• Anti-hepatitis B surface antigen
• Case report
• Idiopathic portal hypertension
• Liver biopsy
• Misdiagnosis

• Alcoholic liver disease
• Focal nodular hyperplasia
• Hepatocellular carcinoma
• Liver
• Magnetic resonance imaging

• Humans
• Male
• Focal Nodular Hyperplasia/diagnostic imaging
• Focal Nodular Hyperplasia/pathology
• Focal Nodular Hyperplasia/etiology
• Focal Nodular Hyperplasia/diagnosis
• Middle Aged
• Female
• Magnetic Resonance Imaging
• Aged
• Adult
• Liver Neoplasms/diagnostic imaging
• Liver Neoplasms/pathology
• Liver Neoplasms/diagnosis
• Carcinoma, Hepatocellular/diagnostic imaging
• Carcinoma, Hepatocellular/pathology
• Carcinoma, Hepatocellular/diagnosis
• Liver/diagnostic imaging
• Liver/pathology
• Liver/blood supply
• Diagnosis, Differential
• Tomography, X-Ray Computed
• Contrast Media/administration & dosage
• Gadolinium DTPA/administration & dosage
• Liver Cirrhosis, Alcoholic/pathology
• Liver Cirrhosis, Alcoholic/diagnostic imaging
• Liver Diseases, Alcoholic/pathology

• Gd-EOB-DTPA
• Hepatobiliary phase
• Hepatocellular carcinoma
• LI-RADS
• Nodule-in-nodule

• Humans
• Carcinoma, Hepatocellular/diagnostic imaging
• Carcinoma, Hepatocellular/pathology
• Liver Neoplasms/diagnostic imaging
• Liver Neoplasms/pathology
• Male
• Female
• Retrospective Studies
• Middle Aged
• Magnetic Resonance Imaging/methods
• Contrast Media
• Gadolinium DTPA
• Aged
• Image Enhancement/methods
• Adult
• Liver/diagnostic imaging
• Liver/pathology

• Gene expression
• HCC
• MKi67
• Outcomes
• Signaling pathways

• Gd-EOB
• Hepatocellular carcinoma
• Liver
• Magnetic resonance imaging
• Nonhypervascular hypointense nodule

• Budd-Chiari syndrome
• computed tomography
• focal nodular hyperplasia
• hepatocellular carcinoma
• liver neoplasms
• magnetic resonance imaging
• review
• ultrasonography

• biomarkers
• diagnostic imaging
• hepatocellular carcinoma
• pathology
• precancerous conditions

• cstc2018jcyjAX0181 Basic Research and Frontier Exploration Project of Chongqing Science and Technology Com-mission

• Benign
• Liver tumor
• Microwave ablation
• Radiofrequency ablation

• Beijing University of Chinese Medicine
• National Science and Technology Major Project

• Cirrhosis
• hepatocellular carcinoma
• liver cancer
• prevention
• surveillance
• ultrasound

• Carcinoma, Hepatocellular/diagnosis
• Carcinoma, Hepatocellular/etiology
• Carcinoma, Hepatocellular/therapy
• Humans
• Liver Cirrhosis
• Liver Neoplasms/diagnosis
• Liver Neoplasms/etiology
• Liver Neoplasms/therapy
• Magnetic Resonance Imaging/methods
• Non-alcoholic Fatty Liver Disease/complications

Hepatic dysplastic nodules (DNs) are a group of neoplastic lesions with a diameter of more than 1 cm that belong to precancerous lesions, with abnormal cytoplasm and cells but without malignant basis in histology. Hepatic DNs lack typical tumor markers and clinical symptoms, and their clinical diagnosis relys mainly on imaging or/and tissue pathological examination. Thanks to the further research on the pathogenesis of hepatic DNs and the development of imaging technology, the combination of medical history, various examinationss, individual tumor markers, and imaging and histopathology techniques can significantly improve the early detection and diagnosis accuracy for hepatic DNs, and reduce the rate of missed and false diagnosis. Due to the potential malignancy risk of hepatic DNs, intervention measures should be carried out on hepatic DNs at all stages, in order to block the transformation process of DNs into hepatocellular carcinoma (HCC), which is of great clinical significance to reduce the incidence and mortality of HCC.

