies are no longer effective. Targeted molecular therapies, such as the multikinase inhibitor sorafenib, provide a modest increase in survival for advanced HCC patients and display significant toxicity. Thus, there is an immense need to identify novel regulators of HCC that might be targeted effectively. The insulin-like growth factor (IGF) axis is commonly abnormal in HCC. Upon activation, the IGF axis controls metabolism, tissue homeostasis, and survival. Insulin-like growth factor-binding protein 7 (IGFBP7) is a secreted protein of a family of low-affinity IGF-binding proteins termed “IGFBP-related proteins” that have been identified as a potential tumor suppressor in HCC. IGFBP7 has been implicated in regulating cellular proliferation, senescence, and angiogenesis. In this review, we provide a comprehensive discussion of the role of IGFBP7 in HCC and the potential use of IGFBP7 as a novel biomarker for drug resistance and as an effective therapeutic strategy.

• HCC
• IGFBP7
• angiogenesis
• apoptosis
• gene therapy
• senescence

The incidence of hepatocellular carcinoma (HCC) continues to increase in Japan, but the clinical characteristics of Japanese patients with HCC have not been well described. The aim of this study was to determine the frequencies and utilities of elevated α-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) levels as biomarkers in cryptogenic HCC.

A total of 2638 patients with HCC diagnosed between 1999 and 2010 in the Nagasaki Association Study of Liver (NASLD) were recruited for this study. The cause of HCC was categorized into 4 groups; HCC-B, HCC-C, HCC-BC, and HCC-nonBC. The significance of factors was examined for HCC-nonBC using logistic regression analysis in all patients.

Multivariate analysis identified age, sex, BMI, alcohol consumption, platelet count, AST, ALT, AFP, DCP, and TNM stage as independent and significant risk factors for HCC-nonBC. According to TNM stage, the median AFP levels in HCC-nonBC with TNM stages I, II, and III were significantly lower than in either HCC-B or HCC-C. In TNM stage IV, the median AFP level in HCC-nonBC was significantly lower than in either HCC-B or HCC-BC. The median DCP levels in HCC-nonBC with TNM stages I and II were significantly higher than those in either HCC-B or HCC-C. In TNM stage III, the median DCP level in HCC-nonBC was significantly higher than that in HCC-C.

DCP was more sensitive than AFP for the diagnosis of early stage cryptogenic HCC. DCP should be used as the main serum test for cryptogenic HCC detection.