• Liver
• Hepatic dysplastic nodule
• Clinical features
• Diagnosis
• Treatment

• Cirrhosis
• Diagnosis
• Hepatocellular carcinoma
• Magnetic resonance imaging
• Neoplasms

• Carcinoma, Hepatocellular/diagnostic imaging
• Diagnosis, Differential
• Diagnostic Imaging/methods
• Humans
• Liver/diagnostic imaging
• Liver/pathology
• Liver Cirrhosis/diagnostic imaging
• Liver Cirrhosis/pathology
• Liver Neoplasms/diagnostic imaging
• Liver Neoplasms/pathology

• Children
• Chronic liver disease
• Hepatocellular carcinoma
• Liver cancer
• Liver neoplasm
• Liver tumor

The development and prognosis of HCC involve complex molecular mechanisms, which affect the effectiveness of its treatment strategies. Tumor mutational burden (TMB) is related to the efficacy of immunotherapy, but the prognostic role of TMB-related genes in HCC has not yet been determined clearly.

In this study, we identified TMB-specific genes with good prognostic value to build diagnostic and prognostic models and provide guidance for the treatment of HCC patients.

Weighted gene co-expression network analysis (WGCNA) was applied to identify the TMB-specific genes. And LASSO method and Cox regression were used in establishing the prognostic model.

The prognostic model based on SMG5 and MRPL9 showed patients with higher prognostic risk had a remarkedly poorer survival probability than their counterparts with lower prognostic risk in both a TCGA cohort (P < 0.001, HR = 1.93) and an ICGC cohort (P < 0.001, HR = 3.58). In addition, higher infiltrating fractions of memory B cells, M0 macrophages, neutrophils, activated memory CD4 + T cells, follicular helper T cells and regulatory T cells and higher expression of B7H3, CTLA4, PD1, and TIM3 were present in the high-risk group than in the low-risk group (P < 0.05). Patients with high prognostic risk had higher resistance to some chemotherapy and targeted drugs, such as methotrexate, vinblastine and erlotinib, than those with low prognostic risk (P < 0.05). And a diagnostic model considering two genes was able to accurately distinguish patients with HCC from normal samples and those with dysplastic nodules. In addition, knockdown of SMG5 and MRPL9 was determined to significantly inhibit cell proliferation and migration in HCC.

Our study helps to select patients suitable for chemotherapy, targeted drugs and immunotherapy and provide new ideas for developing treatment strategies to improve disease outcomes in HCC patients.

• Diagnosis
• Hepatocellular carcinoma (HCC)
• Immune checkpoint
• Prognosis
• TMB

We studied the association between the unfolded protein response (UPR) and carcinogenesis, cancer progression, and survival in hepatocellular carcinoma (HCC). We studied 655 HCC patients from 4 independent cohorts using an UPR score. The UPR was enhanced as normal liver became cancerous and as HCC advanced in stage. The UPR was correlated with cancer cell proliferation that was confirmed by multiple parameters. Significantly, a high UPR score was associated with worse patient survival. Interestingly, though UPR was associated with a high mutational load, it was not associated with immune response, immune cell infiltration, or angiogenesis. To our knowledge, this is the first study to investigate the clinical relevance of the unfolded protein response in HCC.

Hepatocellular carcinoma is a leading cause of cancer death worldwide. The unfolded protein response (UPR) has been revealed to confer tumorigenic capacity in cancer cells. We hypothesized that a quantifiable score representative of the UPR could be used as a biomarker for cancer progression in HCC. In this study, a total of 655 HCC patients from 4 independent HCC cohorts were studied to examine the relationships between enhancement of the UPR and cancer biology and patient survival in HCC utilizing an UPR score. The UPR correlated with carcinogenic sequence and progression of HCC consistently in two cohorts. Enhanced UPR was associated with the clinical parameters of HCC progression, such as cancer stage and multiple parameters of cell proliferation, including histological grade, mKI67 gene expression, and enrichment of cell proliferation-related gene sets. The UPR was significantly associated with increased mutational load, but not with immune cell infiltration or angiogeneis across independent cohorts. The UPR was consistently associated with worse survival across independent cohorts of HCC. In conclusion, the UPR score may be useful as a biomarker to predict prognosis and to better understand HCC.

• GSVA
• hepatocellular cancer
• unfolded protein
• unfolded protein score

• Diagnostic imaging
• Liver cirrhosis
• Liver neoplasms
• Magnetic resonance imaging
• Meta-analysis

• Carcinoma, Hepatocellular
• Diffusion Magnetic Resonance Imaging
• Humans
• Liver Neoplasms
• Magnetic Resonance Imaging
• ROC Curve
• Sensitivity and Specificity

• focal nodular hyperplasia
• liver resection
• pedunculated liver tumor

• Diagnosis
• Sonazoid contrast-enhanced ultrasound (SCEUS)
• gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid magnetic resonance imaging (EOB-MRI)
• hepatocellular carcinoma (HCC)
• histological grade

There is limited scientific evidence on the potential of spectral computed tomography (SCT) for differentiation of nodules in the cirrhotic liver. We aimed to assess SCT-generated material density (MD) parameters for nodule characterisation in cirrhosis.

Dynamic dual-energy SCT scans of cirrhotic patients performed over 3 years were retrospectively reviewed. They were classified as hepatocellular carcinoma (HCC), regenerative or indeterminate, according to the European Association for the Study of the Liver criteria. MD maps were generated to calculate the area under the curve (AUC) and cutoff values to discriminate these nodules in the hepatic arterial phase (HAP) and portal venous phase (PVP). MD maps included iodine concentration density (ICD) of the liver and nodule, lesion-to-normal liver ICD ratio (LNR) and difference in nodule ICD between HAP and PVP.

Three hundred thirty nodules belonging to 300 patients (age 53.0 ± 12.7 years, mean ± standard deviation) were analysed at SCT (size 2.3 ± 0.8 cm, mean ± SD). One hundred thirty-three (40.3%) nodules were classified as HCC, 147 (44.5%) as regenerative and 50 (15.2%) as indeterminate. On histopathology, 136 (41.2%) nodules were classified as HCC, 183 (55.5%) as regenerative and 11 (3.3%) as dysplastic. All MD parameters on HAP and the nodule  difference in ICD could discriminate pathologically proven HCC or potentially malignant nodules from regenerative nodules (p < 0.001). The AUC was 82.4% with a cutoff > 15.5 mg/mL for nodule ICD, 81.3% > 1.8 for LNR-HAP and 81.3% for difference in ICD > 3.5 mg/mL.

SCT-generated MD parameters are viable diagnostic tools for differentiating malignant or potentially malignant from benign nodules in the cirrhotic liver.

The online version contains supplementary material available at 10.1186/s41747-021-00220-6.

• Carcinoma (hepatocellular)
• Iodine
• Liver cirrhosis
• Liver neoplasms
• Tomography (x-ray
• computed)

In view of the unsatisfactory treatment outcome of liver cancer under current treatment, where the mortality rate is high and the survival rate is poor, in this study we aimed to use RNA sequencing data to explore potential molecular markers that can be more effective in predicting diagnosis and prognosis of hepatocellular carcinoma. RNA sequencing data and corresponding clinical information were obtained from multiple databases. After matching with the apoptotic genes from the Deathbase database, 14 differentially expressed human apoptosis genes were obtained. Using univariate and multivariate Cox regression analyses, two apoptosis genes (BAK1 and CSE1L) were determined to be closely associated with overall survival (OS) in HCC patients. And subsequently experiments also validated that knockdown of BAK1 and CSE1L significantly inhibited cell proliferation and promoted apoptosis in the HCC. Then the two genes were used to construct a prognostic signature and diagnostic models. The high-risk group showed lower OS time compared to low-risk group in the TCGA cohort (P < 0.001, HR = 2.11), GSE14520 cohort (P = 0.003, HR = 1.85), and ICGC cohort (P < 0.001, HR = 4). And the advanced HCC patients showed higher risk score and worse prognosis compared to early-stage HCC patients. Moreover, the prognostic signature was validated to be an independent prognostic factor. The diagnostic models accurately predicted HCC from normal tissues and dysplastic nodules in the training and validation cohort. These results indicated that the two apoptosis-related signature effectively predicted diagnosis and prognosis of HCC and may serve as a potential biomarker and therapeutic target for HCC.

• apoptosis
• diagnosis
• hepatocellular carcinoma
• overall survival
• prognosis
• relapse-free survival

We studied the relationship between enhancement of DNA repair and cancer aggressiveness, tumor immune microenvironment, and patient survival in 749 hepatocellular carcinoma (HCC) patients from 5 cohorts using a DNA repair pathway score. We show that the DNA repair pathway was enhanced by the stepwise carcinogenic process of HCC, notably in grade 3 compared to grade 1 or 2 HCC. DNA repair high HCC was associated with worse survival, elevated intratumor heterogeneity, and mutation load, but not with the fraction of immune cell infiltration nor cytolytic activity. The expression of proliferation- and other cancer aggressiveness-related gene sets was also increased. Interestingly, these features were more pronounced in low-grade compared to high-grade HCC. In conclusion, the DNA repair score may be used to understand the role of DNA repair pathways in patient prognosis and treatment sensitivity and be used to improve patient outcome. To our knowledge, this is the first study using DNA repair pathway-related gene set expression data to examine and validate the clinical relevance of DNA repair pathway activity in HCC.

Hepatocellular carcinoma (HCC) is one of the most common malignancies and a leading cause of cancer-related deaths worldwide. In this study, a total of 749 HCC patients from 5 cohorts were studied to examine the relationships between enhancement of DNA repair and cancer aggressiveness, tumor immune microenvironment, and patient survival in HCC, utilizing a DNA repair pathway score. Our findings suggest that the DNA repair pathway was not only enhanced by the stepwise carcinogenic process of HCC, but also significantly enhanced in grade 3 HCC compared with grade 1 and 2 tumors. DNA repair high HCC was associated with worse survival, elevated intratumor heterogeneity, and mutation load, but not with the fraction of immune cell infiltration nor immune response. HCC tumors with a DNA repair high score enriched the cell proliferation- and other cancer aggressiveness-related gene sets. Interestingly, these features were more pronounced in grade 1 and 2 HCC compared to grade 3 HCC. To our knowledge, this is the first study to use DNA repair pathway-related gene set expression data to examine and validate the clinical relevance of DNA repair pathway activity in HCC. The DNA repair score may be used to better understand and predict prognosis in HCC.

• DNA repair
• GSEA
• GSVA
• HCC
• transcriptome
• tumor microenvironment

• R01CA160688 NIH HHS
• P30-CA016056 NCI NIH HHS

Hepatobiliary MRI contrast agents are increasingly being used for liver imaging. In clinical practice, most focal liver lesions do not uptake hepatobiliary contrast agents. Less commonly, hepatic lesions may show variable signal characteristics on hepatobiliary phase. This pictorial essay reviews a broad spectrum of benign and malignant focal hepatic observations that may show hyperintensity on hepatobiliary phase in various clinical settings. In non-cirrhotic patients, focal hepatic observations that show hyperintensity in the hepatobiliary phase are usually benign and typically include focal nodular hyperplasia. In patients with primary or secondary vascular disorders, focal nodular hyperplasia-like lesions arise as a local hyperplastic response to vascular alterations and tend to be iso- or hyperintense in the hepatobiliary phase. In oncologic patients, metastases and cholangiocarcinoma are hypointense lesions in the hepatobiliary phase; however, occasionally they may show a diffuse, central and inhomogeneous hepatobiliary paradoxical uptake with peripheral rim hypointensity. Post-chemotherapy focal nodular hyperplasia-like lesions may be tricky, and their typical hyperintense rim in the hepatobiliary phase is very helpful for the differential diagnosis with metastases. In cirrhotic patients, hepatocellular carcinoma may occasionally appear hyperintense on hepatobiliary phase.

• Gadobenate dimeglumine
• Gadoxetate disodium
• Hepatocellular carcinoma
• Liver neoplasms
• Magnetic resonance imaging

• Benign liver tumors
• Focal nodular hyperplasia
• Hemangioma
• Hepatocellular adenoma

We attempted to establish an ultrasound (US) imaging-diagnostic system for histopathological grades of differentiation of hepatocellular carcinoma (HCC). We conducted a retrospective study of histopathologically confirmed 200 HCCs, classified as early (45 lesions), well- (31 lesions), moderately (68 lesions) or poorly differentiated (diff.) (56 lesions) HCCs. We performed grayscale US to estimate the presence/absence of halo and mosaic signs, Sonazoid contrast-enhanced US (CEUS) to determine vascularity (hypo/iso/hyper) of lesion in arterial and portal phase (PP), and echogenicity of lesion in post-vascular phase (PVP). All findings were of significance for the diagnosis of some (but not all) histological grades (p < 0.001–0.05). Combined findings with a relatively high diagnostic efficacy for early, poorly and moderately diff. HCC were a combination of absence of halo sign and isoechogenicity in PVP of CEUS (accuracy: 93.0%, AUC: 0.908), hypovascularity in PP (accuracy: 78.0%, area under the curve (AUC): 0.750), and a combination of isovascularity in PP and hypoechogenicity in PVP (accuracy: 75.0%, AUC: 0.739), respectively. On the other hand, neither any individual finding nor any combination of findings yielded an AUC of over 0.657 for the diagnosis of well-diff. HCC. Our study provides encouraging data on Sonazoid CEUS in the histological differential diagnosis of HCC, especially in early HCC, and the effectiveness of this imaging method should be further proved by prospective, large sample, multicenter studies.

• contrast-enhanced ultrasound
• diagnosis
• hepatocellular carcinoma
• histological grade

• Cholangiocarcinoma, intrahepatic
• Hepatocellular Adenoma
• Hepatocellular Carcinoma
• Liver Biopsy
• Molecular Pathology

• Atypical HCC
• CT
• Histopathology
• Indeterminate liver lesions
• LI-RADS
• MRI

• Contrast-enhanced ultrasound
• Focal liver lesions
• Fusion imaging
• Hepatocellular carcinoma

Background: Accurate characterization of small (3 cm) hepatocellular carcinoma (sHCC) and dysplastic nodules (DNs) in cirrhotic liver is challenging. We aimed to investigate whether texture analysis (TA) based on T2-weighted images (T2WI) is superior to qualitative diagnosis using gadoxetic acid-enhanced MR imaging (Gd-EOB-MRI) and diffusion-weighted imaging (DWI) for distinguishing sHCC from DNs in cirrhosis.

Materials and methods: Sixty-eight patients with 73 liver nodules (46 HCCs, 27 DNs) pathologically confirmed by operation were included. For imaging diagnosis, three sets of images were reviewed by two experienced radiologists in consensus: a Gd-EOB-MRI set, a DWI set, and a combined set (combination of Gd-EOB-MRI and DWI). For TA, 279 texture features resulting from T2WI were extracted for each lesion. The performance of each approach was evaluated by a receiver operating characteristic analysis. The area under the receiver operating characteristic curve (A_z), sensitivity, specificity, and accuracy were determined.

Results: The performance of TA (A_z = 0.96) was significantly higher than that of imaging diagnosis using Gd-EOB-MRI set (A_z = 0.86) or DWI set (A_z = 0.80) alone in differentiation of sHCC from DNs (P = 0.008 and 0.025, respectively). The combination of Gd-EOB-MRI and DWI showed a greater sensitivity (95.6%) but reduced specificity (66.7%). The specificity of TA (92.6%) was significantly higher than that of the combined set (P < 0.001), but no significant difference was observed in sensitivity (97.8 vs. 95.6%, P = 0.559).

Conclusion: TA-based T2WI showed a better classification performance than that of qualitative diagnosis using Gd-EOB-MRI and DW imaging in differentiation of sHCCs from DNs in cirrhotic liver. TA-based MRI may become a potential imaging biomarker for the early differentiation HCCs from DNs in cirrhosis.

• diffusion magnetic resonance imaging
• gadoxetic acid
• hepatocellular carcinoma
• liver cirrhosis
• texture analysis

• Apparent diffusion coefficient
• Diffusion-weighted imaging
• Hepatocellular carcinoma
• Histologic grade
• Intravoxel incoherent motion

• Adult
• Aged
• Carcinoma, Hepatocellular/complications
• Carcinoma, Hepatocellular/diagnostic imaging
• Carcinoma, Hepatocellular/pathology
• Diagnosis, Differential
• Diffusion Magnetic Resonance Imaging/methods
• Female
• Hepatitis B/complications
• Humans
• Image Interpretation, Computer-Assisted/methods
• Liver/diagnostic imaging
• Liver/pathology
• Liver/virology
• Liver Neoplasms/complications
• Liver Neoplasms/diagnostic imaging
• Liver Neoplasms/pathology
• Male
• Middle Aged
• Neoplasm Grading
• Reproducibility of Results
• Retrospective Studies

• 201704020016 Science and Technology Program of Guangzhou
• 81271562 National Natural Science Foundation of China

In this study, we performed a comprehensively analysis of gene expression and DNA methylation data to establish diagnostic, prognostic, and recurrence models for hepatocellular carcinoma (HCC).

Methods: We collected gene expression and DNA methylation datasets for over 1,200 clinical samples. Integrated analyses of RNA-sequencing and DNA methylation data were performed to identify DNA methylation-driven genes. These genes were utilized in univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses to build a prognostic model. Recurrence and diagnostic models for HCC were also constructed using the same genes.

Results: A total of 123 DNA methylation-driven genes were identified. Two of these genes (SPP1 and LCAT) were chosen to construct the prognostic model. The high-risk group showed a markedly unfavorable prognosis compared to the low-risk group in both training (HR = 2.81; P < 0.001) and validation (HR = 3.06; P < 0.001) datasets. Multivariate Cox regression analysis indicated the prognostic model to be an independent predictor of prognosis (P < 0.05). Also, the recurrence model successfully distinguished the HCC recurrence rate between the high-risk and low-risk groups in both training (HR = 2.22; P < 0.001) and validation (HR = 2; P < 0.01) datasets. The two diagnostic models provided high accuracy for distinguishing HCC from normal samples and dysplastic nodules in the training and validation datasets, respectively.

Conclusions: We identified and validated prognostic, recurrence, and diagnostic models that were constructed using two DNA methylation-driven genes in HCC. The results obtained by integrating multidimensional genomic data offer novel research directions for HCC biomarkers and new possibilities for individualized treatment of patients with HCC.

• DNA methylation-driven genes
• diagnosis
• hepatocellular carcinoma
• prognosis
• recurrence

• Hepatocellular carcinoma (HCC)
• angioarchitecture
• hepatocellular dysplastic nodules
• in vivo fluorescent microscopy
• microvessel density (MVD)

• HCC prognosis
• HCC therapy
• S-adenosylmethionine
• methionine metabolism
• methyladenosyltransferases

• F32 AA020150 NIAAA NIH HHS
• K01 AA022372 NIAAA NIH HHS

• Advances
• CT
• Hepatocellular carcinoma
• MRI
• Ultrasound

• CCl(4)
• HCC
• carbon tetrachloride
• cirrhosis
• hepatocellular carcinoma
• microRNAs
• prophylaxis
• transgenic animals

Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are the 2 most common primary malignant liver tumors, with hepatocellular and bile ductular differentiation, respectively. This article reviews the key histopathological findings of these 2 primary liver cancers and includes a review of the role of ancillary testing for differential diagnosis, risk stratification according to the American Joint Committee on Cancer (AJCC) staging recommendation, and a review of precancerous lesions. A literature review was conducted to identify articles with information relevant to precancerous precursors, current histopathological classification, ancillary testing, and risk stratification of primary malignant liver tumors. The histomorphology of normal liver, preinvasive precursors, primary malignancies, and morphological variants, and the utilization of ancillary tests for the pathological diagnosis are described. Dysplastic nodules are the preinvasive precursors of HCC, and intraductal papillary neoplasms of bile ducts and biliary intraepithelial neoplasia are the preinvasive precursors of CC. Benign liver nodules including focal nodular hyperplasia and adenomas are included in this review, since some forms of adenomas progress to HCC and often they have to be differentiated from well-differentiated HCC. A number of morphological variants of HCC have been described in the literature, and it is necessary to be aware of them in order to render the correct diagnosis. Risk stratification is still dependent on the AJCC staging system. The diagnosis of primary liver carcinomas is usually straightforward. Application of the appropriate ancillary studies aids in the differential diagnosis of difficult cases. The understanding of the carcinogenesis of these malignancies has improved with the standardization of the pathological classification of preinvasive precursors and studies of the molecular pathogenesis. Risk stratification still depends on pathological staging.

• biliary intraepithelial neoplasia
• cholangiocarcinoma
• dysplastic nodule
• focal nodular hyperplasia
• hepatic adenoma
• hepatocellular carcinoma
• intraductal papillary neoplasm

• Adenoma
• Children
• Focal nodular hyperplasia
• Hepatocellular carcinoma
• Hepatocyte-specific contrast media
• Liver
• Magnetic resonance imaging

• Cirrhosis
• Gadoxetic acid
• Hepatobiliary contrast materials
• Liver
• Magnetic resonance imaging

• Apparent diffusion coefficient
• Diffusion magnetic resonance imaging
• Hepatocellular carcinoma
• Magnetic resonance imaging

• Focal nodular hyperplasia
• Hepatocellular adenoma
• Hepatocellular carcinoma
• Hepatocellular nodules
• Liver
• Vascular diseases

• Carcinoma, Hepatocellular/diagnosis
• Carcinoma, Hepatocellular/pathology
• Diagnosis, Differential
• Humans
• Hyperplasia/pathology
• Liver/pathology
• Liver Diseases/diagnosis
• Liver Diseases/pathology
• Liver Neoplasms/diagnosis
• Liver Neoplasms/pathology

• Focal nodular hyperplasia
• Haemangioma
• Hepatic adenoma
• Indication for surgical treatment
• Therapeutic strategies

• Contrast-enhanced ultrasound
• Liver
• Ultrasound

• Algorithms
• Carcinoma, Hepatocellular/diagnostic imaging
• Contrast Media/administration & dosage
• Diagnosis, Differential
• Early Diagnosis
• Humans
• Liver Neoplasms/diagnostic imaging
• Microbubbles
• Practice Guidelines as Topic
• Terminology as Topic
• Ultrasonography/instrumentation
• Ultrasonography/methods

• R01 CA215520 NCI NIH HHS

This study aimed to analyze the influence of the cellular differentiation, the tumor size and the underlying hepatic condition on the enhancement pattern of hepatocellular carcinoma (HCC) on contrast-enhanced ultrasound (CEUS). 276 patients with single lesion ≤ 5 cm who underwent CEUS exam and were pathologically confirmed as HCC were retrospectively enrolled. Enhancement patterns, washout patterns, wash-in time and washout time were observed and recorded. During the arterial phase, more poorly differentiated HCCs (42.5%) and lesions > 3 cm (35.2%) performed inhomogeneous enhancement (p < 0.05). More well differentiated HCCs (63.4%) performed late washout or no washout while compared with moderately (37.8%) or poorly (24.1%) differentiated HCCs (p < 0.05). Poorly differentiated HCCs showed the shortest washout time (83.0 ± 39.8 s), moderately differentiated HCCs showed the moderate washout time (100.4 ± 52.1 s), and well differentiated HCCs showed the longest washout time (132.3 ± 54.2 s) (p < 0.05). Lesions > 3 cm (97.2 ± 51.3 s) washed out more rapidly than lesions ≤ 3 cm (113.9 ± 53.5 s) (p < 0.05). The dynamic enhancement procedure of HCC was influenced by the cellular differentiation and the tumor size. While, hepatic background showed no influence on the dynamic enhancement of HCC.

Dysplastic nodules are premalignant neoplastic nodules found in explanted livers with cirrhosis. Genetic signatures of premalignant dysplastic nodules (DNs) with concurrent hepatocellular carcinoma (HCC) may provide an insight in the molecular evolution of hepatocellular carcinogenesis. We analyzed four patients with multifocal nodular lesions and cirrhotic background by whole-exome sequencing (WES). The genomic profiles of somatic single nucleotide variations (SNV) and copy number variations (CNV) in DNs were compared to those of HCCs. The number and variant allele frequency of somatic SNVs of DNs and HCCs in each patient was identical along the progression of pathological grade. The somatic SNVs in DNs showed little conservation in HCC. Additionally, CNVs showed no conservation. Phylogenetic analysis based on SNVs and copy number profiles indicated a nonlinear segregation pattern, implying independent development of DNs and HCC in each patient. Thus, somatic mutations in DNs may be developed separately from other malignant nodules in the same liver, suggesting a nonlinear model for hepatocarcinogenesis from DNs to HCC.

• copy number variation
• dysplastic nodules
• hepatocellular carcinoma
• single nucleotide variation
• whole-exome sequencing